Aims To investigate if urinary AQP5 serves as a new potential biomarker of diabetic nephropathy. Methods Using an AQP5-specific enzyme-linked immunosorbent assay, we measured serum and urine AQP5 first in a cohort consisting of normal controls (n = 26) and patients with diabetes mellitus (n = 25) or diabetic nephropathy (n = 33) and then in a validation cohort possessing normal controls (n = 10), patients with diabetes mellitus (n = 10) or diabetic nephropathy (n = 14), and patients with chronic kidney disease of unknown etiology (n = 10). We used various statistical methods including Pearson’s correlation coefficient, ANOVA with Holm–Sidak test, Receiver Operator Curve, and multiple logistic regression to analyze the data. Results Urine AQP5/creatinine 1) is significantly higher in diabetic nephropathy than in other two groups, and in diabetic nephropathy stage V than in stage III; 2) correlates with serum creatinine, urine albumin, and multiple other known risk factors of the disease; and 3) improves the clinical models in distinguishing diabetic nephropathy from normal controls and diabetic mellitus. Conclusion Our data suggest that urine AQP5/creatinine may possess diagnostic and prognostic values as a biomarker of diabetic nephropathy.

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Thick, viscous respiratory secretions are a major pathogenic feature of COVID-19 disease, but the composition and physical properties of these secretions are poorly understood. We characterized the composition and rheological properties (i.e. resistance to flow) of respiratory secretions collected from intubated COVID-19 patients. We find the percent solids and protein content are greatly elevated in COVID-19 compared to heathy control samples and closely resemble levels seen in cystic fibrosis, a genetic disease known for thick, tenacious respiratory secretions. DNA and hyaluronan (HA) are major components of respiratory secretions in COVID-19 and are likewise abundant in cadaveric lung tissues from these patients. COVID-19 secretions exhibit heterogeneous rheological behaviors with thicker samples showing increased sensitivity to DNase and hyaluronidase treatment. In histologic sections from these same patients, we observe increased accumulation of HA and the hyaladherin versican but reduced tumor necrosis factor–stimulated gene-6 (TSG6) staining, consistent with the inflammatory nature of these secretions. Finally, we observed diminished type I interferon and enhanced inflammatory cytokines in these secretions. Overall, our studies indicate that increases in HA and DNA in COVID-19 respiratory secretion samples correlate with enhanced inflammatory burden and suggest that DNA and HA may be viable therapeutic targets in COVID-19 infection.

Isolated extramedullary relapse of acute lymphoblastic leukemia (ALL) occurs in soft tissues and various organs outside the testis and central nervous system. Treatments such as hematopoietic stem cell transplantation and more novel modalities such as immunotherapy have eradicated ALL at extramedullary sites. In some instances, survival times for relapsed ALL at these sites are longer than those for relapsed disease involving only the bone marrow. Isolated relapse of ALL in the myocardium is rare, especially in children, making diagnosis and treatment of it difficult. More recent treatment options such as chimeric antigen receptor T-cell therapy carry a high risk of cytokine release syndrome and associated risk of worsening cardiac function. Herein we present the case of an 11-year-old boy who presented with relapsed symptomatic B-cell ALL in the myocardium following allogeneic hematopoietic stem cell transplantation. This is an unusual presentation of relapsed ALL and this case demonstrates the associated challenges in its diagnosis and treatment. The case report is followed by a literature review of the advances in treatment of pediatric leukemia and their application to extramedullary relapse of this disease in particular.

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