Paul D. Berk

Weight Change and Health Outcomes at 3 Years After Bariatric Surgery Among Individuals With Severe Obesity

IMPORTANCEnSevere obesity (body mass index [BMI] ≥35) is associated with a broad range of health risks. Bariatric surgery induces weight loss and short-term health improvements, but little is known about long-term outcomes of these operations.nnnOBJECTIVEnTo report 3-year change in weight and select health parameters after common bariatric surgical procedures.nnnDESIGN AND SETTINGnThe Longitudinal Assessment of Bariatric Surgery (LABS) Consortium is a multicenter observational cohort study at 10 US hospitals in 6 geographically diverse clinical centers. PARTICIPANTS AND EXPOSURE: Adults undergoing first-time bariatric surgical procedures as part of routine clinical care by participating surgeons were recruited between 2006 and 2009 and followed up until September 2012. Participants completed research assessments prior to surgery and 6 months, 12 months, and then annually after surgery.nnnMAIN OUTCOMES AND MEASURESnThree years after Roux-en-Y gastric bypass (RYGB) or laparoscopic adjustable gastric banding (LAGB), we assessed percent weight change from baseline and the percentage of participants with diabetes achieving hemoglobin A1c levels less than 6.5% or fasting plasma glucose values less than 126 mg/dL without pharmacologic therapy. Dyslipidemia and hypertension resolution at 3 years was also assessed.nnnRESULTSnAt baseline, participants (Nu2009=u20092458) were 18 to 78 years old, 79% were women, median BMI was 45.9 (IQR, 41.7-51.5), and median weight was 129 kg (IQR, 115-147). For their first bariatric surgical procedure, 1738 participants underwent RYGB, 610 LAGB, and 110 other procedures. At baseline, 774 (33%) had diabetes, 1252 (63%) dyslipidemia, and 1601 (68%) hypertension. Three years after surgery, median actual weight loss for RYGB participants was 41 kg (IQR, 31-52), corresponding to a percentage of baseline weight lost of 31.5% (IQR, 24.6%-38.4%). For LAGB participants, actual weight loss was 20 kg (IQR, 10-29), corresponding to 15.9% (IQR, 7.9%-23.0%). The majority of weight loss was evident 1 year after surgery for both procedures. Five distinct weight change trajectory groups were identified for each procedure. Among participants who had diabetes at baseline, 216 RYGB participants (67.5%) and 28 LAGB participants (28.6%) experienced partial remission at 3 years. The incidence of diabetes was 0.9% after RYGB and 3.2% after LAGB. Dyslipidemia resolved in 237 RYGB participants (61.9%) and 39 LAGB participants (27.1%); remission of hypertension occurred in 269 RYGB participants (38.2%) and 43 LAGB participants (17.4%).nnnCONCLUSIONS AND RELEVANCEnAmong participants with severe obesity, there was substantial weight loss 3 years after bariatric surgery, with the majority experiencing maximum weight change during the first year. However, there was variability in the amount and trajectories of weight loss and in diabetes, blood pressure, and lipid outcomes.nnnTRIAL REGISTRATIONnclinicaltrials.gov Identifier: NCT00465829.

Thirty-day Mortality After Bariatric Surgery: Independently Adjudicated Causes of Death in the Longitudinal Assessment of Bariatric Surgery

BackgroundMortality following bariatric surgery is a rare event in contemporary series, making it difficult for any single center to draw meaningful conclusions as to cause of death. Nevertheless, much of the published mortality data come from single-center case series and reviews of administrative databases. These sources tend to produce lower mortality estimates than those obtained from controlled clinical trials. Furthermore, information about the causes of death and how they were determined is not always available. The aim of the present report is to describe in detail all deaths occurring within 30xa0days of surgery in the Longitudinal Assessment of Bariatric Surgery (LABS).MethodsLABS is a ten-center observational cohort study of bariatric surgical outcomes. Data were collected prospectively for bariatric surgeries performed between March 2005 and April 2009. All deaths occurring within 30-days of surgery were identified, and cause of death assigned by an independent Adjudication Subcommittee, blinded to operating surgeon and site.ResultsSix thousand one hundred eighteen patients underwent primary bariatric surgery. Eighteen deaths (0.3%) occurred within 30-days of surgery. The most common cause of death was sepsis (33% of deaths), followed by cardiac causes (28%), and pulmonary embolism (17%). For one patient cause of death could not be determined despite examination of all available information.ConclusionsThis study confirms the low 30-day mortality rate following bariatric surgery. The recognized complications of anastomotic leak, cardiac events, and pulmonary emboli accounted for the majority of 30-day deaths.

Baseline characteristics of participants in the Longitudinal Assessment of Bariatric Surgery-2 (LABS-2) study

Baseline characteristics of participants in the Longitudinal Assessment of Bariatric Surgery-2 (LABS-2) study Steven H. Belle, Ph.D., M.Sc.Hyg.*, Paul D. Berk, M.D., William H. Chapman, M.D., Nicholas J. Christian, Ph.D., Anita P. Courcoulas, M.D., M.P.H., F.A.C.S., Greg F. Dakin, M.D., David R. Flum, M.D., M.P.H., F.A.C.S., Mary Horlick, M.D., Wendy C. King, Ph.D., Carol A. McCloskey, M.D., James E. Mitchell, M.D., Emma J. Patterson, M.D., John R. Pender, M.D., Kristine J. Steffen, Pharm.D., Ph.D., Richard C. Thirlby, M.D., Bruce M. Wolfe, M.D., F.A.C.S., Susan Z. Yanovski, M.D., for The LABS Consortium University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania Columbia University Medical Center, New York, New York East Carolina University, Greenville, North Carolina University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania Weill Cornell University Medical Center, New York, New York University of Washington, Seattle, Washington National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland Neuropsychiatric Research Institute, Fargo, North Dakota Legacy Good Samaritan Hospital, Portland, Oregon Virginia Mason Medical Center, Seattle, Washington Oregon Health and Science University, Portland, Oregon Received January 23, 2013; accepted January 29, 2013

Spexin is a Novel Human Peptide that Reduces Adipocyte Uptake of Long Chain Fatty Acids and Causes Weight Loss in Rodents with Diet-induced Obesity

Microarray studies identified Ch12:orf39 (Spexin) as the most down‐regulated gene in obese human fat. Therefore, we examined its role in obesity pathogenesis.

Reporting weight change: Standardized reporting accounting for baseline weight

BACKGROUNDnAlthough it is recognized that a standardized approach to reporting weight change is essential to meaningful comparisons among cohorts and across studies, consensus is lacking. This study aimed to propose a method of reporting weight change that would allow meaningful comparisons among studies of patients who underwent bariatric surgery and to demonstrate its utility using an example from the Longitudinal Assessment of Bariatric Surgery (LABS).nnnMETHODSnRelationships among several measures of weight change are described. Results from an observational, longitudinal cohort study of adults undergoing bariatric surgery and from simulation studies are used to illustrate the proposed method.nnnRESULTSnBaseline weight is a critical parameter when assessing weight change. Men undergoing a bariatric procedure other than gastric bypass or adjustable band tended to have greater weight loss 12 months after surgery than men undergoing gastric bypass when not accounting for baseline weight, but the opposite was found when results were adjusted for baseline weight. Simulation results show that with relatively modest sample sizes, the adjusted weight loss was significantly different between the 2 groups of men.nnnCONCLUSIONnA consistent metric for reporting weight loss after bariatric surgery is essential to interpret outcomes across studies and among subgroups. The baseline weight adjusted percent of weight loss (A%WL) uses a standard population (e.g., the LABS cohort) to account for differences between cohorts with respect to baseline weight, and its use can change the interpretation of results compared with an unadjusted measure.

Facilitated long chain fatty acid uptake by adipocytes remains upregulated relative to BMI for more than a year after major bariatric surgical weight loss

This study examined whether changes in adipocyte long chain fatty acid (LCFA) uptake kinetics explain the weight regain increasingly observed following bariatric surgery.

An editor's look‐back

Most patients infected with hepatitis C virus (HCV) develop chronic hepatitis. Unfortunately, the pathological evolution of this disease over time is not completely understood. We studied 70 HCV-positive patients, from whom 2 to 10 liver biopsy specimens (mean, 3.9) had been obtained during an interval of 1 to 26 years (mean, 8.8 years). Each biopsy specimen was evaluated independently by four pathologists who each provided a numerical score for the grade of portal/periportal necroinflammation (0-4), grade of lobular necroinflammation (0-4), their sum (final grade), and the stage of fibrosis (1-4). The scores were correlated with progression of disease, if any, and transition to cirrhosis. During followup, 35 patients (50%) developed cirrhosis. Cirrhosis developed in all patients with high final grade (>5) of necroinflammation on initial biopsy who were followed for 10 years and in 96% of paS14 BERK HEPATOLOGY, February 2006

The Last Hurrah

This issue of Seminars in Liver Disease, devoted to gut microbiota and hepatic disease and guest edited by Professor EamonnM. M. Quigley, is the journal’s 144th regular quarterly issue since Seminarswas launched in 1981. Its content deals with such currently hot topics as the nature and mechanisms of the ongoing conversation nowknown to occur between the gut and the liver, the implications of that conversation for liver and biliary tract disease, and experimental therapeutic innovations such as fecal microbiota transplants (FMTs), a subject probably considered too revolting to be included in polite conversation at the time of that first issue. Indeed, perusal of the tables of contents of Seminars’ 144 issues provides an interesting summary of the focus of both the science and clinical practice of hepatology over the past 36 years. Although the titles of the issues confirm our discipline’s continuing interest in the diagnosis, pathophysiology, andmanagement of themost prevalent liver diseases— the various forms of viral hepatitis, alcoholic hepatitis, drugrelated liver diseases, diseases of the biliary tract, and a selection of metabolic and genetic disorders—the titles of individual articles confirm the subtle, but progressive infiltration of more and more basic science: not only good old biochemistry and physiology, but also molecular biology, cell biology, immunology, virology, the pathobiology of fibrosis, and modern genetics, among others, into our content. This is as it should be, indeed as it must be, if hepatology as a discipline is to remain, in the service of our patients, at the cutting edge of clinical medicine. The goal of Seminars from the very beginning, established by the original Editorial Board and strongly supported by our Publisher, Henry Stratton, and our subtle, low-key, behindthe-scenes advisor, Hans Popper, was to provide a platform for our readers that—over time—would keep them up-to-date with what was important in both the clinical practice and scientific underpinnings of contemporary hepatology. We believe that we have largely accomplished that goal, a belief supported by Seminars’ Impact Factor, which has averaged 5.9 over the past 10 years, ranking 11th among 78 Gastroenterology and Hepatology journals for which such data are collected. The durable value of the reviews published in Seminars is suggested by its cumulative 5-year Impact Factor, as calculated by Journal Citation Reports. The latest (2015) value is 7.50, ranking 8th among the 78 GI/Liver competitors. The next issue of Seminars will reflect the ideas of my successors, Drs. Gregory Gores and Jordi Bruix. Both are experienced members of Seminars’ Editorial Board, and each has served—over the years—as Guest Editor of several high Impact Factor issues. They fully share my goals for Seminars and those of our founders, but will bring their own new ideas and a new energy to the enterprise, along with an explicit goal to further enhance its impact. It goes without saying that I wish them and the new Editorial Board every success. Editing Seminars has been one of my major professional activities for more than three decades. However, simultaneously with the launching of Seminars, my professional identity and research interests were both evolving. I transformed from a Nathaniel Berlinand Louis Wassermantrained hematologist, interested in myeloproliferative diseases, hemolytic anemias, and the hematologic aspects of bilirubin metabolism, into a Sheila Sherlock-trained hepatologist, focused not just on general clinical hepatology, but more specifically, on hereditary hyperbilirubinemias, hepatic bilirubin disposition, and—in parallel—the hepatic disposition of other classes of organic anions, notably longchain fatty acids (LCFAs). The latter led inexorably to an interest in fatty liver. It was virtually dogma in the early 1980s that LCFA entered cells by passive diffusion.My colleagues and Iwere among the first to establish that LCFAs entered at least some cell types, notably adipocytes, hepatocytes, and cardiac myocytes, by regulatable, facilitated transport. These observations were not initially well received; for several years any reviewer of our manuscripts or grant applications had merely to state, in

New benchmarks for Seminars in Liver Disease.

With the publication of its November 2010 issue, Seminars in Liver Disease completed 30 years of publication. Its first issue, in February 1981, appeared in precisely the same month as the first issue of Hepatology. Having been there at the beginning, I can attest that the launching of these journals was accompanied by considerable angst on the part of those involved in both projects. We are now 32 years into the process and both have surpassed their founders’ wildest dreams. They have thrived in parallel with the astonishing progress in both the scientific underpinnings and the clinical practice of hepatology, as further reflected in the progressive growth of the strikingly vibrant annual meetings of related professional societies such as AASLD and EASL. As indicated on the cover of this (its November 2012) issue, in the past 2 years Seminars in Liver Disease has seen an appreciable increase in its ISI Impact Factor (IF) to a new high of 7.053 (►Fig. 1). Although admittedly imperfect, the IF is widely considered a measure of the esteem in which journals are held both by their regular readers and by their respective fields. The Editors and Editorial Board of Seminars, as well as our publisher, Thieme, are highly appreciative of this vote of confidence in the value of our efforts. But what does it really mean? It may be instructive to review how the IF is determined. By definition, the 2011 IF is the total number of citations during 2011 of articles published in Seminars during the 2 preceding years, 2009 and 2010. Seminars published 75 articles during those 2 years, which were cited a total of 529 times in 2011, for an IF of 529/75 1⁄4 7.053. Sixty-eight of the 75 published articles (90.1%) were cited at least once. All seven articles that were not cited at all were either Forewords to an issue (n 1⁄4 2) or CPC-type articles in the Diagnostic Problems in Hepatology series (n 1⁄4 5). Though infrequently cited, a surveyof our readership someyears ago indicated that the latter were, nonetheless, widely read and very popular. The most frequently cited 15 articles, representing 20% of the total, are drawn from every issue published in 2009– 2010.1–15 Citations, as reflected in the IF, are only one measure of the interest generated by an article and its ultimate impact on the field, and the IF, as currently calculated, may not be the best indicator of the real impact of a journal. The ability of readers to download published articles from the Internet has grown dramatically, and the number of downloads of specific articles typically far exceeds the number of times they are cited in subsequent publications. By now Thieme supports a complete online archive of all articles ever published in Seminars in Liver Disease, going back to the very earliest, published in 1981. Between 2004 and late September 2012, the 100 articles most frequently downloaded from this archive15–114 were downloaded 265,307 times! Individual articles in this top 100 were downloaded 1,549 to 7,295 times! Seminars authors are almost exclusively engaged in various academic aspects of hepatic medicine. Their peers are also largely academicians, who are also writing articles, for Seminars and other publications, on the same and related topics. For these individuals, a high IF suggests that their work is known to and acknowledged by their peers. It is therefore a matter of some personal gratification. Our overall readership is a larger andmore diverse group than our authors. Although we have not formally surveyed their professional roles and interests in the past decade, our impression is that—in addition to our authors—theyare principally a sophisticatedgroup of clinically engaged physicians who turn to Seminars for 5.814 5.000 5.171 5.286 7.053