AKI in COVID-19-Associated Multisystem Inflammatory Syndrome in Children (MIS-C).

Background: Multisystem inflammatory syndrome in children (MIS-C) is a recently identified entity in association with COVID-19. AKI has been widely reported in patients with primary COVID-19 infection. However, there is a paucity of literature regarding renal injury in MIS-C. We aim to characterize AKI in MIS-C in this cohort identified at a major children's hospital in New York City during the COVID-19 pandemic. Methods: We conducted a retrospective cohort study of children 0-20 years old admitted to Morgan Stanley Children's Hospital (MSCH) between April 18th and September 23rd, 2020. Patients were included if they met criteria for MIS-C on the basis of CDC guidelines. All patients were evaluated for the presence of AKI, and AKI was staged according to KDIGO criteria. Results: Of the 57 children who met inclusion criteria, 46% (26 of 57) were found to have AKI. The majority of patients (58%; 15 of 26) were classified as KDIGO stage 1. AKI was present upon admission in 70% of those identified. All patients had resolution of AKI at discharge, with 61% achieving recovery by day 2. One patient required dialysis. When compared with those without renal injury, the AKI cohort was older (P<0.001) and had higher median peak values of CRP (P<0.001), IL-6 (P=0.02), ferritin (P<0.001), and procalcitonin (P=0.02). More patients with AKI had left ventricular systolic dysfunction (P<0.001) and lymphopenia (P=0.01) when compared with those without AKI. No differences in body mass index or sex were found. Conclusions: Although children with MIS-C may develop AKI, our study suggests that most experience mild disease, swift resolution, and promising outcome. Older age, increased inflammation, and left ventricular systolic dysfunction may be risk factors. Our study highlights the substantial differences in epidemiology and outcomes between AKI associated with pediatric MIS-C versus primary COVID-19 infection.

Steroid-resistant nephrotic syndrome: a persistent challenge for pediatric nephrology.

Steroid-resistant nephrotic syndrome remains a challenge to treat, but various efforts are underway to better understand the pathogenesis and improve patient outcomes. This review provides an update on the newer advances in understanding the molecular etiologies for a variety of podocyte abnormalities, potential circulating factors that may initiate and sustain the steroid-resistant state, genetic mutations, and precision medicine treatment modalities in this continuously perplexing disorder.

Arsenic trioxide amplifies cisplatin toxicity in human tubular cells transformed by HPV-16 E6/E7 for further therapeutic directions in renal cell carcinoma.

Human papillomavirus (HPV) DNA integrations may affect therapeutic responses in cancers through ATM network-related DNA damage response (DDR). We studied whether cisplatin-induced DDR was altered in human HK-2 renal tubular cells immortalized by HPV16 E6/E7 genes. Cytotoxicity assays utilized thiazolyl blue dye and DDR was identified by gene expression differences, double-strand DNA breaks, ATM promoter activity, and analysis of cell cycling and side population cells. After cisplatin, HK-2 cells showed greater ATM promoter activity indicating activation of this network, but DDR was muted, since little γH2AX was expressed, DNA strand breaks were absent and cells continued cycling. When HK-2 cells were treated with the MDM2 antagonist inducing p53, nutlin-3, or p53 transcriptional activator, tenovin-1, cell growth decreased but cisplatin toxicity was unaffected. By contrast, arsenic trioxide, which by inhibiting wild-type p53-induced phosphatase-1 that serves responses downstream of p53, and by depolymerizing tubulin, synergistically enhanced cisplatin cytotoxicity including loss of SP cells. Our findings demonstrated that HPV16 E6/E7 altered DDR through p53-mediated cell growth controls, which may be overcome by targeting of WIP1 and other processes, and thus should be relevant for treating renal cell carcinoma.

Management of streptococcal pneumoniae-induced hemolytic uremic syndrome: a case report.

Hemolytic uremic syndrome (HUS) secondary to Streptococcus pneumoniae infections (pHUS) has been well reported in the literature and accounts for roughly 5% of all the cases of HUS. However, this condition is likely under-diagnosed and the incidence is believed to be increasing. Given this increase in incidence of pHUS, it is important to have an understanding of the optimal means to manage the disease. We report a case of a 2-year-old male with pneumonia, acute kidney injury (AKI), microangiopathic hemolytic anemia (MAHA), and thrombocytopenia, diagnosed with pHUS and successfully treated with antibiotics, washed red blood cell (RBC) transfusions, plasma exchange (PE) with 5% albumin replacement, steroids, and hemodialysis. The response seen in our patient adds to the current literature and further supports the use of PE with albumin in patients with pHUS.

Protein kinase C inhibition by tamoxifen antagonizes manic-like behavior in rats: implications for the development of novel therapeutics for bipolar disorder.

RATIONALE: In the context of bipolar disorder (BPD) research it was demonstrated that administration of the structurally dissimilar mood stabilizers lithium and valproate produced a striking reduction in protein kinase C (PKC) in rat brain. In a small clinical study, tamoxifen (a PKC inhibitor) had antimanic efficacy. However, both lithium and valproate exert many biochemical changes and attribution of therapeutic relevance to any molecular findings needs to be based on linking them to behavioral effects. OBJECTIVES: The present study was designed to explore such relationship by studying the effects of PKC inhibition in amphetamine-induced behavioral animal models of mania and changes in GAP-43. METHODS: The effects of two daily tamoxifen (1 mg/kg) i.p. injections on acute or chronic (7 injections) amphetamine (0.5 mg/kg) -induced behaviors and GAP-43 phosphorylation were tested. RESULTS: The study demonstrates that tamoxifen significantly reduced amphetamine-induced hyperactivity in a large open field without affecting spontaneous activity levels and normalized amphetamine-induced increase in visits to the center of an open field (representing risk-taking behavior). Tamoxifen also attenuated amphetamine-induced phosphorylation of GAP-43, a result that is consistent with the behavioral findings. CONCLUSIONS: These results support the possibility that PKC signaling may play an important role in the pathophysiology and treatment of BPD. These findings may have direct clinical implications as they offer a new avenue for attempts to develop more specific drugs for the disorder.

Configurational and nonconfigurational interactions between odorants in binary mixtures.

Studies on odor mixture perception suggest that although odor components can often be identified in mixtures, mixtures can also give rise to novel perceptual qualities that are not present in the components. Using an olfactory habituation task, the authors evaluated how the perceptual similarity between components in a mixture affects the perceptual quality of the mixture itself. Rats perceived binary mixtures composed of similar components as different from their 2 components, whereas binary mixtures composed of dissimilar components were perceived as very similar to their components. Results show that for both types of mixtures, pretraining to Component A reduces subsequent learning about Component B in rats trained in the presence of A.