Renal outcomes in adults with HBV, HIV and HBV/HIV coinfection after 3 years of antiviral therapy in urban Tanzania.

BACKGROUND: An enhanced understanding of renal outcomes in persons with chronic HBV, HIV, and HBV/HIV coinfection is needed to mitigate chronic kidney disease in regions where HBV and HIV are endemic. OBJECTIVES: To investigate changes in estimated glomerular filtration rate (eGFR) in adults with HBV, HIV or HBV/HIV enrolled in a 3 year prospective cohort study of liver outcomes in Dar es Salaam, Tanzania and initiated on antiviral therapy. METHODS: We compared eGFR between and within groups over time using mixed-effects models. RESULTS: Four hundred and ninety-nine participants were included in the analysis (HBV: 164; HIV: 271; HBV/HIV: 64). Mean baseline eGFRs were 106.88, 106.03 and 107.18 mL/min/1.73 m2, respectively. From baseline to Year 3, mean eGFR declined by 4.3 mL/min/1.73 m2 (95% CI -9.3 to 0.7) and 3.7 (-7.8 to 0.5) in participants with HBV and HIV, respectively, and increased by 5.1 (-4.7 to 14.9) in those with HBV/HIV. In multivariable models, participants with HBV had lower eGFRs compared with those with HIV or HBV/HIV and, after adjusting for HBV DNA level and hepatitis B e antigen (HBeAg) status, significantly lower eGFRs than those with HBV/HIV at all follow-up visits. CONCLUSIONS: In this Tanzanian cohort, coinfection with HBV/HIV did not appear to exacerbate renal dysfunction compared with those with either infection alone. Although overall changes in eGFR were small, persons with HBV experienced lower eGFRs throughout follow-up despite their younger age and similar baseline values. Longer-term studies are needed to evaluate continuing changes in eGFR and contributions from infection duration and other comorbidities.

Tecovirimat Use in Ambulatory and Hospitalized Patients With Monkeypox Virus Infection.

ABSTRACT: In this case series of 20 ambulatory and hospitalized adult patients treated for monkeypox virus at a large academic medical center in Chicago, Illinois, tecovirimat use was reserved for those with or at high risk of severe disease, delayed because of logistical and clinical factors, but well tolerated.

Transfusion-Transmitted Cache Valley Virus Infection in a Kidney Transplant Recipient With Meningoencephalitis.

BACKGROUND: Cache Valley virus (CVV) is a mosquito-borne virus that is a rare cause of disease in humans. In the fall of 2020, a patient developed encephalitis 6 weeks following kidney transplantation and receipt of multiple blood transfusions. METHODS: After ruling out more common etiologies, metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) was performed. We reviewed the medical histories of the index kidney recipient, organ donor, and recipients of other organs from the same donor and conducted a blood traceback investigation to evaluate blood transfusion as a possible source of infection in the kidney recipient. We tested patient specimens using reverse-transcription polymerase chain reaction (RT-PCR), the plaque reduction neutralization test, cell culture, and whole-genome sequencing. RESULTS: CVV was detected in CSF from the index patient by mNGS, and this result was confirmed by RT-PCR, viral culture, and additional whole-genome sequencing. The organ donor and other organ recipients had no evidence of infection with CVV by molecular or serologic testing. Neutralizing antibodies against CVV were detected in serum from a donor of red blood cells received by the index patient immediately prior to transplant. CVV neutralizing antibodies were also detected in serum from a patient who received the co-component plasma from the same blood donation. CONCLUSIONS: Our investigation demonstrates probable CVV transmission through blood transfusion. Clinicians should consider arboviral infections in unexplained meningoencephalitis after blood transfusion or organ transplantation. The use of mNGS might facilitate detection of rare, unexpected infections, particularly in immunocompromised patients.

Role of Therapeutic Drug Monitoring in the Treatment of Persistent Mycobacterium abscessus Central Nervous System Infection: A Case Report and Review of the Literature.

A patient presenting with recurrent ventriculoperitoneal shunt infection was found to have Mycobacterium abscessus growing from cerebrospinal fluid (CSF), which remained persistently positive. Therapeutic monitoring of clarithromycin, imipenem, and linezolid in CSF and plasma revealed lower than expected concentrations, prompting alternative therapy and culture clearance on hospital day 42.

Disparities in COVID-19 Monoclonal Antibody Delivery: a Retrospective Cohort Study.

BACKGROUND: Disparities in access to anti-SARS-CoV-2 monoclonal antibodies have not been well characterized. OBJECTIVE: We sought to explore the impact of race/ethnicity as a social construct on monoclonal antibody delivery. DESIGN/PATIENTS: Following implementation of a centralized infusion program at a large academic healthcare system, we reviewed a random sample of high-risk ambulatory adult patients with COVID-19 referred for monoclonal antibody therapy. MAIN MEASURES: We examined the relationship between treatment delivery, race/ethnicity, and other demographics using descriptive statistics, binary logistic regression, and spatial analysis. KEY RESULTS: There was no significant difference in racial composition between patients who did (n = 25) and patients who did not (n = 378) decline treatment (p = 0.638). Of patients who did not decline treatment, 64.8% identified as White, 14.8% as Hispanic/Latinx, and 11.1% as Black. Only 44.6% of Hispanic/Latinx and 31.0% of Black patients received treatment compared to 64.1% of White patients (OR 0.45, 95% CI 0.25-0.81, p = 0.008, and OR 0.25, 95% CI 0.12-0.50, p < 0.001, respectively). In multivariable analysis including age, race, insurance status, non-English primary language, county Social Vulnerability Index, illness severity, and total number of comorbidities, associations between receiving treatment and Hispanic/Latinx or Black race were no longer statistically significant (AOR 1.32, 95% CI 0.69-2.53, p = 0.400, and AOR 1.34, 95% CI 0.64-2.80, p = 0.439, respectively). However, patients who were uninsured or whose primary language was not English were less likely to receive treatment (AOR 0.16, 95% CI 0.03-0.88, p = 0.035, and AOR 0.37, 95% CI 0.15-0.90, p = 0.028, respectively). Spatial analysis suggested decreased monoclonal antibody delivery to Cook County patients residing in socially vulnerable communities. CONCLUSIONS: High-risk ambulatory patients with COVID-19 who identified as Hispanic/Latinx or Black were less likely to receive monoclonal antibody therapy in univariate analysis, a finding not explained by patient refusal. Multivariable and spatial analyses suggested insurance status, language, and social vulnerability contributed to racial disparities.

Real-World Experience of Bamlanivimab for Coronavirus Disease 2019 (COVID-19): A Case-Control Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has strained healthcare systems with patient hospitalizations and deaths. Anti-spike monoclonal antibodies, including bamlanivimab, have demonstrated reduction in hospitalization rates in clinical trials, yet real-world evidence is lacking. METHODS: We conducted a retrospective case-control study across a single healthcare system of nonhospitalized patients, age 18 years or older, with documented positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, risk factors for severe COVID-19, and referrals for bamlanivimab via emergency use authorization. Cases were defined as patients who received bamlanivimab; contemporary controls had a referral order placed but did not receive bamlanivimab. The primary outcome was 30-day hospitalization rate from initial positive SARS-CoV-2 polymerase chain reaction (PCR). Descriptive statistics, including χ 2 and Mann-Whitney U test, were performed. Multivariable logistic regression was used for adjusted analysis to evaluate independent associations with 30-day hospitalization. RESULTS: Between 30 November 2020 and 19 January 2021, 218 patients received bamlanivimab (cases), and 185 were referred but did not receive drug (controls). Thirty-day hospitalization rate was significantly lower among patients who received bamlanivimab (7.3% vs 20.0%, risk ratio [RR] 0.37, 95% confidence interval [CI]: .21-.64, P < .001), and the number needed to treat was 8. On logistic regression, odds of hospitalization were increased in patients not receiving bamlanivimab and with a higher number of pre-specified comorbidities (odds ratio [OR] 4.19 ,95% CI: 1.31-2.16, P < .001; OR 1.68, 95% CI: 2.12-8.30, P < .001, respectively). CONCLUSIONS: Ambulatory patients with COVID-19 who received bamlanivimab had a lower 30-day hospitalization than control patients in real-world experience. We identified receipt of bamlanivimab and fewer comorbidities as protective factors against hospitalization.Bamlanivimab's role in preventing hospitalization associated with coronavirus disease 2019 (COVID-19) remains unclear. In a real-world, retrospective study of 403 high-risk, ambulatory patients with COVID-19, receipt of bamlanivimab compared to no monoclonal antibody therapy was associated with lower 30-day hospitalization.

Biological Mitigation of Antibiotic Resistance Gene Dissemination by Antioxidant-Producing Microorganisms in Activated Sludge Systems.

Antibiotic resistance is the principal mechanism of an evergrowing bacterial threat. Antibiotic residues in the environment are a major contributor to the spread of antibiotic resistance genes (ARGs). Subinhibitory concentrations of antibiotics cause bacteria to produce reactive oxygen species (ROS), which can lead to mutagenesis and horizontal gene transfer (HGT) of ARGs; however, little is known about the mitigation of ARG dissemination through ROS removal by antioxidants. In this study, we examine how antioxidant-producing microorganisms inoculated in replicate activated sludge systems can biologically mitigate the dissemination of ARGs. Through quantitative polymerase chain reaction (qPCR), we showed that antioxidant-producing microorganisms could decrease the persistence of the RP4 plasmid and alleviate enrichment of ARGs (sul1) and class 1 integrons (intl1). Metagenomic sequencing identified the most diverse resistome and the most mutated Escherichia coli ARGs in the reactor that contained antibiotics but no antioxidant-producing microorganisms, suggesting that antioxidant-producing microorganisms mitigated ARG enrichment and mutation. Host classification revealed that antioxidant-producing microorganisms decreased the diversity of ARG hosts by shaping the microbial community through competition and functional pathway changes. Conjugative experiments demonstrated that conjugative transfer of ARGs could be mitigated by coculture with antioxidant-producing microorganisms. Overall, this is a novel study that shows how ARG enrichment and HGT can be mitigated through bioaugmentation with antioxidant-producing microorganisms.

Cost-effectiveness of screening strategies for identifying pediatric diabetes mellitus and dysglycemia.

OBJECTIVE: To conduct a cost-effectiveness analysis of screening strategies for identifying children with type 2 diabetes mellitus and dysglycemia (prediabetes/diabetes). DESIGN: Cost simulation study. SETTING: A one-time US screening program. STUDY PARTICIPANTS: A total of 2.5 million children aged 10 to 17 years. INTERVENTION: Screening strategies for identifying diabetes and dysglycemia. MAIN OUTCOME MEASURES: Effectiveness (proportion of cases identified), total costs (direct and indirect), and efficiency (cost per case identified) of each screening strategy based on test performance data from a pediatric cohort and cost data from Medicare and the US Bureau of Labor Statistics. RESULTS: In the base-case model, 500 and 400 000 US adolescents had diabetes and dysglycemia, respectively. For diabetes, the cost per case was extremely high ($312 000-$831 000 per case identified) because of the low prevalence of disease. For dysglycemia, the cost per case was in a more reasonable range. For dysglycemia, preferred strategies were the 2-hour oral glucose tolerance test (100% effectiveness; $390 per case), 1-hour glucose challenge test (63% effectiveness; $571), random glucose test (55% effectiveness; $498), or a hemoglobin A1c threshold of 5.5% (45% effectiveness; $763). Hemoglobin A1c thresholds of 5.7% and 6.5% were the least effective and least efficient (ranges, 7%-32% and $938-$3370) of all strategies evaluated. Sensitivity analyses for diabetes revealed that disease prevalence was a major driver of cost-effectiveness. Sensitivity analyses for dysglycemia did not lead to appreciable changes in overall rankings among tests. CONCLUSIONS: For diabetes, the cost per case is extremely high because of the low prevalence of the disease in the pediatric population. Screening for diabetes could become more cost-effective if dysglycemia is explicitly considered as a screening outcome.

Evaluation of nonfasting tests to screen for childhood and adolescent dysglycemia.

OBJECTIVE: To assess performance of nonfasting tests to screen children for dysglycemia (prediabetes or diabetes). RESEARCH DESIGN AND METHODS: This was a cross-sectional study of 254 overweight or obese (BMI ≥85th percentile) children aged 10-17 years. Subjects came for two visits to a clinical research unit. For visit one, they arrived fasting and a 2-h glucose tolerance test and HbA(1c) and fructosamine testing were performed. For visit two, they arrived nonfasting and had a random plasma glucose, a 1-h 50-g nonfasting glucose challenge test (1-h GCT), and urine dipstick performed. The primary end point was dysglycemia (fasting plasma glucose ≥100 mg/dL or a 2-h postglucose ≥140 mg/dL). Test performance was assessed using receiver operating characteristic (ROC) curves and calculations of area under the ROC curve. RESULTS: Approximately one-half of children were female, 59% were white, and 30% were black. There were 99 (39%) cases of prediabetes and 3 (1.2%) cases of diabetes. Urine dipstick, HbA(1c) (area under the curve [AUC] 0.54 [95% CI 0.47-0.61]), and fructosamine (AUC 0.55 [0.47-0.63]) displayed poor discrimination for identifying children with dysglycemia. Both random glucose (AUC 0.66 [0.60-0.73]) and 1-h GCT (AUC 0.68 [0.61-0.74]) had better levels of test discrimination than HbA(1c) or fructosamine. CONCLUSIONS: HbA(1c) had poor discrimination, which could lead to missed cases of dysglycemia in children. Random glucose or 1-h GCT may potentially be incorporated into clinical practice as initial screening tests for prediabetes or diabetes and for determining which children should undergo further definitive testing.

Endothelial progenitor cells in primary aldosteronism: a biomarker of severity for aldosterone vasculopathy and prognosis.

CONTEXT: Primary aldosteronism (PA) is associated with a higher incidence of cardiovascular events, probably through mineralocorticoid receptor (MR)-dependent endothelial cell dysfunction, in comparison with essential hypertension (EH). OBJECTIVE: Our objective was to investigate the number and function of endothelial progenitor cells (EPC) in PA and the relationship with arterial stiffness and disease progression. DESIGN AND SETTING: We conducted a prospective study of the change of EPC number and outcome of PA patients after treatment at a tertiary medical center. PRIMARY OUTCOMES: Changes in arterial stiffness and EPC number after treatment and the curability of hypertension were assessed. PATIENTS: A total of 113 PA patients (87 patients diagnosed with aldosterone-producing adenoma, 26 with idiopathic hyperaldosteronism) and 55 patients with EH participated. RESULTS: PA patients had higher arterial stiffness than EH patients (P = 0.006), with a lower numbers of circulating EPC and endothelial colony-forming units (P < 0.05). The differences were ameliorated at 6 months after unilateral adrenalectomy or treatment with spironolactone. Expression of MR was identified in the EPC. The number of circulating EPC was inversely correlated with the plasma aldosterone concentration (P = 0.021), arterial stiffness (P = 0.029) and serum high-sensitivity C-reactive protein (P = 0.03). High-dose aldosterone (10(-5) and 10(-6) m) attenuated EPC proliferation and angiogenesis in vitro. Among the 45 patients who underwent unilateral adrenalectomy, 32 (71%) were cured of hypertension. The preoperative number of EPC [log(EPC number percent) >-3.6] predicted the curability of hypertension after adrenalectomy (P = 0.003). CONCLUSIONS: The relative deficiency of EPC in PA patients may contribute to aldosterone vasculopathy, which can be reversed by adrenalectomy and spironolactone. High aldosterone levels attenuated EPC proliferation and angiogenesis. Circulating EPC number may be a valuable biomarker to identify PA patients with a high incidence of arterial stiffness and to predict postoperative residual hypertension of aldosterone-producing adenoma.

Diagnosis of diabetes using hemoglobin A1c: should recommendations in adults be extrapolated to adolescents?

OBJECTIVE: To compare test performance of hemoglobin A1c (HbA1c) for detecting diabetes mellitus/pre-diabetes for adolescents versus adults in the United States. STUDY DESIGN: Individuals were defined as having diabetes mellitus (fasting plasma glucose [FPG] ≥ 126 mg/dL; 2-hour plasma glucose (2-hr PG) ≥ 200 mg/dL) or pre-diabetes (100 ≤ FPG < 126 mg/dL; 140 ≤ 2-hr PG < 200 mg/dL. HbA1c test performance was evaluated with receiver operator characteristic (ROC) analyses. RESULTS: Few adolescents had undiagnosed diabetes mellitus (n = 4). When assessing FPG to detect diabetes, an HbA1c of 6.5% had sensitivity rates of 75.0% (30.1% to 95.4%) and 53.8% (47.4% to 60.0%) and specificity rates of 99.9% (99.5% to 100.0%) and 99.5% (99.3% to 99.6%) for adolescents and adults, respectively. Additionally, when assessing FPG to detect diabetes mellitus, an HbA1c of 5.7% had sensitivity rates of 5.0% (2.6% to 9.2%) and 23.1% (21.3% to 25.0%) and specificity rates of 98.3% (97.2% to 98.9%) and 91.1% (90.3% to 91.9%) for adolescents and adults, respectively. ROC analyses suggested that HbA1c is a poorer predictor of diabetes mellitus (area under the curve, 0.88 versus 0.93) and pre-diabetes (FPG area under the curve 0.61 versus 0.74) for adolescents compared with adults. Performance was poor regardless of whether FPG or 2-hr PG measurements were used. CONCLUSIONS: Use of HbA1c for diagnosis of diabetes mellitus and pre-diabetes in adolescents may be premature, until information from more definitive studies is available.