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BackgroundCorticosteroids are the mainstay of treatment for immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI), but the optimal duration of therapy has not been established. Prolonged use of corticosteroids can cause numerous adverse effects and may decrease progression-free survival among patients treated with ICPis. We sought to determine whether a shorter duration of corticosteroids was equally efficacious and safe as compared with a longer duration.MethodsWe used data from an international multicenter cohort study of patients diagnosed with ICPi-AKI from 29 centers across nine countries. We examined whether a shorter duration of corticosteroids (28 days or less) was associated with a higher rate of recurrent ICPi-AKI or death within 30 days following completion of corticosteroid treatment as compared with a longer duration (29–84 days).ResultsOf 165 patients treated with corticosteroids, 56 (34%) received a shorter duration of treatment and 109 (66%) received a longer duration. Patients in the shorter versus longer duration groups were similar with respect to baseline and ICPi-AKI characteristics. Five of 56 patients (8.9%) in the shorter duration group and 12 of 109 (11%) in the longer duration group developed recurrent ICPi-AKI or died (p=0.90). Nadir serum creatinine in the first 14, 28, and 90 days following completion of corticosteroid treatment was similar between groups (p=0.40, p=0.56, and p=0.89, respectively).ConclusionA shorter duration of corticosteroids (28 days or less) may be safe for patients with ICPi-AKI. However, the findings may be susceptible to unmeasured confounding and further research from randomized clinical trials is needed.

Background Studies have documented AKI with high-grade proteinuria in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In some patients, biopsies have revealed collapsing glomerulopathy, a distinct form of glomerular injury that has been associated with other viruses, including HIV. Previous patient reports have described patients of African ancestry who developed nephrotic-range proteinuria and AKI early in the course of disease. Methods In this patient series, we identified six patients with coronavirus disease 2019 (COVID-19), AKI, and nephrotic-range proteinuria. COVID-19 was diagnosed by a positive nasopharyngeal swab RT-PCR for SARS-CoV-2 infection. We examined biopsy specimens from one transplanted kidney and five native kidneys. Three of the six patients underwent genetic analysis of APOL1, the gene encoding the APOL1 protein, from DNA extracted from peripheral blood. In addition, we purified genomic DNA from paraffin-embedded tissue and performed APOL1 genotype analysis of one of the native biopsies and the donor kidney graft. Results All six patients were of recent African ancestry. They developed COVID-19-associated AKI with podocytopathy, collapsing glomerulopathy, or both. Patients exhibited generally mild respiratory symptoms, and no patient required ventilator support. Genetic testing performed in three patients confirmed high-risk APOL1 genotypes. One APOL1 high-risk patient developed collapsing glomerulopathy in the engrafted kidney, which was transplanted from a donor who carried a low-risk APOL1 genotype; this contradicts current models of APOL1-mediated kidney injury, and suggests that intrinsic renal expression of APOL1 may not be the driver of nephrotoxicity and specifically, of podocyte injury. Conclusions Glomerular disease presenting as proteinuria with or without AKI is an important presentation of COVID-19 infection and may be associated with a high-risk APOL1 genotype.

The coronavirus disease 2019 (COVID-19) pandemic has created unprecedented strain on health care resources in the United States. Initial reports of AKI rates from Wuhan, China ranged between 3% and 9%, although rates as high as 15% have been reported (1,2). For AKI requiring RRT, intermittent hemodialysis (HD) and continuous RRT (CRRT) have been mainstays of therapy in the United States. However, shortages in supplies, staffing, and available equipment among critically ill patients with COVID-19, particularly in the New York City area, have demanded alternative strategies such as acute peritoneal dialysis treatment for AKI (AKI-PD) that are being implemented. Here, we will review the rationale for the use of AKI-PD and describe potential advantages, criteria for patient selection, and practical considerations on the basis of initial experiences to consider when prescribing and delivering peritoneal dialysis (PD). PD was routine for AKI treatment worldwide well into the 1980s. However, by the 1990s with the development of the central venous catheter for HD and the advent of CRRT, PD became rarely used in higher-resource countries to treat adult patients with AKI (3). The utility and efficacy of PD to treat patients with AKI were re-examined after the publication of a series of articles from Brazil, including a randomized trial, demonstrating that PD provided acceptable care, was not inferior to daily HD in treating acutely ill patients with AKI in terms of patient mortality, and was associated with a shorter duration of AKI and need for RRT (4,5). These findings were confirmed in a randomized trial from Saudi Arabia comparing PD with hemodiafiltration (6). AKI-PD expanded dramatically in lower-resource countries with the advent of the Saving Young Lives Program in 2012, which promoted the use of PD because of minimal infrastructural requirements, including a lack of need for water …

In this review, the authors provide an overview of erenumab, a monoclonal antibody used for the preventative treatment of episodic migraine by targeting theIn this review, the authors give an overview of erenumab, an injectable medication used to prevent migraine headaches. Erenumab has been proven to be significantly effective in patients with episodic migraines when used at doses of 70 or 140 mg. Furthermore, studies have shown sustained benefit starting as early as the first week of treatment as well as improvement in patients' quality of life. Erenumab has been found to be as safe as placebo in some studies, but there have been some reports of a link to high blood pressure and constipation. However, because of its high cost, patients still face significant barriers to access to erenumab. Additional long-term real-world data are needed to understand the current role of erenumab in the treatment of migraine.

BackgroundImmune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer.MethodsWe collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI.ResultsICPi-AKI occurred at a median of 16 weeks (IQR 8–32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3–10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI.ConclusionsPatients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged into a worldwide pandemic of epic proportion. Beyond pulmonary involvement in coronavirus disease 2019 (COVID-19), a significant subset of patients experiences acute kidney injury. Patients who die from severe disease most notably show diffuse acute tubular injury on postmortem examination with a possible contribution of focal macro- and microvascular thrombi. Renal biopsies in patients with proteinuria and hematuria have demonstrated a glomerular dominant pattern of injury, most notably a collapsing glomerulopathy reminiscent of findings seen in human immunodeficiency virus (HIV) in individuals with apolipoprotein L-1 (APOL1) risk allele variants. Although various mechanisms have been proposed for the pathogenesis of acute kidney injury in SARS-CoV-2 infection, direct renal cell infection has not been definitively demonstrated and our understanding of the spectrum of renal involvement remains incomplete. Herein we discuss the biology, pathology, and pathogenesis of SARS-CoV-2 infection and associated renal involvement. We discuss the molecular biology, risk factors, and pathophysiology of renal injury associated with SARS-CoV-2 infection. We highlight the characteristics of specific renal pathologies based on native kidney biopsy and autopsy. Additionally, a brief discussion on ancillary studies and challenges in the diagnosis of SARS-CoV-2 is presented.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged into a worldwide pandemic of epic proportion. Beyond pulmonary involvement in coronavirus disease 2019 (COVID-19), a significant subset of patients experiences acute kidney injury. Patients who die from severe disease most notably show diffuse acute tubular injury on postmortem examination with a possible contribution of focal macro- and microvascular thrombi. Renal biopsies in patients with proteinuria and hematuria have demonstrated a glomerular dominant pattern of injury, most notably a collapsing glomerulopathy reminiscent of findings seen in human immunodeficiency virus (HIV) in individuals with apolipoprotein L-1 (APOL1) risk allele variants. Although various mechanisms have been proposed for the pathogenesis of acute kidney injury in SARS-CoV-2 infection, direct renal cell infection has not been definitively demonstrated and our understanding of the spectrum of renal involvement remains incomplete. Herein we discuss the biology, pathology, and pathogenesis of SARS-CoV-2 infection and associated renal involvement. We discuss the molecular biology, risk factors, and pathophysiology of renal injury associated with SARS-CoV-2 infection. We highlight the characteristics of specific renal pathologies based on native kidney biopsy and autopsy. Additionally, a brief discussion on ancillary studies and challenges in the diagnosis of SARS-CoV-2 is presented.

9507 Background: Cancer is a leading cause of death among KTR, but these patients (pts) have been excluded from trials of immune checkpoint inhibitors due to immunosuppression and risk of allograft loss. We report findings from the first prospective clinical trial of NIVO + TACRO + PRED +/- IPI in KTR with selected advanced cutaneous cancers. Methods: The primary composite endpoint was lack of tumor progression per RECIST v1.1 without allograft loss at 16 weeks (W) on NIVO. Adult KTR with advanced melanoma, basal, cutaneous squamous, or Merkel cell carcinoma (MEL, BCC, CSCC, MCC), for whom non-immune therapies were insufficient were eligible. Immunosuppression was standardized to low-dose TACRO (goal trough 2-5 ng/mL) + PRED 5mg daily; pts then received NIVO 480mg IV q4W. Pts with progressive disease (PD) could receive NIVO 3mg/kg + IPI 1mg/kg IV q3W x 4 followed by NIVO 480mg IV q4W. Donor-derived cell-free DNA (dd-cfDNA) levels were measured q2W as a potential predictor of allograft rejection. Results: From 11/2019 - 4/2021, of 12 pts enrolled, 8 pts with CSCC, MCC or MEL were evaluable for response (Table). All pts experienced PD on NIVO; treatment-related allograft loss (TRAL) occurred in 1 pt. 6 pts then received IPI + NIVO. Responses: 2 (33%) with marked tumor regression at 6W and eventual complete response (CR; 1 with TRAL), and 4 (67%) with PD (1 with TRAL). 7/8 pre-NIVO tumor biopsies contained a paucity of infiltrating immune cells. Only 2/5 on-NIVO biopsies demonstrated moderate immune infiltrates; both of these pts later developed a CR to IPI + NIVO. Rejecting allografts contained dense immune responses (plasma cells, CD4+ & CD8+ lymphocytes, PD-1+ lymphocytes, macrophages, PD-L1+ glomerular endothelium, and focal PD-1 & PD-L1 positivity in renal tubules). In 2/3 pts with TRAL, elevations in dd-cfDNA levels occurred 10 and 15 days earlier than increases in weekly serum creatinine levels. TRAL #3 occurred after discontinuation of study therapy (including TACRO) and dd-cfDNA monitoring. Conclusions: In KTR receiving low-dose TACRO + PRED, NIVO augments tumor immune cell infiltration in some pts but is insufficient to mediate tumor regression. Adding IPI can enhance anti-tumor immunity and mediate tumor regression. TACRO + PRED was insufficient to prevent allograft rejection after PD-1 +/- CTLA-4 blockade in 2/8 pts. In pts with TRAL, increased dd-cfDNA levels preceded increased serum creatinine. Based on these findings, we are modifying the trial therapy regimen to augment anti-tumor immunity and preserve allograft function. Clinical trial information: NCT03816332. [Table: see text]

Understanding peritoneal physiology and technical innovations in peritoneal dialysis has led to a significant reduction in therapy-related complications over the last four decades. Technology and techniques to perform peritoneal dialysis (PD) have evolved and, in its current form, are reliable, easy to use, and come at an acceptable cost. Also, various regimens and modes of PD allow for social interaction and optimizing PD efficiency in terms of solute clearance and fluid removal. Overall, the successful advances in PD techniques have prompted broader utilization and served as the foundation for major ESKD healthcare reform initiatives in the USA to support further growth of home-based dialysis [1]. We will outline procedural principles and details of variations of flow techniques (tidal, intermittent, or continuous), regimens [intermittent PD (IPD or continuous PD (CPD)], and modes of PD (manual or automated). These strategies allow for using tidal PD (TPD), continuous flow peritoneal dialysis (CFPD), assisted peritoneal dialysis, urgent-start PD, incremental PD, and remote patient monitoring (RPM) in clinical practice [2]. We will also outline various approaches that can further enhance the scope of PD usage in specific clinical situations.

Sudden cardiac death (SCD) is reported as leading cause of death in patients on chronic hemodialysis. Arrhythmias are proposed to be a major predisposing factor for SCD. However, triggers for potentially lethal arrhythmias are not well understood. Here we describe a case of 72-year-old man on chronic hemodialysis via permanent Central venous catheter (CVC) who was admitted for evaluation after unwitnessed fall. Within 10 minutes of his first routine dialysis session in the hospital, he had cardiac-arrest. He was successfully resuscitated within 3 minutes. The next day, fifteen minutes into the dialysis session, he had bradycardia with telemetry demonstrating long sinus pause and he lost consciousness. After few minutes of Advanced Cardiac Life Support (ACLS) he regained pulse and consciousness. Further review of the chest X-ray revealed the tip of CVC to be directly touching the distal Superior Vena Cava (SVC) wall. We felt the catheter tip may have migrated after the fall and now is irritating the Sinoatrial node and triggering bradyarrhythmia. Next day, the CVC was exchanged, and the tip was placed higher up in superior vena-cava. After repositioning, we started him on dialysis under intensive monitoring, and he tolerated well without any arrhythmia. Subsequent dialysis was uneventful. We describe a case of recurrent symptomatic intra-dialytic bradycardia due to abnormal positioning of CVC that resolved after the repositioning of the catheter. This case in addition to similar case in nondialysis settlings provides additional insights into mechanisms of fatal arrhythmias in hemodialysis patient having CVC.

This study compared Altmetric scores of neurological research as a marker of “buzz” with citations as a marker of academic attention.

The performance of brain-machine interfaces (BMIs) that continuously control upper limb neuroprostheses may benefit from distinguishing periods of posture and movement so as to prevent inappropriate movement of the prosthesis. Few studies, however, have investigated how decoding behavioral states and detecting the transitions between posture and movement could be used autonomously to trigger a kinematic decoder. We recorded simultaneous neuronal ensemble and local field potential (LFP) activity from microelectrode arrays in primary motor cortex (M1) and dorsal (PMd) and ventral (PMv) premotor areas of two male rhesus monkeys performing a center-out reach-and-grasp task, while upper limb kinematics were tracked with a motion capture system with markers on the dorsal aspect of the forearm, hand, and fingers. A state decoder was trained to distinguish four behavioral states (baseline, reaction, movement, hold), while a kinematic decoder was trained to continuously decode hand end point position and 18 joint angles of the wrist and fingers. LFP amplitude most accurately predicted transition into the reaction (62%) and movement (73%) states, while spikes most accurately decoded arm, hand, and finger kinematics during movement. Using an LFP-based state decoder to trigger a spike-based kinematic decoder [ r = 0.72, root mean squared error (RMSE) = 0.15] significantly improved decoding of reach-to-grasp movements from baseline to final hold, compared with either a spike-based state decoder combined with a spike-based kinematic decoder ( r = 0.70, RMSE = 0.17) or a spike-based kinematic decoder alone ( r = 0.67, RMSE = 0.17). Combining LFP-based state decoding with spike-based kinematic decoding may be a valuable step toward the realization of BMI control of a multifingered neuroprosthesis performing dexterous manipulation.

Sonoclot analysis is a point of care test to monitor the coagulation process, presenting a comprehensive evaluation of the clot formation and retraction as well as platelet function. This randomized double-blinded study was designed to investigate the utility of Sonoclot analysis in monitoring the coagulation profile as also the antifibrinolytic effects of tranexamic acid administered in patients with tetralogy of Fallot undergoing intracardiac repair. Eighty of a total 94 patients were randomly divided into two groups of 40 each. In the study group, TA was administered thrice at a dosage of 10 mg/kg, i.e. before CPB, on CPB and after CPB, whereas in the control group, placebo was administered at the same time intervals. Sonoclot analysis and D-dimer measurement were performed at baseline and following heparin neutralisation. An additional variable, DR 15 (diminishing rate of clot strength at 15 min postmaximal clot strength), was calculated from the Sonoclot graph and was compared with d-dimer levels as a measure of fibrinolysis. The three Sonoclot variables, i.e. activated clotting time, clot rate and platelet function, were deranged at baseline in all the patients. Post-CPB, the change in these variables was not significant. ACT, clot rate and platelet function showed no significant (P > 0.05) difference in both the groups at both the time intervals. DR 15 and d-dimer values were comparable at baseline in both the groups. However, a significant (P < 0.05) difference was seen in these variables in the control group as compared with the TA group following heparin neutralisation. To conclude, Sonoclot analysis is a useful, point of care method for the monitoring of coagulation and fibrinolysis in patients with tetralogy of Fallot undergoing intracardiac repair.

A robust method to help identify the population of neurons used for decoding motor tasks is developed. We use sensitivity analysis to develop a new metric for quantifying the relative contribution of a neuron towards the decoded output, called “fractional sensitivity.” Previous model-based approaches for neuron ranking have been shown to largely depend on the collection of training data. We suggest the use of anensembleof models that are trained on random subsets of trials to rank neurons. For this work, we tested a decoding algorithm on neuronal data recorded from two male rhesus monkeys while they performed a reach to grasp a bar at three orientations (45∘,90∘, or135∘). An ensemble approach led to a statistically significant increase of 5% in decoding accuracy and 25% increase in identification accuracy of simulated noisy neurons, when compared to a single model. Furthermore, ranking neurons based on the ensemble fractional sensitivities resulted in decoding accuracies 10%–20% greater than when randomly selecting neurons or ranking based on firing rates alone. By systematically reducing the size of the input space, we determine the optimal number of neurons needed for decoding the motor output. This selection approach has practical benefits for other BMI applications where limited number of electrodes and training datasets are available, but high decoding accuracies are desirable.

A few kinematic synergies identified by principal component analysis (PCA) account for most of the variance in the coordinated joint rotations of the fingers and wrist used for a wide variety of hand movements. To examine the possibility that motor cortex might control the hand through such synergies, we collected simultaneous kinematic and neurophysiological data from monkeys performing a reach-to-grasp task. We used PCA, jPCA and isomap to extract kinematic synergies from 18 joint angles in the fingers and wrist and analyzed the relationships of both single-unit and multiunit spike recordings, as well as local field potentials (LFPs), to these synergies. For most spike recordings, the maximal absolute cross-correlations of firing rates were somewhat stronger with an individual joint angle than with any principal component (PC), any jPC or any isomap dimension. In decoding analyses, where spikes and LFP power in the 100- to 170-Hz band each provided better decoding than other LFP-based signals, the first PC was decoded as well as the best decoded joint angle. But the remaining PCs and jPCs were predicted with lower accuracy than individual joint angles. Although PCs, jPCs or isomap dimensions might provide a more parsimonious description of kinematics, our findings indicate that the kinematic synergies identified with these techniques are not represented in motor cortex more strongly than the original joint angles. We suggest that the motor cortex might act to sculpt the synergies generated by subcortical centers, superimposing an ability to individuate finger movements and adapt the hand to grasp a wide variety of objects.

Tumoral calcinosis is an uncommon and severe complication of hemodialysis therapy. It is generally associated with the presence of the high serum calcium-and-phosphorus product. We report here a case of a patient on hemodialysis who presented with progressively increasing, multiple, tumor-like, subcutaneous swellings. These are rare manifestations of extraosseous calcification in uremic patients that are termed as tumoral calcinosis. A 25 year-old male presented with multiple, nodular, painful, cutaneous swellings all over his body that had been progressively increasing over the last four years. He was a known case of chronic glumerulonephritis who was on regular hemodialysis. The patient was investigated and diagnosed as having tumoral calcinosis and was treated with a low calcium dialysate of pure reverse osmosis water.