Association of Body Mass Index with Multiple Organ Failure in Hospitalized Patients with COVID-19: A Multicenter Retrospective Cohort Study.

Purpose: This study examines whether excessive adipose tissue, as measured by the body mass index (BMI), is associated with higher systemic markers of inflammation and higher risk of severe acute organ failure among patients with coronavirus disease 2019 (COVID-19). Methods: This was a multicenter retrospective cohort study of 1370 hospitalized adults (18 years or older) with COVID-19 during the first wave of the pandemic. Patient-level variables were extracted from the electronic medical record. The primary predictor variable was the BMI at time of hospital admission, in accordance with the World Health Organization classification. Multivariable logistic regression analyses examined the association of BMI with the composite of acute respiratory distress syndrome (ARDS), as defined by the use of high-flow nasal canula, non-invasive ventilation, or mechanical ventilation, severe acute kidney injury (AKI), as defined by acute dialysis requirement, or in-hospital death. Results: After adjustment for important cofounders, the BMI stratum of > 40 kg/m2 (compared to the BMI < 25 kg/m2 reference group) was associated with higher odds for the composite of ARDS, severe AKI, or in-hospital death (adjusted odds ratio [ORadj] 1.69; 95% confidence interval [CI]1.03, 2.78). As a continuous variable, BMI (per 5-kg/m2 increase) remained independently associated with the composite outcome (ORadj 1.13; 95% CI 1.03, 1.23); patients in higher BMI categories exhibited significantly higher peak levels of C-reactive protein (CRP), a systemic marker of inflammation (P = .01). In a sub-cohort of 889 patients, the association of BMI with the composite outcome was no longer significant after adjustment for the peak level of CRP. Conclusions: Among hospitalized patients with COVID-19, a higher BMI is associated with higher risk of severe organ failure or in-hospital death, which dissipates after adjustment for CRP level. This supports the hypothesis that inflammation is a downstream mediator of adipose tissue on acute organ dysfunction.

Nephrotic-range proteinuria: a potential risk factor for failure of tixagevimab-cilgavimab prophylaxis.

BACKGROUND: Pre-exposure prophylaxis with tixagevimab-cilgavimab has been shown to reduce the incidence of SARS-CoV-2 infection in immunocompromised individuals. Individuals with nephrotic-range proteinuria can lose immunoglobulins such as tixagevimab-cilgavimab in the urine and, therefore, may derive less benefit from tixagevimab-cilgavimab. There are no published studies evaluating the association of nephrotic-range proteinuria with failure of tixagevimab-cilgavimab prophylaxis. METHODS: We conducted a retrospective observational cohort study of all individuals at our center who received tixagevimab-cilgavimab while they had nephrotic-range proteinuria. Each individual in the nephrotic group was matched 1:3 with controls who were matched for B cell depletion therapy in addition to the total dose and date of first tixagevimab-cilgavimab administration. The primary outcome was the development of breakthrough SARS-CoV-2 infection after receiving tixagevimab-cilgavimab. RESULTS: Sixteen patients received tixagevimab-cilgavimab between January 1st, 2022, and June 30th, 2022, at a time when they had nephrotic-range proteinuria. Proteinuria levels and serum creatinine levels were higher while serum albumin levels were lower in the nephrotic group compared to the control group. At a median follow-up of 251 days, 38% of individuals in the nephrotic group had developed breakthrough SARS-CoV-2 infections, compared to only 13% in the control group at a median follow-up of 238 days. Nephrotic-range proteinuria was associated with a higher incidence of breakthrough infection (log-rank P = 0.04). CONCLUSIONS: Nephrotic-range proteinuria may increase the risk of failure of tixagevimab-cilgavimab pre-exposure prophylaxis. Prospective studies to validate these findings and to evaluate the optimal dosing strategy of antibody-based prophylaxis in this group of patients are needed.

Acute on chronic bilateral renal vein thrombosis in the setting of remission of class V lupus nephritis: A case report and literature review.

Renal vein thrombosis (RVT), defined as the presence of a thrombus in the major renal vein or one of its tributaries, can present acutely or go unnoticed resulting in acute kidney injury or chronic kidney disease. RVT is associated with multiple etiologies, including nephrotic syndrome, thrombophilia, autoimmune disorders, and malignancy. Patients with systemic lupus erythematosus (SLE), a multiorgan autoimmune disorder, are predisposed to coagulopathy and thus are at a higher risk of venous and arterial thromboembolism. We describe the case of a 41-year-old man with SLE and biopsy-proven membranous glomerulonephritis (WHO class V lupus nephritis) in clinical remission with no evidence of nephrotic range proteinuria who presented with macroscopic hematuria and was diagnosed with acute-on-chronic bilateral RVT. We discuss the different causes of RVT and compare the clinical presentation, diagnostic imaging findings, and management of acute and chronic RVT.

Factors Associated with Severity of Acute Kidney Injury and Adverse Outcomes in Critically Ill Patients with COVID-19.

BACKGROUND: Acute kidney injury (AKI) is a well-recognized complication of coronavirus disease 2019 (COVID-19). The short and long-term outcomes of patients who develop AKI have not been well characterized. METHODS: In this multicenter retrospective cohort study, we describe the clinical characteristics and outcomes of critically ill adults with severe COVID-19 and AKI. Patient-level variables were extracted from the electronic medical record. Using nadir-to-peak serum creatinine, AKI was defined using the KDIGO definition. Multivariable logistic regression analyses examined factors associated with development of moderate-to-severe (stage 2-3) AKI, severe (stage-3) AKI, and the composite of renal replacement therapy (RRT) or in-hospital death. RESULTS: Among 459 critically ill adults with COVID-19, 371 (80.1%) developed AKI, with 179 (37.9%) developing stage-3 AKI. Male gender, black and Asian/Native American race, lower baseline estimated glomerular filtration rate (eGFR), higher body mass index (BMI), and higher Acute Physiology and Chronic Health Evaluation (APACHE) IV score were more prevalent among patients with severe AKI, as were systemic markers of inflammation. On multivariable analysis, male gender, black and Asian/Native American race, higher APACHE IV score, lower baseline eGFR, and higher BMI (mainly the highest BMI stratum ≥35 kg/m2) were independently associated with higher stages of AKI severity. Male gender, lower baseline eGFR, and higher APACHE IV score were also independently associated with the composite of RRT or in-hospital death. Moderate-to-severe AKI and severe AKI were independently associated with in-hospital death, and there was a significant interaction between BMI and moderate-to-severe AKI for the outcome of in-hospital death. Among 83 (18.1%) patients who required RRT, 27 (32.5%) survived, and 12 (44.4%) remained dialysis-dependent at discharge. At 3 and 6 months, 5 (41.7%) and 4 (33.3%) remained dialysis-dependent, respectively. CONCLUSIONS: AKI is common in critically ill adults with COVID-19. Several patient-level risk factors are associated with higher stages of AKI severity. BMI might be an effect modifier of AKI severity for in-hospital death. Among AKI survivors, there is a high rate of short- and long-term dialysis dependence.

Association of autosomal dominant polycystic kidney disease with cardiovascular disease: a US-National Inpatient Perspective.

PURPOSE: Data on the epidemiology of cardiovascular diseases (CVD) in patients with autosomal dominant polycystic kidney disease (ADPKD) are limited. In this study, we assess the prevalence of CVD in patients with ADPKD and evaluate associations between these two entities. METHODS: Using the National Inpatient Sample database, we identified 71,531 hospitalizations among adults aged ≥ 18 years with ADPKD, from 2006 to 2014 and collected relevant clinical data. RESULTS: The prevalence of CVD in the study population was 42.6%. The most common CVD were ischemic heart diseases (19.3%), arrhythmias (14.2%), and heart failure (13.1%). The prevalence of CVD increased with the severity of renal dysfunction (RD). We found an increase in hospitalizations of patients with ADPKD and CVD over the years (ptrend < 0.01), irrespective of the degree of RD. CVD was the greatest independent predictor of mortality in these patients (OR: 3.23; 95% CI 2.38-4.38 [p < 0.001]). In a propensity matched model of hospitalizations of patients with CKD with and without ADPKD, there was a significant increase in the prevalence of atrial fibrillation/flutter (AF), pulmonary hypertension (PHN), non-ischemic cardiomyopathy (NICM), and hemorrhagic stroke among patients with ADPKD when compared to patients with similar degree of RD without ADPKD. CONCLUSIONS: The prevalence of CVD is high among patients with ADPKD, and the most important risk factor associated with CVD is severity of RD. We found an increase in the trend of hospitalizations of patients with ADPKD associated with increased risk of AF, PHN, NICM, and hemorrhagic stroke. History of CVD is the strongest predictor of mortality among patients with ADPKD.

Country-level determinants of COVID-19 case rates and death rates: An ecological study.

The Coronavirus Disease 2019 (COVID-19) pandemic has had a variable worldwide impact, likely related to country-level characteristics. In this ecological study, we explored the association of COVID-19 case rates (per 100,000 people) and death rates (per 100,000 people) with country-level population health characteristics, economic and human development indicators, and habitat-related variables. To calculate country-level COVID-19 case and death rates, the number of cases and deaths were extracted from the Johns Hopkins Coronavirus Resource Center through September 30, 2021. Country-level population health characteristics, economic, human development, and habitat-related indicators were extracted from several publicly available online sources of international organizations. Results were tabulated according to world zones and country economies. Unadjusted and adjusted multiple imputation linear regression analyses were performed to examine the association between country-level variables (per 1-standard deviation [SD] increase) and COVID-19 case and death rates. To satisfy the linear regression model assumptions of normality of residuals, we used the square root transformation of both outcomes. A total of 187 countries and territories were analyzed, with a median (25th, 75th percentiles) aggregate COVID-19 case rate of 3,605 (463, 8,228) per 100,000, a COVID-19 death rate of 45.9 (8.9, 137.1) per 100,000, and a case-fatality rate of 1.6% (1.2%, 2.6%). On multivariable analyses, each country-level 1-SD higher percentage of adults with obesity (ß coefficient 13.7; 95% confidence interval [CI] 13.7; 8.9, 18.4), percentage of smokers (5.8; 95% CI 1.2, 10.5), percentage of adults with high blood pressure (4.9; 95% CI 0.3, 9.6), and gross national income (GNI) per capita (9.5; 95% CI 4.6, 14.5) was independently associated with higher square root of COVID-19 case rate, while average household size (-1.7; 95% CI -12.3, -3.2) was independently associated with lower square root of COVID-19 case rate. Similarly, each 1-SD higher percentage of adults with obesity (1.76; 95% CI 0.99, 2.52), percentage of adults with high blood pressure (1.11; 95% CI 0.48, 1.74), percentage of adults with physical inactivity (1.01; 95% CI 0.10, 1.191), and travel & tourism competitiveness index (1.05; 95% CI 0.06, 2.04) was independently associated with higher square root of COVID-19 death rate, whereas GNI per capita (-0.92; 95% CI -1.81, -0.03), and average household size (-1.07; 95% CI -1.87, -0.27) was independently associated with lower square root of COVID-19 death rate. This ecological study informs the need to develop country-specific public health interventions to better target populations at high risk for COVID-19, and test interventions to prevent transmission of SARS-CoV-2, taking into consideration cross-country differences in population health characteristics, and economic, human development and habitat-related factors.

A case of herpes simplex 2 encephalitis with an unusual radiographic manifestation.

Herpes Simplex Virus (HSV) continues to be an important pathogen inflicting encephalitis in adults and children globally that entails high morbidity and mortality. Prompt diagnosis and treatment are the keys to minimize potential sequelae of the disease. Although HSV encephalitis-1(HSVE-1) is well recognized for its radiographic manifestation of temporal lobe involvement owing to its pathogenesis, radiographic features of HSVE-2 are less uniform. Lumbar puncture with HSV PCR testing is the gold standard for diagnosis. However, when lumbar puncture is not immediately obtainable, consideration of HSVE should be entertained in compatible clinical setting even in the absence of characteristic radiographic finding. We report a case of type 2 HSVE with atypical radiographic manifestation involving bilateral basal ganglia.

A rare case of herniated duplex collecting system causing obstructive uropathy.

BACKGROUND: An inguinal hernia is the protrusion of intraabdominal organs through an opening in the abdominal wall. Structures such as small and large intestines are commonly contained within inguinal hernias. However, uretero-inguinal hernia of the native collecting system is an extremely rarely reported entity. If unrecognized, acute kidney injury due to obstructive uropathy or serious intraprocedural ureteral injuries during hernia repair can occur. A duplex collecting system is a congenital kidney anomaly with an incidence of 0.8%. A uretero-inguinal hernia involving duplicated ureters has not been previously described in literature. Here we report a case of obstructive uropathy secondary to uretero-inguinal hernia involving duplicated ureters. CASE PRESENTATION: A 78-year-old male known to have a left sided inguinal hernia presented to the Emergency department with two weeks of intermittent suprapubic tenderness, dysuria, frequency, urgency, frothy urine as well as nausea and vomiting. Workup on admission revealed an elevated creatinine of 2.8 mg/dl. CT imaging revealed duplicated left sided ureters with left inguinal hernia containing the ureters. There was cystic ureteral dilation within the herniation sac as well as moderate left hydroureteronephrosis. Patient had an elective inguinal hernia repair with left ureteral stent placement. Following the surgery, he had recovery of kidney function to the previous baseline serum creatinine of 1.5 mg/dl. CONCLUSION: A duplex collecting system arises when two ureteral buds are formed during fetal development. However, diagnosis can be made in rare instances during adulthood when duplex collecting systems are usually found incidentally. Uretero-inguinal hernias have been reported as a common complication of renal transplant. However, uretero-inguinal hernias in native kidneys are considered an uncommon finding, especially with a duplex collecting system. When patients present with herniation and acute kidney injury, it is important to rule out the possibility of uretero-inguinal hernia to minimize complications such as obstructive uropathy and kidney failure. CT scan providing cross-sectional imaging is the ideal modality for identification of the site and etiology of urinary tract obstruction and site of herniation. If during imaging, an obstructive uropathy is observed, a nephroureteral stent or nephrostomy tube can be inserted to protect the ureter as well as relieve the obstruction, respectively.

SGLT2 Inhibitors, GLP-1 Agonists, and DPP-4 Inhibitors in Diabetes and Microvascular Complications: A Review.

The prevalence of diabetes and its associated complications is increasing throughout the decades. Promising diabetes medications were introduced to the market including GLP-1 agonists, DPP-4 inhibitors, and SGLT2 inhibitors aiming to target these complications. The literature lacks sufficient data regarding these new medications and their influence on nephropathy, retinopathy, and neuropathy. This review expands on the major results of effects of the 3 drug classes on microvascular complications. In our review, both SGLT2 inhibitors and GLP-1 agonists appear to have promising nephroprotective outcomes at this stage, with less promising outcomes seen with DPP-4 inhibitors. Moreover, the retinoprotective outcomes of both SGLT2 inhibitors and DPP-4 inhibitors were only tested on mice, while those of GLP-1 agonists were assessed in few trials. In addition, the results of both GLP-1 agonists and DPP-4 inhibitors showed discrepancies in these studies. On the contrary, conclusions regarding the effect of these medications on neuroprotective outcomes cannot be drawn at the time due to the lack of clinical trials targeting these complications. Hence, a clearer picture of the microvascular outcomes will manifest over time with the release of multiple upcoming clinical trials.

Paraneoplastic leukemoid reaction in a patient with metastatic adenocarcinoma of the lung.

Paraneoplastic syndromes in lung malignancies can lead to leukemoid reaction with an elevation of eosinophils, neutrophils, and monocytes. The elevation of these three lineages together due to paraneoplastic syndromes has not been described in literature yet.

Stress, Burnout and Coping Strategies in Preclinical Medical Students.

It is acknowledged that physicians do not seek the same expert aid for themselves as they would offer their patients. In their preclinical years, medical students appear to espouse comparable behavior. To many, medicine is described as a never-ending path that places the student under heavy stress and burnout from the beginning, leaving him/her vulnerable and with insufficient coping methods. Hence, the objective of this study is to 1) explore the prevalence of stress and burnout among preclinical medical students, and 2) propose solutions to decrease stress and burnout and improve medical education in the preclinical years. A detailed scholarly research strategy using Google Scholar, Scopus, Embase, MEDLINE and PubMed was implemented to highlight key themes that are relevant to preclinical medical students' stress and burnout. Stress varied among different samples of medical students and ranged between 20.9% and 90%. Conversely, burnout ranged between 27% and 75%. Methods that help in reducing the incidence of stress and burnout by promoting strategies that focus on personal engagement, extracurricular activities, positive reinterpretation and expression of emotion, student-led mentorship programs, evaluation systems, career counseling and life coaching should be adopted.

Extracurricular activities associated with stress and burnout in preclinical medical students.

This study aims to assess the prevalence of stress and burnout among preclinical medical students in a private university in Beirut, Lebanon, and evaluate the association between extracurricular involvement and stress and burnout relief in preclinical medical students. A cross-sectional survey was conducted on a random sample of 165 preclinical medical students. Distress level was measured using the 12-item General Health Questionnaire (GHQ-12) while that of burnout was measured through the Maslach Burnout Inventory-Student Survey (MBI-SS). The MBI-SS assesses three interrelated dimensions: emotional exhaustion, cynicism, and academic efficacy. Extracurricular activities were divided into four categories: physical exercise, music, reading, and social activities. All selected participants responded. A substantial proportion of preclinical medical students suffered from stress (62%) and burnout (75%). Bivariate and multivariate regression analyses revealed that being a female or a 1st year medical student correlated with higher stress and burnout. Music-related activities were correlated with lower burnout. Social activities or living with parents were associated with lower academic efficacy. The high stress and burnout levels call for action. Addressing the studying conditions and attending to the psychological wellbeing of preclinical medical students are recommendations made in the study.