The Monoclonal Antibody Cocktail in SARS-CoV 2: A Bonanza for Patients With Chronic Lymphocytic Leukemia?

Monoclonal antibody cocktail is currently one of the most promising approaches being studied in the management of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). We present a case of an elderly patient with coronavirus disease (COVID-19) and Chronic lymphocytic leukaemia (CLL) who had recurrent episodes of desaturation and admission in intensive care unit (ICU) despite receiving the treatment for moderate to severe COVID-19. After careful selection, weighing the benefits and risks, the patient was started on the combination of the two monoclonal antibodies, casirivimab and imdevimab. The results suggest that this could be a game changer in COVID-19 with a focused approach of management of COVID-19 positive patients especially in the vulnerable population

Clinical Study of Granulomatous Mastitis- A Rare Entity

Introduction: Granulomatous Mastitis (GM), a rare and benign disorder, has two forms- Idiopathic Granulomatous Mastitis (IGM) and Specific Granulomatous Mastitis (SGM). IGM is caused without any particular discernable and attributable cause while SGM is caused secondary to tuberculosis, other infectious causes like syphilis, fungal, parasitic infections, corynebacterial; Wegener’s granulomatosis, sarcoidosis, reaction to a foreign body, vasculitis etc. Aim: To identify clinical presentations and to formulate a treatment protocol for patients with granulomatous mastitis. Materials and Methods: This study was a prospective descriptive observational study conducted at Government Wenlock Hospital and Kasturba Medical College Hospital, Attavar, Mangalore, Karnataka, India, from October 2015 to March 2018 on 32 patients admitted to the Department of General Surgery in the study centre, who had a histopathological diagnosis of granulomatous mastitis. All the relevant data of the patients: demographic data and clinical findings, any medical co-morbidities was collected by telephonic interview and case sheets, operative notes were studied thoroughly and the patients were followed up for regression of their signs and symptoms at one month, two months and six months of their hospital visits. Results of microbial cultures or stains, imaging (mammography, ultrasound if done) and biopsy results were collected. All the collected data was analysed by Chi-square test and Fisher’s exact test and the p-values <0.05 was considered significant. Results: Total of 32 female patients (13 patients were in the age group of 31-40 years) were analysed in the present study. A total of 27 (84.4%) had last child birth <5 years back. The patients who presented with a left laterality lesion were 25 (78%) with statistically significant difference. A total of 18 (56%) of the patients had a lesion in the upper outer while 11 (34%) in lower outer quadrant of breast. A total of 29 (90.6 %) of patients, the disease was extending upto the areola region. All the patients had a firm lump and out of these, 25 (78.1%) of the patient presented with a painful lump. Inflammatory skin changes were seen in 20 (62%) of the patients. Retraction of nipple was presented in 26 (81%) of the patients. A total of 19 (59.4%) patients underwent an excision biopsy of the lump and 22 (69%) patients were initiated with Antitubercular Therapy (ATT). Conclusion: Granulomatous mastitis is a highly unpredictable disease with frequent flares and periods of inactivity which may falsely be considered as successful treatment. Due to rare nature of this disease, randomisation of all treatment modalities are availabl

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Noncoding variants alter GATA2 expression in rhombomere 4 motor neurons and cause dominant hereditary congenital facial paresis

Hereditary congenital facial paresis type 1 (HCFP1) is an autosomal dominant disorder of absent or limited facial movement that maps to chromosome 3q21-q22 and is hypothesized to result from facial branchial motor neuron (FBMN) maldevelopment. In the present study, we report that HCFP1 results from heterozygous duplications within a neuron-specific GATA2 regulatory region that includes two enhancers and one silencer, and from noncoding single-nucleotide variants (SNVs) within the silencer. Some SNVs impair binding of NR2F1 to the silencer in vitro and in vivo and attenuate in vivo enhancer reporter expression in FBMNs. Gata2 and its effector Gata3 are essential for inner-ear efferent neuron (IEE) but not FBMN development. A humanized HCFP1 mouse model extends Gata2 expression, favors the formation of IEEs over FBMNs and is rescued by conditional loss of Gata3. These findings highlight the importance of temporal gene regulation in development and of noncoding variation in rare mendelian disease

International Consensus Statement on Obstructive Sleep Apnea

Evaluation and interpretation of the literature on obstructive sleep apnea (OSA) allows for consolidation and determination of the key factors important for clinical management of the adult OSA patient. Toward this goal, an international collaborative of multidisciplinary experts in sleep apnea evaluation and treatment have produced the International Consensus statement on Obstructive Sleep Apnea (ICS:OSA). Using previously defined methodology, focal topics in OSA were assigned as literature review (LR), evidence-based review (EBR), or evidence-based review with recommendations (EBR-R) formats. Each topic incorporated the available and relevant evidence which was summarized and graded on study quality. Each topic and section underwent iterative review and the ICS:OSA was created and reviewed by all authors for consensus. The ICS:OSA addresses OSA syndrome definitions, pathophysiology, epidemiology, risk factors for disease, screening methods, diagnostic testing types, multiple treatment modalities, and effects of OSA treatment on multiple OSA-associated comorbidities. Specific focus on outcomes with positive airway pressure (PAP) and surgical treatments were evaluated. This review of the literature consolidates the available knowledge and identifies the limitations of the current evidence on OSA. This effort aims to create a resource for OSA evidence-based practice and identify future research needs. Knowledge gaps and research opportunities include improving the metrics of OSA disease, determining the optimal OSA screening paradigms, developing strategies for PAP adherence and longitudinal care, enhancing selection of PAP alternatives and surgery, understanding health risk outcomes, and translating evidence into individualized approaches to therapy

International consensus statement on obstructive sleep apnea

BACKGROUND: Evaluation and interpretation of the literature on obstructive sleep apnea is needed to consolidate and summarize key factors important for clinical management of the OSA adult patient. Toward this goal, an international collaborative of multidisciplinary experts in sleep apnea evaluation and treatment have produced the International Consensus statement on Obstructive Sleep Apnea (ICS:OSA). METHODS: Using previously defined methodology, focal topics in OSA were assigned as literature review (LR), evidence-based review (EBR), or evidence-based review with recommendations (EBR-R) formats. Each topic incorporated the available and relevant evidence which was summarized and graded on study quality. Each topic and section underwent iterative review and the ICS:OSA was created and reviewed by all authors for consensus. RESULTS: The ICS:OSA addresses OSA syndrome definitions, pathophysiology, epidemiology, risk factors for disease, screening methods, diagnostic testing types, multiple treatment modalities, and effects of OSA and treatment on the multiple comorbidities. Specific focus on outcomes with positive airway pressure (PAP) and surgical treatments were evaluated. CONCLUSION: This review of the literature in OSA consolidates the available knowledge and identifies the limitations of the current evidence. This effort aims to highlight the basis of OSA evidence-based practice and identify future research needs. Knowledge gaps and opportunities for improvement include improving the metrics of OSA disease, determining the optimal OSA screening paradigms, developing strategies for PAP adherence and longitudinal care, enhancing selection of PAP alternatives and surgery, understanding health risk outcomes, and translating evidence into individualized approaches to therapy