Dierkhising, Ross

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.

Background. Obesity is a significant issue in the critically ill population. There is little evidence directing the dosing of venous thromboembolism (VTE) prophylaxis within this population. We aimed to determine whether obesity predisposes medical intensive care unit patients to venous thromboembolism despite standard chemoprophylaxis with 5000 international units of subcutaneous heparin three times daily.Results. We found a 60% increased risk of venous thromboembolism in the body mass index (BMI) ≥ 30 kg/m2group compared to the BMI < 30 kg/m2group; however, this difference did not reach statistical significance. After further utilizing our risk model, neither obesity nor mechanical ventilation reached statistical significance; however, vasopressor administration was associated with a threefold risk.Conclusions. We can conclude that obesity did increase the rate of VTE, but not to a statistically significant level in this single center medical intensive care unit population.

Recent literature has demonstrated concern over the risk of Pneumocystis jirovecii pneumonia (PJP) when administering rituximab with combination chemotherapy such as in R‐CHOP; however, the exact risk and potential need for prophylaxis is unknown. We sought to determine the incidence of PJP infection following R‐CHOP administration in patients with B‐cell lymphoma. Consecutive patients diagnosed with B‐cell lymphoma receiving R‐CHOP were evaluated from chemotherapy initiation until 180 days after the last administration. The primary outcome was cumulative incidence of PJP infection. Secondary endpoints included the association of rituximab, prednisone and subsequent chemotherapy with PJP infection risk. A total of 689 patients (53% male, median age 66 years) were included. Seventy‐three percent of patients completed at least 6 cycles of R‐CHOP treatment. Median rituximab and prednisone cumulative doses were 3950 mg and 5325 mg, respectively. Median daily prednisone dose through end of treatment was 45 mg (range 7.6 mg to 119 mg). The cumulative incidence of PJP was 1.51% (95% CI 0.57–2.43, at maximum follow‐up of 330 days), below 3.5%, the conventional threshold for prophylaxis. Univariate analysis did not detect a statistically significant association between PJP and rituximab, steroids, or receipt of additional chemotherapy in this patient population. Our results demonstrate a low occurrence of Pneumocystis pneumonia during R‐CHOP treatment of B‐cell lymphoma and argue against universal anti‐Pneumocystis prophylaxis in this setting. Further investigations should focus on targeted anti‐Pneumocystis prophylaxis for patients presenting with high‐risk baseline characteristics or when receiving rituximab‐inclusive intensive combination chemotherapy regimens as treatment for other aggressive lymphoma subtypes. Am. J. Hematol. 91:1113–1117, 2016. © 2016 Wiley Periodicals, Inc.

SummaryBackgroundInfectious enteritis is a commonly identified risk factor for irritable bowel syndrome (IBS). The incidence of Clostridium difficile infection (CDI) is on the rise. However, there is limited information on post‐infectious IBS (PI‐IBS) development following CDI and the host‐ and infection‐related risk factors are not known.AimTo determine the incidence and risk factors for PI‐IBS following CDI.MethodsA total of 684 cases of CDI identified from September 2012 to November 2013 were surveyed. Participants completed the Rome III IBS questionnaire and details on the CDI episode. Predictive modelling was done using logistic regression to evaluate risk factors for PI‐IBS development.ResultsA total of 315 CDI cases responded (46% response rate) and 205 were at‐risk (no pre‐CDI IBS) for PI‐IBS development. A total of 52/205 (25%) met the Rome III criteria for IBS ≥6 months following CDI. IBS‐mixed was most common followed by IBS‐diarrhoea. In comparison to those without subsequent PI‐IBS, greater percentage of PI‐IBS patients had CDI symptoms >7 days, nausea, vomiting, abdominal pain during CDI, anxiety and a higher BMI. Using logistic regression, CDI symptoms >7 days [Odds ratio (OR): 2.96, P = 0.01], current anxiety (OR: 1.33, P < 0.0001) and a higher BMI (OR: 1.08, P = 0.004) were independently associated with PI‐IBS development; blood in the stool during CDI was protective (OR: 0.44, P = 0.06).ConclusionsIn this cohort study, new‐onset IBS is common after CDI. Longer CDI duration, current anxiety and higher BMI are associated with the diagnosis of C. difficile PI‐IBS. This chronic sequela should be considered during active management and follow‐up of patients with CDI.

Background: Carbohydrate counting may improve glycemic control in hospitalized cardiology patients by providing individualized insulin doses tailored to meal consumption. The purpose of this study was to compare glycemic outcomes with mealtime insulin dosed by carbohydrate counting versus fixed dosing in the inpatient setting. Materials and Methods: This single-center retrospective cohort study included 225 adult medical cardiology patients who received mealtime, basal, and correction-scale insulin concurrently for at least 72 h and up to 7 days in the interval March 1, 2010–November 7, 2013. Mealtime insulin was dosed by carbohydrate counting or with fixed doses determined prior to meal intake. An inpatient diabetes consult service was responsible for insulin management. Exclusion criteria included receipt of an insulin infusion. The primary end point compared mean daily postprandial glucose values, whereas secondary end points included comparison of preprandial glucose values and mean daily rates of hypoglycemia. Results: Mean postprandial glucose level on Day 7 was 204 and 183 mg/dL in the carbohydrate counting and fixed mealtime dose groups, respectively (unadjusted P =0.04, adjusted P =0.12). There were no statistical differences between groups on Days 2–6. Greater rates of preprandial hypoglycemia were observed in the carbohydrate counting cohort on Day 5 (8.6% vs. 1.5%, P =0.02), Day 6 (1.7% vs. 0%, P =0.01), and Day 7 (7.1% vs. 0%, P =0.008). No differences in postprandial hypoglycemia were seen. Conclusions: Mealtime insulin dosing by carbohydrate counting was associated with similar glycemic outcomes as fixed mealtime insulin dosing, except for a greater incidence of preprandial hypoglycemia. Additional comparative studies that include hospital outcomes are needed.