Citations

AbstractBackgroundThe mechanism by which obesity leads to damage independent of reflux is unclear. We aimed to determine the influence of obesity on mean nocturnal baseline impedance (MNBI), a functional measure of the epithelial barrier, in the presence and absence of acid reflux, using ambulatory pH impedance measurements.MethodsTwenty‐four‐hour pH impedance studies performed off medications in Caucasian men with a normal endoscopic examination were assessed for level of acid exposure and MNBI. Four patient groups were studied: Group 1, Not obese and normal acid exposure; Group 2, Obese and normal acid exposure; Group 3, Not obese and increased acid exposure; and Group 4, Obese with increased acid exposure.ResultsOne hundred patients were studied (25 in each group). Mean esophageal mucosal impedance (MI) was substantially lower in obese patients without reflux (Group 2) and non‐obese patients with reflux (Group 3) compared to normal controls (non‐obese, no reflux, Group 1). MI was progressively lower in the distal (vs the proximal) esophagus in GER patients, compared to those without GER. This difference persisted in the presence or absence of obesity. In contrast, in obese patients, the mean MI was significantly lower throughout the esophagus when compared to the non‐obese patients and also persisted in the presence and absence of accompanying reflux. Obesity and reflux were both independently negatively correlated with MI.ConclusionObesity is associated with abnormal esophageal MNBI. In contrast to gastro‐esophageal reflux, this decrease is pan‐esophageal. These data may support a systemic mechanism by which obesity alters the esophageal barrier function.

Background Hepatic steatosis is strongly associated with cardiovascular disease in the general population. Whether recurrent or de novo, it can occur in the allograft, but the impact on survival and long-term clinical outcomes remains unclear. In this study, we aim to determine both the frequency and impact of allograft steatosis on long-term posttransplant outcomes. Methods A retrospective review of 588 adult liver transplant (LT) recipients (1999-2006) was performed. Cox regression analysis (time-dependent) was used to evaluate differences in time to steatosis post-LT, patient survival, and cardiovascular outcomes. Results Mean age 51.9 ± 10.6 years, 64.6% males, underlying nonalcoholic steatohepatitis (NASH) (9.4%), previous tobacco (52%), pre-LT diabetes mellitus (30.3%), pre-LT hypertension (23.2%), and known cardiovascular disease (9.7%). Overall, 254 recipients developed allograft steatosis (at 10 years: 77.6% NASH recipients, 44.7% Non-NASH recipients). Risk factors for allograft steatosis were female sex (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.09-2.00; P = 0.014), hepatitis C virus diagnosis (HR, 2.49; 95% CI, 1.77-3.94; P < 0.001), and time-dependent BMI (per unit: HR, 1.08; 95% CI, 1.05-1.10; P < 0.001). Allograft steatosis was not associated with post-LT survival (P = 0.25) nor cardiovascular events (HR, 1.08; 95% CI, 0.73-1.59; P = 0.70). Underlying NASH associated with cardiovascular events (HR, 2.04; 95% CI, 1.37-3.04; P < 0.001). Conclusions Allograft steatosis is common but not associated with survival or cardiovascular events in this study. Larger prospective studies are needed to better define the natural history of allograft steatosis.

Left ventricular assist device (LVAD) pump thrombosis occurs in up to 8.4% of patients within 3-months postimplantation. Thromboelastography (TEG) could be used to signal hypercoagulability at LVAD implantation to predict patients at high risk for thrombosis. We sought to evaluate whether TEG maximum amplitude (MA) hypercoagulability (MA ≥69 mm) at the time of LVAD implantation predicts pump thrombosis. A single center, retrospective, nested case–control study was conducted using patients from January 1, 2005, to March 31, 2015. Each pump thrombosis case was matched to two control subjects based on age ± 5 years, sex, and duration of follow-up. A multivariable logistic regression analysis was performed on the matched sets; the odds ratio with 95% confidence interval (CI) was calculated to estimate the relative risk. Thirty-seven age- and sex-matched case–control sets were included for a total of 111 study participants. TEG-MA hypercoagulability occurred in 10.8% of the case group versus 6.8% of controls. There was no association between TEG-MA hypercoagulability and device thrombosis (odds ratio 1.71, 95% confidence interval 0.42–7.05, p = 0.46). Utilization of baseline TEG-MA hypercoagulability to detect individuals at risk for LVAD thrombosis is a novel concept. This study found no significant association between TEG-MA and LVAD thrombosis.

Background Malignancy after liver transplant (LT) is a leading cause of mortality, but data is limited. The aim of this study was to identify patients at higher risk for de novo malignancies after LT in a large multicenter database. Methods The Scientific Registry of Transplant Recipients database comprising all 108 412 LT recipients across the United States between 1987 and March 2015 was analyzed with a median follow-up of 6.95 years. Potential risk factors for malignancies after LT were assessed using Cox regression analysis for the outcome of time to first malignancy. Results Mean age 51.9 ± 10.8 years, 64.6% male, 74.5% white, and 15.8% with previous malignancy. Malignancies during follow-up were 4,483 (41.3%) skin, 1519 (14.0%) hematologic, and 4842 (44.7%) solid organ. The 10-year probability of de novo malignancy was 11.5% (11.3-11.8%). On multivariable analysis, age by decade (hazard ratio [HR], 1.52; P < 0.001), male sex (HR, 1.28; P < 0.001), white race (compared with other races: HR, 1.45-2.04; P < 0.001), multiorgan transplant (HR, 1.35; P < 0.001), previous malignancy (HR, 1.34; P < 0.001), and alcoholic liver disease, autoimmune, nonalcoholic steatohepatitis (HR, 1.35; P < 0.001), and primary sclerosing cholangitis pre-LT (compared with hepatitis C virus, P < 0.001) were associated with higher risk of post-LT malignancy, but type of immunosuppression was not (P = NS). Conclusions This large data set demonstrates the effects of ethnicity/race and etiologies of liver disease, particularly nonalcoholic steatohepatitis as additional risk factors for cancer after LT. Patients with these high-risk characteristics should be more regularly and diligently screened.

Study Objective The extended‐release ( ER ) form of venlafaxine is preferred because of improved patient adherence, but the immediate‐release (IR) form is frequently used after Roux‐en‐Y gastric bypass ( RYGB ) surgery because of concerns for malabsorption. The objective of this study was to determine whether a statistically significant and predictable change in the bioavailability of venlafaxine ER capsules occurs after RYGB . Design Prospective nonblinded single‐dose pharmacokinetic study. Setting Clinical research unit at a large tertiary care medical practice. Patients Ten adult pre–bariatric surgery patients who met the criteria for noncomplicated RYGB were enrolled and served as their own controls. Interventions Patients were administered one venlafaxine ER 75‐mg capsule at two visits—the first visit at least 1 week before undergoing RYGB and the second visit 3–4 months after RYGB . Blood samples were collected at predetermined intervals over 48 hours after each dose, and the pharmacokinetics of venlafaxine were measured. Measurements and Main Results Plasma levels of venlafaxine and its primary metabolite, O ‐desmethylvenlafaxine ( ODV ), were compared at baseline and 3–4 months after RYGB . The areas under the serum concentration–time curves from 0–24 hours ( AUC 0–24 ) for venlafaxine (mean ± SD 734 ± 602 vs 630 ± 553 ng·hr/ml, p=0.22) and ODV (mean ± SD 894 ± 899 vs 1083 ± 972 ng·hr/ml, p=0.07) were similar before and after RYGB . Using a bioequivalence approach, differences in pre‐ RYGB and post‐ RYGB values of AUC 0–24 , peak serum concentration, and time to peak serum concentration were not statistically significant for either venlafaxine or ODV. Conclusion This study suggests that RYGB does not significantly alter the amount of venlafaxine or its active metabolite, ODV , absorbed from a venlafaxine ER capsule or the time over which it is absorbed.

AbstractThe epidemiology of infection after liver transplantation for hilar cholangiocarcinoma has not been systematically investigated. In this study of 124 patients, 255 infections occurred in 105 patients during the median follow‐up of 4.2 years. The median time to first infection was 15.1 weeks (IQR 1.6‐62.6). The most common sites were the abdomen, bloodstream, and musculoskeletal system. Risk factors for any post‐transplant infection were pre‐transplant VRE colonization (Hazard Ratio [HR] 1.9, P=.002), living donor transplantation (HR 6.6, P<.001), longer cold ischemia time (HR 1.05 per 10 minutes, P<.001), donor CMV seropositivity (HR 2.2, P<.001), hepatic artery thrombosis (HR 2.6, P=.005), biliary stricture (HR 3.8, P=.002), intra‐abdominal fluid collection (HR 4.2, P<.001), and re‐operations within 1 month after transplantation (HR 1.7, P=.020). Abdominal infections were independently associated with hemodialysis requirement within 1 month after transplantation (HR 5.6, P=.006), hepatic artery thrombosis (HR 3.3, P=.007), biliary stricture (HR 5.2, P<.001), and abdominal fluid collection (HR 3.7, P=.0002). Bloodstream infections were independently associated with allograft ischemia (HR 17.8, P<.001), biliary stricture (HR 6.5, P=.005), and recipient VRE colonization (HR 4, P<.001). Abdominal infections (HR 2.3, P=.02) and Clostridium difficile infections (HR 4.6, P=.01) were independently associated with increased mortality.

572 Background: There is limited data regarding chemotherapy dosing in obese mCRC patients. Methods: A retrospective, single institution, cohort study of mCRC patients receiving mFOLFOX6 (fluorouracil (5-FU) bolus omitted) was conducted between January 2002 and January 2011. Patients were stratified into: obese (BMI > 30) full dose, obese dose reduced (oxaliplatin (OX) and/or 5-FU), non-obese (BMI 18-29.9) full dose, and non-obese dose reduced. The primary endpoint was incidence of grade 3/4 myelosuppression within the first 12 wks of therapy. Secondary endpoints included incidence of any grade diarrhea and neuropathy, progression free (PFS) and overall survival (OS). Results: Of the 236 patients (72 obese, 164 non-obese), 15 obese and 37 non-obese received a dose reduction. Grade 3/4 myelosuppression occurred in 0 obese OX dose reduced, 3 (7.5%) obese full dose, 1 (8.3%) non-obese dose reduced, and 7 (7.8%) non-obese full dose patients (p=0.93). Grade 3/4 myelosuppression occurred in 0 obese 5-FU dose reduced, 3 (7.5%) obese full dose, 2 (12.5%) non-obese dose reduced, and 6 (7%) non-obese full dose patients (p=0.8). There were no statistically significant differences in the incidence of neuropathy or diarrhea between groups. PFS was longer in OX full dose patients (obese dose reduced, 8.8 mos; obese full dose, 10 mos; non-obese dose reduced, 3.7 mos; non-obese full dose, 10.4 mos; p=0.0094). No difference in PFS was found with 5-FU dosing (p=0.0615). OS favored OX full dose patients (obese dose reduced, 1.6 yrs; obese full dose, 2.4 yrs; non-obese dose reduced, 0.7 yrs; non-obese full dose, 2 yrs; p=0.0006) and 5-FU full dose patients (obese dose reduced, 1.6 yrs; obese full dose, 2.2 yrs; non-obese dose reduced, 1.6 yrs; non-obese full dose, 1.9 yrs; p=0.0287). Conclusions: There is no difference in the incidence of grade 3/4 myelosuppression, diarrhea or neuropathy in obese versus non-obese patients, dose reduced or not. OX dose reductions were associated with reduced PFS and OS. 5-FU dose reductions were associated with reduced OS. Our study supports ASCO recommendations against dose reductions in obese patients receiving chemotherapy.