Combined Liver Transplantation and Gastric Sleeve Resection for Patients With Medically Complicated Obesity and End‐Stage Liver Disease

Obesity is increasingly common before and after liver transplantation (LT), yet optimal management remains unclear. Our aim was to analyze the effectiveness of a multidisciplinary protocol for obese patients requiring LT, including a noninvasive pretransplant weight loss program, and a combined LT plus sleeve gastrectomy (SG) for obese patients who failed to lose weight prior to LT. Since 2006, all patients referred LT with a BMI > 35 were enrolled. There were 37 patients who achieved weight loss and underwent LT alone, and 7 who underwent LT combined with SG. In those who received LT alone, weight gain to BMI > 35 was seen in 21/34, post‐LT diabetes (DM) in 12/34, steatosis in 7/34, with 3 deaths plus 3 grafts losses. In patients undergoing the combined procedure, there were no deaths or graft losses. One patient developed a leak from the gastric staple line, and one had excess weight loss. No patients developed post‐LT DM or steatosis, and all had substantial weight loss (mean BMI = 29). Noninvasive pretransplant weight loss was achieved by a majority, though weight gain post‐LT was common. Combined LT plus SG resulted in effective weight loss and was associated with fewer post‐LT metabolic complications. Long‐term follow‐up is needed.     

Recent advances in liver transplantation

Advances in liver transplantation continue to evolve but are hampered by continued increasing shortages in donor organs. This has resulted in a high incidence of patients dying while on the United Network for Organ Sharing waiting list. Indeed, we continue to assess ways of expanding the donor pool by using marginal donors, living donor liver transplantation, split liver transplantation, domino transplantation, and hepatic support systems to prolong survival long enough for the patient to undergo liver transplantation. Changes in the liver allocation policy to reduce the number of people dying while waiting for an organ are discussed. Implementation of the model for end-stage liver disease allocation system should help alleviate the problem of increasing deaths of patients while on the waiting list. Recurrent disease, particularly recurrent hepatitis C, continues to be a major problem, and effective therapy is needed to prevent both progression of hepatitis C and recurrence in the graft and avoid retransplantation. The use of pegylated interferon in combination with ribavirin holds promise for improving the success in overcoming recurrent hepatitis C. Finally, advances in immunosuppression have reduced the incidence of acute cellular rejection and chronic rejection. However, these therapies have been fraught with metabolic complications that are now affecting quality of life and long-term survival. Tailoring immunosuppressive regimens to the individual patient is discussed.     

Prolonged Mechanical Ventilation After Lung Transplantation—A Single‐Center Study

This single‐center study examines the incidence, etiology, and outcomes associated with prolonged mechanical ventilation (PMV), defined as time to definite spontaneous ventilation >21 days after double lung transplantation (LTx). A total of 690 LTx recipients between January 2005 and December 2012 were analyzed. PMV was necessary in 95 (13.8%) patients with decreasing incidence during the observation period (p < 0.001). Independent predictors of PMV were renal replacement therapy (odds ratio [OR] 11.13 [95% CI, 5.82–21.29], p < 0.001), anastomotic dehiscence (OR 8.74 [95% CI 2.42–31.58], p = 0.001), autoimmune comorbidity (OR 5.52 [95% CI 1.86–16.41], p = 0.002), and postoperative neurologic complications (OR 5.03 [95% CI 1.98–12.81], p = 0.001), among others. Overall 1‐year survival was 86.0% (90.4% for LTx between 2010 and 2012); it was 60.7% after PMV and 90.0% in controls (p < 0.001). Conditional long‐term outcome among hospital survivors, however, did not differ between the groups (p = 0.78). Multivariate analysis identified renal replacement therapy (hazard ratio [HR] 3.55 [95% CI 2.40–5.25], p < 0.001), post‐LTx extracorporeal membrane oxygenation (HR 3.47 [95% CI 2.06–5.83], p < 0.001), and prolonged inotropic support (HR 1.95 [95% CI 1.39–2.75], p < 0.001), among others, as independent predictors of mortality. In conclusion, PMV complicated 14% of LTx procedures and, although associated with increased in‐hospital mortality, outcomes among patients surviving to hospital discharge were unaffected.     

Increased Ca2+ sensitivity and protein expression of SERCA 2a in situations of chronic β3-adrenoceptor deficiency

This study investigated the influence of chronic β₃-adrenoceptor deficiency on myocardial function. Therefore, we investigated Ca²⁺-regulatory proteins, SERCA 2a activity, and myofibrillar and mitochondrial function in hearts of wild-type (WT, n=7) and β₃-adrenoceptor knockout mice (β₃-KNO, n=7). Morphometric heart analysis showed no difference between WT and β₃-KNO. No alterations were observed for the protein expression of the ryanodine receptor or phospholamban. However, in β₃-KNO mice, protein expression of SERCA 2a and phospholamban phosphorylation were significantly increased. These changes were accompanied by an increased SERCA 2a activity in β₃-KNO. Alterations in phospholamban phosphorylation were independent of alterations in β₁/β₂-adrenoceptor distribution and protein expression of G proteins in β₃-KNO. Measurement of myofibrillar Ca²⁺ sensitivity showed no difference in the Ca²⁺/force relation for WT and β₃-KNO. The same seems to hold true for mitochondrial function since the protein expressions of cytochrome c, uncoupling protein 3 and cytochrome c oxidase subunit IV were similar in WT and β₃-KNO. The conclusion is that depression of β₃-adrenergic stimulation may modulate the protein expression of SERCA 2a and phospholamban phosphorylation, thereby improving sarcoplasmic reticulum Ca²⁺ uptake. Thus, β₃-adrenergic depression may be a therapeutic aim in situations of impaired SERCA 2a activity, e.g. for the treatment of heart failure.     

Clostridium difficile toxins A and B can alter epithelial permeability and promote bacterial paracellular migration through HT-29 enterocytes

Clostridium difficile toxins A and B are the widely recognized etiologic agents of antibiotic-associated diseases ranging from diarrhea to pseudomembranous colitis. We hypothesized that C. difficile toxins may alter intestinal epithelial permeability and facilitate bacterial penetration of the intestinal epithelial barrier. Experiments were designed to clarify the effects of C. difficile toxins A and B on the flux of inert particles across HT-29 enterocyte monolayers, and to correlate these results with bacteria-enterocyte interactions. In all experiments, mature, confluent HT-29 cultures were preincubated 16 h with toxin A or B (1-100 ng/mL). To study alterations in epithelial permeability, toxin-treated enterocytes were incubated with 5 pM solutions of 10- and 40-kD inert dextran particles. Toxin A, but not toxin B, was associated with increased dextran flux through enterocyte monolayers. To study bacteria-enterocyte interactions, toxin-treated enterocytes were incubated with 10(8) Salmonella typhimurium, Proteus mirabilis, or Escherichia coli. Although numbers of internalized bacteria were generally unaffected, both toxins were associated with increased bacterial adherence, as well as increased bacterial transmigration through enterocyte monolayers. Bacterial transmigration was significantly greater using toxin A- compared to toxin B-treated enterocytes, consistent with the observation that dextran flux was significantly greater using toxin A- compared to toxin B-treated enterocytes. Thus intestinal colonization with toxigenic C. difficile may facilitate bacterial penetration of the intestinal epithelium by a mechanism involving increased permeability of the intestinal epithelial barrier.     

Comparison of patient reported outcomes after Triathlon? and Kinemax Plus prostheses

INTRODUCTION

The Triathlon^® (Stryker, Kalamazoo, MI, US) total knee replacement was designed to improve patient function and survivorship. The aim of this study was to determine whether the Triathlon^® prosthesis produces better patient reported outcomes than a previous design by the same manufacturer, the Kinemax Plus.

METHODS

The outcome of 233 knees of patients with a mean age of 68 years (range: 40–80 years) who received the Kinemax Plus prosthesis were compared with the outcomes of 220 knees of patients with a mean age of 70 years (range: 42–90 years) who received the Triathlon^® prosthesis. Data were collected via postal questionnaire prior to surgery as well as at 8–12 weeks and at 1 year following surgery. Validated questionnaires were used including the WOMAC^® (Western Ontario and McMaster Universities) pain and function scales, the Knee injury and Osteoarthritis Outcome Score quality of life scale and the self-administered patient satisfaction scale.

RESULTS

This study found that patients who had the Triathlon^® prosthesis had significantly better pain relief (p<0.0001), function (p=0.028), knee related quality of life (p<0.0001) and satisfaction (p=0.0003) at three months after surgery than those who received the Kinemax Plus prosthesis. In addition, knee related quality of life (p=0.002) and satisfaction (p=0.021) were significantly higher at one year after surgery in Triathlon^® patients.

CONCLUSIONS

The findings suggest that return to function and reduction in pain may occur more quickly in patients with a Triathlon^® prosthesis than in those with the Kinemax Plus.     

Prevalence of diabetes mellitus in patients with end-stage liver cirrhosis due to hepatitis C, alcohol, or cholestatic disease

BACKGROUND/AIMS: The aims were to study: 1) the prevalence of diabetes mellitus in patients with end-stage liver cirrhosis due to hepatitis C, alcohol, or cholestatic liver disease, 2) viral and host immunogenetic factors that may predispose to diabetes, and 3) liver transplantation outcome in patients with or without diabetes. METHODS: Fasting blood glucose values of patients who underwent liver transplantation because of hepatitis C-related cirrhosis (73 patients) were compared with those of patients with cirrhosis due to cholestatic (78 patients) or alcoholic liver disease (53 patients) and to a general population. Data on diabetes prevalence in a population without liver cirrhosis was based on the prevalence of diabetes in Olmsted County, Minnesota, residents. HLA was determined using serologic assays. Hepatitis C virus genotypes were determined with polymerase chain reaction amplification and direct sequencing. Hepatitis G RNA was detected with polymerase chain reaction. Liver transplantation outcome in patients with or without diabetes was determined with rejection, retransplantation, or death at 1 year after transplantation as end points. RESULTS: Of 64 patients with hepatitis C alone, 16 (25%) had diabetes before transplantation compared with 1 of 78 (1.3%) with cholestatic liver disease (p= 0.0001) and 10 of 53 (19%) with alcoholic liver disease (p=0.36). Nine patients had hepatitis C plus cholestatic liver disease; one of these (11%) had diabetes. The prevalence of diabetes in patients with cholestatic liver cirrhosis was not different from that of the general population. The frequency of hepatitis G virus coinfection, HLA-DR3, or HLA-DR4 in hepatitis C and diabetes was not different from that of hepatitis C alone. The distribution of hepatitis C virus genotype was similar in those with and those without diabetes. Diabetes was not associated with increased risk of rejection, retransplantation, or death at 1 year after transplantation, and had no impact on overall survival after transplantation. CONCLUSIONS: 1) The risk of diabetes is not increased in patients with liver cirrhosis due to cholestatic liver disease but is in patients with liver cirrhosis due to hepatitis C or alcoholic liver disease; 2) cofactors (age, sex, body mass index, hepatitis G virus coinfection, hepatitis C virus genotype, or HLA-DR3/DR4) did not explain the increased risk of diabetes in patients with hepatitis C; 3) diabetes before liver transplantation did not change the outcome at 1 year after transplantation or survival.