tbuckley/cabot-search huggingface dataset:
Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) in patients (pts) with impaired renal function.
Authors: Vadim S. Koshkin, Pedro C. Barata, Haris Zahoor, Lisa A. Rybicki, Nima Almassi, Alicia M Redden, Amr Farouk Fergany, Jihad Kaouk, Georges-Pascal Haber, Andrew J. Stephenson, Allison Martin, Kimberly D Allman, Jennifer Beach, Moshe Chaim Ornstein, Timothy D. Gilligan, Jorge A. Garcia, Brian I. Rini, Petros Grivas
Journal: Journal of Clinical Oncology (2018)

446 Background: Cisplatin-based NAC followed by radical cystectomy is the standard of care in MIBC but many pts are cisplatin-unfit. Data in pts with low glomerular filtration rate (GFR) who receive cisplatin-based NAC is limited. Methods: A retrospective analysis of pts who received cisplatin-based NAC at Cleveland Clinic (2005-2016) was conducted. Pts with pre-NAC GFR &lt; 60 ml/min by either CG or MDRD formula (low GFR; N = 30) were compared to pts with GFR ≥60 (normal GFR; N = 94) in terms of NAC tolerability and outcomes including pathologic complete (pCR, pT0N0) and partial response (pPR, &lt; pT2N0). A secondary analysis compared 3 groups of pts: GFR &lt; 50ml/min (N = 10), GFR 50-59 ml/min (N = 20), and GFR ≥60 (N = 94). Results: Low GFR pts were older (median age 71 vs 65, p &lt; 0.001) and had higher rates of hydronephrosis (33% vs 15%, p = 0.03). ECOG PS, other demographic and TURBT features (stage, LVI, CIS) did not differ significantly. Low GFR pts were more likely to receive gemcitabine/cisplatin (83% vs 71%, p = 0.04) and get split-dose cisplatin (38% vs 16%, p = 0.02). Split-dose cisplatin use in low GFR pts did not impact NAC tolerability or outcomes. NAC cycles completed (median 3 per group) were comparable, and most low GFR pts (70%) completed intended NAC regimen. Low GFR pts were more likely to have early NAC discontinuation (30% vs 13%, p = 0.03) and NAC modification (delay, dose reduction, discontinuation) (66% vs 40%, p = 0.02). No differences were seen in cystectomy completion rate (93% per group), time to cystectomy, length of stay, surgical complications, and GFR change from baseline. Combined pCR/pPR was higher in normal GFR group (54% vs 25%, p = 0.01). Among pts with very low GFR ( &lt; 50 ml/min), 60% completed intended NAC regimen and 70% had NAC modification. Rates of pCR and pPR were low: 0% and 12%, respectively. Conclusions: Low GFR pts were older, had more NAC discontinuations/modifications and lower pCR/pPR rate, but most completed planned NAC cycles. Relative to normal GFR pts, low GFR pts were not prevented or delayed in getting cystectomy, and had comparable impact of NAC on GFR. For carefully selected pts with GFR &lt; 60 ml/min, cisplatin-based NAC is a treatment option, consistent with prior data.
AFRICAN AMERICANS HAVE BETTER OUTCOMES FOR CONGESTIVE HEART FAILURE IN HOSPITALS WITH MORE RACIALLY DIVERSE PATIENTS: A NATIONWIDE ANALYSIS
Authors: Xin Wei, Yibin Guo, Kevin Gu, Bing Yue, Ahmadreza Moradi, Mariam Khandaker, Chayakrit Krittanawong, Basera Sabharwal, Karan Sud, Xiaochuan Yang, Eyal Herzog
Journal: Journal of the American College of Cardiology (2018)
Effect of crizotinib on disease control in patient with advanced papillary renal cell carcinoma type 1 with MET mutations or amplification: Final results of EORTC 90101 CREATE.
Authors: Patrick Schoffski, Agnieszka Wozniak, Bernard Escudier, Piotr Rutkowski, Alan Anthoney, Sebastian Bauer, Jozef Sufliarsky, Carla M.L.- Van Herpen, Lars Lindner, Viktor Grünwald, Branko Zakotnik, Evelyne Lerut, Maria Debiec-Rychter, Sandrine Marreaud, Michela Lia, Tiana Raveloarivahy, Sandra Collette, Laurence Albiges
Journal: Journal of Clinical Oncology (2018)

580 Background: Papillary renal cell carcinoma type 1(PRCC1) is associated with MET alterations. Our phase II trial assessed the efficacy and safety of crizotinib in patients (pts) with advanced/metastatic PRCC1 with/without MET mutations( MET+, MET-). Methods: Eligible pts with reference pathology-confirmed PRCC1 received oral crizotinib 250mg twice-daily. Pts were attributed to MET+/ MET- sub-cohorts by sequencing of MET exons 16-19 in tumour tissue. Primary endpoint was objective response rate (ORR). If at least 2 of the first 12 eligible/evaluable MET+ pts achieved a confirmed partial (PR) or complete response (RECIST 1.1), a maximum of 35 pts were enrolled. Other endpoints included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS) and rate (PFSR), overall survival (OS) and safety. Results: 23 of 41 pts consenting were eligible, treated and evaluable. In 4 MET+ pts, 2 achieved a PR and 1 had stable disease (SD) (ORR 50%; 95% CI: 6.8-93.7%), DOR was 666 and 1138 days, 1-year PFSR was 75.0% (12.8-96.1%), 1-year OS: 75.0% (12.8-96.1%). Among 16 MET- pts, 1 achieved a PR lasting 302+ days and 11 had SD (ORR: 6.3%; 0.2-30.2%), 1-year PFSR: 27.3% (8.5-50.4%), 1-year OS: 71.8% (41.1-88.4%). Among 3 pts with unknown MET status ( MET?) due to technical failure, 1 achieved a PR lasting 211+ days and 1 had SD (ORR 33.3%, 0.8%-90.6%), 1-year PFSR: 66.7% (5.4-94.5%), 1-year OS: 100%. MET amplification was found post hoc in 1 MET+ (PR, DOR: 1138 days) and 1 MET- case (SD). Common treatment-related AEs were oedema (47.8%), fatigue (47.8%), nausea (39.1%), diarrhoea (39.1%), and blurred vision (34.8%). Conclusions: Crizotinib is active and well tolerated in advanced, metastatic PRCC1, achieving objective responses and long-lasting disease control in pts with MET mutations or amplification. Sporadic, durable responses are also seen in MET-/ MET? cases, suggesting the presence of other alterations of MET or alternative pathways. Clinical trial information: NCT01524926.
The out-of-my-league effect
Authors: Fabrice Le Lec, Theodore Alexopoulos, Béatrice Boulu-Reshef, Marie-Pierre Fayant, Franck Zenasni, Todd Lubart, Nicolas Jacquemet
Journal: Behavioral and Brain Sciences (2017)

Abstract When taking into account the chances of success, strategic mating motivations do imply a bias not toward the most attractive individuals, but toward average or mildly attractive individuals, undermining the explanation of Maestripieri et al. at a fundamental level. This leaves open the possibility of alternative explanations and calls for a full-fledged explicit model of courtship behavior.
Carcinoembryonic antigen‐related cell adhesion molecule 1 controls IL‐2‐dependent regulatory T‐cell induction in immune‐mediated hepatitis in mice
Authors: Andrea Kristina Horst, Claudia Wegscheid, Christoph Schaefers, Birgit Schiller, Katrin Neumann, Sebastian Lunemann, Annika E. Langeneckert, Karl J. Oldhafer, Christina Weiler‐Normann, Karl S. Lang, Bernhard B. Singer, Marcus Altfeld, Linda Diehl, Gisa Tiegs
Journal: Hepatology (2018)

A dysbalance between effector T cells (Tconv) and regulatory T cells (Tregs) and impaired Treg function can cause autoimmune liver disease. Therefore, it is important to identify molecular mechanisms that control Treg homeostasis. Carcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1; CD66a) is an immune coreceptor with dichotomous roles in T‐cell regulation: its short isoform (CEACAM1S) can activate T cells and induce Tregs, whereas its long isoform (CEACAM1L), containing two intracellular immune receptor tyrosine‐based inhibitory motifs, can inhibit activated T‐cell function. In the liver, CEACAM1 has antifibrotic effects in models of nonalcoholic steatohepatitis. However, its role in immune‐mediated hepatitis is unknown. In the mouse model of concanavalin A–induced CD4+ T‐cell‐dependent liver injury, liver damage was aggravated and persisted in Ceacam1−/− mice. Concomitantly, we observed hyperexpansion of Tconv, but reduction of interleukin (IL)‐2 production and hepatic forkhead box protein P3+ (Foxp3+)CD4+ Treg numbers. CEACAM1−/−CD4+ T cells showed impaired IL‐2‐mediated signal transducer and activator of transcription 5 (STAT5) phosphorylation, which correlated with a failure of naïve CEACAM1−/−CD4+ T cells to convert into Tregs in vitro. Furthermore, CEACAM1−/− Tregs expressed reduced levels of Foxp3, CD25, and B‐cell lymphoma 2. Adoptive transfer experiments demonstrated that hepatic Treg expansion and suppressive activity required CEACAM1 expression on both CD4+ T cells and Tregs. We identified predominant CEACAM1S expression on hepatic CD4+ T cells and Tregs from mice with acute liver injury and expression of both isoforms in liver‐derived CD4+ T‐cell clones from patients with liver injury. Conclusion: Our data suggest that CEACAM1S expression in CD4+ T cells augments IL‐2 production and STAT5 phosphorylation leading to enhanced Treg induction and stability, which, ultimately, confers protection from T‐cell‐mediated liver injury. (Hepatology 2018;68:200‐214).
Confidentiality—the final betrayal
Authors: Brian Keighley
Journal: BMJ (2005)

There is no doubt that the general practitioner's job description has changed over the years, and the argument about what doctors who work beyond the hospital gate actually do for their daily crust fills many a column.

As a callow youth, when I started in the discipline, the norm was for the doctor to do just about everything, from suturing minor wounds to amateur midwifery in the middle of the night. Over the years, however, our core job has changed not because of because of new duties that we have acquired, but because of what we have given away.

Midwives deliver the babies—increasingly it seems, in wetsuits; casualty workers sew up the lacerations, health visitors do the vaccinations, CPNs (community psychiatric nurses) follow up the seriously mentally ill, and counsellors and psychologists attend to the rest. Community paediatricians sally out from their hospital clinics; there are liaison nurses for diabetics and Macmillan nurses for the terminals; school nurses have graduated from nits to postcoital contraception, and the practice nurse now seems to do chronic disease management. We have finally …
Triple-negative breast cancer survival in women age 75 and older.
Authors: Judith April Malmgren, Henry G. Kaplan, Mary K. Atwood
Journal: Journal of Clinical Oncology (2013)

1060 Background: Triple-negative breast cancer (TNBC) is associated with a high recurrence rate and poor prognosis, despite high initial response to chemotherapy. It is not known if TNBC patients 75 years older, an age group less likely to be treated with adjuvant chemotherapy, have the same mortality risk as younger women. Methods: We conducted a prospective cohort study of all women presenting with primary TNBC, age 21-89, stage I-III from 1998-2009 identified and tracked by our registry (n=529). Clinical characteristics were chart abstracted at diagnosis and follow up. The Kaplan-Meier method and log rank test were used for disease specific survival (DSS) and overall survival (OS) by age. Results: Mean follow up was 6.6 years, range 1.98-13.41 years. Distribution by age was 92% &lt;75 years (n = 485) and 8% 75+ years (n = 44). The two age groups did not differ by histologic or nuclear grade, stage, or radiation therapy receipt (age 75+ by stage: I = 46%, II = 34%, III 21%, age &lt;75: I = 37%, II = 46%, III = 17% [not significant]). Patients 75 and older were less likely to be treated with adjuvant chemotherapy (32% vs. 91%, Pearson chi square test = 119.32, p &lt;.001). 5 year DSS was not significantly different for patients age &lt;75 years compared to patients age 75+ years (85% vs. 84%). However, 5 year OS was significantly worse for 75 year and older patients (65%) compared to &lt;75 year old patients (83%) (log rank test = 13.97, p &lt; .001). Conclusions: In our institutional cohort, triple-negative breast cancer in older women had similar prognostic indicators (stage and histologic grade) compared to younger women and older women had equivalent disease specific survival in spite of substantially less chemotherapy treatment. At 5 years post diagnosis, women 75 years and older were 18% more likely to die of causes other than breast cancer.
Feasibility of wearable physical activity monitors in cancer patients (PAMCaP).
Authors: Muhammad Shaalan Beg, Tyler Stewart, Arjun Gupta, Ying Dong, Zain Rahimi, Tony Paul, Kimberli Crane, Chad Rethorst
Journal: Journal of Clinical Oncology (2017)

6577 Background: Wearable physical activity monitors (PAMs) provide a degree of functional assessment not possible with prior clinical instruments. Subjective assessments of functional status are prone to inaccuracy and current objective assessment techniques are limited to the research setting. The relevance of physical activity monitors (PAMs) to measure functional status in cancer patients is unclear. The feasibility of using these devices in cancer patients is not known. Methods: This is a prospective pilot trial of a commercially available PAM in cancer patients. Patients with Eastern Cooperative Group performance status (ECOG PS) 0-2 receiving systemic therapy at an NCI Designated Comprehensive Cancer Center were enrolled. (NCT02583815). The primary objective was to determine feasibility of PAM use, defined as device use of more than 50% of the study observation period. Secondary objectives were to correlate PAM-reported measures: median, minimum and maximum steps/day, minutes of activity/day, (light/ fairly active/ very active); with 1) clinician assessed ECOG PS and 2) quality of life tool scores (FACT-G, QIDS, PQSI and BFI). Patient experience with wearable PAMs was assessed at the end of study. Results: We enrolled 32 patients: median age = 56 years (range 23-72), female = 67%, and white = 78%. Most patients had gastrointestinal (52%) and breast (19%) primaries. Clinician assessed PS was ECOG 0 in 56%, 1 in 37% and 2 in 7%. Majority of patients (81%) met the primary end point. Mean PAM measured steps for ECOG 0 was 5911 steps/d, ECOG 1 was 1890 steps/d and ECOG 2 was 845 steps/d (p = 0.002). Minimum steps/day correlated with BFI (r = -0.56, p &lt; .01), FACT-G (r = 0.45, p 0.01) and QIDS (no vs mild vs moderate depression, p 0.01). Patients reported a positive experience with the devices (74%). Conclusions: Wearable PAMs are a feasible tool to measure physical activity in cancer patients receiving systemic therapy. PAM derived measures correlate with clinician assessments of performance status. Future work should develop methods to systematically incorporate PAMs in oncology clinical trials and practice. Clinical trial information: NCT02583815.
Abstract 13327: Prediction of Upcoming Therapeutic Episodes of ICD Through Routine Data in Routine Device Clinic of ICD Patients
Authors: Tamami Fujiishi, Shinichi Niwano, Masami Murakami, Hironori Nakamura, Tazuru Igarashi, Naruya Ishizue, Jun Oikawa, Jun Kishihara, Hidehira Fukaya, Hiroe Niwano, Junya Ako
Journal: Circulation (2015)

Background: Although implantable cardioverter-defibrillator (ICD) prevents sudden death of patients with life-threatening arrhythmia, prediction of upcoming ICD therapy, if possible, would be an im...
The -2518 A/G polymorphism of the monocyte chemoattractant protein-1 as a candidate genetic predisposition factor for secondary myelofibrosis and biomarker of disease severity
Authors: Elena Masselli, Cecilia Carubbi, Benedetta Cambò, Giulia Pozzi, Giuliana Gobbi, Prisco Mirandola, Elena Follini, Luca Pagliaro, Daniela Di Marcantonio, Francesco Bonatti, Antonio Percesepe, Stephen M. Sykes, Franco Aversa, Marco Vitale
Journal: Leukemia (2018)
Trump’s “war” on opioids includes death for drug dealers
Authors: Janice Hopkins Tanne
Journal: BMJ (2018)

President Donald Trump has set out his plan to tackle misuse of drugs, especially opioids, in a speech in Manchester, New Hampshire, a state hard hit by deaths from opioids. It includes death penalties for drug dealers, restriction of prescriptions for opioids, and treatment for people affected by opioid use.

New Hampshire, which Trump once called “a drug infested den,” is also a state with early primary voting that will be important to his bid for re-election in 2020.

Opioids caused an estimated 42 000 deaths in the US in 2016, data from the Centers for Disease …
Transient HIF2A inhibition promotes satellite cell proliferation and muscle regeneration
Authors: Liwei Xie, Amelia Yin, Anna S. Nichenko, Aaron M. Beedle, Jarrod A. Call, Hang Yin
Journal: Journal of Clinical Investigation (2018)

The remarkable regeneration capability of skeletal muscle depends on the coordinated proliferation and differentiation of satellite cells (SCs). The self-renewal of SCs is critical for long-term maintenance of muscle regeneration potential. Hypoxia profoundly affects the proliferation, differentiation, and self-renewal of cultured myoblasts. However, the physiological relevance of hypoxia and hypoxia signaling in SCs in vivo remains largely unknown. Here, we demonstrate that SCs are in an intrinsic hypoxic state in vivo and express hypoxia-inducible factor 2A (HIF2A). HIF2A promotes the stemness and long-term homeostatic maintenance of SCs by maintaining their quiescence, increasing their self-renewal, and blocking their myogenic differentiation. HIF2A stabilization in SCs cultured under normoxia augments their engraftment potential in regenerative muscle. Conversely, HIF2A ablation leads to the depletion of SCs and their consequent regenerative failure in the long-term. In contrast, transient pharmacological inhibition of HIF2A accelerates muscle regeneration by increasing SC proliferation and differentiation. Mechanistically, HIF2A induces the quiescence and self-renewal of SCs by binding the promoter of the Spry1 gene and activating Spry1 expression. These findings suggest that HIF2A is a pivotal mediator of hypoxia signaling in SCs and may be therapeutically targeted to improve muscle regeneration.
Effects of therapeutic horseback riding on post-traumatic stress disorder in military veterans
Authors: Rebecca A. Johnson, David L. Albright, James R. Marzolf, Jessica L. Bibbo, Hayley D. Yaglom, Sandra M. Crowder, Gretchen K. Carlisle, Amy Willard, Cynthia L. Russell, Karen Grindler, Steven Osterlind, Marita Wassman, Nathan Harms
Journal: Military Medical Research (2018)

Large numbers of post-deployment U.S. veterans are diagnosed with post-traumatic stress disorder (PTSD) and/or traumatic brain injury (TBI), leading to an urgent need for effective interventions to reduce symptoms and increase veterans' coping. PTSD includes anxiety, flashbacks, and emotional numbing. The symptoms increase health care costs for stress-related illnesses and can make veterans' civilian life difficult. We used a randomized wait-list controlled design with repeated measures of U.S. military veterans to address our specific aim to test the efficacy of a 6-week therapeutic horseback riding (THR) program for decreasing PTSD symptoms and increasing coping self-efficacy, emotion regulation, social and emotional loneliness. Fifty-seven participants were recruited and 29 enrolled in the randomized trial. They were randomly assigned to either the horse riding group (n = 15) or a wait-list control group (n = 14). The wait-list control group experienced a 6-week waiting period, while the horse riding group began THR. The wait-list control group began riding after 6 weeks of participating in the control group. Demographic and health history information was obtained from all the participants. PTSD symptoms were measured using the standardized PTSD Checklist-Military Version (PCL-M). The PCL-M as well as other instruments including, The Coping Self Efficacy Scale (CSES), The Difficulties in Emotion Regulation Scale (DERS) and The Social and Emotional Loneliness Scale for Adults-short version (SELSA) were used to access different aspects of individual well-being and the PTSD symptoms. Participants had a statistically significant decrease in PTSD scores after 3 weeks of THR (P ≤ 0.01) as well as a statistically and clinically significant decrease after 6 weeks of THR (P ≤ 0.01). Logistic regression showed that participants had a 66.7% likelihood of having lower PTSD scores at 3 weeks and 87.5% likelihood at 6 weeks. Under the generalized linear model(GLM), our ANOVA findings for the coping self-efficacy, emotion regulation, and social and emotional loneliness did not reach statistical significance. The results for coping self-efficacy and emotion regulation trended in the predicted direction. Results for emotional loneliness were opposite the predicted direction. Logistic regression provided validation that outcome effects were caused by riding longer. The findings suggest that THR may be a clinically effective intervention for alleviating PTSD symptoms in military veterans.
ACTIVITY TRACKING DEVICES AS INNOVATIVE MONITORING STRATEGY AFTER PERCUTANEOUS REPAIR OF TRICUSPID AND MITRAL REGURGITATION
Authors: Thomas Stocker, Daniel Braun, Mathias Orban, Felicitas Scheck, Andrea Englmaier, Diana Roesler, Michael Nabauer, Steffen Massberg, Joerg Hausleiter
Journal: Journal of the American College of Cardiology (2018)
Cross border, highly individualised treatment of a patient with challenging extensively drug-resistant tuberculosis
Authors: Onno W. Akkerman, Floris Grasmeijer, Wiel C.M. de Lange, Huib A.M. Kerstjens, Gerard de Vries, Mathieu S. Bolhuis, Jan-Willem Alffenaar, Henderik W. Frijlink, Grace Smith, Roger Gajraj, Rina de Zwaan, Paul Hagedoorn, Martin Dedicoat, Dick van Soolingen, Tjip S. van der Werf
Journal: European Respiratory Journal (2018)

Extensively drug-resistant (XDR) tuberculosis (TB) is defined by resistance to isoniazid, rifampicin, any fluoroquinolone and at least one of the three second line injectable drugs, such as amikacin. Drug toxicity and duration impair adherence to treatment and outcome is rather poor [1]. We report on a particularly challenging XDR-TB patient with persistent non-adherence to treatment and an exceptionally complex drug susceptibility pattern. Crossing borders by treating a patient with difficult to treat XDR-TB; highly individualised but holistic approach <http://ow.ly/JyjK30ielsD>
BMA writes to Hunt to demand assurances before re-entering junior doctor talks
Authors: Abi Rimmer
Journal: BMJ (2015)

The BMA has written to the health secretary, Jeremy Hunt, to seek the clear “concrete assurances” that it wants before agreeing to re-enter negotiations on the junior doctor contract.

The BMA was replying to a letter that Hunt sent to Johann Malawana, chair of the BMA Junior Doctors Committee, on 8 October.1 In that letter, Hunt said that the new contract for junior doctors in England would not cut junior doctors’ pay or increase their working hours. Writing in reply, Malawana said that, if the health secretary was able to give assurances on the matters he had raised, then the BMA would be able to re-enter contract negotiations. “If you will offer us clear assurances on our reasonable needs for a safe contract, we would be in a position to enter negotiations on the number of other areas that …