tbuckley/cabot-search huggingface dataset:
How Adoptive Immunotherapy with Conventional T and Regulatory T Cells Exerts a Gvl Effect without GvHD, after Haploidentical Hematopoietic Transplantation
Authors: Loredana Ruggeri, Alessandra Carotti, Antonio Pierini, Franca Falzetti, Adelmo Terenzi, Elena Urbani, Amico Lucia, Sara Tricarico, Sara Piccinelli, Maria Speranza Massei, Sara Ciardelli, Mauro Di Ianni, Tiziana Zei, Roberta Iacucci Ostini, Valentina Lancellotta, Simonetta Saldi, Olivia Minelli, Rita Tognellini, Mara Merluzzi, Mauro Marchesi, Maurizio Caniglia, Cynthia Aristei, Brunangelo Falini, Massimo Fabrizio Martelli, Andrea Velardi
Journal: Blood (2018)
Successful renal denervation decreases the platelet activation status in hypertensive patients
Authors: Maria T K Zaldivia, Dagmara Hering, Petra Marusic, Yusuke Sata, Rebecca Lee, Murray D Esler, Nay M Htun, Jacqueline Duval, Louise Hammond, Ulrike Flierl, Xiaowei Wang, Grant R Drummond, Antony Walton, Elizabeth E Gardiner, Robert K Andrews, Markus P Schlaich, Karlheinz Peter
Journal: Cardiovascular Research (2019)

Abstract Aims To determine whether renal denervation (RDN) in hypertensive patients affects the platelet activation status. Methods and results We investigated the effect of RDN on the platelet activation status in 41 hypertensive patients undergoing RDN. Ambulatory blood pressure (BP), plasma sympathetic neurotransmitter Neuropeptide Y, and platelet activation markers were measured at baseline, at 3 months, and 6 months after RDN. RDN significantly decreased BP at 3 months (150.6 ± 11.3/80.9 ± 11.4 mmHg to 144.7 ± 12.0/77.1 ± 11.1 mmHg; P &amp;lt; 0.01) and at 6 months (144.3 ± 13.8/78.3 ± 11.1 mmHg; P &amp;lt; 0.01). Plasma levels of the sympathetic neurotransmitter Neuropeptide Y, an indicator of sympathetic nerve activity, were significantly decreased at 3 months (0.29 ± 0.11 ng/mL to 0.23 ± 0.11 ng/mL; P &amp;lt; 0.0001) and at 6 months (0.22 ± 0.12 ng/mL; P &amp;lt; 0.001) after RDN. This was associated with a reduction in platelet membrane P-selectin expression (3 months, P &amp;lt; 0.05; 6 months, P &amp;lt; 0.05), soluble P-selectin (6 months, P &amp;lt; 0.05), circulating numbers of platelet-derived extracellular vesicles (EVs) (3 months, P &amp;lt; 0.001; 6 months, P &amp;lt; 0.01), and phosphatidylserine expressing EVs (3 months, P &amp;lt; 0.001; 6 months, P &amp;lt; 0.0001), indicative of a reduction in platelet activation status and procoagulant activity. Only patients who responded to RDN with a BP reduction showed inhibition of P-selectin expression at 3 months (P &amp;lt; 0.05) and 6 months (P &amp;lt; 0.05) as well as reduction of glycoprotein IIb/IIIa activation at 3 months (P &amp;lt; 0.05). Notably, 13 patients who took aspirin did not show significant reduction in platelet P-selectin expression following RDN. Conclusion Our results imply a connection between the sympathetic nervous system and the platelet activation status and provide a potential mechanistic explanation by which RDN can have favourable effects towards reducing cardiovascular complications.
Achieving a Difference in Involved and Uninvolved Light Chains (dFLC) of Less Than 10mg/L Is the New Goal of Therapy in Systemic AL Amyloidosis: Analysis of 916 Patients Treated Upfront with Bortezomib-Based Therapy
Authors: Richa Manwani, Faye Sharpley, Shameem Mahmood, Sajitha Sachchithanantham, Helen Lachmann, Julian Gillmore, Carol Whelan, Philip Hawkins, Ashutosh D. Wechalekar
Journal: Blood (2018)
Is interval training the magic bullet for fat loss? A systematic review and meta-analysis comparing moderate-intensity continuous training with high-intensity interval training (HIIT)
Authors: Ricardo Borges Viana, João Pedro Araújo Naves, Victor Silveira Coswig, Claudio Andre Barbosa de Lira, James Steele, James Peter Fisher, Paulo Gentil
Journal: British Journal of Sports Medicine (2019)

To compare the effects of interval training and moderate-intensity continuous training (MOD) on body adiposity in humans, and to perform subgroup analyses that consider the type and duration of interval training in different groups.Systematic review and meta-analysis.English-language, Spanish-language and Portuguese-language searches of the electronic databases PubMed and Scopus were conducted from inception to 11 December 2017.Studies that met the following criteria were included: (1) original articles, (2) human trials, (3) minimum exercise training duration of 4 weeks, and (4) directly or indirectly compared interval training with MOD as the primary or secondary aim.Of the 786 studies found, 41 and 36 were included in the qualitative analysis and meta-analysis, respectively. Within-group analyses showed significant reductions in total body fat percentage (%) (interval training: -1.50 [95% CI -2.14 to -0.86, p<0.00001] and MOD: -1.44 [95% CI -2.00 to -0.89, p<0.00001]) and in total absolute fat mass (kg) (interval training: -1.58 [95% CI -2.74 to -0.43, p=0.007] and MOD: -1.13 [95% CI -2.18 to -0.08, p=0.04]), with no significant differences between interval training and MOD for total body fat percentage reduction (-0.23 [95% CI -1.43 to 0.97], p=0.705). However, there was a significant difference between the groups in total absolute fat mass (kg) reduction (-2.28 [95% CI -4.00 to -0.56], p=0.0094). Subgroup analyses comparing sprint interval training (SIT) with MOD protocols favour SIT for loss of total absolute fat mass (kg) (-3.22 [95% CI -5.71 to -0.73], p=0.01). Supervised training, walking/running/jogging, age (<30 years), study quality and intervention duration (<12 weeks) favourably influence the decreases in total absolute fat mass (kg) observed from interval training programmes; however, no significant effect was found on total body fat percentage (%). No effect of sex or body mass index was observed on total absolute fat mass (kg) or total body fat percentage (%).Interval training and MOD both reduce body fat percentage (%). Interval training provided 28.5% greater reductions in total absolute fat mass (kg) than MOD.CRD42018089427.
Prognostic implications of plasma volume status estimates in heart failure with preserved ejection fraction: insights from TOPCAT
Authors: Justin L. Grodin, Steven Philips, Wilfried Mullens, Petra Nijst, Pieter Martens, James C. Fang, Mark H. Drazner, W.H. Wilson Tang, Ambarish Pandey
Journal: European Journal of Heart Failure (2019)
Changing trends in coding for depression among the UK inflammatory bowel disease population
Authors: Jonathan Blackwell, Sonia Saxena, Richard C Pollok
Journal: Gut (2019)

We read with interest the findings of Frolkis et al and welcome the contribution to this challenging field of research.1 An important consideration in the methodology used is the case definition of incident depression, defined as any patient with a code for a depressive disorder in The Health Improvement Network (THIN) database between 1986 and 2012. The authors acknowledge …
Parallel-group controlled trial of esophagectomy versus chemoradiotherapy in patients with clinical stage I esophageal carcinoma (JCOG0502).
Authors: Ken Kato, Hiroyasu Igaki, Yoshinori Ito, Isao Nozaki, Hiroyuki Daiko, Masahiko Yano, Masaki Ueno, Satoru Nakagawa, Masakazu Takagi, Shigeru Tsunoda, Tetsuya Abe, Tetsu Nakamura, Jun Hihara, Yasushi Toh, Yuichi Shibuya, Junki Mizusawa, Hiroshi Katayama, Kenichi Nakamura, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2019)

7 Background: Esophagectomy (E) is the standard of care for stage I esophageal squamous cell carcinoma (ESCC), while chemoradiotherapy (CRT) is a treatment option. A parallel-group controlled trial including randomized arms to confirm the non-inferiority of CRT to E for stage IA ESCC was conducted. Methods: Patients (pts) with thoracic ESCC, adenosquamous cell, or basaloid cell carcinoma with stage IA (T1bN0M0), age 20 to 75, performance status 0 to 1, and adequate organ function were eligible. If pts accepted randomization, they were randomly allocated to E with 2-3 field lymph node dissection (arm A) or CRT (arm B). However, if pts had a preference and refused randomization, they were allocated to pts preference arm, E (arm C) or CRT (arm D). CRT consisted of cisplatin and 5-FU, with radiation at the dose of 60 Gy concurrently. The primary endpoint was overall survival (OS) of arm A and B, secondary endpoint included OS of arm C and D using inverse probability weighting with propensity score. The planned sample size in arm A and B was 114 pts in total with one-sided alpha of 10%, power of 75% and non-inferiority margin of HR as 1.78. The sample size in arm C and D was at least 156 pts in each arm with one-sided alpha of 2.5%, power of 85% and non-inferiority margin of HR as 1.78. Results: Between December 2006 and February 2013, 379 (Arm A: 4, B: 7, C: 209 C, D: 159) pts were enrolled. Primary endpoint was not calculated due to small number of randomized arms. Patients characteristics of arm C and D were as follows; median age: 62 and 65, male (%): 82.8 and 88.1, PS 0 (%): 99.5 and D 98.1. All histologic type was SCC except one basaloid cell carcinoma in arm C. The 3- and 5-year OS were 94.7% and 86.5% in arm C, and 93.1% and 85.5% in arm D (adjusted HR 1.05; 95% CI 0.67-1.64 [&lt; 1.78]).Treatment related death were observed in two pts in arm C and none in arm D. Conclusions: Though the accrual of randomized arms was shortened, CRT showed trend toward non-inferiority compared to E in pts preference arms. CRT is considered as a treatment option for stage IA ESCC with organ preservation. Clinical trial information: UMIN000000551.
Avelumab in patients with previously treated metastatic melanoma: phase 1b results from the JAVELIN Solid Tumor trial
Authors: Ulrich Keilholz, Janice M. Mehnert, Sebastian Bauer, Hugues Bourgeois, Manish R. Patel, Donald Gravenor, John J. Nemunaitis, Matthew H. Taylor, Lucjan Wyrwicz, Keun-Wook Lee, Vijay Kasturi, Kevin Chin, Anja von Heydebreck, James L. Gulley
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> We report phase 1b data from patients enrolled in the JAVELIN Solid Tumor clinical trial (NCT01772004) with unresectable stage IIIC or IV melanoma that had progressed after ≥1 line of therapy for metastatic disease. <h3>Patients and methods</h3> Patients received avelumab (10 mg/kg)—a human anti–PD-L1 antibody. Assessments included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. <h3>Results</h3> As of December 31, 2016, 51 patients were treated and followed for a median of 24.2 months (range, 16.1–31.5). Most patients had cutaneous (<i>n</i>&nbsp;= 28 [54.9%]) or ocular (<i>n</i>&nbsp;= 16 [31.4%]) melanoma and had received a median of 2 prior lines of therapy (range, 0–4), including ipilimumab (<i>n</i>&nbsp;= 26 [51.0%]). The confirmed ORR was 21.6% (95% CI, 11.3–35.3; complete response, 7.8%; partial response, 13.7%). The median duration of response was not estimable (95% CI, 2.6 months-not estimable). Median PFS and OS were 3.1 months (95% CI, 1.4–6.3) and 17.2 months (95% CI, 6.6-not estimable), respectively. Subgroup analyses suggested meaningful clinical activity (ORR [95% CI]) in patients with non-ocular melanoma (31.4% [16.9–49.3]), PD-L1–positive tumors (42.1% [20.3–66.5]), or prior ipilimumab therapy (30.8% [14.3–51.8]). Thirty-nine patients (76.5%) had a treatment-related adverse event (TRAE), most commonly infusion-related reaction (29.4%), fatigue (17.6%), and chills (11.8%); 4 patients (7.8%) had a grade 3 TRAE. Five patients (9.8%) had an immune-related TRAE (all were grade 1/2). No grade 4 TRAEs or treatment-related deaths were reported. <h3>Conclusion</h3> Avelumab showed durable responses, promising survival outcomes, and an acceptable safety profile in patients with previously treated metastatic melanoma. <h3>Trial registration</h3> ClinicalTrials.gov identifier: NCT01772004.
Serial testing of Mycobacterium tuberculosis infection in Chinese village doctors by QuantiFERON-TB Gold Plus, QuantiFERON-TB Gold in-Tube and T-SPOT.TB
Authors: Haoran Zhang, Henan Xin, Dakuan Wang, Shouguo Pan, Zisen Liu, Xuefang Cao, Jinxing Wang, Xiangwei Li, Boxuan Feng, Mufei Li, Qianting Yang, Mingxia Zhang, Qi Jin, Lei Gao
Journal: Journal of Infection (2019)
Zolbetuximab combined with EOX as first-line therapy in advanced CLDN18.2+ gastric (G) and gastroesophageal junction (GEJ) adenocarcinoma: Updated results from the FAST trial.
Authors: Ugur Sahin, Özlem Tureci, Georgy M. Manikhas, Florian Lordick, Andriy Rusyn, Ihor Vynnychenko, Assen Dudov, Igor Bazin, Igor Bondarenko, Bohuslav Melichar, Karl Dhaene, Kai Wiechen, Daniel Maurus, Martin H. Schuler, Salah-Eddin Al-Batran
Journal: Journal of Clinical Oncology (2019)

16 Background: Physiologically, the tight junction protein CLDN18.2 is present only in the gastric mucosa. Upon malignant transformation, CLDN18.2 epitopes are exposed on the cell surface and accessible to targeted therapy. Zolbetuximab (formerly IMAB362) is a chimeric mAb that mediates specific killing of CLDN18.2+ cancer cells through immune effector mechanisms; single-agent activity has been reported in G/GEJ cancer. Methods: Patients (pts) with advanced HER2-negative (HER–) G/GEJ cancer with CLDN18.2 expression of ≥ 2+ staining intensity with the anti-CLDN18 43-14A mAb in ≥ 40% tumor cells were eligible (NCT01630083). Patients were randomized 1:1 to receive first-line EOX ± zolbetuximab (loading dose 800 mg/m 2 , then 600 mg/m 2 ) Q3W. The study was extended with an exploratory arm of 1000 mg/m 2 zolbetuximab + EOX Q3W (data not presented). Primary endpoint was PFS; secondary endpoints included OS, ORR, and safety/tolerability. Results: A total of 161 pts (G, n = 128; GEJ, n = 27; esophagus n = 6) were randomized to receive zolbetuximab (800/600 mg) + EOX (n = 77) or EOX alone (n = 84). In all, 45% of pts had diffuse type histology per Lauren’s classification. Median PFS was longer with zolbetuximab + EOX (7.5 mo) versus EOX alone (5.3 mo; P &lt; 0.0005; HR 0.44; 95% CI 0.29, 0.67). Median OS (13 vs 8.4 mo; P = 0.0008; HR 0.56; 95% CI 0.40, 0.79) and ORR (39 vs 25%; P = 0.022) were also significantly higher with zolbetuximab + EOX versus EOX alone. Increased efficacy was more pronounced in pts with high CLDN18.2 expression (≥ 2+ staining intensity in ≥ 70% tumor cells). Zolbetuximab + EOX was generally well tolerated. Most AEs considered related to zolbetuximab and EOX (ie, nausea, vomiting, neutropenia, anemia) were of grade ≤ 2 severity; there was no significant increase in grade ≥ 3 events with the addition of zolbetuximab to EOX. Conclusions: Addition of zolbetuximab to first-line chemotherapy resulted in significantly longer PFS and OS and higher ORR with manageable toxicity. A phase III trial is evaluating the combination of zolbetuximab plus mFOLFOX6 as first-line treatment of CLDN18.2+/HER2-negative, advanced/metastatic G or GEJ adenocarcinoma (NCT03504397). Clinical trial information: NCT01630083.
How long does a knee replacement last? A systematic review and meta-analysis of case series and national registry reports with more than 15 years of follow-up
Authors: Jonathan T Evans, Robert W Walker, Jonathan P Evans, Ashley W Blom, Adrian Sayers, Michael R Whitehouse
Journal: The Lancet (2019)

BackgroundKnee replacements are the mainstay of treatment for end-stage osteoarthritis and are effective. Given time, all knee replacements will fail and knowing when this failure might happen is important. We aimed to establish how long a knee replacement lasts.MethodsIn this systematic review and meta-analysis, we searched MEDLINE and Embase for case series and cohort studies published from database inception until July 21, 2018. Articles reporting 15 year or greater survival of primary total knee replacement (TKR), unicondylar knee replacement (UKR), and patellofemoral replacements in patients with osteoarthritis were included. Articles that reviewed specifically complex primary surgeries or revisions were excluded. Survival and implant data were extracted, with all-cause survival of the knee replacement construct being the primary outcome. We also reviewed national joint replacement registry reports and extracted the data to be analysed separately. In the meta-analysis, we weighted each series and calculated a pooled survival estimate for each data source at 15 years, 20 years, and 25 years, using a fixed-effects model. This study is registered with PROSPERO, number CRD42018105188.FindingsFrom 4363 references found by our initial search, we identified 33 case series in 30 eligible articles, which reported all-cause survival for 6490 TKRs (26 case series) and 742 UKRs (seven case series). No case series reporting on patellofemoral replacements met our inclusion criteria, and no case series reported 25 year survival for TKR. The estimated 25 year survival for UKR (based on one case series) was 72·0% (95% CI 58·0–95·0). Registries contributed 299 291 TKRs (47 series) and 7714 UKRs (five series). The pooled registry 25 year survival of TKRs (14 registries) was 82·3% (95% CI 81·3–83·2) and of UKRs (four registries) was 69·8% (67·6–72·1).InterpretationOur pooled registry data, which we believe to be more accurate than the case series data, shows that approximately 82% of TKRs last 25 years and 70% of UKRs last 25 years. These findings will be of use to patients and health-care providers; further information is required to predict exactly how long specific knee replacements will last.FundingThe National Institute for Health Research, the National Joint Registry for England, Wales, Northern Ireland, and Isle of Man, and the Royal College of Surgeons of England.
How can we improve oncofertility care for patients? A systematic scoping review of current international practice and models of care
Authors: Antoinette Anazodo, Paula Laws, Shanna Logan, Carla Saunders, Jo Travaglia, Brigitte Gerstl, Natalie Bradford, Richard Cohn, Mary Birdsall, Ronald Barr, Nao Suzuki, Seido Takae, Ricardo Marinho, Shuo Xiao, Chen Qiong-Hua, Nalini Mahajan, Madhuri Patil, Devika Gunasheela, Kristen Smith, Leonard Sender, Cláudia Melo, Teresa Almeida-Santos, Mahmoud Salama, Leslie Appiah, Irene Su, Sheila Lane, Teresa K Woodruff, Allan Pacey, Richard A Anderson, Francoise Shenfield, William Ledger, Elizabeth Sullivan
Journal: Human Reproduction Update (2018)

Fertility preservation (FP) is an important quality of life issue for cancer survivors of reproductive age. Despite the existence of broad international guidelines, the delivery of oncofertility care, particularly amongst paediatric, adolescent and young adult patients, remains a challenge for healthcare professionals (HCPs). The quality of oncofertility care is variable and the uptake and utilization of FP remains low. Available guidelines fall short in providing adequate detail on how oncofertility models of care (MOC) allow for the real-world application of guidelines by HCPs.
Abstract 12556: Prospective Association of Incident Atrial Fibrillation With Resting Heart Rate: The Henry Ford Hospital Exercise Testing (FIT) project
Authors: Amer I Aladin, Mahmoud Al Rifai, Shereen H Rasool, Steven J Keteyian, Clinton A Brawner, Roger S Blumenthal, Mouaz H Al-Mallah, Michael J Blaha, John W McEvoy
Journal: Circulation (2015)

Objective: Autonomic nervous system dysfunction plays an important role in atrial fibrillation (AF) initiation. Research suggests that vagal tone may mediate paroxysmal AF, such that a low resting heart rate (RHR) is associated with incident AF. However, conflicting reports also suggest that elevated RHR identifies risk for AF. Thus, we sought to further clarify the link between RHR and AF, independent of cardiorespiratory fitness (CRF). Methods: We analyzed 51,451 individuals without a history of AF who underwent a clinically-indicated exercise stress test between January 1991 and May 2009. Persons on nodal blocking medications were excluded. Adjusted hazard ratios (HRs) for AF were estimated using Cox models with baseline RHR categorized by &lt;70, 70-85 (reference) and &gt;85 beats-per-minute (bpm) (sensitivity analyses used quartile of RHR). Incident AF was defined by coding for new AF on claims files on ≥three subsequent encounters. We tested for effect modification by age (&lt;60 vs. ≥60 years) and CRF (determined metabolic equivalents [METs] achieved on stress testing). Results: Mean age was 53 ± 13 years, 53% were men and 28% were black. Subjects in the lowest RHR category (&lt;70 bpm) were older, more likely to be male diabetic and hypertensive, but had higher CRF. Compared to RHR 70-85, those with RHR &lt;70 were at increased risk of AF [HR (95% CI), 1.15 (1.06-1.25)] (Table). While there was a trend for higher risk with RHR &gt;85, this was non-significant after full adjustment. The association between low RHR and AF was independent of CRF and, in the sensitivity analysis using RHR quartile, appeared to be driven by excess risk in persons with RHR &lt;64 bpm. There was no interaction by age or CRF level. Conclusion: We found that low RHR had a robust association with incident AF. Persons with low RHR, particularly in the presence of other AF risk factors, may benefit from AF screening and heart rhythm surveillance.
Comparison between a rotatable sphincterotome and a conventional sphincterotome for selective bile duct cannulation
Authors: Akira Kurita, Yasushi Kudo, Kenichi Yoshimura, Tadamasa Takemura, Yoshiharu Mori, Shunjiro Azuma, Makoto Sono, Kohei Yamakawa, Koutarou Watanabe, Satoshi Nishimura, Hiroki Yamashita, Shinsuke Akiyama, Mayuki Omatsu, Shujiro Yazumi
Journal: Endoscopy (2019)

Abstract Background Selective biliary cannulation (SBC) is the first challenge of endoscopic retrograde cholangiopancreatography (ERCP), especially for trainees, and a rotatable sphincterotome may be useful to guide the directional axis of the scope and SBC. Methods We performed a prospective randomized single-center trial, enrolling 200 patients with a native papilla who required therapeutic biliary ERCP. Patients were randomly assigned to the rotatable sphincterotome group (n = 100) or the conventional sphincterotome group (n = 100). The primary endpoint was successful SBC by the trainees within 10 minutes. Results The early and late cannulation success rates did not differ significantly between the groups (P = 0.46 and P &gt; 0.99, respectively). For the patients in whom trainees failed to achieve SBC, the rotatable sphincterotome was used as a rescue cannulation technique in four patients from the conventional group; in no patients in the rotatable group was the conventional sphincterotome used for SBC. Post-ERCP pancreatitis (PEP) occurred in 11 patients (5.5 %; 6 mild, 5 moderate); the incidence did not differ significantly between the two groups (rotatable group 3 %, conventional group 8 %; P = 0.21). The two groups were thus combined for evaluation of the factors relating to cannulation difficulty for trainees, which revealed that orientation of the papilla was a significant factor (P &lt; 0.001). Conclusions The type of sphincterotome used did not affect the success of SBC by trainees. However, orientation of the papilla was revealed to be a significant factor relating to cannulation difficulty for trainees overall.
Prognostic Significance of Neutrophil to Lymphocyte Ratio (NLR) in Relapsed/Refractory Aggressive Lymphoma Salvage Chemotherapy — Analysis of Canadian Cancer Trials Group (CCTG) ly.10 Trial
Authors: Mina Dehghani Mohammadabadi, Annette E Hay, Lois E. Shepherd, Michael Crump, Bingshu E. Chen, Tara Baetz
Journal: Blood (2018)