tbuckley/cabot-search huggingface dataset:
Efficacy and safety of taxane-monotherapy in advanced gastric cancer refractory to triplet chemotherapy with docetaxel, cisplatin, and S-1: A multicenter retrospective study.
Authors: Sadayuki Kawai, Sakura Iizumi, Atsuo Takashima, Yukiya Narita, Masahiro Tajika, Tomohiro Matsushima, Hirofumi Yasui, Kei Muro, Daisuke Takahari, Narikazu Boku
Journal: Journal of Clinical Oncology (2017)

154 Background: While taxane-monotherapy following fluoropyrimidine plus platinum is recognized as the standard treatment strategy for advanced gastric cancer, triplet chemotherapy with docetaxel, cisplatin and S-1 (DCS) is another option for first-line therapy in Japan. However, efficacy of taxane after DCS therapy has not been sufficiently evaluated. Methods: We retrospectively evaluated the efficacy and safety of taxane-monotherapy after DCS between January 2010 and April 2015 for advanced gastric cancer. The taxane-monotherapy included weekly paclitaxel (PTX) (80 mg/m 2 , day 1, 8 and 15 of a 28-day cycle) and triweekly nab-PTX (260 mg/m 2 , day 1). Other selection criteria were: ECOG PS &lt; 2; adequate organ function; no severe ascites; HER2-negative. Results: Thirty of 92 patients who had been treated with DCS received taxane-monotherapy. Fifteen and 15 patients received taxane-monotherapy as the second and third-line treatment, respectively. Patients characteristics of each group (2nd/3rd) were; median age: 64/62 (range 27-75/42-75); ECOG PS ≤ 1: 14/13; number of metastatic sites ≥ 2: 9/12; median taxane-free interval from first-line treatment: 1.6/3.4 (range 0.9-2.3/2.2-8.3) months; median total dose of prior DTX: 349/208 (range 39-844/141-685) mg/m 2 . Number of patients who received PTX/nab-PTX were 10/5 and 13/2 in the second and third line treatment. Median relative dose intensity of taxane was 96.4% (range 57.6-172.9%) in the second-line, 98.5% (44.0-166.8%) in the third-line group. Response rate and disease control rate were 0% and 37.5% in the second-line, and 0% and 38.5% in the third-line group. Median progression free survival and overall survival were 3.4 and 5.8 months in the second-line group, and 2.0 and 4.5 months in the third-line. Grade 3 or 4 neutropenia, anemia, and anorexia, occurred in 33%, 13% and 13% in the second-line group, and 6.7%, 13% and 6.7% in the third–line group, associated with no treatment related death. Conclusions: It is suggested that taxane-monotherapy has acceptable toxicities but insufficient efficacy in advanced gastric cancer patients after DCS therapy.
Uncovered Culprit Plaque Ruptures in Patients With ST-Segment Elevation Myocardial Infarction Assessed by Optical Coherence Tomography and Intravascular Ultrasound With iMap
Authors: Mikkel Hougaard, Henrik Steen Hansen, Per Thayssen, Lisbeth Antonsen, Lisette Okkels Jensen
Journal: JACC. Cardiovascular imaging (2017)
Sixty seconds on . . . 999 calls
Authors: Anne Gulland
Journal: BMJ (2017)

Like the woman who called the ambulance service to find out whether the green part of a potato was poisonous? Unfortunately not, as I enjoy reading about the stupidity of the great unwashed. This is about NHS England overhauling the 999 response service.

Well, you’ll be given short shrift next time you drop the TV remote control and need someone to pick it up (this was a genuine 999 call), or …
A soft robotic exosuit improves walking in patients after stroke
Authors: Louis N. Awad, Jaehyun Bae, Kathleen O’Donnell, Stefano M. M. De Rossi, Kathryn Hendron, Lizeth H. Sloot, Pawel Kudzia, Stephen Allen, Kenneth G. Holt, Terry D. Ellis, Conor J. Walsh
Journal: Science Translational Medicine (2017)

Soft exosuits facilitate more normal walking after stroke.
Astrocytic tight junctions control inflammatory CNS lesion pathogenesis
Authors: Sam Horng, Anthony Therattil, Sarah Moyon, Alexandra Gordon, Karla Kim, Azeb Tadesse Argaw, Yuko Hara, John N. Mariani, Setsu Sawai, Per Flodby, Edward D. Crandall, Zea Borok, Michael V. Sofroniew, Candice Chapouly, Gareth R. John
Journal: Journal of Clinical Investigation (2017)

Lesions and neurologic disability in inflammatory CNS diseases such as multiple sclerosis (MS) result from the translocation of leukocytes and humoral factors from the vasculature, first across the endothelial blood-brain barrier (BBB) and then across the astrocytic glia limitans (GL). Factors secreted by reactive astrocytes open the BBB by disrupting endothelial tight junctions (TJs), but the mechanisms that control access across the GL are unknown. Here, we report that in inflammatory lesions, a second barrier composed of reactive astrocyte TJs of claudin 1 (CLDN1), CLDN4, and junctional adhesion molecule A (JAM-A) subunits is induced at the GL. In a human coculture model, CLDN4-deficient astrocytes were unable to control lymphocyte segregation. In models of CNS inflammation and MS, mice with astrocyte-specific Cldn4 deletion displayed exacerbated leukocyte and humoral infiltration, neuropathology, motor disability, and mortality. These findings identify a second inducible barrier to CNS entry at the GL. This barrier may be therapeutically targetable in inflammatory CNS disease.
Characteristics, Outcome and Pattern of Mutations in Patients with Follicular Lymphoma Who Progressed on BTK Inhibitors (Ibrutinib and acalabrutinib)
Authors: Preetesh Jain, Rashmi Kanagal-Shamanna, Francis San Lucas, Michael Wang, Jorge E. Romaguera, Luis E. Fayad, Yasuhiro Oki, Jason R. Westin, Jeffrey Medeiros, Nathan Fowler
Journal: Blood (2016)
Host gene–microbiome interactions: molecular mechanisms in inflammatory bowel disease
Authors: Hiutung Chu
Journal: Genome Medicine (2017)

Recent studies have identified links between host genetic variants and microbial recognition of the microbiome. Defects in host–microbiome interactions in individuals harboring inflammatory bowel disease risk alleles may result in imbalances of the microbial community, impaired pathogen clearance, and failure to sense beneficial commensal microbes. These findings highlight the importance of maintaining bi-directional communication at the mucosal interface during intestinal homeostasis.
FOLFOX4/XELOX in stage II–III colon cancer: Efficacy results of the Italian three or six colon adjuvant (TOSCA) trial.
Authors: Alberto F. Sobrero, Sara Lonardi, Gerardo Rosati, Maria Di Bartolomeo, Monica Ronzoni, Nicoletta Pella, Mario Scartozzi, Maria Banzi, M. Giulia Zampino, Felice Pasini, Paolo Marchetti, Maurizio Cantore, Alberto Zaniboni, Lorenza Rimassa, Libero Ciuffreda, Daris Ferrari, Vittorina Zagonel, Evaristo Maiello, Eliana Rulli, Roberto Labianca
Journal: Journal of Clinical Oncology (2017)

3501 Background: Six months of oxaliplatin-based treatment has been the standard of care as adjuvant therapy for stage III colon cancer and an accepted option for high-risk stage II. Given the cumulative neurotoxicity associated to oxaliplatin, a shorter duration of therapy, if equally efficacious, would be advantageous for patients and health-care systems. Methods: TOSCA was an open-label, phase III, multicenter, non-inferiority trial randomizing patients with high-risk stage II or stage III radically resected colon cancer to receive 3 months or 6 months of FOLFOX4/XELOX. Primary end-point was relapse-free survival. Results: From June 2007 to March 2013, 3759 patients were accrued from 130 Italian sites, 64% receiving FOLFOX4 and 36% XELOX in either arm. Two thirds were stage III. At the cut-off time for analysis the median time of follow-up was 62 months and 772 relapses or deaths have been observed. The RFS rate at 8 years is 75%. This analysis was done when 82% of the planned number of events was reached, with a power of 72% instead of 80%. The decision to anticipate the analysis was based on the participation to the IDEA joint collaborative analysis of studies sharing this clinical question. The Hazard Ratio of the 3months vs 6 months for relapse/death was 1.14 (95%CI 0.99-1.31, p for non inferiority = 0.253) and the confidence interval crossed the non inferiority limit of 1.20. Conclusions: TOSCA was not able to demonstrate that 3 months of oxaliplatin-based adjuvant treatment is as efficacious as 6 months. Nevertheless , because the absolute difference in RFS between the two treatment durations is small ( less than 3 % at 5 years ), the decision to complete the whole 6-month program should be individualized based on toxicity and patients’ attitude. This study is registered with ClinicalTrials.gov Registration Number: NCT00646607. It was supported by a grant from AIFA (Agenzia Italiana del Farmaco) Grant Code FARM5RWTWZ. Clinical trial information: NCT00646607.
Prehospital immune responses and development of multiple organ dysfunction syndrome following traumatic injury: A prospective cohort study
Authors: Jon Hazeldine, David N. Naumann, Emma Toman, David Davies, Jonathan R. B. Bishop, Zhangjie Su, Peter Hampson, Robert J. Dinsdale, Nicholas Crombie, Niharika Arora Duggal, Paul Harrison, Antonio Belli, Janet M. Lord
Journal: PLoS Medicine (2017)

Almost all studies that have investigated the immune response to trauma have analysed blood samples acquired post-hospital admission. Thus, we know little of the immune status of patients in the immediate postinjury phase and how this might influence patient outcomes. The objective of this study was therefore to comprehensively assess the ultra-early, within 1-hour, immune response to trauma and perform an exploratory analysis of its relationship with the development of multiple organ dysfunction syndrome (MODS).The immune and inflammatory response to trauma was analysed in 89 adult trauma patients (mean age 41 years, range 18-90 years, 75 males) with a mean injury severity score (ISS) of 24 (range 9-66), from whom blood samples were acquired within 1 hour of injury (mean time to sample 42 minutes, range 17-60 minutes). Within minutes of trauma, a comprehensive leukocytosis, elevated serum pro- and anti-inflammatory cytokines, and evidence of innate cell activation that included neutrophil extracellular trap generation and elevated surface expression of toll-like receptor 2 and CD11b on monocytes and neutrophils, respectively, were observed. Features consistent with immune compromise were also detected, notably elevated numbers of immune suppressive CD16BRIGHT CD62LDIM neutrophils (82.07 x 106/l ± 18.94 control versus 1,092 x 106/l ± 165 trauma, p < 0.0005) and CD14+HLA-DRlow/- monocytes (34.96 x 106/l ± 4.48 control versus 95.72 x 106/l ± 8.0 trauma, p < 0.05) and reduced leukocyte cytokine secretion in response to lipopolysaccharide stimulation. Exploratory analysis via binary logistic regression found a potential association between absolute natural killer T (NKT) cell numbers and the subsequent development of MODS. Study limitations include the relatively small sample size and the absence of data relating to adaptive immune cell function.Our study highlighted the dynamic and complex nature of the immune response to trauma, with immune alterations consistent with both activation and suppression evident within 1 hour of injury. The relationship of these changes, especially in NKT cell numbers, to patient outcomes such as MODS warrants further investigation.
Transdermal delivery of gentamicin using dissolving microneedle arrays for potential treatment of neonatal sepsis
Authors: Patricia González-Vázquez, Eneko Larrañeta, Maelíosa T.C. McCrudden, Courtney Jarrahian, Annie Rein-Weston, Manjari Quintanar-Solares, Darin Zehrung, Helen McCarthy, Aaron J. Courtenay, Ryan F. Donnelly
Journal: Journal of Controlled Release (2017)

Neonatal infections are a leading cause of childhood mortality in low-resource settings. World Health Organization guidelines for outpatient treatment of possible serious bacterial infection (PSBI) in neonates and young infants when referral for hospital treatment is not feasible include intramuscular gentamicin (GEN) and oral amoxicillin. GEN is supplied as an aqueous solution of gentamicin sulphate in vials or ampoules and requires health care workers to be trained in dose calculation or selection of an appropriate dose based on the patient's weight band and to have access to safe injection supplies and appropriate sharps disposal. A simplified formulation, packaging, and delivery method to treat PSBI in low-resource settings could decrease user error and expand access to lifesaving outpatient antibiotic treatment for infants with severe infection during the neonatal period. We developed dissolving polymeric microneedles (MN) arrays to deliver GEN transdermally. MN arrays were produced from aqueous blends containing 30% (w/w) of GEN and two polymers approved by the US Food and Drug Administration: sodium hyaluronate and poly(vinylpyrrolidone). The arrays (19×19 needles and 500μm height) were mechanically strong and were able to penetrate a skin simulant to a depth of 378μm. The MN arrays were tested in vitro using a Franz Cell setup delivering approximately 4.45mg of GEN over 6h. Finally, three different doses (low, medium, and high) of GEN delivered by MN arrays were tested in an animal model. Maximum plasma levels of GEN were dose-dependent and ranged between 2 and 5μg/mL. The time required to reach these levels post-MN array application ranged between 1 and 6h. This work demonstrated the potential of dissolving MN arrays to deliver GEN transdermally at therapeutic levels in vivo.
FRI0695 Serious infection across biologic treated patients with rheumatoid arthritis: results from a national registry
Authors: AI Rutherford, S Subesinghe, R Byng-Maddick, K Hyrich, JB Galloway
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Infection is a complication of biologic therapy in RA. <h3>Objectives</h3> To describe the incidence and pattern of serious infection within the British Society for Rheumatology Biologics Register (BSRBR-RA) by drug. <h3>Methods</h3> The BSRBR-RA is a prospective observational study designed to evaluate the safety of biologics. Adverse events are coded using MedDRA defintitions. This analysis included patients with RA starting a biologic. They were considered at risk from their start date until 3 half-lives after stopping their biologic, death, first serious infection, or completion of three years of therapy, whichever came first. Event rates were compared across biologics using Cox proportional hazards with adjustment for age, gender, disease severity and duration, smoking, seropositivity, polypharmacy and baseline steroid usage. <h3>Results</h3> 19,282 patients were included in the analysis with combined follow-up time of 46,771 years. At baseline the mean age was 57 years, 76% female, mean disease duration 12.3 years and mean DAS28 6.1. 22% were current smokers and 64% had a positive rheumatoid factor. The incidence of serious infection for each biologic and hazard ratios for serious infections including by subclass are tabulated. A sensitivity analysis limiting to 1st biologic exposure only did not significantly alter the estimates. A second sensitivity analysis limiting to new starters from 2010 found certolizumab still had a lower point estimate but findings were no longer significant (HR 0.79, CI 0.54–1.16). <h3>Conclusions</h3> Although the incidence of serious infection was lowest with certolizumab it is difficult to draw strong conclusions about comparative safety from observational studies due to channelling bias and unmeasured confounding. Rituximab and tocilizumab both had higher unadjusted rates of infection but in the adjusted model the rate was no different suggesting that patient factors as opposed to the drug itself were responsible for the observed difference. <h3>Disclosure of Interest</h3> A. Rutherford: None declared, S. Subesinghe: None declared, R. Byng-Maddick: None declared, K. Hyrich Grant/research support from: Pfizer, Speakers bureau: Abbvie, J. Galloway Consultant for: Roche, BMS, UCB, Pfizer
Long‐term analysis of phase II studies of single‐agent lenalidomide in relapsed/refractory mantle cell lymphoma
Authors: Thomas E. Witzig, Pier Luigi Zinzani, Thomas M. Habermann, Joseph M. Tuscano, Johannes Drach, Radhakrishnan Ramchandren, Sevgi Kalayoglu Besisik, Kenichi Takeshita, Marie‐Laure Casadebaig Bravo, Lei Zhang, Tommy Fu, Andre Goy
Journal: American Journal of Hematology (2017)

Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma (NHL) with aggressive disease characteristics resulting in multiple relapses after initial treatment. Lenalidomide is an immunomodulatory agent approved in the US for patients with relapsed/refractory MCL following bortezomib based on results from 3 multicenter phase II studies (2 including relapsed/refractory aggressive NHL and 1 focusing on MCL post-bortezomib). The purpose of this report is to provide longer follow-up on the MCL-001 study (follow-ups were 6.8 [NHL-002], 7.6 [NHL-003], and 52.2 [MCL-001] months). The 206 relapsed MCL patients treated with single-agent lenalidomide (25 mg/day PO, days 1 to 21 every 28-days) had a median age of 67 years (63% ≥65 years), 91% with stage III/IV disease, and 50% with ≥4 previous treatment regimens. With a median follow-up of X, the combined best overall response rate (ORR) was 33% (including 11% with complete remission [CR]/CR unconfirmed CRu). Lenalidomide produced rapid and durable responses with a median time to response of 2.2 months and median duration of response (DOR) of 16.6 months (95% CI: 11.1%-29.8%). The safety profile was consistent and manageable; myelosuppression was the most common adverse event (AE). Overall, single-agent lenalidomide showed consistent efficacy and safety in multiple phase II studies of heavily pretreated patients with relapsed/refractory MCL, including those previously treated with bortezomib.
Planned interim analysis of PATRICIA: An open-label, single-arm, phase II study of pertuzumab (P) with high-dose trastuzumab (H) for the treatment of central nervous system (CNS) progression post radiotherapy (RT) in patients (pts) with HER2-positive metastatic breast cancer (MBC).
Authors: Nancy U. Lin, Alisha Stein, Alan Nicholas, Anita M. Fung, Priya Kumthekar, Nuhad K. Ibrahim, Mark D. Pegram
Journal: Journal of Clinical Oncology (2017)

2074 Background: There is currently no clear standard of care to address the management of recurring/multiple intracranial metastases post RT in HER2-positive MBC. The ongoing PATRICIA study (NCT02536339) is evaluating the safety and efficacy of P in combination with high-dose h for patients with HER2-positive MBC with CNS metastases who have CNS progression following RT. Reported herein are results from the protocol-specified interim analysis of PATRICIA. Methods: All eligible patients must have measurable (≥10 mm) CNS progression post RT, and stable non-CNS disease. Patients receive P (840-mg loading dose, then 420 mg every 3 weeks) and high-dose h (6 mg/kg weekly). The primary efficacy endpoint is objective response rate (ORR) in the CNS per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. The interim analysis was planned after 15 patients were enrolled and had ≥2 left ventricular ejection fraction (LVEF) measurements, 2 cycles of study drugs, and 2 response measurements. The study would proceed to full enrollment (n=40) if objective response or stable disease in the CNS was observed in ≥1 of 15 patients and &lt;2 of 15 patients develop congestive heart failure (CHF) related to P or H. Results: As of Sept 6, 2016, 15 patients had been enrolled across 9 sites. Median treatment duration was 4.4 (range 1.2−8.3) months. Six patients discontinued treatment (5 for disease progression; 1 for symptomatic deterioration). Range for duration of response was 1.4−3.3 months. There were no new safety signals for P combined with high-dose h treatment. No patients had CHF or a clinically significant drop in LVEF. Conclusions: Based on early evidence of clinical benefit (ORR 20%) and a lack of new safety signals, the safety and futility boundaries for PATRICIA have been passed and study enrollment continues. Clinical trial information: NCT02536339. [Table: see text]
Results of the HEMO Study suggest that p-cresol sulfate and indoxyl sulfate are not associated with cardiovascular outcomes
Authors: Tariq Shafi, Tammy L. Sirich, Timothy W. Meyer, Thomas H. Hostetter, Natalie S. Plummer, Seungyoung Hwang, Michal L. Melamed, Tanushree Banerjee, Josef Coresh, Neil R. Powe
Journal: Kidney International (2017)
Trade is central to achieving the sustainable development goals: a case study of antimicrobial resistance
Authors: Johanna Hanefeld, Mishal Khan, Göran Tomson, Richard Smith
Journal: BMJ (2017)

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Charting the Future of Cancer Health Disparities Research: A Position Statement From the American Association for Cancer Research, the American Cancer Society, the American Society of Clinical Oncology, and the National Cancer Institute
Authors: Blase N. Polite, Lucile L. Adams-Campbell, Otis W. Brawley, Nina Bickell, John M. Carethers, Christopher R. Flowers, Margaret Foti, Scarlett Lin Gomez, Jennifer J. Griggs, Christopher S. Lathan, Christopher I. Li, J. Leonard Lichtenfeld, Worta McCaskill-Stevens, Electra D. Paskett
Journal: Journal of Clinical Oncology (2017)

The academic field of cancer health disparities was stimulated by the U.S. civil rights movement. Concerns about civil rights led to concerns about equality in health care. The first publications to make the observation that black Americans have higher rates of death as a result of certain cancers
The methodology of surveillance for antimicrobial resistance and healthcare-associated infections in Europe (SUSPIRE): a systematic review of publicly available information
Authors: M. Núñez-Núñez, M.D. Navarro, V. Palomo, N.B. Rajendran, M.D. del Toro, A. Voss, M. Sharland, F. Sifakis, E. Tacconelli, J. Rodríguez-Baño, F. Burkert, E. Carrara, M. von Cube, L. Drgona, K. Gilchrist, H. Goossens, S. Harbarth, D. Hequet, H. Jafri, G. Kahlmeter, S. Kuster, C. Luxemburger, M. McCarthy, M. Niks, A. Oualim, M. Poljak, O. Sandulescu, A. Schweiger, C. Vuong, I. Wiegand, A. Widmer, A.T. Witschi, G. Zanetti, W. Zingg
Journal: Clinical Microbiology and Infection (2017)
Efficacy of oral pre-exposure prophylaxis (PrEP) for HIV among women with abnormal vaginal microbiota: a post-hoc analysis of the randomised, placebo-controlled Partners PrEP Study
Authors: Renee Heffron, R Scott McClelland, Jennifer E Balkus, Connie Celum, Craig R Cohen, Nelly Mugo, Elizabeth Bukusi, Deborah Donnell, Jairam Lingappa, James Kiarie, Tina Fiedler, Matthew Munch, David N Fredricks, Jared M Baeten, Connie Celum, Jared M Baeten, Deborah Donnell, Robert W Coombs, Lisa Frenkel, Craig W Hendrix, Jairam Lingappa, M Juliana McElrath, Kenneth Fife, Edwin Were, Elioda Tumwesigye, Patrick Ndase, Elly Katabira, Elly Katabira, Allan Ronald, Elizabeth Bukusi, Craig Cohen, Jonathan Wangisi, James Campbell, Jordan Tappero, James Kiarie, Carey Farquhar, Grace John-Stewart, Nelly Rwamba Mugo
Journal: The Lancet HIV (2017)