Effect of Physical Activity on the Development and the Resolution of Nonalcoholic Fatty Liver in Relation to Body Mass Index

BACKGROUND Data on whether physical activity (PA) levels are related to nonalcoholic fatty liver disease (NAFLD) when considering body mass index (BMI) are scarce. We assessed whether PA affects the development or resolution of NAFLD in conjunction with BMI changes. METHODS Overall, 130,144 participants who underwent health screening during 2011-2016 were enrolled. According to the PA level in the Korean version of the validated International PA Questionnaire Short Form, participants were classified into the inactive, active, and health-enhancing PA (HEPA) groups. RESULTS In participants with increased BMI, the hazard ratio (HR) and 95% confidence interval after multivariable Cox hazard model for incident NAFLD was 0.97 (0.94-1.01) in the active group and 0.94 (0.89-0.99) in the HEPA group, whereas that for NAFLD resolution was 1.03 (0.92-1.16) and 1.04 (0.88-1.23) (reference: inactive group). With increased BMI, high PA affected only new incident NAFLD. PA enhancement or maintenance of sufficient PA prevented new incident NAFLD. In participants with decreased BMI, the HRs were 0.98 (0.90-1.07) and 0.88 (0.78-0.99) for incident NAFLD and 1.07 (0.98-1.17) and 1.33 (1.18-1.49) for NAFLD resolution in the active and HEPA groups, respectively. With decreased BMI, high PA reduced incident NAFLD and increased NAFLD resolution. Maintenance of sufficient PA led to a considerable resolution of NAFLD. CONCLUSION In this large longitudinal study, PA prevented incident NAFLD regardless of BMI changes. For NAFLD resolution, sufficient PA was essential along with BMI decrease. Maintaining sufficient PA or increasing the PA level is crucial for NAFLD prevention or resolution.

Factors Predisposing to Amblyopia After Exotropia Surgery

Amblyopia (lazy eye) is one of the significant complications of strabismus surgery. It is the most important cause of unilateral visual impairment in both children and adults. The current investigation was achieved to determine the postoperative amblyopia rate and to identify factors predisposing to amblyopia following exotropia surgery among patients who had been referred to Imam Khomeini Hospital in Urmia, Iran. The present investigation is a retrospective study that was conducted over three years (2008-2010). The study consisted of sixty patients who underwent their first strabismus surgery for treatment of horizontal deviation. Patients were followed up for at least 24 months, and the rate of postoperative amblyopia was measured. The preoperative deviation, strabismus type (exotropia vs. esotropia), visual acuity, age at surgery , and the number of operated muscles were analyzed as determining factors of postoperative development of amblyopia. Amblyopia was observed in 50% of cases during the follow-up period. No statistically significant differences were observed between amblyopic and non-amblyopic eyes in terms of sex, age at surgery, strabismus type, and visual acuity. But amblyopic eyes showed higher deviation angles compared to nonamblyopic eyes (<0.001). The Cox hazard model analysis revealed a significant contribution of deviation angle to postoperative development of amblyopia. A larger deviation angle has been identified as a positive predictor of postoperative development of amblyopia in our investigated population. Due to such a high rate of postoperative amblyopia, it seems better to initiate and complete amblyopia therapy before strabismus surgery.

D-dimer Can Be Used to Identify Vicious Phenotype in Gastric Cancer Patients With TNMⅠ-Ⅱ Stages: a Single Institution Experience Over 10 Years Study

BackgroundPart of gastric cancer (GC) patients in early stages still endure early relapse after systematic treatment. This study was designed to identify the value of d-dimer reflecting the bad phenotype in early GC patients. MethodsFrom January 1st 2009 to January 1st 2019, 467 primary GC patients with TNM stage I-II after R0 resection were enrolled, tumor stage was classified by the national comprehensive cancer network guideline 2019. Plasma D-dimer and associated factors were reviewed and analyzed with clinic-pathological characteristics, regularly follow up was proceed when first determined. ResultsThe median follow up is 33 months, and 381/467 GC patient survived after ten years follow up. Although D-dimer was significantly elevated in old age and vascular cancer emboli positive patients. Noteworthy, D-dimer levels displayed an increase in 48/467 GC patients when the cut-off values was 1.5 mg/ml based on the ROC curve in our previous study, log-rank and Cox hazard model analysis showed D-dimer is an independent risk factor for overall survival and disease free survival in this classification. ConclusionPlasma D-dimer represents an easy measurement and lower cost marker for the routine testing to predict highmalignancy phenotype in stage I-II gastric cancer after R0 resection.Clinical registrationChiCTR1900028178

The Novel Fibrosis Index at Diagnosis May Predict All-cause Mortality in Patients With Antineutrophil Cytoplasmic Antibody-associated Vasculitis Without Substantial Liver Diseases.

Objectives: Antineutrophil cytoplasmic antibody associated vasculitis (AAV) is a fatal disease. Currently, predictors of mortality of AAV are based on distribution of organ involvement. Novel fibrosis index (NFI) is an index, which is composed of laboratory results, that reflects the degree of liver fibrosis. The aim of this study is to evaluate whether NFI can predict poor outcomes among patients with AAV without substantial liver diseases. Methods: 210 immunosuppressive drug-naïve AAV patients were retrospectively reviewed. NFI was calculated as follows: NFI= [serum bilirubin x (alkaline phosphatase)2] / [platelet count x (serum albumin)2]. Cut-off of NFI was set at 1.24, and patients were divided into two groups. Poor outcomes were defined as all-cause mortality, relapse, and end-stage renal disease (ESRD). Results: During the median 34.5 months of follow up, twenty-one patients (10%) died, 72 patients (34.3%) relapsed, and 38 patients (18.1%) reached ESRD due to AAV progression. The median calculated NFI was 0.61, and it was higher in AAV patients with all-cause mortality than those without mortality, but it didn’t reach the statistical significance (1.26 vs. 0.59). AAV patients with NFI at diagnosis ≥ 1.24 exhibited a significantly lower cumulative patients’ survival rate than those with NFI at diagnosis < 1.24 (P = 0.002). Multivariate Cox hazard model analysis showed that NFI at diagnosis ≥ 1.24 was an independent predictor of all-cause mortality in AAV (HR 2.850, 95% CI 1.026, 7.910).Conclusions: NFI at diagnosis ≥1.24 may be an independent predictive marker for all-cause mortality in AAV patients without substantial liver diseases.

P0758THE CORRELATION BETWEEN THE MANAGEMENT OF COMORBIDITIES AND THE PROGRESSION OF THE RENAL DYSFUNCTION OR ADVERSE EVENTS OF CHRONIC KIDNEY DISEASE

Background and Aims Several factors, such as anemia, hypertension, hyperuricemia, metabolic acidosis, and chronic kidney disease (CKD)-mineral and bone disorder (MBD), are associated with the progression of CKD or adverse events in CKD patients. However, the significant factors associated with the progression of CKD or adverse events in patients under the condition of appropriate control according to guidelines have not been clarified. Method The study was a 3-year observational study conducted in a single center. In 88 patients with various stages of CKD (not on renal replacement therapy (RRT)) who were treated by nephrologists, blood levels of Hb, ferritin, iron, total iron-binding capacity, and albumin were measured every 3 months, and high-sensitivity C reactive protein (hCRP), β2-microglobulin (MG), HCO3-, and intact-parathyroid hormone (int-PTH), in addition to urinary sodium, potassium, calcium, phosphorus, protein, and β2-MG levels, were measured every 6 months. We also evaluated the doses of iron, erythropoiesis-stimulating agent (ESA), vitamin D, phosphate binder, anti-hypertensive agents, and anti-hyperuricemic agents. All patients were treated according to the clinical practice guidelines for CKD (Japanese Society of Nephrology 2013). A time-dependent Cox hazard model was applied to evaluate the associations between clinical parameters and adverse events (initiation of RRT and hospitalization resulting in cardiovascular disease or infection). Results Unexpectedly, under the condition of appropriate control by nephrologists, hypertension, hyperuricemia, metabolic acidosis, iron metabolism, and inflammation were not selected as significant predictors of the progression of renal dysfunction or adverse events. (Factors associated with the progression of renal dysfunction) In multiple regression analysis, lower baseline blood levels of Hb (β=0.497, P&lt;0.001) and vitamin D 125 (β=0.258, P=0.006) and higher baseline blood levels of int-PTH (β=-0.334, P=0.001), urinary phosphorus (β=0.328, P=0.001), urinary β2-MG (β=-0.225, P=0.031) and urinary protein (β=0.280, P=0.02) were selected as significant predictors of reduced estimated glomerular filtration rate (eGFR) or 1/creatinine (Cr) at the end of the study. (Factors associated with the initiation of RRT and adverse events) In the Cox hazard model, low calcium (HR: 0.37, P=0.026), high phosphate (HR: 5.90, P&lt;0.001), low 1,25-vitamin D (HR: 0.94, P=0.013), high int-PTH (HR: 1.02, P&lt;0.001), use of a phosphate binder (HR: 4.95, P=0.012), and use of vitamin D analogs (HR: 3.75, P=0.014) were selected as risks for adverse events, including the initiation of RRT. Conclusion In this study, we found that among several factors, anemia and CKD-MBD-related factors (phosphate, calcium, vitamin D, int-PTH) were selected as significant predictors of the progression of renal dysfunction. Furthermore, although phosphate binders or vitamin D analogs were administered appropriately, CKD-MBD-related factors (phosphate, calcium, vitamin D, and int-PTH) were associated with RRT initiation or adverse events in these patients. From these results, we presumed that early intervention or strict control of CKD-MBD factors might attenuate the risk for adverse events in CKD patients.

Application of Survival Analysis of TB Patients Using Parametric Model: A Case Study of General Hospital Bayara

Aim: We evaluate the performance of parametric models, mixture of generalized gamma frailty model with Gompertz distribution and compare it with Cox proportional hazard model that is commonly used in the analysis of TB patients and also by [1]. Place and the Duration of the Study: The study was carried out in Bauchi State, Nigeria from January, 2017 to January, 2020. Methodology: In this study secondary data was used and gotten from the patients’ treatment card and TB registers from January 2015 to December 2017. The covariates used were, drug, age, marital status, smoking habit, educational level, weight, category, and risk factor. We used AIC and BIC selection tool to select the model with the lowest value and then compare it with Cox hazard model. Data analysis was done in Stata version 14. Results: The result of the analysis shows that mixture of frailty model with Gompertz baseline distribution has the lowest AIC and BIC value when compared to Cox Proportional model therefore shows a better goodness of fit for our dataset. Conclusion: We therefore conclude that mixture of frailty model with Gompertz baseline distribution model can serve as an alternative to Cox Proportional Model.

Clinical and molecular markers of immune checkpoint inhibitor (ICI) response in dMMR colorectal cancer (CRC) patients (pts).

225 Background: ICIs induce durable responses in dMMR CRC patients. However, clinical and molecular biomarkers of response to ICIs have not been well-established. In this study, we investigated impact of specific MMR gene loss, BRAF V600E mutation and clinical characteristics of pts on clinical outcomes of ICIs. Methods: Pts were eligible if they had confirmed dMMR CRC by IHC or MSI-H by PCR and received ICIs between 01/01/2012 and 05/01/2019 at Winship Cancer Institute of Emory University, Mayo Clinic, Vanderbilt or Stanford University. Due to the functional dependency, the groups were categorized as protein loss of MLH1+PMS2 vs MSH2+MSH6. Log-rank test, Cox hazard model and Fisher’s exact test were used for survival outcomes, the best response and the distribution of variables among the subgroups. Results: A total of 66 pts with dMMR CRC were identified and BRAF status was available for 41 pts. ORRs in MLH1+PMS2 and MSH2+MSH6 groups were 72.9% and 56.5% respectively (P = 0.189). At 2 years, PFS rates were 55.6% and 78.2% for MLH1+PMS2 and MSH2+MSH6 groups respectively (P < 0.001). Pts with BRAF V600E mutations had significantly worse outcomes as compared to pts with wild-type BRAF (2-year PFS rate of 35.0% and 73.3% respectively; P < 0.001). Notably pts < 65 had better 2-year disease control rates when compared to > 65 (71.1% and 41.5% respectively; P < 0.001). We also observed worse 2-year PFS rates in pts with liver metastases (P = 0.014). CRC side and tumor volume did not impact 2-year PFS rates in our cohort. Conclusions: Our data suggest that pts with loss of function in MSH2+MSH6 may have better 2 year-PFS rates compared pts with MLH1+PMS2 even though ORR favored MLH1+PMS2 group suggesting that ORR may not reflect the durability of ICI response in dMMR CRC patients. Consistently, pts with BRAF V600E mutation which is associated with MLH1 promoter methylation had significantly worse 2-year PFS rates. Overall, our findings suggest that BRAFV600E mutation, the affected MMR proteins, pt age, and site of metastasis may impact durability of ICI response in dMMR CRC patients.

The 9-bp Deletion at Position 8272 in Region V of Mitochondrial DNA is Associated with Outcome of Colorectal Cancer

The 9-bp deletion of CCCCCTCTA at position 8272 in region V of mitochondrial DNA is one of the mitochondrial DNA microsatellite instability (mtMSI) sites that associated with cancers. In the present study, we investigated the association of 8272 deletion with the cancer risk and outcome for colorectal cancer (CRC). By the log-rank analysis, the 8272 CCCCCTCTA/del was identified as a prognostic marker for outcome of colorectal cancer patients with the deleted ones associated with shorter postoperative survival. After adjusted with Cox Hazard model, this MSI was associated independently with CRC outcome (relative risk, 2.038; 95%CI, 1.20-3.707; p = 0.020). The analysis of mtMSI can help to identify patient subgroups that are at high risk for poor disease outcomes.