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Insulin resistance and loss of glucose-stimulated acute insulin response (AIR) are the two major and earliest defects in the course of type 2 diabetes. We investigated whether weight loss after bariatric surgery in patients with morbid obesity and type 2 diabetes could restore euglycemia and normal AIR to an intravenous glucose tolerance test (IVGTT). We studied 25 morbidly obese patients-12 with type 2 diabetes, 5 with impaired glucose tolerance, and 8 with normal glucose tolerance (NGT)-before and after a biliopancreatic diversion (BPD) with Roux-en-Y gastric bypass (RYGBP). Twelve individuals with normal BMI served as control subjects. Twelve months after surgery, in the diabetes group, BMI decreased from 53.2 +/- 2.0 to 29.2 +/- 1.7 kg/m(2), fasting glucose decreased from 9.5 +/- 0.83 to 4.5 +/- 0.13 mmol/l, and fasting insulin decreased from 168.4 +/- 25.9 to 37.7 +/- 4.4 pmol/l (mean +/- SE; P < 0.001). AIR, the mean of insulin concentration at 2, 3, and 5 min over basal in the IVGTT, increased by 770 and 935% at 3 and 12 months after surgery, respectively (from 24.0 +/- 22.7 to 209 +/- 43.4 and 248 +/- 33.1 pmol/l, respectively; P < 0,001). Conversely, in the NGT group, the AIR decreased by 40.5% (from 660 +/- 60 to 393 +/- 93 pmol/l; P = 0.027) 12 months after surgery. BPD with RYGBP performed in morbidly obese patients with type 2 diabetes leads to significant weight loss, euglycemia, and normal insulin sensitivity; but most importantly, it restores a normal beta-cell AIR to glucose and a normal relationship of AIR to insulin sensitivity. This is the first study to demonstrate that the lost glucose-induced AIR in patients with type 2 diabetes of mild or moderate severity is a reversible abnormality. [ABSTRACT FROM AUTHOR]

Aim: Evidence on healthcare resource utilization (HCRU) for hospitalized patients with heart failure (HF) and reduced (HFrEF), mildly reduced (HFmrEF) and preserved (HFpEF) ejection fraction is limited. Methods and results: We analysed HCRU in relation to left ventricular ejection fraction (LVEF) phenotypes, clinical features and in‐hospital and 12‐month outcomes in 16 943 patients hospitalized for HF in a worldwide registry. HFrEF was more prevalent (53%) than HFmrEF (17%) or HFpEF (30%). Patients with HFmrEF and HFpEF were older, more often women, with milder symptoms and more comorbidities, but differences were not pronounced. HCRU was high in all three groups; two or more in‐ and out‐of‐hospital services were required by 51%, 49% and 52% of patients with HFrEF, HFmrEF and HFpEF, respectively, and intensive care unit by 41%, 41% and 37%, respectively. Hospitalization length was similar (median, 8 days). Discharge prescription of neurohormonal inhibitors was <80% for each agent in HFrEF and only slightly lower in HFmrEF and HFpEF (74% and 67%, respectively, for beta‐blockers). Compared to HFrEF, 12‐month all‐cause and cardiovascular mortality were lower for HFmrEF (adjusted hazard ratios 0.78 [95% confidence interval 0.59–0.71] and 0.80 [0.70–0.92]) and HFpEF (0.64 [0.59–0.87] and 0.63 [0.56–0.71]); 12‐month HF hospitalization was also lower for HFpEF and HFmrEF (21% and 20% vs. 25% for HFrEF). In‐hospital mortality, 12‐month non‐cardiovascular mortality and 12‐month all‐cause hospitalization were similar among groups. Conclusions: In patients hospitalized for HF, overall HCRU was similarly high across LVEF spectrum, reflecting the subtle clinical differences among LVEF phenotypes during hospitalization. Discharge prescription of neurohormonal inhibitors was suboptimal in HFrEF and lower but significant in patients with HFpEF and HFmrEF, who had better long‐term cardiovascular outcomes than HFrEF, but similar risk for non‐cardiovascular events. [ABSTRACT FROM AUTHOR]

Background: The role of neurohormonal inhibition in chronic heart failure (HF) is well established. There are limited data on the effect of up‐titration of renin–angiotensin inhibitors (RASi) and beta‐blockers (BBs) on clinical outcomes of patients with worsening HF across the left ventricular ejection fraction (LVEF) spectrum. Methods and results: We analysed data from 2345 patients from BIOSTAT‐CHF (80.9% LVEF <40%), who completed a 3‐month up‐titration period after recent worsening of HF. Patients were classified by achieved dose (% of recommended): ≥100%, 50–99%, 1–49%, and none. Recurrent event analysis using joint and shared frailty models was used to examine the association between RASi/BB dose and all‐cause and HF hospitalizations. In the 21 months following up‐titration, 512 patients died and 879 (37.5%) had ≥1 hospitalization. RASi up‐titration was associated, incrementally, with reduced risk of all‐cause hospitalization at all achieved dose levels compared to no treatment [hazard ratio (95% confidence interval): ≥100%: 0.60 (0.49–0.74), P < 0.001; 50–99%: 0.56 (0.46–0.68), P < 0.001; 1–49%: 0.71 (0.59–0.86), P < 0.001]. This association was consistent up to an LVEF of 49% (P < 0.001), and when considering only HF hospitalizations. Up‐titration of BBs was associated with fewer all‐cause hospitalizations only when LVEF was <40% (overall P < 0.001), but with more HF hospitalizations when LVEF was ≥50%. Up‐titration of both RASi/BBs was associated with lower mortality in LVEF up to 49%. Conclusion: After recent worsening of HF, up‐titration of RASi and BBs was associated with a better prognosis in patients with LVEF ≤49%. Up‐titration of BBs was associated with a greater risk of HF hospitalization when LVEF was ≥50%. [ABSTRACT FROM AUTHOR]

Aims: Oral sucrosomial iron (SI) combines enhanced bioavailability and tolerance compared to conventional oral iron along with similar efficacy compared to intravenous iron in several conditions associated with iron deficiency (ID).Methods and Results: In this non-randomized, open-label study, we sought to evaluate prospectively the effects of SI on clinical parameters, exercise capacity and quality of life in 25 patients with heart failure (HF) with reduced ejection fraction (HFrEF) and ID, treated with SI 28 mg daily for 3 months, in comparison to 25 matched HFrEF controls. All patients were on optimal stable HF therapy. Patients were followed for 6 months for death or worsening HF episodes. There were no differences in baseline characteristics between groups. At 3 months, SI was associated with a significant increase in haemoglobin, serum iron and serum ferritin levels (all P ≤ 0.001) along with a significant improvement in 6-min walked distance and Kansas City Cardiomyopathy Questionnaire (all P < 0.01), even after adjustment for baseline parameters; these differences persisted at 6 months. Over the study period, there were no deaths, while 10 patients (20%) in total (four in the SI group and six in the control group), experienced worsening HF (odds ratio 0.51, 95% confidence interval 0.41-6.79, P = 0.482). Drug-associated diarrhoea was reported by one patient in the SI group and led to drug discontinuation; no other adverse events were reported.Conclusions: In this proof-of-concept study, SI was well tolerated and improved exercise capacity and quality of life in HFrEF patients with ID. Randomized studies are required to further investigate the effects of this therapy. [ABSTRACT FROM AUTHOR]

In light of the accumulating evidence on the negative predictive value of soluble urokinase plasminogen activator receptor (suPAR), a group of experts from the fields of intensive care medicine, emergency medicine, internal medicine and infectious diseases frame a position statement on the role of suPAR in the screening of patients admitted to the emergency department. The statement is framed taking into consideration existing publications and our own research experience. The main content of this statement is that sUPAR is a non-specific marker associated with a high negative predictive value for unfavourable outcomes; levels < 4 ng/ml indicate that it is safe to discharge the patient, whereas levels > 6 ng/ml are an alarming sign of risk for unfavourable outcomes. However, the suPAR levels should always be interpreted in light of the patient's history. [ABSTRACT FROM AUTHOR]

Advanced neuroimaging is one of the most important means that we have in the attempt to overcome time constraints and expand the use of intravenous thrombolysis (IVT). We assessed whether, and how, the prior use of advanced neuroimaging (AN), and more specifically CT/MR perfusion post-processed with RAPID software, regardless of time from symptoms onset, affected the outcomes of acute ischemic stroke (AIS) patients who received IVT. Methods. We retrospectively evaluated consecutive AIS patients who received intravenous thrombolysis monotherapy (without endovascular reperfusion) during a six-year period. The study population was divided into two groups according to the neuroimaging protocol used prior to IVT administration in AIS patients (AN+ vs. AN−). Safety outcomes included any intracranial hemorrhage (ICH) and 3-month mortality. Effectiveness outcomes included door-to-needle time, neurological status (NIHSS-score) on discharge, and functional status at three months assessed by the modified Rankin Scale (mRS). Results. The rate of IVT monotherapy increased from ten patients per year (n = 29) in the AN− to fifteen patients per year (n = 47) in the AN+ group. Although the onset-to-treatment time was longer in the AN+ cohort, the two groups did not differ in door-to-needle time, discharge NIHSS-score, symptomatic ICH, any ICH, 3-month favorable functional outcome (mRS-scores of 0–1), 3-month functional independence (mRS-scores of 0–2), distribution of 3-month mRS-scores, or 3-month mortality. Conclusion. Our pilot observational study showed that the incorporation of advanced neuroimaging in the acute stroke chain pathway in AIS patients increases the yield of IVT administration without affecting the effectiveness and safety of the treatment. [ABSTRACT FROM AUTHOR]