An unusual case of scalp ulceration.

ABSTRACT: Granulomatosis with polyangiitis, a form of necrotizing vasculitis can present as a limited variant with the involvement of a single organ system. The superficial protracted form can present as face and scalp ulceration for chronic periods of time. Diagnosis can be established histopathologically by examining the involvement of blood vessels. Here, we present a case of scalp ulceration that was diagnosed as a limited variant and started on steroids and immunosuppressants with excellent response.

Exposure-Response Analyses for Belzutifan to Inform Dosing Considerations and Labeling.

Belzutifan (Welireg, Merck & Co., Inc., Rahway, NJ, USA) is an oral, potent hypoxia-inducible factor-2α inhibitor, recently approved in the United States for the treatment of von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC) and other VHL disease-associated neoplasms. Safety and efficacy were investigated in two clinical studies: a Phase 1 dose escalation/expansion study in solid tumors and RCC and a Phase 2 study in VHL-RCC. A population pharmacokinetic model was used to estimate belzutifan exposures to facilitate exposure-response (E-R) analyses for efficacy and safety endpoints. Relationships between exposure and efficacy (overall response rate, disease control rate, progression-free survival, best overall tumor size response, and other endpoints), safety outcomes (Grade ≥3 anemia, Grade ≥3 hypoxia, and time to first dose reduction/dose interruption), and pharmacodynamic biomarkers (erythropoietin [EPO] and hemoglobin [Hgb]) were evaluated using various regression techniques and time-to-event analyses. Efficacy E-R was generally flat with non-significant positive trends with exposure. The safety E-R analyses demonstrated a lack of relationship for Grade ≥3 hypoxia and a positive relationship for Grade ≥3 anemia, with incidences also significantly dependent on baseline Hgb. Exposure-dependent reductions in EPO and Hgb were observed. Based on the cumulative benefit-risk assessment in VHL disease-associated neoplasms using E-R, no a priori dose adjustment is recommended for any subpopulation. These analyses supported the benefit-risk profile of belzutifan 120 mg once daily dosing in patients with VHL-RCC for labeling and the overall development program.

Screen Time Among Medical and Nursing Students and Its Correlation With Sleep Quality and Attention Span: A Cross-Sectional Study.

BACKGROUND:  Screen time is increasing among students and is also known to affect their lifestyle and health. The study investigated the correlation of screen time with sleep quality and attention span. METHODS: A cross-sectional study was conducted among undergraduate medical and nursing students in November 2021. A total of 192 students were selected randomly and investigated using a structured questionnaire. Sleep behavior was assessed using the Pittsburg Sleep Quality Index. Screen time and attention span were measured for each participant. The screen time data was reported as the median with an IQR. Pearson's correlation was performed to assess the correlation between screen time and sleep behavior and screen time and attention span. RESULTS:  The median screen time for 28 days was 260 (192.2-326.7) hours, and the median non-academic screen time was 250.0 (172.3-328.0) hours. Subjective sleep quality was good among 163 (84.9%) of the study participants. Global sleep quality was poor among 91 (42.2%) participants. The median score of the digit span forward was 6.00 (IQR: 5.00-7.00), and the median score of the digit span backward was 5.00 (IQR: 4.00-6.00). The global sleep score had a strong positive correlation with screen time, with a Pearson's correlation coefficient of 0.86. Forward and backward attention spans were not correlated with sleep scores, with correlation coefficients of 0.037 and 0.071, respectively. CONCLUSION:  Screen time is increasing significantly among medical and nursing undergraduate students, and their sleep is also getting affected. Emphasis should be given to the balance between digitalization and health.

Unicommissural unicuspid aortic valve (UAV) presenting as ascending aortic aneurysm with aortic dissection.

We herein present an exceptionally rare instance of a unicommissural unicuspid aortic valve (UAV) manifesting with an aneurysmal ascending aorta complicated by a type A aortic dissection .

Utilization of Untied Fund and Factors Affecting the Utilization at Sub-Centers of Rural Odisha: A Mixed-Method Study.

Introduction: The untied funds at sub-centers provided flexibility for local action at block and down below levels. Effective utilization of untied fund can strengthen the healthcare. So, our study aims at assessing the knowledge of health workers, male/female (HWF/M), and effectiveness of utilization of untied funds at the sub-center (SC) level. Material and Methods: A mixed method (cross-sectional study and qualitative study) was conducted at Tangi Block, Khordha district, Odisha, in the year 2020. Health workers, male and female in sub-centers, and local stakeholders were interviewed using a structured interview schedule. The tool comprises financial records, a semi-structured questionnaire, and an in-depth interview guide. Universal sampling was adopted. For the cross-sectional study, 24 health workers were male/female, and for the qualitative study, all local stakeholders and 24 health workers female/male were interviewed. The study was conducted as a part of an academic program, and ethics approval was approved by AIIMS Bhubaneswar Institute Ethics Committee. Results: Seven out of 24 sub-centers did not spend any money, with a median unspent amount of 4260 INR (Q1-0, Q3-17300). As many as 36.8% of sub-centers had a delay of 9 months to get the untied fund, which significantly affected the utilization of funds. 37% of HWF/M utilized the fund inappropriately. None of the health workers had complete knowledge regarding the appropriate usage of untied fund. Communication gap, multiple engagements, non-cooperation from officials, delay in technical processing, and irregular Garam Sabha meetings were found to be barriers. Conclusion: Our study found out under-utilization of money in untied fund. Communication gap, non-cooperation form village leaders, poor knowledge, overburdened health workers, improper reporting, and lack of felt need were found to be barriers for prompt utilization.

All that flows across the ventricular septum are not ventricular septal defects.

Coronary cameral fistula is a rare congenital anomaly and clinical presentation depends on the location of the defect, degree of shunting, and associated complications. We present a case of coronary cameral fistula where segmental analysis by echocardiogram helped us to avoid misdiagnosis as a ventricular septal defect.

A Psittacine bite and subcutaneous basidiobolomycosis: A case with a therapeutic challenge.

Basidiobolus ranarum is a saprophyte that can be found in soil, rotting vegetables, and frogs' digestive tracts. Clinically, basidiobolomycosis presents as a persistent infection of subcutaneous tissue affecting the trunk and extremities in an immunocompetent host. We describe a case of subcutaneous basidiobolomycosis in a 56-year-old immunocompetent woman farmer by occupation residing at remote part of central India. This study highlights the traumatic implantation and zoonotic potential of fungal species. Clinical suspicion of fungal etiology and timely mycology laboratory diagnostic support is key to address such cases. This case is documented to emphasize the problems of compliance to treatment specially in remote and poor patients challenging the treatment with complete cure. 2012 Elsevier Ltd. All rights reserved.

Tumor dynamics in patients with solid tumors treated with pembrolizumab beyond disease progression.

While many patients are treated beyond progression (TBP), the magnitude and duration of clinical benefit in these patients have not been fully quantified. Data from 799 patients with melanoma (n = 176), non-small cell lung cancer (NSCLC; n = 146), gastric cancer (GC; n = 87), head and neck squamous cell carcinoma (HNSCC; n = 112), clear-cell renal cell carcinoma (ccRCC; n = 51), and urothelial carcinoma (UC; n = 227) TBP were included. Patients had received pembrolizumab beyond confirmed progressive disease (PD) per RECIST v1.1. A subset of patients displays a 30% reduction in the sum of lesion diameters in the post-progression period (melanoma 24.4%, NSCLC 11.6%, 12.6% GC, 8.9% HNSCC, 15.7% ccRCC, and 13.2% UC). Most patients show stable target lesion dynamics in the post-progression period (melanoma, 64.8%; NSCLC, 72.6%; GC, 69.0%, 75.9% HNSCC, 72.5% ccRCC, 75.3% UC). Pembrolizumab generates meaningful efficacy in a subset of patients treated beyond RECIST v1.1 progression.

Correction: AlCl3@ZnO nanostructured material: an efficient green catalyst for the one-pot solvent-free synthesis of 1,4-dihydropyridines.

[This corrects the article DOI: 10.1039/D3RA04277D.].

AlCl3@ZnO nanostructured material: an efficient green catalyst for the one-pot solvent-free synthesis of 1,4-dihydropyridines.

AlCl3-loaded ZnO nanoparticles have been explored as an efficient catalyst for 1,4-dihydropyridine synthesis under ambient temperature and solvent-free conditions. For this purpose, ZnO nanoparticles were synthesized by a simple solution-based precipitation technique using a stoichiometric amount of zinc sulfate and oxalic acid. The AlCl3@ZnO nanocrystalline catalyst was prepared by loading 20% AlCl3 on ZnO nanoparticles by a simple wet-impregnation technique. This catalyst efficiently performed Hantzsch pyridine reactions with various aromatic aldehydes, ethyl acetoacetate and ammonium acetate. The nanostructured AlCl3-loaded ZnO catalyst was characterized by UV-DRS, XRD, FESEM, EDS, FETEM-STEM-EDS and XPS techniques. The comprehensive characterization reveals the formation of AlCl3-loaded ZnO catalysts with an average particle size of 70-80 nm. The loading of AlCl3 on the ZnO surface was confirmed by minor shifts in the XPS and XRD peaks. FETEM-STEM-EDS also indicates reasonable AlCl3 loading on ZnO nanoparticles. The 20% AlCl3-loaded ZnO nanocatalyst (AlCl3@ZnO) confers 92% yield for the synthesis of 1,4-dihydropyridine under solvent-free and ambient temperature conditions. The synthesized 1,4-dihydropyridines were characterized by 1H-NMR, 13C-NMR, HRMS and FT-IR spectroscopic techniques. The reported catalyst is highly efficient, environmentally friendly and could become an alternative to homogenous and heterogenous catalytic reactions.

Development and Validation of the ScAbIeS Tool for Diagnosing Scabies by Community Healthcare Workers in Resource-Limited Settings.

Introduction Scabies can lead to community outbreaks if not diagnosed early. Developing and validating a relevant tool for diagnosing scabies at the community level is essential to bridging the early diagnosis and treatment gap. Objective The objective of this study is to develop and validate a newer tool to diagnose scabies at the community level by Community Healthcare Workers (CHWs) in resource-limited settings. Methods The developed "ScAbIeS" tool comprised five items divided into two major and three minor criteria. After its development, a longitudinal descriptive study validated the "ScAbIeS" tool. The eligible participants were included in the study through active screening in villages under the Rural Health Training Center (RHTC) Mendhasala. Those villages' Accredited Social Health Activists (ASHS) were included as CHWs for diagnosing scabies using the "ScAbIeS" tool. The participants with skin lesions and/or itching were diagnosed with scabies by CHWs using the "ScAbIeS" tool. The diagnosis of CHWs using the "ScAbIeS" tool was compared with those of physicians, including expert dermatologists, to determine the sensitivity and specificity. Results Kappa's agreement is found to be 0.896 for CHWs and trained physicians regarding the diagnosis of scabies by the "ScAbIeS" tool. Cronbach's alpha is 0.738 for major criteria and 0.565 for minor criteria. 0.778 is found to be Cronbach's alpha for the total scale. The "ScAbIeS" tool is 85% sensitive and 100% specific to diagnose scabies when used by CHWs. Conclusion The "ScAbIeS" tool can be used to diagnose scabies at the community level by CHWs with appropriate training. It will lead to the prevention of complications and community outbreaks of scabies.

Population pharmacokinetic analyses for belzutifan to inform dosing considerations and labeling.

Belzutifan (Welireg, Merck & Co., Inc., Rahway, NJ, USA) is an oral, potent inhibitor of hypoxia-inducible factor 2α, approved for the treatment of certain patients with von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC), central nervous system hemangioblastomas, and pancreatic neuroendocrine tumors. It is primarily metabolized by the polymorphic uridine 5'-diphospho-glucuronosyltransferase (UGT) 2B17 and cytochrome (CYP) 2C19. A population pharmacokinetic (PK) model was built, using NONMEM version 7.3, based on demographics/PK data from three clinical pharmacology (food effect, formulation bridging, and genotype/race effect) and two clinical studies (phase I dose escalation/expansion in patients with RCC and other solid tumors; phase II in patients with VHL). Median (range) age for the combined studies was 55 years (19-84) and body weight was 73.6 kg (42.1-165.8). Belzutifan plasma PK was well-characterized by a linear two-compartment model with first-order absorption and elimination. For patients with VHL, the predicted geometric mean (% coefficient of variation) apparent clearance was 7.3 L/h (51%), apparent total volume of distribution was 130 L (35%), and half-life was 12.39 h (42%). There were no clinically relevant differences in belzutifan PK based on the individual covariates of age, sex, ethnicity, race, body weight, mild/moderate renal impairment, or mild hepatic impairment. In this model, dual UGT2B17 and CYP2C19 poor metabolizers (PMs) were estimated to have a 3.2-fold higher area under the plasma concentration-time curve compared to UGT2B17 extensive metabolizer and CYP2C19 non-PM patients. This population PK analysis enabled an integrated assessment of PK characteristics with covariate effects in the overall population and subpopulations for belzutifan labeling.

Multivariate Parametric Study of Nailfold Capillary Images for Disease Detection.

Nailfold capillaroscopy is a tool which is non-invasive in nature and can be useful for diagnosis, research, therapeutic study and prognosis. Research shows that specific capillary morphology patterns are identified for diabetic subjects, hypertensive subjects and normal controls. In this study, we have proposed RATHEW approach of classifying these three classes of subjects. RATHEW approach employs a three step process for classifying nailfold images: one, identify six abnormality parameters from the image dataset; two, score these abnormality parameters based on the defined scoring rules; and three, combine them mathematically to segregate them into three classes. This technique can be further enhanced to grade the severity of disease and organ involvement. This can bring in a paradigm shift to the disease detection and therapeutic study mechanism.

Atypical Hansen's Disease Mimicking Xanthogranuloma: Role of Cytology.

Fine needle aspiration cytology is a simple, safe, and effective technique that can be used in the diagnosis of cutaneous diseases. Here, we present a case of Hansen's disease with an erythematous dermal nodule mimicking xanthogranuloma clinically. In our scenario, since leprosy is considered eliminated in India, the presentation of patients with classical signs and symptoms is becoming rare. Atypical manifestation of leprosy is increasing day by day, so it is necessary to have a high suspicion of leprosy in every case.