tbuckley/cabot-search huggingface dataset:
Salivary duct carcinoma: Clinical outcomes and prognostic factors in 157 patients and results of androgen deprivation therapy in recurrent disease (n=31)—Study of the Dutch head and neck society (DHNS).
Authors: Eline Boon, Miranda Bel, Winette TA van der Graaf, Robert J.J. van Es, Simone Eerenstein, Robert Baatenburg De Jong, Michiel van den Brekel, Lilly-Ann van der Velden, Max Witjes, Ann Hoeben, Stefan M. Willems, Elisabeth Bloemena, Laura Smit, Sjoukje Oosting, Uta E Flucke, Carla M.L. Van Herpen
Journal: Journal of Clinical Oncology (2016)

6016 Background: Salivary Duct Carcinoma (SDC) is a rare, highly aggressive subtype of salivary gland cancer, which is androgen receptor (AR) positive in most pts. In recurrent disease androgen deprivation therapy (ADT) can be used, however only limited data are available. The aim of this study was to evaluate clinical outcome, to identify prognostic factors for overall survival (OS) and to retrospectively analyze efficacy of ADT. Methods: The nationwide network and registry of histo- and cytopathology (PALGA) identified all adult pts with SDC between 1990 - 2014 in the Netherlands. Lymph node ratio (LNR) was defined as the number of positive LN divided by the total number of LN after neck dissection. Survival analyses were conducted using Kaplan-Meier method. The Cox proportional hazard model was used to identify prognostic factors on uni- and multivariable analyses. Results: A total of 157 pts with SDC were identified. Median age was 66 years, 77% were male. AR and HER2neu were positive in 100% and 44%, respectively. Median number of positive LN was 4 (range 0–97) and median LNR was 0.20. Median OS was 44 months (95% CI 30-48). Multivariable analyses identified male gender, high N-stage and high LNR as significant poor prognostic factors for OS. After median 14 months (range 1-87) 84 pts (54%) had recurrent disease: local recurrence in n = 19 (23%), regional recurrence in n = 31 (37%) and distant metastases in n = 72 (86%). Only 12 (14%) of recurrent pts had local and/or regional recurrence without distant metastases. 31 pts with recurrent SDC were treated with ADT: 4 pts had PR, 10 pts had SD and 17 pts had PD. Median PFS of all ADT treated pts was 3.8 months (range 1-25) and median OS 4 months (range 1–64). In pts with PR or SD (45%) median PFS was 11 months (range 3-25) and median OS was 29 months (range 3-64). Conclusions: More than half of the SDC pts developed recurrent disease. Male gender, high N-stage and high LNR were correlated with worse OS. In this largest series of ADT treated SDC pts, we found clinical benefit (PR + SD) in 45% of pts for a median duration of 11 months and median OS of 29 months. We recommend considering ADT treatment in recurrent SDC.
Survival of patients with cirrhosis and acute peptic ulcer bleeding compared with variceal bleeding using current first‐line therapies
Authors: Alba Ardevol, Gemma Ibañez‐Sanz, Joaquim Profitos, Carles Aracil, Josep M. Castellvi, Edilmar Alvarado, Alba Cachero, Diana Horta, Josep Miñana, Bárbara Gomez‐Pastrana, Oana Pavel, Eva Dueñas, Meritxell Casas, Montserrat Planella, Jose Castellote, Candid Villanueva
Journal: Hepatology (2017)

The presence of cirrhosis increases the mortality of patients with peptic ulcer bleeding (PUB). Both acute variceal bleeding (AVB) and PUB are associated with substantial mortality in cirrhosis. This multicenter cohort study was performed to assess whether the mortality of patients with cirrhosis with PUB is different from that of those with AVB. Patients with cirrhosis and acute gastrointestinal bleeding were consecutively included and treated with somatostatin and proton pump inhibitor infusion from admission and with antibiotic prophylaxis. Emergency endoscopy with endoscopic therapy was performed within the first 6 hours. 646 patients with AVB and 144 with PUB were included. There were baseline differences between groups, such as use of gastroerosive drugs or β‐blockers. Child‐Pugh and Model for End‐Stage Liver Disease MELD scores were similar. Further bleeding was more frequent in the AVB group than those in the PUB group (18% vs. 10%; odds ratio [OR] = 0.50; 95% confidence interval [CI] = 0.29‐0.88). However, mortality risk at 45 days was similar in both groups (19% in the AVB group vs. 17% in the PUB group; OR = 0.85; 95% CI = 0.55‐1.33; P = 0.48). Different parameters, such as Child‐Pugh score, acute kidney injury, acute on chronic liver failure, or presence of shock or bacterial infection, but not the cause of bleeding, were related to the risk of death. Only 2% of the PUB group versus 3% of the AVB group died with uncontrolled bleeding (P = 0.39), whereas the majority of patients in either group died from liver failure or attributed to other comorbidities. Conclusion: Using current first‐line therapy, patients with cirrhosis and acute peptic ulcer bleeding have a similar survival than those with variceal bleeding. The risk of further bleeding is higher in patients with variceal hemorrhage. However, few patients in both groups died from uncontrolled bleeding, rather the cause of death was usually related to liver failure or comorbidities. (Hepatology 2018;67:1458‐1471).
Tumor programmed cell death ligand 1 expression correlates with nodal metastasis in patients with cutaneous squamous cell carcinoma of the head and neck
Authors: Juana María García-Pedrero, Pablo Martínez-Camblor, Susana Diaz-Coto, Pablo Munguia-Calzada, Aitana Vallina-Alvarez, Francisco Vazquez-Lopez, Juan Pablo Rodrigo, Jorge Santos-Juanes
Journal: Journal of the American Academy of Dermatology (2017)
When is it time to start rehab? exploring the optimal timing to initiate active rehabilitation for concussion management in children and adolescents
Authors: Isabelle Gagnon, Danielle M. Dobney CAT (C), Lisa Grilli MSc PT, Helen Kocilowicz, Christine Beaulieu, Meghan Straub, Debbie Friedman
Journal: British Journal of Sports Medicine (2017)

Objective Estimate the influence of time to initiation of active rehabilitation on post-concussion symptom (PCS) severity in youth who are slow to recover from concussion. Design Retrospective analysis of a prospective cohort Setting Concussion clinic of a tertiary care Paediatric Trauma Centre in Canada. Participants 569 youth (14.3±2.3 years) with persistent PCS. Clinic patients’ information is entered prospectively in a clinical database and participants were selected for this study if they 1) participated in the active rehabilitation program, and 2) had available PCS assessments at the intake and follow-up visits. Intervention Active rehabilitation consisting of: aerobic exercise, coordination exercises and, education/motivation. The intervention was initiated with a Physical Therapist in the Concussion clinic continued as a daily home program. The independent variable was time to initiation of the active rehabilitation program measured in weeks (2, 3, 4, 5, 6+). Outcome measure Symptom severity measured by the PCS scale of the SCAT3 at follow-up visit, 2 weeks after initiation of intervention.Main results: Patients initiating active rehabilitation 2 weeks post-injury were significantly less symptomatic at follow-up (Mdn PCS score=5) compared to those starting five (Mdn=17) and six weeks or more (Mdn=17.5) (p=0.0002). Those starting at 3 (Mdn=9) and 4 (Mdn=10) weeks also had significantly less severe symptoms compared to those starting 6 weeks or later (p&lt;0.05). Conclusions The findings suggest that children benefit more from active rehabilitation if it is initiated between two and four weeks post-injury, and have poorer outcomes if it is delayed beyond 6 weeks post-injury. Competing interests None.
Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 compared with rituximab in patients with previously untreated advanced-stage follicular lymphoma: a randomised, double-blind, parallel-group, non-inferiority phase 3 trial
Authors: Won Seog Kim, Christian Buske, Michinori Ogura, Wojciech Jurczak, Juan-Manuel Sancho, Edvard Zhavrid, Jin Seok Kim, José-Ángel Hernández-Rivas, Aliaksandr Prokharau, Mariana Vasilica, Rajinish Nagarkar, Dzhelil Osmanov, Larry W Kwak, Sang Joon Lee, Sung Young Lee, Yun Ju Bae, Bertrand Coiffier
Journal: The Lancet Haematology (2017)
Divide and conquer: identifying acute respiratory distress syndrome subphenotypes
Authors: Manu Shankar-Hari, Daniel F McAuley
Journal: Thorax (2017)

The acute respiratory distress syndrome (ARDS) definition identifies patients with acute onset hypoxaemia and respiratory failure, who have bilateral opacities on chest radiograph that are not fully explained by cardiac failure or fluid overload.1 ARDS is a common illness that accounts for approximately 10% of critical care admissions and 20% of patients requiring mechanical ventilation.2 The hospital mortality in patients with ARDS remains high, increasing from approximately 35% for those with mild disease to 46% for those with severe ARDS.2 This high mortality has remained relatively unchanged in the last 20 years.3 To date, despite decades of research, there is no pharmacological treatment that can modify the underlying biological mechanisms implicated in ARDS and improve patient outcomes.4 Within ARDS populations, there is substantial biological and outcome heterogeneity, with observed differences in dominant pathogenic mechanisms, treatment responses and outcomes.5–7 Identifying ARDS subphenotypes based on pathogenic mechanisms that determine treatment responses irrespective of ARDS severity is defined as predictive enrichment.7 8 The identification of such ARDS subphenotypes will enable improved trial design in ARDS by selecting patients based on responder characteristics to therapeutic interventions, hopefully resulting in improved outcomes.6

In Thorax , Bos et al report a cohort study in 700 ARDS patients, testing the hypothesis that ARDS subgroups exist due to differences in biological characteristics.9 In this retrospective analysis of a prospectively collected cohort, 20 biomarkers were …
NEOINTIMAL CHARACTERISTICS AFTER EVEROLIMUS–ELUTING STENTS IMPLANTATION FOR CHRONIC TOTAL OCCLUSION: OPTICAL COHERENCE TOMOGRAPHIC STUDY
Authors: Naotaka Okamoto, Masami Nishino, Taishi Kato, Ayano Ishiyama, Hiroyuki Onishi, Akihiro Tanaka, Naoki Mori, Daisuke Nakamura, Yasuharu Lee, Takahiro Yoshimura, Masayuki Taniike, Nobuhiko Makino, Hiroyasu Kato, Yasuyuki Egami, Ryu Shutta, Hisaki Morita, Jun Tanouchi, Yoshio Yamada
Journal: Journal of the American College of Cardiology (2013)
Phase I study of AZD1775 with radiation therapy (RT) and temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM) and evaluation of intratumoral drug distribution (IDD) in patients with recurrent GBM.
Authors: Brian Michael Alexander, Manmeet Singh Ahluwalia, Arati Suvas Desai, Jorg Dietrich, Thomas Joseph Kaley, David M. Peereboom, Naoko Takebe, Jeffrey G. Supko, Serena Desideri, Joy D. Fisher, Megan Sims, Xiaobu Ye, Louis B. Nabors, Stuart A. Grossman, Patrick Y. Wen
Journal: Journal of Clinical Oncology (2017)

2005 Background: The standard of care treatment for newly diagnosed GBM is maximal safe surgical resection followed by two DNA damaging agents, RT and TMZ. Cellular response to DNA damage involves checkpoints that halt the cell cycle to allow DNA repair. AZD1775 is an oral small molecular inhibitor of a nuclear tyrosine kinase Wee1, a key regulator of the G2/M checkpoint. Abrogation of the G2/M checkpoint prevents repair and pushes cells into mitosis with unrepaired DNA damage. AZD1775 was shown to enhance TMZ and RT effects in preclinical models. Methods: The Adult Brain Tumor Consortium 1202 trial (NCT01849146) is a phase I, open label, multicenter dose-finding study of AZD1775 in combination with standard RT and TMZ followed by an IDD study for patients undergoing surgery for recurrent GBM. The dose finding portion is comprised of two arms, one with AZD1775 given Monday through Friday during concurrent RT/TMZ and a second arm given with adjuvant TMZ qd x 5d/28d cycle. Each arm had standard 3+3 design. A combination cohort with both concurrent and adjuvant AZD1775 at MTD and analysis of PK/PD and IDD at MTD in patients undergoing surgery for recurrent GBM followed. Results: 51 patients enrolled in the dose finding arms. For the concurrent arm, the MTD was 200 mg. At 275 mg one patient had grade 3 fatigue and another had grade 4 thrombocytopenia and neutropenia. Two of 6 total patients enrolled at 200 mg experienced DLTs (grade 4 neutropenia and grade 3 ALT elevation). The MTD for the adjuvant arm was 425 mg as 1 of 6 patients had DLT (grade 4 decrease in ANC). At 500 mg, 2 of 3 patients experienced intolerable diarrhea despite prophylaxis. Enrollment in the combination cohort is completed and evaluation of safety is underway. The drug concentration in contrast enhancing and non-enhancing brain tumor was 4-8 x and 0.5-2.6 x greater than plasma, respectively for patients on IDD portion. Conclusions: The MTD for AZD1775 in combination with RT/TMZ is 200 mg qd M-F with concurrent RT/TMZ and 425 mg qd x 5d/28d cycle in combination with adjuvant TMZ. IDD and PK/PD analysis is ongoing to inform the decision to proceed to phase II testing. Clinical trial information: NCT01849146.
<i>GGNBP2</i> to suppress tumor growth through modulating ERα action in breast cancer.
Authors: Yunhui Hu, Zi-Jian Lan, Sheng Zhang, Xian Li, Huaxin Zhou, Jixian Ding, Carolyn M. Klinge, Austin J. Cooney, Zhenmin Lei, Jin Zhang
Journal: Journal of Clinical Oncology (2016)

e12009 Background: Gametogenetin binding protein 2 (GGNBP2) is encoded in human chromosome 17q12-q23, a region known as a breast and ovarian cancer susceptibility locus. GGNBP2 has a single C2H2 zinc finger and a consensus LxxLL nuclear receptor (NR) binding motif. It has been reported that GGNBP2 being remarkably down-regulated in several human cancer cell lines. The similar NR binding motifs are also found in some other known breast cancer susceptibility genes such asBRCA1, suggesting that GGNBP2 may function as a candidate of breast cancer susceptibility gene. Methods: A cancer expression array containing 50 pair-wise human normal and breast tumor tissues were utilized to examine GGNBP2 expression in breast cancer samples. To address the potential anti-breast tumor activity of GGNBP2 in vitro, we expressed exogenous GGNBP2 in T47D, MCF-7, MCF-10A and MCF-10F cells. Cell proliferation, migration and invasion were assessed by cell growth curve, wound healing assays and colony formation assays, respectively. In vitro protein-protein interaction and luciferase reporter assays were performed to determine whether GGNBP2 interacts with ERα and modulates its transcriptional activity. qPCR and Western blot were carried out to evaluate the effects of GGNBP2 overexpression on ERa target genes, CCND1 and TFF1 expression. The anti-oncogenic activity of GGNBP2 was further verified by xenograft in mice. Results: GGNBP2 expression is reduced in primary human breast tumors. Overexpression of GGNBP2 selectively inhibits the proliferation of ERα positive breast cancer cells. Stable GGNBP2 overexpression in T47D cells inhibits 17β-estradiol (E2)–stimulated proliferation as well as migration, invasion, anchorageindependent growth in vitro and xenograft tumor growth in mice. We further demonstrate that GGNBP2 protein physically interacts with ERα, inhibits E2-induced activation of estrogen response element-driven reporter activity and attenuates ER target gene expression in T47D cells. Conclusions: GGNBP2 is a novel breast cancer tumor suppressor functioning as a nuclear receptor co-repressor to restrain ERα activity and tumorigenesis in human breast cancer.
What's in a name?
Authors: J. F Bourke, M. F Strack, R. A C Graham-Brown
Journal: BMJ (1993)

register should be well defined.Having a list of recognised qualifications or colleges would be pointless as a potential patient would find it almost impossible to ascertain which were bona fide; in addition, there would be no opportunity to impose sanctions.Lastly, hypnotherapy does not have to be confined to the medical profession as a medical qualification is not a prerequisite to being a good hypnotherapist.Indeed, some lay therapists are better than their medical
SELF-REPORTED INJURY MECHANISMS IN CLIMBERS
Authors: Gareth Jones, Cara Woodard, Paul Sharples, Mark Johnson
Journal: British Journal of Sports Medicine (2017)

Background Climbing is an increasingly popular sport worldwide. However relatively little is known about the mechanisms of injury sustained by climbers. Objective To investigate mechanisms of injury in a representative sample of British climbers. Design Retrospective cross-sectional study. Setting Online survey of active climbers. Patients (or Participants) 369 active climbers (men n=307, mean±SD, age=37.66 ±14.38 years; Women n=62, mean ±SD, age=34.63 ±12.19 years). Interventions (or Assessment of Risk Factors) Epidemiological incidence proportion (IP) and mechanism of injury. Main Outcome Measurements Injuries that resulted in medical intervention and/or withdrawal from participation for ≥1 day. Results Of 369 climbers surveyed, 299 sustained at least 1 injury in the last 12 months resulting from climbing. The IP was 0.810 (95% CI: 0.770–0.850). Thus the average probability of sustaining at least one injury was 81% (95% CI: 77–85). The total number of injuries sustained was 1088 providing a clinical incidence of 2.95 injuries per climber. 94 climbers sustained an acute injury as a result of impact with the climbing surface and/or ground, 212 climbers sustained an injury resulting from chronic overuse and 166 climbers sustained injuries resulting from a non-impact acute trauma. The average probabilities of sustaining injury per mechanism were: impact injury 25.5% (95% CI: 23.2–27.8); acute non-impact injury 45.1% (95% CI: 42.5–47.7) and chronic overuse injury 57.5% (95% CI: 54.9–60.1). Injury from chronic overuse was positively associated with indoor lead operating standard (P=0.007), bouldering operating standard (P&lt; 0.001) and bouldering frequency (P&lt; 0.001). The most common injury site was the fingers with 180 participants (60%) sustaining at least one finger injury. 85 participants sustained at least 1 chronic overuse reinjury. Conclusions The most commonly reported injury mechanism was chronic overuse. The most common site was the fingers. Chronic overuse injuries due to repetitive loading may have been historically preceded by a non-impact acute trauma.
A risk score predicting ICU outcome in solid cancer patients.
Authors: Ting-Hui Wu, Han-Chung Emily Hsiue, Yung-Hsuan Chen, Chiao-Feng Cheng, Po-Chun Yang, Keng-Man Chiang, Pei-Lin Lee
Journal: Journal of Clinical Oncology (2016)

e18113 Background: Admitting cancer patients to the intensive care unit (ICU) remains controversial due to perceived poor outcome. This study aimed to (1) assess the predictive value of Acute Physiology and Chronic Health Evaluation (APACHE) II score, (2) identify prognostic factors, and (3) establish a risk score to predict ICU outcome in solid cancer patients. Methods: A total of 500 adult patients with solid cancer admitted to the 44-bed medical ICU at the National Taiwan University Hospital due to medical complications from January 2013 to December 2014 were reviewed. Patients were randomized 2:1 to training and validation groups. The regression coefficients of the multivariate logistic regression were used to generate the score for each factor. Results: NSCLC (n=123, 24.6%), GI tract malignancy (n=85, 17.0%), and HCC (n=64, 12.8%) were the leading malignancies. The average APACHE II on admission and at 48 hours were 24.7±8.8 and 19.2±7.4 respectively. The ICU mortality rate was 38.4%. APACHE II at admission, at 48 hours, the difference and sum of the two APACHE II scores were unsatisfactory in predicting ICU mortality (AUC= 0.65, 0.66, 0.48, and 0.60 respectively). In multivariate analysis of the training group, APACHE II, invasive mechanical ventilation (IMV), acute kidney injury requiring renal replacement therapy (RRT) and uncontrolled disease (progressive disease or newly diagnosed) were significant predictors of ICU mortality (Table 1). A risk score for ICU mortality was established: APACHE II + 15 x (IMV + RRT + uncontrolled disease). The developed risk score had improved predictive power in both the training and validation groups (AUC = 0.79 and 0.75, respectively). Conclusions: APACHE II is an unsatisfactory predictor of ICU outcome in solid cancer patients. A risk score incorporating underlying cancer status, receipt of invasive interventions, and APACHE II improved prediction of ICU mortality. This score could aid prognosis prediction and clinical decision making. Multivariate logistic regression model for risk score generation. Variables Coefficient Odds ratio (95% C. I.) p value APACHE II 0.081 1.08 (1.04-1.13) <0.001 IMV 1.189 3.29 (1.03-10.44) 0.044 RRT 1.197 3.31 (1.32-8.29) 0.011 Uncontrolled disease 1.187 3.28 (1.36-7.90) 0.008
Vocal fold paralysis on positron emission tomography-CT
Authors: Chelsea Ma, Zachary AK Frosch, Beth Overmoyer, Avraham Z Cooper
Journal: Thorax (2017)

A 58-year-old woman with a 40 pack-year smoking history presented with several weeks of shortness of breath, chest pain radiating to the back and a hoarse voice. Initial chest X-ray showed a new left upper lobe mass concerning for malignancy. She then underwent positron emission tomography(PET)-CT, which revealed a fluorodeoxyglucose (FDG)-avid left hilar lung mass, (figure 1, red arrow) and left supraclavicular and mediastinal lymphadenopathy (figure 1, orange and green arrows). The PET-CT also showed asymmetric FDG uptake of the vocal folds at the level of the thyroid cartilage …
Outcome of Newly Diagnosed Acute Myeloid Leukemia with Hyperleukocytosis: Retrospective Study of JALSG AML201
Authors: Kenji Matsumoto, Shin Fujisawa, Maki Hagihara, Sumihisa Honda, Shigeki Ohtake, Shuichi Miyawaki, Toru Sakura, Dobashi Nobuaki, Kinya Ohata, Yukiyasu Ozawa, Iekuni Ou, Asao Hirose, Tomoya Maeda, Yoshikazu Ito, Noriko Doki, Hitoshi Kiyoi, Kazunori Ohnishi, Tomoki Naoe, Yasushi Miyazaki, Hideaki Nakajima
Journal: Blood (2016)