Study protocol for a randomized controlled trial to explore the effects of personalized lifestyle advices and tandem skydives on pleasure in anhedonic young adults.

BACKGROUND: Anhedonia is generally defined as the inability to feel pleasure in response to experiences that are usually enjoyable. Anhedonia is one of the two core symptoms of depression and is a major public health concern. Anhedonia has proven particularly difficult to counteract and predicts poor treatment response generally. It has often been hypothesized that anhedonia can be deterred by a healthy lifestyle. However, it is quite unlikely that a one-size-fits-all approach will be effective for everyone. In this study the effects of personalized lifestyle advice based on observed individual patterns of lifestyle behaviors and experienced pleasure will be examined. Further, we will explore whether a tandem skydive following the personalized lifestyle advice positively influences anhedonic young adults' abilities to carry out the recommended lifestyle changes, and whether this ultimately improves their self-reported pleasure. METHODS: Our study design is an exploratory intervention study, preceded by a cross-sectional survey as a screening instrument. For the survey, 2000 young adults (18-24 years old) will be selected from the general population. Based on survey outcomes, 72 individuals (36 males and 36 females) with persistent anhedonia (i.e., more than two months) and 60 individuals (30 males and 30 females) without anhedonia (non-anhedonic control group) will be selected for the intervention study. The non-anhedonic control group will fill out momentary assessments of pleasure and lifestyle behaviors three times a day, for one month. The anhedonic individuals will fill out momentary assessments for three consecutive months. After the first month, the anhedonic individuals will be randomly assigned to (1) no intervention, (2) lifestyle advice only, (3) lifestyle advice plus tandem skydive. The personalized lifestyle advice is based on patterns observed in the first month. DISCUSSION: The present study is the first to examine the effects of a personalized lifestyle advice and tandem skydive on pleasure in anhedonic young adults. Results of the present study may improve treatment for anhedonia, if the interventions are found to be effective. TRIAL REGISTRATION: Dutch Trial Register, NTR5498 , registered September 22, 2015 (retrospectively registered).

The influence of OKT3 therapy on hepatocellular carcinoma recurrence following liver transplantation.

INTRODUCTION: Cancer recurrence following orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) is a significant obstacle in up to 10-20% of recipients. Recent evidence suggests that anti-CD3 antibody (OKT3) therapy may be associated with increased rates of HCC recurrence. METHODS: At the University of Colorado Transplant Center, 173 patients underwent OLT for end-stage liver disease with concomitant HCC between 1997 and 2008. Nine clinical and pathologic variables were analyzed to test the association between OKT3 therapy for steroid-resistant rejection (SRR) and HCC recurrence-free survival. RESULTS: Overall, the rate of HCC recurrence in this cohort was low and comparable across treatment groups (8.7%). Multivariate analysis reveals that increasing tumor diameter and differentiation have a negative impact on HCC recurrence-free survival. CONCLUSIONS: While several pathologic variables appear to influence outcome, we found no association between OKT3 therapy for SRR and HCC recurrence or survival.

Sirolimus-based immunosuppression following liver transplantation for hepatocellular carcinoma.

Experience with sirolimus (SRL)-based immunosuppression following orthotopic liver transplantation (OLT) is rapidly accumulating. In combination with calcineurin inhibitors (CNIs), SRL may reduce the incidence of acute rejection and lower overall required drug levels. This study sought to quantify long-term outcome following OLT in patients with cirrhosis and concomitant hepatocellular carcinoma (HCC) who were treated with an SRL-based regimen as a primary therapy. From January 2000 to June 2007, 97 patients underwent OLT for end-stage liver disease and HCC at the University of Colorado Health Sciences Center. Of those, 45 patients received SRL, in addition to CNIs, as a component of their primary immunosuppression regimen post-OLT. Conversely, 52 patients received the standard immunosuppression regimen including CNIs, mycophenolate mofetil, and corticosteroids. The 2 treatment groups were compared with respect to the following variables: age, gender, tumor stage by explant, grade, size, presence of vascular invasion, focality, Child's class, baseline creatinine, and warm and cold ischemic times. The 2 groups were comparable by all factors save for cold ischemic time, which was significantly longer in the CNI-treated group. Overall survival at 1 and 5 years post-OLT for patients treated with SRL was 95.5% and 78.8%, respectively. Conversely, survival in patients treated with CNIs exclusively at the same time intervals was 83% and 62%. Although there was no difference in the incidence of major complications, the SRL group experienced a modest improvement in renal function. Cumulatively, these data suggest a potential survival benefit with SRL-based therapy in patients undergoing OLT for end-stage liver disease and concomitant malignancy.

Choledochoduodenostomy is a safe alternative to Roux-en-Y choledochojejunostomy for biliary reconstruction in liver transplantation.

INTRODUCTION: Bile duct reconstruction during liver transplantation is usually performed by a duct-to-duct anastomosis or a Roux-en-Y choledochojejunostomy (CDJ). Direct anastomosis of the bile duct to the duodenum (choledochoduodenostomy-CDD) is another option for biliary reconstruction. This technique has been used with good outcome for the treatment of choledochal cysts, ampullary stenosis, and major bile duct injuries; however, there is little published experience with CDD in liver transplantation. We provide preliminary evidence that CDD is a safe technique for biliary anastomosis in liver transplant recipients. METHODS: From September 2000 to August 2007 a total of 619 adult first-time cadaveric or living donor liver transplants were performed at the University of Colorado Health and Science Center. Bile duct repair was performed by direct end-to-end anastomosis in 466 patients and by choledocoenterostomy in the remaining 153 patients, 82 of whom were cadaveric recipients. The cadaveric choledocoenterostomy patients were divided into two groups: CDD in 25 and CDJ in 57 recipients. RESULTS: There were no significant differences in the 1-year patient or graft survival between the cadaveric groups. The 1-year patient survival was 100% in the CDD group and 97.1% in the CDJ group. The CDD group did not experience more surgical complications compared to the CDJ group. CONCLUSIONS: Choledochoduodenostomy is a safe alternative to CDJ biliary anastomosis when a duct-to-duct anastomosis cannot be performed. There is no significant difference in mortality, graft survival, or biliary complications. In addition, CDD offers the advantage of postoperative access to the billiary system by endoscopy and avoids complications associated with the CDJ bowel anastomosis.

Hepaticoduodenostomy is an alternative to Roux-en-Y hepaticojejunostomy for biliary reconstruction in live donor liver transplantation.

INTRODUCTION: A Roux-en-Y hepaticojejunostomy (HJ) is usually performed during live donor liver transplantation (LDLT) when a duct-to-duct reconstruction is not possible. However, direct anastomosis of the bile duct to the duodenum (hepaticoduodenostomy [HD]) is an alternative technique for biliary repair that has been previously used for conventional biliary surgery and at our center for cadaveric liver transplant. We provide the first evidence that HD is an alternative technique for biliary reconstruction in LDLT. METHODS: We performed a total of 71 LDLT between 2002 and 2008. An end-to-end anastomosis was used in 30 patients. Forty-one patients had a biliary enteric anastomosis in which seven were reconstructed with an HD. Accessory ducts were fashioned into a common duct or implanted into the duodenum separately. RESULTS: There were no patient deaths or retransplants in a follow-up period that ranged from 90 to 771 days after surgery. One patient was diagnosed with cholangitis that responded to intravenous antibiotics and removal of the stent by endoscopy. CONCLUSIONS: This preliminary case series suggests that that HD is a feasible alternative to HJ biliary anastomosis when a duct-to-duct anastomosis cannot be performed. HD offers the possible advantage of simple postoperative access to the biliary system by endoscopy and avoids complications caused by HJ bowel anastomosis.