tbuckley/cabot-search huggingface dataset:
Bariatric Surgery and Long-term Durability of Weight Loss
Authors: Matthew L. Maciejewski, David E. Arterburn, Lynn Van Scoyoc, Valerie A. Smith, William S. Yancy, Hollis J. Weidenbacher, Edward H. Livingston, Maren K. Olsen
Journal: JAMA Surgery (2016)

Bariatric surgery induces significant weight loss for severely obese patients, but there is limited evidence of the durability of weight loss compared with nonsurgical matches and across bariatric procedures.To examine 10-year weight change in a large, multisite, clinical cohort of veterans who underwent Roux-en-Y gastric bypass (RYGB) compared with nonsurgical matches and the 4-year weight change in veterans who underwent RYGB, adjustable gastric banding (AGB), or sleeve gastrectomy (SG).In this cohort study, differences in weight change up to 10 years after surgery were estimated in retrospective cohorts of 1787 veterans who underwent RYGB from January 1, 2000, through September 30, 2011 (573 of 700 eligible [81.9%] with 10-year follow-up), and 5305 nonsurgical matches (1274 of 1889 eligible [67.4%] with 10-year follow-up) in mixed-effects models. Differences in weight change up to 4 years were compared among veterans undergoing RYGB (n = 1785), SG (n = 379), and AGB (n = 246). Data analysis was performed from September 9, 2014, to February 12, 2016.Bariatric surgical procedures and usual care.Weight change up to 10 years after surgery through December 31, 2014.The 1787 patients undergoing RYGB had a mean (SD) age of 52.1 (8.5) years and 5305 nonsurgical matches had a mean (SD) age of 52.2 (8.4) years. Patients undergoing RYGB and nonsurgical matches had a mean body mass index of 47.7 and 47.1, respectively, and were predominantly male (1306 [73.1%] and 3911 [73.7%], respectively). Patients undergoing RYGB lost 21% (95% CI, 11%-31%) more of their baseline weight at 10 years than nonsurgical matches. A total of 405 of 564 patients undergoing RYGB (71.8%) had more than 20% estimated weight loss, and 224 of 564 (39.7%) had more than 30% estimated weight loss at 10 years compared with 134 of 1247 (10.8%) and 48 of 1247 (3.9%), respectively, of nonsurgical matches. Only 19 of 564 patients undergoing RYGB (3.4%) regained weight back to within an estimated 5% of their baseline weight by 10 years. At 4 years, patients undergoing RYGB lost 27.5% (95% CI, 23.8%-31.2%) of their baseline weight, patients undergoing AGB lost 10.6% (95% CI, 0.6%-20.6%), and patients undergoing SG lost 17.8% (95% CI, 9.7%-25.9%). Patients undergoing RYGB lost 16.9% (95% CI, 6.2%-27.6%) more of their baseline weight than patients undergoing AGB and 9.7% (95% CI, 0.8%-18.6%) more than patients undergoing SG.Patients in the Veterans Administration health care system lost substantially more weight than nonsurgical matches and sustained most of this weight loss in the long term. Roux-en-Y gastric bypass induced significantly greater weight loss among veterans than SG or AGB at 4 years. These results provide further evidence of the beneficial association between surgery and long-term weight loss that has been demonstrated in shorter-term studies of younger, predominantly female populations.
Breast Cancer Incidentally Detected by 18F-Choline PET/CT in a Patient With Recurrent Prostate Carcinoma
Authors: Manuela Vadrucci, Laura Gilardi, Chiara Maria Grana
Journal: Clinical Nuclear Medicine (2016)

A 79-year-old man underwent 18F-choline PET/CT for biochemical recurrence of prostate cancer. PET/CT images showed an area of elevated radiopharmaceutical uptake in a left pelvic node. In addition, a small focus of increased radiolabeled choline accumulation was seen in a small nodule of the right breast, which was later histologically characterized as an infiltrating ductal carcinoma. In this patient, choline PET/CT was critical in localizing prostate cancer recurrence and identifying a second unsuspected malignancy.
Tumor Heterogeneity Detected by 68Ga DOTATOC and 18F-FDG PET/CTs in One Malignant Insulinoma With Involvement of the Portal Splenic Confluence and Ovarian Metastases
Authors: Ophélie Bélissant Benesty, Thibaut Cassou-Mounat, Camille Vatier, Jean-Noël Talbot, Françoise Montravers
Journal: Clinical Nuclear Medicine (2016)

A 67-year-old woman was referred for staging of an insulinoma. CT has shown a pancreatic tumor, a portal thrombus, and an ovarian mass presumed not to be related with the insulinoma. These three lesions were highly positive on 68Ga DOTATOC PET/CT, leading to the hypothesis of a malignant insulinoma with neoplastic vein thrombus and ovarian metastasis, which was subsequently confirmed histologically. Despite severe hypoglycemia preventing fasting, 18F-FDG PET/CT was informative, showing significant uptake by the thrombus, which corresponded to the most aggressive lesion (Ki67 of 3.5% for the primary pancreatic tumor and 19.6% for the thrombus).
Transvenous neurostimulation for central sleep apnoea: a randomised controlled trial
Authors: Maria Rosa Costanzo, Piotr Ponikowski, Shahrokh Javaheri, Ralph Augostini, Lee Goldberg, Richard Holcomb, Andrew Kao, Rami N Khayat, Olaf Oldenburg, Christoph Stellbrink, William T Abraham
Journal: The Lancet (2016)
Global Lung Function Initiative reference equations better describe a middle-aged, healthy French population than the European Community for Steel and Coal values
Authors: Sébastien Hulo, Virginie de Broucker, Jonathan Giovannelli, Nathalie Cherot-Kornobis, Véronique Nève, Annie Sobaszek, Luc Dauchet, Jean-Louis Edmé
Journal: European Respiratory Journal (2016)

Spirometry plays a pivotal role in the clinical evaluation and management of respiratory diseases. Pulmonary function varies with age, height, sex and ethnicity, and test results need to be compared with predicted values and lower limits of normal (LLN) and upper limits of normal (ULN), that are appropriate for the individual being tested [1]. The European Community for Steel and Coal (ECSC) first published reference spirometric values for healthy non-smokers in 1983 based on a collation of regression equations [2]. In 2012, the Global Lung Function Initiative (GLI) presented prediction equations derived from measured values of a large population [1]. These newer statistical procedures provided us for the first time with a single equation for ages from 3 years through to 95 years. Measured values are converted to z-scores which describe how many standard deviations a measured value differs from the predicted value and these are independent of sex, age and height. GLI reference equations better describe a middle-aged, healthy French population than the ECSC values <http://ow.ly/xF773022Xhy>
Ultrasound vs Angiography for Drug-Eluting Stent Implantation
Authors: Abdullah Tunçez, Bülent Behlül Altunkeser
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
NUDT15 Hydrolyzes 6-Thio-DeoxyGTP to Mediate the Anticancer Efficacy of 6-Thioguanine
Authors: Nicholas C.K. Valerie, Anna Hagenkort, Brent D.G. Page, Geoffrey Masuyer, Daniel Rehling, Megan Carter, Luka Bevc, Patrick Herr, Evert Homan, Nina G. Sheppard, Pål Stenmark, Ann-Sofie Jemth, Thomas Helleday
Journal: Cancer Research (2016)

Abstract Thiopurines are a standard treatment for childhood leukemia, but like all chemotherapeutics, their use is limited by inherent or acquired resistance in patients. Recently, the nucleoside diphosphate hydrolase NUDT15 has received attention on the basis of its ability to hydrolyze the thiopurine effector metabolites 6-thio-deoxyGTP (6-thio-dGTP) and 6-thio-GTP, thereby limiting the efficacy of thiopurines. In particular, increasing evidence suggests an association between the NUDT15 missense variant, R139C, and thiopurine sensitivity. In this study, we elucidated the role of NUDT15 and NUDT15 R139C in thiopurine metabolism. In vitro and cellular results argued that 6-thio-dGTP and 6-thio-GTP are favored substrates for NUDT15, a finding supported by a crystallographic determination of NUDT15 in complex with 6-thio-GMP. We found that NUDT15 R139C mutation did not affect enzymatic activity but instead negatively influenced protein stability, likely due to a loss of supportive intramolecular bonds that caused rapid proteasomal degradation in cells. Mechanistic investigations in cells indicated that NUDT15 ablation potentiated induction of the DNA damage checkpoint and cancer cell death by 6-thioguanine. Taken together, our results defined how NUDT15 limits thiopurine efficacy and how genetic ablation via the R139C missense mutation confers sensitivity to thiopurine treatment in patients. Cancer Res; 76(18); 5501–11. ©2016 AACR.
WT1 Expression at the Diagnosis of Childhood AML Has No Prognostic Value but Corresponds with the Biological Characteristics of Leukemic Cells - Results From European Multicenter Study.
Authors: Karolina Kramarzova, Andre Willasch, Bernd Gruhn, Ludmila Boublikova, Hermann Kreyenberg, Eva Rettinger, Martin Zimmermann, Jan Stary, Dirk Reinhardt, Ursula Creutzig, Andrea Pession, Giovanni Cazzaniga, Tiziana Coliva, Peter Bader, Jan Trka
Journal: Blood (2010)
Non-alcoholic fatty liver disease (NAFLD): summary of NICE guidance
Authors: Jessica Glen, Lefteris Floros, Chris Day, Rachel Pryke
Journal: BMJ (2016)

#### What you need to know

There has been a lack of national guidance and care pathways for primary care on when to offer testing for NAFLD. Investigation and referral of suspected NAFLD vary widely. There is currently no licensed treatment for NAFLD, and most people are managed by their general practitioner with a focus on lifestyle advice such as weight loss.

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease from fatty liver to non-alcoholic steatohepatitis, fibrosis, and cirrhosis. At the least advanced end of the spectrum, non-alcoholic fatty liver (NAFL) is an excess of fat in the liver (steatosis) present in 20-30% of the general population and is largely asymptomatic.1 2 3 4 Currently, diagnosis of NAFLD is most commonly made through incidental findings, such as ultrasonography for investigation of persistently abnormal liver function tests, when other suspected causes have been ruled out.

In around 5-6% of patients with NAFL only the condition progresses to non-alcoholic steatohepatitis (NASH), fibrosis, or cirrhosis (see fig 1⇓).5 In this small group there is a risk of death from liver failure or hepatocellular carcinoma, or needing a liver transplant.1 The number of hospital admissions for liver damage at the more severe end of the NAFLD spectrum, fibrosis and cirrhosis, are increasing every year.6



Fig 1  Spectrum of non-alcoholic fatty …
Therapy for Posttraumatic Stress and Alcohol Dependence—Reply
Authors: Edna B. Foa, Carmen P. McLean, David Yusko
Journal: JAMA (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Frequency of concurrent gene mutations and copy number alterations in circulating cell-free DNA (cfDNA) from refractory metastatic CRC patients.
Authors: M. Pia Morelli, Michael J. Overman, Eduardo Vilar Sanchez, Van Karlyle Morris, Imad Shureiqi, Chris R. Garrett, David R. Fogelman, Kanwal Pratap Singh Raghav, Bryan K. Kee, Laurel Deaton, Cathy Eng, Robert A. Wolff, Dragan Sebisanovic, LaiMun Siew, Aubrey Zapanta, Gangwu Mei, Ben Schiller, Helmy Eltoukhy, AmirAli Talasaz, Scott Kopetz
Journal: Journal of Clinical Oncology (2014)

11117 Background: cfDNA allows non-invasive assessment of gene mutations, but has not been reported with copy number alterations. Methodologies to integrate mutation and copy number would allow improved insights into mechanisms of resistance and therapeutic opportunities. Methods: cfDNA extracted from metastatic CRC patient (pt) plasma samples were analyzed by GUARDANT sequencing technology for mutation and amplification of 54 genes. The lower limit of detection was 0.1% mutant alleles in a wild-type background. All patients were enrolled in the ATTACC program for mCRC patients who progressed on standard treatment, and had sequencing of the primary tumor performed for a 46-gene panel. Results: 71 pt plasma samples were analyzed. All pts were refractory to 5-FU-based therapy, with 49 pts previously treated with anti-EGFR monoclonal antibodies (mAbs). In patients treated with EGFR mAbs, 30% of pts (n=15) had detection of KRAS mutations not detectable in the primary tumor, compared to 5% (n=1) of pts without EGFR mAb treatment (odds ratio 8.6, P=0.027). In 6 of the 15 cases, newly detectable KRAS mutations were associated with KRAS gene amplification, compared to 0 of 16 cases with KRAS mutations detected in the primary tumor (P=0.007). 7 ectodomain mutations in EGFR that may alter binding affinity of EGFR mAbs were detected in EGFR mAb treated patients, including S492R (n=4) and three previously unreported mutations G465V, I491R, K467I; concurrent EGFR amplifications were present in 6 of the 7 cases. 14% of EGFR mAbs treated patients developed detectable MET amplifications, which co-existed with KRAS or EGFR mutations in 4 of the 7 cases. Amplifications in EGFR, BRAF, MYC, and SMO were detected in the plasma in 23%, 11%, 11%, and 4% of cases, respectively, representing rates higher than reported in untreated primary tumors. Conclusions: Advances in sequencing and bioinformatics allow detection of copy number alternations from cfDNA in plasma. Copy number alterations in treatment refractory mCRC are more common than previously described, and frequently co-exist with mutations after EGFR mAb treatment.
Premarital Screening for HIV
Authors: C. M. G. Buttery
Journal: JAMA (1988)

To the Editor.  —The analysis of cost-effectiveness and cost efficiency of mass premarital screening for human immunodeficiency virus (HIV) by Cleary et al 1 and the letters to the editor in response to it 2 left out a major factor. There was no discussion of what should be done to prevent the asymptomatic HIV-positive individual from transmitting HIV. In the table included with the letters to the editor 2 the last column is labeled Cost per Prevention.  I know of no studies to show that screening populations, premaritally or otherwise, leads to prevention of infection with HIV.  In convincing our state legislature that there is little value in mass screening of any kind and in preparing for meetings with a select committee of the legislature to study major acquired immunodeficiency syndrome issues, it would be helpful if authors of articles that could have an impact on policy-making would state their
ICE II: An investigational randomized phase II study on epirubicin (E) plus cyclophospamide (C) (or CMF) versus nab-paclitaxel plus capecitabine (PX) as adjuvant chemotherapy for elderly nonfrail patients with an increased risk for relapse of a primary carcinoma of the breast.
Authors: G. Von Minckwitz
Journal: Journal of Clinical Oncology (2010)

TPS104
A first-in-human phase I study of the anti-PD-1 antibody PDR001 in patients with advanced solid tumors.
Authors: Aung Naing, Hans Gelderblom, Justin F. Gainor, Patrick M. Forde, Marcus Butler, Chia-Chi Lin, Sunil Sharma, Maria Ochoa de Olza, Jan H.M. Schellens, Jean-Charles Soria, Matthew H. Taylor, Antonio P. Silva, Zhonggai Li, Sanela Bilic, Scott Cameron, Jeffrey R. Infante
Journal: Journal of Clinical Oncology (2016)

3060 Background: PDR001 is a humanized anti-PD-1 IgG4 antibody that blocks the binding of PD-L1 and PD-L2 to PD-1. PDR001 binds to PD-1 with high affinity and inhibits the biological activity of PD-1. Methods: Phase I dose escalation study of PDR001 given i.v. Q2W or Q4W to adult patients with advanced solid tumors. A Bayesian linear model estimating the dose–exposure relationship and a Bayesian logistic regression model with overdose control were used to guide dose escalation. Preliminary population PK analysis was conducted to estimate PK parameters and assess the impact of weight as a covariate on clearance and volume of distribution. Results: In the dose escalation part of the study, 58 patients have been treated with PDR001 at 5 dose levels and schedules: 1 mg/kg Q2W (16 pts); 3 mg/kg Q2W (15), 10 mg/kg Q2W (11), 3 mg/kg Q4W (6) and 5 mg/kg Q4W (10). 27/58 patients have been treated for > 3 cycles (cycle length: 28 days), and 27/58 remain on treatment at the time of abstract preparation. No dose limiting toxicity was reported. The most common AEs included: nausea, fatigue, anemia, diarrhea, dyspnea, vomiting, abdominal pain and headache. Three cases of hypothyroidism suspected to be related to PDR001 were reported. A single case of grade 3 autoimmune colitis was the only serious AE suspected to be related to PDR001. Approximately dose-proportional increases in exposure were observed from 1–10 mg/kg. PDR001 achieves an AUC0-336h of approximately 1000 µg*day/mL at cycle 3 with 3 mg/kg Q2W or 5 mg/kg Q4W. Based on the population PK analysis, a flat dose of 400 mg Q4W is predicted to achieve mean steady-state Ctrough concentrations of approximately 31 µg/mL (90% CI: 22–42 µg/mL), which exceeds the ex vivo EC50 for PD-1 blockade. The recommended phase 2 dose (RP2D) for PDR001 is therefore 400 mg Q4W. An alternative dosing regimen of 300 mg Q3W is expected to achieve similar exposure to 400 mg Q4W. Conclusions: Based on the preliminary data, PDR001 was well tolerated with a safety profile similar to those of other marketed anti-PD-1 antibodies. Based on the available PK and safety data described above, the RP2D of PDR001 has been declared as 400 mg i.v. Q4W, or 300 mg i.v. Q3W as an option for more convenient scheduling in combination treatment regimens. Clinical trial information: NCT02404441.
Understanding and Communicating Medical Risks for Living Kidney Donors: A Matter of Perspective
Authors: Krista L. Lentine, Dorry L. Segev
Journal: Journal of the American Society of Nephrology (2016)

Communicating the current knowledge of medical outcomes after live kidney donation necessary to support donor candidates in well informed decision-making requires grounding in perspectives of comparison. Baseline risk (without donating), risk attributable to donation, and absolute risk (after donating) need to be considered. Severe perioperative complications and death are rare, but vary by demographic, clinical, and procedure factors. Innovative capture of “healthy” controls designed to simulate donor selection processes has identified higher risk of ESRD attributable to donation in two studies; importantly, however, the absolute 15-year ESRD incidence in donors remains very low (0.3%). In the first decade after donation, the risk of all-cause mortality and cardiovascular events is no higher than in healthy nondonors. Pregnancies in donors may incur attributable risk of gestational hypertension or preeclampsia (11% versus 5% incidence in one study). A modest rise in uric acid levels beginning early after donation, and a small (1.4%) increase in the 8-year incidence of gout, have also been reported in comparisons to healthy nondonors. As in the general population, postdonation outcomes vary by race, sex, and age. Efforts to improve the counseling and selection of living donors should focus on developing tools for tailored risk prediction according to donor characteristics, and ideally, compared with similar healthy nondonors.
Apoptotic activity in patient serum while on an acai juice product in the setting of a slowly rising PSA.
Authors: Elizabeth Kessler, Lih-Jen Su, Xian Lu, Diana Morales, Nicole Chronister, Mary Anduha, Michael Wacker, Xiaoping Yang, Thomas W. Flaig, L. Michael Glode, Elaine Tat Lam
Journal: Journal of Clinical Oncology (2013)

e16055 Background: For patients with a slowly rising PSA, the timing of androgen deprivation therapy (ADT) initiation is highly debated given the long term side effects. In this setting, numerous nutraceuticals, or plant derivatives, such as grape seed, milk thistle, or pomegranate have been shown to slow the growth of prostate cancer (PCa). The acai berry has been shown to be rich in flavinoids with high antioxidant properties and was evaluated in this phase II single-institution study in asymptomatic PCa patients with a rising PSA. The primary endpoint was decline in PSA of 50% from baseline. While flavinoids have been shown to induce cell cycle arrest, understanding the actions of the mix of phytochemicals has not been rigorously undertaken for the acai berry. It has shown proapoptotic effects in vitro on leukemic cell lines, and decreased cytokine production correlated with subsequent anti-esophageal tumorogenesis effects in vivo. In order to better understand the mechanism of action of acai, patient serum samples were analyzed in vitro. Methods: While on trial, patients consumed 2oz of acai juice product daily for 30 weeks. Two serum samples were drawn at weeks 0, 2, 6, and 18 for correlative analysis with the M30 Apoptosense ELISA. This measures caspase cleaved Keratin18 (ccK18) as a marker of early apoptotic activity. Results: An increase from baseline in ccK18 was seen at 2 weeks in a majority of patients (13/19; p= 0.12). Additionally, the one clinical responder on trial had a significantly higher level of ccK18 throughout the trial with a peak at week 6. Baseline ccK18 values did not correlate with clinical outcome (Spearman coefficient r=-0.13, p=0.6). Conclusions: Nutraceuticals may offer a well-tolerated treatment option for slowing the growth of prostate cancer as evidenced by the prolongation in doubling time in 86% of patients in this trial. The rise of ccK18 at week 2 and elevated levels in the responder’s serum suggest there is a pro-apoptotic treatment effect with acai. Additional cytokine analysis, and ratio of necrotic death to apoptotic death is underway in order to compare additional mechanisms. This initial evaluation offers early insight of the mechanism of action of acai in PCa.