Prediction of influential proteins and enzymes of certain diseases using a directed unimodular hypergraph

Protein-protein interaction (PPI) analysis based on mathematical modeling is an efficient means of identifying hub proteins, corresponding enzymes and many underlying structures. In this paper, a method for the analysis of PPI is introduced and used to analyze protein interactions of diseases such as Parkinson's, COVID-19 and diabetes melitus. A directed hypergraph is used to represent PPI interactions. A novel directed hypergraph depth-first search algorithm is introduced to find the longest paths. The minor hypergraph reduces the dimension of the directed hypergraph, representing the longest paths and results in the unimodular hypergraph. The property of unimodular hypergraph clusters influential proteins and enzymes that are related thereby providing potential avenues for disease treatment

Whole-Genome Sequencing to Identify Missed Rifampicin and Isoniazid Resistance Among Tuberculosis Isolates—Chennai, India, 2013–2016

India has a high burden of drug-resistant tuberculosis (DR TB) and many cases go undetected by current drug susceptibility tests (DSTs). This study was conducted to identify rifampicin (RIF) and isoniazid (INH) resistance associated genetic mutations undetected by current clinical diagnostics amongst persons with DR TB in Chennai, India. Retrospectively stored 166 DR TB isolates during 2013–2016 were retrieved and cultured in Löwenstein-Jensen medium. Whole genome sequencing (WGS) and MGIT DST for RIF and INH were performed. Discordant genotypic and phenotypic sensitivity results were repeated for confirmation and the discrepant results considered final. Further, drug resistance-conferring mutations identified through WGS were analyzed for their presence as targets in current WHO-recommended molecular diagnostics. WGS detected additional mutations for rifampicin and isoniazid resistance than WHO-endorsed line probe assays. For RIF, WGS was able to identify an additional 10% (15/146) of rpoB mutant isolates associated with borderline rifampicin resistance compared to MGIT DST. WGS could detect additional DR TB cases than commercially available and WHO-endorsed molecular DST tests. WGS results reiterate the importance of the recent WHO revised critical concentrations of current MGIT DST to detect low-level resistance to rifampicin. WGS may help inform effective treatment selection for persons at risk of, or diagnosed with, DR TB

Incidence and Impact of Ventilator Associated Multidrug Resistant Pneumonia in Patients with SARS-COV2

Introduction. Ventilator Associated Pneumonia (VAP) is associated with significant cost, morbidity, and mortality. There is limited data on the incidence of VAP, appropriate antibiotic timing, and the impact of multidrug resistant VAP in intubated Coronavirus disease-19 (COVID-19) patients. Methods. A retrospective study was conducted at 2 tertiary urban academic centers involving 132 COVID-19 patients requiring invasive mechanical ventilation (IMV). The epidemiology of VAP, the impact of prior empiric antibiotic administration on the development of Multidrug Resistant Organism (MDRO) infections, and the impact of VAP on patient outcomes were studied. Results. The average age of the patients was 60.58% were males, 70% were African-Americans and two-thirds of patients had diabetes, hypertension, or heart disease. The average Body Mass Index (BMI) was 32.9. Forty-one patients (27%) developed VAP. Patients with VAP had a significantly higher Sequential Organ Failure Assessment (SOFA) score prior to Intensive Care Unit (ICU) admission. Sixty percent received empiric antibiotics before initiation of IMV, mostly on hospital admission, and 81% received empiric antibiotics at the time of intubation. The administration of empiric antibiotics was not associated with a higher prevalence of VAP. The prevalence of VAP was 22 per 1000 days on ventilation. No difference in mortality was seen between VAP and non-VAP groups at 49% and 57% respectively (p=0.4). VAP was associated with increased ICU length of stay (LOS), 30 vs. 16 days (p<0.001), and longer hospital LOS 35 vs. 17 days (p<0.001). 40% of VAPs were caused by MDROs. The most common organism was Staphylococcus aureus (28%), with almost half (48%) being methicillin resistant Staphylococcus aureus (MRSA). Conclusion. VAP was a common complication of patients intubated for COVID-19 pneumonia. Most patients received empiric antibiotics upon the hospital and/or ICU admission. There was a 40% incidence of multidrug resistant pneumonia. Patients who developed VAP had almost twice as long hospital and ICU LOS

Risk of coronary artery disease in patients with gout on treatment with Colchicine: A systematic review and meta-analysis

Background: Colchicine has anti-inflammatory properties, but its utility in improving cardiovascular outcomes has been disputed. Here, we study the impact of colchicine on cardiovascular outcomes in patients with gout with and without coronary artery disease (CAD). Methods: Medline, Web of Science and Cochrane Central Register of Controlled Trials were systematically searched to identify relevant studies. Primary outcomes included myocardial infarction (MI), percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). Secondary outcomes included stroke and all-cause mortality. Results: We included 4 observational studies comprising 10,026 patients with gout on treatment with colchicine. There was no significant difference in the risk of myocardial infarction (risk ratio [RR] 0.71; 95% confidence interval [CI], 0.36–1.39), need for PCI, or need for CABG, between patients on colchicine and those not receiving colchicine. Colchicine was associated with a significantly lower risk of all-cause mortality (RR 0.58; 95% CI 0.43–0.79). Conclusion: Non-randomized studies suggest that risk of MI, stroke and revascularization is not higher in gout patients treated with colchicine compared to gout patients without colchicine treatment