Dangerous dietary supplements: Garcinia cambogia-associated hepatic failure requiring transplantation.

Commercial dietary supplements are marketed as a panacea for the morbidly obese seeking sustainable weight-loss. Unfortunately, many claims cited by supplements are unsupported and inadequately regulated. Most concerning, however, are the associated harmful side effects, often unrecognized by consumers. Garcinia cambogia extract and Garcinia cambogia containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we report the first known case of fulminant hepatic failure associated with this dietary supplement. One active ingredient in this supplement is hydroxycitric acid, an active ingredient also found in weight-loss supplements banned by the Food and Drug Administration in 2009 for hepatotoxicity. Heightened awareness of the dangers of dietary supplements such as Garcinia cambogia is imperative to prevent hepatoxicity and potential fulminant hepatic failure in additional patients

Coil-Assisted Retrograde Transvenous Obliteration (CARTO) for the Treatment of Portal Hypertensive Variceal Bleeding: Preliminary Results.

ObjectivesTo describe the technical feasibility, safety, and clinical outcomes of coil-assisted retrograde transvenous obliteration (CARTO) in treating portal hypertensive non-esophageal variceal hemorrhage.MethodsFrom October 2012 to December 2013, 20 patients who received CARTO for the treatment of portal hypertensive non-esophageal variceal bleeding were retrospectively evaluated. All 20 patients had at least 6-month follow-up. All patients had detachable coils placed to occlude the efferent shunt and retrograde gelfoam embolization to achieve complete thrombosis/obliteration of varices. Technical success, clinical success, rebleeding, and complications were evaluated at follow-up.ResultsA 100% technical success rate (defined as achieving complete occlusion of efferent shunt with complete thrombosis/obliteration of bleeding varices and/or stopping variceal bleeding) was demonstrated in all 20 patients. Clinical success rate (defined as no variceal rebleeding) was 100%. Follow-up computed tomography after CARTO demonstrated decrease in size with complete thrombosis and disappearance of the varices in all 20 patients. Thirteen out of the 20 had endoscopic confirmation of resolution of varices. Minor post-CARTO complications, including worsening of esophageal varices (not bleeding) and worsening of ascites/hydrothorax, were noted in 5 patients (25%). One patient passed away at 24 days after the CARTO due to systemic and portal venous thrombosis and multi-organ failure. Otherwise, no major complication was noted. No variceal rebleeding was noted in all 20 patients during mean follow-up of 384±154 days.ConclusionsCARTO appears to be a technically feasible and safe alternative to traditional balloon-occluded retrograde transvenous obliteration or transjugular intrahepatic portosystemic shunt, with excellent clinical outcomes in treating portal hypertensive non-esophageal variceal bleeding

Intestinal transplantation in composite visceral grafts or alone

Under FK 506-based immunosuppression, the entire cadaver small bowel except for a few proximal and distal centimeters was translated to 17 randomly matched patients, of whom two had antigraft cytotoxic antibodies (positive cross-match). Eight patients received the intestine only, eight had intestine in continuity with the liver, and one received a full multivisceral graft that included the liver, stomach, and pancreas. One liver-intestine recipient died after an intestinal anastomotic leak, sepsis, and graft- versus-host disease. The other 16 patients are alive after 1 to 23 months, in one case after chronic rejection, graft removal, and retransplantation. Twelve of the patients have been liberated from total parenteral nutrition, including all whose transplantation was 2 months or longer ago. The grafts have supported good nutrition, and in children, have allowed growth and weight gain. Management of these patients has been difficult and often complicated, but the end result has been satisfactory in most cases, justifying further clinical trials. The convalescence of the eight patients receiving intestine only has been faster and more trouble free than after liver-intestine or multivisceral transplantation, with no greater difficulty in the control of rejection

Intestinal transplantation in composite visceral grafts or alone

Under FK 506-based immunosuppression, the entire cadaver small bowel except for a few proximal and distal centimeters was translated to 17 randomly matched patients, of whom two had antigraft cytotoxic antibodies (positive cross-match). Eight patients received the intestine only, eight had intestine in continuity with the liver, and one received a full multivisceral graft that included the liver, stomach, and pancreas. One liver-intestine recipient died after an intestinal anastomotic leak, sepsis, and graft- versus-host disease. The other 16 patients are alive after 1 to 23 months, in one case after chronic rejection, graft removal, and retransplantation. Twelve of the patients have been liberated from total parenteral nutrition, including all whose transplantation was 2 months or longer ago. The grafts have supported good nutrition, and in children, have allowed growth and weight gain. Management of these patients has been difficult and often complicated, but the end result has been satisfactory in most cases, justifying further clinical trials. The convalescence of the eight patients receiving intestine only has been faster and more trouble free than after liver-intestine or multivisceral transplantation, with no greater difficulty in the control of rejection

The doubly eclipsing quintuple low-mass star system 1SWASP J093010.78+533859.5

Our discovery of 1SWASP J093010.78+533859.5 as a probable doubly eclipsing quadruple system, containing a contact binary with P ~ 0.23 d and a detached binary with P ~ 1.31 d, was announced in 2013. Subsequently, Koo and collaborators confirmed the detached binary spectroscopically, and identified a fifth set of static spectral lines at its location, corresponding to an additional non-eclipsing component of the system. Here we present new spectroscopic and photometric observations, allowing confirmation of the contact binary and improved modelling of all four eclipsing components. The detached binary is found to contain components of masses 0.837 ± 0.008 and 0.674 ± 0.007M⊙, with radii of 0.832 ± 0.018 and 0.669 ± 0.018R⊙ and effective temperatures of 5185+25-20 and 4325+20-15 K, respectively; the contact system has masses 0.86 ± 0.02 and 0.341 ± 0.011M⊙ , radii of 0.79 ± 0.04 and 0.52 ± 0.05R⊙, respectively, and a common effective temperature of 4700 ± 50 K. The fifth star is of similar temperature and spectral type to the primaries in the two binaries. Long-term photometric observations indicate the presence of a spot on one component of the detached binary, moving at an apparent rate of approximately one rotation every two years. Both binaries have consistent system velocities around −11 to −12 km s-1, which match the average radial velocity of the fifth star; consistent distance estimates for both subsystems of d = 78 ± 3 and d = 73 ± 4 pc are also found, and, with some further assumptions, of d = 83 ± 9 pc for the fifth star. These findings strongly support the claim that both binaries – and very probably all five stars – are gravitationally bound in a single system. The consistent angles of inclination found for the two binaries (88.2 ± 0.3°and 86 ± 4°) may also indicate that they originally formed by fragmentation (around 9–10 Gyr ago) from a single protostellar disk, and subsequently remained in the same orbital plane

Effect of Ku80 Deficiency on Mutation Frequencies and Spectra at a LacZ Reporter Locus in Mouse Tissues and Cells

Non-homologous end joining (NHEJ) is thought to be an important mechanism for preventing the adverse effects of DNA double strand breaks (DSBs) and its absence has been associated with premature aging. To investigate the effect of inactivated NHEJ on spontaneous mutation frequencies and spectra in vivo and in cultured cells, we crossed a Ku80-deficient mouse with mice harboring a lacZ-plasmid-based mutation reporter. We analyzed various organs and tissues, as well as cultured embryonic fibroblasts, for mutations at the lacZ locus. When comparing mutant with wild-type mice, we observed a significantly higher number of genome rearrangements in liver and spleen and a significantly lower number of point mutations in liver and brain. The reduced point mutation frequency was not due to a decrease in small deletion mutations thought to be a hallmark of NHEJ, but could be a consequence of increased cellular responses to unrepaired DSBs. Indeed, we found a substantial increase in persistent 53BP1 and γH2AX DNA damage foci in Ku80−/− as compared to wild-type liver. Treatment of cultured Ku80-deficient or wild-type embryonic fibroblasts, either proliferating or quiescent, with hydrogen peroxide or bleomycin showed no differences in the number or type of induced genome rearrangements. However, after such treatment, Ku80-deficient cells did show an increased number of persistent DNA damage foci. These results indicate that Ku80-dependent repair of DNA damage is predominantly error-free with the effect of alternative more error-prone pathways creating genome rearrangements only detectable after extended periods of time, i.e., in young adult animals. The observed premature aging likely results from a combination of increased cellular senescence and an increased load of stable, genome rearrangements

Transarterial chemoembolization plus or minus intravenous bevacizumab in the treatment of hepatocellular cancer: A pilot study

<p>Abstract</p> <p>Background</p> <p>Stimulation of vascular endothelial growth factor (VEGF) has been observed following transarterial chemoembolization (TACE) in hepatocellular cancer (HCC) and may contribute to tumor regrowth. This pilot study examined whether intravenous (IV) bevacizumab, a monoclonal antibody against VEGF, could inhibit neovessel formation after TACE.</p> <p>Methods</p> <p>30 subjects with HCC undergoing TACE at a single academic institution were randomized with a computer-generated allocation in a one to one ratio to either bevacizumab at a dose of 10 mg/kg IV every 14 days beginning 1 week prior to TACE (TACE-BEV arm) or observation (TACE-O arm). Angiography was performed with TACE at day 8, and again at weeks 10 and 14. Repeat TACE was performed at week 14 if indicated. TACE-BEV subjects were allowed to continue bevacizumab beyond week 16. TACE-O subjects were allowed to cross-over to bevacizumab at week 16 in the setting of progressive disease. The main outcome measure was a comparison of neovessel formation by serial angiography. Secondary outcome measures were progression free survival (PFS) at 16 weeks, overall survival (OS), bevacizumab safety, and an analysis of VEGF levels before and after TACE with and without bevacizumab.</p> <p>Results</p> <p>Among the 30 subjects enrolled, 9 of 15 randomized to the TACE-O arm and 14 of 15 randomized to the TACE-BEV arm completed all 3 angiograms. At week 14, 3 of 9 (33%) TACE-O subjects and 2 of 14 (14%) TACE-BEV subjects demonstrated neovascularity. The PFS at 16 weeks was 0.19 in the TACE-O arm and 0.79 in the TACE-BEV arm (<it>p </it>= 0.021). The median OS was 61 months in the TACE-O arm and 49 months in the TACE-BEV arm (<it>p </it>= 0.21). No life-threatening bevacizumab-related toxicities were observed. There were no substantial differences in bevacizumab pharmacokinetics compared to historical controls. Bevacizumab attenuated the increase in VEGF observed post-TACE.</p> <p>Conclusions</p> <p>IV bevacizumab was well tolerated in selected HCC subjects undergoing TACE, and appeared to diminish neovessel formation at week 14.</p> <p>Trial registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00049322">NCT00049322</a>.</p

Landscape approaches for ecosystem management in Mediterranean Islands

This book presents a series of essays, drawing on the twm concepts of ecosystem management and landscape approaches, to elucidate and reflect on the present situation and future evolution of Mediterranean islands. This publication brings together contributions from Mediterranean individuals, non-Mediterranean individuals, islanders and non-islanders there is, after all, no geographical limit on who and what we can learn from. The essays presented here each contribute a specific perspective on the future evolution of Mediterranean islands. This book presents a series of essays, drawing on the twin concepts of ecosystem management and landscape approaches, to elucidate and reflect on the present situation and future evolution of Mediterranean islands. This publication brings together contributions from Mediterranean individuals, non-Mediterranean individuals, islanders and non-islanders; there is, after all, no geographical limit on who and what we can learn from. The essays presented here each contribute a specific perspective on the future evolution of Mediterranean islands. Following this introductory chapter, the first section of the book focuses on the contributions that can be made by the discipline of landscape ecology. loannis Vogiatzakis and Geoffrey Griffiths first explain the concepts and relevance of landscape ecology, also presenting and discussing a range of applied tools that can facilitate landscape planning in Mediterranean islands. Louis F. Cassar then reviews the 'offshoot' discipline of restoration ecology, making a strong case for offsetting the environmental damage inflicted on natural ecosystems over millennia of human occupation, with constructive efforts to effectively restore and/or rehabilitate ecosystems. The two following chapters bring the socio-economic dimension into the discussion. Godfrey Baldacchino first presents two contrasting paradigms for the development of island territories, reviewing the dual influences of ecological and economic factors, and exploring ways in which the two can be brought together in successful development strategies. Gordon Cordina and Nadia Farrugia then address the demographic dimension of development, presenting a model to explain the economic costs of high population densities on islands. The third block of chapters expands on the relevance of social and cultural dynamics to the management of Mediterranean Islands. Isil Cakcï, Nur Belkayali and Ilkden Tazebay explain the evolution of the concept of a 'cultural landscape', focusing on the challenges of managing change in landscapes with strong heritage values. The chapter concludes with a case study on the Turkish island of Gökçeada (lmbros), which is experiencing major challenges in balancing the conservation of a cultural landscape on the one hand, and the management of inevitable change, on the other. Elisabeth Conrad then discusses the role of social capital in managing the landscape resources of Mediterranean islands, reviewing the potential for this intangible social fabric to facilitate or impede the sustainable evolution of island territories. The fourth section includes four chapters, each of which addresses a different aspect relevant to policy development and implementation in Mediterranean islands. Salvino Busuttil presents an essay outlining the political influences on the management of coastal landscapes, the latter so relevant to Mediterranean island territories. The essay derives from the author's professional experience in various policy-related institutions for environmental management within the Mediterranean region. Maggie Roe then reflects on issues of landscape sustainability, focusing on the neglected aspect of intelligence. She discusses ways in which landscape research, knowledge and understanding can feed directly into frameworks for 'sustainable' landscape planning. In the subsequent chapter, Adrian Phillips takes from his substantial experience with international landscape policy, reviewing the gradual emergence of international and national landscape 'tools', to draw out lessons for application in Mediterranean islands. In the final chapter of this section, Riccardo Priore and Damiano Galla present a comprehensive discussion of the European Landscape Convention, the first international instrument to focus exclusively on landscape. The authors explain the innovative character of this convention, and discuss its potential implementation in Mediterranean islands. The publication concludes with a series of case studies, highlighting specific constraints, experiences and opportunities in different Mediterranean islands. Theano Terkenli explores the landscapes of tourism in Mediterranean islands - perhaps no other industry has played such a fundamental role in shaping the evolution of Mediterranean landscapes in recent years. The author reviews the theoretical relationship between landscape and tourism across Mediterranean islands, before focusing on the specific case of the Greek Cycladic islands. In the following chapter, Alex Camilleri, Isabella Colombini and Lorenzo Chelazzi present an in-depth review of the context and challenges being faced on a number of minor Mediterranean islands, namely those of the Tuscan archipelago (Elba, Giglio, Capraia, Montecristo, Pianosa, Gorgona and Giannutri), and Comino, the latter forming part of the Maltese archipelago. The comparison between these various islands enables an appreciation of both commonalities across these islands, as well as considerations that are specific to the context of each in dividual island. JeremyBoissevain then adopts an anthropological lens to review the cautionary tale of landscape change in Malta, exploring underlying causes of landscape destruction and limited civil engagement. In the subsequent chapter, Jala Makhzoumi outlines the richness of Mediterranean islands' rural landscapes, focusing on olive landscapes in Cyprus. Her research demonstrates the economic and ecological robustness of various olive cultivation practices, and whilst warning of several threats to such sustainable regimes, she outlines strategies for reconfiguring our approach to rural heritage, in order to integrate such assets into sustainable development strategies. Finally, Stephen Morse concludes the section with an evaluation of sustainable development indicators, and the contribution that these can make towards enhancing the management of Mediterranean island territories. He illustrates his arguments with reference to the two island states of Malta and Cyprus. To conclude, in the final chapter of this publication, we review key insights emerging from the various chapters, and summarize considerations for ecosystem management and sustainable development in Mediterranean Islands. We truly hope that this publication makes some contribution towards safeguarding the "magic' of Mediterranean islands, whilst embracing their dynamic characteristics.Published under the patronage of UNESCO and with the support of the Maltese National Commission for UNESCOpeer-reviewe

Blood Transfusion Requirement and not Preoperative Anaemia is associated with Perioperative Complications following Intracorporeal Robotic Assisted Radical Cystectomy

OBJECTIVES: To assess the prevalence of preoperative anaemia and the impact of preoperative anaemia and blood transfusion requirement on 30- and 90-day complications in a cohort of patients undergoing robotic assisted radical cystectomy with intracorporeal urinary diversion (iRARC). PATIENTS & METHODS: IRARC was performed on 166 patients between June 2011-March 2016. Prospective data was collected for patient demographics, clinical and pathological characteristics, perioperative variables, transfusion requirements and hospital length of stay. Thirty- and 90-day complications were classified according to the modified Memorial Sloan-Kettering Cancer Center Clavian-Dindo system. RESULTS: Preoperative anaemia was common (43.4%) and greatest in patients receiving neoadjuvant chemotherapy (48.6%) (p<0.001). Patients with preoperative anaemia were significantly more likely to have an Ileal conduit (p=0.033), higher cystectomy stage (≥pT3) (p=0.028) and a lower lymph node yield (p=0.031). Preoperative anaemia was not associated with increased perioperative morbidity but was associated with the need for blood transfusion (p=0.001). Blood transfusion was required in 20.4% of patients with intraoperative and postoperative blood transfusion rate was 10.2% and 13.9% respectively. The 30-day all complication rate and 30-day major complication rate was 55.4% and 15.7% respectively while 90-day all complication rate and 90-day major complication rate were 65.7% and 19.3% respectively. Intraoperative blood transfusion was not associated with increased complications but postoperative blood transfusion requirement was independently associated with perioperative morbidity: all 30 day complications (p=0.003), all 90-day complications (p=0.009) and 90-day major complications (p=0.004). CONCLUSION: The presence of preoperative anaemia in patients undergoing iRARC is not associated with increased surgical risk although preoperative anaemic patients were significantly more likely to require blood transfusion. Blood transfusion requirement and specifically postoperative blood transfusion is independently associated with perioperative morbidity and is an important factor for the optimisation of postoperative outcomes