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Coronavirus disease 2019 (COVID-19) is a global public health emergency with many clinical facets, and new knowledge about its pathogenetic mechanisms is deemed necessary; among these, there are certainly coagulation disorders. In the history of medicine, autopsies and tissue sampling have played a fundamental role in order to understand the pathogenesis of emerging diseases, including infectious ones; compared to the past, histopathology can be now expanded by innovative techniques and modern technologies. For the first time in worldwide literature, we provide a detailed postmortem and biopsy report on the marked increase, up to 1 order of magnitude, of naked megakaryocyte nuclei in the bone marrow and lungs from serious COVID-19 patients. Most likely related to high interleukin-6 serum levels stimulating megakaryocytopoiesis, this phenomenon concurs to explain well the pulmonary abnormal immunothrombosis in these critically ill patients, all without molecular or electron microscopy signs of megakaryocyte infection.

Background and objectivesADPKD is erroneously perceived as a not rare condition, which is mainly due to the repeated citation of a mistaken interpretation of old epidemiological data, as reported in the Dalgaard's work (1957). Even if ADPKD is not a common condition, the correct prevalence of ADPKD in the general population is uncertain, with a wide range of estimations reported by different authors. In this work, we have performed a meta-analysis of available epidemiological data in the European literature. Furthermore we collected the diagnosis and clinical data of ADPKD in a province in the north of Italy (Modena). We describe the point and predicted prevalence of ADPKD, as well as the main clinical characteristics of ADPKD in this region.MethodsWe looked at the epidemiological data according to specific parameters and criteria in the Pubmed, CINAHL, Scopus and Web of Science databases. Data were summarized using linear regression analysis. We collected patients’ diagnoses in the Province of Modena according to accepted clinical criteria and/or molecular analysis. Predicted prevalence has been calculated through a logistic regression prediction applied to the at-risk population.ResultsThe average prevalence of ADPKD, as obtained from 8 epidemiological studies of sufficient quality, is 2.7: 10,000 (CI95 = 0.73–4.67). The point prevalence of ADPKD in the province of Modena is 3.63: 10,000 (CI95 = 3.010–3.758). On the basis of the collected pedigrees and identification of the at-risk subjects, the predicted prevalence in the Province of Modena is 4.76: 10,000 (CI 95% = 4.109–4.918).ConclusionAs identified in our study, point prevalence is comparable with the majority of the studies of literature, while predicted prevalence (4.76: 10,000) generally appears higher than in the previous estimates of the literature, with a few exceptions. Thus, this could suggest that undiagnosed ADPKD subjects, as predicted by our approach, could be relevant and will most likely require more clinical attention. Nevertheless, our estimation, in addition to the averaged ones derived from literature, not exceeding the limit of 5:10,000 inhabitants, are compatible with the definition of rare disease adopted by the European Medicines Agency and Food and Drug Administration.

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Background and objectivesImmunohistopathology is an essential technique in the diagnostic workflow of a kidney biopsy. Deep learning is an effective tool in the elaboration of medical imaging. We wanted to evaluate the role of a convolutional neural network as a support tool for kidney immunofluorescence reporting.Design, setting, participants, & measurementsHigh-magnification (×400) immunofluorescence images of kidney biopsies performed from the year 2001 to 2018 were collected. The report, adopted at the Division of Nephrology of the AOU Policlinico di Modena, describes the specimen in terms of “appearance,” “distribution,” “location,” and “intensity” of the glomerular deposits identified with fluorescent antibodies against IgG, IgA, IgM, C1q and C3 complement fractions, fibrinogen, and κ- and λ-light chains. The report was used as ground truth for the training of the convolutional neural networks.ResultsIn total, 12,259 immunofluorescence images of 2542 subjects undergoing kidney biopsy were collected. The test set analysis showed accuracy values between 0.79 (“irregular capillary wall” feature) and 0.94 (“fine granular” feature). The agreement test of the results obtained by the convolutional neural networks with respect to the ground truth showed similar values to three pathologists of our center. Convolutional neural networks were 117 times faster than human evaluators in analyzing 180 test images. A web platform, where it is possible to upload digitized images of immunofluorescence specimens, is available to evaluate the potential of our approach.ConclusionsThe data showed that the accuracy of convolutional neural networks is comparable with that of pathologists experienced in the field.

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Background. Although diabetic kidney disease (DKD) could affect up to one-third of patients with diabetes mellitus (DM), these patients can develop kidney diseases different from DKD, or these conditions can superimpose on DKD. Several potential predictors of nondiabetic kidney disease (NDKD) have been proposed, but there are no definitive indications available for kidney biopsy in diabetic patients. Methods. We designed a single-center, cross-sectional, and retrospective cohort study to identify clinical and laboratory factors associated with a diagnosis of NDKD after native kidney biopsy in diabetic patients and to investigate differences in time to end-stage kidney disease (ESKD) in patients with a diagnosis of DKD and NDKD. Results. Of 142 patients included in our analysis, 89 (62.68%) had a histopathological diagnosis of NDKD or mixed NDKD + DKD. Patients in the NDKD group had significantly lower HbA1C, lower prevalence of diabetic retinopathy (DR), and less severe proteinuria, and there was a lower proportion of patients with nephrotic syndrome; the DKD group had significantly lower proportion of patients with hematological conditions. In the multivariate binary logistic regression, only absence of DR and presence of a hematological condition significantly predicted NDKD after adjustment for age and sex. Time to ESKD was significantly higher in patients with NDKD or mixed forms than in those with DKD. Conclusions. After a careful selection, more than half of kidney biopsies performed in diabetic patients can identify NDKD (alone or with concomitant DKD). Absence of DR and coexistence of a hematological condition (especially MGUS) were strong predictors of NDKD in our cohort.