tbuckley/cabot-search huggingface dataset:
Highlights of the year in JACC2004
Authors: Anthony N. DeMaria, Ori Ben-Yehuda, Daniel Berman, Gregory K. Feld, Barry H. Greenberg, James D. Knoke, Kirk U. Knowlton, Wilbur Y.W. Lew, Jagat Narula, David Sahn, Sotirios Tsimikas
Journal: Journal of the American College of Cardiology (2004)
The myeloid heat shock transcription factor 1/β‐catenin axis regulates NLR family, pyrin domain‐containing 3 inflammasome activation in mouse liver ischemia/reperfusion injury
Authors: Shi Yue, Jianjun Zhu, Ming Zhang, Changyong Li, Xingliang Zhou, Min Zhou, Michael Ke, Ronald W. Busuttil, Qi‐Long Ying, Jerzy W. Kupiec‐Weglinski, Qiang Xia, Bibo Ke
Journal: Hepatology (2016)

Heat shock transcription factor 1 (HSF1) has been implicated in the differential regulation of cell stress and disease states. β‐catenin activation is essential for immune homeostasis. However, little is known about the role of macrophage HSF1‐β‐catenin signaling in the regulation of NLRP3 inflammasome activation during ischemia/reperfusion (I/R) injury (IRI) in the liver. This study investigated the functions and molecular mechanisms by which HSF1‐β‐catenin signaling influenced NLRP3‐mediated innate immune response in vivo and in vitro . Using a mouse model of IR‐induced liver inflammatory injury, we found that mice with a myeloid‐specific HSF1 knockout (HSF1 M‐KO ) displayed exacerbated liver damage based on their increased serum alanine aminotransferase levels, intrahepatic macrophage/neutrophil trafficking, and proinflammatory interleukin (IL)‐1β levels compared to the HSF1‐proficient (HSF1 FL/FL ) controls. Disruption of myeloid HSF1 markedly increased transcription factor X‐box‐binding protein (XBP1), NLR family, pyrin domain‐containing 3 (NLRP3), and cleaved caspase‐1 expression, which was accompanied by reduced β‐catenin activity. Knockdown of XBP1 in HSF1‐deficient livers using a XBP1 small interfering RNA ameliorated hepatocellular functions and reduced NLRP3/cleaved caspase‐1 and IL‐1β protein levels. In parallel in vitro studies, HSF1 overexpression increased β‐catenin (Ser552) phosphorylation and decreased reactive oxygen species (ROS) production in bone‐marrow‐derived macrophages. However, myeloid HSF1 ablation inhibited β‐catenin, but promoted XBP1. Furthermore, myeloid β‐catenin deletion increased XBP1 messenger RNA splicing, whereas a CRISPR/CRISPR‐associated protein 9‐mediated XBP1 knockout diminished NLRP3/caspase‐1. Conclusion: The myeloid HSF1‐β‐catenin axis controlled NLRP3 activation by modulating the XBP1 signaling pathway. HSF1 activation promoted β‐catenin, which, in turn, inhibited XBP1, leading to NLRP3 inactivation and reduced I/R‐induced liver injury. These findings demonstrated that HSF1/β‐catenin signaling is a novel regulator of innate immunity in liver inflammatory injury and implied the therapeutic potential for management of sterile liver inflammation in transplant recipients. (H epatology 2016;64:1683‐1698).
External Validation of the Estimation of Physiologic Ability and Surgical Stress (E-PASS) Risk Model to Predict Operative Risk in Perihilar Cholangiocarcinoma
Authors: Robert J. S. Coelen, Pim B. Olthof, Susan van Dieren, Marc G. H. Besselink, Olivier R. C. Busch, Thomas M. van Gulik
Journal: JAMA Surgery (2016)

Resection of perihilar cholangiocarcinoma (PHC) is high-risk surgery, with reported operative mortality up to 17%. Therefore, preoperative risk assessment is needed to identify high-risk patients and anticipate postoperative adverse outcomes.To provide external validation of the Estimation of Physiologic Ability and Surgical Stress (E-PASS) risk model in a Western PHC cohort.The E-PASS variables were obtained from a database that included 156 consecutive patients who underwent resection for suspected PHC between January 1, 2000, and December 31, 2015, at the Academic Medical Center, Amsterdam, the Netherlands. The accuracy of E-PASS using intraoperative variables and its modified form that can be used before surgery (mE-PASS) in predicting mortality was assessed by area under the curve analysis (discrimination) and by the Hosmer-Lemeshow goodness-of-fit test (calibration).In-hospital mortality, severe morbidity (Clavien-Dindo grade≥III), and a high Comprehensive Complication Index.Among 156 patients included in the study, the median age was 63 years, and 62.8% (n = 98) were male. Of them, 85.3% (n = 133) underwent major liver resection. Severe morbidity occurred in 51.3% (n = 80), and in-hospital mortality was 13.5% (n = 21). Both E-PASS and mE-PASS had adequate discriminative performance, with areas under the curve of 0.78 (95% CI, 0.67-0.88) and 0.79 (95% CI, 0.70-0.89), respectively, while E-PASS showed better calibration (P = .33 vs P = .02, Hosmer-Lemeshow goodness-of-fit test). The ratios of observed to expected mortality were 1.31 for E-PASS and 1.24 for mE-PASS. Both models were able to distinguish groups with low risk, intermediate risk, and high risk, with observed mortality rates of 0.0% to 3.6%, 8.3% to 9.0%, and 25.0% to 28.3%, respectively. Severe morbidity and a high Comprehensive Complication Index were more frequently observed among high-risk patients.Both E-PASS models accurately identify patients at high risk of postoperative in-hospital mortality after resection for PHC. The mE-PASS model can be used before surgery in outpatient settings and allows for risk assessment and shared decision making.
Pegylated liposomal doxorubicin and vinorelbine in metastatic breast cancer: Final results of a phase II trial.
Authors: A. A. Elsaid, N. M. Awad
Journal: Journal of Clinical Oncology (2010)

e11050 Background: Pegylated liposomal doxorubicin (PLD) has demonstrated equivalent antitumor activity to conventional doxorubicin and a significantly lower risk of cardiotoxicity when given as single agent or in combination with cyclophosphamide, but there is limited experience with the combination of PLD and vinorelbine. This phase II study was performed to evaluate the efficacy and safety of the PLD and vinorelbine in patients with metastatic breast cancer. Methods: From August 2004 to August 2007, 51 patients with metastatic breast cancer were treated with PLD (35 mg/m2) and vinorelbine (25 mg/m2 D1, 8) in 3-weeks intervals for up to eight cycles. Results: The overall response rate was 50% and 78% of patients derived a clinical benefit. Median time to progression and overall survival were 10.0 months (95% CI, 6.9-13.1 months) and 25 months (95% CI, 22.1-29.8 months), respectively. Median duration of response was 12.0 months (95% CI 7.1-16.9). A total of 408 courses were evaluable for toxicity: grade 3 and 4 neutropaenia affected 14 patients and 3 patients, respectively. Grade 3 and 4 palmar-plantar erythrodysesthesia syndrome was documented in five cases and one case, whereas grade 3 and 4 mucositis occurred in six cases and two cases, respectively. Grade 2 cardiac toxicity was observed in only one case. Conclusions: The combination of pegylated liposomal doxorubicin and vinorelbine is an active and well-tolerated regimen in patients with metastatic breast cancer. No significant financial relationships to disclose.
IgA vasculitis with severe gastrointestinal symptoms may be an unusual manifestation of varicella zoster virus reactivation
Authors: Y. Ushigome, Y. Yamazaki, T. Shiohara
Journal: British Journal of Dermatology (2016)

Immunoglobulin A vasculitis (IAV), formerly called Henoch-Schonlein purpura, is an acute leukocytoclastic vasculitis of unknown etiology that is manifested as palpable purpura or petechiae associated with arthralgia, abdominal pain, and nephritis.1, 2

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Predicting men at high risk for PSA failure after salvage radiotherapy for rising PSA following prostatectomy
Authors: O. K. MacDonald, A. V. D’Amico, N. Sadetsky, D. C. Shrieve, A. W. Bakst, P. R. Carroll
Journal: Journal of Clinical Oncology (2006)

4570 Background: Single and multi-institutional reports have published results indicating 5-year PSA response rates of 30 to 50% in men following salvage radiotherapy (RT) for rising PSA after radical prostatectomy (RP) depending upon the patient and disease factors. We analyzed a longitudinal observational database of men who received salvage RT following RP for their prostate cancer to evaluate for predictors of PSA failure despite salvage RT. Methods: Data from the Cancer of the Prostate Strategic Urologic Research Endeavor database (CaPSURE) identified 5,336 men with RP between 1989 and 2004; 200 underwent salvage RT ≥6 months after RP. PSA recurrence following salvage RT was defined as a PSA &gt;0.2 ng/mL. A measure of the association between clinical and pathologic characteristics in men experiencing PSA failure following salvage RT was examined using a chi-square metric. Univariable and multivariable analyses of predictors for PSA recurrence using a Cox proportional hazard regression model were performed. Results: After a mean follow-up of 18 months (range 1 to 131 months), 121 (62%) men experienced PSA recurrence at a mean 13.7 months after salvage RT. Significant associations between time to PSA recurrence after salvage RT were found with the clinical risk group (p &lt; .01), clinical T category (p &lt; .01), race/ethnicity (p = .04), extraprostatic extension (p &lt; .01), seminal vesicle invasion (p &lt; .01), and pre-salvage RT PSA level (p &lt; .01). The pre-salvage RT PSA level (p = .003) and seminal vesicle invasion (p = .02) remained significantly associated with time to PSA recurrence on multivariable analysis. Conclusions: The pre-salvage RT PSA level and the presence of seminal vesicle invasion were significantly associated with time to PSA recurrence following salvage RT within the CaPSURE database. Men with these risk factors are at increased risk for PSA recurrence despite salvage RT suggesting that these men would be ideal candidates for entry onto phase III studies comparing salvage RT plus systemic therapy with salvage RT alone at the time of post-operative PSA failure. [Table: see text]
Ruxolitinib and Lenalidomide As a Combination Therapy for Patients with Myelofibrosis
Authors: Daver Naval, Jorge E. Cortes, Elias Jabbour, Naveen Pemmaraju, Nitin Jain, Zeev Estrov, Steven M. Kornblau, Jan A. Burger, Hagop M. Kantarjian, Kate J Newberry, Srdan Verstovsek
Journal: Blood (2014)
Better late than Now-or-Never: The case of interactive repair phenomena
Authors: Patrick G. T. Healey, Christine Howes, Julian Hough, Matthew Purver
Journal: Behavioral and Brain Sciences (2016)

Empirical evidence from dialogue, both corpus and experimental, highlights the importance of interaction in language use - and this raises some questions for Christiansen & Chater's (C&C's) proposals. We endorse C&C's call for an integrated framework but argue that their emphasis on local, individual production and comprehension makes it difficult to accommodate the ubiquitous, interactive, and defeasible processes of clarification and repair in conversation.
Graded Prognostic Index for Gastroesophageal Cancer with Brain Metastases.
Authors: Vidhya Karivedu, Suresh Kumar Balasubramanian, Samuel T. Chao, Xuefei Jia, Paul Elson, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2016)

2022 Background: Brain metastasis (BM) is a rare but serious neurologic complication of gastro esophageal cancers (GEC). The Disease Specific Graded Prognostic Assessment (DS-GPA) which is based solely on Karnofsky performance scale (KPS) is a commonly used prognostic index in patients with BM. We evaluated DS-GPA and other potential prognostic factors for overall survival (OS) in GECBM at our institution. Methods: With IRB approval, the Cleveland Clinic Brain Tumor and Neuro-Oncology Center’s database was used to identify GECBM patients treated between 2002 and 2014. Overall survival (OS) from the diagnosis of GECBM was the primary endpoint. Cox proportional hazards models with stepwise variable selection were used to identify independent prognostic factors. Results: Sixty three patients with median age of 62 years (range; 33-79), were included for analysis. KPS was 90-100 in 22 patients (38%), 70-80 in 30 (52%) and <70 in 6 (10%) patients. Single BM was noted in 25 (40%), 2-3 BM in 19 (30%) and >3 BM in 19 (30%) patients. Forty nine patients (78%) were symptomatic at diagnosis. Twenty nine (46%) patients had supratentorial BM, 12 (19%) had infratentorial BM and 22 (35%) had both supra-and infratentorial BM at diagnosis. Initial therapy included whole brain radiation (WBRT) in 29 (48%), stereotactic radiosurgery (SRS) in 13 (21%), WBRT + SRS in 6 (10%), Surgery (S) + SRS in 2 (3%), S + WBRT in 9 (15%), S + SRS + WBRT in 1 (2%), while 1 patient received only chemotherapy. Median OS from diagnosis of BM was 4.5 months (95% C.I. 3.4-6.8). In multivariate analysis KPS, number of BM and symptoms were independent predictors of OS. Combining these factors a revised GPA with three groups was defined: unfavorable (total points <10), intermediate (11-13), and favorable (>13 points) with median OS of 2.5, 5.0 and 8.8 months, respectively. Conclusions: A revised DS-GPA for GECBM based on KPS (performance status), number of BM and symptoms is proposed. Factors No. of points Hazard ratio P valve Number of BM 1.54 (1.08-2.18) 0.042 1 6 2-3 3 >3 0 Colon cancer specific GPA (KPS) 0.73 (0.54-0.99) 0.045 100 8 90 6 80 4 70 2 <70 0 Symptoms 0.47 (0.23-0.97) 0.017 Symptomatic 0 Asymptomatic 5 Revised GPA No. Points Median OS (months) Unfavorable 0-10 2.5 Intermediate 11-13 5.0 Favorable >13 8.8
Law and medicine
Authors: B. D. Hirsch
Journal: JAMA (1982)

Beginning with this issue,<i>JAMA</i>will be publishing a LAW AND MEDICINE feature. LAW AND MEDICINE will consist of brief legal articles relating to the practice of medicine or areas of the law that are of interest to physicians. These articles will be prepared by lawyers in the American Medical Association Office of General Counsel and other medicolegal experts. The first, "Duty to Warn Third Parties," appears on page 431. As stated on its masthead, "The Journalis a forum for open and responsible discussion of matters relevant to the field of medicine. Its mission is education: to inform its readers of progress in clinical medicine, medical research, and of developments in other fields of interest to physicians."<i>JAMA</i>believes that it can provide physician readers with a valuable service by bringing to their attention legal information and analysis compiled by experienced lawyers and physicians who have been involved in
Re: UGT1A1*28 Genotype and Irinotecan-Induced Neutropenia: Dose Matters
Authors: Wataru Ichikawa, Kazuhiro Araki, Ken-Ichi Fujita, Wataru Yamamoto, Hisashi Endo, Fumio Nagashima, Ryuhei Tanaka, Toshimichi Miya, Keiji Kodama, Yu Sunakawa, Masaru Narabayashi, Yuichi Ando, Yuko Akiyama, Kaori Kawara, Yasutsuna Sasaki
Journal: JNCI Journal of the National Cancer Institute (2008)
Therapeutic and Preventive Implications of Moonshot in Hereditary Cancer Syndromes
Authors: Osama Diab, Lakshmi Manogna Chintalacheruvu, Henry T. Lynch
Journal: JAMA Oncology (2016)

This Viewpoint discusses the significance of investing billions of dollars in genomic sequencing and the implications of finding a hereditary mutation in patients with metastatic cancer using next-generation sequencing.
18F-fluoromisonidazole PET and Activity of Neoadjuvant Nintedanib in Early HER2-Negative Breast Cancer: A Window-of-Opportunity Randomized Trial
Authors: Miguel Quintela-Fandino, Ana Lluch, Luis Manso, Isabel Calvo, Javier Cortes, José Angel García-Saenz, Miguel Gil-Gil, Noelia Martinez-Jánez, Antonio Gonzalez-Martin, Encarna Adrover, Raquel de Andres, Gemma Viñas, Antonio Llombart-Cussac, Emilio Alba, Juan Guerra, Begoña Bermejo, Esther Zamora, Fernando Moreno-Anton, Sonia Pernas Simon, Alfredo Carrato, Antonio Lopez-Alonso, María José Escudero, Ruth Campo, Eva Carrasco, José Palacios, Francisca Mulero, Ramon Colomer
Journal: Clinical Cancer Research (2016)

Purpose: We previously detected promising efficacy of neoadjuvant nintedanib (a multityrosine kinase inhibitor, TKI) in early HER2-negative breast cancer. In a preclinical study, we monitored stromal hypoxia with 18F-fluoromisonidazole-positron emission tomography (18F-FMISO-PET); we found that reoxygenation of tumors (or lack of it) during a window-of-opportunity (WoO) treatment with TKIs correlated with the benefit (or lack of it) from TKI-plus-chemotherapy combinations. We studied the predictive role of 18F-FMISO-PET for the TKI nintedanib in the neoadjuvant setting in a phase II WoO randomized trial.Experimental Design: Patients were randomized to a 14-day WoO of nintedanib preceded and followed by an 18F-FMISO-PET, followed by nintedanib plus weekly paclitaxel (Arm A) or an 18F-FMISO-PET followed by weekly paclitaxel (Arm B) before surgery. The endpoint was residual cancer burden (RCB). The objective was to detect the patients with no response (RCB-III) on the basis of the baseline or evolutive 18F-FMISO-PET values/changes.Results: One-hundred and thirty HER2-negative patients were randomized. Seventeen (27.9%), 34 (55.7%), and 8 (13.1%) patients had an RCB of III, II, and I/0, respectively, in Arm A. In this arm, baseline hypoxic tumors had a 4.4-fold higher chance of experiencing RCB = 3 (P = 0.036) compared with baseline normoxic tumors. Nintedanib WoO induced tumor reoxygenation in 24.5% of the patients; those not reoxygenating showed a trend toward higher chance of experiencing RCB-III (6.4-fold; P = 0.09). In Arm B, 18F-FMISO-PET lacked predictive/prognostic value.Conclusions: Baseline hypoxic tumors (measured with 18F-FMISO-PET) do not benefit from neoadjuvant nintedanib. Clin Cancer Res; 23(6); 1432-41. ©2016 AACR.
The quality of diabetic care in patients with cancer.
Authors: K. Enright, M. K. Krzyzanowska
Journal: Journal of Clinical Oncology (2010)

e19547 Background: Diabetes, a common comorbidity in cancer patients, has been associated with higher overall and cancer specific mortality. Suboptimal diabetic care among cancer patients may be at least partially contributing to this excess mortality. Methods: Using the National Health and Nutrition Examination Survey (NHANES 1999-2006) we compared the quality of diabetic care in diabetic cancer survivors to adults with diabetes but no history of cancer. Quality of care was assessed using the National Diabetic Quality Improvement Alliance criteria (HbA1C, blood pressure, cholesterol, frequency of screening tests). Suboptimal care was defined as having 3 or more quality indicators that were not achieved. Results: 228 survivors, and 882 age and sex matched controls were identified. There was no significant difference in the individual quality indicators between survivors and controls, nor in the proportion receiving suboptimal care (27.8 v 31.7%). The majority of participants attained the targets for HbA1C (82.4 v. 81.7%), and reported routine blood pressure and cholesterol screening (92.1 v 95.8% and 78.8 v 83.7%). A lower percentage of patients in both groups had ideal blood pressure (57.3 v 53.9%) or cholesterol (60.3 v 53.9%) control. Among survivors, insurance status and cancer type were significantly associated with the likelihood of suboptimal care. Compared to privately insured patients, those with no health insurance were more likely to receive suboptimal care (OR 4.2), while those with Medicare coverage were less likely to receive suboptimal care (OR 0.59). Compared with breast cancer patients, those with a history of colon (OR 2.7) or gynecological cancer (OR 3.8) were more likely to receive suboptimal care. There was no significant association between likelihood of suboptimal care and age, income, race or comorbidities. Conclusions: There was no significant difference in the quality of diabetic care received by survivors compared with controls, but the quality of care could be improved for all diabetic patients. Among survivors, those with a history of gynaecological or colon cancer, and those without health insurance represent groups at highest risk of suboptimal diabetic care and serve as potential target groups for quality care initiatives. No significant financial relationships to disclose.
MenB vaccine programme cuts cases of meningitis and septicaemia in infants
Authors: Jacqui Wise
Journal: BMJ (2016)

The number of cases of meningitis and septicaemia caused by meningococcal group B infection in infants has halved since the introduction of a new vaccine last year, Public Health England reports.1

All newborn babies in the United Kingdom are now routinely offered the vaccination against meningococcal group B, the world’s first infant programme to use this vaccine. In the 10 months since the programme began only 37 recorded cases of meningococcal B were recorded in infants aged under 1, compared with an average of 74 in the same …
High-Dose Carfilzomib and Dexamethasone As First-Line Treatment in Symptomatic Multiple Myeloma
Authors: Tomer M Mark, Sujitha Yadlapati, Lyubov Neglyad, Jennifer Bourke, David Jayabalan, Adriana C Rossi, Roger N Pearse, Arthur Perry, Karen Pekle, Kathleen Pogonowski, Linda Tegnestam, Xiangao Huang, Maurizio Di Liberto, Scott Ely, Morton Coleman, Selina Chen-Kiang, Ruben Niesvizky
Journal: Blood (2015)
Comment on Podmore et al. Association of Multiple Biomarkers of Iron Metabolism and Type 2 Diabetes: The EPIC-InterAct Study. Diabetes Care 2016;39:572–581
Authors: Luca Mascitelli, Mark R. Goldstein, Leo R. Zacharski
Journal: Diabetes Care (2016)

Podmore et al. (1) reported the largest and most comprehensive study to date implicating iron excess in the pathogenesis of type 2 diabetes (T2D). Dose-related statistical associations existed between levels of body iron (ferritin levels) and increased T2D risk in men and women. By contrast, increasing percent transferrin saturation (%TSAT) levels predicted reduced risk in women. Similar trends for %TSAT levels were shown for men that did not reach statistical significance. Rising ferritin likely represented increased potentially damaging levels of redox active iron, whereas rising %TSAT levels likely represented protective effects of transferrin scavenging of redox active iron. The authors cautioned that iron-T2D risk associations could represent reverse causation or …
Supplemental Oxygen and Risk of Surgical Site Infection
Authors: Martin J O'Neill
Journal: JAMA (2004)

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