The Upper Esophageal Sphincter Distensibility Index Measured Using Functional Lumen Imaging Probe Identifies Defective Barrier Function of the Upper Esophageal Sphincter

Background/Aims@#The mechanism via which supra-esophageal symptoms are generated is unclear. We assessed upper esophageal sphincter (UES) function in novel fashion using functional lumen imaging probe (FLIP) topography. We hypothesize that symptoms related to aspiration of esophageal contents may be associated with a more distensible UES. @*Methods@#FLIP and reflux symptom index score data from patients undergoing diagnostic evaluation for an esophageal complaint over a 10-month period were analyzed retrospectively. UES distensibility on FLIP was studied at 40-70 mL volumes with in-depth analysis at 50 and 60 mL. Symptoms were compared between patients with low, middle, and high UES-distensibility index (UES-DI). Receiveroperating characteristic analysis was performed to determine associations between the UES-DI and individual reflux symptom index symptom item scores. @*Results@#One hundred and eleven subjects were included. Overall, the associations between UES-DI and symptoms that could be related to supra-esophageal aspiration were strongest at the 50 mL FLIP volume. Choking item score was highest in the high UES-DI group (2.8) vs 1.4 (P < 0.001) in the middle UES-DI and 1.1 (P = 0.004) in the low UES-DI groups. Similarly, the cough item score was highest in the high UES-DI group (2.7) vs 1.5 (P = 0.009) and 0.9 (P = 0.002) groups. @*Conclusion@#A higher UES-DI measures defective barrier function which could may be the main pathophysiology that generates supra-esophageal symptoms.

COV-ID: A LAMP sequencing approach for high-throughput co-detection of SARS-CoV-2 and influenza virus in human saliva

The COVID-19 pandemic has created an urgent need for rapid, effective, and low-cost SARS-CoV-2 diagnostic testing. Here, we describe COV-ID, an approach that combines RT-LAMP with deep sequencing to detect SARS-CoV-2 in unprocessed human saliva with high sensitivity (5-10 virions). Based on a multi-dimensional barcoding strategy, COV-ID can be used to test thousands of samples overnight in a single sequencing run with limited labor and laboratory equipment. The sequencing-based readout allows COV-ID to detect multiple amplicons simultaneously, including key controls such as host transcripts and artificial spike-ins, as well as multiple pathogens. Here we demonstrate this flexibility by simultaneous detection of 4 amplicons in contrived saliva samples: SARS-CoV-2, influenza A, human STATHERIN, and an artificial SARS spike-in. The approach was validated on clinical saliva samples, where it showed 100% agreement with RT-qPCR. COV-ID can also be performed directly on saliva adsorbed on filter paper, simplifying collection logistics and sample handling.

Convalescent Plasma and Improved Survival in Patients with Hematologic Malignancies and COVID-19

Convalescent plasma may benefit immunocompromised individuals with COVID-19, including those with hematologic malignancy. We evaluated the association of convalescent plasma treatment with 30-day mortality in hospitalized adults with hematologic malignancy and COVID-19 from a multi-institutional cohort. 143 treated patients were compared to 823 untreated controls. After adjustment for potential confounding factors, convalescent plasma treatment was associated with improved 30-day mortality (hazard ratio, 0.60; 95% CI, 0.37-0.97). This association remained significant after propensity-score matching (hazard ratio, 0.52; 95% CI, 0.29-0.92). These findings suggest a potential survival benefit in the administration of convalescent plasma to patients with hematologic malignancy and COVID-19.

Glucodynamics and glucocracy in type 2 diabetes mellitus: clinical evidence and practice-based opinion on modern sulfonylurea use, from an International Expert Group (South Asia, Middle East & Africa) via modified Delphi method.

Type 2 diabetes mellitus (T2DM) is a global epidemic. According to international guidelines, the management protocol of T2DM includes lowering of blood glucose, along with preventing disease-related complications and maintaining optimal quality of life. Further, the guidelines recommend the use of a patient-centric approaches for the management of T2DM; however, Asian population is underrepresented in landmark cardiovascular outcome trials (CVOTs). There are several guidelines available today for the diagnosis and management of T2DM, and hence there is much confusion among practitioners about which guidelines to follow. A group of thirty international clinical experts comprising of endocrinologists, diabetologists and cardiologist from South Asia, Middle East and Africa met at New Delhi, India on February 8 and 9, 2020 and developed an international expert opinion statements via a structured modified Delphi method on the glucodynamic properties of OADs and the glucocratic treatment approach for the management of T2DM. In this modified Delphi consensus report, we document the glucodynamic properties of Modern SUs in terms of glucoconfidence, glucosafety, and gluconomics. According to glucodynamics theory, an ideal antidiabetic drug should be efficacious, safe, and affordable. Modern SUs as a class of OADs that have demonstrated optimal glucodynamics in terms of glucoconfidence, glucosafety, and gluconomics. Hence, modern SUs are most suitable second line drug after metformin for developing countries. Based on the current evidence, we recommend a glucocratic approach for the treatment of T2DM, where an individualized treatment plan with phenotype, lifestyle, environmental, social, and cultural factors should be considered for persons with T2DM in the South Asian, Middle Eastern and African regions.

Outcomes and Cardiovascular Comorbidities in a Predominantly African-American Population with COVID-19

ImportanceRacial disparities in COVID-19 outcomes have been amplified during this pandemic and reports on outcomes in African-American (AA) populations, known to have higher rates of cardiovascular (CV) comorbidities, remain limited. ObjectiveTo examine prevalence of comorbidities, rates of hospitalization and survival, and incidence of CV manifestations of COVID-19 in a predominantly AA population in south metropolitan Chicago. Design, Setting, ParticipantsThis was an observational cohort study of COVID-19 patients encountered from March 16 to April 16, 2020 at the University of Chicago. Deidentified data were obtained from an institutional data warehouse. Group comparisons and logistic regression modeling based on baseline demographics, clinical characteristics, laboratory and diagnostic testing was performed. ExposuresCOVID-19 was diagnosed by nasopharyngeal swab testing and clinical management was at the discretion of treating physicians. Main Outcomes and MeasuresPrimary outcomes were hospitalization and in-hospital mortality, and secondary outcomes included incident CV manifestations of COVID-19 in the context of overall cardiology service utilization. ResultsDuring the 30 day study period, 1008 patients tested positive for COVID-19 and 689 had available encounter data. Of these, 596 (87%) were AA and 356 (52%) were hospitalized, of which 319 (90%) were AA. Age > 60 years, tobacco use, BMI >40 kg/m2, diabetes mellitus (DM), insulin use, hypertension, chronic kidney disease, coronary artery disease (CAD), and atrial fibrillation (AF) were more common in hospitalized patients. Age > 60 years, tobacco use, CAD, and AF were associated with greater risk of in-hospital mortality along with several elevated initial laboratory markers including troponin, NT-proBNP, blood urea nitrogen, and ferritin. Despite this, cardiac manifestations of COVID-19 were uncommon, coincident with a 69% decrease in cardiology service utilization. For hospitalized patients, median length of stay was 6.2 days (3.4-11.9 days) and mortality was 13%. AA patients were more commonly hospitalized, but without increased mortality. Conclusions and RelevanceIn this AA-predominant experience from south metropolitan Chicago, CV comorbidities and chronic diseases were highly prevalent and associated with increased hospitalization and mortality. Insulin-requiring DM and CKD emerged as novel predictors for hospitalization. Despite the highest rate of comorbidities reported to date, CV manifestations of COVID-19 and mortality were relatively low. The unexpectedly low rate of mortality merits further study. KEY POINTSO_ST_ABSQuestionsC_ST_ABSWhat comorbidities are present in African Americans (AA) with COVID-19 and what are the associations with subsequent hospitalization and mortality? What is the incidence of COVID-19-associated cardiac manifestations requiring cardiology service utilization? FindingsIn this observational cohort study that included 689 patients with COVID-19 from south metropolitan Chicago (87% AA), cardiovascular (CV) comorbidities were highly prevalent and more common in those that required hospitalization. In addition to AA, age > 60 years, tobacco use, BMI >40 kg/m2, diabetes mellitus, hypertension, chronic kidney disease, coronary artery disease (CAD), and atrial fibrillation (AF) were more common in those hospitalized. Age > 60 years, tobacco use, CAD, and AF were associated with in-hospital mortality. Despite this, cardiac manifestations of COVID-19 were uncommon, and cardiology service utilization was low. In-hospital mortality was 13%. AA patients were more commonly hospitalized, but without increased mortality. MeaningIn a predominantly AA population with COVID-19 at a major academic hospital located in south metropolitan Chicago, CV comorbidities were common and were risk factors for hospitalization and death. Although the highest rates of comorbidities to date were present in this cohort, mortality was relatively low and merits further study.

Engineered in-vitro cell line mixtures and robust evaluation of computational methods for clonal decomposition and longitudinal dynamics in cancer.

Characterization and quantification of tumour clonal populations over time via longitudinal sampling are essential components in understanding and predicting the response to therapeutic interventions. Computational methods for inferring tumour clonal composition from deep-targeted sequencing data are ubiquitous, however due to the lack of a ground truth biological data, evaluating their performance is difficult. In this work, we generate a benchmark data set that simulates tumour longitudinal growth and heterogeneity by in vitro mixing of cancer cell lines with known proportions. We apply four different algorithms to our ground truth data set and assess their performance in inferring clonal composition using different metrics. We also analyse the performance of these algorithms on breast tumour xenograft samples. We conclude that methods that can simultaneously analyse multiple samples while accounting for copy number alterations as a factor in allelic measurements exhibit the most accurate predictions. These results will inform future functional genomics oriented studies of model systems where time series measurements in the context of therapeutic interventions are becoming increasingly common. These studies will need computational models which accurately reflect the multi-factorial nature of allele measurement in cancer including, as we show here, segmental aneuploidies.

Annulo-nucleoplasty using Disc-FX in the management of lumbar disc pathology: early results.

BACKGROUND: Back pain due to Lumbar Disc Disease is a major clinical problem. The treatment options range from physiotherapy to fusion surgery. A number of minimally invasive procedures have also been developed in the recent past for its management. Disc-FX is a new minimally invasive technique that combines percutaneous discectomy, nuclear ablation and annular modification. Literature on its role in the management of lumbar disc pathology is scarce. METHODS: We included 24 consecutive patients who underwent the Disc-FX for back pain due to lumbar disc pathology non-responsive to non-operative treatment for a period of at least 6 months. Based on Magnetic Resonance Imaging (MRI) these patients fell into 2 groups - those with degenerative disc disease (DDD) (n = 12) and those with a contained lumbar disc herniation (CLDH)(n = 12). They were evaluated using the Visual analogue scale (VAS), Oswestry Disability Index (ODI) and Short Form-36 (SF-36) scores preoperatively and postoperatively. RESULTS: The mean age was 37.9 years (21-53 years). There were 17 males and 7 females. One patient in each subgroup was excluded from the final evaluation. Significant improvement was seen in all outcome measures. The overall rate of reintervention for persistent symptoms was 18.18% (4/22); in the CLDH subgroup, it was 36.36% (4/11). CONCLUSIONS AND LEVEL OF EVIDENCE: Early results after the Disc-FX procedure suggest that it s a reasonable treatment option for patients with back pain due to lumbar disc disease, especially for those with DDD who fail conservative treatment. It could be an alternative to procedures like fusion or disc replacement. This study presents Level IV evidence. CLINICAL RELEVANCE: We feel that our study establishes Disc-FX as a modality of treating symptomatic lumbar disc disease due to DDD. However, longer term prospective studies are needed to prove this and to evaluate its role in the treatment of patients with CLDH.