tbuckley/cabot-search huggingface dataset:
Validation of the postneoadjuvant therapy pathological stage of the American Joint Committee on Cancer (AJCC) 8th Edition for predicting outcomes of esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiotherapy (CRT) followed by esophagectomy.
Authors: Tsung-hao Liu, Hung-Yang Kuo, Jhe-Cyuan Guo, Chia-Chi Lin, Ta-Chen Huang, Min-Shu Hsieh, Jang-Ming Lee, Chih-Hung Hsu
Journal: Journal of Clinical Oncology (2018)

138 Background: The AJCC 8 th edition staging system introduces a new postneoadjuvant therapy staging category (ypTNM-8 th ) for ESCC patients receiving neoadjuvant treatment followed by esophagectomy. Whether this new staging category has better prognostic prediction than the pathological staging category of AJCC 7 th edition (ypTNM-7 th ) needs validation. Methods: We enrolled ESCC patients receiving neoadjuvant paclitaxel/cisplatin-based CRT (RT = 40Gy) followed by esophagectomy from three phase II trials conducted in the National Taiwan University Hospital. The prognostic prediction abilities of the ypTNM-8 th and the ypTNM-7 th on patients’ survivals were compared using Cox regression, concordance index (C-index), R-square, and Akaike information criteria (AIC). Results: A total 135 patients (M:F = 127: 8, median age:53.0 years) were enrolled. With a median follow-up of 31.3 months, the median PFS and OS of all patients were 24.4 months (95% CI: 15.4-33.5) and 33.9 months (95% CI: 22.6-45.1), respectively. In univariate analysis, both ypTNM-8 th and ypTNM-7 th had statistically significant prognostic effects for PFS and OS. In multivariate analysis on OS, the ypTNM-8 th demonstrated a statistically significant predicting effect (P = 0.015) while the ypTNM-7 th did not (P = 0.051). Although there is no statistically different between ypTNM-8 th and ypTNM-7 th by R-square analysis, the ypTNM-8 th had lower AIC and C-index for both PFS and OS, meaning an better efficiency of predicting survivals, than ypTNM-7 th . Conclusions: The new ypTNM-8 th may have better prognostic prediction for OS of locally advanced ESCC patients receiving neoadjuvant CRT than the ypTNM-7 th . (Granted by 106-HCH029)
Retrospective observational study of salvage line ramucirumab monotherapy (RAM) for patients (pts) with unresectable advanced gastric cancer (AGC) which was refractory to fluoropyrimidine and taxanes.
Authors: Naoki Fukuda, Sadayuki Kawai, Katsuhiro Omae, Seiichiro Mitani, Takeru Wakatsuki, Ken Kato, Shigenori Kadowaki, Daisuke Takahari, Narikazu Boku, Kei Muro, Nozomu Machida
Journal: Journal of Clinical Oncology (2018)

129 Background: RAM showed a survival benefit over best supportive care in second-line treatment after failure of fluoropyrimidine-containing chemotherapy for pts with advanced gastric or gastro-esophageal junction adenocarcinoma (AGC). In clinical practice, RAM is used for some pts who have disease refractory to fluoropyrimidine and taxanes in salvage line setting. Methods: We retrospectively evaluated efficacy and safety of RAM in salvage lines between June 2015 and April 2017 for AGC at four Japanese institutions. All pts received 2 or more prior regimens containing fluoropyrimidine and taxanes, but not ramucirumab. We also explored prognostic factors for progression free survival (PFS) and overall survival (OS). Results: Fifty-one pts were collected. Pts' characteristics were as follows; median age: 67 (range 39-84) years; ECOG performance status ≤ 1: 43 (84%) pts; HER2 positive: 17 (33%) pts; number of metastatic sites ≥ 2: 29 (57%); number of prior therapies 2/3/4/5: 7(14%)/25(49%)/12(24%)/7(14%) pts. Median PFS and OS were 1.9 (95% confidence interval [CI]: 1.6-2.2) and 5.1 (95% CI: 4.1-6.8) months, respectively. Twelve-week PFS rate was 25.5%. Objective response rate in 43 pts who had measurable disease was 2%. Disease control rate was 35%. Grade 3 adverse events (AEs) occurred in 7 (13%) pts such as anemia in 2 (4%), fatigue in 1 (2%), hypertension in 2 (4%), proteinuria in 2 (4%), intestinal bleeding in 1 (2%), and others in 2 (4%) pts. No grade 4 AEs and treatment related deaths were observed. Although multivariate analyses suggested that absence of primary tumor and neutrophil lymphocyte ratio &lt; 2.5 at baseline were associated with better PFS, while statistically significant prognostic factors for OS were not identified in this study. Conclusions: Salvage line RAM showed acceptable toxicities and comparable efficacy with those reported in previous studies of second-line setting. It is suggested that RAM could be considered for salvage line treatment after fluoropyrimidine and taxanes containing regimens.
Investments in Community-Based Longitudinal Studies Continue to Bear Fruit
Authors: Ruben C. Gur
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Changes in inflammation and insulin pathways mediate the association between resistance training and breast cancer survival
Authors: Mike Fillon
Journal: CA A Cancer Journal for Clinicians (2018)

Key Points Changes in biomarkers reflecting inflammation and insulin‐related pathways help to explain why resistance exercises are beneficial for survivors of breast cancer, and should be safely added to stretching and aerobics routines. In addition to fitness measures, resistance exercises also may improve mood, sleep, and other quality‐of‐life measures.
The subclonal complexity of STIL-TAL1+ T-cell acute lymphoblastic leukaemia
Authors: Caroline L Furness, Marcela B Mansur, Victoria J Weston, Luca Ermini, Frederik W van Delft, Sarah Jenkinson, Rosemary Gale, Christine J Harrison, Maria S Pombo-de-Oliveira, Marta Sanchez-Martin, Adolfo A Ferrando, Pamela Kearns, Ian Titley, Anthony M Ford, Nicola E Potter, Mel Greaves
Journal: Leukemia (2018)

Single-cell genetics were used to interrogate clonal complexity and the sequence of mutational events in STIL-TAL1+ T-ALL. Single-cell multicolour FISH was used to demonstrate that the earliest detectable leukaemia subclone contained the STIL-TAL1 fusion and copy number loss of 9p21.3 (CDKN2A/CDKN2B locus), with other copy number alterations including loss of PTEN occurring as secondary subclonal events. In three cases, multiplex qPCR and phylogenetic analysis were used to produce branching evolutionary trees recapitulating the snapshot history of T-ALL evolution in this leukaemia subtype, which confirmed that mutations in key T-ALL drivers, including NOTCH1 and PTEN, were subclonal and reiterative in distinct subclones. Xenografting confirmed that self-renewing or propagating cells were genetically diverse. These data suggest that the STIL-TAL1 fusion is a likely founder or truncal event. Therapies targeting the TAL1 auto-regulatory complex are worthy of further investigation in T-ALL.
The impact of social protection and poverty elimination on global tuberculosis incidence: a statistical modelling analysis of Sustainable Development Goal 1
Authors: Daniel J Carter, Philippe Glaziou, Knut Lönnroth, Andrew Siroka, Katherine Floyd, Diana Weil, Mario Raviglione, Rein M G J Houben, Delia Boccia
Journal: The Lancet Global Health (2018)

BackgroundThe End TB Strategy and the Sustainable Development Goals (SDGs) are intimately linked by their common targets and approaches. SDG 1 aims to end extreme poverty and expand social protection coverage by 2030. Achievement of SDG 1 is likely to affect the tuberculosis epidemic through a range of pathways. We estimate the reduction in global tuberculosis incidence that could be obtained by reaching SDG 1.MethodsWe developed a conceptual framework linking key indicators of SDG 1 progress to tuberculosis incidence via well described risk factor pathways and populated it with data from the SDG data repository and the WHO tuberculosis database for 192 countries. Correlations and mediation analyses informed the strength of the association between the SDG 1 subtargets and tuberculosis incidence, resulting in a simplified framework for modelling. The simplified framework linked key indicators for SDG 1 directly to tuberculosis incidence. We applied an exponential decay model based on linear associations between SDG 1 indicators and tuberculosis incidence to estimate tuberculosis incidence in 2035.FindingsEnding extreme poverty resulted in a reduction in global incidence of tuberculosis of 33·4% (95% credible interval 15·5–44·5) by 2035 and expanding social protection coverage resulted in a reduction in incidence of 76·1% (45·2–89·9) by 2035; both pathways together resulted in a reduction in incidence of 84·3% (54·7–94·9).InterpretationFull achievement of SDG 1 could have a substantial effect on the global burden of tuberculosis. Cross-sectoral approaches that promote poverty reduction and social protection expansion will be crucial complements to health interventions, accelerating progress towards the End TB targets.FundingWorld Health Organization.
Comment on Santema et al. Hyperbaric Oxygen Therapy in the Treatment of Ischemic Lower-Extremity Ulcers in Patients With Diabetes: Results of the DAMO2CLES Multicenter Randomized Clinical Trial. Diabetes Care 2018;41:112–119
Authors: Mesut Mutluoglu
Journal: Diabetes Care (2018)

I read with great interest the article by Santema et al. (1) published recently in Diabetes Care .

Two years ago, when I first read about the protocol of this study (2) that claimed to address one of the most controversial issues of hyperbaric oxygen therapy (HBOT), I was filled with the hope that it would help clarify the debate on the topic. While I applaud the authors’ effort on conducting such a demanding study, the aberration from the initial protocol, particularly with regard to the sample …
Abstract 14540: Genetic Variations Optimized Treatment Benefit of the Angiotensin-Converting- Enzyme Inhibitors in Patients With Stable Coronary Artery Disease: A 12-Year Follow-Up Study
Authors: Jen-kuang Lee, Cho-Kai Wu, Yu-Lian Lin, Fu-Tien Chiang
Journal: Circulation (2011)

BACKGROUND:  The objective of this study was to evaluate the effects of angiotensin converting enzyme (ACE) inhibitors and pharmacogenetic interaction in patients with coronary artery disease (CAD).   METHODS:  Subjects with angiographic CAD were recruited from 1995 to 2003. Baseline characteristics and genetic polymorphisms (ACE gene insertion/deletion [I/D] polymorphism, six polymorphisms of the angiotensinogen [AGT] gene, and A1166C polymorphisms of the angiotensin II type I receptor gene [AGT1R]) were collected. Patients were randomized to 2 groups (ACE inhibitor or No-ACE inhibitor) and followed for up to 12 years. Kaplan-Meier curves and Cox regression models were used to demonstrate the survival and major cardiovascular events (MACE) event-free survival trend. Pharmacogenetic effects were determined by several Cox regression models.   RESULTS:  Of the 784 patients, 432 were treated with ACE inhibitors and 352 were not. Prescription of ACE inhibitors was associated with a lower rate of MACE at 4000 days. In addition, ACE I/D gene D and AGT1R gene C allele were associated with a higher rate of MACE in a multivariate regression analysis (HR: 1.49, 95% CI: 1.26∼1,75,  P  = 0.008; HR: 1.42, 95% CI: 1.04∼1,94,  P  = 0.027, respectively). This effect could be attenuated by the pharmacogenetic interaction of ACE inhibitors and the ACE gene (ACE inhibitors*ACE gene, HR: 0.8, 95% CI: 0.62∼0.94,  P  = 0.03).   CONCLUSIONS:  The use of ACE inhibitors was associated with a significant decrease in MACE in patients diagnosed with CAD. Genetic variants were also associated with event-free survival, but their effects were modified by the use of ACE inhibitors.
Simultaneous positron emission tomography and ultrafast ultrasound for hybrid molecular, anatomical and functional imaging
Authors: Jean Provost, Anikitos Garofalakis, Joevin Sourdon, Damien Bouda, Béatrice Berthon, Thomas Viel, Mailyn Perez-Liva, Charlotte Lussey-Lepoutre, Judith Favier, Mafalda Correia, Mathieu Pernot, Johanna Chiche, Jacques Pouysségur, Mickael Tanter, Bertrand Tavitian
Journal: Nature Biomedical Engineering (2018)
RELATION BETWEEN ACHILLES TENDON THICKENING AND SEVERITY OF CORONARY ARTERY DISEASE DESPITE CLINICALLY DIAGNOSED FAMILIAL HYPERCHOLESTEROLEMIA IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION
Authors: Hideki Kitahara, Takashi Nakayama, Yoshihide Fujimoto, Yoshio Kobayashi
Journal: Journal of the American College of Cardiology (2018)
Preliminary biomarker and pharmacodynamic data from a phase I study of single-agent bispecific antibody T-cell engager GBR 1302 in subjects with HER2-positive cancers.
Authors: Martin Wermke, Juergen Alt, John S. Kauh, Jonathan Back, Yacine Salhi, Venkateshwar Reddy, Eliel Bayever, Sebastian Ochsenreither
Journal: Journal of Clinical Oncology (2018)

69 Background: HER2 is overexpressed in many solid tumors and is a validated therapeutic target. GBR 1302 is a HER2xCD3 bispecific antibody engineered (using Glenmark’s BEAT ® platform) to direct T-cells to HER2-expressing tumor cells. GBR1302-101 (NCT02829372) is an ongoing, multicenter, open-label, first-in-human study of GBR 1302 in subjects with HER2-positive cancers to evaluate the safety, tolerability, and preliminary efficacy of GBR 1302, and to elucidate the mechanism(s) by which it redirects T-cells to tumor and enhances cytolytic activity of cytotoxic T-cells. Methods: Adults with progressive HER2-positive solid tumors with no available standard or curative treatment receive intravenous GBR 1302 on Day 1 and Day 15 in 28-day treatment cycles at escalating dose levels, starting at 1 ng/kg. The first 4 cohorts consist of a single subject; subsequent cohorts enroll using a 3+3 design. The primary and secondary efficacy and safety endpoints of this trial will be reported at the end of the study. Preliminary pharmacodynamic (PD) data are reported for cellular biomarkers and cytokines as assessed by FACS and ELISA in peripheral blood. Results: Beginning at 30 ng/kg dosing of GBR 1302 (Cohort 4), numbers of peripheral blood CD3, CD4, and CD8 positive T-cell populations decreased within 6 hours of initiating administration, but recovered to levels at or above baseline by 48 hours. A parallel, transient increase was observed in peripheral blood cytokines (IL-2, IL-6, IL-10, IFN-γ, TNF-α). At doses greater than 30 ng/kg, more pronounced cytokine increases were observed, which normalized at 12 hours. At the highest dose level for which data are available (n = 8 subjects; Cohort 5), changes from baseline in cytokine expression at ~340 hours were greater by ~60-fold for IL-6, ~30-fold for IL-2, ~3-fold for IFN-γ, ~5-fold for TNF-α, and ~18-fold for IL-10. Two subjects treated at 100 ng/kg experienced Grade 1 cytokine release syndrome, evidenced by short-lived fever spikes. Dose escalation is ongoing. Conclusions: Preliminary PD data indicate changes in peripheral T-cell populations and inflammatory cytokines following GBR 1302 treatment. Clinical trial information: NCT02829372.
THE INCREMENTAL PROGNOSTIC VALUE OF LEFT VENTRICULAR MECHANICAL DISPERSION IN PATIENTS AFTER ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION
Authors: Rachid Abou, Laurien Goedemans, Dilek Yilmaz, Edgard Prihadi, Pieter van der Bijl, Martin Schalij, Nina Ajmone Marsan, Jeroen J. Bax, Victoria Delgado
Journal: Journal of the American College of Cardiology (2018)
Scarring in Patients With <i>PIK3CA</i>-Related Overgrowth Syndromes
Authors: Jack E. Steiner, Catherine E. Cottrell, Jenna L. Streicher, John N. Jensen, David M. King, Patricia E. Burrows, Dawn H. Siegel, Megha M. Tollefson, Beth A. Drolet, Katherine B. Püttgen
Journal: JAMA Dermatology (2018)

Patients with somatic overgrowth commonly require surgical intervention to preserve function and improve cosmesis. To our knowledge no observation of scarring outcomes in this population has been published to date.To observe the frequency of abnormal scarring in patients with somatic overgrowth and sequencing-verified mutations in the PIK3CA gene.This retrospective study evaluated scarring outcomes in patients with PIK3CA-related overgrowth. Samples of affected tissue were sequenced between July 2015 and October 2016. Medical records from multiple large academic tertiary care centers were reviewed for surgical history and scar descriptions, and clinical photographs were assessed by 2 surgeons (J.N.J. and D.M.K.) to confirm abnormal scarring. Analysis of medical records and photographs was performed between April 2017 and June 2017 by a multidisciplinary team from dermatology, plastic surgery, orthopedic surgery, radiology, and genetics departments. All patients considered for the study were diagnosed with somatic overgrowth and previously had affected tissue sent for next-generation sequencing. Those with pathogenic PIK3CA variants and 1 or more prior surgical procedures were reviewed.Presence of excessive scarring in patients with PIK3CA overgrowth.A total of 57 patients with segmental overgrowth syndromes were sequenced. Of the 57 patients, 25 (44%) had pathogenic or likely pathogenic variants in PIK3CA. Of those with pathogenic PIK3CA variants, 6 (24%) had past surgical procedures, all with preoperative and postoperative photographs. Of 6 patients with PIK3CA-related overgrowth and a history of 1 or more surgical procedure, 4 (67%) developed excessive scarring. The cohort with abnormal scarring comprised 3 females and 1 male, with a median age of 8.5 years. All abnormal scarring occurred in affected overgrowth tissue. Three of the 4 patients developed the excessive scarring after debulking procedures for overgrowth and/or vascular malformations of the upper or lower extremity.Excessive scarring occurred frequently in patients with PIK3CA-related overgrowth syndromes. The risk of abnormal scarring should therefore be discussed preoperatively. Given the activating nature of these PIK3CA variants, we suggest that the excessive scarring may be owing in part to up-regulation of the PI3K-Akt-mTOR pathway. Additional studies are needed to assess scarring outcomes in patients with other types of overgrowth.
Tivozanib combined with nivolumab: Phase Ib/II study in metastatic renal cell carcinoma (mRCC).
Authors: Bernard Escudier, Philippe Barthelemy, Alain Ravaud, Sylvie Negrier, Michael N. Needle, Laurence Albiges
Journal: Journal of Clinical Oncology (2018)

618 Background: Tivozanib is a VEGFR-TKI with high specificity and lower incidence of class effect adverse events. As combinations of vascular endothelial growth factor receptor tyrosine kinase inhibitiors (VEGFR-TKIs) and checkpoint inhibitors have proven to be toxic, alternatives with an improved AE profile are required. We present safety data from a phase Ib/II combination of tivozanib and nivolumab Methods: In this phase Ib/II study, tivozanib was administered orally at two dose levels, 1.0 mg and 1.5 mg, once daily for 21 days every 28 day cycle in combination with nivolumab 240 mg every 14 days intravenously. Results: Eighteen patients have been enrolled. Phase Ib is complete. Safety data is available for 13, 3 at 1.0 mg tivo; 10 at 1.5 mg tivo. The median age was 62; 11 patients were ECOG 0 and 5 ECOG 1; and there were 13 males. 16 had clear cell histology No patient in phase Ib experienced an DLT in cycle 1. Patients in phase II are receiving tivozanib at 1.5 mg. All patients experienced at least one AE. The most common adverse events were hypertension, asthenia, mucositis, diarrhea, hand foot syndrome, arthralgia, and pruritis. Five patients (38%) had grade 3-4 AEs. One patient had both elevated serum lipase and amylase and one patient had an SAE of symptomatic malignant hypertension complicated by a seizure. The other grade 3-4 AEs were pneumonitis, stomatitis, and elevated ALT. Conclusions: As expected from a VEGFR-TKI with high specificity and a preferable toxicity pattern as a single agent, the combination of tivozanib with nivolumab is safe and manageable at full dose of both drugs. Efficacy is pending. This data is based on limited exposure and should be interpreted with caution. Additional patients are being enrolled and treated. This begs the question if tivozanib could be added to a triple combination with ipilimumab and nivolumab. Clinical trial information: NCT03136627. [Table: see text]
Leaders, mentors, and bullies
Authors: Peter Cross
Journal: BMJ (2005)

It doesn't seem that long ago that leadership was a dirty word. Something that had to be done covertly while being mindful of the sensitivities of multidisciplinary colleagues. But those times are behind us, and doctors once again are expected to lead from the front.

Whether leadership skills are innate or can be taught is a moot point. On page 163 Julie Sladden writes about an innovatory leadership …
INHIBITION OF MIR-128-3P BY TONGXINLUO PROTECTS HUMAN CARDIOMYOCYTES FROM ISCHEMIA/REPERFUSION INJURY VIA UPREGULATION OF P70S6K1/P-P70S6K1
Authors: Guihao Chen, Chuansheng Xu, Yuejin Yang, Jie Zhang, Qing Li
Journal: Journal of the American College of Cardiology (2018)
Key points for overseas doctors to consider
Authors: Shaaz Maboob
Journal: BMJ (2004)

<i>Overseas doctor</i> Shaaz Maboob <i>now works at the NHS London work programme office, on behalf of London strategic health authorities and workforce development confederations, specifically to look after the needs of overseas doctors. He outlines what overseas doctors should consider before they come to the United Kingdom and at every stage after that</i>