Region 11 MELD Na Exception Prospective Study

Introduction. Hyponatremia complicates cirrhosis and predicts short term mortality, including adverse outcomes before and after liver transplantation. Material and methods. From April 1, 2008, through April 2, 2010, all adult candidates for primary liver transplantation with cirrhosis, listed in Region 11 with hyponatremia, were eligible for sodium (Na) exception. Results. Patients with serum sodium (SNa) less than 130 mg/dL, measured two weeks apart and within 30 days of Model for End Stage Liver Disease (MELD) exception request, were given preapproved Na exception. MELD Na was calculated [MELD + 1.59 (135-SNa/30 days)]. MELD Na was capped at 22, and subject to standard adult recertification schedule. On data end of follow-up, December 28, 2010, 15,285 potential U.S. liver recipients met the inclusion criteria of true MELD between 6 and 22. In Region 11, 1,198 of total eligible liver recipients were listed. Sixty-two (5.2%) patients were eligible for Na exception (MELD Na); 823 patients (68.7%) were listed with standard MELD (SMELD); and 313 patients (26.1%) received HCC MELD exception. Ninety percent of MELD Na patients and 97% of HCC MELD patients were transplanted at end of follow up, compared to 49% of Region 11 standard MELD and 40% of U.S.A. standard MELD (USA MELD) patients (p \u3c 0.001); with comparable dropout rates (6.5, 1.6, 6.9, 9% respectively; p = 0.2). MELD Na, HCC MELD, Region 11 SMELD, and USA MELD post-transplant six-month actual patient survivals were similar (92.9, 92.8, 92.2, and 93.9 %, respectively). Conclusion. The Region 11 MELD Na exception prospective trial improved hyponatremic cirrhotic patient access to transplant equitably, and without compromising transplant efficacy

Impact of Hepatopulmonary Syndrome on Quality of Life and Survival in Liver Transplant Candidates

Hepatopulmonary syndrome (HPS) affects 10%–30% of patients with cirrhosis and portal hypertension, but the impact on functional status, quality of life, and survival is poorly defined. We assessed the impact of HPS in patients evaluated for liver transplantation

The impact of left ventricular hypertrophy on survival in candidates for liver transplantation: LVH in Cirrhosis

Left ventricular hypertrophy (LVH) occurs in 12% to 30% of patients with cirrhosis; however, its prognostic significance is not well studied. We assessed the association of LVH with survival in patients undergoing a liver transplantation (LT) evaluation. We performed a multicenter cohort study of patients undergoing an evaluation for LT. LVH was defined with transthoracic echocardiography. The outcome of interest was all-cause mortality. LVH was present in 138 of 485 patients (28%). Patients with LVH were older, more likely to be male and African American, and were more likely to have hypertension. Three hundred forty-five patients did not undergo transplantation (212 declined, and 133 were waiting): 36 of 110 patients with LVH (33%) died, whereas 57 of 235 patients without LVH (24%) died (P = 0.23). After LT, 8 of 28 patients with LVH (29%) died over the course of 3 years, whereas 9 of 112 patients without LVH (8%) died (P = 0.007). This finding was independent of conventional risk factors for LVH, and all deaths for patients with LVH occurred within 9 months of LT. No clinical or demographic characteristics were associated with mortality among LVH patients. In conclusion, the presence of LVH is associated with an early increase in mortality after LT, and this is independent of conventional risk factors for LVH. Further studies are needed to confirm these findings and identify factors associated with mortality after transplantation to improve outcomes

Risk factors and impact of chronic obstructive pulmonary disease in candidates for liver transplantation

Chronic obstructive pulmonary disease (COPD) may cause significant symptoms and have an impact on survival. Smoking is an important risk factor for COPD and is common in candidates for liver transplantation; however, the risk factors for and outcomes of COPD in this population are unknown. We performed a prospective cohort study of 373 patients being evaluated for liver transplantation at 7 academic centers in the United States. COPD was characterized by expiratory airflow obstruction and defined as follows: prebronchodilator forced expiratory volume in 1 second/forced vital capacity < 0.70. Patients completed the Liver Disease Quality of Life Questionnaire 1.0, which included the Short Form-36. The mean age of the study sample was 53 ± 9 years, and 234 (63%) were male. Sixty-seven patients (18%, 95% confidence interval 14%–22%) had COPD, and 224 (60%) had a history of smoking. Eighty percent of patients with airflow obstruction did not previously carry a diagnosis of COPD, and 27% were still actively smoking. Older age and any smoking (odds ratio = 3.74, 95% confidence interval 1.94–7.23, P < 0.001) were independent risk factors for COPD. Patients with COPD had worse New York Heart Association functional class and lower physical component summary scores on the 36-Item Short Form but had short-term survival similar to that of patients without COPD. In conclusion, COPD is common and often undiagnosed in candidates for liver transplantation. Older age and smoking are significant risk factors of COPD, which has adverse consequences on functional status and quality of life in these patients

Clinical risk factors for portopulmonary hypertension

Portopulmonary hypertension affects up to 6% of patients with advanced liver disease, but the predictors and biologic mechanism for the development of this complication are unknown. We sought to determine the clinical risk factors for portopulmonary hypertension in patients with advanced liver disease. We performed a multicenter case-control study nested within a prospective cohort of patients with portal hypertension recruited from tertiary care centers. Cases had a mean pulmonary artery pressure >25 mm Hg, pulmonary vascular resistance >240 dynes · second · cm−5, and pulmonary capillary wedge pressure ≤ 15 mm Hg. Controls had a right ventricular systolic pressure < 40 mm Hg (if estimable) and normal right-sided cardiac morphology by transthoracic echocardiography. The study sample included 34 cases and 141 controls. Female sex was associated with a higher risk of portopulmonary hypertension than male sex (adjusted odds ratio =2.90, 95% confidence interval 1.20-7.01, P = 0.018). Autoimmune hepatitis was associated with an increased risk (adjusted odds ratio = 4.02, 95% confidence interval 1.14-14.23, P = 0.031), and hepatitis C infection was associated with a decreased risk (adjusted odds ratio =0.24, 95% confidence interval 0.09-0.65, P =0.005) of portopulmonary hypertension. The severity of liver disease was not related to the risk of portopulmonary hypertension

Genetic Risk Factors for Hepatopulmonary Syndrome in Patients With Advanced Liver Disease

Hepatopulmonary syndrome (HPS) affects 10%–30% of patients with cirrhosis and portal hypertension and significantly increases mortality. Studies in experimental models indicate that pulmonary angiogenesis contributes to the development of HPS, but pathogenesis in humans is poorly understood. We investigated genetic risk factors for HPS in patients with advanced liver disease

Hepatic gene expression during treatment with peginterferon and ribavirin: Identifying molecular pathways for treatment response

The reasons for hepatitis C treatment failure remain unknown but may be related to different host responses to therapy. In this study, we compared hepatic gene expression in patients prior to and during peginterferon and ribavirin therapy. In the on-treatment group, patients received either ribavirin for 72 hours prior to peginterferon alpha-2a injection or peginterferon alpha-2a for 24 hours, prior to biopsy. The patients were grouped into rapid responders (RRs) with a greater than 2-log drop and slow responders (SRs) with a less than 2-log drop in hepatitis C virus RNA by week 4. Pretreatment biopsy specimens were obtained from a matched control group. The pretreatment patients were grouped as RRs or SRs on the basis of the subsequent treatment response. Gene expression profiling was performed with Affymetrix microarray technology. Known interferon-stimulated genes (ISGs) were induced in treated patients. In the pretreatment group, future SRs had higher pretreatment ISG expression than RRs. On treatment, RRs and SRs had similar absolute ISG expression, but when it was corrected for the baseline expression with the pretreatment group, RRs showed a greater fold change in ISGs, whereas SRs showed a greater change in interferon (IFN)-inhibitory pathways. The patients pretreated with ribavirin had heightened induction of IFN-related genes and down-regulation of genes involved in IFN inhibition and hepatic stellate cell activation

Interactivity and Reward-Related Neural Activation during a Serious Videogame

This study sought to determine whether playing a “serious” interactive digital game (IDG) – the Re-Mission videogame for cancer patients – activates mesolimbic neural circuits associated with incentive motivation, and if so, whether such effects stem from the participatory aspects of interactive gameplay, or from the complex sensory/perceptual engagement generated by its dynamic event-stream. Healthy undergraduates were randomized to groups in which they were scanned with functional magnetic resonance imaging (FMRI) as they either actively played Re-Mission or as they passively observed a gameplay audio-visual stream generated by a yoked active group subject. Onset of interactive game play robustly activated mesolimbic projection regions including the caudate nucleus and nucleus accumbens, as well as a subregion of the parahippocampal gyrus. During interactive gameplay, subjects showed extended activation of the thalamus, anterior insula, putamen, and motor-related regions, accompanied by decreased activation in parietal and medial prefrontal cortex. Offset of interactive gameplay activated the anterior insula and anterior cingulate. Between-group comparisons of within-subject contrasts confirmed that mesolimbic activation was significantly more pronounced in the active playgroup than in the passive exposure control group. Individual difference analyses also found the magnitude of parahippocampal activation following gameplay onset to correlate with positive attitudes toward chemotherapy assessed both at the end of the scanning session and at an unannounced one-month follow-up. These findings suggest that IDG-induced activation of reward-related mesolimbic neural circuits stems primarily from participatory engagement in gameplay (interactivity), rather than from the effects of vivid and dynamic sensory stimulation

On the Role of Object Information in Action Observation: An fMRI Study

Observing other people’s actions activates a network of brain regions that is also activated during the execution of these actions. Here, we used functional magnetic resonance imaging to test whether these “mirror” regions in frontal and parietal cortices primarily encode the spatiomotor aspects or the functional goal-related aspects of observed tool actions. Participants viewed static depictions of actions consisting of a tool object (e.g., key) and a target object (e.g., keyhole). They judged the actions either with regard to whether the objects were oriented correctly for the action to succeed (spatiomotor task) or whether an action goal could be achieved with the objects (function task). Compared with a control condition, both tasks activated regions in left frontoparietal cortex previously implicated in action observation and execution. Of these regions, the premotor cortex and supramarginal gyrus were primarily activated during the spatiomotor task, whereas the middle frontal gyrus was primarily activated during the function task. Regions along the intraparietal sulcus were more strongly activated during the spatiomotor task but only when the spatiomotor properties of the tool object were unknown in advance. These results suggest a division of labor within the action observation network that maps onto a similar division previously proposed for action execution

Surgical treatment of patients with acute cholecystitis: Tokyo Guidelines

Cholecystectomy has been widely performed in the treatment of acute cholecystitis, and laparoscopic cholecystectomy has been increasingly adopted as the method of surgery over the past 15 years. Despite the success of laparoscopic cholecystectomy as an elective treatment for symptomatic gallstones, acute cholecystitis was initially considered a contraindication for laparoscopic cholecystectomy. The reasons for it being considered a contraindication were the technical difficulty of performing it in acute cholecystitis and the development of complications, including bile duct injury, bowel injury, and hepatic injury. However, laparoscopic cholecystectomy is now accepted as being safe for acute cholecystitis, when surgeons who are expert at the laparoscopic technique perform it. Laparoscopic cholecystectomy has been found to be superior to open cholecystectomy as a treatment for acute cholecystitis because of a lower incidence of complications, shorter length of postoperative hospital stay, quicker recuperation, and earlier return to work. However, laparoscopic cholecystectomy for acute cholecystitis has not become routine, because the timing and approach to the surgical management in patients with acute cholecystitis is still a matter of controversy. These Guidelines describe the timing of and the optimal surgical treatment of acute cholecystitis in a question-and-answer format