tbuckley/cabot-search huggingface dataset:
Immune phenotypes predict survival in patients with glioblastoma multiforme
Authors: Haouraa Mostafa, Andrej Pala, Josef Högel, Michal Hlavac, Elvira Dietrich, M. Andrew Westhoff, Lisa Nonnenmacher, Timo Burster, Michael Georgieff, C. Rainer Wirtz, E. Marion Schneider
Journal: Journal of Hematology & Oncology (2016)

Glioblastoma multiforme (GBM), a common primary malignant brain tumor, rarely disseminates beyond the central nervous system and has a very bad prognosis. The current study aimed at the analysis of immunological control in individual patients with GBM.Immune phenotypes and plasma biomarkers of GBM patients were determined at the time of diagnosis using flow cytometry and ELISA, respectively.Using descriptive statistics, we found that immune anomalies were distinct in individual patients. Defined marker profiles proved highly relevant for survival. A remarkable relation between activated NK cells and improved survival in GBM patients was in contrast to increased CD39 and IL-10 in patients with a detrimental course and very short survival. Recursive partitioning analysis (RPA) and Cox proportional hazards models substantiated the relevance of absolute numbers of CD8 cells and low numbers of CD39 cells for better survival.Defined alterations of the immune system may guide the course of disease in patients with GBM and may be prognostically valuable for longitudinal studies or can be applied for immune intervention.
Health outcomes during the 2008 financial crisis in Europe: systematic literature review
Authors: Divya Parmar, Charitini Stavropoulou, John P A Ioannidis
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To systematically identify, critically appraise, and synthesise empirical studies about the impact of the 2008 financial crisis in Europe on health outcomes. <b>Design</b>&nbsp;Systematic literature review. <b>Data sources</b>&nbsp;Structural searches of key databases, healthcare journals, and organisation based websites. <b>Review methods</b>&nbsp;Empirical studies reporting on the impact of the financial crisis on health outcomes in Europe, published from January 2008 to December 2015, were included. All selected studies were assessed for risk of bias. Owing to the heterogeneity of studies in terms of study design and analysis and the use of overlapping datasets across studies, studies were analysed thematically per outcome, and the evidence was synthesised on different health outcomes without formal meta-analysis. <b>Results</b>&nbsp;41 studies met the inclusion criteria, and focused on suicide, mental health, self rated health, mortality, and other health outcomes. Of those studies, 30 (73%) were deemed to be at high risk of bias, nine (22%) at moderate risk of bias, and only two (5%) at low risk of bias, limiting the conclusions that can be drawn. Although there were differences across countries and groups, there was some indication that suicides increased and mental health deteriorated during the crisis. The crisis did not seem to reverse the trend of decreasing overall mortality. Evidence on self rated health and other indicators was mixed. <b>Conclusions</b>&nbsp;Most published studies on the impact of financial crisis on health in Europe had a substantial risk of bias; therefore, results need to be cautiously interpreted. Overall, the financial crisis in Europe seemed to have had heterogeneous effects on health outcomes, with the evidence being most consistent for suicides and mental health. There is a need for better empirical studies, especially those focused on identifying mechanisms that can mitigate the adverse effects of the crisis.
Outcomes After Percutaneous Coronary Intervention or Bypass Surgery in Patients With Unprotected Left Main Disease
Authors: Rafael Cavalcante, Yohei Sotomi, Cheol W Lee, Jung-Min Ahn, Vasim Farooq, Hiroki Tateishi, Erhan Tenekecioglu, Yaping Zeng, Pannipa Suwannasom, Carlos Collet, Felipe N Albuquerque, Yoshinobu Onuma, Seung-Jung Park, Patrick W Serruys
Journal: Journal of the American College of Cardiology (2016)
P0490 : NK cell dynamics in chronic hepatitis B patients are associated with HBsAg clearance after combination treatment with peginterferon ALFA-2A and adefovir
Authors: F. Stelma, A. de Niet, L. Jansen, R.B. Takkenberg, H.L Janssen, M.J. Sinnige, N.A. Kootstra, E.M. van Leeuwen, H.W. Reesink
Journal: Journal of Hepatology (2015)
The placenta as the tree of life
Authors: Silvia Chiarelli, Ludovica Sandei
Journal: BMJ (2016)

The helical course of the umbilical vessels was recorded by Jacobus Berengarius in 1521, and in 1600 Hieronymus Fabricius ab Acquapendente provided the first illustrations in his book De formatu foetu .

Both left and right helices may occur in the umbilical cord; the left:right ratio is 7:1, while absent coiling …
Phase I Study of the Anti-CD22 Antibody–Drug Conjugate Pinatuzumab Vedotin with/without Rituximab in Patients with Relapsed/Refractory B-cell Non-Hodgkin Lymphoma
Authors: Ranjana H. Advani, Daniel Lebovic, Andy Chen, Mark Brunvand, Andre Goy, Julie E. Chang, Ephraim Hochberg, Sreeni Yalamanchili, Robert Kahn, Dan Lu, Priya Agarwal, Randall C. Dere, Hsin-Ju Hsieh, Surai Jones, Yu-Waye Chu, Bruce D. Cheson
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Pinatuzumab vedotin is an antibody–drug conjugate with the potent antimicrotubule agent monomethyl auristatin E (MMAE) conjugated to an anti-CD22 antibody via a protease-cleavable linker. This phase I study determined its recommended phase II dose (RP2D) and evaluated its safety, tolerability, and antitumor activity alone and with rituximab in relapsed/refractory (r/r) non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Experimental Design: Patients received escalating doses of pinatuzumab vedotin every 21 days. Clinical activity at the RP2D alone or with rituximab was evaluated in r/r diffuse large B-cell lymphoma (DLBCL) and r/r indolent NHL (iNHL) patients. Results: Seventy-five patients received single-agent pinatuzumab vedotin. The RP2D was 2.4 mg/kg, based on dose-limiting toxicities (DLT) of grade 4 neutropenia &amp;gt;7 days in 1 of 3 patients and grade 4 neutropenia &amp;lt;7 days in 2 of 3 patients treated at 3.2 mg/kg (maximum assessed dose). No DLTs occurred at 2.4 mg/kg. At the RP2D, neutropenia was the most common grade ≥3 adverse event. Peripheral neuropathy–related grade ≥2 adverse events most frequently resulted in treatment discontinuation. Rituximab cotreatment did not impact safety, tolerability, or pharmacokinetics of pinatuzumab vedotin. Unconjugated MMAE exposure was much lower than antibody-conjugated MMAE exposure, without accumulation with repeat dosing. At the RP2D, objective responses were observed in DLBCL (9/25) and iNHL (7/14) patients; 2 of 8 patients treated with pinatuzumab vedotin (RP2D) and rituximab had complete responses. CLL patients showed no objective responses. Conclusions: The RP2D of pinatuzumab vedotin alone and with rituximab was 2.4 mg/kg, which was well tolerated, with encouraging clinical activity in r/r NHL. Clin Cancer Res; 23(5); 1167–76. ©2016 AACR.
From Bedside To Bench: Molecular Benchmarking Of An Fc-Optimized CD19 Antibody Used In Treatment Of Relapsed and Refractory Pediatric B-Lineage Acute Lymphoblastic Leukemia
Authors: Ursula J.E. Seidel, Ludger Grosse-Hovest, Patrick Schlegel, Martin Hofmann, Friedhelm R. Schuster, Kai-Erik Witte, Steffen Aulwurm, Rouwen Teltschik, Elwira Pyz, Hans-Georg Rammensee, Gundram Jung, Rupert Handgretinger, Peter Lang
Journal: Blood (2013)
A pilot study of vascular endothelial growth factor inhibition with bevacizumab in patients with lymphedema following breast cancer treatment
Authors: K. Miller, D. Christmon, S. Perkins, J. Sun, B. Schneider, A. Storniolo, S. Clare, U. Ozerdem, G. Sledge
Journal: Journal of Clinical Oncology (2009)

9523 Background: Lymphedema is a significant long-term complication of primary therapy for breast cancer. Anecdotally, several patients (pts) with metastatic disease treated with bevacizumab monotherapy noted improvement in long-standing lymphedema. This pilot study was conducted to explore these observations prospectively. Methods: We used an existing biospecimen bank to conduct a case-control study to compare VEGF-A, -C, -D and VEGFR-3 serum concentrations in breast cancer pts with and without lymphedema (matched for age and LN status). In a separate pilot trial, pts with significant unilateral lymphedema receive bevacizumab, 15 mg/kg every 3 weeks. Baseline assessments include arm volume, interstitial fluid pressure (IFP), extracellular fluid volume by lymphometer (ECF), quality of life (QOL) and plasma VEGF-C, -D, and R3. IFP is measured serially for 24 hours after the first treatment; arm volume, ECF, QOL, and plasma VEGF-C/D/R3 are assessed at 3 and 6 weeks. Results: Samples were available for 16 pts with chronic lymphedema and 31 matched controls. Median VEGF-C levels were significantly increased in pts with lymphedema (6895 pg/ml vs. 5349 pg/ml, p=0.001). Twelve pts have been enrolled in the pilot trial. Median duration of lymphedema was 6.3 years (0.5–16.6) Median time since surgery was 5.5 years (1.9–17.6); median time since radiation (n=10) was 5.1 years (1.3–8.3). Complete IFP data is available in 9 pts. Baseline IFP was significantly higher in the affected compared to unaffected arm (7.63 vs. -0.87 mmHg; p=0.0023). Mean IFP in the affected arm decreased an average of 41.9% 24 hours after bevacizumab infusion (7.63 vs. 4.88 mmHg; p=0.07). ECF, VEGF-1, and VEGF-R3 levels all significantly decreased three weeks after initial treatment. Two patients met the definition of response with a ≥ 25% reduction in excess arm volume though the mean difference in excess arm volume did not significantly change (p=0.19). Conclusions: Preliminary data supports the hypothesis that VEGF plays a central role in the development and persistence of lymphedema after local therapy for breast cancer. Bevacizumab acutely decreases IFP, leading to a decrease in ECF and modest improvement in arm volume. [Table: see text]
Efficacy and safety of trastuzumab (T-mab) and paclitaxel for T-mab naïve patients with HER2 positive previously treated metastatic gastric cancer (JFMC45-1102).
Authors: Akira Miki, Kazuhiro Nishikawa, Hirokazu Noshiro, Akira Tsuburaya, Yasunori Nishida, Yasuhide Yamada, Hiroto Miwa, Yoshinori Sakai, Kazuhiro Yoshida, Yasuhiro Kodera, Narikazu Boku, Satoshi Morita, Junichi Sakamoto, Shigetoyo Saji, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2013)

63 Background: The global, randomized, Phase III ToGA study showed that the first-line treatment of trastuzumab (T-mab) combined with capecitabine and cisplatin a survival (OS) benefit for patients (pts) with HER2-positive metastatic gastric cancer (mGC). However, there is no report concerning about the efficacy and safety of T-mab containing second-line treatment for T-mab naïve patients with HER2-positive mGC. Therefore, we planned a phase II study of paclitaxel plus trastuzumab in this setting. Methods: JFMC45-1102 is multicentre Phase II study. Patient (pts) with HER2 positive (IHC3+ or IHC2+/FISH+), histologically confirmed gastric adenocarcinoma, age≥20, received one or more prior chemotherapy but no prior therapy with T-mab, normal left ventricular ejection fraction (LVEF ≥ 50%) were eligible. Pts received paclitaxel (80 mg/m 2 on days 1, 8, and, 15 q4w) plus T-mab (8 mg/kg for the initial dose, followed by 6 mg/kg q3w) until disease progression, unacceptable toxicity or patient’s refusal. The primary endpoint was overall response rate evaluated according to RECIST ver1.0 (ORR; Threshold and expected ORR would be 15% and 30%), and the secondary endpoints include progression free survival (PFS), time to treatment failure (TTF), overall survival (OS) and safety. A LVEF assessment was repeated every three months. Results: Between November 2011 to March 2012, 45 pts were enrolled. Pts characteristics were: gender (M/F); 36/9, median age; 69, ECOG PS0/1/2; 34/10/1, advanced/recurrence; 25/20, number of prior treatment (1/2): 40/5. At 16 weeks, 43 pts were ORR and disease control rate (CR+PR+SD) were 37.2% (95% CI; 23.0%-53.3%) and 83.7%(95% CI; 69.3%-93.2%), respectively. The LVEF assessment was performed in 31 patients. More than 10% decrease in LVEF was observed in only one patient, although total incidence of decrease in LVEF was 56% (17/31 pts). Conclusions: Combination chemotherapy of paclitaxel plus trastuzumab is generally well tolerated and showed promising activity for T-mab native patients with HER2-positive previously treated advanced or recurrent gastric cancer. Clinical trial information: UMIN000006223.
What's Missing in Chronic Myeloid Leukemia Research: The Paucity of Studies Linking Health-Related Quality of Life to Adverse Events From the Perspectives of Patients, Physicians and Family Caregivers
Authors: Javier Pinilla-Ibarz, Maryam Navaie, Jessica C. Smith, Anne C. Beaubrun, Lauren E. McCullough, Anita H. Hickey, Ronald W. Toseland
Journal: Blood (2011)
Effect of Drug Interactions and Adherence on Coagulation Control of Patients Treated With Warfarin
Authors: Roberto Lozano, María-Esther Franco
Journal: JAMA Cardiology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Charles Leslie MacAdams
Authors: Barbara Kermode-Scott
Journal: BMJ (2016)

Canadian cardiac anaesthetist who died hours after climbing Mount Everest



Canadian cardiac anaesthetist Charles MacAdams was a skilled physician, highly respected for his exemplary care and outstanding compassion. He taught, researched, and provided clinical care at the Foothills Medical Centre, Libin Cardiovascular Institute of Alberta, and University of Calgary in Calgary, Alberta, Canada. MacAdams also spent many months developing, teaching, and supervising critical care and cardiac anaesthesia at the Tribhuvan University Institute of Medicine in Kathmandu in Nepal.

Charlie, as he was known to friends and family, was popular with his colleagues, students, and patients. He was passionate about his family, science, medicine, mentoring, research, adventure, his desire to make the world a better place, mountaineering, hiking, sailing, running, great conversations, boxer dogs, the Rockies, and Nepal. In May this year, Charlie MacAdams happily combined many of his passions during a trip that combined medical education and mountaineering in Nepal. He achieved a very special goal when he successfully completed the ascent and descent of the North Col of Mount Everest (7020 m). After the descent, he apparently went to sleep on the night of 10 May at Mount Everest’s base camp in Tibet, exhausted but exhilarated. He died in his tent during that night. He was 61 years old.



MacAdams’s son, …
The prognostic impact of <i>KRAS</i> mutation in colorectal cancer patients: A meta-analysis of phase III clinical trials.
Authors: Clarinda Wei Ling Chua, Dawn QQ Chong, Ravindran Kanesvaran, Wai Meng David Tai, Chee Kian Tham, Patrick Tan, Arul Earnest, Iain B. Tan
Journal: Journal of Clinical Oncology (2014)

e14515 Background: Activating KRAS mutations predict non-response to cetuximab and panitumumab in advanced colorectal cancer. However, its role as a prognostic marker is contentious. Methods: From a systematic review of Pubmed and Embase, we identified phase III studies reporting survival outcomes for patients with KRAS wild type (WT) and mutant (MT) colorectal cancer. Treatment arms involving planned anti-epidermal growth factor receptor (EGFR) therapy were excluded. Survival outcomes were extracted, pooled and reported as hazard ratios (HR) under a random-effects model. The outcome measures were disease free survival (DFS) for adjuvant trials and progression free survival (PFS) and overall survival (OS) for metastatic trials. Results: There were3,965 articles met the initial search criteria. We identified 26 articles describing 19 unique phase III trials. Altogether, 10,127 patients were included in the pooled analysis; 37% of patients had KRAS MT colorectal cancer. In adjuvant trials, patients with KRAS MT tumors had inferior DFS (HR: 1.21 (95% CI, 1.00 to 1.47), p=0.05. In metastatic trials, patients with KRAS MT tumors had inferior PFS (HR: 1.13 (95% CI: 1.06 to 1.21), p<0.001 and OS (HR 1.27 (95% CI: 1.17 to 1.38), p<0.001. The pooled median OS ratio was 1.17 (95% CI: 1.09 - 1.28). Inferior survival outcomes were consistently observed amongst patients receiving systemic therapy in the first or second line settings and in patients receiving irinotecan, oxaliplatin, or bevacizumab therapy. Conclusions: In addition to being a predictive biomarker, KRAS mutation is associated with inferior survival outcomes in patients receiving standard of care therapy. In colorectal cancer, KRAS mutation is prognostic.
Phase 1 Dose-Escalation Study of 90yttrium-Labeled Anti-CD22 Epratuzumab Tetraxetan in Adults with Refractory/Relapsed CD22+ B-Cell Acute Lymphoblastic Leukemia (B-ALL)
Authors: Patrice Chevallier, Thomas Eugene, Nelly Robillard, Françoise Isnard, Franck E Nicolini, Martine Escoffre-Barbe, Françoise Huguet, Mathilde Hunault, Antoine Marcais, Thierry Guillaume, Jacques Delaunay, Pierre Peterlin, Xavier Thomas, Norbert Ifrah, Simona Lapusan, Caroline bodet-Milin, Alain faivre Chauvet, Claire Le Houerou, David M Goldenberg, William A Wegener, Françoise Kraeber-Bodere
Journal: Blood (2014)
Increased Survival Secondary to Decreased Perioperative Complications in Open Aortic Aneurysm Repair Using Epidural Anesthesia
Authors: Gale L. Tang
Journal: JAMA Surgery (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
The Influenza Virus Polymerase Complex: An Update on Its Structure, Functions, and Significance for Antiviral Drug Design
Authors: Annelies Stevaert, Lieve Naesens
Journal: Medicinal Research Reviews (2016)

Influenza viruses cause seasonal epidemics and pandemic outbreaks associated with significant morbidity and mortality, and a huge cost. Since resistance to the existing anti-influenza drugs is rising, innovative inhibitors with a different mode of action are urgently needed. The influenza polymerase complex is widely recognized as a key drug target, given its critical role in virus replication and high degree of conservation among influenza A (of human or zoonotic origin) and B viruses. We here review the major progress that has been made in recent years in unravelling the structure and functions of this protein complex, enabling structure-aided drug design toward the core regions of the PA endonuclease, PB1 polymerase, or cap-binding PB2 subunit. Alternatively, inhibitors may target a protein-protein interaction site, a cellular factor involved in viral RNA synthesis, the viral RNA itself, or the nucleoprotein component of the viral ribonucleoprotein. The latest advances made for these diverse pharmacological targets have yielded agents in advanced (i.e., favipiravir and VX-787) or early clinical testing, besides several experimental inhibitors in various stages of development, which are all covered here.
Tumor Eradication by Cisplatin Is Sustained by CD80/86-Mediated Costimulation of CD8+ T Cells
Authors: Elham Beyranvand Nejad, Tetje C. van der Sluis, Suzanne van Duikeren, Hideo Yagita, George M. Janssen, Peter A. van Veelen, Cornelis J.M. Melief, Sjoerd H. van der Burg, Ramon Arens
Journal: Cancer Research (2016)

Certain cytotoxic chemotherapeutic drugs are immunogenic, stimulating tumor immunity through mechanisms that are not completely understood. Here we show how the DNA-damaging drug cisplatin modulates tumor immunity. At the maximum tolerated dose (MTD), cisplatin cured 50% of mice with established murine TC-1 or C3 tumors, which are preclinical models of human papillomavirus (HPV)-associated cancer. Notably, the curative benefit of cisplatin relied entirely upon induction of tumor-specific CD8+ T cells. Mechanistic investigations showed that cisplatin stimulated tumor infiltration of inflammatory antigen-presenting cells (APC) expressing relatively higher levels of the T-cell costimulatory ligands CD70, CD80, and CD86. Cell death triggered by cisplatin was associated with the release of at least 19 proteins in the tumor environment that could act as damage-associated molecular patterns and upregulate costimulatory molecules, either alone or in concert, but the responsible proteins remain unknown. Essentially, the curative effect of cisplatin was abrogated in mice lacking expression of CD80 and CD86 on APCs. Furthermore, cisplatin treatment was improved by CTLA-4 blockade, which increases the availability of CD80/86 to bind to CD28. In contrast, there was no effect of CD27 stimulation, which replaces CD70 interaction. At the cisplatin MTD, cure rates could also be increased by vaccination with synthetic long peptides, whereas cures could also be achieved at similar rates at 80% of the MTD with reduced side effects. Our findings reveal an essential basis for the immunogenic properties of cisplatin, which are mediated by the induction of costimulatory signals for CD8+ T-cell-dependent tumor destruction. Cancer Res; 76(20); 6017-29. ©2016 AACR.
Long-term Management of Panuveitis and Iris Heterochromia in an Ebola Survivor
Authors: Jessica G. Shantha, Ian Crozier, Jay B. Varkey, Colleen S. Kraft, G. Marshall Lyon, Aneesh K. Mehta, Renee Donahue Carlson, Charles E. Hill, Gokul Kumar, Matthew R. Debiec, Purnima S. Patel, Timothy W. Olsen, Robert B. Nussenblatt, Daniel F. Martin, Ute Ströher, Timothy M. Uyeki, Bruce S. Ribner, Justine R. Smith, Steven Yeh
Journal: Ophthalmology (2016)
Sexual health and quality of life are impaired in hidradenitis suppurativa: a multicentre cross-sectional study
Authors: I.C. Janse, I.E. Deckers, A.D. van der Maten, A.W.M. Evers, J. Boer, H.H. van der Zee, E.P. Prens, B. Horváth
Journal: British Journal of Dermatology (2016)

BackgroundHidradenitis suppurativa (HS) has a major impact on patients' quality of life (QoL). Although it has commonly been assumed that HS impairs sexual health, only a single case–control study has been performed on sexual functioning in a small group of patients with HS.