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IMPORTANCE Preventive interventions are needed to protect residents and staff of skilled nursing and assisted living facilities from COVID-19 during outbreaks in their facilities. Bamlanivimab, a neutralizing monoclonal antibody against SARS-CoV-2, may confer rapid protection from SARS-CoV-2 infection and COVID-19.OBJECTIVE To determine the effect of bamlanivimab on the incidence of COVID-19 among residents and staff of skilled nursing and assisted living facilities. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, single-dose, phase 3 trial that enrolled residents and staff of 74 skilled nursing and assisted living facilities in the United States with at least 1 confirmed SARS-CoV-2 index case. A total of 1175 participants enrolled in the study from August 2 to November 20, 2020. Database lock was triggered on January 13, 2021, when all participants reached study day 57.INTERVENTIONS Participants were randomized to receive a single intravenous infusion of bamlanivimab, 4200 mg (n = 588), or placebo (n = 587). MAIN OUTCOMES AND MEASURESThe primary outcome was incidence of COVID-19, defined as the detection of SARS-CoV-2 by reverse transcriptase-polymerase chain reaction and mild or worse disease severity within 21 days of detection, within 8 weeks of randomization. Key secondary outcomes included incidence of moderate or worse COVID-19 severity and incidence of SARS-CoV-2 infection. RESULTSThe prevention population comprised a total of 966 participants (666 staff and 300 residents) who were negative at baseline for SARS-CoV-2 infection and serology (mean age, 53.0 [range, 18-104] years; 722 [74.7%] women). Bamlanivimab significantly reduced the incidence of COVID-19 in the prevention population compared with placebo (8.5% vs 15.2%; odds ratio, 0.43 [95% CI, 0.28-0.68]; P < .001; absolute risk difference, −6.6 [95% CI, −10.7 to −2.6] percentage points). Five deaths attributed to COVID-19 were reported by day 57; all occurred in the placebo group. Among 1175 participants who received study product (safety population), the rate of participants with adverse events was 20.1% in the bamlanivimab group and 18.9% in the placebo group. The most common adverse events were urinary tract infection (reported by 12 participants [2%] who received bamlanivimab and 14 [2.4%] who received placebo) and hypertension (reported by 7 participants [1.2%] who received bamlanivimab and 10 [1.7%] who received placebo).CONCLUSIONS AND RELEVANCE Among residents and staff in skilled nursing and assisted living facilities, treatment during August-November 2020 with bamlanivimab monotherapy reduced the incidence of COVID-19 infection. Further research is needed to assess preventive efficacy with current patterns of viral strains with combination monoclonal antibody therapy.

Abstract. Human renal dysplasia is a collection of disorders in which kidneys begin to form but then fail to differentiate into normal nephrons and collecting ducts. Dysplasia is the principal cause of childhood end-stage renal failure. Two main theories have been considered in its pathogenesis: A primary failure of ureteric bud activity and a disruption produced by fetal urinary flow impairment. Recent studies have documented deregulation of gene expression in human dysplasia, correlating with perturbed cell turnover and maturation. Mutations of nephrogenesis genes have been defined in multiorgan dysmorphic disorders in which renal dysplasia can feature, including Fraser, renal cysts and diabetes, and Kallmann syndromes. Here, it is possible to begin to understand the normal nephrogenic function of the wild-type proteins and understand how mutations might cause aberrant organogenesis.Congenital anomalies of the kidney and urinary tract (CAKUT) account for one third of all anomalies detected by routine fetal ultrasonography (1). A recent UK audit of childhood end-stage renal failure reported that CAKUT was the cause in~40% of 882 individuals (2). Acquired glomerulonephritis and congenital nephrotic syndromes, respectively, accounted for just 18% and 8% of cases, with other diseases being rare (nephronophthisis, 5%; cystinosis, 3%; polycystic kidney diseases [PKD], 3%). With improvements in dialysis and transplantation, a new cohort of children with severe CAKUT is surviving to adulthood (3,4). The spectrum of diseases encompassed by the term "CAKUT" is wide, including kidney anomalies such as aplasia, hypoplasia, multicystic dysplastic kidneys, ureteric anomalies such as megaureter, ureteropelvic junction obstruction, ureterovesical junction obstruction or incompetence, duplex kidneys/ureters, and anomalies of the bladder and urethra (5). Approximately half of the CAKUT cases associated with end-stage renal failure in children have patent urinary tracts, whereas the rest have obstructive nephropathy (2). The latter are mainly boys with bladder outflow obstruction (BOO) and posterior urethral valves (2,6). Some renal functional impairment may be superimposed postnatally from bacterial pyelonephritis and/or persistent urinary flow impairment causing renal atrophy and fibrosis. However, the primary "hit" in CAKUT is clearly a developmental one, and the main renal pathology is renal dysplasia (RD). In her landmark book Normal and Abnormal Development of the Kidney published in 1972 (7), Edith Potter emphasized that one must understand normal development to generate realistic hypotheses on the pathogenesis of congenital malformations. Here, we summarize normal human kidney development, using Potter's work (7) as a basis but also incorporating recent summaries (8,9).The metanephric human kidney precursor forms 28 d after fertilization when ureteric bud (UB) branches from the mesonephric duct (MD). In the next few days, renal mesenchyme (RM) condenses from intermediate mesoderm around the UB tip, or ampulla. Ultimately...

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Abstract-We tested the hypothesis that endothelial dysfunction could cause placentation-related defects, persist after the complicated pregnancy, and probably cause cardiovascular disease later in life. Brachial arterial reactivity and factors related to endothelial dysfunction, such as circulating cholesterol, uric acid, nitrites, L-arginine, asymmetrical dimethylarginine, vascular endothelial growth factor, and soluble vascular endothelial growth factor receptor-1, in women with previous healthy pregnancies (nϭ22), patients with severe preeclampsia (nϭ25), or patients with recurrent pregnancy loss (nϭ29), at day 10 of the luteal phase of an ovulatory cycle an average of 11 to 27 months after pregnancy were evaluated. Both groups with placentation defects had a significant decrease in endothelium-dependent dilatation, a higher rate of endothelial dysfunction, lower serum nitrites, and higher cholesterol as compared with control subjects; subjects with previous preeclampsia additionally had higher normal blood pressures and a greater parental prevalence of cardiovascular disease. Patients with recurrent pregnancy loss also demonstrated a significantly lower endotheliumindependent vasodilatation. A trend to an inverse correlation was found between serum cholesterol serum and endothelial-mediated vasodilatation in the whole study population. Uric acid, L-arginine, asymmetrical dimethylarginine, vascular endothelial growth factor, and soluble vascular endothelial growth factor receptor-1 were similar in all of the groups. We postulate that endothelial dysfunction may represent a link between preeclampsia and increased cardiovascular disease latter in life and propose that women with unexplained recurrent miscarriages are also at increased cardiovascular risk. The identification and correction of endothelial dysfunction detected during the reproductive stage on obstetric outcome and on cardiovascular diseases needs to be elucidated. Key Words: endothelial dysfunction Ⅲ endothelium-mediated vasodilatation Ⅲ pregnancy Ⅲ preeclampsia Ⅲ recurrent abortion Ⅲ cardiovascular risk P reeclampsia not only elevates obstetric morbidity and mortality, but also places the mother at increased risk for developing cardiovascular disease (CVD) later in life. Indeed, subjects with preeclampsia are susceptible to hypertension, obesity/metabolic syndrome, and to CVD particularly if the preeclampsia is complicated by preterm birth. [1][2][3][4] Interestingly, subjects with recurrent spontaneous abortions have also been reported to be at increased risk for the development of cerebrovascular disease later in life. 5 This suggests that there may be underlying risk factors of CVD that predispose to both preeclampsia and/or spontaneous abortions, 2 conditions that represent different degrees of placentation defects.One potential unifying mechanism could involve the presence of endothelial dysfunction before the obstetric complication. Maternal endothelial dysfunction could impair the invasion of extravillous trophoblasts into the spiral arter...