Extracellular vesicles (EVs) are implicated in the crosstalk between adipocytes and other metabolic organs, and an altered biological cargo has been observed in EVs from human obese adipose tissue ...(AT). Yet, the role of adipocyte-derived EVs in pancreatic β cells remains to be determined. Here, we explored the effects of EVs released from adipocytes isolated from both rodents and humans and human AT explants on survival and function of pancreatic β cells and human pancreatic islets. EVs from healthy 3T3-L1 adipocytes increased survival and proliferation and promoted insulin secretion in INS-1E β cells and human pancreatic islets, both those untreated or exposed to cytokines or glucolipotoxicity, whereas EVs from inflamed adipocytes caused β cell death and dysfunction. Human lean adipocyte-derived EVs produced similar beneficial effects, whereas EVs from obese AT explants were harmful for human EndoC-βH3 β cells. We observed differential expression of miRNAs in EVs from healthy and inflamed adipocytes, as well as alteration in signaling pathways and expression of β cell genes, adipokines, and cytokines in recipient β cells. These in vitro results suggest that, depending on the physiopathological state of AT, adipocyte-derived EVs may influence β cell fate and function.
Aim
To report on clinical outcomes of simultaneous integrated boost intensity‐modulated radiation therapy (IMRT) and concurrent chemotherapy as per Radiation Therapy Oncology Group (RTOG) 0529 ...protocol in anal cancer patients.
Methods
Clinical stage T1–T4 N0–N3 anal cancer patients were submitted to concomitant chemoradiation. Patients with cT2N0 disease were prescribed 50.4 Gy/28 fractions to the gross tumor planning target volume (PTV) and 42 Gy/28 fractions to the elective nodal PTV. Patients staged as cT3–T4/N0–N3 were given 54 Gy/30 fractions to the macroscopic anal PTV, while clinical nodes were prescribed 50.4 Gy/30 fractions if <3 cm or 54 Gy/30 fractions if ≥3 cm; elective nodal PTV was prescribed 45 Gy/30 fractions. Two cycles of concomitant 5‐fluorouracil and mitomycin C were planned for all patients. Oncological outcomes, acute and late toxicity profiles and pattern of failure were reported.
Results
The 3‐year colostomy‐free survival rate was 64% (95% CI 0.52–0.75). The 3‐year local control, disease‐free and overall survival rates were 69% (95% CI 0.57–0.79), 71% (95% CI 0.59–0.80) and 79% (95% CI 0.66–0.87), respectively. The cumulative incidence of colostomies was 15.1% (95% CI 8.15–23.88) at 24 months. The cumulative incidence of cancer‐specific deaths was 16.4% (95% CI 8.60–26.47) at 36 months. Major acute toxicity consisted of hematological (G3–G4: 26%) and cutaneous (G3–G4: 16%) events. Only one case of ≥G3 late toxicity was documented.
Conclusions
Simultaneous integrated boost IMRT and concurrent chemotherapy as per RTOG 0529 protocol seems to be safe and feasible with consistent oncological outcomes and a mild acute and late toxicity profile in anal cancer patients.
Aims
To identify metabolic phenotypes at increased risk of impaired glucose tolerance (IGT) in Italian overweight/obese children (
n
= 148, age 5–10 years) and adolescents (
n
= 531, age ...10–17.9 year).
Methods
Phenotypes were defined as follows: obesity by the 95th cut-points of the Center for Disease Control body mass index reference standards, impaired fasting glucose (fasting plasma glucose ≥100 mg/dl), high circulating triglycerides (TG), TG/HDL cholesterol ≥2.2, waist-to-height ratio (WTHR) >0.6, and combination of the latter with high TG or TG/HDL cholesterol ≥2.2.
Results
In the 148 obese children, TG/HDL-C ≥ 2.2 (OR 20.19; 95 % CI 2.50–163.28,
p
= 0.005) and the combination of TG/HDL-C ≥ 2.2 and WTHR > 0.60 (OR 14.97; 95 % CI 2.18–102.76,
p
= 0.006) were significantly associated with IGT. In the 531 adolescents, TG/HDL-C ≥ 2.2 (OR 1.991; 95 % CI 1.243–3.191,
p
= 0.004) and the combination with WTHR > 0.60 (OR 2.24; 95 % CI 1.29–3.87,
p
= 0.004) were associated with significantly increased risk of IGT. In the whole sample, having high TG levels according to the NIH National Heart, Lung and Blood Institute Expert Panel was not associated with an increased risk of presenting IGT.
Conclusions
TG/HDL-C ratio can be useful, particularly in children, to identify obese young patients at risk of IGT. Its accuracy as screening tool in a general population needs to be verified. The combination of TG/HDL-C ratio and WTHR > 0.6 did not improve prediction. Having high TG according to the NIH definition was not associated with increased risk of developing IGT.
Severe/medically complicated obesity in childhood, and particularly in adolescence, is a real disability that requires an intensive and continuous approach which should follow the procedures and ...schedule of rehabilitation medicine. Given the lack of a specific document focusing on children and adolescents, the Childhood Obesity Study Group set out to explore the available evidence for the treatment of severe or medically complicated obesity and to set standards tailored to the specific context of the Italian Health Service. Through a series of meetings and electronic communications, the writing committee (selected from members of the Study Group) selected the key issues, explored the literature and produced a draft document which was submitted to the other experts until the final synthesis was approved by the group. In brief, the following issues were involved: (1) definition and epidemiology; (2) identification of common goals designed to regain functional competence and limit the progression of metabolic and psychological complications; (3) a multi-professional team approach; (4) the care setting. This paper is an expert opinion document on the rehabilitation of severe and medically complicated obesity in children and adolescents produced by experts belonging to the Childhood Obesity Study Group of the Italian Society for Pediatric Endocrinology and Diabetology (ISPED).
An alternative approach to the allogeneic transfusion is patient's blood collection before the operation, using or not using the human recombinant erythropoietin. The aim of this study is to evaluate ...the percentage of people undergoing an elective operation for colorectal carcinoma who could avoid allogeneic blood due to blood predonation.
From January 1999 to April 2002, 249 patients (140 males and 109 females) underwent an operation for colorectal cancer. The most important parameter, used to estimate which patients are candidates for autologous blood predonation, is the before-treatment hemoglobin level. The other parameters we considered are the age of the patient, the absence of uncontrolled hypertension or clinically significant pathologies (except colorectal cancer), and the iron shortage.
Retrospective cohort study.
36.5% of the patients satisfied every criterion to begin autologous predonation without using the human recombinant erythropoietin; instead, 23.7% of patients needed the administration of the human recombinant erythropoietin and additional iron. The valuation of the transfusional prospects, based on sex and cancer location is very interesting.
Autologous blood predeposit in preoperational time turns out to be a method of increasing importance, thanks to the human recombinant erythropoietin.
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