Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

A common polymorphism in NR1H2 (LXRbeta) is associated with preeclampsia

<p>Abstract</p> <p>Background</p> <p>Preeclampsia is a frequent complication of pregnancy and a leading cause of perinatal mortality. Both genetic and environmental risk factors have been identified. Lipid metabolism, particularly cholesterol metabolism, is associated with this disease. Liver X receptors alpha (NR1H3, also known as LXRalpha) and beta (NR1H2, also known as LXRbeta) play a key role in lipid metabolism. They belong to the nuclear receptor superfamily and are activated by cholesterol derivatives. They have been implicated in preeclampsia because they modulate trophoblast invasion and regulate the expression of the endoglin (CD105) gene, a marker of preeclampsia. The aim of this study was to investigate associations between the <it>NR1H3 </it>and <it>NR1H2 </it>genes and preeclampsia.</p> <p>Methods</p> <p>We assessed associations between single nucleotide polymorphisms of <it>NR1H3 </it>(rs2279238 and rs7120118) and <it>NR1H2 </it>(rs35463555 and rs2695121) and the disease in 155 individuals with preeclampsia and 305 controls. Genotypes were determined by high-resolution melting analysis. We then used a logistic regression model to analyze the different alleles and genotypes for those polymorphisms as a function of case/control status.</p> <p>Results</p> <p>We found no association between <it>NR1H3 </it>SNPs and the disease, but the <it>NR1H2 </it>polymorphism rs2695121 was found to be strongly associated with preeclampsia (genotype C/C: adjusted odds ratio, 2.05; 95% CI, 1.04-4.05; <it>p </it>= 0.039 and genotype T/C: adjusted odds ratio, 1.85; 95% CI, 1.01-3.42; <it>p </it>= 0.049).</p> <p>Conclusions</p> <p>This study provides the first evidence of an association between the <it>NR1H2 </it>gene and preeclampsia, adding to our understanding of the links between cholesterol metabolism and this disease.</p

Dancing in time: feasibility and acceptability of a contemporary dance programme to modify risk factors for falling in community dwelling older adults

Background: Falls are a common cause of injury in older adults, with the prevention of falls being a priority for public health departments around the world. This study investigated the feasibility, and impact of an 8 week contemporary dance programme on modifiable physical (physical activity status, mobility, sedentary behaviour patterns) and psychosocial (depressive state, fear of falling) risk factors for falls. Methods: An uncontrolled ‘pre-post’ intervention design was used. Three groups of older (60 yrs.+) adults were recruited from local community groups to participate in a 3 separate, 8 week dance programmes. Each programme comprised two, 90 min dance classes per week. Quantitative measures of physical activity, sedentary behaviour, depression, mobility and fear of falling were measured at baseline (T1) and after 8 weeks of dance (T2). Weekly attendance was noted, and post-study qualitative work was conducted with participants in 3 separate focus groups. A combined thematic analysis of these data was conducted. Results: Of the 38 (Mean Age = 77.3 ± 8.4 yrs., 37 females) who attended the dance sessions, 22 (21 females; 1 male; mean age = 74.8, ±8.44) consented to be part of the study. Mean attendance was 14.6 (±2.6) sessions, and mean adherence was 84.3% (±17). Significant increases in moderate and vigorous physical activity were noted, with a significant decrease in sitting time over the weekdays (p < 0.05). Statistically significant decreases in the mean Geriatric Depression Scale (p < 0.05) and fear of falling (p < 0.005) score were noted, and the time taken to complete the TUG test decreased significantly from 10.1 s to 7.7 s over the 8 weeks (p < 0.005). Themes from the focus groups included the dance programme as a means of being active, health Benefits, and dance-related barriers and facilitators. Conclusions: The recruitment of older adults, good adherence and favourability across all three sites indicate that a dance programme is feasible as an intervention, but this may be limited to females only. Contemporary dance has the potential to positively affect the physical activity, sitting behaviour, falls related efficacy, mobility and incidence of depression in older females which could reduce their incidence of falls. An adequately powered study with control groups are required to test this intervention further

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

Use of Biomarkers in the Evaluation and Treatment of Hypertensive Patients

The current definition of hypertension is based on blood pressure values, and blood pressure also drives treatment decisions, is the most important treatment monitoring tool and helps estimating risk of hypertension related organ damage. In an era of precision medicine additional biomarkers are needed in the diagnosis and management of patients with hypertension. In this review we outline the areas in which functional, imaging and circulating biomarkers could help in a more individualised definition of hypertension and associated risk. We will cover biomarkers for diagnosis; of pathophysiology and prediction of hypertension; response to treatment, organ damage; and to monitor treatment. A clear focus is on the vasculature, the heart and the kidneys, whereas we see a need to further develop biomarkers of cerebral function in order to diagnose cognition deficits and monitor changes in cognition in the future to support addressing the growing burden of hypertension associated vascular dementia

Primary skeletal muscle myoblasts from chronic heart failure patients exhibit loss of anti-inflammatory and proliferative activity

BACKGROUND: Peripheral skeletal muscle wasting is a common finding with adverse effects in chronic heart failure (HF). Whereas its clinical relevance is beyond doubt, the underlying pathophysiological mechanisms are not yet fully elucidated. We aimed to introduce and characterize the primary culture of skeletal muscle cells from individual HF patients as a supportive model to study this muscle loss. METHODS AND RESULTS: Primary myoblast and myotubes cultures were successfully propagated from the m. vastus lateralis of 6 HF patients with reduced ejection fraction (HFrEF; LVEF <45 %) and 6 age and gender-matched healthy donors. HFrEF cultures were not different from healthy donors in terms of morphology, such as myoblast size, shape and actin microfilament. Differentiation and fusion indexes were identical between groups. Myoblast proliferation in logarithmic growth phase, however, was attenuated in the HFrEF group (p = 0.032). In addition, HFrEF myoblasts are characterized by a reduced TNFR2 expression and IL-6 secretion (p = 0.017 and p = 0.016; respectively). CONCLUSION: Biopsy derived primary skeletal muscle myoblasts of HFrEF patients produce similar morphological and myogenic differentiation responses as myoblasts of healthy donors, though demonstrate loss of anti-inflammatory and proliferative activity

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries