Severe disease from SARS-CoV-2 infection often progresses to multi-organ failure and results in an increased mortality rate amongst these patients. However, underlying mechanisms of SARS- CoV-2-induced multi-organ failure and subsequent death are still largely unknown. Cytokine storm, increased levels of inflammatory mediators, endothelial dysfunction, coagulation abnormalities, and infiltration of inflammatory cells into the organs contribute to the pathogenesis of COVID-19. One potential consequence of immune/inflammatory events is the acute progression of generalized edema, which may lead to death. We, therefore, examined the involvement of water channels in the development of edema in multiple organs and their contribution to organ dysfunction in a Murine Hepatitis Virus-1 (MHV-1) mouse model of COVID-19. Using this model, we recently reported multi-organ pathological abnormalities and animal death similar to that reported in humans with SARS-CoV-2 infection. We now identified an alteration in protein levels of AQPs 1, 4, 5, and 8 and associated oxidative stress, along with various degrees of tissue edema in multiple organs, which correlate well with animal survival post-MHV-1 infection. Furthermore, our newly created drug (a 15 amino acid synthetic peptide, known as SPIKENET) that was designed to prevent the binding of spike glycoproteins with their receptor(s), angiotensin- converting enzyme 2 (ACE2), and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) (SARS-CoV-2 and MHV-1, respectively), ameliorated animal death and reversed altered levels of AQPs and oxidative stress post-MHV-1 infection. Collectively, our findings suggest the possible involvement of altered aquaporins and the subsequent edema, likely mediated by the virus-induced inflammatory and oxidative stress response, in the pathogenesis of COVID- 19 and the potential of SPIKENET as a therapeutic option.

Alagille syndrome (ALGS) is a multisystem autosomal dominant developmental disorder caused predominantly by pathogenic variants in JAGGED1 (JAG1), and also by pathogenic variants in NOTCH2 in a much smaller number of individuals. Clinical presentation is highly variable and includes liver, heart, eye, skeleton, and facial abnormalities, with a subset of individuals also presenting with kidney, vascular, and central nervous system phenotypes. Hepatocellular carcinoma (HCC) is a rare complication of ALGS, though little is known about its incidence or etiology among affected individuals. Previous reports have identified HCC occurrence in both pediatric and adult cases of ALGS. We present a case report of HCC in a 58‐year‐old woman with a pathogenic JAG1 variant and no overt hepatic features of ALGS. Through a comprehensive literature review, we compile all reported pediatric and adult cases, and further highlight one previously reported case of HCC onset in an adult ALGS patient without any hepatic disease features, similar to our own described patient. Our case report and literature review suggest that ALGS‐causing variants could confer risk for developing HCC regardless of phenotypic severity and highlight a need for a cancer screening protocol that would enable early detection and treatment in this at‐risk population.

Parents of infants at risk of neurodevelopmental impairment require clear and individualized information about what to expect for their child, yet data suggest they have difficulty knowing how to ask for this information. Here, we pilot a Question Prompt List (QPL) with parents of infants at risk of neurodevelopmental impairment. To assess real-time use of the QPL, we recorded family meetings and collected data from parents and clinicians about the QPL experience. Qualitative data were analyzed using directed content analysis. Ten parents were enrolled. In family meetings, clinicians universally acknowledged the QPL and most used the QPL to guide meeting content. All parents who used the QPL found it useful and would recommend the tool to others. In interviews, parents described that the QPL offered novel questions and facilitated more prepared answers from the team. Future studies should test the impact of this QPL on parent understanding and communication quality.

Objectives: Sensorineural hearing loss (SNHL) is a common sensory deficit affecting pediatric populations. The majority of pediatric SNHL is genetic in etiology, with over 123 identified nonsyndromic causative genes. One such gene is STRC, which has been identified as the second most frequent autosomal recessive nonsyndromic gene associated with SNHL in multiple populations. The objective of this study was to investigate the phenotypic presentation and incidence of audiologic progression in pediatric patients with STRC-related hearing loss (HL).Methods: Thirty-nine pediatric patients with confirmed HL and biallelic pathogenic STRC mutations were identified at two pediatric hospitals. A retrospective chart review was completed including demographics, medical history, genetic testing results, and audiologic data. HL progression was assessed using air conduction thresholds from pure-tone audiograms and auditory brain stem responses, and masked bone conduction thresholds from pure-tone audiograms.Results: Thirty-six patients had homozygous STRC deletions. Three were compound heterozygotes. All patients had bilateral, symmetric SNHL. Baseline HL was mild in 39% of ears, moderate in 52%, and moderate-severe in 3%. Of the 31 patients for which sufficient data were available to evaluate progression, 18 (58%) had some degree of progressive HL. Among these 31 patients assessed for progression, the mean hearing threshold declined by 0.6 dB per year (95% confidence interval: 0.5, 0.8; P < .001).Conclusions: These biallelic STRC patients displayed HL ranging from mild to moderate-severe at baseline and progressing in 58%. The variability of the STRC phenotype and the possibility of audiologic progression should be considered in the clinical management of pediatric STRC-related SNHL.