tbuckley/cabot-search huggingface dataset:
A retrospective cohort study of inpatient chemotherapy utilization in hospitalized advanced lung cancer patients in the United States.
Authors: Hyunseok Kang, Sungjin Kim, Zhengjia Chen, Bassel F. El-Rayes, Johann Christoph Brandes, Nabil F. Saba, Fadlo Raja Khuri, Suresh S. Ramalingam, Taofeek Kunle Owonikoko
Journal: Journal of Clinical Oncology (2013)

6611 Background: The administration of chemotherapy to patients with limited performance status and within 6 weeks of death is considered an indicator of poor quality care. We assessed predictors of inpatient chemotherapy use and the risk of death in hospitalized lung cancer patients treated with chemotherapy in the US. Methods: Data were obtained from all US states that contributed to the Nationwide Inpatient Sample (NIS) by Agency for Health Care Research and Quality (AHRQ) in 2006 and 2010. Lung cancer diagnoses and inpatient chemotherapy were identified using Clinical Classification Software (CCS) code which is based on ICD9 and CPT codes. Univariate and multivariate analyses were performed to compare patients based on chemotherapy administration using ANOVA, chi-square test, and logistic regression. Initial analysis in the 2006 NIS data was validated in the 2010 NIS data. Results: 24,025 and 24,323 eligible hospitalized lung cancer patients including 1,005 (4.2 %) and 869 (3.6 %) patients treated with chemotherapy were identified in 2006 and 2010 respectively. Female gender, radiation use, urban location and longer length of stay (LOS) were significantly associated with receipt of chemotherapy. Chemotherapy administration was associated with prolonged hospital stay (14.1 ± 9.8 vs. 8.8 ± 8.1 days, p&lt;.001) and increased odds of death in unadjusted analyses. Adjusted analysis showed significant increased odds of death in chemotherapy-treated patients with metastatic disease (vs. no metastasis); poor performance status indicated by severe loss of function (vs. minor/moderate loss of function) and increased LOS (Table). Conclusions: Inpatient administration of chemotherapy to hospitalized US lung cancer patients is associated with higher mortality and can be explained by treatment given to patients with high co-morbidity and disease burden. [Table: see text]
Targetable fusions of the FRK tyrosine kinase in ALK-negative anaplastic large cell lymphoma
Authors: G Hu, S Dasari, Y W Asmann, P T Greipp, R A Knudson, H K Benson, Y Li, B W Eckloff, J Jen, B K Link, L Jiang, J S Sidhu, L E Wellik, T E Witzig, N N Bennani, J R Cerhan, R L Boddicker, A L Feldman
Journal: Leukemia (2017)
Management of a Lassa fever outbreak, Rhineland-Palatinate, Germany, 2016
Authors: Lutz Ehlkes, Maja George, Gerhard Samosny, Florian Burckhardt, Manfred Vogt, Stefan Bent, Klaus Jahn, Philipp Zanger
Journal: Eurosurveillance (2017)

Due to rapid diagnosis and isolation of imported cases, community outbreaks of viral haemorrhagic fevers (VHF) are considered unlikely in industrialised countries. In March 2016, the first documented locally acquired case of Lassa fever (LF) outside Africa occurred, demonstrating the disease's potential as a cross-border health threat. We describe the management surrounding this case of LF in Rhineland-Palatinate - the German federal state where secondary transmission occurred. Twelve days after having been exposed to the corpse of a LF case imported from Togo, a symptomatic undertaker tested positive for Lassa virus RNA. Potential contacts were traced, categorised based on exposure risk, and monitored. Overall, we identified 21 contact persons with legal residency in Rhineland-Palatinate: seven related to the index case, 13 to the secondary case, and one related to both. The secondary case received treatment and recovered. Five contacts were quarantined and one was temporarily banned from work. No further transmission occurred. Based on the experience gained during the outbreak and a review of national and international guidelines, we conclude that exposure risk attributable to corpses may currently be underestimated, and we present suggestions that may help to improve the anti-epidemic response to imported VHF cases in industrialised countries.
Complement Activation in a Murine Model of Sickle Cell Disease: Inhibition of Vaso-Occlusion By Blocking C5 Activation
Authors: Terry Robert Schaid, Julia Nguyen, Chunsheng Chen, Fuad Abdulla, Trevor Killeen, Hao Nguyen, Joseph Edmund, Margaret A Lindorfer, Ronald P Taylor, Agustin P Dalmasso, John D Belcher, Gregory M Vercellotti
Journal: Blood (2016)
Gastrointestinal symptoms in elite athletes: time to recognise the problem?
Authors: Jamie N Pugh, Robert Fearn, James P Morton, Graeme L Close
Journal: British Journal of Sports Medicine (2017)

Gastrointestinal (GI) symptoms can arise from a number of physiological and pathological processes including inflammation, infection and malignancy.1 Such symptoms are a common cause for referral to secondary care. They impair quality of life, even in the absence of organic pathology.2 

GI symptoms are common in endurance sports, particularly running. Prevalence of symptoms varies depending on the event, assessment tool used and what is classified as a ‘symptom’ in each study, but between 30% and 90% of individuals have reported GI symptoms.3 However, there has been less research in examining the prevalence of such symptoms in other sports, particularly at elite level. This is surprising given that many of the factors associated with GI damage and symptoms are commonly …
Multidrug- and extensively drug-resistant tuberculosis: a persistent problem in the European Union and European Economic Area
Authors: C Ködmön, V Hollo, E Huitric, A Amato-Gauci, D Manissero
Journal: Eurosurveillance (2010)

Since 2008, the European Centre for Disease Prevention and Control has been collecting data from the European Union (EU) and European Economic Area (EEA) on resistance to first- and second-line drugs against tuberculosis (TB). In 2008, the proportion of multidrug-resistant tuberculosis (MDR TB) was 6.0% of the total case load for 25 countries reporting data. Extensively drug-resistant (XDR TB) reporting has increased since 2007 and was observed in 7.3% of the MDR TB cases in 13 reporting countries. MDR TB remains a threat and XDR TB is now established within the EU/EEA borders.
Evaluating Comorbidities, Natural History, and Predictors of Early Resolution in a Cohort of Children With Chronic Urticaria
Authors: Elena Netchiporouk, Denis Sasseville, Linda Moreau, Youssef Habel, Elham Rahme, Moshe Ben-Shoshan
Journal: JAMA Dermatology (2017)

Chronic urticaria (CU) affects 0.1% to 0.3% of children. Most cases have no identifiable trigger and are classified as chronic spontaneous urticaria (CSU). At least half of patients with CSU may have an autoimmune etiology that can be determined in vitro using the basophil activation test (BAT). While 30% to 55% of CU cases resolve spontaneously within 5 years in adults, the natural history and predictors of resolution in children are not known.To assess the comorbidities, natural history of CU, and its subtypes in children and identify predictors of resolution.We followed a pediatric cohort with chronic urticaria that presented with hives lasting at least 6 weeks between 2013 and 2015 at a single tertiary care referral center.Data were collected on disease activity, comorbidities, physical triggers, BAT results, complete blood cell count, C-reactive protein levels, thyroid-stimulating hormone levels, and thyroid peroxidase antibodies.We assessed the rate of resolution (defined as absence of hives for at least 1 year with no treatment) and the association with clinical and laboratory markers.The cohort comprised 139 children younger than 18 years old. Thirty-one patients (20%) had inducible urticaria, most commonly cold induced. Six children had autoimmune comorbidity, such as thyroiditis and type 1 diabetes. Autoimmune disorders (24 patients [17%]) and CU (17 patients [12%]) were common in family members. Positive BAT results (CD63 levels > 1.8%) were found in 58% of patients. Patients with positive BAT results (CD63 level >1.8%) were twice as likely to resolve after 1 year compared with negative BAT results (hazard ratio [HR], 2.33; 95% CI, 1.08-5.05). In contrast, presence of basophils decreased the likelihood of resolution (HR, 0.40; 95% CI, 0.20-0.99). No correlation with age was found. Chronic urticaria resolved in 43 patients, with a rate of resolution of 10.3% per year. Levels of CD63 higher than 1.8% and absence of basophils were associated with earlier disease resolution.Resolution rate in children with CU is low. The presence of certain biomarkers (positive BAT result and basophil count) may help to predict the likelihood of resolution.
What you need to know about cancer drugs
Authors: Fiona Godlee
Journal: BMJ (2017)

Last year, writing in The BMJ , Peter Wise told us that cytotoxic chemotherapy had done little to extend life of people with cancer (doi:10.1136/bmj.i5792). Most of the added years were due to earlier diagnosis and treatment, he said, and he called for higher bars to drug approval, accurate and impartial information for patients, and rejigging of our clinical priorities.

This week brings further news in a similar vein. A systematic study of cancer drugs approved by the European Medicines Agency in recent years finds that most had no supporting …
Safety, pharmacodynamic, and pharmacokinetic profile of TSR-042, an anti–PD–1 monoclonal antibody, in patients (pts) with advanced solid tumors
Authors: J.C. Sachdev, A. Patnaik, J. Waypa, J. Pelusi, M. Beeram, E. Im, D. Jenkins, K. McEachern, S. Lu, W. Guo, R. Tran, V. Reichert, D. Bobilev, V. Kansra, G.J. Weiss
Journal: Annals of Oncology (2017)
Recommandations pour la gestion de la prophylaxie post-exposition au VIH après expositions sexuelles, à des drogues injectables ou d'autres expositions en Europe
Authors: J Almeda, J Casabona Barbarà, B Simon, M Gérard, D Rey, V Puro, T Thomas
Journal: Eurosurveillance (2004)

La prophylaxie post-exposition au VIH (PEP) est le traitement standard en cas d'exposition accidentelle des personnels soignants au VIH (exposition professionnelle). Un tel standard n'existe pas en cas d'expositions non professionnelles. En Eu
Efficacy of single administration of tumor-infiltrating lymphocytes (TIL) in heavily pretreated patients with metastatic melanoma following checkpoint therapy.
Authors: Amod Sarnaik, Harriet M. Kluger, Jason Alan Chesney, Jyothi Sethuraman, Anandharamen Veerapathran, Michelle Simpson-Abelson, Michael T. Lotze, Bente Larsen, Steven A. Fischkoff, Sam Suzuki, Lei Wang, Mariam Mirgoli, Maria Fardis, Brendan D. Curti
Journal: Journal of Clinical Oncology (2017)

3045 Background: Adoptive cell therapy with TIL involves collection of autologous lymphocytes from the tumor via surgical resection, ex vivo expansion of TIL, lymphodepletion of the patient prior to infusion of TIL using Fludarabine and Cyclophosphamide, followed by infusion of TIL. Up to 6 doses of IL-2 (600,000 IU/kg) is administered to support multiplication of TIL and engraftment. Here, we present the preliminary results from an ongoing, multi-site Phase 2 study of TIL for advanced metastatic melanoma. Methods: Patients with advanced metastatic melanoma who have failed at least one prior systemic therapy were enrolled. Primary objective of the study was to characterize safety profile of LN-144. At baseline, patients had a median age of 56 (41-72) years; 44% were ≥ 60 years old. Median sum of tumor diameters for the target lesions was 10.4 cm, and median of 3 prior therapies. All enlisted patients had prior anti-PD1 as well as anti-CTLA4 and 67% had received ≥ 3 prior therapies. Responses were assessed by RECIST 1.1. TIL products were centrally manufactured. No complications arose from shipment of tumors or TIL. Results: Results are presented through 31 Jan 2017 for the first 9 infused patients evaluable by two assessments. Eight of 9 patients received all 6 doses of IL-2 per protocol. The most common (≥3 patients) non-hematologic grade 3-4 TEAE was hypophosphatemia. No neurotoxicity of grade ≥ 3 was reported. There were no deaths or discontinuations due to SAEs related to study treatment. ORR was 33% (CR = 11%, PR = 22%, SD = 22%, PD = 33%, NE = 11%). Mean time to best response was 3.0 months and median duration of follow up was 3.6 months (1.1+, 12.1). Responses were observed in patients with tumors carrying wild type or BRAF mutations. All patients demonstrated persistence of TIL on day 14 post-infusion. Conclusions: Cell therapy with TIL is an effective treatment with acceptable safety profile for advanced metastatic melanoma patients who are refractory to anti-PD1. TIL products can be centrally manufactured for broad clinical application. This study will be expanded to enroll patients with a shorter manufacturing process as well as offering retreatment for study patients. Clinical trial information: NCT02360579.
Response to pembrolizumab in patients with mismatch repair deficient (dMMR) colorectal cancer (CRC).
Authors: Alexis Diane Leal, Jonas Paludo, Heidi D. Finnes, Axel Grothey
Journal: Journal of Clinical Oncology (2017)

3558 Background: Anti-programmed death-1 (PD-1) antibodies have been shown to be effective in the treatment of dMMR CRC. We describe an updated analysis from a cohort of 19 patients (pts) with dMMR CRC treated with pembrolizumab. Methods: Pts were identified through review of the Mayo Clinic electronic medical record (EMR) and chemotherapy administration records from May 2015 through January 2017. All pts with dMMR CRC who received treatment with pembrolizumab were included. The EMR was reviewed to identify demographic, clinical, pathologic and treatment details. Overall survival (OS), progression free survival (PFS) and disease control rate (DCR = CR+PR+SD) are reported. Time to event analysis was calculated using the Kaplan-Meier method. Results: Nineteen pts were included in this analysis; median age at diagnosis was 48.6 years (range 25-93); 53% were female. Most primary tumors were right sided (n = 12; 63%), 6 (32%) were left sided and 1 (5%) was a tumor of unknown primary within the bowel. Twelve (63%) pts received ≥2 lines of therapy prior to pembrolizumab (range 1-4). Five pts received 2 mg/kg every 3 weeks, 11 received 200 mg/day every 3 weeks and 2 pts received 10 mg/kg (1 every 2 weeks, the other every 3 weeks). The most common alterations identified were loss of MLH1 (11/15) and PMS2 (12/15); 4 pts had germline mutations (mut) identified. KRAS mut was identified in 6/16 pts and 2 pts had BRAF mut. Three pts had MLH1 hypermethylation. Median number of cycles of pembrolizumab was 8 (range 1-35+), with 13 (68%) pts receiving ≥6 cycles. DCR at first assessment was 68%, with 5% CR, 47% PR and 16% SD. Median follow-up from diagnosis was 29 months (95% CI 18-42). Median OS was 103 months (95% CI 85-103); 12-month OS was 89%. Median OS from PD-1 therapy was 16.1 months (95% CI 16-NR); 12-month OS from PD-1 therapy was 79%. Median PFS was NR (95% CI 5-NR); 12-month PFS was 54%. At time of analysis, 9 pts remain on PD-1 therapy; 5 pts have died; 3 have received subsequent therapy. Conclusions: Anti-PD1 blockade with pembrolizumab can provide long lasting benefit in dMMR mCRC, even in heavily pretreated pts.
Prognostic impact of early complete metabolic response on FDG-PET, in BRAF V600 mutant metastatic melanoma patients treated with combination vemurafenib &amp; cobimetinib
Authors: W. Xu, J. Frederickson, J. Callahan, A. Ribas, R. Gonzalez, A.C. Pavlick, O. Hamid, T. Gajewski, I. Puzanov, A. Daud, D. Colburn, N. Choong, M. Wongchenko, R. Hicks, G.A. McArthur
Journal: Annals of Oncology (2017)
Interim pharmacokinetic (PK) and pharmacodynamic (PD) data from the first-in-human study of NUC-3373, a pyrimidine nucleotide analogue, in patients with advanced solid tumors
Authors: E. Ghazaly, V.K. Woodcock, P. Spilipoulou, L. Spiers, J. Moschandreas, L. Griffiths, C. Gnanaranjan, D.J. Harrison, T.R.J. Evans, S.P. Blagden
Journal: Annals of Oncology (2017)
New-generation chromoendoscopy may increase confidence in the DISCARD2 study
Authors: Osamu Toyoshima, Keisuke Hata, Shuntaro Yoshida, Masahide Arita
Journal: Gut (2017)

We read with interest the article by Rees et al , which assessed narrow band imaging (NBI) optical diagnosis of small colorectal polyps in routine clinical practice (the DISCARD2 study).1 Several modalities can potentially be used for screening colonoscopy. The quality of white light endoscopy (WL) has greatly improved after the advent of high-definition endoscopy. Chromoendoscopy (CE) with indigo carmine is one of the traditional dye spraying methods for clearer visualisation of subtle lesions. Image-enhanced endoscopy is also becoming popular, and the new NBI system has improved brightness and contrast relative to those of the first-generation systems.

The study by Rees et al did not show the usefulness of NBI in a multicentre routine (non-specialist) clinical practice for differentiating adenoma from non-adenomatous lesions and concluded that routine use of NBI was not recommended outside of specialist centres. This is an …
Protein arginine methyl transferase 1– and Jumonji C domain‐containing protein 6–dependent arginine methylation regulate hepatocyte nuclear factor 4 alpha expression and hepatocyte proliferation in mice
Authors: Jie Zhao, Abby Adams, Ben Roberts, Maura O'Neil, Anusha Vittal, Timothy Schmitt, Sean Kumer, Josiah Cox, Zhuan Li, Steven A. Weinman, Irina Tikhanovich
Journal: Hepatology (2017)

Alcohol is a well-established risk factor for hepatocellular carcinoma (HCC), but the mechanisms by which it promotes liver cancer are not well understood. Several studies have shown that cellular protein arginine methylation is inhibited by alcohol. Arginine methylation is controlled by the reciprocal activity of protein arginine methyltransferases, primarily protein arginine methyl transferase 1 (PRMT1), and a demethylase Jumonji C domain-containing protein 6 (JMJD6). The aim of this study was to explore the role of arginine methylation changes in alcohol pathogenesis. We found that PRMT1 activity is inhibited in livers of mice fed with alcohol compared to pair-fed mice. Using hepatocyte-specific PRMT1 knockout mice, we identified that loss of PRMT1 results in enhanced hepatocyte proliferation and a 33% increase in liver size. This increased hepatocyte proliferation was associated with reduced expression of hepatocyte nuclear factor 4 alpha (Hnf4α), an important regulator of liver tumorigenesis. We found that PRMT1 regulates Hnf4α expression directly through arginine methylation at the (Hnf4α) promoter. In the absence of PRMT1, JMJD6 can demethylate the Hnf4α promoter and suppress its expression. We were able to restore Hnf4α expression and abolish the increase in hepatocyte proliferation by knockdown of JMJD6 in PRMT1 knockout mice. Knockdown of JMJD6 in alcohol-fed mice similarly increased Hnf4α expression. We then examined whether loss of arginine methylation might play a role in alcohol-associated liver cancers. We examined 25 human HCC specimens and found a strong correlation (R = 0.8; P < 0.01) between arginine methylation levels and Hnf4α expression in these specimens, suggesting that the above mechanism is relevant in patients.Taken together, these data suggest that PRMT1 inhibition, such as induced by alcohol, may result in epigenetic changes leading to loss of Hnf4α. This effect may contribute to alcohol's ability to promote liver tumors. (Hepatology 2018;67:1109-1126).
Influence of sequencing of chemotherapy and radiotherapy regarding adverse effects of the cytostatic treatment: Results of the ADEBAR trial
Authors: H. L. Sommer, J. K. Jueckstock, E. Genss, K. Annecke, B. Rack, D. Steinfeld-Birg, N. Harbeck, M. Kiechle-Bahat, W. J. Janni, K. Friese
Journal: Journal of Clinical Oncology (2007)

559 Background: The ADEBAR-trial was designed as a multicenter randomised phase III study for high risk primary breast cancer (BC) pts., i.e. with more than 3 axillary lymph node metastases. Primary objective of the trial was to evaluate the benefit of a sequential anthracycline-docetaxel regimen (E 90 C-D: 4 cycles epirubicin [E] 90 mg/m 2 plus cyclophosphamide [C] 600 mg/m 2 q21 days followed by 4 cycles docetaxel [D] 100mg/m 2 q21 days) compared to dose-intensive anthracycline- containing polychemotherapy (FE 120 C: 6 cycles E 60 mg/m 2 d 1+8, 5-FU 500mg/m 2 d 1+8 and C 75 mg/m 2 d 1–14, q4 weeks). Patients and Methods: The study started in 2001 and was closed in 2005. By this time 200 actively participating sites had recruited a total number of 1,502 patients. One of the stratification issues was the sequencing of chemotherapy and radiotherapy. All patients were required to receive adjuvant radiotherapy. However the timing of irradiation, either in a sandwich setting after the first half of chemotherapy cycles or after completion of the entire cytostatic treatment was at the discretion of the study sites. In a toxicity-analysis in December 2006, the influence of sequencing of chemotherapy and radiotherapy was analyzed in 980 patients. Results: In 223 pts. radiotherapy was performed midtime after the first half of chemotherapy cycles, 757 pts. received radiotherapy only after completing the entire cytostatic treatment and before starting endocrine treatment, if applicable. Hospitalisation occurred in 32.7 % (73 pts.) of the sandwich group and in 27.9% (211 pts.) of the sequential group (p-value = 0.160). Interval prolongation was necessary in 37.7% (84 pts.) versus 31.6% (239 pts.) in the sequential group, (p-value = 0.089). The target dose was reduced in 15.7% (35 pts.) in the sandwich group and in 20.2% (153 pts.) of the sequential group, (p-value = 0.132). SAEs occurred in 29.6% (66 pts.) in the sandwich group versus 23.1% (175 pts.), (p-value = 0.048). Conclusion: No consistent association between treatment toxicity and the timing of chemotherapy and radiotherapy was observed. Because in this high risk patient group, the prevention of systemic relapse is most important, chemotherapy should be completed before the start of radiotherapy. No significant financial relationships to disclose.