Showing papers by "Institute of Chartered Accountants of Nigeria published in 2016"

Human gut microbes impact host serum metabolome and insulin sensitivity

Abstract: Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.

Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology

Abstract: OBJECTIVE: Individuals with obesity and type 2 diabetes differ from lean and healthy individuals in their abundance of certain gut microbial species and microbial gene richness Abundance of Akkermansia muciniphila, a mucin-degrading bacterium, has been inversely associated with body fat mass and glucose intolerance in mice, but more evidence is needed in humans The impact of diet and weight loss on this bacterial species is unknown Our objective was to evaluate the association between faecal A muciniphila abundance, faecal microbiome gene richness, diet, host characteristics, and their changes after calorie restriction (CR) DESIGN: The intervention consisted of a 6-week CR period followed by a 6-week weight stabilisation diet in overweight and obese adults (N=49, including 41 women) Faecal A muciniphila abundance, faecal microbial gene richness, diet and bioclinical parameters were measured at baseline and after CR and weight stabilisation RESULTS: At baseline A muciniphila was inversely related to fasting glucose, waist-to-hip ratio and subcutaneous adipocyte diameter Subjects with higher gene richness and A muciniphila abundance exhibited the healthiest metabolic status, particularly in fasting plasma glucose, plasma triglycerides and body fat distribution Individuals with higher baseline A muciniphila displayed greater improvement in insulin sensitivity markers and other clinical parameters after CR These participants also experienced a reduction in A muciniphila abundance, but it remained significantly higher than in individuals with lower baseline abundance A muciniphila was associated with microbial species known to be related to health CONCLUSIONS: A muciniphila is associated with a healthier metabolic status and better clinical outcomes after CR in overweight/obese adults The interaction between gut microbiota ecology and A muciniphila warrants further investigation TRIAL REGISTRATION NUMBER: NCT01314690

Physicians' adherence to guideline‐recommended medications in heart failure with reduced ejection fraction: data from the QUALIFY global survey

Abstract: Aims To assess physicians' adherence to guideline-recommended medications for the treatment of chronic heart failure (CHF) with reduced ejection fraction. Methods and results QUALIFY is an international prospective observational longitudinal survey of 7092 CHF outpatients recruited 1–15 months after hospitalization for heart failure from September 2013 to December 2014 in 547 centres in 36 countries. We constructed a five-class guideline adherence score for angiotensin converting enzyme inhibitors (ACEIs), beta-blockers, angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists, and ivabradine. The adherence score was good in 67%, moderate in 25%, and poor in 8% of patients. Adherence was lower in women than men but there were differences in age (65.7 ± 12.5 years women vs. 62.2 ± 12.4 years men, P 67 years (median) (11% vs. 16.2%, P = 0.005). Geographic variations were observed with lower adherence scores in Central/Eastern European countries. The proportion of patients at target dose and ≥50% of target dose was low (27.9% and 63.3% for ACEIs, 14.8% and 51.8% for beta-blockers, 6.9% and 39.5% for ARBs, and 6.9% and 39.5% for ivabradine, respectively). It was also lower in patients most recently hospitalized (<6 vs. ≥6 months) except for beta-blockers. Conclusion This international survey shows that adherence to guideline-recommended medications is relatively satisfactory but the dosage of recommended CHF medications is usually suboptimal. Action plans aimed at improving adherence to guidelines are required.

Brain injury during venovenous extracorporeal membrane oxygenation

Abstract: Purpose The frequency of neurological events and their impact on patients receiving venovenous extracorporeal membrane oxygenation (VV-ECMO) are unknown. We therefore study the epidemiology, risk factors, and impact of cerebral complications occurring in VV-ECMO patients.

Predictive factors of bleeding events in adults undergoing extracorporeal membrane oxygenation

Abstract: Bleeding is the most frequent complication associated with extracorporeal membrane oxygenation (ECMO) support in critically ill patients. Nonetheless, risk factors for bleeding have been poorly described especially those associated with coagulation anomalies and anticoagulant therapy during ECMO support. The aim of this study is to describe bleeding complications in critically ill patients undergoing ECMO and to identify risk factors for bleeding events. We retrospectively analysed ICU charts of adults who received either veno-venous (VV) or veno-arterial (VA) ECMO support in two participating ICUs between 2010 and 2013. Characteristics of patients with and without bleeding complications, as per the Extracorporeal Life Support Organisation (ELSO) definition, were compared, and the impact of bleeding complications on patient outcomes was assessed using survival analysis. Variables that were independently associated with bleeding, including daily clinical and biological variables during ECMO courses, were modelled. Of the 149 ECMO episodes (111 VA ECMO and 38 VV ECMO) performed in 147 adults, 89 episodes (60 %) were complicated by at least one bleeding event. The most common bleeding sources were: ECMO cannula (37 %), haemothorax or cardiac tamponade (17 %) and ear–nose and throat (16 %). Intra-cranial haemorrhage occurred in five (2.2 %) patients. Bleeding complications were independently associated with worse survival [adjusted hazard ratio (HR) 2.17, 95 % confidence interval (CI) 1.07–4.41, P = 0.03]. Higher activated partial thromboplastin time (aPTT) [adjusted odds ratio (OR) 3.00, 95 % CI 1.64–5.47, P < 0.01], APACHE III score [adjusted OR 1.01, 95 % CI 1.01–1.02, P = 0.01] and ECMO following surgery [adjusted OR 3.04, 95 % CI 1.62–5.69, P < 0.01] were independently associated with greater risk of bleeding occurrence. A similar association between bleeding and higher aPTT was found when non-post-surgical VA ECMO was considered separately. Bleeding events based on the ELSO bleeding definition occurred in more than 60 % of ECMO episodes and were associated with hospital mortality. We identified higher aPTT prior bleeding as an independent risk factor for bleeding event, suggesting that better control of the aPTT (through a better control of either coagulopathy or anticoagulation) may improve patients’ outcome.

Associations between ventilator settings during extracorporeal membrane oxygenation for refractory hypoxemia and outcome in patients with acute respiratory distress syndrome: a pooled individual patient data analysis : Mechanical ventilation during ECMO.

Abstract: Extracorporeal membrane oxygenation (ECMO) is a rescue therapy for patients with acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate associations between ventilatory settings during ECMO for refractory hypoxemia and outcome in ARDS patients. In this individual patient data meta-analysis of observational studies in adult ARDS patients receiving ECMO for refractory hypoxemia, a time-dependent frailty model was used to determine which ventilator settings in the first 3 days of ECMO had an independent association with in-hospital mortality. Nine studies including 545 patients were included. Initiation of ECMO was accompanied by significant decreases in tidal volume size, positive end-expiratory pressure (PEEP), plateau pressure, and driving pressure (plateau pressure − PEEP) levels, and respiratory rate and minute ventilation, and resulted in higher PaO2/FiO2, higher arterial pH and lower PaCO2 levels. Higher age, male gender and lower body mass index were independently associated with mortality. Driving pressure was the only ventilatory parameter during ECMO that showed an independent association with in-hospital mortality [adjusted HR, 1.06 (95 % CI, 1.03–1.10)]. In this series of ARDS patients receiving ECMO for refractory hypoxemia, driving pressure during ECMO was the only ventilator setting that showed an independent association with in-hospital mortality.

The genetics underlying acquired long QT syndrome: impact for genetic screening

Abstract: Aims Acquired long QT syndrome (aLQTS) exhibits QT prolongation and Torsades de Pointes ventricular tachycardia triggered by drugs, hypokalaemia, or bradycardia. Sometimes, QTc remains prolonged despite elimination of triggers, suggesting the presence of an underlying genetic substrate. In aLQTS subjects, we assessed the prevalence of mutations in major LQTS genes and their probability of being carriers of a disease-causing genetic variant based on clinical factors. Methods and results We screened for the five major LQTS genes among 188 aLQTS probands (55 ± 20 years, 140 females) from Japan, France, and Italy. Based on control QTc (without triggers), subjects were designated ‘true aLQTS’ (QTc within normal limits) or ‘unmasked cLQTS’ (all others) and compared for QTc and genetics with 2379 members of 1010 genotyped congenital long QT syndrome (cLQTS) families. Cardiac symptoms were present in 86% of aLQTS subjects. Control QTc of aLQTS was 453 ± 39 ms, shorter than in cLQTS (478 ± 46 ms, P < 0.001) and longer than in non-carriers (406 ± 26 ms, P < 0.001). In 53 (28%) aLQTS subjects, 47 disease-causing mutations were identified. Compared with cLQTS, in ‘true aLQTS’, KCNQ1 mutations were much less frequent than KCNH2 (20% [95% CI 7–41%] vs. 64% [95% CI 43–82%], P < 0.01). A clinical score based on control QTc, age, and symptoms allowed identification of patients more likely to carry LQTS mutations. Conclusion A third of aLQTS patients carry cLQTS mutations, those on KCNH2 being more common. The probability of being a carrier of cLQTS disease-causing mutations can be predicted by simple clinical parameters, thus allowing possibly cost-effective genetic testing leading to cascade screening for identification of additional at-risk family members.

Effectiveness of interventions to enhance healing of chronic ulcers of the foot in diabetes: a systematic review

Abstract: The outcome of management of diabetic foot ulcers remains a challenge, and there remains continuing uncertainty concerning optimal approaches to management. It is for these reasons that in 2008 and 2012, the International Working Group of the Diabetic Foot (IWGDF) working group on wound healing published systematic reviews of the evidence to inform protocols for routine care and to highlight areas, which should be considered for further study. The same working group has now updated this review by considering papers on the interventions to improve the healing of chronic ulcers published between June 2010 and June 2014. Methodological quality of selected studies was independently assessed by two reviewers using Scottish Intercollegiate Guidelines Network criteria. Selected studies fell into the following ten categories: sharp debridement and wound bed preparation with larvae or hydrotherapy; wound bed preparation using antiseptics, applications and dressing products; resection of the chronic wound; oxygen and other gases, compression or negative pressure therapy; products designed to correct aspects of wound biochemistry and cell biology associated with impaired wound healing; application of cells, including platelets and stem cells; bioengineered skin and skin grafts; electrical, electromagnetic, lasers, shockwaves and ultrasound and other systemic therapies, which did not fit in the aforementioned categories. Heterogeneity of studies prevented pooled analysis of results. Of the 2161 papers identified, 30 were selected for grading following full text review. The present report is an update of the earlier IWGDF systematic reviews, and the conclusion is similar: that with the possible exception of negative pressure wound therapy in post-operative wounds, there is little published evidence to justify the use of newer therapies. Analysis of the evidence continues to present difficulties in this field as controlled studies remain few and the majority continue to be of poor methodological quality.

Feasibility and safety of low-flow extracorporeal carbon dioxide removal to facilitate ultra-protective ventilation in patients with moderate acute respiratory distress sindrome

Abstract: Mechanical ventilation with a tidal volume (VT) of 6 mL/kg/predicted body weight (PBW), to maintain plateau pressure (Pplat) lower than 30 cmH2O, does not completely avoid the risk of ventilator induced lung injury (VILI). The aim of this study was to evaluate safety and feasibility of a ventilation strategy consisting of very low VT combined with extracorporeal carbon dioxide removal (ECCO2R). In fifteen patients with moderate ARDS, VT was reduced from baseline to 4 mL/kg PBW while PEEP was increased to target a plateau pressure – (Pplat) between 23 and 25 cmH2O. Low-flow ECCO2R was initiated when respiratory acidosis developed (pH 60 mmHg). Ventilation parameters (VT, respiratory rate, PEEP), respiratory compliance (CRS), driving pressure (DeltaP = VT/CRS), arterial blood gases, and ECCO2R system operational characteristics were collected during the period of ultra-protective ventilation. Patients were weaned from ECCO2R when PaO2/FiO2 was higher than 200 and could tolerate conventional ventilation settings. Complications, mortality at day 28, need for prone positioning and extracorporeal membrane oxygenation, and data on weaning from both MV and ECCO2R were also collected. During the 2 h run in phase, VT reduction from baseline (6.2 mL/kg PBW) to approximately 4 mL/kg PBW caused respiratory acidosis (pH < 7.25) in all fifteen patients. At steady state, ECCO2R with an average blood flow of 435 mL/min and sweep gas flow of 10 L/min was effective at correcting pH and PaCO2 to within 10 % of baseline values. PEEP values tended to increase at VT of 4 mL/kg from 12.2 to 14.5 cmH2O, but this change was not statistically significant. Driving pressure was significantly reduced during the first two days compared to baseline (from 13.9 to 11.6 cmH2O; p < 0.05) and there were no significant differences in the values of respiratory system compliance. Rescue therapies for life threatening hypoxemia such as prone position and ECMO were necessary in four and two patients, respectively. Only two study-related adverse events were observed (intravascular hemolysis and femoral catheter kinking). The low-flow ECCO2R system safely facilitates a low volume, low pressure ultra-protective mechanical ventilation strategy in patients with moderate ARDS.

Micronutrient and Protein Deficiencies After Gastric Bypass and Sleeve Gastrectomy: a 1-year Follow-up

Abstract: Roux-en-Y gastric bypass (GBP) and sleeve gastrectomy (SG) have increased dramatically, potentially increasing the prevalence of nutritional deficiencies. The aim of this study was to analyze the effects of food restriction during the first year after bariatric surgery (BS) on nutritional parameters. Twenty-two and 30 obese patients undergoing GBP and SG were prospectively followed at baseline and 3, 6, and 12 months after BS (N = 14 and N = 19 at T12). We evaluated food intake and nutrient adequacy (T0, T3, T12), as well as serum vitamin and mineral concentration (T0, T3, T6, T12). At baseline, GBP and SG patients had similar clinical characteristics, food intake, nutrient adequacy, and serum concentration. The drastic energy and food reduction led to very low probabilities of adequacy for nutrients similar in both models (T3, T12). Serum analysis demonstrated a continuous decrease in prealbumin during the follow-up, indicating mild protein depletion in 37 and 38 % of GBP patients and 57 and 52 % of SG patients, respectively, at T3 and T12. Conversely, despite the low probabilities of adequacy observed at T3 and T12, systematic multivitamin and mineral supplementation after GBP and SG prevented most nutritional deficiencies. GBP and SG have comparable effects in terms of energy and food restriction and subsequent risk of micronutrient and protein deficiencies in the first year post BS. Such results advocate for a cautious monitoring of protein intake after GPB and SG and a systematic multivitamin and mineral supplementation in the first year after SG.

Gene therapy for the treatment of heart failure: promise postponed

Abstract: Gene therapy has emerged as a powerful tool in targeting the molecular mechanisms implicated in heart failure. Refinements in vector technology, including the development of recombinant adeno-associated vectors, have allowed for safe, long-term, and efficient gene transfer to the myocardium. These advancements, coupled with evolving delivery techniques, have placed gene therapy as a viable therapeutic option for patients with heart failure. However, after much promise in early-phase clinical trials, the more recent larger clinical trials have shown disappointing results, thus forcing the field to re-evaluate current vectors, delivery systems, targets, and endpoints. We provide here an updated review of current cardiac gene therapy programmes that have been or are being translated into clinical trials.

The SOS-framework (Systems of Sedentary behaviours): An international transdisciplinary consensus framework for the study of determinants, research priorities and policy on sedentary behaviour across the life course: A DEDIPAC-study

Abstract: Background Ecological models are currently the most used approaches to classify and conceptualise determinants of sedentary behaviour, but these approaches are limited in their ability to capture the complexity of and interplay between determinants. The aim of the project described here was to develop a transdisciplinary dynamic framework, grounded in a system-based approach, for research on determinants of sedentary behaviour across the life span and intervention and policy planning and evaluation. Methods A comprehensive concept mapping approach was used to develop the Systems Of Sedentary behaviours (SOS) framework, involving four main phases: (1) preparation, (2) generation of statements, (3) structuring (sorting and ranking), and (4) analysis and interpretation. The first two phases were undertaken between December 2013 and February 2015 by the DEDIPAC KH team (DEterminants of DIet and Physical Activity Knowledge Hub). The last two phases were completed during a two-day consensus meeting in June 2015. Results During the first phase, 550 factors regarding sedentary behaviour were listed across three age groups (i.e., youths, adults and older adults), which were reduced to a final list of 190 life course factors in phase 2 used during the consensus meeting. In total, 69 international delegates, seven invited experts and one concept mapping consultant attended the consensus meeting. The final framework obtained during that meeting consisted of six clusters of determinants: Physical Health and Wellbeing (71 % consensus), Social and Cultural Context (59 % consensus), Built and Natural Environment (65 % consensus), Psychology and Behaviour (80 % consensus), Politics and Economics (78 % consensus), and Institutional and Home Settings (78 % consensus). Conducting studies on Institutional Settings was ranked as the first research priority. The view that this framework captures a system-based map of determinants of sedentary behaviour was expressed by 89 % of the participants. Conclusion Through an international transdisciplinary consensus process, the SOS framework was developed for the determinants of sedentary behaviour through the life course. Investigating the influence of Institutional and Home Settings was deemed to be the most important area of research to focus on at present and potentially the most modifiable. The SOS framework can be used as an important tool to prioritise future research and to develop policies to reduce sedentary time.

Statins, antidiabetic medications and liver histology in patients with diabetes with non-alcoholic fatty liver disease.

Abstract: Background Type-2 diabetes mellitus (T2DM) is a risk factor for progressive non-alcoholic fatty liver disease (NAFLD). Drugs commonly prescribed in patients with T2DM may affect liver histology by interfering with lipid metabolism and insulin resistance/secretion. Aim We studied if statins or antidiabetic agents were associated with non-alcoholic steatohepatitis (NASH) and significant fibrosis (SF). Methods We performed a cross-sectional study of 346 diabetics with biopsy-proven NAFLD. T2DM was defined as fasting glucose ≥7 mmol/L or glycated haemoglobin ≥6.5% and/or use of antidiabetics. NASH was defined according to the FLIP algorithm and SF as F2–4 Kleiner9s stages. Results 84% of patients were on antidiabetic therapy and 45% on statins. NASH and SF were present in 57% and 48% of patients. Statin-treated patients were older, more frequently male and with poorer glycaemic control despite more frequent antidiabetic therapy than those without statins; however, the prevalence of NASH (57%vs56%, p=0.868) and SF (48%vs48%, p=0.943) was not different between statin users and non-users. NASH was more common in patients on metformin or insulin than in those not treated with these drugs (60%vs47%, p=0.026; 68%vs53%, p=0.017). SF was more common in those treated with sulfonylureas (57%vs44%, p=0.030). Multivariate analyses confirmed that use of statins was independently and negatively associated with both NASH (OR (95% CI) 0.57 (0.32 to 1.01), p=0.055) and SF (OR (95% CI) 0.47 (0.26 to 0.84), p=0.011). Moreover, we found independent associations between insulin use and NASH (OR (95% CI) 2.24 (1.11 to 4.54), p=0.025) and sulfonylureas use and SF (OR (95% CI) 2.04 (1.11 to 3.74), p=0.022). Conclusions Several medications used in patients with diabetes are differently associated with NAFLD histology. Statin use is negatively associated, while insulin and sulfonylureas are positively associated with NASH and SF. A wider use of statins may be warranted in this high-risk population.

IWGDF guidance on use of interventions to enhance the healing of chronic ulcers of the foot in diabetes

Abstract: Department of Diabetes and Endocrinology, Derby Teaching Hospitals NHS FT, Derby, UK Department of Endocrinology, Skåne University Hospital, Malmö, Sweden Department of Plastic Surgery, Medstar Georgetown University. Hospital, Washington DC, USA Pitié-Salpêtrière Hospital, APHP, Paris 6 University, ICAN, Paris, France St George’s Vascular Institute, St George’s Healthcare NHS Trust, London, UK Vice-Chancellors’ Office, Cardiff University, Cardiff, UK Department of Diabetes and Endocrinology, Nottingham University Hospitals NHS Trust, Nottingham, UK

Removing Batch Effects from Longitudinal Gene Expression - Quantile Normalization Plus ComBat as Best Approach for Microarray Transcriptome Data

Abstract: Technical variation plays an important role in microarray-based gene expression studies, and batch effects explain a large proportion of this noise. It is therefore mandatory to eliminate technical variation while maintaining biological variability. Several strategies have been proposed for the removal of batch effects, although they have not been evaluated in large-scale longitudinal gene expression data. In this study, we aimed at identifying a suitable method for batch effect removal in a large study of microarray-based longitudinal gene expression. Monocytic gene expression was measured in 1092 participants of the Gutenberg Health Study at baseline and 5-year follow up. Replicates of selected samples were measured at both time points to identify technical variability. Deming regression, Passing-Bablok regression, linear mixed models, non-linear models as well as ReplicateRUV and ComBat were applied to eliminate batch effects between replicates. In a second step, quantile normalization prior to batch effect correction was performed for each method. Technical variation between batches was evaluated by principal component analysis. Associations between body mass index and transcriptomes were calculated before and after batch removal. Results from association analyses were compared to evaluate maintenance of biological variability. Quantile normalization, separately performed in each batch, combined with ComBat successfully reduced batch effects and maintained biological variability. ReplicateRUV performed perfectly in the replicate data subset of the study, but failed when applied to all samples. All other methods did not substantially reduce batch effects in the replicate data subset. Quantile normalization plus ComBat appears to be a valuable approach for batch correction in longitudinal gene expression data.

Nonalcoholic fatty liver disease and obstructive sleep apnea.

Abstract: Obstructive sleep apnea (OSA) and more importantly its hallmark, chronic intermittent hypoxia (CIH), are established factors in the pathogenesis and exacerbation of nonalcoholic fatty liver disease (NAFLD). This has been clearly demonstrated in rodent models exposed to intermittent hypoxia, and strong evidence now also exists in both paediatric and adult human populations. OSA and CIH induce insulin-resistance and dyslipidemia which are involved in NAFLD physiopathogenesis. CIH increases the expression of the hypoxia inducible transcription factor HIF1α and that of downstream genes involved in lipogenesis, thereby increasing β-oxidation and consequently exacerbating liver oxidative stress. OSA also disrupts the gut liver axis, increasing intestinal permeability and with a possible role of gut microbiota in the link between OSA and NAFLD. OSA patients should be screened for NAFLD and vice versa those with NAFLD for OSA. To date there is no evidence that treating OSA with continuous positive airway pressure (CPAP) will improve NAFLD but it might at least stabilize and slow its progression. Nevertheless, these multimorbid patients should be efficiently treated for all their metabolic co-morbidities and be encouraged to follow weight stabilization or weight loss programs and physical activity life style interventions.

MCM8 and MCM9 Nucleotide Variants in Women With Primary Ovarian Insufficiency.

Abstract: Objective: To assess the frequency of variants, including biallelic pathogenic variants, in MCM8 and MCM9, other genes related to MCM8/9 and DNA damage repair (DDR) pathway in participants with primary ovarian insufficiency (POI). Design: MCM8, MCM9 and genes encoding DDR proteins that have been implicated in reproductive aging were sequenced among POI participants. Setting: Academic research institution Participants: All were diagnosed with POI prior to the age of 40 and presented with elevated FSH levels. Interventions: None Main Outcome Measures: We identified nucleotide variants in MCM8, MCM9, and genes thought to be involved in the DNA damage response pathway and/or implicated in reproductive aging. Results: MCM8 was sequenced in 155 POI participants, while MCM9 was sequenced in 151 participants. Three out of 155 (2%) participants carried possibly damaging heterozygous variants in MCM8, while 7 of 151 (5%) individuals carried possibly damaging heterozygous variants in MCM9. One participant carried a ...

Multicenter Experience With Catheter Ablation for Ventricular Tachycardia in Lamin A/C Cardiomyopathy

Abstract: Background— Lamin A/C ( LMNA ) cardiomyopathy is a genetic disease with a proclivity for ventricular arrhythmias. We describe the multicenter experience with percutaneous catheter ablation of sustained monomorphic ventricular tachycardia (VT) in LMNA cardiomyopathy. Methods and Results— Twenty-five consecutive LMNA mutation patients from 4 centers were included (mean age, 55±9 years; ejection fraction, 34±12%; VT storm in 36%). Complete atrioventricular block was present in 11 patients; 3 patients were on mechanical circulatory support for severe heart failure. A median of 3 VTs were inducible per patient; in 82%, mapping was consistent with origin from scar in the basal left ventricle, particularly the septum, but also basal inferior wall and subaortic mitral continuity. After multiple procedures (median 2/patient; transcoronary alcohol in 6 and surgical cryoablation in 2 patients), acute success (noninducibility of any VT) was achieved in only 25% of patients. Partial success (inducibility of a nonclinical VT only: 50%) and failure (persistent inducibility of clinical VT: 12.5%) was attributed to intramural septal substrate in 13 of 18 patients (72%). Complications occurred in 25% of patients. After a median follow-up of 7 months after the last procedure, 91% experienced ≥1 VT recurrence, 44% received or were awaiting mechanical circulatory support or transplant for end-stage heart failure, and 26% died. Conclusions— Catheter ablation of VT associated with LMNA cardiomyopathy is associated with poor outcomes including high rate of arrhythmia recurrence, progression to end-stage heart failure, and high mortality. Basal septal scar and intramural VT origin makes VT ablation challenging in this population.

Nutritional and Protein Deficiencies in the Short Term following Both Gastric Bypass and Gastric Banding

Abstract: Background The number of morbidly obese patients undergoing bariatric surgery (BS) has increased dramatically in recent years. Therefore, monitoring food intake and its consequences in terms of nutritional status is necessary to prevent nutritional deficiencies. The aim of this study was to analyze the effect of food restriction on nutritional parameters in the short-term (≤3 months) period after BS in morbid obesity. Method In a prospective study, we followed 22 obese women who underwent Roux-en-Y gastric bypass (GBP) or adjustable gastric banding (AGB) at baseline (T0) and 1 (T1) and 3 (T3) months after surgery. We evaluated food intake, nutrient adequacy and serum concentrations of vitamins and minerals known to be at risk for deficiency following BS. Results Before surgery, we observed suboptimal food intakes, leading to a risk of micronutrient deficiencies. Serum analysis confirmed nutritional deficiencies for iron and thiamine for 27 and 23% of the patients, respectively. The drastic energy and food reduction seen in the short term led to very low probabilities of adequacy for nutrients equivalent across both surgeries. Serum analysis demonstrated a continuous decrease in prealbumin during the follow-up, indicating mild protein depletion in 21 and 57% of GBP patients and 50 and 63% of AGB patients, respectively, at T1 and T3. Regarding vitamins and minerals, systematic supplementation after GBP prevented most nutritional deficiencies. By contrast, AGB patients, for whom there is no systematic supplementation, developed such deficiencies. Conclusions Our results suggest that cautious monitoring of protein intake after BS is mandatory. Furthermore, AGB patients might also benefit from systematic multivitamin and mineral supplementation at least in the short term.

Accumulation and Changes in Composition of Collagens in Subcutaneous Adipose Tissue After Bariatric Surgery.

Abstract: Extracellular matrix (ECM) in sc adipose tissue (scAT) undergoes pathological remodeling during obesity. However, its evolution during weight loss remains poorly explored. Objective: The objective of the investigation was to study the histological, transcriptomic, and physical characteristics of scAT ECM remodeling during the first year of bariatric surgery (BS)-induced weight loss and their relationships with metabolic and bioclinical improvements. Design, Setting, Patients, and Interventions: A total of 118 morbidly obese candidates for BS were recruited and followed up during 1 year after BS. Main Outcome Measures: scAT surgical biopsy and needle aspiration as well as scAT stiffness measurement were performed in three subgroups before and after BS. Fourteen nonobese, nondiabetic subjects served as controls. Results: Significantly increased picrosirius-red-stained collagen accumulation in scAT after BS was observed along with fat mass loss, despite metabolic and inflammatory improvements and undetectable changes of scAT stiffness. Collagen accumulation positively associated with M2-macrophages (CD163+ cells) before BS but negatively afterward. Expression levels of genes encoding ECM components (eg, COL3A1, COL6A1, COL6A2, ELN), cross-linking enzymes (eg, lysyl oxidase [LOX], LOXL4, transglutaminase), metalloproteinases, and their inhibitors were modified 1 year after BS. LOX expression and protein were significantly decreased and associated with decreased fat mass as well as other cross-linking enzymes. Although total collagen I and VI staining decreased 1 year after BS, we found increased degraded collagen I and III in scAT, suggesting increased degradation. Conclusions: After BS-induced weight loss and related metabolic improvements, scAT displays major collagen remodeling with an increased picrosirius-red staining that relates to increased collagen degradation and importantly decreased cross-linking. These features are in agreement with adequate ECM adaptation during fat mass loss - See more at: http://press.endocrine.org/doi/10.1210/jc.2015-3348#sthash.PLeUvzKd.dpuf

PPAR-γ Agonists for the Treatment of Major Depression: A Review.

Abstract: Introduction: Selective agonists of the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-γ) are used for the treatment of type 2 diabetes. We reviewed their efficacy and safety for the treatment of major depression and the association of their potential antidepressant effects with changes in biomarkers of metabolism and inflammation. Methods: From 8 studies, 4 open-label trials, and 4 randomized controlled trials (RCT) (3 vs. placebo and 1 vs. metformin), 448 patients with major depression were included, of which 209 patients received PPAR-γ agonists (pioglitazone or rosiglitazone) for 6–12 weeks, either alone or in add-on therapy to conventional treatments. Results: PPAR-γ agonists have antidepressant effects in the 4 open-label studies and in 3 out of 4 RCT. No major adverse event was reported. Improvement in depression scores was associated with improvement in 3 biomarkers of insulin resistance (homeostatic model assessment [HOMA-IR], oral glucose tolerance test, and fasting plasma glucose) and 1 biomarker of inflammation (interleukin-6) among 21 biomarkers studied. Conclusion: PPAR-γ agonists may have antidepressant properties, which need to be assessed in further studies of major depressive episodes.

Personalized medicine for ARDS: the 2035 research agenda

Abstract: In the last 20 years, survival among patients with acute respiratory distress syndrome (ARDS) has increased substantially with advances in lung-protective ventilation and resuscitation. Building on this success, personalizing mechanical ventilation to patient-specific physiology for enhanced lung protection will be a top research priority for the years ahead. However, the ARDS research agenda must be broader in scope. Further understanding of the heterogeneous biology, from molecular to mechanical, underlying early ARDS pathogenesis is essential to inform therapeutic discovery and tailor treatment and prevention strategies to the individual patient. The ARDSne(x)t research agenda for the next 20 years calls for bringing personalized medicine to ARDS, asking simultaneously both whether a treatment affords clinically meaningful benefit and for whom. This expanded scope necessitates standard acquisition of highly granular biological, physiological, and clinical data across studies to identify biologically distinct subgroups that may respond differently to a given intervention. Clinical trials will need to consider enrichment strategies and incorporate long-term functional outcomes. Tremendous investment in research infrastructure and global collaboration will be vital to fulfilling this agenda.

D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile

Abstract: Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposition in vivo. The mutation profoundly impacts helical structure stability of D25V-variant, which is remarkably fibrillogenic under physiological conditions in vitro producing typical amyloid fibrils in its lipid-free form. D25V apolipoprotein C-III is a new human amyloidogenic protein and the first conferring cardioprotection even in the unfavourable context of renal failure, extending the evidence for an important cardiovascular protective role of apolipoprotein C-III deficiency. Thus, fibrate therapy, which reduces hepatic APOC3 transcription, may delay amyloid deposition in affected patients.

Mobile applications in oncology: is it possible for patients and healthcare professionals to easily identify relevant tools?

Abstract: Aim: Mobile applications represent promising tools in management of chronic diseases, both for patients and healthcare professionals, and especially in oncology. Among the large number of mobile health (mhealth) applications available in mobile stores, it could be difficult for users to identify the most relevant ones. This study evaluated the business model and the scientific validation for mobile applications related to oncology.Methods: A systematic review was performed over the two major marketplaces. Purpose, scientific validation, and source of funding were evaluated according to the description of applications in stores. Results were stratified according to targeted audience (general population/patients/healthcare professionals).Results: Five hundred and thirty-nine applications related to oncology were identified: 46.8% dedicated to healthcare professionals, 31.5% to general population, and 21.7% to patients. A lack of information about healthcare professionals’ involvement in the developm...

Ten situations in which ECMO is unlikely to be successful.

Abstract: Extracorporeal membrane oxygenation (ECMO) used for respiratory or cardiac support is frequently considered a rescue therapy when ‘‘conventional’’ management fails. Although the prognoses of these patients have steadily improved over the last decade, the technique is still marred by high mortality (30–70 %). Moreover, ECMO is expensive—in supplies, human resources, and time— which encourages restraining its use for patients who are more likely to survive. Efforts have recently been made to identify the main risk factors associated with ECMO failure for both acute respiratory distress syndrome (ARDS) (Table 1) and refractory cardiogenic shock. We describe below ten situations in which ECMO is unlikely to be successful. 1. Wrong choice of ECMO configuration

Left atrial aging: a cardiac magnetic resonance feature-tracking study

Abstract: Importance of left atrial (LA) phasic function evaluation is increasingly recognized for its incremental value in terms of prognosis and risk stratification. LA phasic deformation in the pathway of normal aging has been characterized using echocardiographic speckle tracking. However, no data are available regarding age-related variations using feature-racking (FT) techniques from standard cine magnetic resonance imaging (MRI). We studied 94 healthy adults (41 ± 14 yr, 47 women), who underwent MRI and Doppler echocardiography on the same day for left ventricular (LV) diastolic function evaluation. From cine MRI, longitudinal strain and strain rate, radial motion fraction, and radial relative velocity, respectively, corresponding to the reservoir, conduit, and LA contraction phases, were measured using dedicated FT software. Longitudinal strain and radial motion fraction decreased gradually and significantly with aging for both reservoir (r > 0.31, P 0.54, P 0.44, P 0.54, P < 0.001), and these associations tended to be stronger in women than in men. Finally, associations of LA functional indexes with age were stronger in individuals with lower transmitral early-to-atrial maximal velocity ratio and mitral annulus maximal longitudinal velocity, as well as higher transmitral early maximal-to-mitral annulus maximal longitudinal velocity ratio, highlighting the LV-LA interplay. Age-related changes in LA phasic function indexes were quantified by cine MRI images using a FT technique and were significantly related to age and LV diastolic function.