Recent clinical data has suggested a correlation between Coronavirus disease 19 (COVID-19) and diabetes. Here, we describe the detection of SARS-CoV-2 viral antigen in pancreatic beta cells in autopsy samples from individuals with COVID-19. Single-cell RNA-sequencing and immunostaining from ex vivo infections confirmed that multiple types of pancreatic islet cells were susceptible to SARS-CoV-2, eliciting a cellular stress response and the induction of chemokines. Upon SARS-CoV-2 infection, beta cells showed a lower expression of insulin and a higher expression of alpha and acinar cell markers, including glucagon and trypsin1, respectively, suggesting cellular transdifferentiation. Trajectory analysis indicated that SARS-CoV-2 induced eIF2 pathway-mediated beta cell transdifferentiation, a phenotype that could be reversed with trans -integrated stress response inhibitor ( trans -ISRIB). Altogether, this study demonstrates an example of SARS-CoV-2 infection causing cell fate change, which provides further insight into the pathomechanisms of COVID-19.
The Clinical Islet Transplantation 07 (CIT07) protocol uses antithymocyte globulin and etanercept induction, islet culture, heparinization, and intensive insulin therapy with the same low-dose tacrolimus and sirolimus maintenance immunosuppression as in the Edmonton protocol. To determine whether CIT07 improves engrafted islet β-cell mass, our center measured β-cell secretory capacity from glucose-potentiated arginine tests at days 75 and 365 after transplantation and compared those results with the results previously achieved by our group using the Edmonton protocol and normal subjects. All subjects were insulin free, with CIT07 subjects receiving fewer islet equivalents from a median of one donor compared with two donors for Edmonton protocol subjects. The acute insulin response to glucose-potentiated arginine (AIRpot) was greater in the CIT07 protocol than in the Edmonton protocol and was less in both cohorts than in normal subjects, with similar findings for C-peptide. The CIT07 subjects who completed reassessment at day 365 exhibited increasing AIRpot by trend relative to that of day 75. These data indicate that engrafted islet β-cell mass is markedly improved with the CIT07 protocol, especially given more frequent use of single islet donors. Although several peritransplant differences may have each contributed to this improvement, the lack of deterioration in β-cell secretory capacity over time in the CIT07 protocol suggests that low-dose tacrolimus and sirolimus are not toxic to islets.
Selection of an optimal donor pancreas is the first key task for successful islet isolation. We conducted a retrospective multicenter study in 11 centers in North America to develop an islet donor scoring system using donor variables. The data set consisting of 1,056 deceased donors was used for development of scoring system to predict islet isolation success (defined as post-purification islet yield >400,000 islet equivalents). With an aid of univariate logistic regression analyses, we developed North American Islet Donor Score (NAIDS) ranging 0 through 100 points. The c-index in the development cohort was 0.73 [95% confidence interval 0.70 - 0.76]. The success rate increased proportionally as NAIDS increased, from 6.8% success in NAIDS < 50 points to 53.7% success in NAIDS ≥ 80 points. We further validated NAIDS using a separate set of data consisting of 179 islet isolations. Comparable outcome of NAIDS was observed in the validation cohort. The NAIDS may be a useful tool for donor pancreas selection in the clinical practice. Apart from its utility in clinical decision-making, the NAIDS may also be used in research setting as a standardized measurement of pancreas quality.
Buschke-Lowenstein tumor is a relatively rare sexually transmitted disease. It is a neoplasm of the anogenital region which has benign appearance on histopathology but is locally destructive. It carries a high recurrence rate and a significant potential for malignant transformation. Human papilloma virus has been implicated as an etiologic agent for this tumor. Since this disease is rare and no controlled studies exist, radical excision of this anogenital lesion is generally recommended as the first line therapy and close vigilance and followup are essential. We have discussed an overview of etiopathogenesis, clinical presentation, diagnosis, and management of this uncommonly encountered disease.
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