Clinical efficacy of Azithromycin for COVID-19 management: A systematic meta-analysis of meta-analyses.

BACKGROUND: Azithromycin has been adopted as a component of the COVID-19 management protocol throughout the global healthcare settings but with a questionable if not downright unsubstantiated evidence base. OBJECTIVES: In order to amalgamate and critically appraise the conflicting evidence around the clinical efficacy of Azithromycin (AZO) vis a vis COVID-19 management outcomes, a meta-analysis of meta-analyses was carried out to establish an evidence-based holistic status of AZO vis a vis its efficacy as a component-in-use of the COVID-19 management protocol. METHODS: A comprehensive systematic search was carried out through PubMed/Medline, Cochrane and Epistemonikos with a subsequent appraisal of abstracts and full-texts, as required. The Quality of Reporting of Meta-analyses (QUOROM) checklist and the Assessment of Multiple Systematic Reviews (AMSTAR) methodology were adopted to assess the methodological quality of the included meta-analyses. Random-effects models were developed to calculate summarized pool Odds Ratios (with 95% confidence interval) for the afore determined primary and secondary outcomes. RESULTS: AZO, when compared with best available therapy (BAT) including or excluding Hydroxychloroquine, exhibited statistically insignificant reduction in mortality [(n= 27,204 patients) OR= 0.77 (95% CI: 0.51-1.16) (I2= 97%)], requirement of mechanical ventilation [(n= 14,908 patients) OR= 1.4 (95% CI: 0.58-3.35) (I2= 98%)], induction of arrhythmia [(n= 9,723 patients) OR= 1.21 (95% CI: 0.63-2.32) (I2= 92%)] and QTc prolongation (a surrogate for torsadogenic effect) [(n= 6,534 patients) OR= 0.62 (95% CI: 0.23-1.73) (I2= 96%)]. CONCLUSION: The meta-analysis of meta-analyses portrays AZO as a pharmacological agent that does not appear to have a comparatively superior clinical efficacy than BAT when it comes to COVID-19 management. Secondary to a very real threat of anti-bacterial resistance, it is suggested that AZO be discontinued and removed from COVID-19 management protocols.

Determination of the Absolute Configuration of Ballonigrin Lactone A Using Density Functional Theory Calculations.

We report the determination of the absolute configuration of a diterpenoid, namely, ballonigrin lactone A (BLA), by comparison of the computed optical rotations, [α]D, of its two diastereomers using density functional theory (DFT) calculations to the experimental [α]D value of +22.4. One of the diastereomers having configurations 4S, 5R, 6S, 10S, 15S was named "α-BLA," and the other one with configuration 4S, 5R, 6S, 10S, 15R was called "ß-BLA". Six conformers for each diastereomer (α-BLA and ß-BLA) of BLA were identified through their conformational analysis. [α]D values of these six conformations for each diastereomer were calculated using DFT at the mPW1PW91/6-311G(d,p)/SMDChloroform level of theory, leading to the conformationally averaged [α]D values of -96.8 for α-BLA and +65.1 for ß-BLA. Thus, it was found that the experimental [α]D value of +22.4 was of 4S, 5R, 6S, 10S, 15R, i.e., ß-BLA. Experimental and computed nuclear magnetic resonance (NMR) data were also compared, and this comparison was in accordance with the conclusion drawn from the comparison of [α]D values. Finally, the results were augmented with the calculation of the DP4 analysis, and the probability obtained also endorsed our earlier calculations.

Not All That Is Droopy Post Ad26.COV2.S (JNJ) Vaccine Is Bell's Palsy: A Rare Case of Isolated Dorsal Pontine Stroke Causing Ipsilateral Complete Hemi-Facial Palsy.

The Ad26.COV2.S vaccine, developed by Janssen (Beerse, Belgium), the pharmaceutical wing of Johnson & Johnson (JNJ), is one of the three vaccines approved for use against coronavirus disease 2019 (COVID-19) infection in the United States. We present a case of a 66-year-old female who presented to the emergency department with a one-day history of nausea, vomiting, room-spinning vertigo, and complete right facial weakness immediately after getting vaccinated with Ad26.COV2.S. Initial workup focused on uncovering a possible association between the vaccine and Bell's palsy. However, her prior history of stroke, presence of predisposing risk factors, and additional symptoms of nausea, vomiting, and vertigo prompted further neurological testing, which revealed an isolated right pontine lacunar infarct involving the right facial colliculus, mimicking Bell's palsy. Isolated dorsal pontine lesion presenting as hemifacial palsy is very rare and can be easily missed by clinicians. Relevant history and thorough neurological examination can help guide appropriate diagnostic testing and prevent potential biases. It is crucial for clinicians to know the distinguishing features between true Bell's palsy and acute brainstem infarction masquerading as Bell's.

A Retrospective Review of the Natural Progression of Cardiac Vegetation.

INTRODUCTION: Infective endocarditis (IE) is a life-threatening condition with an annual mortality of up to 40%. Vegetations are the hallmark of IE, however, factors that affect the initial size and changes in size remain unclear. Our study aims to investigate the natural history of cardiac vegetation, including changes in size and/or resolution with adequate treatment, and to analyze factors that influence size and potential for persistence. MATERIAL AND METHODS: We conducted a retrospective review of 102 patients admitted with native-valve endocarditis at Henry Ford Health System from September 1, 2017, to June 30, 2019. We included patients treated with six weeks of intravenous antibiotics who had both a diagnostic and a follow-up echocardiogram after antibiotic completion. The primary outcome was the change in vegetation size. Secondary measures included pathogen identification, valve involvement, number of complications, associated IV drug use, and co-infection with hepatitis B/C. RESULTS: Of the 102 patients reviewed, 30 patients matched the inclusion criteria. There was a significant decrease in vegetation size after adequate antibiotic treatment. However, complete resolution was not often seen. A statistically significant relationship was seen between vegetation size, IV drug use, and Staphylococcal species (including both methicillin-susceptible Staphylococcus aureus [MSSA] and methicillin-resistant S. aureus [MRSA]), whereas a history of hepatitis B or C was not significantly related to vegetation size. CONCLUSION: Large vegetation may predict a higher risk of embolic complications and can be reduced with IV antibiotics, although complete resolution is not likely. IV drug use and Staphylococcal endocarditis influence vegetation size and embolic complications. We argue that these subgroups should be prioritized for early surgical intervention.

Detection of hepatitis through proteases and protease inhibitors genes expression and identification of HCV untypable genotype in Abbottabad, Pakistan.

Liver cancer is the 5th most common cancer caused mainly due to the late detection of hepatitis. Therefore, the early detection of hepatitis through genetic markers boosts effective and remedial management. In addition, to determine the occurrence of hepatitis C virus (HCV), genotyping is indispensable as majority of hepatitis cases remain undiagnosed. The current study was designed to find the gene expression of proteases and proteases inhibitors in different hepatitis patients and to determine HCV genotypes mainly focusing on untypeable genotypes of HCV in Abbottabad, Pakistan. PCR was conducted to find the expression of proteases and protease inhibitors genes in hepatitis patients and healthy individuals. HCV genotyping was done by PCR based method and untypeable genotypes were sequenced and verified using online tools. Controlled individuals showed normal expression of cystatin C and leptin, low expression of cathepsin B while high expression of other studied genes including cathepsin D and G, TPP1 and serpin B1 could be seen. Hepatitis A patients showed high expression of leptin while other genes showed low expression. Hepatitis B patients revealed considerable variations in the cathepsin and cystatin C gene expression. Therefore, low cystatin C (high cathepsin B) and/or high cystatin C (low cathepsin B) levels can be regarded as a potential marker for hepatitis B. Hepatitis C infected patients showed high gene expression of cystatin C and leptin, so they could be useful markers for the diagnostics and prediction of the severity of HCV infections. While genotyping findings showed that about 45% of total PCR positive samples (110) were found to be of 3a genotype followed by 3b in 18%, 1a in 13.6% and 1b in 10%. About 9% of infections turned out to be mixed infections, whereas only 4.5% were untraceable by our genotyping system. Sequencing of untypeable genotypes and applying online tools revealed that the described untypeable genotypes of HCV were in fact variants of 3a genotype. Furthermore, full length characterization of these variants could help to classify them into types and subtypes. Keywords: hepatitis; genotyping; genes expression; proteases and protease inhibitors; ML; NJ.

Additive Value of Preprocedural Computed Tomography Planning Versus Stand-Alone Transesophageal Echocardiogram Guidance to Left Atrial Appendage Occlusion: Comparison of Real-World Practice.

Background Transesophageal echocardiogram is currently the standard preprocedural imaging for left atrial appendage occlusion. This study aimed to assess the additive value of preprocedural computed tomography (CT) planning versus stand-alone transesophageal echocardiogram imaging guidance to left atrial appendage occlusion. Methods and Results We retrospectively reviewed 485 Watchman implantations at a single center to compare the outcomes of using additional CT preprocedural planning (n=328, 67.6%) versus stand-alone transesophageal echocardiogram guidance (n=157, 32.4%) for left atrial appendage occlusion. The primary end point was the rate of successful device implantation without major peri-device leak (>5 mm). Secondary end points included major adverse events, total procedural time, delivery sheath and devices used, risk of major peri-device leak and device-related thrombus at follow-up imaging. A single/anterior-curve delivery sheath was used more commonly in those who underwent CT imaging (35.9% versus 18.8%; P<0.001). Additional preprocedural CT planning was associated with a significantly higher successful device implantation rate (98.5% versus 94.9%; P=0.02), a shorter procedural time (median, 45.5 minutes versus 51.0 minutes; P=0.03) and a less frequent change of device size (5.6% versus 12.1%; P=0.01), particularly device upsize (4% versus 9.4%; P=0.02). However, there was no significant difference in the risk of major adverse events (2.1% versus 1.9%; P=0.87). Only 1 significant peri-device leak (0.2%) and 5 device-related thrombi were detected in follow-up (1.2%) with no intergroup difference. Conclusions Additional preprocedural planning using CT in Watchman implantation was associated with a higher successful device implantation rate, a shorter total procedural time, and a less frequent change of device sizes.