Notes

Ureterocalyceal Fistula: An infrequent Complication of Laparoscopic Incomplete Nephrectomy.
The prevalence of venous thromboembolic event (VTE) and arterial thromboembolic event (ATE) thromboembolic events in patients with COVID-19 remains largely unknown.

In this meta-analysis, we systematically searched for observational studies describing the prevalence of VTE and ATE in COVID-19 up to 30 September 2020.

We analysed findings from 102 studies (64 503 patients). The frequency of COVID-19-related VTE was 14.7% (95% CI 12.1% to 17.6%, I
=94%; 56 studies; 16 507 patients). The overall prevalence rates of pulmonary embolism (PE) and leg deep vein thrombosis were 7.8% (95% CI 6.2% to 9.4%, I
=94%; 66 studies; 23 117 patients) and 11.2% (95% CI 8.4% to 14.3%, I
=95%; 48 studies; 13 824 patients), respectively. Few were isolated subsegmental PE. The VTE prevalence was significantly higher in intensive care unit (ICU) (23.2%, 95% CI 17.5% to 29.6%, I
=92%, vs 9.0%, 95% CI 6.9% to 11.4%, I
=95%; p
<0.0001) and in series systematically screening patients compared with series testing symptomatic patients (25.2% vs 12.7%, p
=0.04). The frequency rates of overall ATE, acute coronary syndrome, stroke and other ATE were 3.9% (95% CI 2.0% to to 3.0%, I
=96%; 16 studies; 7939 patients), 1.6% (95% CI 1.0% to 2.2%, I
=93%; 27 studies; 40 597 patients) and 0.9% (95% CI 0.5% to 1.5%, I
=84%; 17 studies; 20 139 patients), respectively. Metaregression and subgroup analyses failed to explain heterogeneity of overall ATE. High heterogeneity limited the value of estimates.

Patients admitted in the ICU for severe COVID-19 had a high risk of VTE. Conversely, further studies are needed to determine the specific effects of COVID-19 on the risk of ATE or VTE in less severe forms of the disease.
Patients admitted in the ICU for severe COVID-19 had a high risk of VTE. Conversely, further studies are needed to determine the specific effects of COVID-19 on the risk of ATE or VTE in less severe forms of the disease.
Patients may accrue wait time for kidney transplantation when their eGFR is ≤20 ml/min. However, Black patients have faster progression of their kidney disease compared with White patients, which may lead to disparities in accruable time on the kidney transplant waitlist before dialysis initiation.

We compared differences in accruable wait time and transplant preparation by CKD-EPI estimating equations in Chronic Renal Insufficiency Cohort participants, on the basis of estimates of kidney function by creatinine (eGFR
), cystatin C (eGFR
), or both (eGFR
). We used Weibull accelerated failure time models to determine the association between race (non-Hispanic Black or non-Hispanic White) and time to ESKD from an eGFR of ≤20 ml/min per 1.73 m
. We then estimated how much higher the eGFR threshold for waitlisting would be required to achieve equity in accruable preemptive wait time for the two groups.

By eGFR
, 444 CRIC participants were eligible for waitlist registration, but the potential time between eGFR ≤20 ml/min per 1.73 m
and ESKD was 32% shorter for Blacks versus Whites. By eGFR
, 435 participants were eligible, and Blacks had 35% shorter potential wait time compared with Whites. By the eGFR
equation, 461 participants were eligible, and Blacks had a 31% shorter potential wait time than Whites. We estimated that registering Blacks on the waitlist as early as an eGFR of 24-25 ml/min per 1.73 m
might improve racial equity in accruable wait time before ESKD onset.

Policies allowing for waitlist registration at higher GFR levels for Black patients compared with White patients could theoretically attenuate disparities in accruable wait time and improve racial equity in transplant access.
Policies allowing for waitlist registration at higher GFR levels for Black patients compared with White patients could theoretically attenuate disparities in accruable wait time and improve racial equity in transplant access.
Interstitial fibrosis, tubular atrophy (IFTA), and glomerulosclerosis are indicators of irrecoverable kidney injury. Modern machine learning (ML) tools have enabled robust, automated identification of image structures that can be comparable with analysis by human experts. ML algorithms were developed and tested for the ability to replicate the detection and quantification of IFTA and glomerulosclerosis that renal pathologists perform.

A renal pathologist annotated renal biopsy specimens from 116 whole-slide images (WSIs) for IFTA and glomerulosclerosis. A total of 79 WSIs were used for training different configurations of a convolutional neural network (CNN), and 17 and 20 WSIs were used as internal and external testing cases, respectively. The best model was compared against the input of four renal pathologists on 20 new testing slides. Further, for 87 testing biopsy specimens, IFTA and glomerulosclerosis measurements made by pathologists and the CNN were correlated to patient outcome using classic statiwhich renal-pathologist time is restricted or unavailable.A comprehensive understanding of the kinetics and evolution of the human B cell response to SARS-CoV-2 infection will facilitate the development of next-generation vaccines and therapies. Here, we longitudinally profiled this response in mild and severe COVID-19 patients over a period of five months. Serum neutralizing antibody (nAb) responses waned rapidly but spike (S)-specific IgG+ memory B cells (MBCs) remained stable or increased over time. Analysis of 1,213 monoclonal antibodies (mAbs) isolated from S-specific MBCs revealed a primarily de novo response that displayed increased somatic hypermutation, binding affinity, and neutralization potency over time, providing evidence for prolonged antibody affinity maturation. B cell immunodominance hierarchies were similar across donor repertoires and remained relatively stable as the immune response progressed. Cross-reactive B cell populations, likely re-called from prior endemic beta-coronavirus exposures, comprised a small but stable fraction of the repertoires and did not contribute to the neutralizing response. The neutralizing antibody response was dominated by public clonotypes that displayed significantly reduced activity against SARS-CoV-2 variants emerging in Brazil and South Africa that harbor mutations at positions 501, 484 and 417 in the S protein. Overall, the results provide insight into the dynamics, durability, and functional properties of the human B cell response to SARS-CoV-2 infection and have implications for the design of immunogens that preferentially stimulate protective B cell responses.Hyperinflammation contributes to lung injury and subsequent acute respiratory distress syndrome (ARDS) with high mortality in patients with severe coronavirus disease 2019 (COVID-19). To understand the underlying mechanisms involved in lung pathology, we investigated the role of the lung-specific immune response. We profiled immune cells in bronchoalveolar lavage fluid and blood collected from COVID-19 patients with severe disease and bacterial pneumonia patients not associated with viral infection. By tracking T cell clones across tissues, we identified clonally expanded tissue-resident memory-like Th17 cells (Trm17 cells) in the lungs even after viral clearance. These Trm17 cells were characterized by a a potentially pathogenic cytokine expression profile of IL17A and CSF2 (GM-CSF). Interactome analysis suggests that Trm17 cells can interact with lung macrophages and cytotoxic CD8+ T cells, which have been associated with disease severity and lung damage. High IL-17A and GM-CSF protein levels in the serum of COVID-19 patients were associated with a more severe clinical course. Collectively, our study suggests that pulmonary Trm17 cells are one potential orchestrator of the hyperinflammation in severe COVID-19.
We surveyed UK practice and compliance with the National Institute for Health and Care Excellence (NICE) 'recent-onset chest pain' guidance (Clinical Guideline 95, 2016) as a service quality initiative. We aimed to evaluate the diagnostic utility and efficacy of CT coronary angiography (CTCA), NICE-guided investigation compliance, invasive coronary angiography (ICA) use and revascularisation.

A prospective analysis was conducted in nine UK centres between January 2018 and March 2020. The reporter decided whether the CTCA was diagnostic. Coronary artery disease was recorded with the Coronary Artery Disease-Reporting and Data System (CAD-RADS). Local electronic records and picture archiving/communication systems were used to collect data regarding functional testing, ICA and revascularisation. Duplication of coronary angiography without revascularisation was taken as a surrogate for ICA overuse.

5293 patients (mean age, 57±12 years; body mass index, 29±6 kg/m²; 50% men) underwent CTCA, with a 96% diagnostt leading to revascularisation.
Early use of insertable cardiac monitor (ICM) is recommended for patients with unexplained syncope following initial clinical workup, due to its superior ability to establish symptom-rhythm correlation compared with conventional testing (CONV). However, ICMs incur higher upfront costs, and the impact of additional diagnoses and resulting treatment on downstream costs and outcomes is unclear. We aimed to evaluate the cost-effectiveness of ICM compared with CONV for the diagnosis of arrhythmia in patients with unexplained syncope, from a US payer perspective.

A Markov model was developed to estimate lifetime costs and benefits of arrhythmia diagnosis with ICM versus CONV, considering all related diagnostic and arrhythmia-related treatment costs and consequences. Cohort characteristics and costs were informed by original claims database analyses. Risks of mortality, syncopal recurrence, injury due to syncope and quality of life consequences from syncopal events were identified from the literature.

ICM was ated event costs.
Our model projected that early ICM for the diagnosis of unexplained syncope reduced long-term costs, and led to an improvement in overall clinical outcomes by shortening time to arrhythmia treatment. The cost of ICM was outweighed by savings arising from fewer downstream diagnostic episodes, and the increased cost of treatment was counterbalanced by fewer syncope-related event costs.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of Coronavirus Disease 2019 (COVID-19). There is a dire need for novel effective antivirals to treat COVID-19, as the only approved direct-acting antiviral to date is remdesivir, targeting the viral polymerase complex. A potential alternate target in the viral life cycle is the main SARS-CoV-2 protease 3CLpro (Mpro). The drug candidate PF-00835231 is the active compound of the first anti-3CLpro regimen in clinical trials. Here, we perform a comparative analysis of PF-00835231, the pre-clinical 3CLpro inhibitor GC-376, and the polymerase inhibitor remdesivir, in alveolar basal epithelial cells modified to express ACE2 (A549+ACE2 cells). We find PF-00835231 with at least similar or higher potency than remdesivir or GC-376. A time-of-drug-addition approach delineates the timing of early SARS-CoV-2 life cycle steps in A549+ACE2 cells and validates PF-00835231's early time of action. In a model of the human polarized airway epithelium, both PF-00835231 and remdesivir potently inhibit SARS-CoV-2 at low micromolar concentrations.
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