tbuckley/cabot-search huggingface dataset:
Development of a novel nomogram predicting nonsentinel lymph node metastases among patients with breast cancer after neoadjuvant chemotherapy (NACT): A transSENTINA substudy.
Authors: Cornelia Liedtke, Dennis Goerlich, Ingo Bauerfeind, Tanja Fehm, Barbara Fleige, Annette Lebeau, Annette Staebler, Gunter Von Minckwitz, Michael Untch, Thorsten Kuehn
Journal: Journal of Clinical Oncology (2014)

1100 Background: The optimal timing for sentinel lymph node biopsy (SLNB) in the setting of NACT is still unclear. Recent studies such as SENTINA suggest that performing SLNB in patients with a cN+ status before, converting to cN0 after NACT (arm C) results in a non-acceptable false-negative rate. Therefore, there is a need to predict non-SLN status and tailor axillary surgery after NACT. The goal of this study was to develop an optimized nomogram based on data from SENTINA trial patients. Methods: The SENTINA trial with 1,737 patients from 104 institutions was previously described in detail. 181 patients in arm C were analyzed as a development set. Risk factors for non-sentinel node involvement have been selected based on prior univariate logistic regression analysis using a threshold of p<=0.2 and subsequent multivariable logistic regression using a backward selection procedure applying the likelihood ratio test. Validation of the model was carried out using a leave-one-out-validation (LOOV). The performance of the nomograms was evaluated by the area under the receiver operator curve (AUC). Results: Selected variables of the final prediction model comprised number of positive resected lymph nodes (OR=1.656, CI: 1.025-2.677, p=0.039), sonographic diameter of largest lymph node (OR=1.126, CI: 1.037-1.223, p=0.005) and tumor diameter after NACT (OR=1.180, CI: 0.962-1.447, p=0.112). A preliminary nomogram was built and yielded a mean AUC of 0.75252 (SD=0.004576, min=0.748, max=0.766) in LOO-validation. Selecting a cutpont of 36%, a sensitivity of 82% and a specificity of 49% may be reached. Additional analyses are ongoing and results will be presented. Conclusions: We developed a nomogram for prediction of non-sentinel lymph node metastases following NACT using the SENTINA patient database. The nomogram yielded AUC values comparable to previously presented nomograms. A provisional cutpoint for clinical decision making is described. External validation is planned.
Systematic review of rash in cancer patients receiving ibrutinib and idelalisib.
Authors: Zhe Hou, Viswanath Reddy Belum, Maria Lia Palomba, Ysebaert Loic, Vincent Sibaud, Mario E. Lacouture
Journal: Journal of Clinical Oncology (2015)

e12655 Background: Ibrutinib is a BTK inhibitor approved for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL) and Waldenstrom’s macroglobulinemia. Idelalisib is a PI3Kδ inhibitor currently approved as monotherapy for relapsed follicular B-cell non-Hodgkin lymphoma and relapsed small lymphocytic lymphoma (SLL), and in combination with rituximab for relapsed CLL. The incidence and risk of rash with these agents has not been systematically ascertained. Methods: We searched the Pubmed, Web of Science, ASCO and American Society of Hematology meetings’ abstracts to identify clinical trials of ibrutinib and idelalisib, reporting skin rash in their safety data. Results: In all, 5 trials were included. The incidence of all-grade rash with ibrutinib ranged from 15% - 28%; a high-grade rash was noted in 0-2%. In patients receiving idelalisib, 10% -13% developed an all-grade rash, while 2% experienced a high-grade rash. Conclusions: Ibrutinib and idelalisib frequently lead to a maculopapular rash that may affect consistent dosing and quality of life. These findings highlight the urgent need for its characterization, proper counseling and management strategies, to improve adherence and optimal clinical outcomes. DRUG NAME PHASE INDICATION DOSAGE CONTROL/ OTHER ARM PATIENTS (NUMBER) ALL-GRADE1 RASH HIGH-GRADE RASH DRUG CONTROL DRUG CONTROL DRUG CONTROL IBRUTINIB Ib/II CLL,SLL 420 mg PO daily N/A 852 N/A 23 (27%) N/A 0 (0%) N/A Ib/II CLL,SLL 420 mg PO daily N/A 1163 N/A 32 (28%) N/A N/A N/A II MCL 560 mg PO daily N/A 111 N/A 17 (15%) N/A 2 (2%) N/A IDELALISIB II Indolent non-Hodgkin’s lymphomas 150 mg PO BID N/A 125 N/A 16 (13%) N/A 2 (2%) N/A III CLL Idelalisib 150 mg PO BID + rituximab4 Rituximab4 110 107 11 (10%) 6 (6%) 2 (2%) 0 (0%) 1CTCAE v4.0. 2Including 34 patients receiving ibrutinib of 840 mg PO daily. 3Including 39 patients receiving ibrutinib of 840 mg PO daily. 4Rituximab is dosed at 375 mg/m2 then 500 mg/m2x 8 doses.
Abstract 19743: Electrophysiological and Cerebrovascular Effects of Selective Antegrade Cerebral Perfusion in Moderate Hypothermia vs. Deep Hypothermic Circulatory Arrest in a Rat Model
Authors: Alessio Rungatscher, Daniele Linardi, Elisabetta Milani, Tiziano Menon, Maddalena Tessari, Grygory Tsenov, Andrea del Pilar Rodriguez, Giang Tong, Katharina Schmitt, Giovanni Battista Luciani, Giuseppe Faggian
Journal: Circulation (2015)

Introduction: Selective antegrade cerebral perfusion (SACP) is adopted by many surgical groups as an alternative to deep hypothermic circulatory arrest. However there are still no preclinical evidences to support this strategy. Hypothesis: We hypothesize that SACP in moderate hypothermia vs DHCA could have different modulation of electrophysiological and cerebrovascular processes in vivo. Methods: Extra-corporeal circulation with central cannulation was instituted in male Wistrar rats. Animals were randomized to DHCA (16-18°C) or SACP (left carotid artery cannulation; 10 ml/kg/min) in moderate hypothermia (26-28°C). After 20 min of circulatory arrest, rats underwent 60 min of reperfusion / rewarming. EEG activity was recorded during all experiments. Neurological deficit score and survival were determined after 24 hours. Thereafter animals were scarified and brain snap-frozen and analyzed. Results: EEG activity 2-40 Hz (Power Spectrum Analysis) decreased in all rats during circulatory arrest. However, SACP determined fast recovery of brain activity and less decreased EEG power spectral density compared to DHCA (p &lt;0.05). After 24 h survival and neurologic deficit scores were not different in the two groups. However histological damage scores, brain TNF-α, caspase-3, TUNEL and GSH/GSSG ratio were attenuated in SACP compared to DHCA (all p&lt;0.05). Conclusions: Selective antegrade cerebral perfusion in moderate hypothermia is superior to DHCA in restoring brain electrical activity and in reducing apoptosis, oxidative stress and neuroinflammation.
Identification of a 62‐kDa major allergen from <i>Artemisia</i> pollen as a putative galactose oxidase
Authors: W. Fu, Z. Gao, L. Gao, J. Jin, M. Liu, Y. Sun, S. Wu, L. Wu, H. Ma, Y. Dong, X. Wang, B. Gao, H. Wang, J. H. Akkerdaas, S. A. Versteeg, R. van Ree
Journal: Allergy (2017)

Abstract Background Around 20 years ago, a 60‐ to 70‐kDa protein was reported as a major allergen of mugwort ( Artemisia vulgaris ) pollen. This study was to identify and characterize its molecular properties. Methods Sera from 113 Chinese and 20 Dutch Artemisia ‐allergic/sensitized subjects (and pools thereof) were used to identify the 60‐ to 70‐kDa allergen. Pollen extracts of seven Artemisia species were compared by immunoblotting. Transcriptomics and proteomics (mass spectrometry) of A. annua pollen were used to identify the putative 60‐ to 70‐kDa Artemisia allergen. Both the natural purified and recombinant allergens were evaluated for IgE reactivity by ImmunoCAP. Fourteen Chinese Artemisia ‐allergic patients were tested intradermally with purified natural allergen. Results Immunoblots revealed two major bands at 12 and 25 kDa, and a weak band at 70 kDa for all seven Artemisia species. Using a combined transcriptomic and proteomic approach, the high molecular mass allergen in A. annua pollen was shown to be a 62‐kDa putative galactose oxidase, with a putative N‐glycosylation site. More than 94% of Artemisia pollen‐allergic patients had IgE response to this allergen. Although recognition of a nonglycosylated recombinant version was only confirmed in a minority (16%) and at much lower IgE levels, this discrepancy cannot be explained simply by reactivity to the carbohydrate moiety on the natural allergen. Intradermal testing with the natural allergen was positive in five of nine sensitized patients. Conclusions The previously reported 60‐ to 70‐kDa allergen of Artemisia pollen is most likely a 62‐kDa putative galactose oxidase here designated Art an 7.
Deciphering the intra-tumoural T cell receptor repertoire in patients with NSCLC within the lung TRACERx study
Authors: K. Joshi, J.L. Reading, M. Ismail, T. Oakes, R. Rosenthal, I. Uddin, M. Jamal-Hanjani, N. McGranahan, Y.N.S. Wong, A.J. Furness, A.B. Aissa, M. Werner Sunderland, A. Georgiou, S. Veeriah, J. Czyzewska-Khan, T. Marafioti, K. Peggs, C. Swanton, B.M. Chain, S. Quezada
Journal: Annals of Oncology (2017)
Perceptions of Prognosis and Treatment Risk in Older Patients with Acute Myeloid Leukemia
Authors: Areej El-Jawahri, Gregory A. Abel, Joseph Greer, Amir T. Fathi, David P. Steensma, Thomas W. LeBlanc, Daniel J. DeAngelo, Martha Wadleigh, Gabriela S. Hobbs, Julia Foster, Andrew Mark Brunner, Philip C. Amrein, Richard M. Stone, Jennifer S Temel
Journal: Blood (2017)
Emergency Department Stroke Care
Authors: William J. Meurer, Kevin Ward, Eva L. Feldman
Journal: JAMA Neurology (2017)

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Contact Precautions for Multidrug-Resistant Organisms—Reply
Authors: Daniel J. Morgan, Richard P. Wenzel, Gonzalo Bearman
Journal: JAMA (2017)

In Reply Dr Peterson mischaracterizes our rejection of active surveillance and other ineffective contact precaution practices for MRSA and VRE. The premise of our Viewpoint was that medicine should follow the most rigorous clinical evidence available to inform policy until more data exist.
A phase III trial to compare atezolizumab (atezo) vs best supportive care (BSC) following adjuvant chemotherapy in patients (pts) with completely resected NSCLC: IMpower010.
Authors: Heather A. Wakelee, Nasser K. Altorki, Eric Vallieres, Caicun Zhou, Yunxia Zuo, Michael Howland, Fan Xia, Alan Sandler, Enriqueta Felip
Journal: Journal of Clinical Oncology (2017)

TPS8576 Background: The anti–PD-L1 mAb atezo blocks the interaction between PD-L1 and its receptors PD-1 and B7.1 and restores anti-tumor immunity. In the OAK trial, pts with 2L/3L advanced NSCLC had improved mOS in the atezo arm (13.8 mo) vs the docetaxel (doc) arm (9.6 mo), with a survival benefit observed regardless of PD-L1 expression levels on tumor cells (TC) or tumor-infiltrating immune cells (IC). However, more effective treatment options are needed for pts with early-stage NSCLC. A global Phase III, randomized, open-label trial, IMpower010 (NCT02486718), is being conducted to evaluate the efficacy and safety of atezo vs BSC following adjuvant cisplatin (cis)–based chemotherapy (chemo) in pts with resected stage IB (tumors ≥ 4 cm)-IIIA NSCLC. Methods: Pts eligible for study must have complete tumor resection 4 to 12 weeks prior to enrollment for pathologic stage IB (tumors ≥ 4 cm)-IIIA NSCLC, be adequately recovered from surgery, be able to receive cis-based adjuvant chemo and have an ECOG PS 0-1. Pts with other malignancies, autoimmune disease, hormonal cancer or radiation therapy within 5 years and prior chemo or immunotherapy are excluded from study. Approximately 1127 pts will be enrolled regardless of PD-L1 status. Pts will receive up to four 21-d cycles of cis-based chemo (cis [75 mg/m 2 IV, d 1] + vinorelbine [30 mg/m 2 IV, d 1, 8], doc [75 mg/m 2 IV, d 1] or gemcitabine [1250 mg/m 2 IV, d 1, 8], or pemetrexed [500 mg/m 2 IV, d 1; only non-squamous NSCLC]). No adjuvant radiation therapy is permitted. After adjuvant chemo, eligible pts will be randomized 1:1 to receive 16 cycles of atezo 1200 mg q3w or BSC. Stratification factors include sex, histology (squamous vs non-squamous), disease stage (IB vs II vs IIA) and PD-L1 status by IHC (TC2/3 [≥ 5% expressing PD-L1] and any IC vs TC0/1 [ &lt; 5%] and IC2/3 vs TC0/1 and IC0/1 [ &lt; 5%]). The primary endpoint is disease-free survival; secondary endpoints include OS and safety. Exploratory biomarkers, including PD-L1 expression, immune- and tumor-related biomarkers before, during and after treatment with atezo and at radiographic disease recurrence, or confirmation of new primary NSCLC, will be evaluated. Clinical trial information: NCT02486718.
Abstract 12897: The Synergistic Effects of Fatigue and Depression on Use of Medical Services in Patients With Heart Failure
Authors: Seongkum Heo, Jean McSweeney, Pao-Feng Tsai, Songthip Ounpraseuth
Journal: Circulation (2016)

Introduction: Heart failure (HF) is an expensive clinical condition, which imparts a considerable burden on patients and society. Fatigue and depression are the most common physical and psychological symptoms, and together may have more impact on use of medical services than one symptom alone. Hypothesis: We hypothesized that fatigue and depression would have the synergistic effects on use of different medical services controlling for common covariates. Methods: We conducted a secondary data analysis of a university medical center electronic database (N = 582, mean age 63 ± 14 years, 54% males). Data were collected on fatigue, depression, covariates (i.e., sociodemographic and clinical characteristics, vital signs, laboratory tests [serum troponin, albumin, triglycerides, creatinine, sodium, hemoglobin, monocytes, and neutrophils], and medication [beta-blockers, antidepressants, and angiotensin converting enzyme inhibitors]), and frequency of medical service use based on CPT codes. Patients were categorized into one of four symptom groups based on ICD-9 codes: no symptom, fatigue only, depression only, and fatigue and depression. General linear regression was used to analyze the data. Results: The mean number of total medical service use was 96.5 ± 84.3 over 3 years. The mean number in the fatigue and depression group (152.6 ± 103.4) was greater than the fatigue only (122.9 ± 97.9, p = .016), depression only (84.3 ± 62.0, p &lt; .001), and no symptom groups (61.7 ± 46.7, p &lt; .001) controlling for covariates. In further analyses, the numbers of medical service use in the fatigue and depression group compared with the other groups were greater in evaluation and management services (e.g., inpatient and outpatient services, p &lt; .001), radiology services (e.g., diagnostic imaging and ultrasound, p &lt; .001), and medicine services (e.g., medical services and procedures such as cardiovascular, p &lt; .05). Conclusion: Fatigue and depression showed synergistic impact on the number of total medical service use. Clinicians should assess and manage fatigue and depression together and provide interventions to manage them effectively to assist in reducing medical service use.
AAV5–Factor VIII Gene Transfer in Severe Hemophilia A
Authors: Savita Rangarajan, Liron Walsh, Will Lester, David Perry, Bella Madan, Michael Laffan, Hua Yu, Christian Vettermann, Glenn F. Pierce, Wing Y. Wong, K. John Pasi
Journal: New England Journal of Medicine (2017)

Patients with hemophilia A rely on exogenous factor VIII to prevent bleeding in joints, soft tissue, and the central nervous system. Although successful gene transfer has been reported in patients with hemophilia B, the large size of the factor VIII coding region has precluded improved outcomes with gene therapy in patients with hemophilia A.
MIPSS70: Mutation-Enhanced International Prognostic Score System for Transplantation-Age Patients With Primary Myelofibrosis
Authors: Paola Guglielmelli, Terra L. Lasho, Giada Rotunno, Mythri Mudireddy, Carmela Mannarelli, Maura Nicolosi, Annalisa Pacilli, Animesh Pardanani, Elisa Rumi, Vittorio Rosti, Curtis A. Hanson, Francesco Mannelli, Rhett P. Ketterling, Naseema Gangat, Alessandro Rambaldi, Francesco Passamonti, Giovanni Barosi, Tiziano Barbui, Mario Cazzola, Alessandro M. Vannucchi, Ayalew Tefferi
Journal: Journal of Clinical Oncology (2017)

Purpose To develop a prognostic system for transplantation-age patients with primary myelofibrosis (PMF) that integrates clinical, cytogenetic, and mutation data. Patients and Methods The study included 805 patients with PMF age ≤ 70 years recruited from multiple Italian centers and the Mayo Clinic (Rochester, MN), forming two independent learning and validation cohorts. A Cox multivariable model was used to select from among a list of 22 variables those that were predictive of overall survival (OS). Integrated clinical and genetic prognostic models with (MIPSS70-plus) or without (MIPSS70) cytogenetic information were developed. Results Multivariable analysis identified the following as significant risk factors for OS: hemoglobin < 100 g/L, leukocytes > 25 × 109/L, platelets < 100 × 109/L, circulating blasts ≥ 2%, bone marrow fibrosis grade ≥ 2, constitutional symptoms, absence of CALR type-1 mutation, presence of high-molecular risk mutation (ie, ASXL1, EZH2, SRSF2, IDH1/ 2), and presence of two or more high-molecular risk mutations. By assigning hazard ratio (HR)-weighted points to these variables, three risk categories were delineated for the MIPSS70 model; 5-year OS was 95% in low-risk, 70% in intermediate-risk, and 29% in high-risk categories, corresponding to median OS of 27.7 years (95% CI, 22 to 34 years), 7.1 years (95% CI, 6.2 to 8.1 years), and 2.3 years (95% CI, 1.9 to 2.7 years), respectively. In the MIPSS70-plus model, which included cytogenetic information, four risk categories were delineated, with 5-year OS of 91% in low-risk, 66% in intermediate-risk (HR, 3.2; 95% CI, 1.9 to 5.2), 42% in high-risk (HR, 6.4; 95% CI, 4.1 to 10.0), and 7% very high-risk categories (HR, 17.0; 95% CI, 9.8 to 29.2). Both models remained effective after inclusion of older patients in the analysis. Conclusion MIPSS70 and MIPSS70-plus provide complementary systems of risk stratification for transplantation-age patients with PMF and integrate prognostically relevant clinical, cytogenetic, and mutation data.
European cluster of imported falciparum malaria from Gambia
Authors: T Jelinek, C Schade Larsen, H Siikamäki, B Myrvang, P Chiodini, J Gascón, L Visser, A Kapaun, G Just-Nübling
Journal: Eurosurveillance (2008)

A cluster of 56 patients returning from Gambia with falciparum malaria has been noted in several countries of the European Union since September this year. TropNetEurop, the European Network on Imported Infectious Disease Surveillance, collected and reported the cases. Lack of awareness and, consequently, of prophylactic measures against malaria were apparent in the majority of patients.
Risques d’infections dues à l’eau dans un environnement naturel ou artificiel
Authors: G Nichols
Journal: Eurosurveillance (2006)

L’exposition a un milieu - naturel ou artificiel - contamine par des selles d’humains ou d’animaux peut etre responsable de la survenue de diarrhees chez l’homme. Les jeunes enfants sont plus particulierement sensibles aux pathogenes impliques et au risque d’une telle exposition. Si, chez l’enfant, les diarrhees sont le plus souvent relativement benignes et peuvent assurer une certaine protection a l’âge adulte, certaines peuvent etre graves. Deux articles publies dans ce numero d’Eurosurveillance decrivent des epidemies survenues dans un tel contexte. L’une, decrite par Chikwe Ihekweazu et al, est liee a l’exposition a un cours d’eau contamine par Escherichia coli provenant de dejections animales [1]; l’autre, decrite par Melanie Jones et al, est liee a l’exposition lors d’une attraction aquatique contaminee par Cryptosporidium parvum provenant de dejections animale ou humaines [2].
Hematopoietic Stem Cell Transplantation from Full Matched Alternative Donor Has Same Results As Those from Matched Sibling for Patients with Beta-Thalassemia Major —a Large-Cohort Multicenter Study from China
Authors: Yuelin He, Hua Jiang, Changgang Li, Yiping Zhu, Xuedong Wu, Jianyun Liao, Hebi Jiang, Sixi Liu, Xue Yang, Xiaoqin Feng, Yuqiong Ren, Chunfu Li
Journal: Blood (2017)
Sistema Europeo de Vigilancia de Resistencias Antimicrobianas (EARSS) : objetivos y organización
Authors: S L A M Bronzwaer, W Goettsch, B Olsson-Liljequist, M C J Wale, A Vatopoulos, M. J.W Sprenger
Journal: Eurosurveillance (1999)

Una vigilancia europea eficaz exige el consenso y la intervencion activa de todos los participantes. Con esta frase concluia la conferencia de la Union Europea (UE), celebrada el mes de septiembre de 1998 en Dinamarca (1), sobre la necesidad de establecer una vigilancia de los microorganismos resistentes (la amenaza microbiana). Los patrones de resistencia a los antibioticos varian enormemente entre los estados miembros de la UE (2,3). Los estudios sugieren que las politicas y pautas sobre uso de antibioticos pueden afectar la prevalencia de resistencias (4,5).
Philippines halts dengue immunisation campaign owing to safety risk
Authors: Owen Dyer
Journal: BMJ (2017)

The Philippines has halted a dengue immunisation campaign and all marketing of the world’s first approved dengue vaccine, Sanofi Pasteur’s Dengvaxia, after post-market testing confirmed that it can increase the risk of severe dengue in people who have never been exposed to the virus.

The vaccine is at the centre of a growing political scandal in the Philippines, where 830 000 schoolchildren have already been vaccinated in a campaign that continued unmodified despite a World Health Organization warning in July 2016 that Dengvaxia may pose a threat to people who had never been infected.

As anti-vaccine protestors demonstrated outside the Philippines Congress, …
NHS may have to abandon waiting times targets because of funding shortfall, leaders say
Authors: Anne Gulland, Gareth Iacobucci
Journal: BMJ (2017)

Leaders of the NHS in England have warned that the service may be forced to abandon waiting time targets and ignore new clinical guidelines next year in light of the chancellor’s budget settlement last week, which was lower than they had asked for.

NHS England’s board, meeting on Thursday 30 November, produced a paper saying that it was important to be “realistic about what can be expected from the remaining available funds.”1

But England’s health secretary, Jeremy Hunt, said that the government expected waiting time standards to be met given the “significant increase” the NHS received in the budget.

The chancellor of the exchequer, Philip Hammond, pledged an extra £2.8bn (€3.2bn; $3.7bn) for the NHS over the next two years. But this fell short of the £4bn that NHS England’s chief executive, Simon Stevens, and others estimated was needed to …