Abdominal Visceral Infarction in 3 Patients with COVID-19.

A high incidence of thrombotic events has been reported in patients with coronavirus disease (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We report 3 clinical cases of patients in Italy with COVID-19 who developed abdominal viscera infarction, demonstrated by computed tomography.

Genetic Drivers of Kidney Defects in the DiGeorge Syndrome.

BACKGROUND: The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. METHODS: We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. RESULTS: We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P=4.5×10-14). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. CONCLUSIONS: We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.).

[Frail nephropathic patients: maximum conservative therapy or dialysis? Results from a retrospective observational study].

Background and objectives: Chronic dialysis in frail nephropathic patients can worsen the symptom load and their functional autonomy, increasing the risk of early mortality. It is key to evaluate if dialysis treatment represents a real advantage for these patients; Maximum Conservative Therapy (MCT) associated with palliative care, could improve their residual quality of life, avoiding dialysis. The aim of this work is to describe the application and the relative terms of MCT in a complete series of cases followed in our Nephrological Clinic. Study design and setting: This is a retrospective observational study on a cohort of 48 frail nephropathic patients in MCT and 58 on dialysis, in the period between January 2013 and December 2019. The place of death, Incidence Rate (IR) and Incidence Rate Ratio (IRR) related to survival and hospitalization rates were studied. Results: The average duration of MCT was 9.7 months vs 13.5 months of dialysis treatment. One-year probability of survival of dialysis patient was 0.52 [CI 0.38-0.64] vs 0.48 [CI 0.33-0.62] in MCT patients; however, dialysis patients had higher rates of hospitalization (IR 2.780 vs 1.269 in MCT patients), IRR 2.19 [CI 1.66-2.89], according to literature [13]. 67% of dialysis patients died in hospital versus 35% of MCT patients. 34% of MCT patients are still alive at the time of data analysis (January 31, 2020); no dialysis patients are still alive on the same date. Conclusions: The use of dialysis has shown a marginal, even though significant, effect on the average survival of frail nephropathic patients; however, they present a higher hospitalization rate, with consequent impact on the quality of life. The choice of the treatment (MCT vs dialysis) should not be merely based on the presence of comorbidities, but rather on the type of comorbidity found, which represents each time an element in favor of MCT or dialysis.

Determinants of inappropriate setting allocation in the care of patients with type 2 diabetes: A population-based study in Reggio Emilia province.

The study aims to describe the distribution of patients with type 2 diabetes (T2D) by care plan and to highlight determinants of underuse and overuse of integrated care (IC). This cross-sectional study included all T2D patients resident in Reggio Emilia on 31/12/2015 based on the population-based diabetes registry. Eligibility for IC requires good glycaemic control, no rapid insulin, no kidney failure and no diabetes complications. We calculated the proportion of IC underuse and overuse and adjusted prevalence estimate using multivariate logistic regression. Determinants were age, sex, citizenship, district of residence and time since diagnosis. Of 29,776 patients, 15,364 (51.6%) were in diabetes clinic plan, 9851 (33.1%) in IC plan and 4561 (15.3%) not in any care plan (i.e., in Other group). There were 10,906 (36.6%) patients eligible for IC, of whom 1000 in Other group. When we adjusted for all covariates and restricted the analysis to patients included in care plans, the proportion of those eligible for IC plan but cared for in diabetes clinic plan (i.e. underuse of IC) was 28% (n = 3028/9906; 95%CI 27-29). Similarly, the proportion of those not eligible for IC but cared for in IC plan (i.e. overuse of IC) was 11% (n = 1720/11,896; 95%CI 10-11).The main determinant of both IC underuse and overuse was the district of residence. Foreign status was associated with underuse (37%; 95%CI 33-43), while old age (≥80 years) with both underuse (36%; 95%CI 0.33-0.38) and overuse (23%; 95%CI 22-25). The criterion for suspension of IC plan most frequently found was renal failure, followed by hospitalization for diabetes-related complications. Patients are more often allocated to more specialized settings than not. Healthcare provider-related factors are the main determinants of inappropriate setting allocation.

Correction: Determinants of inappropriate setting allocation in the care of patients with type 2 diabetes: A population-based study in Reggio Emilia province.

[This corrects the article DOI: 10.1371/journal.pone.0219965.].

Pazopanib in Renal Cell Carcinoma Dialysis Patients: A Mini-Review and a Case Report.

BACKGROUND: Sporadic data are available about pazopanib use in patients with metastatic renal cell carcinoma (mRCC) undergoing dialysis and no systematic review has been previously performed about this issue. OBJECTIVE: The objective of the present mini-review is to provide an overview of clinical outcomes of pazopanib in this population, in order to support the clinical oncologist for the treatment choice and management. RESULTS: All the literature ever published about mRCC dialysis patients receiving pazopanib, until August 2015, was evaluated: only two case series emerged from our search and one more patient from our department was also included, with a total of 11 mRCC dialysis patients overall. Moreover, we described our case of intrapatient dose titration of pazopanib during dialysis. CONCLUSION: The continued treatment schedule, the short half-life, the predominantly hepatic metabolism, the wide possibility of dose modulation, the favorable tolerability profile and the similar efficacy respect to sunitinib represent factors in favor of pazopanib as first line mRCC treatment in dialysis patients. The knowledge and the good management of toxicity during pazopanib treatment can lead, also in dialysis patients, to the best and longest application of the drug, taking into account the concept of a dose escalation guided by toxicity as a marker of efficacy. The review, together with our single case report, confirmed the efficacy, the good tolerability and the maneuverability of pazopanib treatment in mRCC patients undergoing dialysis.

Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens.

We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six new genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geospatial distribution of risk alleles is highly suggestive of multi-locus adaptation, and genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN.