DON\u27T BLAME THE VACCINE

Background: The mRNA COVID vaccine is a rare cause of myocarditis in young patients. We describe a case of cardiogenic shock with extensive workup ruling out COVID vaccine induced myocarditis. Case: 42-year-old female who drinks 5 Monster energy drinks and 3-4 cups of coffee daily presented to the hospital with palpitations two weeks following her mRNA COVID vaccine. EKG showed atrial tachycardia with heart rates of 160 beats per minute. Adenosine and Lopressor were administered resulting in hemodynamic instability requiring norepinephrine. An echocardiogram showed dilated cardiomyopathy with ejection fraction of 15%. Right heart catheterization was performed, and the cardiac index was 1.22 L/min/m², systemic vascular resistance was 1918 dynes*sec*cm-5 and wedge pressure was 31 mm Hg. The patient was started on nitroprusside, furosemide, and milrinone drips and she began to improve. The patient was adamant the vaccine is what triggered her heart failure and extensive testing was performed to rule out COVID vaccine induced myocarditis. Workup showed normal coronary arteries and no evidence of infiltrative disease or myocarditis on cardiac MRI. The etiology was from tachycardia induced cardiomyopathy triggered by excessive stimulants and the patient had successful atrial tachycardia ablation of the right superior pulmonary vein. She was discharged on medical therapy for heart failure and advised to stop drinking energy drinks. Decision-making: Once the patient did not respond to the rate controlling agents an echocardiogram showed reduced ejection fraction. Right heart catheterization confirmed cardiogenic shock and nitroprusside and milrinone were started to help reduce afterload and improve contractility. Workup to exclude COVID induced myocarditis lead to the diagnosis of tachycardia induced cardiomyopathy and atrial tachycardia ablation was performed. Conclusion: We report a case of cardiogenic shock with workup diagnosing tachycardia induced cardiomyopathy induced from a combination of excessive monster energy drinks and coffee. She was treated successfully with afterload reduction, inotrope support, and atrial tachycardia ablation

Compression wraps as adjuvant therapy in the management of acute systolic heart failure

BACKGROUND: Guidelines recommend targeting decongestion in management of decompensated HF, with lower extremity edema often serving as the clinical target. LECW are seldom used in the acute setting, with a paucity of data on efficacy in HF, despite serving as a cornerstone of chronic lymphedema management. PRIMARY OBJECTIVE: Study the efficacy and safety of LECW in acute decompensated HF. METHODS: Open-label, randomized, parallel-group clinical trial. PRIMARY OUTCOMES: Days on intravenous (IV) diuretic therapy, total hospital length of stay (LOS), and 30-day all-cause readmission. RESULTS: 32 patients were enrolled, with 29 patients completing the study. Enrollment was suspended due to the COVID-19 pandemic. Overall LOS was shorter in the intervention group (3.5 vs 6 days, p = 0.05), with no significant difference in total days on IV diuresis or 30-day readmission rate with use of LECW. Fewer patients required continuous diuretic infusion after treatment with LECW (0 vs 7 patients, p = 0.027). The intervention group scored significantly better on the MLWHF (55.5 vs 65, p = 0.021), including both the physical and emotional dimension scores. No adverse events were reported with use of LECW, including a significantly lower incidence of AKI (1 vs 13 patients, p = 0.005). CONCLUSION: The use of LECW resulted in reduced hospital LOS compared to standard therapy, with no difference in days of IV diuresis administration or 30-day readmission. Treatment with LECW also resulted in less continuous IV diuretic therapy, fewer incidence of AKI, and improved quality of life. Trends toward less escalation of diuresis, and greater reduction in edema were also observed

A Precision Medicine Approach Uncovers a Unique Signature of Neutrophils in Patients With Brushite Kidney Stones

Introduction: We have previously found that papillary histopathology differs greatly between calcium oxalate and brushite stone formers (SF); the latter have much more papillary mineral deposition, tubular cell injury, and tissue fibrosis. Methods: In this study, we applied unbiased orthogonal omics approaches on biopsied renal papillae and extracted stones from patients with brushite or calcium oxalate (CaOx) stones. Our goal was to discover stone type-specific molecular signatures to advance our understanding of the underlying pathogenesis. Results: Brushite SF did not differ from CaOx SF with respect to metabolic risk factors for stones but did exhibit increased tubule plugging in their papillae. Brushite SF had upregulation of inflammatory pathways in papillary tissue and increased neutrophil markers in stone matrix compared with those with CaOx stones. Large-scale 3-dimensional tissue cytometry on renal papillary biopsies showed an increase in the number and density of neutrophils in the papillae of patients with brushite versus CaOx, thereby linking the observed inflammatory signatures to the neutrophils in the tissue. To explain how neutrophil proteins appear in the stone matrix, we measured neutrophil extracellular trap (NET) formation-NETosis-and found it significantly increased in the papillae of patients with brushite stones compared with CaOx stones. Conclusion: We show that increased neutrophil infiltration and NETosis is an unrecognized factor that differentiates brushite and CaOx SF and may explain the markedly increased scarring and inflammation seen in the papillae of patients with brushite stones. Given the increasing prevalence of brushite stones, the role of neutrophil activation in brushite stone formation requires further study

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Holospiniferoside: A New Antitumor Cerebroside from The Red Sea Cucumber Holothuria spinifera: In Vitro and In Silico Studies

Chemical investigation of the methanolic extract of the Red Sea cucumber Holothuria spinifera led to the isolation of a new cerebroside, holospiniferoside (1), together with thymidine (2), methyl-α-d-glucopyranoside (3), a new triacylglycerol (4), and cholesterol (5). Their chemical structures were established by NMR and mass spectrometric analysis, including gas chromatography–mass spectrometry (GC–MS) and high-resolution mass spectrometry (HRMS). All the isolated compounds are reported in this species for the first time. Moreover, compound 1 exhibited promising in vitro antiproliferative effect on the human breast cancer cell line (MCF-7) with IC$_{50}$ of 20.6 µM compared to the IC50 of 15.3 µM for the drug cisplatin. To predict the possible mechanism underlying the cytotoxicity of compound 1, a docking study was performed to elucidate its binding interactions with the active site of the protein Mdm2–p53. Compound 1 displayed an apoptotic activity via strong interaction with the active site of the target protein. This study highlights the importance of marine natural products in the design of new anticancer agents

Injury burden in individuals aged 50 years or older in the Eastern Mediterranean region, 1990–2019: a systematic analysis from the Global Burden of Disease Study 2019

Background: Injury poses a major threat to health and longevity in adults aged 50 years or older. The increased life expectancy in the Eastern Mediterranean region warrants a further understanding of the ageing population's inevitable changing health demands and challenges. We aimed to examine injury-related morbidity and mortality among adults aged 50 years or older in 22 Eastern Mediterranean countries. Methods: Drawing on data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we categorised the population into adults aged 50–69 years and adults aged 70 years and older. We examined estimates for transport injuries, self-harm injuries, and unintentional injuries for both age groups, with sex differences reported, and analysed the percentage changes from 1990 to 2019. We reported injury-related mortality rates and disability-adjusted life-years (DALYs). The Socio-demographic Index (SDI) and the Healthcare Access and Quality (HAQ) Index were used to better understand the association of socioeconomic factors and health-care system performance, respectively, with injuries and health status in older people. Healthy life expectancy (HALE) was compared with injury-related deaths and DALYs and to the SDI and HAQ Index to understand the effect of injuries on healthy ageing. Finally, risk factors for injury deaths between 1990 and 2019 were assessed. 95% uncertainty intervals (UIs) are given for all estimates. Findings: Estimated injury mortality rates in the Eastern Mediterranean region exceeded the global rates in 2019, with higher injury mortality rates in males than in females for both age groups. Transport injuries were the leading cause of deaths in adults aged 50–69 years (43·0 [95% UI 31·0–51·8] per 100 000 population) and in adults aged 70 years or older (66·2 [52·5–75·5] per 100 000 population), closely followed by conflict and terrorism for both age groups (10·2 [9·3–11·3] deaths per 100 000 population for 50–69 years and 45·7 [41·5–50·3] deaths per 100 000 population for ≥70 years). The highest annual percentage change in mortality rates due to injury was observed in Afghanistan among people aged 70 years or older (400·4% increase; mortality rate 1109·7 [1017·7–1214·7] per 100 000 population). The leading cause of DALYs was transport injuries for people aged 50–69 years (1798·8 [1394·1–2116·0] per 100 000 population) and unintentional injuries for those aged 70 years or older (2013·2 [1682·2–2408·7] per 100 000 population). The estimates for HALE at 50 years and at 70 years in the Eastern Mediterranean region were lower than global estimates. Eastern Mediterranean countries with the lowest SDIs and HAQ Index values had high prevalence of injury DALYs and ranked the lowest for HALE at 50 years of age and HALE at 70 years. The leading injury mortality risk factors were occupational exposure in people aged 50–69 years and low bone mineral density in those aged 70 years or older. Interpretation: Injuries still pose a real threat to people aged 50 years or older living in the Eastern Mediterranean region, mainly due to transport and violence-related injuries. Dedicated efforts should be implemented to devise injury prevention strategies that are appropriate for older adults and cost-effective injury programmes tailored to the needs and resources of local health-care systems, and to curtail injury-associated risk and promote healthy ageing. Funding: Bill & Melinda Gates Foundation

Assessing performance of the Healthcare Access and Quality Index, overall and by select age groups, for 204 countries and territories, 1990–2019: a systematic analysis from the Global Burden of Disease Study 2019

Health-care needs change throughout the life course. It is thus crucial to assess whether health systems provide access to quality health care for all ages. W measured the Healthcare Access and Quality (HAQ) Index overall and for select age groups in 204 locations from 1990 to 2019. For GBD 2019, HAQ Index construction methods were updated to use the arithmetic mean of scaled mortality-to-incidence ratios (MIRs) and risk-standardised death rates (RSDRs) for 32 causes of death that should not occur in the presence of timely, quality health care. Across locations and years, MIRs and RSDRs were scaled from 0 (worst) to 100 (best) separately, putting the HAQ Index on a different relative scale for each age group. We estimated absolute convergence for each group on the basis of whether the HAQ Index grew faster in absolute terms between 1990 and 2019 in countries with lower 1990 HAQ Index scores than countries with higher 1990 HAQ Index scores and by Socio-demographic Index (SDI) quintile. Interpretation Although major gaps remain across levels of social and economic development, convergence in the young group is an encouraging sign of reduced disparities in health-care access and quality. However, divergence in the working and post-working groups indicates that health-care access and quality is lagging at lower levels of social and economic development. To meet the needs of ageing populations, health systems need to improve health-care access and quality for working-age adults and older populations while continuing to realise gains among the young