Clinical profiles and quality of care of subjects with type 2 diabetes according to their cardiovascular risk: an observational, retrospective study

Background: The European Society of Cardiology (ESC) recently defined cardiovascular risk classes for subjects with diabetes. Aim of this study was to explore the distribution of subjects with type 2 diabetes (T2D) by cardiovascular risk groups according to the ESC classification and to describe the quality indicators of care, with particular regard to cardiovascular risk factors. Methods: The study is based on data extracted from electronic medical records of patients treated at the 258 Italian diabetes centers participating in the AMD Annals initiative. Patients with T2D were stratified by cardiovascular risk. General descriptive indicators, measures of intermediate outcomes, intensity/appropriateness of pharmacological treatment for diabetes and cardiovascular risk factors, presence of other complications and overall quality of care were evaluated. Results: Overall, 473,740 subjects with type 2 diabetes (78.5% at very high cardiovascular risk, 20.9% at high risk and 0.6% at moderate risk) were evaluated. Among people with T2D at very high risk: 26.4% had retinopathy, 39.5% had albuminuria, 18.7% had a previous major cardiovascular event, 39.0% had organ damage, 89.1% had three or more risk factors. The use of DPP4-i markedly increased as cardiovascular risk increased. The prescription of secretagogues also increased and that of GLP1-RAs tended to increase. The use of SGLT2-i was still limited, and only slightly higher in subjects with very high cardiovascular risk. The overall quality of care, as summarized by the Q score, tended to be lower as the level of cardiovascular risk increased. Conclusions: A large proportion of subjects with T2D is at high or very high risk. Glucose-lowering drug therapies seem not to be adequately used with respect to their potential advantages in terms of cardiovascular risk reduction. Several actions are necessary to improve the quality of care

A peptide-nucleic acid targeting miR-335-5p enhances expression of cystic fibrosis transmembrane conductance regulator (CFTR) gene with the possible involvement of the CFTR scaffolding protein NHERF1

(1) Background: Up-regulation of the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) might be of great relevance for the development of therapeutic protocols for cystic fibrosis (CF). MicroRNAs are deeply involved in the regulation of CFTR and scaffolding proteins (such as NHERF1, NHERF2 and Ezrin). (2) Methods: Content of miRNAs and mRNAs was analyzed by RT-qPCR, while the CFTR and NHERF1 production was analyzed by Western blotting. (3) Results: The results here described show that the CFTR scaffolding protein NHERF1 can be upregulated in bronchial epithelial Calu-3 cells by a peptide-nucleic acid (PNA) targeting miR-335-5p, predicted to bind to the 3′-UTR sequence of the NHERF1 mRNA. Treatment of Calu-3 cells with this PNA (R8-PNA-a335) causes also up-regulation of CFTR. (4) Conclusions: We propose miR-335-5p targeting as a strategy to increase CFTR. While the efficiency of PNA-based targeting of miR-3355p should be verified as a therapeutic strategy in CF caused by stop-codon mutation of the CFTR gene, this approach might give appreciable results in CF cells carrying other mutations impairing the processing or stability of CFTR protein, supporting its application in personalized therapy for precision medicine

Stenting versus balloon dilatation in patients with tracheal benign stenosis: The STROBE trial

Background: It is well known that benign tracheal stenosis represents an obstacle to open surgery, and that its treatment could be challenging. Two endoscopic techniques have so far been adopted to restore tracheal patency: balloon dilatation (BA) through laryngoscopy, and tracheal stenting (ST) with rigid bronchoscopy. The main objective of this study was to compare the efficacy of BA and ST to treat benign tracheal stenosis not eligible for surgery. We also compared the rate of adverse events in the two treatment groups. Methods: A retrospective, observational cohort study was carried out at the University Hospital of Modena (Italy) from November 2012 to November 2017 in two separate departments. Patients were considered to be “stabilized” (primary outcome) if they did not report significant respiratory symptoms, or restenosis in the long-term (2 years) following the endoscopic procedure. Results: Sixty-six patients were included in the study (33 in the BA and 33 in the ST group, respectively). Unadjusted Kaplan–Meier estimates showed a greater therapeutic effect of ST compared to BA at 2 years (hazard ratio = 3.9 95%CI [1.5–9.8], p =.01). After adjusting for confounders, stratified analyses showed that this effect was significant in patients with complex stenosis, idiopathic etiology, and degree of stenosis >70%. Compared with BA, ST showed a higher rate of adverse events (p =.01). Conclusions: Compared to BA, ST seems to be more effective in achieving stabilization of tracheal patency in complex benign tracheal stenosis, although burdened with a significantly higher number of adverse effects. These findings warrant future prospective study for confirmation. Level of evidence: 3

Inter-population variations in concentrations, determinants of and correlations between 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE): a cross-sectional study of 3161 men and women from Inuit and European populations.

The study is part of a collaborative project (Inuendo), aiming to assess the impact of dietary persistent organochlorine pollutants (POPs) on human fertility. The aims with the present study are to analyze inter-population variations in serum concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE), to assess inter-population variations in biomarker correlations, and to evaluate the relative impact of different determinants for the inter-individual variations in POP-biomarkers. CB-153 concentrations were much higher in Inuits and Swedish fishermen's populations than in the populations from Eastern Europe, whereas the pattern was different for p,p'-DDE showing highest concentrations in the Kharkiv population. The correlations between the POP-biomarkers varied considerably between the populations, underlining that exposure sources differ and that the choice of representative biomarkers of overall POP exposure has to be based on an analysis of the specific exposure situation for each population. Age and gender were consistent determinants of serum POPs; seafood was of importance only in the Inuit and Swedish populations

Effects of cytokine blocking agents on hospital mortality in patients admitted to ICU with acute respiratory distress syndrome by SARS-CoV-2 infection: Retrospective cohort study

Background: The use of cytokine-blocking agents has been proposed to modulate the inflammatory response in patients with COVID-19. Tocilizumab and anakinra were included in the local protocol as an optional treatment in critically ill patients with acute respiratory distress syndrome (ARDS) by SARS-CoV-2 infection. This cohort study evaluated the effects of therapy with cytokine blocking agents on in-hospital mortality in COVID-19 patients requiring mechanical ventilation and admitted to intensive care unit. Methods: The association between therapy with tocilizumab or anakinra and in-hospital mortality was assessed in consecutive adult COVID-19 patients admitted to our ICU with moderate to severe ARDS. The association was evaluated by comparing patients who received to those who did not receive tocilizumab or anakinra and by using different multivariable Cox models adjusted for variables related to poor outcome, for the propensity to be treated with tocilizumab or anakinra and after patient matching. Results: Sixty-six patients who received immunotherapy (49 tocilizumab, 17 anakinra) and 28 patients who did not receive immunotherapy were included. The in-hospital crude mortality was 30,3% in treated patients and 50% in non-treated (OR 0.77, 95% CI 0.56-1.05, p=0.069). The adjusted Cox model showed an association between therapy with immunotherapy and in-hospital mortality (HR 0.40, 95% CI 0.19-0.83, p=0.015). This protective effect was further confirmed in the analysis adjusted for propensity score, in the propensity-matched cohort and in the cohort of patients with invasive mechanical ventilation within 2 hours after ICU admission. Conclusions: Although important limitations, our study showed that cytokine-blocking agents seem to be safe and to improve survival in COVID-19 patients admitted to ICU with ARDS and the need for mechanical ventilation

Inter-population variations in concentrations, determinants of and correlations between 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE): a cross-sectional study of 3161 men and women from Inuit and European populations

BACKGROUND: The study is part of a collaborative project (Inuendo), aiming to assess the impact of dietary persistent organochlorine pollutants (POPs) on human fertility. The aims with the present study are to analyze inter-population variations in serum concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE), to assess inter-population variations in biomarker correlations, and to evaluate the relative impact of different determinants for the inter-individual variations in POP-biomarkers. METHOD: In study populations of 3161 adults, comprising Greenlandic Inuits, Swedish fishermen and their wives, and inhabitants from Warsaw, Poland and Kharkiv, Ukraine, serum concentrations of CB-153 and p,p'-DDE, were analysed by gas chromatography-mass spectrometry. RESULTS: The median serum concentrations of CB-153 were for male and female Inuits 200 and 110, for Swedish fishermen 190 and their wives 84, for Kharkiv men and women 44 and 27, and for Warsaw men and women 17 and 11 ng/g lipids, respectively. The median serum concentrations of p,p'-DDE were for Kharkiv men and women 930 and 650, for male and female Inuits 560 and 300, for Warsaw men and women 530 and 380, and for Swedish fishermen 240 and their wives 140 ng/g lipids, respectively. The correlation coefficients between CB-153 and p,p'-DDE varied between 0.19 and 0.92, with the highest correlation among Inuits and the lowest among men from Warsaw. Men had averagely higher serum concentrations of CB-153 and p,p'-DDE, and there were positive associations between age and the POP-biomarkers, whereas the associations with BMI and smoking were inconsistent. Dietary seafood was of importance only in the Inuit and Swedish populations. CONCLUSION: CB-153 concentrations were much higher in Inuits and Swedish fishermen's populations than in the populations from Eastern Europe, whereas the pattern was different for p,p'-DDE showing highest concentrations in the Kharkiv population. The correlations between the POP-biomarkers varied considerably between the populations, underlining that exposure sources differ and that the choice of representative biomarkers of overall POP exposure has to be based on an analysis of the specific exposure situation for each population. Age and gender were consistent determinants of serum POPs; seafood was of importance only in the Inuit and Swedish populations

Implementing a guideline for the treatment of type 2 diabetics: results of a Cluster- Randomized Controlled Trial (C-RCT)

<p>Abstract</p> <p>Background</p> <p>In Italy many diabetics still lack adequate care in general practice. We assessed the effectiveness of different strategies for the implementation of an evidence-based guideline for the management of non-complicated type 2 diabetes among General Practitioners (GPs) of Lazio region.</p> <p>Methods</p> <p>Three-arm cluster-randomised controlled trial with GPs as units of randomisation (clusters). 252 GPs were randomised either to an active strategy (training module with administration of the guideline), or to a passive dissemination (administration of the guideline only), or to usual care (control). Data on prescriptions of tests and drugs were collected by existing information systems, whereas patients' data came from GPs' databases. Process outcomes were measured at the cluster level one year after the intervention. Primary outcomes concerned the measurement of glycosilated haemoglobin and the commissioning of micro- and macrovascular complications assessment tests. In order to assess the physicians' drug prescribing behaviour secondary outcomes were also calculated.</p> <p>Results</p> <p>GPs identified 6395 uncomplicated type 2 patients with a high prevalence of cardiovascular risk factors. Data on GPs baseline performance show low proportions of glycosilated haemoglobin assessments. Results of the C-RCT analysis indicate that the active implementation strategy was ineffective relating to all primary outcomes (respectively, OR 1.06 [95% IC: 0.76–1.46]; OR 1.07 [95% IC: 0.80–1.43]; OR 1.4 [95% IC:0.91–2.16]. Similarly, passive dissemination of the guideline showed no effect.</p> <p>Conclusion</p> <p>In our region compliance of GPs with guidelines was not enhanced by a structured learning programme. Implementation through organizational measures appears to be essential to induce behavioural changes.</p> <p>Trial registration</p> <p>ISRCTN80116232</p

Quality of life and treatment satisfaction in adults with Type 1 diabetes: A comparison between continuous subcutaneous insulin infusion and multiple daily injections

Aims: The aim of this case-control study was to compare quality of life (QoL) and treatment satisfaction in adults with Type 1 diabetes (T1DM) treated with either continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). Methods: Consecutive patients aged between 18 and 55 years, and attending diabetes clinics for a routine visit, completed the Diabetes-Specific Quality-of-Life Scale (DSQOLS), the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and the SF-36 Health Survey (SF-36). Case (CSII) and control subjects (MDI) were recruited in a 1 : 2 ratio. Results: Overall, 1341 individuals were enrolled by 62 diabetes clinics; 481 were cases and 860 control subjects. Cases had a longer diabetes duration and were more likely to have eye and renal complications. Age, school education, occupation and HbA1c were similar. Of control subjects, 90% followed glargine-based MDI regimens and 10% used NPH-based MDI regimens. On multivariate analysis, after adjusting for socioeconomic and clinical characteristics, scores in the following areas of the DSQOLS were higher in cases than control subjects: diet restrictions (β = 5.96; P &lt; 0.0001), daily hassles (β = 3.57; P = 0.01) and fears about hypoglycaemia (β = 3.88; P = 0.006). Treatment with CSII was also associated with a markedly higher DTSQ score (β = 4.13; P &lt; 0.0001) compared with MDI. Results were similar when CSII was compared separately with glargine- or NPH-based MDI regimens. Conclusions: This large, non-randomized, case-control study suggests quality of life gains deriving from greater lifestyle flexibility, less fear of hypoglycaemia, and higher treatment satisfaction, when CSII is compared with either glargine-based or NPH-based MDI regimens. © 2008 The Authors

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR &lt; 60 mL/min/1.73 m2) or eGFR reduction &gt; 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR &lt; 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR &gt; 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Chromatin and epigenetics: current biophysical views

Recent advances in high-throughput sequencing experiments and their theoretical descriptions have determined fast dynamics of the "chromatin and epigenetics" field, with new concepts appearing at high rate. This field includes but is not limited to the study of DNA-protein-RNA interactions, chromatin packing properties at different scales, regulation of gene expression and protein trafficking in the cell nucleus, binding site search in the crowded chromatin environment and modulation of physical interactions by covalent chemical modifications of the binding partners. The current special issue does not pretend for the full coverage of the field, but it rather aims to capture its development and provide a snapshot of the most recent concepts and approaches. Eighteen open-access articles comprising this issue provide a delicate balance between current theoretical and experimental biophysical approaches to uncover chromatin structure and understand epigenetic regulation, allowing free flow of new ideas and preliminary results