Multi-Organ Histopathological Changes in a Mouse Hepatitis Virus Model of COVID-19.

Infection with SARS-CoV-2, the virus responsible for the global COVID-19 pandemic, causes a respiratory illness that can severely impact other organ systems and is possibly precipitated by cytokine storm, septic shock, thrombosis, and oxidative stress. SARS-CoV-2 infected individuals may be asymptomatic or may experience mild, moderate, or severe symptoms with or without pneumonia. The mechanisms by which SARS-CoV-2 infects humans are largely unknown. Mouse hepatitis virus 1 (MHV-1)-induced infection was used as a highly relevant surrogate animal model for this study. We further characterized this animal model and compared it with SARS-CoV-2 infection in humans. MHV-1 inoculated mice displayed death as well as weight loss, as reported earlier. We showed that MHV-1-infected mice at days 7-8 exhibit severe lung inflammation, peribronchiolar interstitial infiltration, bronchiolar epithelial cell necrosis and intra-alveolar necrotic debris, alveolar exudation (surrounding alveolar walls have capillaries that are dilated and filled with red blood cells), mononuclear cell infiltration, hyaline membrane formation, the presence of hemosiderin-laden macrophages, and interstitial edema. When compared to uninfected mice, the infected mice showed severe liver vascular congestion, luminal thrombosis of portal and sinusoidal vessels, hepatocyte degeneration, cell necrosis, and hemorrhagic changes. Proximal and distal tubular necrosis, hemorrhage in interstitial tissue, and the vacuolation of renal tubules were observed. The heart showed severe interstitial edema, vascular congestion, and dilation, as well as red blood cell extravasation into the interstitium. Upon examination of the MHV-1 infected mice brain, we observed congested blood vessels, perivascular cavitation, cortical pericellular halos, vacuolation of neuropils, darkly stained nuclei, pyknotic nuclei, and associated vacuolation of the neuropil in the cortex, as well as acute eosinophilic necrosis and necrotic neurons with fragmented nuclei and vacuolation in the hippocampus. Our findings suggest that the widespread thrombotic events observed in the surrogate animal model for SARS-CoV-2 mimic the reported findings in SARS-CoV-2 infected humans, representing a highly relevant and safe animal model for the study of the pathophysiologic mechanisms of SARS-CoV-2 for potential therapeutic interventions.

Short-term outcomes of 59 dogs treated for ilial body fractures with locking or non-locking plates.

OBJECTIVE: To determine the influence of plating systems on the clinical outcomes in dogs treated for ilial fractures. DESIGN: Retrospective study. ANIMALS: Fifty-nine dogs (63 hemipelves). METHODS: Radiographs and medical records of dogs with ilial fractures presented to Iowa State University between 2003 and 2019 were reviewed. After fracture reduction, fractures were fixed with a locking plate system (LPS) or non-locking plate system (NLS). Perioperative, long-term complications, and follow-up data were recorded. The frequency of implant failure and pelvic collapse were compared using a logistic and linear regression analysis, respectively. Where the univariate test was statistically significant, a multivariate analysis across categories was performed to identify statistically different categories. RESULTS: LPS and NLS implants were used in 25/63 and 38/63 hemipelves, respectively. Median follow-up time was 8 weeks (3-624 weeks). Implant failure occurred in 18/63 (29%) of fracture repairs, consisting of 17 with NLS and 1 with LPS. Revision surgery was recommended in five cases of implant failure, all with NLS. The probability of implant failure was higher when fractures were fixed with NLS (p = .0056). All other variables evaluated did not seem to influence outcome measures. CONCLUSION: The variable with the most influence on the outcomes of dogs treated for ilial fractures consisted of the fixation method (NLS vs. LPS). Fractures repaired with NLS were nearly 20 times more likely to fail than those repaired with LPS. CLINICAL RELEVANCE: Surgeons should consider repairing ilial body fractures in dogs with LPS to reduce the risk of short-term implant failure.

Longitudinal Observations on the Mineral Metabolism of Dialysis Patients at the University Hospital.

A retrospective review was performed from November 2011 through June 2012 in 49 stable patients receiving ambulatory hemodialysis at the dialysis unit of the University Hospital in San Juan. Measurements of serum phosphate, serum calcium (corrected to albumin levels), intact parathyroid hormone (PTH), and pulse pressure were obtained at 3-month intervals over the course of a 9-month observation period. These longitudinal observations assessed the efficiency of treatment, with the objective being to determine the nature of and then implement such changes as would improve the patients' outcomes. Thirty-three of the 49 patients appeared to have fairly good control of their PTH levels during the observation period. Sixteen patients had levels over 300 pg/ml, and, using Stata data analysis software, a linear relationship with phosphate levels was obtained (p = 0.021, R2 = 0.1037, adjusted R2 = 0.0855). Pulse pressure (PP) measurements obtained at each observation interval showed the following increases: 69% at 3 months, 65% at 6 months, and 57% at 9 months. Calcium-containing phosphate binders were used in one third of the population and vitamin D analogs in 50%. A trend towards a rise in PP was observed as calcium levels increased over 9.5 mg/dl. It is concluded that those patients experiencing that rise need close supervision to avoid the increasing morbidity and mortality associated with mineral metabolism derangement. Wide PPs were observed in these patients during the 9 months of observation, denoting persistent arterial stiffness suggestive of an increase in calcium balance.