Phase II Study of First-Line Trebananib Plus Sorafenib in Patients with Advanced Hepatocellular Carcinoma.

LESSONS LEARNED: Trebananib leveraging anti-angiogenic mechanism that is distinct from the classic sorafenib anti-vascular endothelial growth factor inhibition did not demonstrate improved progression-free survival at 4 months in patients with advanced hepatocellular carcinoma (HCC).In support of previously reported high Ang-2 levels' association with poor outcome in HCC for patients, trebananib treatment with lower baseline Ang-2 at study entry was associated with improved overall survival to 22 months and may suggest future studies to be performed within the context of low baseline Ang-2. BACKGROUND: Ang-1 and Ang-2 are angiopoietins thought to promote neovascularization via activation of the Tie-2 angiopoietin receptor. Trebananib sequesters Ang-1 and Ang-2, preventing interaction with the Tie-2 receptor. Trebananib plus sorafenib combination has acceptable toxicity. Elevated Ang-2 levels are associated with poor prognosis in hepatocellular carcinoma (HCC). METHODS: Patients with HCC, Eastern Cooperative Oncology Group ≤2, and Childs-Pugh A received IV trebananib at 10 mg/kg or 15 mg/kg weekly plus sorafenib 400 mg orally twice daily. The study was planned for ≥78% progression-free survival (PFS) rate at 4 months relative to 62% for sorafenib historical control (power = 80% α = 0.20). Secondary endpoints included safety, tolerability, overall survival (OS), and multiple biomarkers, including serum Ang-2. RESULTS: Thirty patients were enrolled sequentially in each of the two nonrandomized cohorts. Demographics were comparable between the two arms and the historical controls. PFS rates at 4 months were 57% and 54% on the 10 mg/kg and 15 mg/kg trebananib cohorts, respectively. Median OS was 17 and 11 months, respectively. Grade 3 and above events noted in ≥10% of patients included fatigue, hypertension, diarrhea, liver failure, palmar-plantar erythrodysesthesia syndrome, dyspnea, and hypophosphatemia. One death was due to hepatic failure. Serum Ang-2 dichotomized at the median was associated with improved OS in both cohorts. CONCLUSION: There was no improvement in PFS rate at 4 months in either cohort, when compared with sorafenib historical control.

Arterial blood pressure and cardiovascular responses to yoga practice.

CONTEXT: Yoga is qualitatively different from any other mode of physical activity in that it consists of a unique combination of isometric muscular contractions, stretching exercises, relaxation techniques, and breathing exercises. In particular, yoga postures consist of systemic isometric contractions that are known to elicit marked increases in mean blood pressure that are not observed during dynamic exercise. Stretching can also induce increases in blood pressure and sympathetic nerve activity in the muscles. Currently, not much is known about changes in blood pressure and other cardiovascular responses to yoga practice. OBJECTIVE: The study intended to determine the acute effects of one session of hatha yoga practice on blood pressure and other cardiovascular responses. To gain insight into the long-term effects of yoga practice, both novice (n = 19) and advanced (n = 18) yoga practitioners were studied. DESIGN: The two groups were matched for age, gender, BMI, and blood pressure. SETTING: The setting was a research laboratory at a university. PARTICIPANTS: Thirty-six apparently healthy, nonobese, sedentary, or recreationally active individuals from the community participated in the study. Intervention The intervention comprised one session of yoga practice, in which participants followed a custom made instructional video providing a yoga routine that consisted of a series of 23 hatha-based yoga postures. OUTCOME MEASURES: Prior to arriving at the laboratory, each participant completed a research health questionnaire, a training-status questionnaire, and a yoga-experience questionnaire. Prior to the yoga practice, each participant's height, body fat percentage, trunk or lumbar flexibility, and arterial stiffness as assessed by carotid femoral pulse wave velocity (cfPWV) were measured. For each posture during the yoga practice, the study continuously measured systolic, mean, and diastolic blood pressures, heart rate, stroke volume, and cardiac output. RESULTS: Systolic, mean, and diastolic blood pressures increased significantly during the yoga practice. The magnitude of these increases in blood pressure was greatest with standing postures. Heart rate and cardiac output increased significantly during yoga practice, especially with standing postures. Overall, no differences existed in cardiovascular responses between the novice and advanced practitioners throughout the yoga testing session; cfPWV velocity was significantly and inversely associated with lumbar flexion but not with sit-and-reach test scores. CONCLUSIONS: The research team concluded that a variety of hatha yoga postures, especially standing postures, evoked significant increases in blood pressure. The elevation in blood pressure due to yoga practice was associated with increases in cardiac output and heart rate, which are responses similar to those observed in isometric exercise. The lack of obvious differences in blood pressure and other cardiovascular responses between novice and advanced yoga practitioners suggests that long-term yoga practice does not attenuate acute yoga responses.

The new military medical ethics: legacies of the Gulf Wars and the War on Terror.

United States military medical ethics evolved during its involvement in two recent wars, Gulf War I (1990-1991) and the War on Terror (2001-). Norms of conduct for military clinicians with regard to the treatment of prisoners of war and the administration of non-therapeutic bioactive agents to soldiers were set aside because of the sense of being in a 'new kind of war'. Concurrently, the use of radioactive metal in weaponry and the ability to measure the health consequences of trade embargos on vulnerable civilians occasioned new concerns about the health effects of war on soldiers, their offspring, and civilians living on battlefields. Civilian medical societies and medical ethicists fitfully engaged the evolving nature of the medical ethics issues and policy changes during these wars. Medical codes of professionalism have not been substantively updated and procedures for accountability for new kinds of abuses of medical ethics are not established. Looking to the future, medicine and medical ethics have not articulated a vision for an ongoing military-civilian dialogue to ensure that standards of medical ethics do not evolve simply in accord with military exigency.

Traditional surgeons in sub-Saharan Africa: images from south Sudan.

Itinerant traditional surgeons work throughout sub-Saharan Africa and perform many procedures including: tooth extraction, abortion, injections, incising and draining abscesses, uvulectomy, circumcision, inguinal hernia surgery, non-invasive cataract luxation, and surgery on closed and open fractures. Cutting and injection equipment are not cleaned and are used on a rapid succession of up to 10 patients in a single clinic session. These procedures cause haemorrhage, septicaemia, tetanus, gangrene, contractures, abscesses, airway obstruction, keloids, iatrogenic fistulae, lacerations of vital organs, loss of limbs, and death. Recent work suggesting that many cases of HIV infection may be caused by medical exposure lend a new urgency to researching the work of traditional surgeons. Collaborative programmes for re-training and re-shaping the work of these practitioners is more likely to be effective in reducing the morbidity than attempts to suppress their work.