The Silent Epidemic of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes in Children and Adolescents in Italy During the COVID-19 Pandemic in 2020

To compare the frequency of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in Italy during the COVID-19 pandemic in 2020 with the frequency of DKA during 2017-2019

Thermal Analysis

www.elsevier.com/locate/archger The influence of lifestyle on cardiovascular risk factor

Efficacy and Safety of a First Line Combined Therapeutic Approach for Young CLL Patients with Advanced or Progressive Disease Stratified According to the Biologic Features: First Analysis of the GIMEMA Multicenter Study LLC0405.

Eighty-one previously untreated CLL patients, ≤60 years, with advanced/progressive disease were included in the GIMEMA LLC0405 prospective multicenter study. Patients were stratified according to the biologic features. High risk (HR) patients were defined by the presence of: 1) 17p- (≥20% of analyzed cells), or 2) 11q- with ≥1 additional unfavorable factor (IGHV germline; Zap-70+ ≥10%; CD38+ ≥7%), or 3) germline IGHV or mutated VH3-21 and ≥2 unfavorable factors (Zap-70; CD38; 6q-; trisomy 12). Low risk (LR) patients were defined by the absence of the above features. HR patients received 4 monthly courses of fludarabine and campath-1H (FluCam; Flu 30 mg/m2 iv; Cam 30 mg iv, days 1-3). Responding patients underwent post-induction therapy: reduced intensity PBSC allogeneic transplant or, in the absence of a sibling donor, an autologous PBSC transplant or, in the absence of a sufficient harvest, Cam sc, 30 mg weekly for a maximum of 12 weeks. For LR patients, treatment included 6 monthly courses of fludarabine and cyclophosphamide (FC; fludarabine 30 mg/m2 iv and cyclophosphamide 250 mg/m2, days 1-3). All patients received bactrim prophylaxis. FluCam-treated patients underwent weekly CMV antigenemia monitoring and valacyclovir prophylaxis (2g/8h). In the presence of severe granulocytopenia, G-CSF was recommended and darbepoietin given in case of anemia (Hb <11g/dl). MRD was monitored in peripheral blood (PB) and marrow by four color-flow cytometry. The median age of patients was 55 years (range: 30-60), Rai stages III-IV were recorded in 23% of cases, 35% of patients showed “bulky” nodes (Ǿ ≥5 cm), 35% had 100 x 109/L or more PB lymphocytes and 51% increased β2 M values. A HR profile was found in 43 patients (53%) and a LR profile in 38 (47%). Within HR patients, 93% were IGHV unmutated, 69% CD38+, 80% Zap-70+, 40% 11q- and 21% 17p-. LR patients showed one or more unfavorable biologic factors in less than a third of cases (IgVH unmutated 21%, CD38+ 17%, Zap-70+ 29%); 13q- was recorded in 42% of cases, no detectable abnormalities in 39%, trisomy 12+ in 11% and 6q- in 8%. On an intention-to treat basis, a response was observed in 79% of HR cases (CR 26%, MRD- 19%) and in 87% of LR cases (CR 55%, MRD- 18%). In univariate analysis, age, IgG levels, β2 M, IgVH status, CD38 and Zap-70 played a significant role on CR achievement in HR patients, while CD38 was the only significant parameter for LR patients. As post-remission therapy, 2 HR patients received Cam , while 11 underwent a transplant procedure (allogeneic: 4, autologous: 7). The PFS probability at 36 months was 44% (95% CI: 36.9-51.8) for HR patients and 64% (95%CI: 53.6-76.7) for LR patients. In univariate analysis, β2 M and Zap-70 showed a significant effect on the PFS of HR patients, while a higher PB lymphocyte count (≥60x109/L) was associated with a lower PFS (p=0.07) in LR patients. The CR rate and PFS at 36 months after FluCam were 18% and 18% for 11q- patients, and 11% and 49% for 17p- patients. The OS probability at 36 months was 81% (95% CI: 71-93.3) for HR patients and 89% (95%CI:80.2-98.6) for LR patients. Cytogenetic abnormalities played a significant role (p=.02) on OS probability of HR patients. In particular, 17p- was associated with a lower survival probability (p=.04), while the OS of LR patients was influenced by the lymphocyte count (p=0.05). All transplanted patients are alive with a median follow-up of 31 months (range:16-42). Granulocytopenia was observed in 21% of cases treated with FluCam and in 32% of those treated with FC. Grade III-IV infections were recorded in 7% of FluCam-treated patients and in 13% of FC- treated patients. Asymptomatic CMV reactivation was detected in 3 FluCam-treated cases (7%). No FluCam-related deaths were observed, while 4 FC-related deaths were recorded (febrile granulocytopenia, 2 cases; cerebral hemorrhage, 1; cerebral abscesses of unknown origin, 1). In conclusion, an unfavorable biologic profile was observed in about half young CLL patients requiring first line treatment. Front-line FluCam was well tolerated and effective for most young CLL patients with an unfavorable biologic profile. However, our results suggest that FluCam is not the optimal treatment approach for 11q- patients. Front-line FC was associated with a high CR rate and prolonged PFS and OS probabilities in patients with a favorable biologic profile. Nevertheless, in young CLL patients FC-related severe granulocytopenia was a frequent reason of treatment failure

Corrigendum: The silent epidemic of diabetic ketoacidosis at diagnosis of type 1 diabetes in children and adolescents in italy during the covid-19 pandemic in 2020

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A new role of AMP-activated protein kinase in regulating proliferation of mesenchymal stem cells

Purpose: Natriuretic peptides (NPs) administered during early reperfusion are protective in models of myocardial infarction. A previous study examining the endogenous components of B-type natriuretic peptide (BNP) protection of reperfused myocardium, implicated both sarcolemmal (s) KATP and mitochondrial (m) KATP channels. The indirect evidence characterising the relationship between BNP signalling and KATP was obtained using sulphonylurea receptor inhibitors in a rat isolated heart model of ischaemia-reperfusion injury. Here we seek to further examine the relationship between NPs and sKATP openings using single channel electrophysiology. Given our previous findings and the overarching consensus that cardioprotective autacoids open KATP channels, it was hypothesised that NPs elicit sKATP opening. Methods: Cardiomyocyte isolation. Left ventricular cardiomyocytes were isolated from male Sprague-Dawley rat hearts subjected to enzymatic digestion with Liberase Blendzyme DL. Cardiomyocytes were cultured overnight in Medium 199, prior to patch clamp. Single channel patch clamp. Single channel recordings at room temperature (22°C) were made from cell attached patches bathed in Na+ Locke, pH 7.2. The recording pipette contained high KCl (140 mM), pH 7.2. Recordings (45 sec) were made over a range of patch potentials (0, -30, -60, -90, -120 mV), in the absence (control) and in the presence of bath applied BNP (10, 100 nM and 1 µM), pinacidil (200 µM) or pinacidil vehicle (DMSO, 0.25%). Recordings were also made with BNP and pinacidil applied concomitantly. Data are mean ± S.E.M. Results: The current voltage relationship of sKATP under control conditions was linear at –ve patch potentials, the mean conductance being 52.9 ± 1.8 pS (n = 18 hearts, n = 35 cells). Pinacidil caused a four fold increase in sKATP open probability compared to control. Mean channel conductance in the presence of pinacidil was 59.9 ± 1.9 pS (n = 16 hearts, n = 44 cells). Interestingly BNP at all concentrations had negligible effects on sKATP open probability and unitary conductance. However, BNP at all concentrations and patch potentials inhibited pinacidil induced sKATP openings, restoring channel open probability to baseline. Conclusion: These data illustrate the inhibitory effect of NP signalling on sKATP function in the cardiomyocyte under normoxia. They are concordant with the inhibitory effect of atrial NP on KATP in the pancreatic beta cell, but are in apparent conflict with the current cardioprotection paradigm. However, differential effects on sKATP and mKATP and the effects of hypoxia-reoxygenation require further exploration

Surgeons’ practice and preferences for the anal fissure treatment: results from an international survey

The best nonoperative or operative anal fissure (AF) treatment is not yet established, and several options have been proposed. Aim is to report the surgeons' practice for the AF treatment. Thirty-four multiple-choice questions were developed. Seven questions were about to participants' demographics and, 27 questions about their clinical practice. Based on the specialty (general surgeon and colorectal surgeon), obtained data were divided and compared between two groups. Five-hundred surgeons were included (321 general and 179 colorectal surgeons). For both groups, duration of symptoms for at least 6 weeks is the most important factor for AF diagnosis (30.6%). Type of AF (acute vs chronic) is the most important factor which guide the therapeutic plan (44.4%). The first treatment of choice for acute AF is ointment application for both groups (59.6%). For the treatment of chronic AF, this data is confirmed by colorectal surgeons (57%), but not by the general surgeons who prefer the lateral internal sphincterotomy (LIS) (31.8%) (p = 0.0001). Botulin toxin injection is most performed by colorectal surgeons (58.7%) in comparison to general surgeons (20.9%) (p = 0.0001). Anal flap is mostly performed by colorectal surgeons (37.4%) in comparison to general surgeons (28.3%) (p = 0.0001). Fissurectomy alone is statistically significantly most performed by general surgeons in comparison to colorectal surgeons (57.9% and 43.6%, respectively) (p = 0.0020). This analysis provides useful information about the clinical practice for the management of a debated topic such as AF treatment. Shared guidelines and consensus especially focused on operative management are required to standardize the treatment and to improve postoperative results