Brain Circulation

Beyond reperfusion: Enhancing endogenous restorative functions after an ischemic stroke Melissa Wills, Yuchuan Ding Brain Circulation 2020 6(4):223-224

Neurocysticercosis and movement disorders: A literature review Jamir Pitton Rissardo, Ana Letícia Fornari Caprara, Ícaro Durante Brain Circulation 2020 6(4):225-241 Neurocysticercosis (NCC) is a specific form of cysticercosis that affects the central nervous system. It is caused by the tapeworm Taenia solium, which is often found in pigs. NCC is considered one of the “great simulator/mimickers” of other diseases. In this context, movement disorders (MDs) can occur in a small percentage of individuals with NCC. This review aims to evaluate the clinicoepidemiological profile, pathological mechanisms, and historical features of NCC-associated MD. Relevant reports in six databases were identified and assessed by two reviewers without language restriction. A total of 71 reports containing 148 individuals who developed an MD related to NCC were identified. NCC-associated MD included parkinsonism (n = 47), ataxia (n = 32), chorea (n = 18), dystonia (n = 13), tremor (n = 8), myokymia (n = 6), myoclonus (n = 4), ballism (n = 1), tics (n = 1), and others (n = 18). The mean and median ages were 36.58 (standard deviation: 20.51) and 35 years (age range: 1–88 years), respectively. There was a slight predominance of female sex (52.17%). On follow-up, 58.90% of the individuals had a full recovery; two deaths were reported. We believe that the majority of cases reported were only diagnosed because patients had classical clinical manifestations generally investigated by neuroimaging, resulting in incidental findings suggestive of NCC, which were later supported by laboratory examinations. Therefore, the association between NCC and MD is probably underreported. Clinicians should be wary of this association, mainly in endemic areas for cysticercosis.

Mini review (Part I): An experimental concept on exercise and ischemic conditioning in stroke rehabilitation Qingzhu Wang, Melissa Wills, Zhenzhen Han, Xiaokun Geng, Yuchuan Ding Brain Circulation 2020 6(4):242-247 Stroke remains a leading cause of adult death and disability. Poststroke rehabilitation is vital for reducing the long-term sequelae of brain ischemia. Recently, physical exercise training has been well established as an effective rehabilitation tool, but its efficacy depends on exercise parameters and the patient's capacities, which are often altered following a major cerebrovascular event. Thus, ischemic conditioning as a rehabilitation intervention was considered an “exercise equivalent,” but the investigation is still in its relative infancy. In this mini-review, we discuss the potential for physical exercise or ischemic conditioning and its relation to angiogenesis, neurogenesis, and plasticity in stroke rehabilitation. This allows the readers to understand the context of the research and the application of ischemic conditioning in poststroke rehabilitation.

Clinical application of nitric oxide in ischemia and reperfusion injury: A literature review Shangqian Jiang, Chaitu Dandu, Xiaokun Geng Brain Circulation 2020 6(4):248-253 Ischemia–reperfusion injury (IRI) is a series of multifactorial cellular events that lead to increased cellular dysfunction after the restoration of oxygen delivery to hypoxic tissue, which can result in acute heart failure and cerebral dysfunction. This injury is severe and would lead to significant morbidity and mortality and poses an important therapeutic challenge for physicians. Nitric oxide (NO) minimizes the deleterious effects of IRI on cells. NO donors, such as organic nitrates and sodium nitroprusside, are used systematically to treat heart failure, angina, and pulmonary hypertension. Inhaled NO gas was approved by the FDA in 1999 to treat hypoxic newborns, and its beneficial ameliorations reach outside the realm of lung disease. This review will summarize the clinical application of NO in IRI.

How to remove those bloody collections: Nonsurgical treatment options for chronic subdural hematoma Ho Jun Yun, Yuchuan Ding Brain Circulation 2020 6(4):254-259 Chronic subdural hematoma (CSDH) is one of the most prevalent neurosurgical disorders. Patients with CSDH commonly present with altered mental status, focal neurological deficit, and/or headache. The first-line treatment for CSDH is surgical evacuation. Although the surgical procedures for CSDH have been considered relatively “straightforward,” they are not without any risk. The elderly are especially prone to show poor surgical outcomes. To make matters worse, many elderly patients are on anticoagulants and antiplatelet agents, increasing the risk of re-bleeding before and after surgery. These complications have led clinicians to search for nonsurgical alternatives. Dexamethasone should be used with caution for selected patients given its side effects. Tranexamic acid may be utilized as an adjunct therapy to surgery, but more randomized clinical trials are needed to evaluate its definitive efficacy. Interesting results of middle meningeal artery embolization (MMAE) have been reported from case studies. However, the risks associated with MMAE, including intracerebral hemorrhage, stroke, and vasospasm, have not been properly studied yet. The clinical benefits of atorvastatin and angiotensin-converting enzyme inhibitors are uncertain for CSDH. In conclusion, surgical intervention continues to be the first-line treatment while nonsurgical treatment options may be considered an adjunct therapy especially for recurrent hematoma or to reduce the volume of a hematoma.

Blocking pro-inflammatory platelet-activating factor receptors and activating cell survival pathways: A novel therapeutic strategy in experimental ischemic stroke Ludmila Belayev, Andre Obenaus, Pranab K Mukherjee, Eric J Knott, Larissa Khoutorova, Madigan M Reid, Cassia R Roque, Lawrence Nguyen, Jeong Bin Lee, Nicos A Petasis, Reinaldo B Oria, Nicolas G Bazan Brain Circulation 2020 6(4):260-268 OBJECTIVE: Acute ischemic stroke triggers complex neurovascular, neuroinflammatory, and synaptic alterations. This study explores whether blocking pro-inflammatory platelet-activating factor receptor (PAF-R) plus selected docosanoids after middle cerebral artery occlusion (MCAo) would lead to neurological recovery. The following small molecules were investigated: (a) LAU-0901, a PAF-R antagonist that blocks pro-inflammatory signaling; and (b) derivatives of docosahexaenoic acid (DHA), neuroprotectin D1 (NPD1), and aspirin-triggered NPD1 (AT-NPD1), which activates cell survival pathways and are exert potent anti-inflammatory activity in the brain. MATERIALS AND METHODS: Sprague-Dawley rats received 2 h MCAo and LAU-0901 (30 or 60 mg/kg, 2 h after stroke), NPD1, and AT-NPD1 (333 μg/kg), DHA (5 mg/kg), and their combination were administered intravenous at 3 h after stroke. Behavior testing and ex vivo magnetic resonance imaging were conducted on day 3 or 14 to assess lesion characteristics and lipidomic analysis on day 1. Series 1 (LAU-0901 + NPD1, 14d), Series 2 (LAU-0901 + AT-NPD1, 3d), and Series 3 (LAU-0901 + DHA, 1d). RESULTS: All combinatory groups improved behavior compared to NPD1, AT-NPD1, or DHA treatments alone. Total lesion volumes were reduced with LAU-0901 + NPD1 by 62% and LAU-0901 + AT-NPD1 by 90% treatments versus vehicle groups. LAU-0901 and LAU-0901 + DHA increased the production of vasoactive lipid mediators (prostaglandins: PGE2, PGF2-α, 6-keto-PGF1-α, and PGD2) as well an inflammatory regulating mediator hydroxyoctadecadienoic acid. In contrast, LAU-0901 and LAU-0901 + DHA decreased the production of 12-hydroxyeicosatetraenoic acid, a pro-inflammatory mediator. CONCLUSION: Combination therapy with LAU-0901 and selected docosanoids is more effective than the single therapy, affording synergistic neuroprotection, with restored pro-homeostatic lipid mediators and improved neurological recovery. Altogether, our findings support the combinatory therapy as the basis for future therapeutics for ischemic stroke.

Blood-transfusion-related posterior reversible encephalopathy syndrome – A description of a new case and review of the literature Mukesh Dube, Rashi Rathore Brain Circulation 2020 6(4):269-273 Posterior reversible encephalopathy syndrome (PRES) is a neurological syndrome associated with headache, altered mental status, seizures, and visual disturbances and characterized by white matter vasogenic edema affecting predominantly the posterior occipital and parietal lobes of the brain. Neurological complications of blood transfusion are uncommon, and blood-transfusion-related PRES is seldom reported. We report here one such case of PRES. A 61-year-old Asian woman with chronic anemia presented with a history of fall, causing fracture of the left femur neck. As her hemoglobin was 5 g per deciliter, she was transfused with four units of packed cells in three consecutive days. At the time of admission, she was alert, normotensive, and afebrile. Later, she developed mild headache and had a generalized tonic-clonic seizure. Her brain magnetic resonance (MR) imaging showed edema in bilateral frontal lobes and parieto-occipital lobes with normal MR venogram, consistent with PRES. We described her disorder as blood-transfusion-related PRES. Immunologic, as well as non-immunologic complications of blood transfusion, are known but, PRES is rare. Cumulative effects of blood transfusion on blood flow, blood viscosity, endothelial dysfunction leads to blood-brain barrier dysfunction, which culminates into vasogenic edema and vasoconstriction despite normal systemic blood pressure, leading to blood-transfusion-related PRES.

Rapid temporary coiling of the parent artery for the management of intraprocedural aneurysm rupture Muhammad Waqas, Kunal Vakharia, Bennett R Levy, Steven B Housley, Rimal H Dossani, Andrew Gong, Justin Cappuzzo, Elad I Levy Brain Circulation 2020 6(4):274-279 Intraprocedural rupture (IPR) of an intracranial aneurysm is the most feared complication of primary and stent-assisted coiling because it carries a high risk of morbidity and mortality. The endovascular strategy applied to control IPR depends on the cause of the rupture and stage of the procedure. Rupture during primary or stent-assisted coiling is traditionally managed with the use of continued packing, balloon microcatheter placement, or in rare cases, with parent artery sacrifice. In this technical note, we describe the use of temporary coiling of the parent artery to control IPR in three cases. Temporary parent artery coiling creates a subocclusive state, resulting in aneurysmal blood flow reduction without interruption of blood flow to the distal territory. Flow reduction combined with the thrombogenicity of the previously deployed coils results in hemostasis. In the cases presented here, IPR occurred during the late stage of coiling. In each case, parent artery coiling was performed along with heparin reversal. After confirmation of hemostasis, the coils were retrieved to restore normal blood flow. We demonstrate that the technique of temporary parent artery coiling may be a safe and effective option for the management of IPR during primary or stent-assisted coiling.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia,

Telephone consultation 11855 int 1193,

Clinical Pulmonary Medicine

Vaping-associated Lung Injury Successfully Treated With Pulse Dose Corticosteroids Electronic cigarettes were developed for the inhalation of flavored nicotine, tetrahydrocannabinol and cannabidiol via cannabis oil. Recently, there has been an outbreak of vaping-induced lung injuries ranging in severity. We report 3 previously healthy male patients, who presented with acute respiratory failure with a recent history of electronic cigarette use, ultimately diagnosed with lipoid pneumonia. All 3 patients received intravenous high-dose, pulse corticosteroids for short duration with dramatic improvement.

Corticosteroids for COVID-19-Associated ARDS Systemic corticosteroids have emerged as a possible therapy to mitigate lung injury in severe COVID-19 infection. Here, we provide historical context for corticosteroid administration in acute respiratory failure due to viral infection and review existing data for the use of systemic corticosteroids for SARS-CoV-2 infection. The results of these limited data consistently suggest a mortality benefit for patients with COVID-19-associated acute respiratory distress syndrome with no existing evidence to suggest harm.

The Complex Relationship Between Poor Sleep Quality and Chronic Obstructive Pulmonary Disease Sleep-related symptoms are prevalent among patients with chronic obstructive pulmonary disease (COPD). The disease process often manifests with nocturnal respiratory symptoms. Long-acting antimuscarinic medications improve nocturnal COPD symptoms, though their effect on sleep quality requires further investigation. Those with COPD often suffer from comorbidities that negatively impact sleep, including obstructive sleep apnea (OSA) and mood disorders such as anxiety and depression. Sleep quality is also predictive of COPD exacerbations. Patients with concurrent COPD and OSA suffer from overlap syndrome (OVS), characterized by a synergistic effect on poor health outcomes. The intersection of COPD and OSA offers the clinical pulmonary audience a useful lens for ongoing basic, clinical, and translational research. Patients with OVS experience higher mortality compared with either COPD or OSA alone. This observation is attributable to the compound effect each condition has on adverse cardiovascular events. A complex interplay exists between COPD, sleep symptoms, and OSA. COPD appears to influence important nonanatomical contributors to OSA. The presence of underlying COPD makes the definitive diagnosis of OSA a challenge. Chronic noninvasive ventilation (NIV) is the backbone of therapy for OVS, OSA, and hypercarbic COPD. NIV is additionally a well-established treatment for acute COPD exacerbations and emerging research demonstrates that NIV decreases mortality and hospitalizations in patients with hypercarbic COPD. Clinicians often need to individualize therapeutic interventions for patients with COPD, OSA, and OVS, balancing the benefits and adverse effects of such interventions. NIV can have unwanted impact on the quality of life for some patients with COPD. Certain medications used for COPD, such as corticosteroids, have adverse effects on sleep quality. Future therapeutic approaches are needed to improve the sleep symptoms and health outcomes of patients suffering from COPD and OVS.

Excessive Dynamic Airway Collapse: A COPD/Asthma Mimic or a Treatment-emergent Consequence of Inhaled Corticosteroid Therapy: Case Series and Brief Literature Review Excessive dynamic airway collapse (EDAC) is a clinical entity characterized by narrowing of larger airways during tidal breathing. Symptoms of EDAC can be similar to chronic obstructive airway disease (COPD)/asthma and EDAC can coexist with airway disease. More recently widespread use of inhaled corticosteroids (ICS) among patients with COPD/asthma has been implicated for the emergence of EDAC. In this report, we describe 6 adult patients presenting with chronic cough with a background diagnosis of either COPD or asthma on ICS, who were noted to have EDAC. We also made an attempt to briefly review the earlier published reports on EDAC. Our review suggested that EDAC is prevalent among patients with previous diagnosis of COPD/asthma and with ICS use. Female sex, older age, higher body mass index, and presence of gastroesophageal reflux disease (GORD), and chronic upper respiratory tract infections (URTI) may be a risk factor for EDAC. Chronic barking cough and shortness of breath are the common clinical presentation and acute presentation could be triggered by lower respiratory tract infection and episodic presentations can be related to chronic recurrent aspiration secondary to GORD or chronic URTI. Dynamic computed tomography of the chest and bronchoscopy are useful in the diagnosis. Pulmonary function tests could be variable, demonstrating normal, obstructive, or restrictive pattern. Management of EDAC with weight loss strategies, addressing GORD and URTI issues and antibiotics during acute lower respiratory tract infection may be helpful. Noninvasive positive pressure ventilation may be beneficial in some patients. ICS should be used wisely to prevent the emergence of EDAC among patients with chronic airway disease.

Immune-related Pulmonary Toxicity From Cancer Immunotherapy: A Systematic Approach Immune checkpoint inhibitors (ICIs) are one of the major advances in cancer treatment. ICIs have shown significant benefit in treating several types of cancer. Currently there are 6 ICIs available in the United States and multiple ICIs in the pipeline. Immune checkpoint signaling leads to immune tolerance of cancer cells through downregulation of T-cell activation. The reversal in tumor-tolerance and self-tolerance effected by ICIs likely drives both T-cell–mediated toxicity and immune-related adverse effects (irAEs); however, the exact mechanism remains not completely understood. Pulmonary irAEs are among the most feared high-grade irAEs leading to discontinuation of ICIs and, not uncommonly, treatment-related death. Because of the high degree of morbidity and mortality associated with pulmonary irAEs and the exponential growth of ICI use, clinicians must increasingly be facile in diagnosing and managing these irAEs.

The Diagnosis of Hypersensitivity Pneumonitis and the Role of Lung Biopsy Hypersensitivity pneumonitis (HP) refers to a collective noun of diffuse lung diseases encompassing some degree of bronchiolar and interstitial granulomatous inflammation that results from persistent inhalation exposure and consequent immune sensitization to a large potential diversity of (predominantly) organic antigens in predisposed individuals. In suspected cases of HP, forceps transbronchial lung biopsy (TBLB) has been traditionally performed on a case-by-case basis along with bronchoalveolar lavage. This option has been subject to some debate and its use is more restrained in the presence of a chronic fibrotic form of HP—where surgical lung biopsy is classically recommended in the face of the need for a more reliable differentiation from fibrotic idiopathic interstitial pneumonias. We intended to assess the diagnostic contribution of conventional TBLB in the combined multidisciplinary diagnosis of an HP patient cohort. A retrospective evaluation of all the diagnostic elements and level of confidence from all HP cases followed in an interstitial lung disease ILD outpatient clinic of a district hospital center (Centro Hospitalar do Baixo Vouga), from June 2015 to August 2019, and simultaneously evaluated in a multidisciplinary team discussion of the same hospital, comprising an interstitial lung disease dedicated lung physician, a chest radiologist, 2 rheumatologists, and a pathologist. We identified 78 patients (mean age: 70.5 y, interquartile range: 58.5 to 78.0) with a slight female predominance. Most of the patients (61.5%) had chronic/fibrotic HP. The most frequently identified inducing antigens were avian antigens in 59.0% of cases, followed by molds in 20.5%. Of the 72 patients who underwent bronchofibroscopy, 36.1% (n=26) conventional TBLB performed, predominantly in the segments of the right lower lobe with an average number of 3.9 biopsies (SD±1.4) accomplished per patient. In 50.0% of the cases submitted to TBLB, the biopsies showed representative material with histologic features (definite or supportive) which had some degree of contribution for the diagnostic discussion. Among the patients where TBLBs were not performed or whose results were found to be devoid of significant findings, 73.1% were still diagnosed as HP without the need for surgical video-assisted thoracoscopic lung biopsy/transbronchial lung cryobiopsy (VATS/TBLCB) on the grounds of other diagnostic elements; 15.4% of patients were diagnosed with HP after a VATS/TBLCB procedure. Lastly, around 11.5% of patients were considered to have an unacceptable risk for VATS/TBLCB but, on the basis of clinical, radiologic, and immunologic elements received a multidisciplinary provisional diagnosis still with a reasonable level of confidence. Regarding complications with TBLB, there were 2 cases of moderate bleeding (7.6%) and 1 pneumothorax (3.8%) that did not require drainage. Notwithstanding its limitations, TBLB can still have a role in the diagnostic workup of HP, namely in acute/inflammatory HP, adding definite or supportive histologic information for multidisciplinary discussion in up to 50% of cases. TBLB can augment diagnostic yield at the expense of only a minimal increase of risk, as it is a universally available technique that can be performed along with bronchoalveolar lavage. This has important implications, particularly in centers devoid of TBLCB, as a surgical biopsy can be avoided in approximately half of patients who are eventually diagnosed with HP.

Bronchoscopy in the COVID-19 Era Bronchoscopy is an aerosol-generating procedure with important diagnostic and therapeutic indications. However, in the era of the coronavirus disease 2019 (COVID-19) pandemic, airway procedures can put health care providers at an increased risk of exposure and transmission of COVID-19. We have reviewed and summarized guidelines from various societies of respiratory medicine to stratify the indications for bronchoscopy and optimize preprocedural, procedural, and postprocedural preparation. Appropriate measures can help decrease exposure to health care workers when performing this aerosol-generating procedure.

Is a Trial of Observation Safer Than Intervention With Spontaneous Pneumothorax? Synopsis: Modest evidence that a conservative approach to the treatment of primary spontaneous pneumothorax is noninferior to intervention.

Home, Hospice, or Hospital: Where Are Our Patients With Chronic Lung Disease Dying? Synopsis: This cross-sectional study examined the differences in place of death among patients with chronic lung disease living in the United States from 2003 to 2017. Overall, there was a shift toward home and hospice deaths and away from hospital or nursing facility deaths. However, important differences in race, education, and socioeconomic status indicate the pressing need for further research into how to best care for all patients with chronic lung disease at the end of their lives.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia,

Telephone consultation 11855 int 1193,

Melanoma Research

Antibody-drug conjugates: an evolving approach for melanoma treatment Melanoma continues to be an aggressive and deadly form of skin cancer while therapeutic options are continuously developing in an effort to provide long-term solutions for patients. Immunotherapeutic strategies incorporating antibody-drug conjugates (ADCs) have seen varied levels of success across tumor types and represent a promising approach for melanoma. This review will explore the successes of FDA-approved ADCs to date compared to the ongoing efforts of melanoma-targeting ADCs. The challenges and opportunities for future therapeutic development are also examined to distinguish how ADCs may better impact individuals with malignancies such as melanoma.

MicroRNAs expression associated with aggressive clinicopathological features and poor prognosis in primary cutaneous melanomas Several studies have focused on identifying microRNAs involved in the pathogenesis of melanoma. However, its association with clinicopathological features has been scarcely addressed. The aim of this study is to identify microRNAs expression profiles related to aggressive clinicopathological and molecular features, and to analyze the association with melanoma survival. A retrospective and observational study was performed in a series of 179 formalin-fixed paraffin embedded primary cutaneous melanomas. First, a screening analysis on a discovery set (n = 22) using miRNA gene chip array (Affymetrix, Santa Clara, California, USA) was performed. Differentially expressed microRNAs were detected employing the software Partek Genomic Suite. Validation of four microRNAs was subsequently performed in the entire series (n = 179) by quantitative real time PCR (qRT-PCR). MicroRNAs expression screening analysis identified 101 microRNAs differentially expressed according to Breslow thickness (≤1 mm vs. >1 mm), 79 according to the presence or absence of ulceration, 78 according to mitosis/mm2 (<1 mitosis vs. ≥1 mitosis) and 97 according to the TERT promoter status (wt vs. mutated). Six microRNAs (miR-138-5p, miR-130b-3p, miR-30b-5p, miR-34a-5p, miR-500a-5p, miR-339-5p) were selected for being validated by qRT-PCR in the discovery set (n = 22). Of those, miR-138-5p, miR-130b-3p, miR-30b-5p, miR-34a-5p were selected for further analysis in the entire series (n = 179). Overexpression of miR-138-5p and miR-130b-3p was significantly associated with greater Breslow thickness, ulceration, and mitosis. TERT mutated melanomas overexpressed miR-138-5p. Kaplan–Meier survival analysis showed poorer survival in melanomas with miR-130b-3p overexpression. Our findings provide support for the existence of a microRNA expression profile in melanomas with aggressive clinicopathological features and poor prognosis.

Transcriptional analysis of metastatic uveal melanoma survival nominates NRP1 as a therapeutic target Uveal melanoma is a rare form of melanoma with particularly poor outcomes in the metastatic setting. In contrast with cutaneous melanoma, uveal melanoma lacks BRAF mutations and demonstrates very low response rates to immune-checkpoint blockade. Our objectives were to study the transcriptomics of metastatic uveal melanoma with the intent of assessing gene pathways and potential molecular characteristics that might be nominated for further exploration as therapeutic targets. We initially analyzed transcriptional data from The Cancer Genome Atlas suggesting PI3K/mTOR and glycolysis as well as IL6 associating with poor survival. From tumor samples collected in a prospective phase II trial (A091201), we performed a transcriptional analysis of human metastatic uveal melanoma observing a novel role for epithelial-mesenchymal transition associating with survival. Specifically, we nominate and describe initial functional validation of neuropillin-1 from uveal melanoma cells as associated with poor survival and as a mediator of proliferation and migration for uveal melanoma in vitro. These results immediately nominate potential next steps in clinical research for patients with metastatic uveal melanoma.

Clinical outcomes and secondary glaucoma after gamma-knife radiosurgery and Ruthenium-106 brachytherapy for uveal melanoma: a single institution experience We retrospectively analyzed data from records of 48 patients (48 eyes) treated with gamma-knife (n = 18) or Ruthenium-106 brachytherapy (n = 30) for uveal melanoma, in our Ocular Oncology Unit between December 2013 and September 2019, with the aim to evaluate treatment outcomes, and incidence and risk factors for secondary glaucoma. Patients demographics and tumor characteristics at diagnosis were recorded. Follow-up data were collected regarding local tumor control, treatment complications, enucleation need, metastases occurrence and survival status. The median follow-up period was 33.7 months in the gamma-knife group and 26.2 months in the brachytherapy group. The mean tumor thickness, the largest basal diameter and the tumor volume were significantly higher in the gamma-knife group than in the brachytherapy group. The local tumor control rate was 100% in the brachytherapy group and 77.8% in the gamma-knife group. In the gamma-knife group, six patients were enucleated, no patient treated with brachytherapy underwent enucleation. The overall survival rate was 96.7% in the brachytherapy group and 94.44% in the gamma-knife group. Secondary glaucoma occurred in 10 patients after gamma-knife and in one patient after brachytherapy: it should be emphasized that larger lesions were treated with gamma-knife, whereas smaller tumors were selected for brachytherapy. We found a significative correlation of tumor thickness (P value = 0.043) and volume (P value = 0.040) with secondary glaucoma occurrence after gamma-knife treatment. Moreover, secondary glaucoma significantly correlated with radiation retinopathy in the gamma-knife group (P value = 0.009). This study shows preliminary clinical results that could be useful for further studies with more patients and longer follow-up.

Anti-programmed cell death-1 therapy in octogenarian and nonagenarian advanced/metastatic melanoma patients Immunotherapy with anti-programmed cell death-1 (PD-1) agents is an effective treatment for metastatic melanoma. Octogenarians and nonagenarians represent a significant cohort of melanoma patients. This multicenter retrospective analysis enrolled 499 patients treated with nivolumab or pembrolizumab. Seventy-three patients were aged 80–100, 218 patients were aged 65–79, and 208 patients were <65 years old. Baseline parameters were comparable. The median overall survival (OS) was 14.7, 18.7, 25.9, and the median progression-free survival (PFS) was 8.7, 7.7, and 6.2 months in the age groups of 80–100, 65–79, and <65 years, respectively. The median melanoma-specific survival (MSS) was 22.5, 27.8, and 31.6 months in the age groups of 80–100, 65–79, and <65 years, respectively. There was no statistically significant difference in OS (P = 0.2897), PFS (P = 0.7155), and MSS (P = 0.9235) between the group of 80–100 years old vs. 65–79 and vs. <65 years old patients. Overall response rate and disease control rate was similar in all groups (P = 0.06974 and P = 0.89435, respectively). Overall, the immune-related adverse event (irAE) rate was comparable in the three age groups (41, 34, and 37.5% in the groups of patients aged 80–100, 65–79, and <65 years, respectively). Also, the rates of G3 and G4 irAEs were comparable (4, 6, and 7% in the groups of patients, respectively). The efficacy and toxicity of anti-PD-1 therapy in octogenarians and nonagenarians with metastatic melanoma are similar as in patients aged <65 years and 65–79 years. The patients’ age should not be considered as an exclusion criterion for anti-PD-1 treatment.

Postapproval trials versus patient registries: comparability of advanced melanoma patients with brain metastases Postapproval trials and patient registries have their pros and cons in the generation of postapproval data. No direct comparison between clinical outcomes of these data sources currently exists for advanced melanoma patients. We aimed to investigate whether a patient registry can complement or even replace postapproval trials. Postapproval single-arm clinical trial data from the Medicines Evaluation Board and real-world data from the Dutch Melanoma Treatment Registry were used. The study population consisted of advanced melanoma patients with brain metastases treated with targeted therapies (BRAF- or BRAF-MEK inhibitors) in the first line. A Cox hazard regression model and a propensity score matching (PSM) model were used to compare the two patient populations. Compared to patients treated in postapproval trials (n = 467), real-world patients (n = 602) had significantly higher age, higher ECOG performance status, more often ≥3 organ involvement and more symptomatic brain metastases. Lactate dehydrogenase levels were similar between both groups. The unadjusted median overall survival (mOS) in postapproval clinical trial patients was 8.7 (95% CI, 8.1–10.4) months compared to 7.2 (95% CI, 6.5–7.7) months (P < 0.01) in real-world patients. With the Cox hazard regression model, survival was adjusted for prognostic factors, which led to a statistically insignificant difference in mOS for trial and real-world patients of 8.7 (95% CI, 7.9–10.4) months compared to 7.3 (95% CI, 6.3–7.9) months, respectively. The PSM model resulted in 310 matched patients with similar survival (P = 0.9). Clinical outcomes of both data sources were similar. Registries could be a complementary data source to postapproval clinical trials to establish information on clinical outcomes in specific subpopulations.

Safety and efficacy of combination nivolumab plus ipilimumab in patients with advanced melanoma: results from a North American expanded access program (CheckMate 218) CheckMate 218, a North American expanded access program (EAP), investigated nivolumab plus ipilimumab in patients with advanced melanoma. Safety and efficacy, including 2-year survival in clinically relevant patient subgroups, are reported. Eligible patients were aged ≥18 years with unresectable stage III/IV melanoma, an Eastern Cooperative Oncology Group performance status of 0/1, and no prior checkpoint inhibitors. Patients received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for 4 cycles (induction) followed by nivolumab 3 mg/kg every 2 weeks (maintenance) until progression or unacceptable toxicity or a maximum of 48 weeks. Safety and overall survival (OS) data were collected. This EAP included 754 treated patients from the USA (n = 580) and Canada (n = 174). Median follow-up time was 17.8 months. All-grade and grade 3–4 treatment-related adverse events were reported in 96% and 53% of patients and led to treatment discontinuation in 36% and 26% of patients, respectively. OS rates at 12 and 24 months were 82% [95% confidence interval (CI) 79–84] and 70% (95% CI 66–74), respectively. Twenty-four-month OS rates were 63% in patients aged ≥75 years, 56% in patients with elevated lactate dehydrogenase levels, 73% in patients with BRAF wild-type tumors, 70% in patients with BRAF mutant tumors, and 56% in patients with mucosal melanoma. In this EAP, nivolumab plus ipilimumab demonstrated high survival rates and safety outcomes consistent with those from randomized clinical trials, further supporting the use of this combination for advanced melanoma across multiple subgroups.

Safety and efficacy of electrochemotherapy in a series of patients with nonmetastasized primary or recurrent anorectal malignant melanoma Anorectal malignant melanoma (AMM) is a rare malignant tumor. Surgery remains the gold standard but new adjuvant treatments to allow local sphincter-saving are warranted. Electrochemotherapy (ECT) is an alternative to surgery in selected cohorts of patients. To evaluate safety and efficacy of ECT in a retrospective series of patients with primary or recurrent AMM in terms of local disease control, local progression free and overall survival. Seven primary and one recurrent AMM underwent ECT. Patients were followed at 1 and 2 months and at the longest available follow-up with clinical examination and/or ultrasound. One month after ECT 6/8 (75%) patients showed complete response, 1/8 partial response (12.5%) and 1/8 stable disease (12.5%), confirmed at 2 months. Bleeding stopped in all patients, and pain was absent or mild/moderate in all patients. No serious adverse events were observed. At 1 year of follow-up seven out of eight patients were alive (87.5%), four were disease-free and three were alive with disease. At the longest available follow-up (mean 4.9 ± 2.0 years) five out of eight (62.5%) of patients were still alive. Our study showed that ECT is well tolerated and effective in the treatment of patients with anal melanoma with good local control of disease.

Hemophagocytic lymphohistiocytosis of a melanoma patient under BRAF/MEK-inhibitor therapy following anti-PD1 inhibitor treatment: a case report and review to the literature Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening condition. HLH in infants and young children is usually inherited, which is then classified as primary HLH. Secondary HLH, in contrast, is caused by many different conditions such as infections, cancer or medication and affects mostly adults. HLH is a hyperinflammatory condition, which may mimic an acute septic shock. We report on a 68-year-old patient with malignant melanoma with lymph node metastases. Due to the lymphogenic progression, treatment was switched from nivolumab to dabrafenib and trametinib. Twenty-one days after initiation of BRAF/MEK inhibitor therapy, the patient presented to our emergency department with clinical signs of infection such as fever and fatigue. Laboratory tests showed excessive inflammation levels without identifying an underlying pathogen. Two days later, the patient developed an increasing pancytopenia. After extending the diagnosis, we found very high ferritin levels, hypertriglyceridemia, hypofibrinogenemia and a soluble CD25 receptor. Based on the laboratory results, prolonged fever and splenomegaly, we were able to diagnose HLH as the underlying condition. We immediately initiated treatment with intravenous prednisone, which remarkably improved the clinical symptoms. After full recovery, we reinitiated anti-tumor treatment with vemurafenib and cobimetinib, which was tolerated without side effects. Due to the relatively nonspecific nature of the clinical signs and symptoms and the significant overlap with other diseases such as sepsis, the diagnosis of HLH is often delayed. This explains, in part, the high morbidity and mortality rate. Our case shows that early treatment with steroids is effective. However, much work remains in order to raise awareness and improve the understanding of the pathophysiology of this condition.

Life-threatening polymyositis with spontaneous hematoma induced by nivolumab in a patient with previously resected melanoma Single-agent anti-PD1 antibodies are usually very well tolerated, but serious toxicity can still occur. Despite the PD-1 pathway seems to be relevant in the pathogenesis of immune-related myositis, anti-PD1-related myositis is generally a rare side effect of the treatment and usually not serious. However, its frequency is likely to increase as the use of immune checkpoint blockades. We present here a case of life-threatening polymyositis with associated spontaneous muscular hematoma in a patient treated with single-agent nivolumab in the adjuvant setting. Spontaneous hematoma is an extremely rare complication with unclear etiology of idiopathic myositis. Very few cases have been reported in the literature and their outcome has been often fatal. To our knowledge, this is the first case of autoimmune myositis and spontaneous heamatoma associated with the administration of single-agent checkpoint blockade. Anti-PD1 antibodies have changed the treatment landscape for a number of cancer entities in the past few years. When given as single agent they are usually very well tolerated, but serious rare toxicity can still occur. We present here a case of polymyositis with associated spontaneous muscular hematoma in a patient treated with single agent nivolumab.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia,

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Cancer Research and Therapeutics

Effectiveness of mouthrinses in prevention and treatment of radiation induced mucositis: A systematic review Varsha Manoharan, Nusrath Fareed, Hemant Battur, Sanjeev Khanagar, Jaseela Praveena Journal of Cancer Research and Therapeutics 2020 16(8):1-10 Mucositis is a frequent, severe consequence of radiation therapy among patients undergoing radiotherapy for the head-and-neck cancer, often requiring hospitalization and even breaks or discontinuity in treatment. Mouth rinsing with various agents has demonstrated effectiveness in the prevention and treatment of radiation-induced mucositis (OM), but evidence for the same is lacking. This systematic review is therefore conducted with the aim of assessing the evidence for the effectiveness of mouthrinses in prevention and treatment of OM. Joanna Briggs Institute guidelines were followed to conduct this review. Six databases were searched and a total of 25 randomized clinical trials published over a period of the past 31 years were included for qualitative synthesis. Analysis of 25 studies revealed that 1299 participants, aged 46–69 years were assigned to the test groups and control groups. A total of 16 different formulations were studied among patients over a duration of 6 days to 1 year in varying dosages. The overall preventive fraction ranged from 1.9% to 77.8% for a reduction in clinical grades of mucositis, 7.6%–83.3% for a reduction in pain and 20%–50% for a reduction in bacterial counts. Adverse effects such as mouth burning, altered taste, sore throat, have been reported, especially with chlorhexidine and benzydamine hydrochloride. Evidence for the included studies is IC and ID. Studies using herbal based products and tissue regenerating agents revealed comparatively better effectiveness with lesser side effects. However, the number of studies to support such a claim is very limited.

Thyroid paraganglioma: A case-based systematic review of literature Pritinanda Mishra, Somanath Padhi, Gayatri Behera Journal of Cancer Research and Therapeutics 2020 16(8):11-21 Thyroid paragangliomas are distinctly rare primary thyroid neoplasms with nearly 75 cases reported worldwide. Due to their similar embryological origin and cytohistomorphology with other thyroid neoplasms, they may pose great diagnostic challenges for pathologists, radiologists, endocrinologists, as well as surgeons leading to unnecessary aggressive therapy. With recent advances in molecular genetics, the prognostic significance of such seemingly innocuous thyroid neoplasms has been better understood. In this manuscript, we describe such a case and present a systematic review of all reported cases till date giving an update on our current knowledge regarding their diagnostic pitfalls, pathology, and molecular genetics.

The relevance of long noncoding RNAs in colorectal cancer biology and clinical settings Atefeh Talebi, Mazaher Azizpour, Shahram Agah, Mohsen Masoodi, Gholam Reza Mobini, Abolfazl Akbari Journal of Cancer Research and Therapeutics 2020 16(8):22-33 Colorectal cancer (CRC) is one of the most frequent causes of cancer-related death worldwide. The prognosis of the malignancy and patient survival is commonly poor. Therefore, the discovery of pertinent biomarkers is essential to provide an accurate diagnosis and effective therapy. Newly, a group of noncoding RNAs named long noncoding RNAs (lncRNAs) has been found to involve in CRC development and progression. In this review, we highlighted the biological function of lncRNAs and reviewed their potentials as clinical tools in the CRC. A literature search of PubMed, EMBASE, MEDLINE, Web of Science, Scopus, and Cochrane Library using the MeSH terms “CRC,” “long noncoding RNA,” “lncRNA,” and relevant was completed. The review included all articles that reported on the significance and role of lncRNAs in CRC development and clinical settings. All identified articles were cross-referenced for further articles, and any unavailable online were retrieved from hardcopy archive libraries. CRC-related lncRNAs could regulate a number of cellular processes, and their dysregulations have been suggested as potential biomarkers.

Predicting outcome of advanced head-and-neck cancer by measuring tumor blood perfusion in patients receiving neoadjuvant chemotherapy Kishore Singh, Rubu Sunku, Arun K Rathi, Gaurav S Pradhan Journal of Cancer Research and Therapeutics 2020 16(8):34-38 Purpose: The purpose of this study was to correlate treatment response with tumor blood perfusion in patient of advanced head-and-neck cancer undergoing neoadjuvant chemotherapy. Materials and Methods: A total of 40 patients of advanced head-and-neck cancer, who were planned for neoadjuvant chemotherapy, were included in the study. All patients underwent diagnostic computed tomography (CT) with perfusion study for staging and quantitative measurement of tumor volume as well as perfusion parameters (including tumor blood volume, blood flow, permeability, and time to peak enhancement), at baseline and after completion of neoadjuvant chemotherapy. Total 3 cycles of neoadjuvant chemotherapy with paclitaxel, cisplatin, and 5 fluorouracil were given. Tumor response was evaluated in terms of change in tumor volume and correlated with perfusion parameters. Results: Out of 40 patients, 22 patients had more than 50% reduction in tumor volume, who were grouped as responder and remaining 18 patients had <50% decrease in tumor volume, grouped as nonresponder. Both the groups were similar in terms of age, gender, performance status, stage, nodal status, or addiction. Baseline CT scan shows a significant difference in tumor blood flow (P = 0.048) and marginal difference in time to peak enhancement (P = 0.058) in two groups. However, there is no difference in tumor blood volume (P = 0.32) and permeability surface area (P = 0.07). Conclusions: Evaluation of tumor blood flow by perfusion CT is helpful in predicting chemotherapy outcome and deciding appropriate treatment modality, but further evaluation with more number of patients is required for validating the predictive role of each perfusion parameters.

Butyrylcholinesterase: An economical marker of disease activity in oral squamous cell carcinoma before and after therapy Shradha Gagan Jaiswal, Gagan Rajesh Jaiswal Journal of Cancer Research and Therapeutics 2020 16(8):39-42 Introduction: Biomarkers which can predict disease progression and serve as prognostic indicators are necessary for better management of oral cancer. Studies have shown that Cholinesterase plays an important role in cellular proliferation, differentiation and may have a possible involvement in tumor growth. Aim and Objective: The present study is aimed to determine the utility of serum Butyrylcholinesterase (BChe) levels as a marker for progression of oral squamous cell carcinoma (OSCC) in relation to the grade of the tumor and to determine if any variation occurred in the levels of BChe before and after therapy. Materials and Methods: A total of 120 patients were included in the study and divided into two groups as Group A-30 patients (healthy individuals) and Group B-90 cases of histopathologically diagnosed OSCC. The blood sample was collected before surgery, re-collected after the completion of radiotherapy (i.e., 3 and 6 months postsurgery) and analyzed biochemically for the concentration of BCh. Statistical Analysis: Paired t-test, ANOVA, and post hoc test (Bonferroni) were used for determining the statistical significance. Results: BChe levels were lower in OSCC (2940.32–1405.50 u/l when compared with controls (11149.60–11243.07 unit/l) and this difference was statistically significant. Postoperatively at 3 months, the serum BChe levels of OSCC patients increased almost two-fold compared to the preoperative values, and this difference was also statistically significant (P = 0.000) After 6 months, these levels further increased but did not reach those of controls. Conclusion: BChe can be used as an inexpensive, easy to use, noninvasive biomarker for the evaluation of disease-free survival in OSCC patients.

Good prognostic factor in patients with nonmetastatic nasopharyngeal carcinoma: Programmed death ligand-1 expression in tumor cells Hayriye Sahinli, Nalan Akyürek, Mukaddes Yılmaz, Olcay Kandemir, Ayşe Ocak Duran, Sezer Kulaçoǧlu, Gökhan Uçar, Elif Acar, Ahmet Özet, O Berna Ç. Öksüzoǧlu, Nuriye Y Özdemir Journal of Cancer Research and Therapeutics 2020 16(8):43-47 Purpose: Programmed death ligand-1 (PD-L1) is the main ligand for programmed death-1 (PD-1), and is one of the major targets for cancer immunotherapy. Only a few studies are available for the clinical significance of PD-1/PD-L1 in nasopharyngeal carcinoma (NPC). There is a controversial association between PD-L1 expression and survival in NPC. This study aimed at defining any potential association between PD-L1 expression in tumor cells (TCs) and prognosis in NPC. Patients and Methods: A total of seventy NPC patients treated between January 2008 and December 2016 were included in the study. PD-L1 expression was assessed by immunohistochemistry (IHC) in tumor specimens. The IHC assay was considered positive if ≥5% of TCs are stained. Clinicopathological variables were documented. Variables included in the analysis were PD-L1 expression, clinicopathological characteristics, and prognosis. Results: The estimated 5-year overall survival (OS) rate was 62%. Nearly 55.7% (n = 39) of the TCs tested positive for PD-L1 expression. No associations were found between the level of PD-L1 in TCs and clinicopathological characteristics. Comparisons between patients with PD-L1-positive tumors and PD-L1-negative tumors revealed that OS was statistically significantly longer in patients with PD-L1-positive tumors as assessed by the univariate Cox regression analysis (hazard ratio [HR], 0.378; 95% confidence interval, 0.158–0.905; P = 0.029) and Kaplan–Meier curves (P = 0.023). Conclusion: PD-L1 expression is an important prognostic factor in NPC. PD-L1 expression positively correlates with survival.

Eyelid carcinoma: An experience from a tertiary cancer center Shivakumar Thiagarajan, Ameya Bahani, Devendra Chaukar, Anil K Dcruz Journal of Cancer Research and Therapeutics 2020 16(8):48-52 Context: Eyelid carcinoma is rare tumors of the head and neck. They are rarely lethal but can be associated with significant morbidity if not treated early and appropriately. There are limited data available from world over and in particular the Indian subcontinent regarding eyelid carcinoma and its prognostic factors influencing treatment outcomes. Setting and Design:Retrospective study of patients treated in a tertiary cancer center between 2005 and 2016. Methodology: In this study, 51 patients with eyelid carcinoma treated at single tertiary cancer center were included. The demographic, clinical data, which includes the treatment received, histopathology report and follow–up, were recorded. All the relevant variables influencing disease-free survival (DFS) were analyzed. Results: Sebaceous carcinoma was the most common eyelid carcinoma followed by squamous cell carcinoma and basal cell carcinoma in descending order in this series. Lower eyelid was involved most often. The incidence of nodal metastasis was low (14%). Multivariate analysis revealed that margin status influenced the DFS (P= 0.001) (hazard ratios = 15.9 [95% confidence interval: 1.8–135.2]). The 5 years' DFS was 70%. Conclusion: Eyelid tumors are less common cancer with good prognosis if treated appropriately. The morbidity associated with treatment can be reduced if treated early.

Cytopathology-histopathology correlation and the effect of nodule diameter on diagnostic performance in patients undergoing thyroid fine-needle aspiration biopsy Nusret Yilmaz, Guven Baris Cansu, Serap Toru, Ramazan Sari, Guzide Gokhan Ocak, Cumhur Arici, Hasan Ali Altunbas, Mustafa Kemal Balci Journal of Cancer Research and Therapeutics 2020 16(8):53-58 Introduction: Although thyroid fine-needle aspiration biopsy (FNAB) is established to have a good overall sensitivity and specificity, various outcomes have been reported on its performance in large nodules. The aim of the study was to evaluate the diagnostic performance of FNAB and the effect of the nodule diameter on its diagnostic performance. Materials and Methods: The outcomes of a total of 7319 patients who underwent FNAB over the course of 5 years were analyzed retrospectively and 648 patients who had undergone post-FNAB thyroidectomy or lobectomy were included in the study. FNAB results were classified according to the Bethesda system. After evaluating the compatibility between cytology and pathology results, all-nodules and diameter-based (<4 cm and ≥4 cm) sensitivity, specificity, false positivity, false negativity, and accuracy rates of FNAB were calculated. Results: Sensitivity of FNAB was 85.4% for all nodules, 88.3% for nodules <4 cm, and 75.8% for nodules >4 cm (P < 0.001). Specificity was 58.4% for all nodules, 49.3% for nodules <4 cm, and 75.1% for nodules >4cm (P < 0.001). While false positivity was 41.6% for all nodules, it was 50.7% for nodules smaller than 4 cm and was 24.9% for nodules larger than 4 cm (P < 0.001). False negativity was 14.6% for all nodules and was 11.7% for nodules smaller than 4 cm and 24.2% for nodules larger than 4 cm (P < 0.001). Finally, among the entire set of nodules, the accuracy was 64.4%, which was 59.2% in nodules smaller than 4 cm, and 75.2% in nodules larger than 4 cm (P < 0.001). Conclusion: Despite a higher rate of false negativity, FNAB has higher specificity and accuracy in large nodules than those in the small nodules. Nodule diameter should not be used alone as a criterion to recommend thyroidectomy to the patient.

The radioprotective effect of melatonin against radiation-induced DNA double-strand breaks in radiology Farid Esmaely, Aziz Mahmoudzadeh, Mohsen Cheki, Alireza Shirazi Journal of Cancer Research and Therapeutics 2020 16(8):59-63 Objective: The objective of this study is to observe the effect of 100-mg melatonin in reducing the levels of double-strand breaks (DSB) induced by 10 mGy and 100 mGy X-ray in peripheral lymphocyte applying H2AX immunofluorescence microscopy and comparing the different efficacies of melatonin ingestion 1 and 2 h before irradiation. Materials and Methods: Informed consent was obtained from five healthy males, nonathlete, and nonsmoking human volunteers aged between 25 and 35 years. Each volunteer was given a single oral dose of 100 mg melatonin at 9 a.m. Blood samples were collected in vacutainer tubes (without any preservative to separate the serum, and with heparin as an anticoagulant for separating leukocytes for in vitro exposure to gamma radiation) 5–10 min before then 1 and 2 h after melatonin ingestion. Afterward, each sample was subdivided into nonirradiated and irradiated groups (10 mGy and 100 mGy). After irradiation, lymphocytes of samples were separated. The isolated lymphocytes in each group were permeabilized for DSB assessment and stained against the phosphorylated histone variant γH2AX. Results: Melatonin ingestion 1 and 2 h before irradiation caused a significant reduction in γH2AX foci. Results further indicate that the change in ingestion of melatonin from 1 to 2 h before exposure had no significant effect. In addition, melatonin administration showed no side effects. Conclusion: The present study showed that melatonin will prove effective in radioprotection against ionizing radiation (IR)-induced DNA damage in human lymphocytes. Our results suggest ingestion of 100-mg melatonin by patients before exposure to IR in radiology.

Estimation of cancer risk due to radiation exposure for some daily consumption of foods Akbar Abbasi, Vali Bashiry Journal of Cancer Research and Therapeutics 2020 16(8):64-67 Aims: Considering the increasing concern about the cancer risk caused by environmental radiological effects related to the food consumption, the study was carried out evaluate the activity concentrations and cancer risk assessments of 226 Ra,232 Th, and 40 K in 72 food samples collected from different suppliers in Tehran Province of Iran. Subjects and Methods: The specific activity concentration was determined by means of a high-resolution high-purity germanium gamma-spectroscopy system. The collected various sample groups were wheat, rice, meat, milk, and mushroom. Results: The maximum concentration of 226 Ra and 232 Th was found in the wheat sample, equal to 0.7862 Bq/kg and 0.968 Bq/kg, respectively, whereas for 40 K, it was 598.35 Bq/kg in the milk sample. The annual effective dose rate ranged from 2.47 μSv/y in mushroom to 64.66 μSv/y in rice. The average excess lifetime cancer risk (ELCR) was varied from 1.60 × 10–5 for mushroom to 4.20 × 10–4 for milk, with the total ELCR value from main daily diets 1.37 × 10–3, which was a little more than the acceptable ELCR limit of 10–3. Conclusions: The ELCR due to five main daily diets was a little more than the acceptable ELCR limit of 10–3 for radiological risk in general.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia,

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Neurological Sciences and Neurophysiology

Neuroinflammation in Alzheimer’s disease continuum Aslihan Taskiran-Sag, Müge Yemişçi Neurological Sciences and Neurophysiology 2020 37(4):155-163 Aging population brings an ever-increasing global burden of dementia, and Alzheimer's disease (AD) is the most frequent type worldwide. Many years of research have introduced characteristic cerebral histopathological and molecular changes in this disease. However, all attempts to establish an effective treatment have failed. In this review, we aim to address the basic evidence regarding the role of inflammatory mediators in AD and their link to the other pathogenetic pathways. Novel findings based on advanced biotechnology and bioinformatics are covered briefly, as well.

Long latency reflexes in patients with postural instability and ataxia Ersin Deneri, Nesibe Tilek, Aysel Çoban, Cengiz Tataroğlu Neurological Sciences and Neurophysiology 2020 37(4):164-169 Objectives: Distal electrical stimulation of an upper extremity mixed nerve can generate a reflex response from the trapezius muscle. This reflex response may have a central neural pathway and can be affected by postural changes. Materials and Methods: In this study, long latency reflexes (LLRs) from both distal and trapezius muscle were evaluated in patients with Parkinson's disease (PD) with and without postural dysfunction and in patients with cerebellar ataxias. Thirty-three patients with PD, 10 patients with degenerative cerebellar ataxia and 22 healthy volunteers were included in the study. LLRs were recorded from ipsilateral thenar and trapezius muscles. Latencies and amplitudes of LLRs obtained from thenar (thenar LLR) and trapezius (trapezius LLR) muscles were analyzed. Results: In patients with PD, thenar LLRs showed significant shortening in the onset latencies and significant increase in the amplitudes in comparison with healthy controls. Trapezius LLRs did not show any significant difference in latencies or amplitudes; however, these responses showed a significant absence in one or two components in patients with Parkinson's disease with postural dysfunction. Additionally, this reflex was not recorded in patients with cerebellar ataxia. Conclusion: Trapezius LLRs can give some information regarding the physiology of neural circuits responsible for postural arrangement. Cerebellar connections may have a major role in the generation of trapezius LLRs.

The role of vestibular evoked myogenic potential and the video head impulse test in patients with multiple sclerosis without radiologic findings Reyhan Surmeli, Mehmet Sürmeli, Gözde Günay, Ayşe Destina Yalçın, Ayşe Aslı Şahin Yılmaz, Fatma Kulalı Neurological Sciences and Neurophysiology 2020 37(4):170-175 Objective: The aim is to evaluate the vestibular system using the video head impulse test (vHIT) and vestibular evoked myogenic potentials (VEMP) in patients with multiple sclerosis (MS) without central vestibular involvement in magnetic resonance imaging (MRI), and to determine whether there was subclinical vestibular system impairment. Materials and Methods: The study comprised 27 patients with MS and 26 healthy participants. The participants had no lesions in the central vestibular system in an MRI taken in the past 3 months. Detailed neuro-otologic and neuro-ophthalmologic examinations were performed on all participants. Then, the Dizziness Handicap Inventory (DHI) was completed for subjective vestibular system evaluation. In addition, vHIT and cervical VEMP (cVEMP) were performed for objective vestibular system evaluation. The results were analyzed statistically. Results: The mean age of the patients in the MS group was 39.3 ± 11.4 years and 42.7 ± 9.7 years in the control group. The median DHI score was 4 (range, 0–8) in the MS group and 2 (range, 0–6) in the control group. There were no statistically significant differences between the DHI score averages of the groups. The mean vestibulo ocular reflex (VOR) gain in vHIT was 0.76 ± 0.21 in the MS group and 0.99 ± 0.13 in the control group. VOR gain was statistically significantly lower in patients with MS. The VOR gain cut-off level was considered as 0.8. Gain level was below the cut-off level in 53.7% of patients with MS. There was no cVEMP response in 31.5% of patients with MS. In addition, patients with MS had prolonged P1 and N1 latencies and decreased P1-N1 peak-to-peak amplitudes. Conclusion: We found subclinical involvement in electrophysiologic tests (vHIT and cVEMP) in patients with MS without MRI lesions and without subjective vestibular system symptoms. We believe that vHIT and cVEMP can be used for subclinical evaluation in patients with MS without central vestibular system involvement in MRI.

The association between causes and electrophysiology in myoclonus: When and why electrophysiology? Meral E Kiziltan, Aysegül Gündüz, M Hazal Ser, S Naz Yeni, Çigdem Özkara, Veysi Demirbilek, Cengiz Yalçınkaya, Günes Kızıltan Neurological Sciences and Neurophysiology 2020 37(4):176-182 Objective: We aimed to identify the possible causes of myoclonus and related electrophysiological features in a cohort of young patients. Patients and Methods: We performed a retrospective analysis of all clinical and electrophysiological recordings of patients who had myoclonus and were under 60 years between 2005 and 2018. The clinical data included age at examination, gender, age at onset, and main neurological or systemic findings, underlying cause and electrophysiological features constituted surface electromyogram, long-loop reflexes, electroencephalography, and somatosensory-evoked potentials. Results: In the study period, we identified 155 patients with myoclonus. Myoclonus was most commonly related with epilepsy and movement disorders. Myoclonus with epilepsy was the leading cause between 10 and 30 years, whereas myoclonus with movement disorders was more common after 30 years. In our country, SSPE was an important cause of myoclonus under the 20 years of age. We identified cortico-subcortical subtype followed by cortical, cortical reflex, subcortical-basal ganglia, subcortical-brainstem and propriospinal subtypes, and correlated these subtypes with relevant disorders. Conclusion: The electrophysiological classification provides anatomical subtyping, which is favorable in diagnosing certain cases such as brainstem and propriospinal myoclonus. Certain characteristics such as reflex nature of myoclonus and accompanying features narrow the list of differentials and help in making the diagnosis.

Sleep disorders in a shift worker population sample in Turkey Duygu Kurt Gok, İlker Ünal, Kezban Aslan Neurological Sciences and Neurophysiology 2020 37(4):183-189 Aims: This study aims to determine the sleep quality of night-shift workers, determine the prevalence and characteristics of sleep disorders related to shift work, and compare sleep characteristics between shift workers and day workers. Subjects and Methods: The study included 1473 individuals employed in three different areas (health, security, and labor) as shift (78.5%) or day (21.5%) workers in the city of Adana, Turkey. Data were collected using a structured questionnaire consisting of 132 questions. The questionnaire included demographic data, education level, socioeconomic status, shift schedule, accompanying health problems, sleep disorders and sleeping habits, the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, the Berlin Questionnaire, and the Restless Legs Syndrome (RLS) scale. Statistical Analysis Used: The SPSS for Windows 20.00 software package was used for statistical analyses. Results: Day workers and shift workers exhibited excessive daytime sleepiness in 17.1% and 24.9% (P = 0.004), poor sleep quality in 41.5% and 44.3% (P = 0.374), chronic insomnia in 8% and 16.2% (P < 0.001), RLS in 4.7% and 5.3% (P = 0.818), and sleep-disordered breathing in 7.3% and 7% (P = 0.864), respectively. Conclusions: Shift work significantly compromises sleep quality. In particular, fixed night shifts or rotating shift workers experience relatively higher rates of decline in subjective sleep quality, excessive daytime sleepiness, and chronic insomnia compared with day workers.

The ratios of estradiol and progesterone to testosterone influence the severity of facioscapulohumeral muscular dystrophy Ceren Hangul, Selen Bozkurt, Ugur Bilge, Sebahat Ozdem, Hasan Altunbas, Hilmi Uysal, Filiz Koc, Sibel Berker Karauzum Neurological Sciences and Neurophysiology 2020 37(4):190-196 Background: Facioscapulohumeral muscular dystrophy (FSHD) occurs as a consequence of genetic deletion of D4Z4 repeats on chromosome 4q35. Onset of FSHD is earlier in males, suggesting that testosterone may trigger the disease. In accordance, the rapid progression of disease in women after menopause suggests a protective role for estrogen and progesterone. No studies have examined levels of all these hormones in relation with the severity of FSHD. Aims: To evaluate the possible correlation between the severity of FSHD with sex hormones, age, and genetic deletion on chromosome 4q35. Subjects and Methods: D4Z4 repeat units were investigated in 33 patients (19 males/14 females) with FSHD. In the blood samples, luteinizing hormone, follicle-stimulating hormone, free estriol, estradiol, free testosterone and total testosterone, progesterone, 17-OH progesterone, prolactin, albumin, and fibrinogen were measured. The severity of FSHD was identified using a Clinical Severity Score (CSS) scaling system. Spearman's correlation and regression analyses were performed as statistical analyses. Results: Age (P = 0.001, r = 0.541) and total testosterone (P = 0.045, r = 0.351) were positively correlated, and the progesterone/total testosterone (P = 0.025, r = −0.390) and estradiol/total testosterone ratios (P = 0.025, r = −0.389) were negatively correlated with the severity of FSHD. Conclusions: Our results indicate that age, total testosterone, ratios of estradiol and progesterone to total testosterone, but not deletion on chromosome 4q35, have a significant relation with the severity of FSHD. Given that both estrogen and testosterone treatment are considered in therapy, our results suggest that estrogen and progesterone but not testosterone are likely to be more effective on the severity of FSHD.

Botulinum toxin injections for neurological disorders: Experience between 1994 and 2019 Cem Boluk, Yesim Gökçe, Aysegül Gündüz, Nurten Uzun Adatepe, Feray Karaali Savrun, Asim Kaytaz, Meral E Kızıltan Neurological Sciences and Neurophysiology 2020 37(4):197-202 Aim: Reported results of botulinum toxin (BoNT) injections vary widely in different studies and in different neurological disorders. The aim of this study was to investigate the efficacy and safety of BoNT injections for each neurological disorder and to report our experience in this area since 1994. Materials and Methods: All patients who were injected with BoNT since 1994 were included in this retrospective study. Age, gender, etiology, specific diagnosis, time from first symptom to first injection, type of BoNT (onabotulinum toxin-abobotulinum toxin), doses, treatment response, and complications were extracted from patient files. Etiologies were classified into five main groups: hyperkinetic movement disorders, focal spasticity, painful conditions, sialorrhea, and hyperhidrosis. Positive treatment response was defined as any objective clinical improvement determined by the attending physician and declared by the patient. Results: We determined that 1792 patients were considered for BoNT injections. Among them, 341 were not found to be suitable for injections or did not accept to have the procedure done. In total, 1451 different patients were included in the study. The most common indications for BoNT injection were hyperkinetic movement disorders (72.3%) and focal spasticity (15.2%). Other disorders included painful conditions, hyperhidrosis, and sialorrhea. In 74.3% of the patients, the only injected toxin was onabotulinum toxin, whereas 10.2% of the patients were injected only with abobotulinum toxin. In 14.7% of the patients, the injection type was changed from one to the other, due to ineffectiveness or unavailability. Response rates were 95.4% for focal spasticity, 92.6% for hyperkinetic movement disorders, 81.1% for painful conditions, 66.7% for hyperhidrosis, and 63.1% for sialorrhea. Severe complications were seen in 0.6% of the patients. Conclusion: BoNT injections seem to be effective in all of the neurological disorders which we investigated. Except for mild cosmetic complications, BoNT is generally safe in experienced hands.

Agomelatine is superior to melatonin in pain suppression: An experimental study Ali Okan Yucel, Devrim Demir-Dora, Mehmet Ferit İsbir, Babür Dora Neurological Sciences and Neurophysiology 2020 37(4):203-207 Objective: Agomelatine is a synthetic analog of melatonin with selective agonist action on melatonin MT1 and MT2 receptors and antagonistic effect on serotonin 5HT2c receptors. Similar to melatonin, it also has antinociceptive properties. There are only a few studies comparing the antinociceptive effects of agomelatine to melatonin. Methods: Male Wistar albino rats were grouped into seven treatment groups and a control group (8 animals each). Treatment groups received intraperitoneal injections of agomelatine 25 mg/kg, 35 mg/kg and 50 mg/kg; agomelatine 35 mg/kg + luzindole 10 mg/kg; melatonin 60 mg/kg and 90 mg/kg and melatonin 60 mg/kg + sertraline 10 mg/kg. Animals were placed on a hot plate and time to pain avoidance behavior was measured. Results: Agomelatine 25 mg/kg, 35 mg/kg and 50 mg/kg were significantly superior to placebo (all p < 0. 0001); agomelatine 35 mg/kg and 50 mg/kg were significantly superior to melatonin 60 mg/kg (p < 0.05 and p < 0.01, respectively) and melatonin 90 mg/kg (p < 0.001 and p < 0.001, respectively) in prolonging reaction times. Agomelatine 50 mg/kg was superior to melatonin 60 mg/kg + sertraline 10 mg/kg (p < 0,05); on the contrary; agomelatine 25 mg/kg was significantly inferior to this combination in prolonging reaction times (p = 0,041). Melatonin 90 mg/kg but not 60 mg/kg was significantly superior to placebo in prolonging reaction times (p < 0.0001). Both agomelatine 50 mg/kg and 35 mg/kg were superior to agomelatine 25 mg/kg (p < 0.0001 and p = 0.002, respectively), but the difference between agomelatine 50 mg/kg and 35 mg/kg was not significant. Conclusions: We demonstrated that agomelatine is superior to melatonin on pain behavior in a dose -dependent manner using an experimental pain model. The a ddition of a serotonergic agent increased the antinociceptive effect of melatonin in regard to agomelatine, but high doses of agomelatine were still more effective, suggesting a dose -dependent effect of agomelatine on 5-HT2c receptors.

Management of hardware infections in deep-brain stimulation: A 4-year, single-center experience Vural Hamzaoglu, Hakan Özalp, Okan Doğu, Nevra Öksüz, Sabri Aydın, Tolga Akbıyık, Ahmet Dağtekin, Emel Avcı, Celal Bağdatoğlu Neurological Sciences and Neurophysiology 2020 37(4):208-214 Objectives: The introduction of deep-brain stimulation (DBS) was a milestone in the treatment of movement disorders, intractable epilepsy, and severe psychiatric disorders. We aimed to identify risk factors for hardware infection in patients with these conditions who underwent DBS at our center over a 4-year period. Materials and Methods: Bilateral DBS was performed in seventy patients by the Department of Neurosurgery at the Mersin University School of Medicine between April 2016 and January 2020. The surgical indication was Parkinson's disease in 48 patients, dystonia in 11 patients (10 primary generalized and 1 secondary), and tremor in 11 patients (10 essential tremor and 1 other). Results: Infection was detected in eight patients (11.4%). There were no hardware complications other than infection or postoperative intracerebral hematomas. The entire device was explanted in four (50%) patients with infection; device explantation occurred at 3, 13, 19, and 42 months after surgery. The other 4 (50%) patients who developed infection were successfully treated with antibiotics without complication. A patient with primary dystonia who underwent bilateral globus pallidus interna DBS sustained a severe acute subdural hematoma due to trauma 45 days after electrode implantation but prior to stimulation. We elected not to explant the device after hematoma evacuation; delayed stimulation programming was successful. Conclusion: DBS surgeries are susceptible to complications related to the anatomic target, hardware, and the procedure itself. Infection is the most common complication; however, there is no established protocol for its treatment. Antibiotics and partial removal of the device may be a rational approach.

Craniopharyngiomas: Analysis of 68 surgical cases Emrah Akcay, Hakan Yılmaz, Hüseyin Berk Benek, Alper Tabanlı, Alaettin Yurt Neurological Sciences and Neurophysiology 2020 37(4):215-220 Objective: Although craniopharyngiomas are benign pathologies, they have surgical challenges due to their locations, infiltrations, and potential for neuroendocrine problems. We evaluated the surgical outcomes, complications, the neuroendocrine problems in patients who underwent total or subtotal resection, and to reveal the ideal treatment regimen. Materials and Methods: We retrospectively reviewed 68 patients who received pathologic results of craniopharyngioma between 1999 and 2019 in our neurosurgery clinic. The demographic characteristics, hormone levels, resection ratio (total/subtotal), residue and recurrence rate, and the complications after surgery were used in the analysis. Results: Twenty-six (38.2%) patients underwent total tumor removal, and 42 (61.8%) had subtotal removal. Fifteen (22%) patients had recurrence. Of the total tumor removal group, only one patient was determined as having recurrence. We detected hypothalamic–pituitary system deficiency in 15 patients with total removal and nine patients with subtotal removal. Of the 37 patients who had lesions smaller than 4 cm, only one died and 30 were in good health after surgery. Of the 31 patients who had lesions larger than 4 cm, five died and 15 were in poor or moderate health. Conclusion: Tumor size is one of the most important factors affecting surgical results. Subtotal tumor removal is associated with tumor recurrence and total removal with serious hypothalamic deficiency symptoms.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia,

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Preventive and Clinical Dental Research

Effect of titanium oxide and zirconium oxide nanoparticle incorporation on the flexural strength of heat-activated polymethyl methacrylate denture base resins – An in vitro experimental study Prasanth Viswambharan, AR Adhershitha International Journal of Preventive and Clinical Dental Research 2020 7(4):91-95 Introduction: Flexural strength is one of the most important properties which determine the clinical success of dentures. Even though titanium oxide nanoparticles (nano-TiO2) and zirconium oxide nanoparticles (nano-ZrO2) are extensively used to modify the properties of polymethyl methacrylate (PMMA) resin, there is negligible documentation in the literature comparing these two. Aim: The aim of the study is to find out and compare the effect of incorporation of 1 weight % nano-TiO2 and nano-ZrO2 on the flexural strength of heat-activated PMMA resin. Materials and Methods: 1 weight % of TiO2 and ZrO2 nanoparticles were weighed using a digital weighing balance and mixed with PMMA resin powder using the geometric dilution method. Sixty “35 mm × 10 mm × 3 mm” rectangular-shaped specimens fabricated were divided into three different groups, each containing twenty samples each. The specimens were loaded to failure at a crosshead speed of 1 mm/min and with 500 N load cell in a Universal Instron Testing Machine, Model 3345. Flexural strength was registered by the machine with 0.001 MPa precision. Results: PMMA with nano-TiO2 group had the maximum flexural strength, load at maximum flexure, and load at break followed by unreinforced PMMA and PMMA with nano-ZrO2. Statistically significant difference was noted between the three groups (P < 0.001). Post hoc analysis using Tukey's post hoc test showed a statistically significant difference for all three pair-wise comparison. Conclusions: Within the limitations of this study, it can be concluded that nano-TiO2 greatly enhanced the flexural strength, load at maximum flexure load, and load at break of PMMA resin, whereas nano-ZrO2 significantly reduced these properties of PMMA.

Prevalence of periodontal diseases in orthodontic patients Ujjwal Priyadarsi, Mohammad Shahbaz Alam, Abid Hussain, Farrukh Azam, Priyanka Kumari, Md Abu Nafe International Journal of Preventive and Clinical Dental Research 2020 7(4):96-98 Objective: The objective was to investigate the association between orthodontic treatment and periodontitis in a representative sample of Jharkhand. Methodology: The clinical examinations at six sites per tooth were assessed using visible plaque index (VPI), gingival bleeding index (GBI), bleeding on probing (BOP), periodontal probing depth (PPD), and clinical attachment loss (CAL). A manual Williams probe (Neumar, São Paulo, Brazil) was used, except for the VPI. Data analysis was done. Results: The median percentage values of sites positive for VPI, GBI, and BOP were calculated for each group and compared using a Mann–Whitney test and the mean values for PPD and CAL with a Student's t-test. Intragroup comparisons between teeth were performed with Tukey's analysis of variance. The level of significance was set at 5%. Conclusion: The use of orthodontic appliances is not necessarily related to worsening periodontal conditions. The results of the present study reinforce the importance of susceptibility to periodontal disease independent of the presence of a well-known retentive plaque factor, i.e., orthodontic appliances and/or bands.

Awareness and attitude toward COVID-19 among the students of a rural tertiary care center and dental college: A cross-sectional study AR Adhershitha, Prasanth Viswambharan, Sheela Virginia Rodrigues International Journal of Preventive and Clinical Dental Research 2020 7(4):99-103 Introduction: Awareness, attitude, and practice play a major role in containing any infectious disease. Coronavirus disease 2019 (COVID-19) has no definitive treatment or vaccines; hence, it is momentous to spread awareness regarding the prevention strategies. It is crucial for the government and concerned authorities to understand the students' perception and attitude in the time of the current pandemic. Aim: The aim of this study is to assess the level of awareness among the students of Government Dental College Alappuzha, a rural tertiary care center and Dental College in Kerala, India, regarding COVID-19 and their attitude toward the pandemic. Methodology: Questionnaire which included 21 items was used for the research. Observed data were coded, tabulated, and analyzed using IBM SPSS Statistics for Windows (Version 20.0. Armonk, NY, USA: IBM Corp.). The total awareness score calculated was 20. Comparison between gender (males/females) and study groups (preclinical students/clinical students) was made using the Chi-square test. Comparison of total awareness scores between study groups was made using independent t-test. Results: Most of the study participants across study groups regularly kept track of the latest news on COVID-19 and perceived it to be of moderate or very dangerous risk though they were quite optimistic of its control. About 96% of males and 82% of females felt it is necessary to get mental health help if one panics in lieu of the pandemic situation. The mean total awareness score (out of 20) was 15.16 ± 1.81. There was no significant difference in total awareness score based on gender (15.23 ± 2.24 for males and 15.15 ± 1.71 for females) and also among the category of students (14.88 ± 1.94 for preclinical students and 15.35 ± 1.69 among clinical students). Conclusions: Attempts should be made for increasing the awareness regarding the preferred method of hand hygiene, protocol for performing aerosol-generating procedures, and airborne infection isolation room.

Knowledge attitude and practice of school personnel on COTPA Dhwani Desai, Dhvani Desai International Journal of Preventive and Clinical Dental Research 2020 7(4):104-106 Background: The “Cigarettes and Other Tobacco Products (Prohibition of Advertisement and Regulation of Trade and Commerce, Production, Supply, and Distribution) Act (COTPA)” has been formulated to control the Tobacco epidemic in India. School personnel serve as role models for students and have daily interaction with students, while college students may be under the influence of adolescent behavior and cigarettes is easier to procure. Materials and Methods: A cross-sectional questionnaire-based study carried out on a convenience sample of 100 school personnel aged 18–60 years, participated in the study. Five schools were undertaken in this study on the basis of convenience sampling. All the school personnel preseent on the day of conduction of survey were included in the study. Results: The awareness of school personnel in relation to COTPA ranges between 21% and 79% whereas least awareness (80%) was seen in relation to loose cigarettes not to be sold. Conclusion: The present study indicates that participants have lesser and inappropriate knowledge and attitude toward COTPA and majority of not taken any step to implement COTPA in their work place

Trends in the patterns of maxillofacial fractures in Kolkata Gourab Das, Dhritiman Pathak, Bharat Shukla, Ruchira Shukla, Dazy Patel, Krishna Mondal International Journal of Preventive and Clinical Dental Research 2020 7(4):107-110 Background:- The maxillofacial skeleton is commonly fractured due to its prominent position. Maxillofacial fractures lead to cosmetic disfigurement as well as problems in oral functioning. Aim: The aim of this study was to determine the incidence, etiology, mode, and the pattern of fractures in the maxillofacial region. Methods: A retrospective study of maxillofacial injuries at ESIC Medical College and Hospital, Joka (Kolkata) between Feb 2018 to April 2019 was conducted and data extracted from patients who were either treated in emergency room or in outpatient department. Results and Conclusion: The study concluded that better road safety laws need to be enforced along with the improvement of the education and socio-economic setup.

Temporomandibular disorders: An updated review M Nazargi Mahabob International Journal of Preventive and Clinical Dental Research 2020 7(4):111-114 A group of conditions related to temporomandibular joint (TMJ) is called as “temporomandibular disorder” (TMD). Several attempts were made to classify TMD based on the frequency of occurrence, etiology, and anatomy, but they have had some shortfalls, and one mostly accepted is diagnostic criteria/TMD classification. TMD is a group of clinical problems; it involves either TMJ or its associated structures separately or combination. Any factor that affects one part of the system is likely to have an impact on the other parts also, so it is essential to approach carefully when considering likely signs and symptoms of TMD. About 20%–30% of the adult populations are affected to some degree of TMD, and it is predominately affected young and middle-aged adults. The prevalence rate of TMD problems twice common in females than the males. The etiology of TMD is inconclusive, and now, it has been accepted that multiple factors play a role in TMD. Since it is multifactorial, treatment should be planned according to that and varies patient to patient. Majority of the patients having mild-to-moderate TMD and conservative treatment approach over surgery results in satisfactory outcomes. The aim of this review is to evaluate the recent updates and propose solutions for patients with TMD.

Prosthodontic rehabilitation of an edentulous hemimandibulectomy patient Saumil Chetan Sampat, Mistry Saloni, Banga Parmeet, Dole Vinay, Dubey Amol International Journal of Preventive and Clinical Dental Research 2020 7(4):115-118 Edentulous patients with lateral discontinuity defects of the mandible pose a challenge for the prosthodontist. With variable degrees of bony and soft-tissue resection, the prosthodontic prognosis is dependent on a number of complex factors. Complete dentures in such patients are primarily given for improvement of esthetics. In a selected few patients, however, such prosthesis may improve speech and masticatory function. This case report describes the use of two rows of nonanatomic teeth (in the maxillary denture) on the unresected side to broaden the occlusal table, thus fulfilling the patient's needs and requirements.

Apexification in primary central incisor Nandita Mohan, Shriyam Sharan, Supreeya Patel, Divya Nigam, Aarti Kumari, Silpi Chatterjee International Journal of Preventive and Clinical Dental Research 2020 7(4):119-121 The upper deciduous incisors are frequently the teeth most commonly affected either by dental caries or due to the impact of trauma. In such cases, there may be complete coronary destruction of teeth. As they erupt around 7½–9 months of age and the roots only complete at approximately 18–24 months, pulp involvement may occur even before the end of this process. Hereby, we highlight the case of a 15-month-old male patient who reported with a history of trauma. Treatment plan of apexification was made after confirming with multiple radiographs. Root-end closure was obtained after a period of 7 months.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia,

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Medical Journal

Reliability of international hip dysplasia institute classification for the developmental dysplasia of the hip among different medical personnel in Iraq Jagar Omar Doski Mustansiriya Medical Journal 2020 19(2):41-44 Background: The international hip dysplasia institute (IHDI) classification is a new method for quantifying the severity of the developmental dysplasia of the hip (DDH). Objectives: This study aimed to compare the reliability of this classification between different medical personnel such as pediatricians, general practitioners, and family doctors in addition to orthopedic surgeons and radiologists. Methods: Hundred pelvic radiographic films (with 200 hips) were randomly selected from the files of children already diagnosed and treated as DDH cases. These films were analyzed by 12 independent observers of four different specialties: three orthopedic surgeons (Ortho Group), three radiologists (Radio Group), three pediatricians (Pediat Group), and three general practitioners (GP Group). Results: The average measures (Cronbach's alpha) for the intraclass correlation coefficient (ICC) for absolute agreement between all observers was 0.874 (with 95% confidence intervals between 0.780 and 0.925). This was considered as having a good level of reliability and agreement between all observers. The ICC for agreement between the observers of radio group showed the highest score (0.904) while that between those of GP Group had the lowest one (0.826). However, during the comparison between the mean score of each group with that of the other groups by the one-way ANOVA method, there was no statistically significant difference between all groups (P values were 0.563, 0.415, 0.399, and 0.291 respectively). Conclusion: The IHDI classification method for cases of DDH has a good level of reliability among different medical personnel regardless of their specialties.

Management of florid diabetic retinopathy Faiz I Shakarchi, Ahmed F Shakarchi, Shadha A Al-Bayati Mustansiriya Medical Journal 2020 19(2):45-48 Background: Florid diabetic retinopathy (FDR) is a severe form of proliferative diabetic retinopathy associated with high risk of blindness. Aim: The aim of this study is to evaluate the efficacy and safety of prompt intravitreal injection of bevacizumab followed by complete pan-retinal photocoagulation (PRP) for treating eyes with FDR. Setting and Design: Prospective, interventional case series. Patients and Methods: Patients with FDR were treated initially with intravitreal injections of bevacizumab 1.25 mg. One week after the injection, patients were sent for wide field fluorescein angiography (WFA), and PRP was performed in two sessions, 2 weeks apart. Patients were examined every 2–4 weeks to determine the status of new vessels (NVs). Additional laser burns were applied in cases with recurrence of NVs. Statistical Analysis: Numbers and percentages were calculated and reported. Results: Eleven patients (18 eyes) with FDR were included. All included patients had poorly controlled diabetes mellitus with mean glycated hemoglobin of 10.6%. One week after the injection, all eyes showed clinical regression of NVs. WFA showed extensive areas of peripheral retinal capillary nonperfusion. Eight weeks after the injection, three eyes (16.7%) showed recurrent increase in NVs, and additional laser therapy was performed for these eyes with special attention to ablating the areas of peripheral capillary non-perfusion. After 16 weeks from the primary treatment, 15 eyes (83.3%) had complete neovascular regression on clinical and angiographic assessment. Pars planavitrectomy was required for three eyes (16.7%) with tractional retinal detachment (2 eyes) or macular epi-retinal membranes (one eye). Conclusions: According to this study, most cases with FDR stabilized after prompt bevacizumab injection followed by complete PRP with special attention for ablating the peripheral capillary nonperfusion areas, guided by WFA images.

Male circumcision using bone cutter with thermal cautery Salih Abdul Kafi Hammoodi Al-Ani Mustansiriya Medical Journal 2020 19(2):49-53 Background: Bone cutter is a widely used procedure to cut the prepuce during circumcision. Aim of the study: The aim of the study was to assess the safety of circumcision of male using bone cutter with thermal cautery, including the operative time and healing time and the effect of dressing on rate of infection and bleeding. Materials and Methods: Over 20 years period from 1996 till 2015, six thousands of males were circumcised under local anesthesia (in form local infiltration of 1% plain lidocaine 5 min before circumcision and xylocaine spray after the procedure) using a bone cutter with thermal cautery, the first assistant is to fix the upper limbs, while the main assistant is to fix the knees in a fully extended position by the left hand, while the right hand used to elevate the two mosquitoes, then by using thermal cautery to cut the foreskin above the jaw of bone cutter and by using S-ring in certain situation to fix the bone cutter tightly. Results: Six thousands males were included in this study. The mean operative time was 1-2 minutes, healing time was 5-7 days, 387 cases (6.45%) developed early & late complications, 180 (3%) bleeding, 195 (3.25%) developed infection, 3 (0.05%) with mild glans injury need dressing only for 24-48 hours only 9 (0.15%) need re-circumcision later on in the same procedure. Conclusions: Bone cutter with thermal cautery circumcision is feasible with a relatively lower complications rate, shorter operative time, and short healing time.

Evaluation of maternal serum sestrin2 levels in preeclampsia and their relationship with the Disease severity Raghad Ahmed Fadhil, Lilyan W Sersam Mustansiriya Medical Journal 2020 19(2):54-58 Background: Preeclampsia (PE) is considered one of the major causes of both maternal and fetal mortality and morbidity. Advances have been made on understanding the pathophysiology of this pregnancy-specific disorder. Sestrin2 (SESN2) is a metabolic regulator protein, whose expression is induced in response to exposure to different adverse effects such as hypoxia, DNA damage, or oxidative stress, thus acting as cytoprotective. Objective: The objective of the study was to investigate the levels of maternal serum SESN2 in preeclamptic and uncomplicated pregnancies and their association with the disease severity. Patients and Methods: This was a case–control study conducted at the Department of Obstetrics and Gynecology at Al-Yarmouk Teaching Hospital in Iraq – Baghdad city from the first of March till the end of November 2019. The study included a total of 92 pregnant women, 27 with a healthy pregnancy, 33 with nonsevere PE, and another 32 having severe PE. From all participants, blood samples were collected for the evaluation of serum SESN2 levels using enzyme-linked immunosorbent assay. Results: The mean readings of SESN2 for normal pregnancies were 5.22 ± 1.71 ng/ml which was significantly lower than that for the nonsevere PE group (8.41 ± 1.42 ng/ml), while SESN2 levels were the highest among those with severe PE (16.92 ± 5.15 ng/ml). A negative correlation was found between each of GA at delivery, birth interval, and birth weight and the SESN2 level (P = 0.001); while mean arterial pressure positively correlated with SESN2 levels (P = 0.001), the cutoff value for the diagnosis of severe PE was 9.95 ng/ml (sensitivity of 93.8% and specificity of 98.8%). Conclusion: Maternal serum SESN2 levels are significantly higher in pregnancies complicated by severe PE than nonsevere PE and control groups. It could be a useful biomarker that can help in diagnosing severe PE.

Assessment of left ventricular longitudinal function in hypertensive patients without left ventricular hypertrophy by mitral annular plane systolic excursion Samara Mohammad Khider, Ghalib Al-Shareefi Mustansiriya Medical Journal 2020 19(2):59-65 Background: Hypertension is an important risk factor for many cardiovascular diseases worldwide. Assessment of left ventricular (LV) systolic function has a major diagnostic and prognostic importance in patients with hypertension. The use of mitral annular plane systolic excursion in the assessment of LV systolic dysfunction is helpful especially in cases of poor imaging quality, “since good imaging quality is needed for the modern echocardiographic techniques. Objectives: Detection of early subclinical LV longitudinal systolic dysfunction in hypertensive patients without LV hypertrophy (LVH) with preserved ejection fraction by mitral annular plane systolic excursion. Patients and Methods: A comparative case-control study which took place at Al-Yarmouk Teaching Hospital in Baghdad/Iraq from October 2018 to October 2019. The study population consisted of 60 patients without LVH and 60 healthy subjects considered as controls. Echocardiographic parameters for left ventricular systolic assessments were done for all subjects. Results: Mean peak annular systolic velocity was significantly lower in hypertensive patients without LVH compared to controls (P = 0.034). There was no significant difference between hypertensive patients without LVH and controls regarding mitral annular plane systolic excursion (P = 0.4). There was positive linear correlation between mitral annular plane systolic excursion and peak annular systolic velocity for hypertensive patients without LVH (r = 0.535, P = 0.015). Conclusion: Although there was a significant linear correlation between mitral annular plane systolic excursion and peak systolic velocity and both are considered as a surrogate for LV longitudinal systolic function, mitral annular plane systolic excursion cannot be used for assessment of LV longitudinal systolic function in patients with hypertension without LVH.

The portrayal of microbes in respiratory medicine M V Raghavendra Rao, Vijay K Chennamchetty, Dilip Mathai, Mahendra Kumar Verma, Tiara Calvo Leon, Pamphil Igman, Surekha Bhat, Mohammad Ismail Nizami, Sanjay Kumar Agarwal, Lakshmi Hitesh Billa, Abrar A Khan Mustansiriya Medical Journal 2020 19(2):66-72 Respiratory diseases caused by a number of infectious agents including Streptococcal pneumonia, streptococcal pyogenes, Klebsiella pneumonia H. influenzae, Legionella pneumophilia, Mycoplasma pneumonia, Coxiella Bunetii, chlamydia pisittaci. These microbes enter into the lungs and cause primary cases of pneumonia. The whole respiratory epithelium down to the internal bronchioles is ciliated. The cilia and the thin film of mucus covering them have the critical function of trapping foreign particles, including bacteria, and propelling them toward the pharynx. They contribute to the prevention of respiratory infection as they do the macrophages utilizing their secretory, phagocytic, and bactericidal activity. Despite the wonderful defense, the bacterium escapes and settles in the lungs to produce diseases. Pneumonia is the term used to describe inflammation of the lung. Pneumococcal pneumonia is characterized by homologous consolidation of one or more lobes or segments. Pneumococcal pneumonia occurs at all ages but most frequently in early and middle adult life. Pneumonia is characterized with the rise in body temperature 39-40oC, remain associated with painful cough initially dry, but later patient develops production of tenacious sputum, which is often rusty and occasionally bloodstained. Staphylococcal pneumonia is caused due to Streptococcus aureus, which may occur either as a primary respiratory infection or as a blood-borne infection from a staphylococcal lesion elsewhere in the body. Klebsiella pneumonia is caused due to K. pneumoniae, a rare disease with high mortality. There is usually massive consolidation and excavation of one or more lobes, with the upper lobes being most often involved and with large amounts of purulent sputum, sometimes characteristic red currant jelly sputum. Legionella pneumonia is caused by Gram-negative bacillus L. pneumophila, which is usually transmitted in water droplets from infected cisterns used to provide water for showers, particularly in warm climates. It is often a serious and occasionally a fatal illness. C. psittaci causes psittacosis (ornithosis), a systemic illness contracted from infected birds. Pneumonia associated with it may be extensive, with severe toxemia. M. pneumoniae is a pleomorphic bacterium; symptoms of mycoplasma pneumonia are mild compared to other cases of pneumonia (walking pneumonia). On the other hand, liver function test derangements and dyselectrolytemia are more common. It is susceptible to tetracyclines though a few strains are sensitive only to erythromycin.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia,

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Otolaryngology & Head and Neck Surgery

Imaging-based navigation technologies in head and neck surgery Purpose of review Image guided navigation has had significant impact in head and neck surgery, and has been most prolific in endonasal surgeries. Although conventional image guidance involves static computed tomography (CT) images attained in the preoperative setting, the continual evolution of surgical navigation technologies is fast expanding to incorporate both real-time data and bioinformation that allows for improved precision in surgical guidance. With the rapid advances in technologies, this article allows for a timely review of the current and developing techniques in surgical navigation for head and neck surgery. Recent findings Current advances for cross-sectional-based image-guided surgery include fusion of CT with other imaging modalities (e.g., magnetic resonance imaging and positron emission tomography) as well as the uptake in intraoperative real-time ‘on the table’ imaging (e.g., cone-beam CT). These advances, together with the integration of virtual/augmented reality, enable potential enhancements in surgical navigation. In addition to the advances in radiological imaging, the development of optical modalities such as fluorescence and spectroscopy techniques further allows the assimilation of biological data to improve navigation particularly for head and neck surgery. Summary The steady development of radiological and optical imaging techniques shows great promise in changing the paradigm of head and neck surgery. Correspondence to Jonathan C. Irish, MD, Princess Margaret Cancer Centre and University Health Network, TECHNA Institute, Guided Therapeutic (GTx) Program, Toronto, 200 Elizabeth St 8NU-882, Toronto, ON, Canada, M5G 2C4. Tel: +1 (416) 340 3113; e-mail: Jonathan.Irish Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Oral potentially malignant disorders: new insights for future treatment Purpose of review The purpose of this review is to define the issues regarding oral potentially malignant disorders (OPMDs) and provide an overview of currently available treatments and ongoing clinical trials for future opportunities. Recent findings Nowadays, the treatment of choice of OPMD is surgery, whose role in preventing malignant transformation is however limited because of the high rate of recurrence and field cancerization. There have been several attempts of combining systemic therapies with surgery to reduce risk of malignant transformation. The identification of biomarkers that could predict malignant transformation is crucial in better tailoring the risk profile and possible therapeutic approaches. Summary Loss of heterozygosity remains the most predictive marker of malignant transformation; however, role of specific microRNA and OPMD immune infiltration are emerging as potential biomarkers. Given the failure of previous trials with various chemopreventive strategies, new strategies should be defined to address the issue of systemic prevention of malignant transformation. Recent updates about immune infiltration and the immune-equilibrium concept for OPMD could shed light into new preventive approaches. Correspondence to Paolo Bossi, Department of Medical and Surgical Specialties, Medical Oncology, Radiological Sciences and Public Health University of Brescia, ASST-Spedali Civili, Piazzale Spedali Civili 1, 25123 Brescia, Italy. Tel: +39 0303998969; e-mail: paolo.bossi Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Therapeutic challenges in radiation-induced salivary gland cancers Purpose of review To give an overview of recent advances in therapeutic approaches of radiation-induced salivary gland cancers (ri-SGCs). Recent findings Reirradiation with protons and carbon ions demonstrated to be feasible, safe and to offer good local control rates, with the possibility of overcoming radioresistance and dosimetric issues in previously irradiated cancer patients. Chromosomal rearrangements, gene fusions and expression profiles are important to identify specific cancer subtypes and can guide tailored systemic therapy. Summary Ri-SGCs are rare and heterogeneous. Patients are often heavily pretreated and at risk of toxicities, and their management remain challenging. A multidisciplinary approach in referral centers is mandatory. Knowledge about SGCs cellular and molecular mechanisms is constantly evolving. In the last years, novel advances in therapeutic approaches, such as carbon ion radiotherapy, are emerging as safe and effective options in active treatment, but further efforts are needed to offer tailored personalized treatments and to improve survival. Correspondence to Sara Ronchi, MD, Radiation Oncology Clinical Department, National Center for Oncological Hadrontherapy (CNAO), Strada Campeggi 53, 27100 Pavia, Italy. Tel: +39 0382078501; e-mail: sara.ronchi Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

A roadmap of six different pathways to improve survival in laryngeal cancer patients Purpose of review Laryngeal cancer continues to require improvement in earlier stage diagnosis and better imaging delineation of disease, and hence ‘more evidence-based’ selection of treatment, as recent evidence suggests that related mortality, in the last decades, has not significantly decreased worldwide. Even though the reasons are not fully understood, there persists an urgency for a review and development of future strategies to embrace such clinical and diagnostic challenges from a political, societal, as well as scientific and clinical points of view. Recent findings This review of the published literature suggests that survival improvement in laryngeal cancer may be achieved by fuelling and combining at least some or all of six targeted agendas: documentation of disease global incidence and national burden monitoring; development and implementation of high-quality cancer registries; education on risk factors and hazardous habits associated with laryngeal cancer for the general population; active modification of proven at-risk population lifestyles; centralization of treatment; and use of machine learning of gathered ‘big data’ and their integration into approaches for the optimization of prevention and treatments strategies. Summary Laryngeal cancer should be tackled on several fronts, commencing with disease monitoring and prevention, up to treatment optimisation. Available modern resources offer the possibility to generate significant advances in laryngeal cancer management. However, each nation needs to develop a comprehensive approach, which is an essential prerequisite to obtain meaningful improvement on results. Correspondence to Patrick J. Bradley, 10 Chartwell Grove, Mapperley Plains, Nottingham NG3 5RD, UK. E-mail: pjbradley Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Immediate dental implant placement and restoration in the edentulous mandible in head and neck cancer patients: a systematic review and meta-analysis Purpose of review Oral rehabilitation with dental implants in head and neck cancer (HNC) patients is challenging. After tooth removal prior to radiotherapy, immediate placement of dental implants during panendoscopy or surgery is thought to reduce the oral rehabilitation time improving patients’ quality of life. Recent findings There is lack of consensus on the timing of dental implant placement and loading protocols. The aim of this study was to perform a systematic review of the literature regarding the performance and survival rate of immediately inserted dental implants placed prior to radiotherapy. Of 1003 articles, 10 were finally included comparing immediate vs. delayed placement of implants and comparing the effect of radiotherapy on immediately placed implants. Meta-analysis demonstrated a slightly higher survival of immediately placed implants compared with postponed placed implants [risk ratio: 0.92, 95% confidence interval (95% CI): 0.48–1.78, P = 0.81, I2 = 0%]. The other meta-analysis comparing radiotherapy vs. nonradiotherapy showed a clearly better survival of immediately placed implants not having received radiotherapy (risk ratio: 5.02, 95% CI: 0.92–27.38, P = 0.10, I2  = 56%). Summary Guidelines are recommended for immediate dental implant placement in the edentulous mandible in HNC patients prior to radiotherapy to allow homogeneity regarding the treatment protocols and thus comparison of treatment outcomes. Correspondence to Frank K.J. Leusink, MD, PhD, Amsterdam UMC, location VUmc, Department of Oral and Maxillofacial Surgery, De Boelelaan 1118, 1081 HZ Amsterdam, The Netherlands. Tel: +31 20 444 1023; fax: +31 20 444 1005; e-mail: f.leusink Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Website (www.co-otolaryngology.com). This is an-open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Treatment of persistent/recurrent nodal disease in nasopharyngeal cancer Purpose of review Persistent or recurrent disease in the neck lymphatics is an unusual pattern of failure in nasopharyngeal carcinoma (NPC) after definitive radiotherapy or chemoradiotherapy. The purpose of this review is to critically synthesize the current knowledge regarding salvage treatment of this unique form of failure in NPC. Recent findings Surgery in the form of radical neck dissection has been established as the standard salvage treatment with 5-year regional control of 60–86%. Recent shift in paradigm has resulted in the use of modified or selective neck dissection as salvage surgery in some centers. Risk factors for poor survival outcome include recurrent nodal disease, number of involved lymph nodes, extracapsular extension, high lymph node ratio, and positive resection margin. There are no well controlled studies on the role of additional radiotherapy or chemotherapy to improve local control or survival after salvage neck dissection in this group of patients with regional failure. Summary There is limited literature regarding the extent of surgical dissection in treating nodal persistent or recurrent disease. Prospective studies are also needed to determine whether adjuvant therapy improves treatment outcomes. Correspondence to Wai-Tong Ng, Department of Clinical Oncology, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Pokfulam, Hong Kong SAR, China. Tel: +852 2255 4352; fax: +852 2872 6426; e-mail: ngwt1 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia,

Telephone consultation 11855 int 1193,

Anesthesia & Analgesia

Clinical Outcomes of Pregnant and Postpartum Extracorporeal Membrane Oxygenation Patients BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) as a rescue therapy for cardiopulmonary failure is expanding in critical care medicine. In this case series, we describe the clinical outcomes of 21 consecutive pregnant or postpartum patients that required venovenous (VV) or venoarterial (VA) ECMO. Our objective was to characterize maternal and fetal survival in peripartum ECMO and better understand ECMO-related complications that occur in this unique patient population. METHODS: Between January 2009 and June 2019, all pregnant and postpartum patients treated with ECMO for respiratory or circulatory failure at a single quaternary referral center were identified. For all patients, indications for ECMO, maternal and neonatal outcomes, details of ECMO support, and anticoagulation and bleeding complications were collected. RESULTS: Twenty-one obstetric patients were treated with ECMO over 10 years. Thirteen patients were treated with VV ECMO and 8 patients were treated with VA ECMO. Six patients were pregnant at the time of cannulation and 3 patients delivered while on ECMO; all 6 maternal and infant dyads survived to hospital discharge. The median gestational age at cannulation was 28 weeks (interquartile range [IQR], 24–31). In the postpartum cohort, ECMO initiation ranged from immediately after delivery up to 46 days postpartum. Fifteen women survived (72%). Major bleeding complications requiring surgical intervention were observed in 7 patients (33.3%). Two patients on VV ECMO required bilateral orthotopic lung transplantation and 1 patient on VA ECMO required orthotopic heart transplantation to wean from ECMO. CONCLUSIONS: Survival for mother and neonate are excellent with peripartum ECMO in a high-volume ECMO center. Neonatal and maternal survival was 100% when ECMO was used in the late second or early third trimester. Based on these results, ECMO remains an important treatment option for peripartum patients with cardiopulmonary failure.

Efficiency Metrics at an Academic Freestanding Ambulatory Surgery Center: Analysis of the Impact on Scheduled End-Times BACKGROUND: Understanding the impact of key metrics on operating room (OR) efficiency is important to optimize utilization and reduce costs, particularly in freestanding ambulatory surgery centers. The aim of this study was to assess the association between commonly used efficiency metrics and scheduled end-time accuracy. METHODS: Data from patients who underwent surgery from May 2018 to June 2019 at an academic freestanding ambulatory surgery center was extracted from the medical record. Unique operating room days (ORDs) were analyzed to determine (1) duration of first case delays, (2) turnover times (TOT), and (3) scheduled case duration accuracies. Spearman’s correlation coefficients and mixed-effects multivariable linear regression were used to assess the association of each metric with scheduled end-time accuracy. RESULTS: There were 1378 cases performed over 300 unique ORDs. There were 86 (28.7%) ORDs with a first case delay, mean (standard deviation [SD]) 11.2 minutes (15.1 minutes), range of 2–101 minutes; the overall mean (SD) TOT was 28.1 minutes (19.9 minutes), range of 6–83 minutes; there were 640 (46.4%) TOT >20 minutes; the overall mean (SD) case duration accuracy was −6.6 minutes (30.3 minutes), range of −114 to 176; and there were 389 (28.2%) case duration accuracies ≥30 minutes. The mean (SD) scheduled end-time accuracy was 6.9 minutes (68.3 minutes), range of −173 to 229 minutes; 48 (15.9%) ORDs ended ≥1 hour before scheduled end-time and 56 (18.6%) ORDs ended ≥1 hour after scheduled end-time. The total case duration accuracy was strongly correlated with the scheduled end-time accuracy (r = 0.87, 95% confidence interval [CI], 0.84-0.89, P < .0001), while the total first case delay minutes (r = 0.12, 95% CI, 0.01-0.21, P = .04) and total turnover time (r = −0.16, 95% CI, 0.21-0.05, P = .005) were less relevant. Case duration accuracy had the highest association with the dependent variable (0.95 minutes changed in the difference between actual and schedule end time per minute increase in case duration accuracy, 95% CI, 0.90-0.99, P < .0001), compared to turnover time (estimate = 0.87, 95% CI, 0.75-0.99, P < .0001) and first case delay time (estimate = 0.83, 95% CI, 0.56-1.11, P < .0001). CONCLUSIONS: Standard efficiency metrics are similarly associated with scheduled end-time accuracy, and addressing problems in each is requisite to having an efficient ambulatory surgery center. Pursuing methods to narrow the gap between scheduled and actual case duration may result in a more productive enterprise.

Postoperative Morbidity and Mortality in Diabetic Patients After Fast-Track Hip and Knee Arthroplasty: A Prospective Follow-up Cohort of 36,762 Procedures BACKGROUND: Diabetes increases the risk of adverse outcomes in surgical procedures, including total hip and knee arthroplasty (THA/TKA), and the prevalence of diabetic patients undergoing these procedures is high, ranging from approximately 8% to 20%. However, there is still a need to clarify the role of diabetes and antihyperglycemic treatment in a fast-track THA/TKA setting, which otherwise may decrease morbidity. Consequently, we investigated the association between diabetes and antihyperglycemic treatment on length of stay (LOS) and complications following fast-track THA/TKA within a multicenter fast-track collaboration. METHODS: We used an observational study design on data from a prospective multicenter fast-track collaboration on unselected elective primary THA/TKA from 2010 to 2017. Complete follow-up (>99%) was achieved through The Danish National Patient Registry, antihyperglycemic treatment established through the Danish National Database of Reimbursed Prescriptions and types of complications leading to LOS >4 days, 90-day readmission or mortality obtained by scrutinizing health records and discharge summaries. Patients were categorized as nondiabetic and if diabetic into insulin-, orally, and dietary-treated diabetic patients. RESULTS: A total of 36,762 procedures were included, of which 837 (2.3%) had insulin-treated diabetes, 2615 (7.1%) orally treated diabetes, and 566 (1.5%) dietary-treated diabetes. Overall median LOS was 2 (interquartile range [IQR]: 1–3) days, and mean LOS was 2.4 (standard deviation [SD], 2.5) days. The proportion of patients with LOS >4 days was 6.0% for nondiabetic patients, 14.7% for insulin-treated, 9.4% for orally treated, and 9.5% for dietary-treated diabetic patients. Pharmacologically treated diabetes (versus nondiabetes) was independently associated with increased odds of LOS >4 days (insulin-treated: odds ratio [OR], 2.2 [99.6% confidence interval {CI}, 1.3–3.7], P < .001; orally treated: OR, 1.5 [99.6% CI, 1.0-2.1]; P = .002). Insulin-treated diabetes was independently associated with increased odds of “diabetes-related” morbidity (OR, 2.3 [99.6% CI, 1.2-4.2]; P < .001). Diabetic patients had increased renal complications regardless of antihyperglycemic treatment, but only insulin-treated patients suffered significantly more cardiac complications than nondiabetic patients. There was no increase in periprosthetic joint infections or mortality associated with diabetes. CONCLUSIONS: Patients with pharmacologically treated diabetes undergoing fast-track THA/TKA were at increased odds of LOS >4 days. Although complication rates were low, patients with insulin-treated diabetes were at increased odds of postoperative complications compared to nondiabetic patients and to their orally treated counterparts. Further investigation into the pathogenesis of postoperative complications differentiated by antihyperglycemic treatment is needed.

Intermittent Hypoxia and Effects on Early Learning/Memory: Exploring the Hippocampal Cellular Effects of Pediatric Obstructive Sleep Apnea This review provides an update on the neurocognitive phenotype of pediatric obstructive sleep apnea (OSA). Pediatric OSA is associated with neurocognitive deficits involving memory, learning, and executive functioning. Adenotonsillectomy (AT) is presently accepted as the first-line surgical treatment for pediatric OSA, but the executive function deficits do not resolve postsurgery, and the timeline for recovery remains unknown. This finding suggests that pediatric OSA potentially causes irreversible damage to multiple areas of the brain. The focus of this review is the hippocampus, 1 of the 2 major sites of postnatal neurogenesis, where new neurons are formed and integrated into existing circuitry and the mammalian center of learning/memory functions. Here, we review the clinical phenotype of pediatric OSA, and then discuss existing studies of OSA on different cell types in the hippocampus during critical periods of development. This will set the stage for future study using preclinical models to understand the pathogenesis of persistent neurocognitive dysfunction in pediatric OSA.

Development and Evaluation of a Risk-Adjusted Measure of Intraoperative Hypotension in Patients Having Nonemergent, Noncardiac Surgery BACKGROUND: Intraoperative hypotension is common and associated with organ injury and death, although randomized data showing a causal relationship remain sparse. A risk-adjusted measure of intraoperative hypotension may therefore contribute to quality improvement efforts. METHODS: The measure we developed defines hypotension as a mean arterial pressure <65 mm Hg sustained for at least 15 cumulative minutes. Comparisons are based on whether clinicians have more or fewer cases of hypotension than expected over 12 months, given their patient mix. The measure was developed and evaluated with data from 225,389 surgeries in 5 hospitals. We assessed discrimination and calibration of the risk adjustment model, then calculated the distribution of clinician-level measure scores, and finally estimated the signal-to-noise reliability and predictive validity of the measure. RESULTS: The risk adjustment model showed acceptable calibration and discrimination (area under the curve was 0.72 and 0.73 in different validation samples). Clinician-level, risk-adjusted scores varied widely, and 36% of clinicians had significantly more cases of intraoperative hypotension than predicted. Clinician-level score distributions differed across hospitals, indicating substantial hospital-level variation. The mean signal-to-noise reliability estimate was 0.87 among all clinicians and 0.94 among clinicians with >30 cases during the 12-month measurement period. Kidney injury and in-hospital mortality were most common in patients whose anesthesia providers had worse scores. However, a sensitivity analysis in 1 hospital showed that score distributions differed markedly between anesthesiology fellows and attending anesthesiologists or certified registered nurse anesthetists; score distributions also varied as a function of the fraction of cases that were inpatients. CONCLUSIONS: Intraoperative hypotension was common and was associated with acute kidney injury and in-hospital mortality. There were substantial variations in clinician-level scores, and the measure score distribution suggests that there may be opportunity to reduce hypotension which may improve patient safety and outcomes. However, sensitivity analyses suggest that some portion of the variation results from limitations of risk adjustment. Future versions of the measure should risk adjust for important patient and procedural factors including comorbidities and surgical complexity, although this will require more consistent structured data capture in anesthesia information management systems. Including structured data on additional risk factors may improve hypotension risk prediction which is integral to the measure’s validity.

Do Elderly Patients With Diastolic Dysfunction Require Higher Doses of Norepinephrine During General Anesthesia for Noncardiac Surgeries? A Prospective Observational Study BACKGROUND: Diastolic dysfunction is a risk factor for postoperative major cardiovascular events. During anesthesia, patients with diastolic dysfunction might experience impaired hemodynamic function and worsening of diastolic function, which in turn, might be associated with a higher incidence of postoperative complications. We aimed to investigate whether patients with diastolic dysfunction require higher doses of norepinephrine during general anesthesia. Furthermore, we aimed to examine the association between the grade of diastolic dysfunction and the E/e’ ratio during anesthesia. A high E/e’ ratio corresponds to elevated filling pressures and is an important measure of impaired diastolic function. METHODS: We conducted a prospective observational cohort study at a German university hospital from February 2017 to September 2018. Patients aged ≥60 years and undergoing general anesthesia (ie, propofol and sevoflurane) for elective noncardiac surgery were enrolled. Exclusion: mitral valve disease, atrial fibrillation, and implanted mechanical device. The primary outcome parameter was the administered dose of norepinephrine within 30 minutes after anesthesia induction (μg·kg−1 30 min−1). The secondary outcome parameter was the change of Doppler echocardiographic E/e’ from ECHO1 (baseline) to ECHO2 (anesthesia). Linear models and linear mixed models were used for statistical evaluation. RESULTS: A total of 247 patients were enrolled, and 200 patients (75 female) were included in the final analysis. Diastolic dysfunction at baseline was not associated with a higher dose of norepinephrine during anesthesia (P = .6953). The grade of diastolic dysfunction at baseline was associated with a decrease of the E/e’ ratio during anesthesia (P < .001). CONCLUSIONS: We did not find evidence for an association between diastolic dysfunction and impaired hemodynamic function, as expressed by high vasopressor support during anesthesia. Additionally, our findings suggest that diastolic function, as expressed by the E/e’ ratio, does not worsen during anesthesia.

Fiber-Needle Swept-Source Optical Coherence Tomography for the Real-Time Visualization of the Transversus Abdominis Plane Block Procedure in a Swine Model BACKGROUND: Fascia blocks (eg, the transversus abdominis plane [TAP] block) target the intermuscular fascia layers. Ultrasound techniques have allowed peripheral blocks to be performed with accuracy and safety, however, with limitations. Optical coherence tomography (OCT) is based on low-coherence interferometry. In this study, we examined the ability of OCT to identify the TAP. METHODS: A swept-source OCT probe was placed in a 17-gauge needle to obtain imaging. The needle was inserted within 2 different angle ranges (0°–30° and 30°–60°) on a slice of pork belly to assess imaging characteristics. A series of real-time OCT imaging of the muscle, fascia, and interfascial space was obtained. The tissue location of the needle tip was identified using near-infrared (NIR) imaging. In vivo OCT imaging was further done on 3 female 6-month-old native Chinese Landrance Duroc pigs. Real-time images of tissue layers were obtained with needle insertion. Ultrasound imaging of the OCT needle probe was also performed at the same time for needle trajectory guidance. After imaging, the OCT probe was removed, and 5 mL of normal saline was injected via the needle to confirm correct fascia plane identification. RESULTS: In and ex vivo studies showed clear visual distinction of muscle, fascia, and interfascial layer with OCT, with limitations. Independent validation of OCT criteria for the muscle/fascia differentiation by 20 OCT readers for the in vivo data demonstrated the sensitivity = 0.91, specificity = 0.90, and accuracy = 0.89. Although the angle of needle entry affected the depth of OCT penetration in the muscle, the attenuation coefficient values of the fascia and muscle tissue were statistically different (P < .001) and with high area under the receiver operating characteristics (ROC) curve (AUC) (AUC = 0.93 in 0°–30° and AUC = 1 in 30°–60°) for fascia identification. CONCLUSIONS: This study introduced a novel needle imaging probe method to identify the transversus abdominis fascia plane in real-time. Quantitative calculation of the attenuation coefficients can further aid objective identification by providing direct confirmation of the tip position, increasing the first-pass success rate, and decreasing the need for needle repositioning. Combining OCT and ultrasound may improve the accuracy of anesthetics placement.

Incidence, Mortality, and Characteristics of 18 Pediatric Perioperative Cardiac Arrests: An Observational Trial From 22,650 Pediatric Anesthesias in a German Tertiary Care Hospital BACKGROUND: Recently, a very low incidence of 3 per 10,000 and a mortality of 30% were reported for pediatric perioperative cardiac arrest (POCA). However, high-risk patients, namely children already anesthetized on the intensive care unit (ICU), were excluded. This study investigates the incidence and mortality of POCA in children in whom anesthesia was induced in the ICU or in the operating room using real-world data. In addition, different classifications of POCA were compared with respect to outcome relevance. METHODS: This is a retrospective observational study conducted at a German level 1 perinatal center and tertiary care hospital between 2008 and 2018. Children ≤15 years who underwent an anesthetic procedure and suffered from POCA (defined as any condition requiring chest compressions and/or defibrillation) from the beginning of care provided by an anesthesiologist to 60 minutes after anesthesia or sedation were included. Primary end points were incidence and mortality of POCA in children with anesthesia induced in the ICU versus in the operating room. Secondary end points included incidences and outcomes with respect to the pathophysiological cause (respiratory versus circulatory associated). RESULTS: There were 18 POCA during 22,650 anesthetic procedures (incidence 7.9 per 10,000; 95% confidence interval [CI], 4.7-12.5). Thirty-day mortality was 3.5 per 10,000 (95% CI, 1.5-6.9). Incidence and mortality were higher in children in whom anesthesia was induced in the ICU versus in the operating room (incidence: 131.6; 95% CI, 57 to 257.6 versus 4.5; 95% CI, 2.2-8.3; P < .001; and mortality: 82.2; 95% CI, 26.7-190.8 versus 1.4; 95% CI, 0.3-3.9; P < .001). Mortality in circulatory-induced POCA (n = 8; 44%) was 100%, in respiratory-induced POCA (n = 9; 50%) 0% (P < .001). CONCLUSIONS: Children with anesthesia induction in the ICU represent a high-risk population for POCA and POCA-associated mortality. POCA classification should be based on the individual cause (respiratory versus circulatory) rather than on the perioperative phase or the responsible specialty.

A Bayesian Comparison of Frailty Instruments in Noncardiac Surgery: A Cohort Study BACKGROUND: Frailty—a multidimensional syndrome related to age- and disease-related deficits—is a key risk factor for older surgical patients. However, it is unknown which frailty instrument most accurately predicts postoperative outcomes. Our objectives were to quantify the probability of association and relative predictive performance of 2 frailty instruments (ie, the risk analysis index-administrative [RAI-A] and 5-item modified frailty index [mFI-5]) with postoperative outcomes in National Surgical Quality Improvement Program (NSQIP) data. METHODS: Retrospective cohort study using Bayesian analysis of NSQIP hospitals. Adults having inpatient small or large bowel surgery 2010–2015 (derivation cohort) or intermediate to high risk mixed noncardiac surgery in 2016 (validation cohort) had preoperative frailty assigned using 2 unique approaches (RAI-A and mFI-5). Probabilities of association were calculated based on posterior distributions and relative predictive performance using posterior predictive distributions and Bayes factors for 30-day mortality (primary outcome) and serious complications (secondary outcome). RESULTS: Of 50,630 participants, 7630 (14.0%) died and 19,545 (38.6%) had a serious complication. Without adjustment, the RAI-A and mFI-5 had >99% probability being associated with mortality with a ≥2.0 odds ratio (ie, large effect size). After adjustment for NSQIP risk calculator variables, only the RAI-A had ≥95% probability of a nonzero association with mortality. Similar results arose when predicting postoperative complications. The RAI-A provided better predictive accuracy for mortality than the mFI-5 (minimum Bayes factor 3.25 × 1014), and only the RAI-A improved predictive accuracy beyond that of the NSQIP risk calculator (minimum Bayes factor = 4.27 × 1013). Results were consistent in leave-one-out cross-validation. CONCLUSIONS: Translation of frailty-related findings from research and quality improvement studies to clinical care and surgical planning will be aided by a consistent approach to measuring frailty with a multidimensional instrument like RAI-A, which appears to be superior to the mFI-5 when predicting outcomes for inpatient noncardiac surgery.

Assessment of Anesthesia Capacity in Public Surgical Hospitals in Guatemala BACKGROUND: International standards for safe anesthetic care have been developed by the World Federation of Societies of Anaesthesiologists (WFSA) and the World Health Organization (WHO). Whether these standards are met is unknown in many nations, including Guatemala, a country with universal health coverage. We aimed to establish an overview of anesthesia care capacity in public surgical hospitals in Guatemala to help guide public sector health care development. METHODS: In partnership with the Guatemalan Ministry of Public Health and Social Assistance (MSPAS), a national survey of all public hospitals providing surgical care was conducted using the WFSA anesthesia facility assessment tool (AFAT) in 2018. Each facility was assessed for infrastructure, service delivery, workforce, medications, equipment, and monitoring practices. Descriptive statistics were calculated and presented. RESULTS: Of the 46 public hospitals in Guatemala in 2018, 36 (78%) were found to provide surgical care, including 20 district, 14 regional, and 2 national referral hospitals. We identified 573 full-time physician surgeons, anesthesiologists, and obstetricians (SAO) in the public sector, with an estimated SAO density of 3.3/100,000 population. There were 300 full-time anesthesia providers working at public hospitals. Physician anesthesiologists made up 47% of these providers, with an estimated physician anesthesiologist density of 0.8/100,000 population. Only 10% of district hospitals reported having an anesthesia provider continuously present intraoperatively during general or neuraxial anesthesia cases. No hospitals reported assessing pain in the immediate postoperative period. While the availability of some medications such as benzodiazepines and local anesthetics was robust (100% availability across all hospitals), not all hospitals had essential medications such as ketamine, epinephrine, or atropine. There were deficiencies in the availability of essential equipment and basic intraoperative monitors, such as end-tidal carbon dioxide detectors (17% availability across all hospitals). Postoperative care and access to resuscitative equipment, such as defibrillators, were also lacking. CONCLUSIONS: This first countrywide, MSPAS-led assessment of anesthesia capacity at public facilities in Guatemala revealed a lack of essential materials and personnel to provide safe anesthesia and surgery. Hospitals surveyed often did not have resources regardless of hospital size or level, which may suggest multiple factors preventing availability and use. Local and national policy initiatives are needed to address these deficiencies.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia,

Telephone consultation 11855 int 1193,

Medicine

Editorial Rajendra N Srivastava Apollo Medicine 2020 17(4):239-239

Cytological evaluation of p16Ink4a in precancerous lesions of the cervix: Conventional papanicolaou smears Seema Singhal, Vinod Kumar Arora Apollo Medicine 2020 17(4):240-245 Background: Cancer of the uterine cervix is the second most common cancer among women worldwide. More than three fourths of these patients are diagnosed at advanced stages, leading to poor prospects of long term survival and cure. Introduction of Papanicolaou (Pap test) cytological screening for cervical precancerous lesions has significantly reduced the incidence and mortality of cervical cancer. Human papillomavirus (HPV) DNA testing has been recently demonstrated to be efficient to be integrated into screening programs, so it can be used to triage women with equivocal cytological abnormalities and also identifies women at risk of residual or recurrent disease after treatment of cervical intraepithelial neoplasia. However, it fails into triage low grade lesions. HPV DNA test confirms infection by the virus, present in 99% of cases. However, it does not discriminate between transient and persistent infection as it is crucial because it is the persistent infection which progresses to neoplasia. Histological assessment of cervical biopsy that is considered as “gold standard” can be hampered by intra and inter observer variability. A more specific triage marker is required to identify women who would need colposcopy. Hence, p16INK4a has emerged as a new diagnostic and prognostic biomarker. Aims and objectives: This study was conducted to evaluate the utility of staining of p16INK4a on conventional Pap smears and its comparison with corresponding biopsies. Material and Methods: 50 cases of conventional Papanicolaou stained cervical smears cases were randomly selected from the archive of cytopathology laboratory. The cervical smears were re-evaluated for adequacy, preservation of cells, cytomorphology and various lesions were categorized according to The Bethesda system 2001 (TBS) classification. Consecutive such cases were selected for which both cytological and histological material were available. Immunostaining of cervical cytological specimens for p16 was performed using monoclonal murine antibody, clone 16P04, JC2. Ready to use antibody was used for immunostaining as per manufacturer's protocol. Results: Out of the 50 smears of preneoplastic and invasive lesions, ASCUS was seen in 5 cases, LSIL in 10 cases, HSIL in 20 cases, SCC in 20 cases and AGUS in 5 cases. Of the 5 cases of ASCUS, histopathology showed 3 chronic cervicitis and 1 each in CIN-1 and CIN-2. Histopathological diagnosis of 10 cases of LSIL showed 6 CIN-1 and 2 each in CIN-2 and chronic cervicitis. Similarly, for 10 cases of HSIL, 3 were CIN-2, 5 CIN-3 and 2 SCC. All 20 cases of carcinoma showed SCC while 5 cases of AGUS showed 4 chronic cervicitis and one adenocarcinoma. Immunohistochemical staining of p16INK4A showed weak positivity in 3 cases of chronic cervicitis and 4 cases of CIN-1. In CIN-2 cases, 66.67% showed strong positivity, CIN-3 showed 80% while both carcinoma and adenocarcinoma showed 100% strong positivity. The sensitivity of immunohistochemical staining of p16INK4A was 77.5%, specificity was 100%, PPV 100% and NPV 52.6%. The relation between histological and cytological immunostaining of p16INK4A. Conclusion: p16INK4A is a reliable marker for dysplastic squamous and glandular cervical cells both in tissue sections and in cervical smears. p16 immunostaining can be easily performed on CPS, and there is high concordance of positivity on smears and tissue sections.

Intraoperative ultrasound in neurosurgical procedures V A Kiran Kumar, N A Sai Kiran, B Girija Kumari, Ranabir Pal, V Umamaheswar Reddy, Amit Agrawal Apollo Medicine 2020 17(4):246-251 Introduction: The objective of the present study was to study the utility and the effectiveness of intraoperative ultrasound in neurosurgical procedures and to assess the outcome. Material and Methods: In this prospective study, operative procedures by a single surgeon under intraoperative ultrasound localization for basal ganglia/thalamic haematoma or traumatic brain contusions or brain tumours were included. Ultrasound scanning of the brain was performed before and after the excision of the lesion and during the procedure to verify the extent of removal of the lesion. Results: 74 patients underwent surgery for brain tumor/basal ganglia bleed/head injury with hemorrhagic contusion with the help of intraoperative ultrasound. Gross tumor resection was noted in 25 out of 36 cases of brain tumors (69.44%), complete evacuation of hematoma was noted in 14 out of 34 cases(41.2%) of basal ganglia bleed and in 2 out of 4 cases (50%) of intracerebral contusion. As per Modified Rankin scale (MRS)score, among the brain tumor cases, all patients had fared well in recovery and had better MRS scores except in one patient who expired during postoperative period. Conclusions: IoUS is a widely accessible, cheap, portable and less space occupying and reliable imaging tool to follow and modify the surgical plan in real time, and is more accurate and helpful in complete tumor resection, evacuation of intracerebral bleeds and contusions, and biopsy of deep seated lesions. It is easy and safe to handle with no risk of radiation.

Prevalence of Side Effects of Propofol Anesthesia among Adult and Pediatric Patients Undergoing Surgery Khaled D Alsaeiti, Fathi M Elbraky, Salem A Ibkhatra, Khawla A Al-Zoubi, Ghada A Alagoury, Fatima F Al-Farajani, Hawa Al-Kharaz, Fatima A Al-Megrahi Apollo Medicine 2020 17(4):252-255 Introduction: Propofol is a short-acting medication that lowers awareness and causes a transient memory loss. It is given intravenously. The aim of this study was to assess the prevalence of various side effects of the use of propofol as an anesthetic in various surgical procedures and to compare their prevalence among adults and children. Materials and Methods: One hundred patients were included in the study, fifty adults and fifty of children, who underwent various types of surgery and received propofol anesthesia, at Pediatrics Hospital, Benghazi Medical Center (BMC) and Al-Hawari hospital, from September to November 2019. Results: The mean age was 6.37 ± 4.18 years in the pediatric group (ranging from 1 to 15 years) and 40.0 ± 17.03 years in the adult group (range from 16 to 97 years). The indication of surgery among the adult group was cholecystectomy (14 patients, 28%), followed by ENT operations (12 patients, 24%), while the indication of surgery among the pediatric group was tonsillectomy (20 patients, 40%), followed by hernia repair (15 patients, 30%). Thirty-five adults (70%) and 40 children (80%) suffered different types of complications during the study. Pain at the site of propofol injection was the most common complication. It was observed in 21 adult patients (42%) and 23 children (46%). Bronchospasm developed among 11 children who underwent tonsillectomy. Low blood pressure was more prevalent among adult patients (14 patients, 28%). An arrhythmia was developed in nine patients (six adults and three children). Two adults and five children experienced delayed recovery from anesthesia. The recovery time was 14.67 ± 8.37 min (5â€"45 min), Conclusion: Burning at site of propofol injection is the most common side effect of propofol anesthesia; other complications need further evaluation by more detailed studies.

A review of chronic relapsing inflammatory optic neuropathy Pushpendra Nath Renjen, Dinesh Mohan Chaudhari, Kamal Ahmad, Shivangi Garg, Anjali Mishra Apollo Medicine 2020 17(4):256-258 Chronic relapsing inflammatory optic neuropathy (CRION), initially described in 2003, is a form of recurrent optic neuritis (ON) that has relatively good response/dependency to steroid treatment. In demyelinating ON, patients present with periorbital ache and pain elicited by eye movement, which usually begins insidiously and worsens, in synchrony with or preceding a reduction in vision, which deteriorates over days. The etiology of CRION is unknown. However, the excellent response to corticosteroids and the need for immunosuppressive therapy to prevent relapse suggests an immunomediated origin.

Recurrent respiratory papillomatosis: A challenging clinical entity Santosh Kumar Swain, Sidharth Mohanty, Bulu Nahak, Mahesh Chandra Sahu Apollo Medicine 2020 17(4):259-263 Recurrent respiratory papillomatosis (RRP) is a benign lesion seen in the respiratory airway caused by human papillomatosis virus (HPV).RRP can affects children to young adults. Most of the childhood RRP occur at birth which contaminated from birth canals of the mother. In adult ages, the infections transmitted via sexual route. The lesions are often seen as exophytic nodules, mostly in the larynx and occasionally at the nasopharynx, tracheobronchial trees and lung parenchyma. This disease is often unpredictable and varies from spontaneous remission to aggressive persistent or recurrence in nature.RRP has chance for malignant transformation to squamous cell carcinoma although it is a rare happening. The diagnosis is confirmed by histopathological study. Presently there is no definite treatment for RRP available. Surgery is the treatment of choice along with several adjuvant therapies available. The aim of this review article is to describe the detail etiology, epidemiology, clinical presentations, investigations and treatment of RRP.

A Reflection on the Use of Additive Manufacturing in Nephrology for Education and Surgical Planning Azhar Equbal, Shahid Akhtar, Md. Asif Equbal Apollo Medicine 2020 17(4):264-266 Additive manufacturing (AM) or three-dimensional printing (3DP) is a new technology known for rapid fabrication of customized or finely detailed parts with decreased cost. The technology uses the principle of layer by layer-based manufacturing of parts following the bottom-up approach. In recent years, AM technologies have seen a rapid development in various fields of engineering, medical, and aeronautics. Development in technology and biomaterials has made AM more novel and approachable techniques for complex medical treatments. In the current work, a reflection on the use of AM technology in the field nephrology has been presented. At present, AM technologies are used in conceptualizing and fabricating urological instruments, planning surgeries, and educating the apprentices and patients. The review primarily aimed to present the use of AM for education and surgical planning in nephrology. The study will also discuss the limitation and future scope of AM in the field of nephrology.

Diabetes Mellitus and Periodontitis: Relevance of the Diabolic Duo in India Sumidha Bansal, Sangeeta Dhir, Subhash Kumar Wangnoo Apollo Medicine 2020 17(4):267-271 Diabetes and periodontitis are highly prevalent diseases. Chronic nature, along with shared risk factors, magnifies the complexity of both the diseases. Periodontal treatment results in clinically relevant reductions in HbA1c, and the presence of diabetes worsens the periodontal health and vice-versa. This paper presents an overview on the pathogenic mechanisms, impact of intervention, and significance of interprofessional collaborations for holistic management in diabetes and periodontitis.

Choleteryl ester storage disease: A rare cause of adrenal calcifications in children Fatiha Benmiloud, Maria Rkain, A El Aouali, A Babakhouya, Noufissa Benajiba Apollo Medicine 2020 17(4):272-274 Cholesteryl ester storage disease (CESD) in children is a rare anatomo-clinical entity, characterized by a secondary lysosomal accumulation and an autosomal recessive mutation in the LIPA gene, which results from a lysosomal acid lipase (LAL) deficiency. The work of this paper is based on our observation of a 25-month-old infant, who had an abdominal distension with a hepatomegaly of 13 cm. The abdomen X-ray has shown some bilateral adrenal calcifications. The results of the biological assessment : the hepatic check showed a slight cytolysis, triglycerides increased to 5.4 g.l with a reduced rate of high density lipoproteins. The blood smear has shown the presence of intracytoplasmic lipid vacuoles in the lymphocytes, with a positive MGG staining and a negative PAS staining. The activity of the LAL enzyme has decreased to 3.6%. This observation joins the rare pediatric cases of the CESD and highlights the interest in a simply available radiological examination to make a guidance diagnosis of a complex metabolic disorder.

Xanthogranulomatous osteomyelitis Seema Singhal, Chander Shekher Apollo Medicine 2020 17(4):275-276 Xanthogranulomatous osteomyelitis (XO) is a type of chronic osteomyelitis characterized by collection of foamy macrophages admixed with mononuclear cells. Xanthogranulomatous inflammation is characterized by the presence of histiocytes, foamy macrophages, activated plasma cells, and presence of suppurative foci and hemorrhage. It has been encountered in various tissues such as gallbladder, kidney, urinary bladder, fallopian tube, ovary, vagina, prostate, testis, epididymis, colon, and appendix. Very rarely, it can affect lungs, brain, or bone. Only three cases of XO have been described previously in the literature till date.

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