Search

RATIONALE: In predominantly White populations, early chronic obstructive pulmonary disease (COPD) (i.e., COPD in people aged

Background and Purpose: Clinical trials on stroke prevention in patients with atrial fibrillation have consistently shown clinical benefit from either warfarin or non–vitamin K antagonist oral anticoagulants (NOACs). NOAC-treated patients have consistently reported to be at lower risk for intracerebral hemorrhage (ICH) than warfarin-treated patients. The aims of this prospective, multicenter, multinational, unmatched, case-control study were (1) to investigate for risk factors that could predict ICH occurring in patients with atrial fibrillation during NOAC treatment and (2) to evaluate the role of CHA 2 DS 2 -VASc and HAS-BLED scores in the same setting. Methods: Cases were consecutive patients with atrial fibrillation who had ICH during NOAC treatment. Controls were consecutive patients with atrial fibrillation who did not have ICH during NOAC treatment. As within the CHA 2 DS 2 -VASc and HAS-BLED scores there are some risk factors in common, several multivariable logistic regression models were performed to identify independent prespecified predictors for ICH events. Results: Four hundred nineteen cases (mean age, 78.8±8.1 years) and 1526 controls (mean age, 76.0±10.3 years) were included in the study. From the different models performed, independent predictors of ICH were increasing age, concomitant use of antiplatelet agents, active malignancy, high risk of fall, hyperlipidemia, low clearance of creatinine, peripheral artery disease, and white matter changes. Low doses of NOACs (given according to label or not) and congestive heart failure were inversely associated with the risk of ICH. HAS-BLED and CHA 2 DS 2 -VASc scores performed poorly in predicting ICH with areas under the curves of 0.496 (95% CI, 0.468–0.525) and 0.530 (95% CI, 0.500–0.560), respectively. Conclusions: Several risk factors were associated to ICH in patients treated with NOACs for stroke prevention but not HAS-BLED and CHA 2 DS 2 -VASc scores.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/., Smoking is the most well-established cause of chronic airflow obstruction (CAO) but particulate air pollution and poverty have also been implicated. We regressed sex-specific prevalence of CAO from 41 Burden of Obstructive Lung Disease study sites against smoking prevalence from the same study, the gross national income per capita and the local annual mean level of ambient particulate matter (PM2.5) using negative binomial regression. The prevalence of CAO was not independently associated with PM2.5 but was strongly associated with smoking and was also associated with poverty. Strengthening tobacco control and improved understanding of the link between CAO and poverty should be prioritised., Supported by Wellcome Trust grant 085790/Z/08/Z for the BOLD (Burden of Obstructive Lung Disease) Study. The initial BOLD programprogramme was funded in part by unrestricted educational grants to the Operations CenterCentre in Portland, Oregon from Altana, Aventis, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Merck, Novartis, Pfizer, Schering-Plough, Sepracor, and the University of Kentucky (Lexington, KY). A full list of local funders can be found at https://www.boldstudy.org.

World COPD Day raises awareness about chronic obstructive pulmonary disease (COPD). COPD accounts for over 150,000 US deaths per year. A major challenge is that COPD receives only a fraction of the research funding provided to other major diseases. Control of COPD is dependent on developing new approaches to diagnose the disease earlier with a recognition of either pre-COPD or established COPD based on symptoms, lung structural change and/or loss of lung function that occurs before meeting long established criteria for a population-based definition of obstruction. Optimization of current therapies improves lung function, exercise capacity, quality of life, and survival. New pathways of disease progression are being identified creating new opportunities for development of therapies that could stop or cure this disease.

Purpose of review In this review, we will discuss the current status and recent developments in precision medicine in chronic obstructive pulmonary disease (COPD) through the lens of treatable traits. Recent findings Although the term 'treatable traits' in the treatment of COPD is relatively recent, this concept has been used for many years if one considers interventions such as long-term oxygen therapy or alpha-1 antitrypsin replacement therapy. Recent advances have included expanding the definition of COPD to include a broader population of people with lower respiratory disease but not meeting the strict criteria for obstruction, advances in imaging to aid in the diagnosis and treatment of COPD, advances in understanding symptoms and exacerbations to define severity, using biomarkers to guide therapy and better understanding and addressing polymorbidity and frailty. In addition, there is a concerted effort to use these concepts to identify COPD patients earlier in the disease process wherein disease modification may be possible. Summary Focusing on subsets of patients with COPD with certain characteristics should lead to better outcomes and fewer adverse effects from treatment. Video abstract http://links.lww.com/COPM/A30.

Background Vasopressors and inotropes are the primary pharmacologic agents in the management of cardiogenic shock. Increased use of these agents in the setting of cardiogenic shock treated with the Impella is associated with increased mortality. This study evaluates the use of vasopressors and inotropes as predictors of mortality in patients treated with the Impella for acute cardiogenic shock. Methods This retrospective study included 276 patients treated with the Impella 2.5, Impella CP, or Impella 5.0 from March 2011 to January 2020 at a single, tertiary referral center for acute cardiogenic shock. Results All-cause in-hospital mortality was 44.6%. Mortality significantly increased with escalating use of vasopressors and inotropes, with the most significant increase in mortality from use of 2 agents to the use of 3 agents (8.1% vs 39.7%, p Conclusions The escalating need for vasopressors and inotropes and particular combinations of these agents are significant predictors of mortality that may help determine whether the Impella or higher level of support is more appropriate to treat acute cardiogenic shock. Summary Increased use and use of particular combinations of vasopressors and inotropes significantly predict mortality in patients with acute cardiogenic shock treated with the Impella. Increasing from the use of 2 to 3 agents demonstrated the greatest mortality increase. Those treated with only vasopressors had greater mortality compared to those treated with a combination that included 1 inotrope.

Although therapeutic options for patients with advanced renal cell carcinoma (RCC) have increased in the past decade, no biomarkers are yet available for patient stratification or evaluation of therapy resistance. Given the dynamic and heterogeneous nature of clear cell RCC (ccRCC), tumor biopsies provide limited clinical utility, but liquid biopsies could overcome these limitations. Prior liquid biopsy approaches have lacked clinically relevant detection rates for patients with ccRCC. This study employed ccRCC‐specific markers, CAIX and CAXII, to identify circulating tumor cells (CTC) from patients with metastatic ccRCC. Distinct subtypes of ccRCC CTCs were evaluated for PD‐L1 and HLA‐I expression and correlated with patient response to therapy. CTC enumeration and expression of PD‐L1 and HLA‐I correlated with disease progression and treatment response, respectively. Longitudinal evaluation of a subset of patients demonstrated potential for CTC enumeration to serve as a pharmacodynamic biomarker. Further evaluation of phenotypic heterogeneity among CTCs is needed to better understand the clinical utility of this new biomarker., Circulating tumor cells (CTCs) were evaluated for their expression of programmed death ligand‐1 (PD‐L1) and human leukocyte antigen class I (HLA‐I), so that biomarkers of therapeutic resistance of clear cell renal cell carcinoma can be developed. CTCs were captured with antibody‐conjugated magnetic beads against EpCAM and CAIX then probed for CAXII and CK expression using microfluidic technology.

Chronic venous insufficiency (CVI) is extraordinarily prevalent in our aging population with over 30 million people in the United States suffering from the disease. There is a paucity of data analyzing the effects of CVI on outcomes following total knee arthroplasty (TKA). The purpose of this study was to utilize a nationwide administrative claims database to determine whether patients with CVI undergoing TKA have higher rates of: (1) in-hospital lengths of stay (LOS); (2) readmission rates; (3) medical complications; (4) implant-related complications; and (5) costs of care compared to controls. Using a nationwide database, we matched patients with CVI undergoing TKA to controls without CVI undergoing TKA in a 1:5 ratio by age, sex, and medical comorbidities associated with CVI. Primary outcomes analyzed within the study included LOS, 90-day readmission rates, 90-day medical complications, 2-year implant-related complications, in addition to 90-day total global episode of care costs. The query yielded 1,265,534 patients with (n = 210,926) and without (n = 1,054,608) CVI undergoing primary TKA. Patients with CVI had significantly longer LOS (4 vs. 3 days, p

Stem cell-based treatments have been extensively explored in the last few decades to develop therapeutic strategies aimed at providing effective alternatives for those human pathologies in which surgical or pharmacological therapies produce limited effects. Among stem cells of different sources, mesenchymal stem cells (MSCs) offer several advantages, such as the absence of ethical concerns, easy harvesting, low immunogenicity and reduced tumorigenesis risks. Other than a multipotent differentiation ability, MSCs can release extracellular vesicles conveying proteins, mRNA and microRNA. Thanks to these properties, new therapeutic approaches have been designed for the treatment of various pathologies, including ocular diseases. In this review, the use of different MSCs and different administration strategies are described for the treatment of diabetic retinopathy, glaucoma, and retinitis pigmentosa. In a large number of investigations, positive results have been obtained by in vitro experiments and by MSC administration in animal models. Most authors agree that beneficial effects are likely related to MSC paracrine activity. Based on these considerations, many clinical trials have already been carried out. Overall, although some adverse effects have been described, promising outcomes are reported. It can be assumed that in the near future, safer and more effective protocols will be developed for more numerous clinical applications to improve the quality of life of patients affected by eye diseases.

Nicola A Hanania,1 Scott Caveney,2 Tedi Soule,2 Lee Tombs,3 Sally Lettis,4 Courtney Crim,5,6 David M Mannino,7 Hitesh Patel,2 Isabelle H Boucot4 1Airways Clinical Research Center, Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, USA; 2US Medical Affairs, GlaxoSmithKline, Research Triangle Park, NC, USA; 3Precise Approach Ltd, Contingent Worker on Assignment at GlaxoSmithKline, Brentford, Middlesex, UK; 4Statistics, GlaxoSmithKline, Brentford, Middlesex, UK; 5R&D, GlaxoSmithKline, Research Triangle Park, NC, USA; 6Internal Medicine - Division of Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 7Department of Preventive Medicine and Environmental Health, University of Kentucky, College of Public Health, Lexington, KY, USACorrespondence: Nicola A HananiaAirways Clinical Research Center, Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, USAEmail hanania@bcm.eduIntroduction: Concerns have been raised about the practical use and clinical benefits of medications and inhalers in older patients with chronic obstructive pulmonary disease (COPD). Here, we report analyses according to age from five clinical trials evaluating medications administered using the ELLIPTA dry-powder inhaler (DPI).Methods: Efficacy and safety according to age groups (< 65 and ≥ 65 years) were assessed using data from five clinical trials in patients ≥ 40 years of age with symptomatic COPD. There was a mix of pre-specified and post hoc analyses of two 24-week trials with fluticasone furoate (FF)/vilanterol (VI) 100/25 μg; one 24-week trial with umeclidinium (UMEC) 62.5 μg; and two 12-week trials with UMEC 62.5 μg + FF/VI 100/25 μg. The primary endpoint was trough forced expiratory volume in 1 second (FEV1) obtained 23 and 24 hours after dosing on the last day of the study.Results: A total of 2876 patients < 65 years of age and 2148 patients ≥ 65 years of age were enrolled across all studies of whom 1333 and 1111 patients, respectively, received treatment at the doses presented. Statistically significant and clinically meaningful treatment differences in improvement from baseline in mean trough FEV1 were reported for active comparators versus placebo at study end for both < 65 and ≥ 65 years subgroups (FF/VI vs placebo: 143 mL and 111 mL; UMEC vs placebo: 110 mL and 123 mL; UMEC + FF/VI vs placebo + FF/VI: 136 mL and 105 mL; p< 0.001 for all comparisons). The incidence of adverse events reported for active treatments was similar between age groups.Conclusion: These data provide evidence to support the use of FF/VI, UMEC, or UMEC + FF/VI, all delivered via the ELLIPTA DPI, to treat older (≥ 65 years) and younger (< 65 years) patients with COPD.Keywords: COPD, elderly, ELLIPTA dry-powder inhaler, fluticasone furoate/vilanterol, multiple-inhaler triple therapy, umeclidinium

Background In the Informing the Pathway of COPD Treatment (IMPACT) trial, single-inhaler triple-therapy fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI) reduced moderate/severe exacerbation rates vs FF/VI and UMEC/VI in patients with symptomatic COPD and a history of exacerbations, with a similar safety profile. Research Question Are trial outcomes with single-inhaler triple-therapy FF/UMEC/VI vs FF/VI and UMEC/VI affected by age in patients with symptomatic COPD and a history of exacerbations? Study Design and Methods IMPACT was a phase III, double-blind, 52-week trial. Patients ≥ 40 years of age with symptomatic COPD and ≥ 1 moderate/severe exacerbation in the previous year were randomly assigned 2:2:1 to FF/UMEC/VI 100/62.5/25 μg, FF/VI 100/25 μg, or UMEC/VI 62.5/25 μg. End points assessed by age included annual rate of moderate/severe exacerbations, change from baseline (CFB) in trough FEV1, proportion of St. George’s Respiratory Questionnaire (SGRQ) responders (≥ 4 units decrease from baseline in SGRQ total score), and safety. Results The intention-to-treat population comprised 10,355 patients; 4,724 (46%), 4,225 (41%), and 1,406 (14%) were ≤ 64, 65 to 74, and ≥ 75 years of age, respectively. FF/UMEC/VI reduced on-treatment moderate/severe exacerbation rates vs FF/VI (% reduction [95% CI]: ≤ 64 years, 8% [−1 to 16]; P = .070; 65-74 years, 22% [14-29]; P Interpretation FF/UMEC/VI reduced the rate of moderate/severe exacerbations and improved lung function and health status vs FF/VI and UMEC/VI irrespective of age for most end points, with a similar safety profile. Clinical Trial Registration ClinicalTrials.gov; No.: NCT02164513; URL: www.clinicaltrials.govCTT116855

The bone-tendon-bone (BTB) autograft is widely used for anterior cruciate ligament (ACL) reconstruction. However, the primary disadvantages of this technique include postoperative kneeling pain, the risk of perioperative patellar fracture, and graft-tunnel mismatch. Therefore, a single bone plug technique for ACL reconstructions was developed to mitigate the disadvantages of the BTB technique. To differentiate this graft, we have coined the term BTA, for bone-tendon-autograft. The middle third of the patellar tendon is used with a typical width of 10 to 11 mm. A standard tibial tubercle bone plug is harvested. The length of the patellar tendon and graft construct is then measured. If the tendon is >45 mm and the construct at least 70 mm, then we proceed with the BTA technique. At the inferior pole of the patella, electrocautery is used to harvest the tendon from the patella. The advantages of this technique include faster graft harvest and preparation. Obviating the patellar bone plug harvest should eliminate the risk of perioperative patellar fracture and theoretically will mitigate donor site morbidity and kneeling pain, 2 of the most commonly cited complications of the use of BTB autografts for ACL reconstruction. In conclusion, the BTA technique is a reliable technique for ACL reconstruction.

Intravenous thrombolysis (IVT)-ineligible patients undergoing direct thrombectomy tended to have poorer functional outcome as compared with IVT-eligible patients undergoing bridging therapy. We aimed to assess radiological and functional outcomes in large vessel occlusion-related stroke patients receiving direct thrombectomy in the presence of absolute exclusion criteria for IVT vs relative exclusion criteria for IVT and vs non-exclusion criteria for IVT. A cohort study on prospectively collected data from 2282 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke cohort for treatment with direct thrombectomy (n = 486, absolute exclusion criteria for IVT alone; n = 384, absolute in combination with relative exclusion criteria for IVT; n = 777, relative exclusion criteria for IVT alone; n = 635, non-exclusion criteria for IVT). After adjustment for unbalanced variables (model 1), ORs for 3-month death was higher in the presence of absolute exclusion criteria for IVT alone (vs relative exclusion criteria for IVT alone) (1.595, 95% CI 1.042–2.440) and in the presence of absolute exclusion criteria for IVT alone (vs non-exclusion criteria for IVT) (1.235, 95% CI 1.014–1.504). After adjustment for predefined variables (model 2: age, sex, pre-stroke mRS ≤ 1, NIHSS, occlusion in the anterior circulation, onset-to-groin time, and procedure time), ORs for 3-month death was higher in the presence of absolute exclusion criteria for IVT alone (vs relative exclusion criteria for IVT alone) (1.235, 95% CI 1.014–1.504) and in the presence of absolute exclusion criteria for IVT alone (vs non-exclusion criteria for IVT) (1.246, 95% CI 1.039–1.495). No significant difference was found between the groups as regards any type of intracerebral hemorrhage and parenchymal hematoma within 24 h, successful and complete recanalization after procedure, and modified Rankin Scale score 0–2 at 3 months. After adjustment for predefined variables of model 2, ORs for death were higher in the presence of recent administration of IV heparin (OR: 2.077), platelet count

Introduction The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing. Materials and Methods Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39–2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16–1.80). Discussion our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events. Conclusions Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT.

In the case of our patient, the synergic action of endocrine therapy and chemotherapy plus dual anti-HER2 combination allowed a complete disease control. Therapy should be scheduled by considering the two cancers as individual entities. The approach to breast cancer is changing from being considered a singular disease to a multiform one, according to current research focused on biological markers such as HER2, ERs, and PRs, with important implications in clinical, prognostic, and therapeutic features.

Long-term consequences of cervical artery dissection (CeAD), a major cause of ischemic stroke in young people, have been poorly investigated. The Italian Project on Stroke at Young Age - Cervical Artery Dissection (IPSYS CeAD) project is a multicenter, hospital-based, consecutively recruiting, observational, cohort study aimed to address clinically important questions about long-term outcome of CeAD patients, which are not covered by other large-scale registries. Patients with radiologically diagnosed CeAD were consecutively included in the registry. Baseline demographic and clinical variables, as well as information on risk factors, were systematically collected for each eligible patient. Follow-up evaluations were conducted between 3 and 6 months after the initial event (t1) and then annually (t2 at 1 year, t3 at 2 years , and so on), in order to assess outcome events (long-term recurrent CeAD, any fatal/nonfatal ischemic stroke, transient ischemic attack (TIA), or other arterial thrombotic event, and death from any cause). Between 2000 and 2019, data from 1530 patients (age at diagnosis, 47.2 ± 11.5 years; women, 660 [43.1%]) have been collected at 39 Italian neurological centers. Dissection involved a single vessel in 1308 (85.5%) cases and caused brain ischemia in 1303 (85.1%) (190 TIA/1113 ischemic stroke). Longitudinal data are available for 1414 (92.4%) patients (median follow-up time in patients who did not experience recurrent events, 36.0 months [25th to 75th percentile, 63.0]). The collaborative IPSYS CeAD effort will provide novel information on the long-term outcome of CeAD patients. This could allow for tailored treatment approaches based on patients' individual characteristics.

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.

The literature has shown an increase in prevalence of Crohn's disease (CD) within the United States alongside a concomitant rise in primary total knee arthroplasty (TKA) procedures. As such, with these parallel increases, orthopaedic surgeons will invariably encounter CD patients requiring TKA. Limited studies exist evaluating the impact of this disease on patients undergoing the procedure; therefore, this study endeavors to determine whether CD patients undergoing primary TKA have higher rates of (1) in-hospital lengths of stay (LOS), (2) medical complications, and (3) episode of care (EOC) costs. To accomplish this, a nationwide database was queried from January 1, 2005 to March 31, 2014 to identify patients undergoing TKA. The study group, patients with CD, was randomly matched to the controls, patients without CD, in a 1:5 ratio after accounting for age, sex, and medical comorbidities associated with CD. Patients consuming corticosteroids were excluded, as they are at risk of higher rates of adverse events following TKA. This query ultimately yielded a total of 96,213 patients, with 16,037 in the study cohort and 80,176 in the control one. The study compared in-hospital (LOS), 90-day medical complications, and day of surgery and total global 90-day EOC costs between CD and non-CD patients undergoing primary TKA. The results found CD patients undergoing primary TKA had significantly longer in-hospital LOS (4- vs. 3 days, p

The most common pathology of the blood-vessel organ system is thrombosis or undesirable clotting of the blood. Thrombosis is life threatening as more than 25% of such cases lead to sudden death from stroke and myocardial infarction. Even though the process of thrombosis has been extensively investigated with animal models, its exact pathobiology in different blood vessels is not yet fully understood and drug assessment remains unpredictable. This is primarily because the cause for thrombus formation is multifactorial and depends on the interplay of flow patterns within the blood vessel, the vessel wall or endothelium, extracellular matrix, parenchymal tissue, and the cellular and plasma components of the blood. Current in vitro and animal models do not mimic or dissect this organ-level complexity faithfully. However, microfluidic technology has recently been deployed to effectively recapitulate blood-endothelial–epithelial interactions in the onset of thrombosis in blood vessels. This technology is promising because it permits inclusion of primary human cells and blood obtained from patients, which is currently lacking in other in vitro models of thrombosis. In this review, we summarize the current state-of-the-art and practices in microfluidics and expected improvements in this field that will impact basic understanding of thrombosis, drug discovery and personalized medicine.

Vitamin D might play a role in counteracting COVID-19, albeit strong evidence is still lacking in the literature. The present multicenter real-practice study aimed to evaluate the differences of 25(OH)D3 serum levels in adults tested for SARS-CoV-2 (acute COVID-19 patients, subjects healed from COVID-19, and non-infected ones) recruited over a 6-month period (March–September 2021). In a sample of 117 subjects, a statistically significant difference was found, with acute COVID-19 patients demonstrating the lowest levels of serum 25(OH)D3 (9.63 ± 8.70 ng/mL), significantly lower than values reported by no-COVID-19 patients (15.96 ± 5.99 ng/mL, p = 0.0091) and healed COVID-19 patients (11.52 ± 4.90 ng/mL, p &gt, 0.05). Male gender across the three groups displayed unfluctuating 25(OH)D3 levels, hinting at an inability to ensure adequate levels of the active vitamin D3 form (1α,25(OH)2D3). As a secondary endpoint, we assessed the correlation between serum 25(OH)D3 levels and pro-inflammatory cytokine interleukin-6 (IL-6) in patients with extremely low serum 25(OH)D3 levels (&lt, 1 ng/mL) and in a subset supplemented with 1α,25(OH)2D3. Although patients with severe hypovitaminosis-D showed no significant increase in IL-6 levels, acute COVID-19 patients manifested high circulating IL-6 at admission (females = 127.64 ± 22.24 pg/mL, males = 139.28 ± 48.95 ng/mL) which dropped drastically after the administration of 1α,25(OH)2D3 (1.84 ± 0.77 pg/mL and 2.65 ± 0.92 ng/mL, respectively). Taken together, these findings suggest that an administration of 1α,25(OH)2D3 might be helpful for treating male patients with an acute COVID-19 infection. Further studies on rapid correction of vitamin D deficiency with fast acting metabolites are warranted in COVID-19 patients.

[Background] The global prevalence of chronic obstructive pulmonary disease (COPD) has increased markedly in recent decades. Given the scarcity of resources available to address global health challenges and respiratory medicine being relatively under-invested in, it is important to define research priorities for COPD globally. In this paper, we aim to identify a ranked set of COPD research priorities that need to be addressed in the next 10 years to substantially reduce the global impact of COPD., [Methods] We adapted the Child Health and Nutrition Research Initiative (CHNRI) methodology to identify global COPD research priorities., [Results] 62 experts contributed 230 research ideas, which were scored by 34 researchers according to six pre-defined criteria: answerability, effectiveness, feasibility, deliverability, burden reduction, and equity. The top-ranked research priority was the need for new effective strategies to support smoking cessation. Of the top 20 overall research priorities, six were focused on feasible and cost-effective pulmonary rehabilitation delivery and access, particularly in primary/community care and low-resource settings. Three of the top 10 overall priorities called for research on improved screening and accurate diagnostic methods for COPD in low-resource primary care settings. Further ideas that drew support involved a better understanding of risk factors for COPD, development of effective training programmes for health workers and physicians in low resource settings, and evaluation of novel interventions to encourage physical activity., [Conclusions] The experts agreed that the most pressing feasible research questions to address in the next decade for COPD reduction were on prevention, diagnosis and rehabilitation of COPD, especially in low resource settings. The largest gains should be expected in low- and middle-income countries (LMIC) settings, as the large majority of COPD deaths occur in those settings. Research priorities identified by this systematic international process should inform and motivate policymakers, funders, and researchers to support and conduct research to reduce the global burden of COPD., National Institute for Health Research (NIHR), Health Data Research UK.

The normal wound healing process is characterized by a complex, highly integrated cascade of events, requiring the interactions of many cell types, including inflammatory cells, fibroblasts, keratinocytes and endothelial cells, as well as the involvement of growth factors and enzymes. However, several diseases such as diabetes, thermal injury and ischemia could lead to an impaired wound healing process characterized by wound hypoxia, high levels of oxygen radicals, reduced angiogenesis, decreased collagen synthesis and organization. Polydeoxyribonucleotide (PDRN) has been used to improve wound healing through local and systemic administration thanks to its ability to promote cell migration and growth, angiogenesis, and to reduce inflammation on impaired wound healing models in vitro, in vivo and clinical studies. In light of all these observations, the aim of this review is to provide a full overview of PDRN applications on skin regeneration. We reviewed papers published in the last 25 years on PubMed, inserting “polydeoxyribonucleotide and wound healing” as the main search term. All data obtained proved the ability of PDRN in promoting physiological tissue repair through adenosine A2A receptor activation and salvage pathway suggesting that PDRN has proven encouraging results in terms of healing time, wound regeneration and absence of side effects.

Background: Intestinal ischemia/reperfusion injury (IRI) remains a clinical event that contributes to high morbidity and mortality rates. Intestinal epithelium is exposed to histological and vascular changes following tissue ischemia. Prolyl endopeptidase (PREP), involved in inflammatory responses, could be targeted for recovery from the permanent consequences following intestinal ischemia. Our aim was to investigate the role of PREP inhibitor KYP-2047 in tissue damage, angiogenesis, and endothelial barrier permeability after intestinal IRI in mice. Methods: KYP-2047 treatments were performed 5 min prior to intestinal damage. Intestinal IRI was induced in mice by clamping the superior mesenteric artery and the celiac trunk for 30 min, followed by 1 h of reperfusion. Results: PREP inhibition by KYP-2047 treatment reduced intestinal IR-induced histological damage and neutrophil accumulation, limiting inflammation through decrease of NF-ĸB nuclear translocation and fibrotic processes. KYP-2047 treatment restored barrier permeability and structural alteration following intestinal IRI, attenuating neovascular processes compromised by ischemia/reperfusion. Additionally, loss of epithelial cells during intestinal ischemia occurring by apoptosis was limited by KYP-2047 treatment, which showed strong effects counteracting apoptosis and DNA damage. Conclusions: These findings provide the first evidence that PREP inhibition through KYP-2047 inhibitor use could be a validate strategy for resolving alterations of intestinal epithelium the pathophysiology of intestinal disease.

Aims 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 1 diabetes (T1D) by cardiovascular risk groups according to the ESC classification and to describe the quality indicators of care. 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 (Associazione Medici Diabetologi) Annals initiative. Patients with T1D were stratified by cardiovascular risk. Measures of intermediate outcomes, intensity/appropriateness of pharmacological treatment, and overall quality of care were evaluated. Results Overall, 29.368 subjects with type 1 diabetes (64.7% at very high cardiovascular risk, 28.5% at high risk and 6.8% at moderate risk) were evaluated. A lack of use of drugs in case of high values and an inadequate control despite the antihypertensive and lipid-lowering treatment was recognized. The overall quality of care tended to be lower as the level of cardiovascular risk increased. Conclusion A large proportion of subjects with T1D is at high or very high risk. Antihypertensive and lipid-lowering treatment seem not adequately used. Several actions are necessary to improve the quality of care.

Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a common clinical presentation of chronic airways disease in which patients show some features usually associated with asthma, and some usually associated with COPD. There is ongoing debate over whether ACO is a discrete clinical entity, or if it is part of a continuum of airways disease. Furthermore, there is considerable variation among current definitions of ACO, which makes diagnosis potentially challenging for clinicians. Treating ACO may be equally challenging because ACO is an understudied population, and the evidence base for its management comes largely from asthma and COPD studies, the relevance of which deserves careful consideration. In this review, we synthesize the various approaches to ACO diagnosis and evaluate the role of currently available diagnostic tests. We describe the potential benefits of existing asthma and COPD therapies in treating patients with ACO, and the value of a "treatable traits" approach to ACO management. Throughout the review, we highlight some of the pressing, unanswered questions surrounding ACO that are relevant to the clinical community. Ultimately, addressing these questions is necessary if we are to improve clinical outcomes for this complex and heterogeneous patient population.

Our multi-institutional university consortium implemented a gastroschisis pathway in 2015 to standardize and improve care by promoting avoidance of routine intubation and paralysis during silo placement, expeditious abdominal wall closure, discontinuation of antibiotics/narcotics within 48 h of closure, and early initiation/advancement of feeds.Adherence to the gastroschisis pathway was prospectively monitored. Outcomes for the contemporary cohort (2015-2018) were compared with a historical cohort (2007-2012).Good adherence to the pathway was observed for 70 cases of inborn uncomplicated gastroschisis. The contemporary cohort had significantly lower median mechanical ventilator days (2 versus 5; p 0.01) and antibiotic days (5.5 versus 9; p 0.01) as well as earlier days to initiation of feeds (12 versus 15; p 0.01). However, no differences were observed in length of stay (28 versus 29 days; p = 0.70). A skin closure technique was performed in 66% of the patients, of which 46% were performed at bedside without intubation, the assistance of an operating-room team, or general anesthesia.In this study, adherence to a clinical pathway for gastroschisis across different facilities was feasible and led to reduction in exposure to mechanical ventilation and antibiotics. The adoption of a bedside skin closure technique appears to facilitate compliance with the pathway.Level II/III TYPE OF STUDY: Prospective comparative study with historical cohort.

Background and Purpose— Despite treatment with oral anticoagulants, patients with nonvalvular atrial fibrillation (AF) may experience ischemic cerebrovascular events. The aims of this case-control study in patients with AF were to identify the pathogenesis of and the risk factors for cerebrovascular ischemic events occurring during non–vitamin K antagonist oral anticoagulants (NOACs) therapy for stroke prevention. Methods— Cases were consecutive patients with AF who had acute cerebrovascular ischemic events during NOAC treatment. Controls were consecutive patients with AF who did not have cerebrovascular events during NOACs treatment. Results— Overall, 713 cases (641 ischemic strokes and 72 transient ischemic attacks; median age, 80.0 years; interquartile range, 12; median National Institutes of Health Stroke Scale on admission, 6.0; interquartile range, 10) and 700 controls (median age, 72.0 years; interquartile range, 8) were included in the study. Recurrent stroke was classified as cardioembolic in 455 cases (63.9%) according to the A-S-C-O-D (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; D, dissection) classification. On multivariable analysis, off-label low dose of NOACs (odds ratio [OR], 3.18; 95% CI, 1.95–5.85), atrial enlargement (OR, 6.64; 95% CI, 4.63–9.52), hyperlipidemia (OR, 2.40; 95% CI, 1.83–3.16), and CHA 2 DS 2 -VASc score (OR, 1.72 for each point increase; 95% CI, 1.58–1.88) were associated with ischemic events. Among the CHA 2 DS 2 -VASc components, age was older and presence of diabetes mellitus, congestive heart failure, and history of stroke or transient ischemic attack more common in patients who had acute cerebrovascular ischemic events. Paroxysmal AF was inversely associated with ischemic events (OR, 0.45; 95% CI, 0.33–0.61). Conclusions— In patients with AF treated with NOACs who had a cerebrovascular event, mostly but not exclusively of cardioembolic pathogenesis, off-label low dose, atrial enlargement, hyperlipidemia, and high CHA 2 DS 2 -VASc score were associated with increased risk of cerebrovascular events.

Background There are several reports on underdiagnosis of COPD, while little is known about COPD overdiagnosis and overtreatment. We describe the overdiagnosis and the prevalence of spirometrically defined false positive COPD, as well as their relationship with overtreatment across 23 population samples in 20 countries participating in the BOLD Study between 2003 and 2012. Methods A false positive diagnosis of COPD was considered when participants reported a doctor's diagnosis of COPD, but postbronchodilator spirometry was unobstructed (FEV1/FVC > LLN). Additional analyses were performed using the fixed ratio criterion (FEV1/FVC Results Among 16,177 participants, 919 (5.7%) reported a previous medical diagnosis of COPD. Postbronchodilator spirometry was unobstructed in 569 subjects (61.9%): false positive COPD. A similar rate of overdiagnosis was seen when using the fixed ratio criterion (55.3%). In a subgroup analysis excluding participants who reported a diagnosis of "chronic bronchitis" or "emphysema" (n = 220), 37.7% had no airflow limitation. The site-specific prevalence of false positive COPD varied greatly, from 1.9% in low- to middle-income countries to 4.9% in high-income countries. In multivariate analysis, overdiagnosis was more common among women, and was associated with higher education; former and current smoking; the presence of wheeze, cough, and phlegm; and concomitant medical diagnosis of asthma or heart disease. Among the subjects with false positive COPD, 45.7% reported current use of respiratory medication. Excluding patients with reported asthma, 34.4% of those with normal spirometry still used a respiratory medication. Conclusions False positive COPD is frequent. This might expose nonobstructed subjects to possible adverse effects of respiratory medication.

The primary study objective is to compare the outcomes of patients taking oral anticoagulant medications in two distinct populations treated according to different management models (comprehensive vs. usual care). (Design: regional prospective cohort study; setting: hospital admission data from two regions). Eligible partecipants were patients taking oral anticoagulant drugs (vitamin K antagonist or direct oral anticoagulants), residents in the Vicenza and Cremona districts from February 1st, 2016 to June 30th, 2017. Patients were identified by accessing the administrative databases of patient drug prescriptions. The primary study outcome was admission to the Emergency Department for stroke, systemic arterial embolism, recurrence of venous thromboembolism or major bleeding. The study evaluated outcomes in 14,226 patients taking oral anticoagulants, of whom 6725 being followed in Cremona with a comprehensive management model. There were 19 and 45 thromboembolic events over 6205 and 6530 patient-years in the Cremona and Vicenza cohort, respectively (IRR 0.44, 95% CI 0.24-0.77). The reduction of events in the Cremona cohort was almost entirely explained by a decrease of events in patients taking VKA (IRR 0.41, 95% CI 0.20-0.78) but not DOACs (IRR 1.08, 95% CI 0.25-5.24). The rate of major bleeding was non-significantly higher in Cremona than in Vicenza (IRI 1.32; 95% CI 0.74-2.40). Across the two cohorts, the risk of bleeding was lower in patients being treated with DOACs rather than warfarin (10/4574 vs. 42/8161 event/person-years, respectively, IRR 0.42 95% CI 0.19-0.86). We conclude that a comprehensive management model providing centralized dose prescription and follow-up may significantly reduce the rate of thromboembolic complications, without substantially increasing the number of bleeding complications. Patients treated with direct oral anticoagulants appear to have a rate of thromboembolic complications comparable to VKA patients under the best management model, with a reduction of major bleeding.

This article reviews the status of biomarkers useful in the diagnosis and progression of chronic obstructive pulmonary disease (COPD). Biomarkers have been the focus of a great deal of COPD-related research in recent years, although useful markers in these specific arenas remain elusive.No biomarker other than lung function has been shown to be useful, to date, for the diagnosis of COPD. The best blood-based biomarkers for the progression of COPD may involve combinations of individual markers, such as CC16, fibrinogen and sRAGE. New imaging metrics, such as central airway collapse, pulmonary vascular changes and central airway branch variation, may be able to provide valuable prognostic and information, although these remain confined to research applications.Blood-based biomarkers for diagnosing and determining the progression of COPD remain disappointingly elusive. Although there have been some advances in nonblood-based markers, such as those from imaging, exhaled breath or physiologic assessment, these remain limited, for the most part, to research applications. Moving toward better markers that could be used in clinical application in the screening and diagnosis of COPD that could also provide prognostic information remains an important goal of research.

Background: Obesity is one of the most widespread epidemics of our time. In fact, currently 65.7% of US adults age 20 and older are overweight, while 30.6% are obese. It has been well-established that obesity has numerous adverse effects on long-term health, however the specific effect on patients treated for sepsis and septic shock is unclear. Body Mass Index (BMI) is a measure of total body fat content and surrogate marker for obesity. In our study, we aimed to identify if BMI was an independent risk factor for poor survival or increased length of stay (LOS) in patients with sepsis. Methods: We retrospectively selected patients with diagnostic codes of sepsis and septic shock who were admitted to the ICU over three years. These patients were further separated into groups of alive and deceased. Based on their perceived association with mortality in sepsis, numerous variables were investigated, such as BMI, LOS, age, cirrhosis, chronic kidney disease (CKD), lactate, age, multiple organ dysfunction syndrome (MODS), and APACHE II scores. Specifically, BMI was classified into sub-groups, including underweight (BMI30). The alive and deceased groups were initially compared for any significant differences with univariate analysis. Thereafter, the significant variables were analyzed using multivariate analysis to assess whether any were able to independently predict mortality in sepsis. Results: Our study selected 293 patients with sepsis, including 185 alive and 108 deceased. Interestingly, our univariate analysis revealed that underweight and obese patients exhibited slightly less mortality in sepsis compared to normal and overweight patients. However, these results did not reach statistical significance, with a p-value of 0.30; this was confirmed in multivariate analysis, which resulted in a p-value of 0.08. Additionally, underweight, overweight, and obese patients had a slightly decreased median LOS in the ICU and hospital compared to patients with normal BMI. Nevertheless, these results were not significant either, with ICU LOS p-value of 0.22 and hospital LOS p-value of 0.45. Univariate analysis identified certain variables that reached statistical significance, including cirrhosis (p2 (p=0.03), median lactate (p=0.05), age (p>.01), and APACHE II scores (p>0.01). Multivariate analysis of these variables established that only the presence of cirrhosis (p=0.03), age (p Conclusion: The data suggests that normal BMI in patients with sepsis may result in increased mortality and LOS both in the ICU and hospital, though this was not statistically significant. Other variables that were significant independent predictors for mortality in sepsis were cirrhosis, mean age, and mean APACHE II score. As the obesity epidemic continues to rise, further inquiry into the association of BMI and mortality in sepsis is needed.

Background: The social isolation due to the COVID-19-related lockdown has had an impact on social media consumption around the world. This study examines the relationship between fear of COVID-19, maladaptive Facebook use and disordered eating. Methods: Structural Equation Modeling was used to analyse two-wave survey data (T0: Italian first lockdown; T1: after two months) from 115 Italian subjects (91.3% females; mean age = 28.60 ± 7.31) with self-reported dysfunctional eating behaviors. Participants were assessed on Facebook use, dysfunctional eating cognitions, and fear of COVID-19. Results: Participants’ disordered eating cognitions increased during the pandemic. At T0, higher fear of COVID-19 was positively associated to time spent on Facebook, which in turn predicted disordered eating cognitions at T1. Moreover, maladaptive Facebook use mediated the relationship between daily time on Facebook and Shape concerns.Conclusions: The findings of this study suggest an influence of dysfunctional Facebook use in increasing disordered eating cognitions during the pandemic.

Objectives To analyze the characteristics and outcome of Impella mechanical circulatory support (MCS) for Takotsubo syndrome (TS) with cardiogenic shock. Background TS is an acute heart failure syndrome characterized by transient severe reduction of left ventricular (LV) systolic function, with cardiogenic shock occurring in around 10% of patients. Since inotropes should be avoided due to their role in TS pathogenesis and aggravation of LV outflow tract obstruction, the use of MCS as treatment is a viable treatment option, however, studies are lacking. Methods The catheter-based ventricular assist device (cVAD) registry and local MCS databases were screened for TS patients with cardiogenic shock (TS-CS) supported with an Impella percutaneous ventricular assist device (pVAD). Patient and treatment characteristics and in-hospital outcomes were retrospectively analyzed. Results At 10 US and European centers, 16 TS-CS patients supported with an Impella pVAD were identified between December 2013 and May 2018 (mean age, 61.8 ± 15.5 years; 87.5% women). LV ejection fraction (LVEF) at presentation was severely reduced (mean, 19.4 ± 8.3%). Prior to MCS, 13 patients (81.3%) were mechanically ventilated, 4 patients (25.0%) had been resuscitated, and mean serum lactate was 4.7 ± 3.5 mmol/L. Mean duration of Impella support was 1.9 ± 1.0 days (range, 1–4 days). Thirteen patients (81.3%) survived to discharge, and all survivors experienced cardiac recovery with significant improvement of LVEF at discharge compared to baseline (20.4 ± 8.8 vs. 52.9 ± 12.0, P Conclusions This is the first series of TS-CS patients supported with an Impella pVAD. Mortality was low, and LV systolic function recovered in all survivors. Prospective studies of Impella support in this special condition are warranted.

Objective To investigate the potential association between neutrophil degranulation and patterns of myocardial dysfunction in a cohort of patients with type 2 diabetes mellitus (T2DM). Background Two distinct phenotypes of diabetic cardiomyopathy have been described: a restrictive phenotype with diastolic dysfunction (restrictive/DD) and a dilative phenotype with systolic dysfunction (dilative/SD). However, the underlying determinants of these two patterns are not yet recognized. Methods In this single-centre, observational, cross-sectional study, 492 patients were recruited. Ultrasonographic measurements were performed by two experienced sonographers, blinded to the clinical data of the participants. Serum biomarkers of neutrophil degranulation were measured by enzyme-linked immunosorbent sandwich assay (ELISA). Results After adjustment for confounders, resistin, myeloperoxidase, matrix metalloproteinase 8 and matrix metalloproteinase 9/tissue inhibitor of metalloproteinases 1 complex were positively associated with the restrictive/DD pattern compared with the normal pattern. Similarly, MPO was positively associated with the dilative/SD pattern compared with the normal pattern, and resistin was negatively associated with the dilative/SD pattern compared with the restrictive/DD pattern. Conclusions Neutrophil degranulation is associated with the restrictive/DD echocardiographic pattern in patients with T2DM, but not with the normal pattern and dilative/SD patterns. Neutrophils could have a pivotal role in the pathogenesis of myocardial dysfunction, and particularly diastolic dysfunction, in patients with T2DM.

Objective: To investigate the impact of albumin levels on the aspirin efficacy, since aspirin inhibits platelet aggregation (PA) by cyclooxygenase one irreversible acetylation that is less effective in patients with type 2 diabetes mellitus (T2DM).Patients and Methods: A total of 612 aspirin (100 mg/day)-treated T2DM patients were followed-up for 54.4 ± 7.3 months. The primary endpoint, a composite of cardiovascular events (CVEs) including CV death, myocardial infarction, ischemic stroke and coronary revascularization, was analysed according to baseline values of serum albumin (≥ or < 3.5 g/dL). Serum thromboxane (Tx)B2 was also measured.Results: 250 (40.8%) patients had serum albumin < 3.5 g/dL; these patients were overweight and had higher values of fibrinogen (p = 0.009), high sensitivity C-reactive protein (p = 0.001) and fasting plasma glucose (p < 0.0001) compared to those with albumin ≥ 3.5 g/dL. During follow-up, 86 CVEs were recorded, 49 and 37 in patients with serum albumin < or ≥3.5 g/dL, respectively (p = 0.001). At multivariable Cox regression analysis, serum albumin < 3.5 g/dL (hazard ratio [HR] 1.887, 95% confidence interval [CI] 1.136–3.135, p = 0.014), age (HR 1.552 for every 10 years, 95%CI 1.157–2.081, p = 0.003), fasting plasma glucose (HR 1.063, 95%CI 1.022–1.105, p = 0.002) and beta-blocker use (HR 0.440, 95%CI 0.270–0.717, p = 0.001) were associated to CVEs. Serum TxB2 levels (n = 377) were 0.32 ± 0.12 and 0.24 ± 0.12 ng/ml in patients with albumin < or ≥ 3.5 g/dL, respectively (p < 0.001).Conclusion: In T2DM patients, the efficacy of aspirin varies according to albumin levels. Hypoalbuminemia associated with impaired TxB2 inhibition and an increased risk of long-term CVEs.

OBJECTIVES To compare in-hospital outcomes of bailout support to prophylactic support with percutaneous ventricular assist devices (pVAD) for high-risk nonemergent percutaneous coronary intervention (HRPCI). BACKGROUND Prophylactic support with pVAD for a HRPCI is used in patients felt to be at risk for hemodynamic collapse during PCI. An alternative strategy of bailout pVAD support in the event of hemodynamic collapse is also entertained. METHODS We compared the outcomes of patients entered in the cVAD database who underwent Impella Protected PCI (ProPCI group) with patients from the cVAD and USpella databases receiving bailout Impella support for hemodynamic collapse during HRPCI (Bailout group). RESULTS A total of 1,028 patients supported with Impella pVAD were entered into the cVAD database as of July 2019 and were included in this analysis. Of those 971 were in the ProPCI group and 57 in the Bailout group. Patients in the Bailout group were more often female (50.9%vs. 27.2%, p = .0002) with higher median baseline left ventricular ejection fraction (LVEF) (40%vs. 30%, p

Background Fibrinogen is the first qualified prognostic/predictive biomarker for exacerbations in patients with chronic obstructive pulmonary disease (COPD). The IMPACT trial investigated fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus FF/VI and UMEC/VI in patients with symptomatic COPD at risk of exacerbations. This analysis used IMPACT trial data to examine the relationship between fibrinogen levels and exacerbation outcomes in patients with COPD. Methods 8094 patients with a fibrinogen assessment at Week 16 were included, baseline fibrinogen data were not measured. Post hoc analyses were performed by fibrinogen quartiles and by 3.5 g/L threshold. Endpoints included on-treatment exacerbations and adverse events of special interest (AESIs). Results Rates of moderate, moderate/severe, and severe exacerbations were higher in the highest versus lowest fibrinogen quartile (0.75, 0.92 and 0.15 vs 0.67, 0.79 and 0.10, respectively). The rate ratios (95% confidence interval [CI]) for exacerbations in patients with fibrinogen levels ≥ 3.5 g/L versus those with fibrinogen levels Conclusions Rate and risk of exacerbations was higher in patients with higher fibrinogen levels. This supports the validity of fibrinogen as a predictive biomarker for COPD exacerbations, and highlights the potential use of fibrinogen as an enrichment strategy in trials examining exacerbation outcomes. Trial registration: NCT02164513

Objective: The purpose of this scoping review is to explore the extent to which self-management of youth and young adults with special health care needs is reported in the health care transition literature. Introduction: It is essential for youth and young adults with special health care needs to learn the self-management skills, to the extent possible, that are essential in maintaining the stability of their chronic condition to seamlessly transfer to adult care and live independently. Acquisition of self-management competencies for chronic care management is an essential component of health care transition preparation. Inclusion criteria: The inclusion criteria will be based upon age and condition designation. The age range of participants will include youth and young adults, aged nine to 35 years, who have special health care needs. Inclusion criteria consists of both non-categorical and diagnostic specific terminology for youth and young adults with a childhood acquired chronic condition. Non-categorical terms used include ''long-term chronic condition,'' ''special health care needs,'' ''medical complex condition,'' ''complex care needs,'' ''developmental disability,'' ''intellectual disability,'' ''mental health condition,'' ''emotional disabilities,'' ''physical disabilities,'' ''chronic illness,'' and ''chronic condition.'' Methods: The following databases will be accessed for this health care transition scoping review: CINAHL, Cochrane CENTRAL, Embase, Ovid MEDLINE, PsycINFO, and Web of Science. Relevant gray literature will be accessed as well. The Covidence software platform will be used to review citations and full-text articles. Two reviewers will independently review abstracts and full texts of studies, and extract data using the data extraction tool. Any conflicts will be resolved with a third reviewer. Review findings will be presented in tabular format and narrative synthesis based upon the scoping review objective.

Diabetes and cancer frequently coexist in the same subject, often with relevant clinical effects on the management and prognosis of the comorbid patient. The existing guidelines, however, do not appropriately address many clinical issues in this setting. Although collaboration between diabetologists and oncologists should play an important role in achieving appropriate levels of care, close coordination or agreement between these specialists is seldom offered. There is an urgent need for greater interdisciplinary integration between all specialists involved in this setting, for a shared approach ensuring that organisational silos are overcome. To this end, the Italian Associations of Medical Diabetologists (AMD) and the Italian Association of Medical Oncology (AIOM) recently established a dedicated Working Group on `Diabetes and Cancer'. The working group outlined a diagnostic and therapeutic clinical pathway dedicated to hospitalised patients with diabetes and cancer. In this article, we describe the Italian proposal including some suggested measures to assess, monitor and improve blood glucose control in the hospital setting, to integrate different specialists from both areas, as well as to ensure discharge planning and continuity of care from the hospital to the territory. (C) 2019 Elsevier B.V. All rights reserved.

Purpose Respiratory diseases caused by nontuberculous mycobacteria (NTM) have become a significant concern for patients and healthcare providers. We aimed to compare symptoms experienced during the past two weeks at a single point in time by patients with NTM lung disease (NTMLD) who were currently on any medication to treat their NTMLD versus those not on any therapies. Methods We analyzed responses to a "Burden of NTM Survey" developed by the COPD Foundation. The study population included 266 individuals with NTMLD. Using adjusted penalized logistic regression models, we determined associations between the self-reported symptoms and the use of any medication to treat NTMLD. Results Based on available data, most respondents were aged 50 and older (95.1%), of female gender (93.1%), and had been living with NTMLD for more than five years (55.7%). Many respondents reported symptoms that bother them very often or daily. After adjustment for age and gender, duration of living with NTMLD, and other respiratory illnesses, patients on medication had significantly larger odds of reporting difficulty in walking 500 meters without stopping, difficulty in interacting with others, fatigue or lack of energy, feelings of sadness or depression related to illness, and shortness of breath, wheezing or other difficulties. Conclusion In this study, patients currently on any medication to treat their NTMLD reported more symptoms associated with their NTMLD. Further investigations are needed to explore whether increased symptoms are related to differences in disease severity and/or medication effects.

Background Prior studies in animal models showed that increased cardiac expression of TRIB3 has a pathogenic role in inducing left ventricular mass (LVM). Whether alterations in TRIB3 expression or function have a pathogenic role in inducing LVM increase also in humans is still unsettled. In order to address this issue, we took advantage of a nonsynonymous TRIB3 Q84R polymorphism (rs2295490), a gain-of-function amino acid substitution impairing insulin signalling, and action in primary human endothelial cells which has been associated with insulin resistance, and early vascular atherosclerosis. Methods SNP rs2295490 was genotyped in 2426 White adults in whom LVM index (LVMI) was assessed by validated echocardiography-derived measures. Results After adjusting for age and sex, LVMI progressively and significantly increased from 108 to 113, to 125 g/m2 in Q84Q, Q84R, and R84R individuals, respectively (Q84R vs. Q84Q, P = 0.03; R84R vs. Q84Q, P Conclusions We found that the gain-of-function TRIB3 Q84R variant is significantly associated with left ventricular mass in a large sample of White nondiabetic individual of European ancestry.

Type 2 diabetes mellitus (T2DM) is associated with oxidative stress but the underlying mechanisms promoting oxidative stress as well as its relationship with cardiovascular events is still unclear. In 375 T2DM patients who were followed-up for approximately 5 years we measured the serum levels of soluble NOX2-derived peptide (sNOX2-dp), a marker of Nox2 activation, and albumin, a powerful antioxidant protein. In the entire cohort soluble Nox2 and serum albumin were significantly correlated (r = -0.348, P 0.0001). During the follow-up 49 cardiovascular events (CVE) were registered, of which 45 were non-fatal myocardial infarction (MI); patients with non-fatal MI had significantly higher soluble NOX2/albumin ratio compared to cardiovascular events-free patients. Cox regression analysis showed a significant association between sNox2-dp/serum albumin ratio and the incidental risk of non-fatal MI (HR 1.106, CI95% 1.020-1.198, P = 0.014). The study suggests that redox status imbalance negatively influences vascular outcomes in T2DM.