Impact of body mass index in liver transplantation for nonalcoholic fatty liver disease and alcoholic liver disease.

BACKGROUND: This study evaluates long-term outcomes and body mass index (BMI) following liver transplantation (LT) for non-alcoholic fatty liver disease (NAFLD) in comparison with alcoholic liver disease (ALD). METHODS: Patient and graft survival were compared using Kaplan Meier curves and log rank test. Multivariable analysis of recipient and donor characteristics was performed as determinants of patient survival. BMI at listing was compared with BMI post-LT. RESULTS: Patient survival at 1-, 3-, 5- and 10 years post-LT was similar in the ALD group (n = 195) compared with the NAFLD group (n = 84) (93% vs. 93%, 91% vs. 89%, 86% vs. 77%, 64% vs. 66% respectively, p = 0.21). One patient in the NAFLD group was re-transplanted and none in the ALD group therefore graft survival was also similar (p = 0.20). Multivariable analysis didn't identify any significant predictors of reduced survival. In comparison with the ALD group, BMI was significantly higher in the NAFLD group at listing (31 vs. 27, p < 0.001), 3-months post-LT (28 vs. 26, p < 0.05) and 6-months post-LT (29 vs. 27, p < 0.05) but was equivalent by 5-years post-LT (29 vs. 30, p = 0.80). CONCLUSIONS: NAFLD patients had similar patient and graft survival post-LT compared to ALD. NAFLD patients returned to listing BMI by one-year post-LT but by 5-years post-LT there was no difference in BMI between the groups.

Sildenafil citrate for the prevention of high altitude hypoxic pulmonary hypertension: double blind, randomized, placebo-controlled trial.

Exaggerated hypoxic pulmonary vasoconstriction is a key factor in the development of high altitude pulmonary edema (HAPE). Due to its effectiveness as a pulmonary vasodilator, sildenafil has been proposed as a prophylactic agent against HAPE. By conducting a parallel-group double blind, randomized, placebo-controlled trial, we investigated the effect of chronic sildenafil administration on pulmonary artery systolic pressure (PASP) and symptoms of acute mountain sickness (AMS) during acclimatization to high altitude. Sixty-two healthy lowland volunteers (36 male; median age 21 years, range 18 to 31) on the Apex 2 research expedition were flown to La Paz, Bolivia (3650 m), and after 4-5 days acclimatization ascended over 90 min to 5200 m. The treatment group (n=20) received 50 mg sildenafil citrate three times daily. PASP was recorded by echocardiography at sea level and within 6 h, 3 days, and 1 week at 5200 m. AMS was assessed daily using the Lake Louise Consensus symptom score. On intention-to-treat analysis, there was no significant difference in PASP at 5200 m between sildenafil and placebo groups. Median AMS score on Day 2 at 5200 m was significantly higher in the sildenafil group (placebo 4.0, sildenafil 6.5; p=0.004) but there was no difference in prevalence of AMS between groups. Sildenafil administration did not affect PASP in healthy lowland subjects at 5200 m but AMS was significantly more severe on Day 2 at 5200 m with sildenafil. Our data do not support routine prophylactic use of sildenafil to reduce PASP at high altitude in healthy subjects with no history of HAPE. TRIALS REGISTRATION NUMBER: NCT00627965.

Incidence and predictors of acute mountain sickness among trekkers on Mount Kilimanjaro.

We investigated the incidence of AMS amongst a general population of trekkers on Mount Kilimanjaro, using the Lake Louise consensus scoring system (LLS). Additionally we examined the effect of prophylactic acetazolamide and different ascent profiles. Climbers on 3 different ascent itineraries were recruited. At 2743 m we recruited 177 participants (mean age 31, range [18-71]) who completed LLS together with an epidemiological questionnaire. At 4730 m participants (n=189, male=108, female=68, mean age 33, range [1871]) completed LLS, 136 of whom had been followed up from 2730 m. At 2743 m, 3% (5/177) of climbers were AMS positive, and 47% (89/189) of climbers from all itineraries were AMS positive at 4730 m. Of climbers attempting the Marangu itineraries, 33% (45/136) were taking acetazolamide. This group had a similar rate of AMS and no statistical difference in severity of LLS when compared with those not taking prophylactic drugs. We also did not demonstrate a difference between the incidence of AMS in climbers who did or did not take a rest day at 3700 m. However, there was a significant reduction in the incidence of AMS amongst pre-acclimatized subjects. Consistent with previous work, we found that the rate of AMS on Mount Kilimanjaro is high. Furthermore, at these fast ascent rates, there was no evidence of a protective effect of acetazolamide or a single rest day. There is a need to increase public awareness of the risks of altitude sickness and we advocate a pragmatic "golden rules" approach (http://www.altitude.org/altitude_sickness.php).

Mortality on Mount Everest, 1921-2006: descriptive study.

OBJECTIVE: To examine patterns of mortality among climbers on Mount Everest over an 86 year period. DESIGN: Descriptive study. SETTING: Climbing expeditions to Mount Everest, 1921-2006. PARTICIPANTS: 14,138 mountaineers; 8030 climbers and 6108 sherpas. MAIN OUTCOME MEASURE: Circumstances of deaths. RESULTS: The mortality rate among mountaineers above base camp was 1.3%. Deaths could be classified as involving trauma (objective hazards or falls, n=113), as non-traumatic (high altitude illness, hypothermia, or sudden death, n=52), or as a disappearance (body never found, n=27). During the spring climbing seasons from 1982 to 2006, 82.3% of deaths of climbers occurred during an attempt at reaching the summit. The death rate during all descents via standard routes was higher for climbers than for sherpas (2.7% (43/1585) v 0.4% (5/1231), P<0.001; all mountaineers 1.9%). Of 94 mountaineers who died after climbing above 8000 m, 53 (56%) died during descent from the summit, 16 (17%) after turning back, 9 (10%) during the ascent, 4 (5%) before leaving the final camp, and for 12 (13%) the stage of the summit bid was unknown. The median time to reach the summit via standard routes was earlier for survivors than for non-survivors (0900-0959 v 1300-1359, P<0.001). Profound fatigue (n=34), cognitive changes (n=21), and ataxia (n=12) were the commonest symptoms reported in non-survivors, whereas respiratory distress (n=5), headache (n=0), and nausea or vomiting (n=3) were rarely described. CONCLUSIONS: Debilitating symptoms consistent with high altitude cerebral oedema commonly present during descent from the summit of Mount Everest. Profound fatigue and late times in reaching the summit are early features associated with subsequent death.

Abnormal sympathoadrenal development and systemic hypotension in PHD3-/- mice.

Cell culture studies have implicated the oxygen-sensitive hypoxia-inducible factor (HIF) prolyl hydroxylase PHD3 in the regulation of neuronal apoptosis. To better understand this function in vivo, we have created PHD3(-/-) mice and analyzed the neuronal phenotype. Reduced apoptosis in superior cervical ganglion (SCG) neurons cultured from PHD3(-/-) mice is associated with an increase in the number of cells in the SCG, as well as in the adrenal medulla and carotid body. Genetic analysis by intercrossing PHD3(-/-) mice with HIF-1a(+/-) and HIF-2a(+/-) mice demonstrated an interaction with HIF-2alpha but not HIF-1alpha, supporting the nonredundant involvement of a PHD3-HIF-2alpha pathway in the regulation of sympathoadrenal development. Despite the increased number of cells, the sympathoadrenal system appeared hypofunctional in PHD3(-/-) mice, with reduced target tissue innervation, adrenal medullary secretory capacity, sympathoadrenal responses, and systemic blood pressure. These observations suggest that the role of PHD3 in sympathoadrenal development extends beyond simple control of cell survival and organ mass, with functional PHD3 being required for proper anatomical and physiological integrity of the system. Perturbation of this interface between developmental and adaptive signaling by hypoxic, metabolic, or other stresses could have important effects on key sympathoadrenal functions, such as blood pressure regulation.