tbuckley/cabot-search huggingface dataset:
A1C Targets Should Be Personalized to Maximize Benefits While Limiting Risks
Authors: Matthew C. Riddle, Hertzel C. Gerstein, Rury R. Holman, Silvio E. Inzucchi, Bernard Zinman, Sophia Zoungas, William T. Cefalu
Journal: Diabetes Care (2018)

A set of guidance statements recently published by the American College of Physicians (ACP) advocates relaxation of goals for control of glycated hemoglobin (A1C) by people with type 2 diabetes (T2D) (1). This publication advises that “clinicians should reevaluate HbA1c levels and revise treatment strategies on the basis of changes in the balance of benefits and harms.” Specifically, it proposes reducing pharmacotherapy for any person when A1C is <6.5%, seeking a level between 7 and 8% for “most patients,” and aiming only to minimize symptoms without any specific A1C goal for those over age 80 years or with chronic medical conditions likely to limit life expectancy. These recommendations are at odds with those of other professional organizations, including the American Diabetes Association (ADA) (2–5). We believe the ACP recommendations fail to consider several important bodies of scientific evidence, and if they are widely adopted in clinical practice, the recent progress in management of diabetes may be threatened. Each of the ACP’s recommendations requires specific comments. These will be followed by a more general discussion of our concerns.

The ACP’s main justification for decreasing therapy whenever A1C is <6.5% is the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial’s finding of ∼20% increased mortality—mostly from cardiovascular (CV) events—when the median A1C attained by intensive treatment was 6.4% (6). However, this generalized advice does not acknowledge experience in other trials. In contrast to ACCORD, the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial (7) and the Veterans Affairs Diabetes Trial (VADT) (8), which similarly enrolled high-risk patients and sought A1C levels <7%, did not show increased short-term CV risk or mortality. Importantly, the newly diagnosed, low-risk participants in the UK Prospective Diabetes Study (UKPDS) also showed no tendency toward increased early mortality …
Rituximab Is Ineffective for Treatment of Fatigue in Primary Biliary Cholangitis: A Phase 2 Randomized Controlled Trial
Authors: Amardeep Khanna, Laura Jopson, Denise Howel, Andrew Bryant, Andrew Blamire, Julia L. Newton, David E. Jones
Journal: Hepatology (2018)

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. Half of patients experience debilitating fatigue, which is currently untreatable. Previous studies have shown muscle bioenergetic abnormalities in PBC, including increased muscle acidosis with exercise linked to the antimitochondrial antibody (AMA) diagnostic of the disease, and reduced anaerobic threshold. In this study we addressed the hypothesis that fatigue in PBC is driven by muscle bioenergetic abnormality related to AMA, and that AMA reduction with B-cell depletion therapy will improve fatigue. In our single-center phase 2 randomized controlled trial, 57 participants aged 18 years or older with PBC and moderate to severe fatigue were randomized to receive two doses of either rituximab (1000 mg) or saline (placebo). The primary outcome measure was fatigue severity assessed using the PBC-40 fatigue domain at 3 months. Secondary outcome measures included patient-reported outcomes and immunological and bioenergetics disease parameters. Experimental outcomes included biochemical markers of disease severity. Improvement in fatigue score at 3 months was seen in both arms, with no significant difference (adjusted mean difference -0.9 [95% confidence interval -4.6 to 3.1]). Little difference was observed in other patient-reported outcomes or physical activity. Significant anaerobic threshold improvement was seen in the rituximab group, only but this was not associated with fatigue improvement. No treatment-emergent serious adverse events were seen. Conclusions: Rituximab was safe over the 12-month study period but showed no evidence of effectiveness for the treatment of fatigue in PBC. Anaerobic threshold improvement was seen, potentially linking AMA with muscle bioenergetics dysfunction; however, this was not related to improvement in fatigue. Rituximab had some evidence of a beneficial effect on alkaline phosphatase levels in this largely ursodeoxycholic acid (UDCA)-responding, early-disease stage cohort. (Hepatology 2018; 00:000-000).
Association of Smoking Status With Recurrence, Metastasis, and Mortality Among Patients With Localized Prostate Cancer Undergoing Prostatectomy or Radiotherapy
Authors: Beat Foerster, Carmen Pozo, Mohammad Abufaraj, Andrea Mari, Shoji Kimura, David D’Andrea, Hubert John, Shahrokh F. Shariat
Journal: JAMA Oncology (2018)

<h3>Importance</h3> Studies investigating the association of cigarette smoking with prostate cancer incidence and outcomes have revealed controversial results. <h3>Objective</h3> To systematically review and analyze the association of smoking status with biochemical recurrence, metastasis, and cancer-specific mortality among patients with localized prostate cancer undergoing primary radical prostatectomy or radiotherapy. <h3>Data Sources</h3> A systematic search of original articles published between January 2000 and March 2017 was performed using PubMed, MEDLINE, Embase, and Cochrane Library databases in March 2017. <h3>Study Selection</h3> Observational studies reporting Cox proportional hazards regression or logistic regression analyses were independently screened. <h3>Data Extraction and Synthesis</h3> This systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and the Cochrane Handbook for Systematic Reviews of Interventions. Available multivariable hazard ratios (HRs) and corresponding 95% CIs were included in quantitative analysis. A risk-of-bias assessment was completed for nonrandomized studies. <h3>Main Outcomes and Measures</h3> Prespecified outcomes of interest were biochemical recurrence, metastasis, and cancer-specific mortality. <h3>Results</h3> A total of 5157 reports were identified, of which 16 articles were selected for qualitative analysis and 11 articles were selected for quantitative analysis. All included studies were observational and nonrandomized and comprised a total of 22 549 patients. Overall, 4202 patients (18.6%) were current smokers. The overall median follow-up was 72 months. Current smokers had a statistically significantly higher risk of biochemical recurrence (HR, 1.40; 95% CI, 1.18-1.66;<i>P</i> &lt; .001 [10 studies]), as did former smokers (HR, 1.19; 95% CI, 1.09-1.30;<i>P</i> &lt; .001 [7 studies]). Current smokers were also at a higher risk of metastasis (HR, 2.51; 95% CI, 1.80-3.51;<i>P</i> &lt; .001 [3 studies]) and cancer-specific mortality (HR, 1.89; 95% CI, 1.37-2.60;<i>P</i> &lt; .001 [5 studies]), whereas former smokers were not (metastasis: HR, 1.61; 95% CI, 0.65-3.97;<i>P</i> = .31 [2 studies]; cancer-specific mortality: HR, 1.05; 95% CI, 0.81-1.37;<i>P</i> = .70 [4 studies]). <h3>Conclusions and Relevance</h3> Current smokers at the time of primary curative treatment for localized prostate cancer are at higher risk of experiencing biochemical recurrence, metastasis, and cancer-specific mortality.
The Body’s Largest Artery Aids in Building a Better Trachea
Authors: Rebecca Voelker
Journal: JAMA (2018)

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
Hypertension and increased endothelial mechanical stretch promote monocyte differentiation and activation: roles of STAT3, interleukin 6 and hydrogen peroxide
Authors: Roxana Loperena, Justin P Van Beusecum, Hana A Itani, Noah Engel, Fanny Laroumanie, Liang Xiao, Fernando Elijovich, Cheryl L Laffer, Juan S Gnecco, Jonathan Noonan, Pasquale Maffia, Barbara Jasiewicz-Honkisz, Marta Czesnikiewicz-Guzik, Tomasz Mikolajczyk, Tomasz Sliwa, Sergey Dikalov, Cornelia M Weyand, Tomasz J Guzik, David G Harrison
Journal: Cardiovascular Research (2018)

Monocytes play an important role in hypertension. Circulating monocytes in humans exist as classical, intermediate, and non-classical forms. Monocyte differentiation can be influenced by the endothelium, which in turn is activated in hypertension by mechanical stretch. We sought to examine the role of increased endothelial stretch and hypertension on monocyte phenotype and function. Human monocytes were cultured with confluent human aortic endothelial cells undergoing either 5% or 10% cyclical stretch. We also characterized circulating monocytes in normotensive and hypertensive humans. In addition, we quantified accumulation of activated monocytes and monocyte-derived cells in aortas and kidneys of mice with Angiotensin II-induced hypertension. Increased endothelial stretch enhanced monocyte conversion to CD14++CD16+ intermediate monocytes and monocytes bearing the CD209 marker and markedly stimulated monocyte mRNA expression of interleukin (IL)-6, IL-1β, IL-23, chemokine (C-C motif) ligand 4, and tumour necrosis factor α. STAT3 in monocytes was activated by increased endothelial stretch. Inhibition of STAT3, neutralization of IL-6 and scavenging of hydrogen peroxide prevented formation of intermediate monocytes in response to increased endothelial stretch. We also found evidence that nitric oxide (NO) inhibits formation of intermediate monocytes and STAT3 activation. In vivo studies demonstrated that humans with hypertension have increased intermediate and non-classical monocytes and that intermediate monocytes demonstrate evidence of STAT3 activation. Mice with experimental hypertension exhibit increased aortic and renal infiltration of monocytes, dendritic cells, and macrophages with activated STAT3. These findings provide insight into how monocytes are activated by the vascular endothelium during hypertension. This is likely in part due to a loss of NO signalling and increased release of IL-6 and hydrogen peroxide by the dysfunctional endothelium and a parallel increase in STAT activation in adjacent monocytes. Interventions to enhance bioavailable NO, reduce IL-6 or hydrogen peroxide production or to inhibit STAT3 may have anti-inflammatory roles in hypertension and related conditions.
Role of habit in treatment adherence among adults with cystic fibrosis
Authors: Zhe Hui Hoo, Benjamin Gardner, Madelynne A Arden, Simon Waterhouse, Stephen J Walters, Michael J Campbell, Daniel Hind, Chin Maguire, Jane Dewar, Martin J Wildman
Journal: Thorax (2018)

Among adults with cystic fibrosis (CF), medication adherence is low and reasons for low adherence are poorly understood. Our previous exploratory study showed that stronger 'habit' (ie, automatically experiencing an urge to use a nebuliser) was associated with higher nebuliser adherence. We performed a secondary analysis of pilot trial data (n=61) to replicate the earlier study and determine whether habit-adherence association exists in other cohorts of adults with CF. In this study, high adherers also reported stronger habit compared with low adherers. Habit may be a promising target for self-management interventions. TRIAL REGISTRATION NUMBER: ACtiF pilot, ISRCTN13076797.
Checkpoint inhibitor-induced polymyalgia rheumatica controlled by cobimetinib, a MEK 1/2 inhibitor
Authors: Karmela Kim Chan, Anne R Bass
Journal: Annals of the Rheumatic Diseases (2018)

We read with great interest the recently published paper by Kostine et al 1 reporting on musculoskeletal immune-related adverse events (IRAE) related to cancer immunotherapy. We applaud the authors for being able to identify the incidence of these side effects and of their relation to tumour response.

Of particular interest to us is the fact that most of the musculoskeletal IRAE were polymyalgia-like. We are eager to add to that discussion by presenting this case of checkpoint inhibitor-induced polymyalgia rheumatica (PMR) that was partially treated by targeted therapy with a MEK 1/2 inhibitor.

A 70-year-old woman presented in November 2015 with rectal cancer that was locally invasive and metastatic to peritoneum and lung. She failed chemotherapy (5-fluorouracil, leucovorin and irinotecan) and in September 2016 was enrolled in a trial of atezolizumab (anti-PD-L1) every 2 weeks plus cobimetinib (a MEK 1/2 inhibitor). Cobimetinib was given daily for 3 …
Making Lung Cancer Clinical Trials More Inclusive: Recommendations for Expanding Eligibility Criteria
Authors: Philip Bonomi, Gideon Blumenthal, Andrea Stern Ferris, David J. Stewart, Wendy K.D. Selig, Lee M. Krug, Jeff Allen, Gwynn Ison, Corey J. Langer, Allen Melemed, Lauretta Odogwu, Upal Basu Roy, Alan Sandler
Journal: Journal of Thoracic Oncology (2018)
Abstract MP93: Actigraphy Measured Sleep Indices and Adiposity: The Multi-Ethnic Study of Atherosclerosis
Authors: Rachel Ogilvie, Susan Redline, Alain G Bertoni, Xiaoli Chen, Moyses Szklo, Pamela Ouyang, Pamela Lutsey
Journal: Circulation (2016)

Background: Previous findings on sleep and adiposity in adults have been inconsistent. Limitations of these studies include self-reported sleep measures, one measure of adiposity, and racially/ethnically homogenous populations. Objectives: We examined the cross-sectional relationship between indices of objectively measured sleep and adiposity in 2,146 MESA Sleep study participants. Methods: Sleep duration, sleep efficiency (% time asleep during sleep period), and night-to-night variability in sleep duration were assessed using at-home 7-day actigraphy and were modeled categorically. Adiposity was measured as body mass index (BMI) and waist circumference (WC). Multivariate linear models were used to examine relationships between sleep exposures and each outcome. In models with dichotomous outcomes, we used logistic regression post-estimation commands to calculate adjusted probabilities standardized to the total population for each sleep measure category. These probabilities were used to calculate prevalence differences for overweight (BMI 25-29.9 kg/m 2 ), obesity (BMI ≥ 30 kg/m 2 ), and abdominal obesity (men: WC ≥102 cm; women ≥88 cm). Results: Of 2146 participants (mean age 68.6 years), 53.7% were female, 30% were white, 46.2% Black/African American, 5.0% Chinese, and 41.9% Hispanic. Participants who slept &lt;6 hours/night had significantly higher BMI and WC relative to those who slept 7-8 hours. Those who slept &lt;5 hours had a 15% excess prevalence of obesity (BMI ≥ 30 vs. &lt;25 kg/m 2 ) (95% CI: 0.07-0.23) and a 10% excess prevalence of abdominal obesity (95% CI: 0.03-0.17) compared to those who slept 7-8 hours. Poor sleep efficiency and greater night-to-night sleep variability were also associated with a greater prevalence of obesity. Conclusions: Among a multi-racial/ethnic cohort, we found robust associations across multiple indices of sleep and adiposity. Targeting sleep characteristics may be of benefit in obesity interventions, but more research is needed to rule out reverse causality.
Premature Cardiac Disease and Death After Preterm Preeclampsia in Women Whose Infant Was Small for Gestational Age—Reply
Authors: Joel G. Ray
Journal: JAMA Cardiology (2018)

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 Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Cardiology journal
Oral vitamin-A-coupled valsartan nanomedicine: High hepatic stellate cell receptors accessibility and prolonged enterohepatic residence
Authors: Nesrine S. El-Mezayen, Wessam F. El-Hadidy, Wessam M. El-Refaie, Thanaa I. Shalaby, Mahmoud M. Khattab, Aiman S. El-Khatib
Journal: Journal of Controlled Release (2018)
Multicenter phase 2 study to identify the optimal neo-adjuvant combination scheme of ipilimumab (IPI) and nivolumab (NIVO) (OpACIN-neo).
Authors: Elisa A. Rozeman, Alexander Christopher Jonathan Van Akkooi, Alexander M. Menzies, Myles Smith, Richard A. Scolyer, Loes M. Pronk, Maria Gonzales, Christoph Hoeller, Johan Hansson, James M. G. Larkin, Georgina V. Long, Christian U. Blank
Journal: Journal of Clinical Oncology (2018)

TPS9606 Background: The outcome of high risk stage III melanoma patients (pts) is poor, with a 5 year overall survival (OS) rate of < 50%. Adjuvant (adj) high dose IPI significantly improves 5 year progression free survival (PFS) and OS and adj NIVO improves the median PFS even more. In stage IV pts, the combination of IPI and NIVO improves response rates (RR) and PFS compared to monotherapy, but at cost of higher toxicity. Neo-adjuvant (neoadj) treatment may be a favorable approach as immune checkpoint inhibition (ICI) is of greatest value at the moment of TCR triggering and therefore dependent on the amount of antigen. The phase Ib OpACIN study compared neoadj versus adj IPI plus NIVO. The pathological RR (pRR) was 80% in the neoadj arm, and to date after a median follow-up of 24 months, none of the responders has relapsed, while 4/10 pts have relapsed in the adj arm. Moreover, pts in the neoadj arm expanded more tumor-resident TCR clones than adj treated pts. Neoadj IPI+NIVO was feasible, but toxicity was high with 90% grade 3/4 immuun-related adverse events (irAE) in both arms. This raises the question whether neoadj IPI plus NIVO can be alternatively scheduled to reduce toxicity but preserve efficacy. Methods: The aim of the multi-center phase 2 OpACIN-neo trial is to identify an optimal neoadj combination scheme of IPI and NIVO. 90 pts with resectable stage III melanoma will be randomized 1:1:1 between three different combination schemes of IPI and NIVO (Arm A: 2x IPI 3mg/kg plus NIVO 1mg/kg q3wks, Arm B: 2x IPI 1mg/kg plus NIVO 3mg/kg q3wks, Arm C: 2x IPI 3mg/kg q3wks directly followed by 2x NIVO 3mg/kg q2wks). All pts will undergo surgery at week 6. Primary endpoints are rate of grade 3 and 4 irAEs, pRR, and radiologic RR according to RECIST 1.1. Major inclusion criteria are: ≥1 measurable lymph node metastases (according to RECIST 1.1) that can be biopsied, no history of in-transit metastases in the last 6 months, and naïve for ICI. Baseline biopsies and blood samples (week 0, 6, 12) will be taken. An interim analysis was planned after 13 pts had been accrued to each arm (according to the Simon stage-2 design). Pre-specified activity goals for the first stage of accrual were met; until now 56 of 90 pts have been enrolled. Clinical trial information: NCT02977052.
Corrigendum re: “Influence of Modified Posterior Reconstruction of the Rhabdosphincter on Early Recovery of Continence and Anastomotic Leakage Rates after Robot-Assisted Radical Prostatectomy” [Eur Urol 2011;59:72–80]
Authors: Rafael F. Coelho, Sanket Chauhan, Marcelo A. Orvieto, Ananthakrishnan Sivaraman, Kenneth J. Palmer, Geoff Coughlin, Vipul R. Patel
Journal: European Urology (2018)
Anaphylaxis admissions to pediatric intensive care units in France
Authors: G. Pouessel, F. Chagnon, C. Trochu, J. Labreuche, S. Lejeune, M. Recher, A. Deschildre, S. Leteurtre
Journal: Allergy (2018)

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Phase I Study of CC-486 Alone and in Combination with Carboplatin or nab-Paclitaxel in Patients with Relapsed or Refractory Solid Tumors
Authors: Daniel D. Von Hoff, Drew W. Rasco, Elisabeth I. Heath, Pamela N. Munster, Jan H.M. Schellens, Nicolas Isambert, Christophe Le Tourneau, Bert O'Neil, Ron H.J. Mathijssen, Jose A. Lopez-Martin, W. Jeff Edenfield, Miguel Martin, Patricia M. LoRusso, Gordon L. Bray, Jorge DiMartino, Aaron Nguyen, Kejian Liu, Eric Laille, Johanna C. Bendell
Journal: Clinical Cancer Research (2018)

Purpose: This large two-part, three-arm phase I study examined the safety and tolerability of CC-486 (an oral formulation of azacitidine, a hypomethylating agent) alone or in combination with the cytotoxic agents, carboplatin or nab-paclitaxel, in patients with advanced unresectable solid tumors.Patients and Methods: Part 1 (n = 57) was a dose escalation of CC-486 alone (arm C) or with carboplatin (arm A) or nab-paclitaxel (arm B). The primary endpoint was safety, MTD, and recommended part 2 dose (RP2D) of CC-486. In part 2 (n = 112), the primary endpoint was the safety and tolerability of CC-486 administered at the RP2D for each treatment arm, in tumor-specific expansion cohorts. Secondary endpoints included pharmacokinetics, pharmacodynamics, and antitumor activity of CC-486.Results: At pharmacologically active doses CC-486 in combination with carboplatin or nab-paclitaxel had a tolerable safety profile and no drug-drug interactions. The CC-486 RP2D was determined as 300 mg (every day, days 1-14/21) in combination with carboplatin (arm A) or as monotherapy (arm C); and 200 mg in the same dosing regimen in combination with nab-paclitaxel (arm B). Albeit limited by the small sample size, CC-486 monotherapy resulted in partial responses (three/eight) and stable disease (four/eight) in patients with nasopharyngeal cancer. Three of the stable disease responses lasted more than 150 days.Conclusions: CC-486 is well tolerated alone or in combination with carboplatin or nab-paclitaxel. Exploratory analyses suggest clinical activity of CC-486 monotherapy in nasopharyngeal cancer and provided the basis for an ongoing phase II clinical trial (ClinicalTrials.gov identifier: NCT02269943). Clin Cancer Res; 24(17); 4072-80. ©2018 AACR.