tbuckley/cabot-search huggingface dataset:
Phase II study of biweekly gemcitabine and docetaxel as first-line treatment for advanced disease in elderly non-small cell lung cancer (NSCLC) patients.
Authors: C. Llorca, G. Esquerdo, J. Muñoz, A. Sanchez-Hernandez, J. Gómez-Codina, O. Juan Vidal, S. Maciá, S. Catot, V. Giner, F. Aparisi
Journal: Journal of Clinical Oncology (2010)

e18066 Background: Standard treatment for patients with good PS stage IIIB/IV NSCLC currently includes a two- drug platinum-based chemotherapy regimen, but optimum treatment for elderly patients is less well defined. Thus, this study has been conducted to assess the efficacy and toxicity of biweekly gemcitabine plus docetaxel in elderly patients with NSCLC. Methods: Patients ≥70 years old with cytological or histological confirmation of advanced (stage IIIB/IV) NSCLC, PS≤1, measurable lesion according RECIST criteria, adequate bone marrow, renal, and hepatic function were included. Patients with prior systemic therapy for NSCLC and/or symptomatic brain metastases were not allowed. Patients received biweekly docetaxel 50 mg/m2 iv, gemcitabine 2,000 mg/m2 iv days 1 and 14, during 24 weeks. Toxicity was evaluated according to CTCAE 3.0. Results: Forty-nine patients were included in this interim analysis, 20.4% PS=0 and 79.6% PS=1. Main characteristics of patients are shown in the Table. Median number of lesions was 3. A total of 151 cycles (median=3, range 1-6) were administered. Median relative dose intensity was 90.0% for docetaxel and gemcitabine. Over 49 patients analysed, 8 patients achieved PR (16.3%), 21 SD (42.9%), 10 PD (20.4%) and 10 (20.4%) were not evaluable (4 due to death, 2 due to adverse event, 1 due to toxicity, 3 due to withdrawal/missing). Overall response rate was 16.3% (95%CI:6.0%-26). Median follow-up time was 4.1 months (0.2-18.4). Toxicities are shown in the Table. Conclusions: Docetaxel and gemcitabine administered every 14 days as first line treatment for advanced disease in elderly NSCLC patients seems to be a safe and active regimen. Patients' characteristics Age (yr) Median 76.0 Range 71.1-84.8 Histology (%) Squamous 38.8 Adenocarcinoma 32.7 Sites of metastases (%) Pleura 25.0 Ganglionar 25.0 Lymph nodes 22.9 Adrenal gland 20.8 Liver 16.7 Bones 14.7 Prior treatment (%) Radiotherapy 8.5 Current smokers (%) 26.5 Main comorbidities (%) COPD 58.5 Cardiovascular 39.0 Help for daily living activities (%) 97.6 Toxicities Grade IV (%) Leucopenia 4.1 Grade III nonhematological (%) Asthenia 12.2 Anorexia 4.1 Febrile neutropenia 6.1 Grade III hematological (%) Leucopenia 8.2 Neutropenia 8.2 No significant financial relationships to disclose.
Mechanisms underlying increased mortality risk in patients with heart failure and reduced ejection fraction randomly assigned to adaptive servoventilation in the SERVE-HF study: results of a secondary multistate modelling analysis
Authors: Christine Eulenburg, Karl Wegscheider, Holger Woehrle, Christiane Angermann, Marie-Pia d'Ortho, Erland Erdmann, Patrick Levy, Anita K Simonds, Virend K Somers, Faiez Zannad, Helmut Teschler, Martin R Cowie
Journal: The Lancet Respiratory Medicine (2016)
Is REDD1 a Metabolic Éminence Grise ?
Authors: Christopher Lipina, Harinder S Hundal
Journal: Trends in Endocrinology and Metabolism (2016)

REDD1 has been implicated in a range of cellular processes due, at least in part, to its ability to interact with proteins that impact protein homeostasis and metabolic function Several obesity-related factors, including hyperinsulinaemia, hyperlipidaemia, and hypoxia, have been shown to upregulate REDD1, which may facilitate the development of insulin resistance through impaired PKB/Akt-directed signalling. Genetic inhibition of REDD1 has been reported to impair insulin sensitivity through dysregulation of the mTORC1/S6K pathway. Emerging evidence suggests that REDD1 acts as a key regulator of mitochondrial oxidative capacity and lipogenesis, as well as modulating insulin production and secretion. Understanding the role of REDD1 in insulin action and energy homeostasis may provide a roadmap toward designing strategies to counteract obesity-related metabolic disorders. Regulated in development and DNA damage response 1 (REDD1) has been functionally linked to the control of diverse cellular processes due, at least in part, to its ability to repress mammalian or mechanistic Target of Rapamycin (mTOR) Complex-1 (mTORC1), a key protein complex controlled by hormonal and nutrient cues. Notably, emerging evidence suggests that REDD1 also regulates several pathways involved in modulating energy balance and metabolism. Herein, we discuss evidence implicating REDD1 as a key modulator of insulin action and metabolic function, including its potential contribution to mitochondrial biology and pancreatic islet function. Collectively, the available evidence suggests that REDD1 has a more prominent role in energy homeostasis than was previously thought, and implicates REDD1 as a potential therapeutic target for treatment of metabolic disorders. Regulated in development and DNA damage response 1 (REDD1) has been functionally linked to the control of diverse cellular processes due, at least in part, to its ability to repress mammalian or mechanistic Target of Rapamycin (mTOR) Complex-1 (mTORC1), a key protein complex controlled by hormonal and nutrient cues. Notably, emerging evidence suggests that REDD1 also regulates several pathways involved in modulating energy balance and metabolism. Herein, we discuss evidence implicating REDD1 as a key modulator of insulin action and metabolic function, including its potential contribution to mitochondrial biology and pancreatic islet function. Collectively, the available evidence suggests that REDD1 has a more prominent role in energy homeostasis than was previously thought, and implicates REDD1 as a potential therapeutic target for treatment of metabolic disorders.
Optic Nerve Head Development in Healthy Infants and Children Using Handheld Spectral-Domain Optical Coherence Tomography
Authors: Aarti Patel, Ravi Purohit, Helena Lee, Viral Sheth, Gail Maconachie, Eleni Papageorgiou, Rebecca J. McLean, Irene Gottlob, Frank A. Proudlock
Journal: Ophthalmology (2016)

PurposeTo determine feasibility of optic nerve head (ONH) imaging and to characterize ONH development in full-term infants without sedation using handheld spectral-domain optical coherence tomography (SD OCT).DesignProspective cross-sectional study.ParticipantsThree hundred fifty-two children aged between 1 day and 13 years.MethodsAll participants were imaged using handheld SD OCT without sedation during a single scan session. The percentage of successful scans was calculated. Interexaminer reproducibility and differences between right and left eyes were assessed using intraclass correlation coefficients (ICCs). Images were analyzed using ImageJ software. The developmental trajectories over time for ONH parameters were calculated using fractional polynomial modelling.Main Outcome MeasuresDisc and cup diameter (expressed as distance in micrometers and visual angle in degrees), cup depth, Bruch's membrane opening–minimum rim width (BMO-MRW), retinal thickness, and retinal nerve fiber layer (RNFL; 1700 μm and 6° from the disc center).ResultsOn average, 70% of participants were imaged successfully. Interexaminer reliability was excellent (ICC, >0.89) for diametric and retinal thickness parameters. Right and left eyes were similar for diametric measurements (ICC, >0.79), but more variable for nasal BMO-MRW, RNFL, and retinal thickness. The mean disc and cup diameter increase by 30% and 40%, respectively, between birth and 13 years of age when expressed as a distance measure, but remained constant (at 5°–5.5° and 2°, respectively) when expressed as a visual angle with reference to the eye nodal point. The peripapillary temporal RNFL demonstrated a marked initial decrease of nearly 35% between birth and approximately 18 months of age. This was followed by a slow increase up to 12 years of age when measured at 1700 μm from the disc center, although there was little change when measured at 6° from the disc center.ConclusionsWe demonstrated feasibility of handheld SD OCT imaging of the ONH in full-term infants and children without anaesthesia or sedation. This is the first in vivo handheld SD OCT study to describe the development of ONH parameters during the critical early years of visual maturation. Our results provide a normative database for use in routine practice and further studies of ONH pathologic features.
Case 38-1980
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Robert H. Schapiro, Austin L. Vickery
Journal: New England Journal of Medicine (1980)

Presentation of CaseA 44-year-old man was admitted to the hospital because of gastrointestinal bleeding.There was a long history of alcohol abuse, accompanied by a seizure disorder that was controlled with phenytoin sodium. Five years before admission peripheral edema developed. One year later ascites was found, and results of tests of liver function were slightly abnormal. Three years before entry the patient discontinued phenytoin sodium, and two weeks later he returned to this hospital because of confusion that followed a grand-mal seizure. On physical examination he appeared chronically ill and confused. The liver and spleen were not felt, and . . .
Pattern of aromatase inhibitor use in males.
Authors: M. Subar, C. J. Kuntz, S. Lust
Journal: Journal of Clinical Oncology (2010)

6091 Background: Third generation AIs [anastrozole(A), exemestane(E), letrozole(L)] are FDA-indicated in postmenopausal women with hormone responsive breast cancer (BrCa). Though not approved for use in males, AI use is described in BrCa, prostate ca, hypogonadism, to prevent gynecomastia, and for short stature in adolescents. This study evaluates how AIs are prescribed to males in a U.S. population. Methods: Deidentified pharmacy claims from Medco Health Solutions, Inc. members continuously eligible from 6/1/2007-11/30/2008 were analyzed. Males with claims for an AI were characterized by age, treatment regimen, other medications used, and specialty of prescriber. AI indication was inferred from these characteristics. Results: Claims from 25,710,785 males were analyzed. Over 4,000 males had a claim for an AI (A = 3,109; L = 904; E = 103) during the target period, comprising 3.6% of all AI prescriptions (Rx); < 18 year-old (yo) n = 772 (median 14); 18-64yo n = 2,747 (median 47) ; ≥ 65 yo n = 597 (median 73). In males < 18 yo new to AIs (483), 64% were prescribed by endocrinologists, and many used prior (118) and/or concurrent (152) growth hormone suggesting use for short stature (compendia-listed). Among men 18-64 new to AIs (1972), concurrent androgens were prescribed in 36% and AIs were most frequently prescribed by urologists, followed by endocrinologists, oncologists and psychiatrists. In men ≥ 65 yo new to AIs (356), concurrent androgens were prescribed 20%, and 28% were prescribed by oncologists. Among all males ≥ 18 yo, AIs were dosed < daily in 41%, but when written by an oncologist, 99% were daily. Conclusions: These findings provide initial insight into prescribing patterns for AIs in males. Treatment by urologists and concurrent use of androgens suggest use for hypogonadism or related conditions. Daily dosing by oncologists and use in men ≥ 65 yo suggests use for BrCa. These findings have implications regarding safety and costs of off-label use of cancer drugs particularly when available clinical evidence to support benefits is limited. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Medco Health Solutions
Anti‐IgE Monoclonal Antibody (Omalizumab) in Refractory and Relapsing Eosinophilic Granulomatosis With Polyangiitis (Churg‐Strauss): Data on Seventeen Patients
Authors: Marie Jachiet, Maxime Samson, Vincent Cottin, Jean‐Emmanuel Kahn, Guillaume Le Guenno, Philippe Bonniaud, Hervé Devilliers, Laurence Bouillet, Anne Gondouin, Fatma Makhlouf, Nadine Meaux‐Ruault, Helder Gil, Boris Bienvenu, André Coste, Matthieu Groh, Violaine Giraud, Stéphane Dominique, Bertrand Godeau, Xavier Puéchal, Chahera Khouatra, Marc Ruivard, Claire Le Jeunne, Luc Mouthon, Loïc Guillevin, Benjamin Terrier
Journal: Arthritis & Rheumatology (2016)

To describe the efficacy and safety of omalizumab, an anti-IgE monoclonal antibody, in patients with refractory and/or relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA).We conducted a nationwide retrospective study including EGPA patients who received omalizumab. Response was defined as the absence of asthma and/or sinonasal exacerbations with a prednisone dosage of ≤7.5 mg/day (complete response) or >7.5 mg/day (partial response).Seventeen patients (median age 45 years) received omalizumab for severe steroid-dependent asthma (88%) and/or sinonasal involvement (18%). After a median follow-up of 22 months, 6 patients (35%) achieved a complete response, 5 patients (30%) achieved a partial response, and 6 patients (35%) had no improvement. The median Birmingham Vasculitis Activity Score decreased from 2.5 at baseline to 0.5 at 12 months. The median number of exacerbations per month decreased from 1 at baseline to 0 at 12 months, and the median forced expiratory volume in 1 second increased from 63% of the percent predicted at baseline to 85% of the percent predicted at 12 months. The median prednisone dosage decreased from 16 mg/day at baseline to 11 mg/day at 6 months and 9 mg/day at 12 months. Omalizumab was discontinued in 8 patients (47%) during follow-up, because of remission (12.5%), adverse event despite disease remission (12.5%), refractory disease (25%), or relapse (50%). Relapses included retrobulbar optic neuritis attributable to EGPA in 2 patients and severe asthma flare in 2 others.The results of this study suggest that omalizumab may have a corticosteroid-sparing effect in EGPA patients with asthmatic and/or sinonasal manifestations, but reducing the corticosteroid dose may also increase the risk of severe EGPA flares, which raises the question of the safety of omalizumab in patients with EGPA.
Continuous intravenous injection of Mesna can effectively prevent Hemorrhagic cystitis in hematopoietic stem cell transplantation and retain the Mesna's concentration in urine: 394 cases reported within 11 years
Authors: Qianli Jiang, Hao Huang, Qifa Liu, Jing Sun, Hongsheng Zhou, Zhiping Fan, Yu Zhang, Fen Huang, Yanyan Chai, Dan Xu, Qiusui Mai, Qi Wei, Guo-Pan Yu, Xiaofang Li, Min Dai, Na Xu, Dandan Zhou, Haiyun Zhao, Ke feng Shen, Yongjun Zhou, Fanyi Meng
Journal: Blood (2014)
Extension of overall survival in patients with metastatic renal cell carcinoma who received HD IL-2 followed by targeted therapy and/or immune checkpoint blockade from the PROCLAIM registry.
Authors: Joseph Clark, David F. McDermott, Janice P. Dutcher, Michael K.K. Wong, Howard Kaufman, Gregory A. Daniels, Michael Morse, Jessica C. Perritt, Hong Hua, Tharaknath Rao
Journal: Journal of Clinical Oncology (2016)

4548 Background: High dose IL-2 (HD IL-2) can provide durable responses in patients with metastatic renal cell carcinoma (mRCC). PROCLAIM (www.proclaimregistry.com, NCT01415167) is an IL-2 registry with over 44 participating sites that captures real-world patient population survival and outcomes. Herein, we report on contemporary patient experience sequencing HD IL-2 with targeted therapy (TT) and immune checkpoint blockade (ICB) in mRCC. Methods: Patients were prospectively enrolled into the registry as of 2011 and must have received at least one dose of HD IL-2 for this analysis. Statistics and survival analysis were performed on datasets as of December 2, 2015. Results: The mOS for all mRCC patients (n=411) was not reached (NR), with a median follow-up of 21 months. The overall response rate (ORR) for the 382 patients with available data was 17.8%. The mOS for those who experienced complete response (CR, n=15), partial response (PR, n=53), or stable disease (SD, n=145) was not reached while in patients with progressive disease (PD, n=169), mOS was 17 months. Survival for patients treated with TT or ICB following HD IL-2 were further analyzed and described in Table 1. Treatments prior to HD IL-2 include chemotherapy (n=12), TT (n=74), immunotherapy (n=8), radiation (n=64), and surgery (n=389). Conclusions: This analysis of the national IL-2 registry reveals that HD IL-2 therapy followed by TT and/or ICB is potentially associated with survival benefit. HD IL-2 continues to be a valuable treatment option for eligible patients with mRCC. Clinical trial information: NCT01415167.Survival for patients with and without therapy after HD IL-2. Groups (treatment after HD IL-2) N mOS (months) 1, 2, 3 Year Survival (%) Targeted Therapy 190 35.5 81,63,50 Targeted Therapy & Immune Checkpoint Blockade 13 (12 aPD-1, 1 aPD-1 +aCTLA-4) NR 100,80,80 Immune Checkpoint Blockade 12 (7 aPD-1, 2 aPDL-1, 3 aPD-1+aCTLA-4) NR 90,79,79 No Targeted Therapy or Immune Checkpoint Blockade 196 NR 76,65,65 TT may include inhibitors of VEGF, mTOR, or, EGFR pathways.
Association Between Overnight Extubations and Outcomes in the Intensive Care Unit
Authors: Hayley B. Gershengorn, Damon C. Scales, Andrew Kramer, Hannah Wunsch
Journal: JAMA Internal Medicine (2016)

Little is known about the timing of extubations for patients in the intensive care unit (ICU) who undergo mechanical ventilation (MV) or whether overnight extubation is safe.To describe the frequency of overnight extubations and assess the association between overnight extubations and clinical outcomes.This retrospective cohort study included adults (aged ≥18 years) undergoing MV performed in US ICUs as part of the Project IMPACT database from October 1, 2000, to March 29, 2009. Data were analyzed from January 1, 2015, to July 5, 2016.Overnight extubation defined as occurring from 7 pm to 6:59 am.Multilevel multivariable regression analyses (clustered by individual ICU) were used to identify factors associated with overnight extubation. Propensity-matched pairs were created of patients undergoing overnight vs daytime extubation (separately for patients with MV duration <12 and ≥12 hours). Outcomes, including frequency of reintubation in the ICU, ICU and hospital mortality, and ICU and hospital length of stay (LOS), were assessed using χ2 and Mann-Whitney tests.The cohort consisted of 97 844 patients (40.8% men; 59.2% women; mean [SD] age, 58.3 [17.9] years) across 165 ICUs. Of these, 20.1% of patients underwent overnight extubation and the percentage decreased over time (23.3% in 2000-2001 vs 18.8% in 2009; P = .001). After multivariable adjustment, duration of MV of less than 12 hours had the greatest association with overnight extubation (compared with 12 hours to <1 day: adjusted odds ratio [AOR], 0.20 [95% CI, 0.19-0.21]; 1 to <2 days: AOR, 0.26 [95% CI, 0.24-0.28]; 2 to <7 days: AOR, 0.22 [95% CI, 0.21-0.24]; and ≥7 days: AOR, 0.24 [95% CI, 0.22-0.26]). In all, 4518 propensity-matched pairs had MV duration of less than 12 hours and 5761 had MV duration of at least 12 hours. For MV duration of less than 12 hours, reintubation rates were similar for overnight and daytime extubations (5.9% and 5.6%, respectively; P = .50), but mortality was increased for patients undergoing overnight extubation (ICU, 5.6% vs 4.6%, P = .03; hospital, 8.3% vs 7.0%, P = .01). The ICU LOS was shorter for overnight vs daytime extubations (median [interquartile range], 1.1 [0.8-2.3] vs 1.4 [0.9-2.5] days; P < .001), and hospital LOS was similar (median [interquartile range], 7.0 [4.0-12.0] vs 7.0 [3.0-12.0] days; P = .03). Patients with MV duration of at least 12 hours who underwent overnight extubation had more frequent reintubation in the ICU (14.6% vs 12.4%; P < .001) and higher mortality in the ICU (11.2% vs 6.1%; P < .001) and in the hospital (16.0% vs 11.1%; P < .001), with no differences in LOS.Approximately one-fifth of patients with MV in US ICUs undergo overnight extubation. These patients have higher rates of ICU and hospital mortality than patients undergoing extubation during the daytime. Further studies are needed to understand why overnight extubation results in poorer outcomes.
Fracture incidence after liver transplantation: results of a 10 year audit
Authors: T. K. Das, M. Premaor, I. Debiram, G. Alexander, J. E. Compston
Journal: Gut (2011)

<h3>Introduction</h3> High rates of fracture were initially reported following liver transplant but the impact of subsequent changes in immunosuppressive regimens and use of bone protective therapy on fracture rate has not been reported. The aim of this study was to document clinical fracture incidence during the period 1998–2008 in a single transplant centre, following introduction of a bone management protocol. <h3>Methods</h3> In an audit of all patients with a first liver transplant during this period records were retrieved from 531 of 592 eligible patients (1998–2007). All fractures were verified radiologically. <h3>Results</h3> The mean follow-up period was 61.4 months. Prior to transplant 5.6% of patients had a history of fracture. Incident clinical fractures post-transplant were recorded in 15 (3.5%) of patients. The most common fracture site was the spine and the median time since fracture to transplant was 26 months (range 2–83). <h3>Conclusion</h3> In conclusion, the authors have demonstrated low rates of fracture in patients undergoing liver transplantation at our centre over the past 10 years. The use of lower doses of prednisolone for immunosuppression and administration of bone protective therapy to high-risk patients are both likely to have contributed.
Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD
Authors: Raphael Carapito, Nicolas Jung, Marius Kwemou, Meiggie Untrau, Sandra Michel, Angélique Pichot, Gaëlle Giacometti, Cécile Macquin, Wassila Ilias, Aurore Morlon, Irina Kotova, Petya Apostolova, Annette Schmitt-Graeff, Anne Cesbron, Katia Gagne, Machteld Oudshoorn, Bronno van der Holt, Myriam Labalette, Eric Spierings, Christophe Picard, Pascale Loiseau, Ryad Tamouza, Antoine Toubert, Anne Parissiadis, Valérie Dubois, Xavier Lafarge, Myriam Maumy-Bertrand, Frédéric Bertrand, Luca Vago, Fabio Ciceri, Catherine Paillard, Sergi Querol, Jorge Sierra, Katharina Fleischhauer, Arnon Nagler, Myriam Labopin, Hidetoshi Inoko, Peter A. von dem Borne, Jürgen Kuball, Masao Ota, Yoshihiko Katsuyama, Mauricette Michallet, Bruno Lioure, Régis Peffault de Latour, Didier Blaise, Jan J. Cornelissen, Ibrahim Yakoub-Agha, Frans Claas, Philippe Moreau, Noël Milpied, Dominique Charron, Mohamad Mohty, Robert Zeiser, Gérard Socié, Seiamak Bahram
Journal: Blood (2016)
No room for sexism
Authors: Fiona Godlee
Journal: BMJ (2016)

It is perhaps no great surprise that two traditionally macho cultures—Australia and surgery—combine to harbour sexist attitudes. But the extent of the harassment of Australia’s female surgeons, and the impunity with which senior surgeons meted out the abuse, has only recently been fully acknowledged. That it has is thanks to the courage of one woman in speaking out. Vascular surgeon Gabrielle McMullin’s description of an entrenched culture of sexual harassment caused a media storm last year, followed by a flood of corroborative stories from female surgeons who had experienced …