The long-term outcome of patients with IgA nephropathy who present with normal renal function, microscopic hematuria, and minimal or no proteinuria is not well described. Here, we studied 141 Caucasian patients with biopsy-proven IgA nephropathy who had minor abnormalities at presentation and a median follow-up of 108 months. None of the patients received corticosteroids or immunosuppressants. We reviewed renal biopsies using the Oxford classification criteria. In this sample, 46 (32%) patients had mesangial proliferation, whereas endocapillary proliferation, focal glomerulosclerosis, and tubulointerstitial abnormalities were uncommon. Serum creatinine increases .50% and .100% were observed in five (3.5%) patients and one (0.7%) patient, respectively; no patients developed ESRD. After 10, 15, and 20 years, 96.7%, 91.9%, and 91.9% of patients maintained serum creatinine values less than a 50% increase, respectively. Using Cox proportional hazards regression, the presence of segmental glomerulosclerosis was the only factor that significantly associated with a .50% increase in serum creatinine. Clinical remission occurred in 53 (37.5%) patients after a median of 48 months. Proteinuria.0.5 and .1.0 g/24 h developed in 21 (14.9%) and 6 (4.2%) patients, respectively. Median proteinuria at the end of follow-up was 0.1 g/24 h, with 41 (29.1%) patients having no proteinuria. At presentation, 23 (16.3%) patients were hypertensive compared with 30 (21.3%) patients at the end of follow-up; 59 (41.8%) patients were treated with reninangiotensin blockers because of hypertension or increasing proteinuria. In summary, the long-term prognosis for Caucasian patients with IgA nephropathy who present with minor urinary abnormalities and normal renal function is excellent.

Despite the fact that the cell cycle is a fundamental process of life, a detailed quantitative understanding of gene regulation dynamics throughout the cell cycle is far from complete. Single-cell RNA-sequencing (scRNA-seq) technology gives access to these dynamics without externally perturbing the cell. Here, by generating scRNA-seq libraries in different cell systems, we observe cycling patterns in the unspliced-spliced RNA space of cell cycle-related genes. Since existing methods to analyze scRNA-seq are not efficient to measure cycling gene dynamics, we propose a deep learning approach (DeepCycle) to fit these patterns and build a high-resolution map of the entire cell cycle transcriptome. Characterizing the cell cycle in embryonic and somatic cells, we identify major waves of transcription during the G1 phase and systematically study the stages of the cell cycle. Our work will facilitate the study of the cell cycle in multiple cellular models and different biological contexts.

We analyzed the incidence of lower extremity amputations (LEAs) in the 3rd Health Care Area of Madrid before and after the March 2008 introduction of a multidisciplinary team for managing diabetic foot disease. We compared the amputation rates in people with and without diabetes during 2 periods: before (2001-2007) and after (2008-2011) the introduction of a Multidisciplinary Diabetic Foot Unit (MDFU). We also analyzed the trend of the amputation rates by joinpoint regression analysis and measured the annual percentage change (APC). During the study period, 514 nontraumatic LEAs were performed, 374 (73%) in people with diabetes and 140 (27%) in people without the disease. The incidence of LEAs showed a significant reduction in major amputations in people with diabetes, from 6.1 per 100 000 per year (95% confidence interval [CI] = 4.9 to 7.2), in the 2001 to 2007 period, to 4.0 per 100 000 per year (95% CI = 2.6 to 5.5) in the 2008 to 2011 period (P = .020). There were no changes in incidence of minor or total amputations in the diabetic population or in amputations in the nondiabetic population during the study period. Joinpoint regression analysis showed a significant reduction in the incidence of major LEAs in diabetic population with an APC of -6.6% (95% CI = -10.2 to -2.8; P = .003), but there were no other significant changes. This study demonstrates that the introduction of a multidisciplinary team, coordinated by an endocrinologist and a podiatrist, for managing diabetic foot disease is associated with a reduction in the incidence of major amputations in patients with diabetes.

Background: This study reviews the mortality of patients with diabetic foot ulcers (DFU) from the first consultation with a Multidisciplinary Diabetic Foot Team (MDFT) and analyzes the main cause of death, as well as the relevant clinical factors associated with survival. Methods: Data of 338 consecutive patients referred to the MDFT center for a new DFU during the 2008–2014 period were analyzed. Follow-up: until death or until 30 April 2020, for up to 12.2 years. Results: Clinical characteristics: median age was 71 years, 92.9% had type 2 diabetes, and about 50% had micro-macrovascular complications. Ulcer characteristics: Wagner grade 1–2 (82.3%), ischemic (49.2%), and infected ulcers (56.2%). During follow-up, 201 patients died (59.5%), 110 (54.7%) due to cardiovascular disease. Kaplan—Meier curves estimated a reduction in survival of 60% with a 95% confidence interval (95% CI), (54.7–65.3) at 5 years. Cox regression analysis adjusted to a multivariate model showed the following associations with mortality, with hazard ratios (HRs) (95% CI): age, 1.07 (1.05–1.08); HbA1c value < 7% (53 mmol/mol), 1.43 (1.02–2.0); active smoking, 1.59 (1.02–2.47); ischemic heart or cerebrovascular disease, 1.55 (1.15–2.11); chronic kidney disease, 1.86 (1.37–2.53); and ulcer severity (SINBAD system) 1.12 (1.02–1.26). Conclusion: Patients with a history of DFU have high mortality. Two less known predictors of mortality were identified: HbA1c value < 7% (53 mmol/mol) and ulcer severity.

Background Antiviral prophylaxis is recommended in cytomegalovirus (CMV)-seropositive kidney transplant (KT) recipients receiving antithymocyte globulin (ATG) as induction. An alternative strategy of premature discontinuation of prophylaxis after CMV-specific cell-mediated immunity (CMV-CMI) recovery (immunoguided prevention) has not been studied. The aim of this study was to evaluate whether it is effective and safe to discontinue prophylaxis when CMV-CMI is detected and to continue with preemptive therapy. Methods In this open-label, non-inferiority clinical trial, patients were randomized 1:1 to follow immunoguided strategy, receiving prophylaxis (valganciclovir 900 mg daily) until CMV-CMI recovery or to receive fixed-duration prophylaxis until day +90. After prophylaxis, preemptive therapy (valganciclovir 900 mg twice daily) was indicated in both arms until month 6. The primary and secondary outcomes were incidence of CMV disease and replication, respectively, within the first 12 months. Desirability of outcome ranking (DOOR) assessed two deleterious events (CMV disease/replication and neutropenia). Results A total of 150 CMV-seropositive KT recipients were randomly assigned. There was no difference in the incidence of CMV disease (0% vs. 2.7%; P = 0.149) and replication (17.1% vs. 13.5%; log-rank test, P = 0.422) between both arms. Incidence of neutropenia was lower in the immunoguided arm (9.2% vs. 37.8%; OR, 6.0; P &lt; 0.001). A total of 66.1% of patients in the immunoguided arm showed a better DOOR, indicating a greater likelihood of a better outcome. Conclusions Prophylaxis can be prematurely discontinued in CMV-seropositive KT patients receiving ATG when CMV-CMI is recovered since no significant increase in the incidence of CMV replication or disease is observed.

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ABSTRACThematopoietic transplant units in Spain. Eligible subjects were patients over 18 years of age who had undergone an allo-HSCT at least six months prior to enrollment, with transfusional iron overload (serum ferritin ≥1000 ng/mL or transfusional load ≥20 units (~100 mL/kg) of packed red blood cells) and absolute neutrophil count over 1 x 10

A BS TRACT: Background: Fragile X-associated tremor/ ataxia syndrome is a neurodegenerative disease of late onset developed by carriers of the premutation in the fragile x mental retardation 1 (FMR1) gene. Pathological features of neurodegeneration in fragile X-associated tremor/ ataxia syndrome include toxic levels of FMR1 mRNA, ubiquitin-positive intranuclear inclusions, white matter disease, iron accumulation, and a proinflammatory state. Objective: The objective of this study was to analyze the presence of cerebral microbleeds in the brains of patients with fragile X-associated tremor/ataxia syndrome and investigate plausible causes for cerebral microbleeds in fragile X-associated tremor/ataxia syndrome. Methods: We collected cerebral and cerebellar tissue from 15 fragile X-associated tremor/ataxia syndrome cases and 15 control cases carrying FMR1 normal alleles. We performed hematoxylin and eosin, Perls and Congo red stains, ubiquitin, and amyloid β protein immunostaining. We quantified the number of cerebral microbleeds, amount of iron, presence of amyloid β within the capillaries, and number of endothelial cells containing intranuclear inclusions. We evaluated the relationships between pathological findings using correlation analysis. Results: We found intranuclear inclusions in the endothelial cells of capillaries and an increased number of cerebral microbleeds in the brains of those with fragile X-associated tremor/ataxia syndrome, both of which are indicators of cerebrovascular dysfunction. We also found a suggestive association between the amount of capillaries that contain amyloid β in the cerebral cortex and the rate of disease progression. Conclusion:We propose microangiopathy as a pathologic feature of fragile X-associated tremor/ataxia syndrome.