Higher obesity class is associated with more severe esophageal symptoms and reflux burden but not altered motor function or contractile reserve.

BACKGROUND: Patients with obesity often report esophageal symptoms, with abnormal reflux and esophageal motility suggested as potential mechanisms. However, prior studies showed varying results, often limited by study design/size and esophageal function/symptom measures utilized. We aimed to examine the relationship between obesity and objective esophageal function testing and patient-reported outcomes, utilizing prospective symptom, manometric and reflux monitoring data with impedance. METHODS: Adults referred for high-resolution impedance-manometry (HRiM) and multichannel intraluminal impedance-pH monitoring (MII-pH) to evaluate esophageal symptoms were enrolled. Validated symptom and health-related quality of life (HR-QOL) instruments were prospectively collected: GERDQ, reflux symptoms index (RSI), dominant symptom intensity (DSI, multiplied 5-point Likert scales for symptom frequency/severity), global symptom severity (GSS, 100-point visual analog scale), and Short Form-12 (SF-12) for HR-QOL. Esophageal function testing measures were compared across body mass index (BMI) categories and correlated with patient-reported outcomes. KEY RESULTS: Seven hundred and fifty four patients were included (Normal:281/Overweight:253/Class I obesity:137/Class II/III obesity:83). Reflux burden measures on MII-pH (acid exposure time, total reflux episodes, bolus exposure time), conclusive pathologic reflux (Lyon), and hiatal hernia were increased in higher obesity classes compared to normal BMI. Class II/III obesity was associated with more normal/hypercontractile swallows, less ineffective swallows, and better bolus transit on HRiM. BMI correlated positively with GERDQ/RSI/DSI/GSS, and negatively with physical component score (SF-12). Esophageal symptom severity and HR-QOL correlated strongly with MII-pH findings, but not HRiM measures. CONCLUSIONS/INFERENCES: Obesity is associated with increased esophageal symptom burden and worse physical HR-QOL, which correlate with higher acid/bolus reflux burden but not altered esophageal motility/transit/contractile reserve.

10-Year trend in the prevalence and predictors of depression among patients with heart failure in the USA from 2007-2016.

BACKGROUND: Heart failure (HF) constitutes a major public health problem in the USA with self-management playing a key role in treatment. Depressed patients often have poor insights which correlates with increased rates of adverse events such as emergency room visits, admissions and readmissions, length of hospital stay and mortality. AIM: To determine the prevalence, trends, and predictors of depression among community-based patients with HF in the USA, and its association with self-perceived health status. METHODS: Using the 2007 through 2016 NHANES data, we identified patients with HF aged 20-80 years with completed PHQ-9 depression screening questionnaire. PHQ-9 scores ≥10 were considered diagnostic for depression. The Chi square test was used for comparison of prevalence of depression between subgroups with p < 0.05 considered statistically significant. RESULTS: The prevalence of depression among community-based patients with HF was 17.3% and remained stable from 2007 through 2016. Female participants, persons <60years, individuals with low socioeconomic status, and never married individuals were more likely to be depressed, comparatively. After controlling for confounders, living in poverty was the lone predictor of depression with OR 5.1 (95% CI 1.4-17.9), compared to those with incomes ≥3 times the poverty threshold. Depressed individuals were more likely to report a poor health status (76.4%) compared to non-depressed individuals (45.9%), p < 0.001. CONCLUSION: Over 1 in 6 community-based patients with HF suffers from depression with women, individuals <60years, never married, and persons with low socioeconomic status shouldering a disproportionately higher burden.

Disparities and drivers of early age at diagnosis of congestive heart failure in the USA.

AIM: Heart failure (HF) constitutes a major public health problem in the USA due to its high morbidity and mortality. Age at diagnosis of HF would refine burden quantification, budgeting, disease surveillance and assessment of interventions. We set out to determine the median age at diagnosis of HF and drivers of young age at diagnosis among patients 20 years or older in the USA. METHODS AND RESULTS: We utilized NHANES data collected across five survey cycles (2007-2016). Included were individuals aged 20 to 80 years diagnosed of HF with valid entries for age at diagnosis. Differences in age at diagnosis between groups and major drivers for younger age at diagnosis were assessed using linear regression models with p-values <0.05 considered statistically significant. The prevalence of HF in the USA was 2.44% with a median age at diagnosis of 59 years (IQR 47-70). Non-Hispanic (NH) Blacks -4.94 years (95% CI -7.95 to -1.93), individuals living below the poverty line -5.79 years (95% CI -10.36 to -1.01), obese persons -5.63 years (95% CI -8.35 to -2.92), individuals without health insurance -4.31 years (95% CI -7.87 to -0.75) and those without hypertension -3.99 years (95% CI -7.19 to -0.78) were diagnosed at significantly younger ages than their respective counterparts. CONCLUSION: The median age at diagnosis of HF in the USA is 59 years. NH Blacks, living in poverty, lack of health insurance and obesity are the main drivers of early age at diagnosis of HF in the USA.

Elevated Liver Enzymes in Patients with Type 2 Diabetes Mellitus and Non-alcoholic Fatty Liver Disease.

Background Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver condition. Approximately 70% of type 2 diabetes mellitus (T2DM) patients have a fatty liver; the progression to non-alcoholic steatohepatitis (NASH) dramatically increases the risks of cirrhosis and hepatocellular carcinoma. The aim of our study was to assess the profile of liver enzymes in subjects with T2DM and NAFLD. Method This was a cross-sectional clinic-based study in patients with T2DM. An ultrasonography of the abdomen was done in all patients in order to examine the presence of a fatty liver. Body mass index (BMI), lipid profile, and liver enzymes were also analyzed in all patients. Institutional Review Board (IRB) approval was provided by the National Academy of Medical Sciences, Bir Hospital, Nepal. Unpaired t-test, Chi-square/Fisher's exact test (for categorical variables), and the Pearson/Spearman correlation test were used to find a significant difference, association, and correlation between two or more groups, respectively. The Statistical Package for Social Sciences (SPSS)® Statistics, version 16 (IBM SPSS Statistics, Armonk, NY) was used to analyse the data. Results The study was carried out in 210 patients, and out of the 210 patients, 119 (56.6%) were male and 91 (43.3%) were female. The patients were divided into two groups, i.e., the normal alanine aminotransferase (ALT) group and the elevated ALT group. The mean age of the patients was 56.28 ± 12.3 years in the normal alanine aminotransferase (ALT) group and 58.6 ± 24.7 in the elevated ALT group. The number of T2DM patients with a fatty liver was 117 (55.7%) and those with a non-fatty liver was 93 (44.2%) based on an ultrasonography scan. Subjects with NAFLD had a significantly higher ALT (p < 0.001) but no significant rise in serum aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) levels. The area under the receiver operating characteristic (AUROC) curve for the prediction of fatty liver based solely on the ALT was 0.84 with the confidence interval (CI) between 0.76 and 0.92 (p < 0.05). Conclusions Non-alcoholic fatty liver disease is highly prevalent in patients with T2DM. Timely diagnosis and management of the abnormal liver parameters may help to minimize liver-related morbidity and mortality in the diabetic population.

TLR9 ligation in pancreatic stellate cells promotes tumorigenesis.

Modulation of Toll-like receptor (TLR) signaling can have protective or protumorigenic effects on oncogenesis depending on the cancer subtype and on specific inflammatory elements within the tumor milieu. We found that TLR9 is widely expressed early during the course of pancreatic transformation and that TLR9 ligands are ubiquitous within the tumor microenvironment. TLR9 ligation markedly accelerates oncogenesis, whereas TLR9 deletion is protective. We show that TLR9 activation has distinct effects on the epithelial, inflammatory, and fibrogenic cellular subsets in pancreatic carcinoma and plays a central role in cross talk between these compartments. Specifically, TLR9 activation can induce proinflammatory signaling in transformed epithelial cells, but does not elicit oncogene expression or cancer cell proliferation. Conversely, TLR9 ligation induces pancreatic stellate cells (PSCs) to become fibrogenic and secrete chemokines that promote epithelial cell proliferation. TLR9-activated PSCs mediate their protumorigenic effects on the epithelial compartment via CCL11. Additionally, TLR9 has immune-suppressive effects in the tumor microenvironment (TME) via induction of regulatory T cell recruitment and myeloid-derived suppressor cell proliferation. Collectively, our work shows that TLR9 has protumorigenic effects in pancreatic carcinoma which are distinct from its influence in extrapancreatic malignancies and from the mechanistic effects of other TLRs on pancreatic oncogenesis.

Virtual reality robotic surgery warm-up improves task performance in a dry laboratory environment: a prospective randomized controlled study.

BACKGROUND: Preoperative simulation warm-up has been shown to improve performance and reduce errors in novice and experienced surgeons, yet existing studies have only investigated conventional laparoscopy. We hypothesized that a brief virtual reality (VR) robotic warm-up would enhance robotic task performance and reduce errors. STUDY DESIGN: In a 2-center randomized trial, 51 residents and experienced minimally invasive surgery faculty in General Surgery, Urology, and Gynecology underwent a validated robotic surgery proficiency curriculum on a VR robotic simulator and on the da Vinci surgical robot (Intuitive Surgical Inc). Once they successfully achieved performance benchmarks, surgeons were randomized to either receive a 3- to 5-minute VR simulator warm-up or read a leisure book for 10 minutes before performing similar and dissimilar (intracorporeal suturing) robotic surgery tasks. The primary outcomes compared were task time, tool path length, economy of motion, technical, and cognitive errors. RESULTS: Task time (-29.29 seconds, p = 0.001; 95% CI, -47.03 to -11.56), path length (-79.87 mm; p = 0.014; 95% CI, -144.48 to -15.25), and cognitive errors were reduced in the warm-up group compared with the control group for similar tasks. Global technical errors in intracorporeal suturing (0.32; p = 0.020; 95% CI, 0.06-0.59) were reduced after the dissimilar VR task. When surgeons were stratified by earlier robotic and laparoscopic clinical experience, the more experienced surgeons (n = 17) demonstrated significant improvements from warm-up in task time (-53.5 seconds; p = 0.001; 95% CI, -83.9 to -23.0) and economy of motion (0.63 mm/s; p = 0.007; 95% CI, 0.18-1.09), and improvement in these metrics was not statistically significantly appreciated in the less-experienced cohort (n = 34). CONCLUSIONS: We observed significant performance improvement and error reduction rates among surgeons of varying experience after VR warm-up for basic robotic surgery tasks. In addition, the VR warm-up reduced errors on a more complex task (robotic suturing), suggesting the generalizability of the warm-up.