tbuckley/cabot-search huggingface dataset:
Can Kampo medicine prolong the life of metastatic colorectal cancer (MCRC) patients with chemotherapy?
Authors: K. Sasaki, K. Oono, K. Harada, T. Someya, Y. Takada, T. Furuhata, K. Hirata
Journal: Journal of Clinical Oncology (2009)

e15120 Background: Many in vivo and in vitro studies have shown that Kampo medicine has various biological and immunological activities, including anti-cancer effect. However, we have little data on efficacy of survival period on MCRC patients (pts) with chemotherapy and Kampo therapy. The aim of this study was to evaluate the survival benefit on MCRC pts treated with Kampo medicine and chemotherapy. Methods: From 2002 to 2007, we treated 66 patients with MCRC. These patients were treated with chemotherapy (CPT-11 + S-1) and/or Kampo medicine (Jyuzen-Taiho-To, TJ-48) on out-patient basis. TJ-48 was given orally at a dose of 7.5g, three times daily. We randomly divided the MCRC pts following two treatment groups; chemotherapy plus Kampo medicine (Group A, n=33) and chemotherapy only (Group B, n=33). Results: Pts and tumor characteristics were much the same between the two groups at baseline. Pts treated with Kampo medicine in combination with chemotherapy (Group A) had a median survival of 20.5 months compared with 15 months for Group B (p=0.12). One and 2 years survival rates were 72% and 13%. No toxic death was reported. The overall 1, 2 and 3 years survival rate were 69, 24 and 12% respectively in Group A, 57, 0 and 0% in Group B. Adverse events did not increase in Group A. TJ-48 is low cost medicine ($1.8 / day). All patients were treated on an out-patient clinic. Conclusions: These results confirmed that the Kampo medicine is helpful and capable of prolonging the survival periods in pts with MCRC. No significant financial relationships to disclose.
Bexarotene improves median survival (MS) in untreated, advanced NSCLC, when given in combination with carboplatin/paclitaxel
Authors: R. Bordoni, M. Saleh, S. Khanwani, T. Page, M. Auerbach, F. Steinbaum, R. Ghalie
Journal: Journal of Clinical Oncology (2006)

17070 Background: Bexarotene (bex) is a subclass specific, synthetic rexinoid analogue, that preferentially binds and modulates the expression of RXR subclass of receptors α, β, and γ. It induces concentration-dependent repression of multiple genes (cyclin D1/D3, total EGFR, pEGFR) inhibiting cell growth, angiogenesis, invasion and metastasis, inducing differentiation, and apoptosis in tumor cells. Several phase-I/II trials suggested increased survival in patients with advanced NSCLC. Methods: Stage-IIIB with pleural effusion &amp; Stage-IV chemo-naïve patients, ECOG 0–2, were enrolled and treated with carboplatin IV AUC-6 d-1 and paclitaxel IV 100 mg/m 2 d-1, 8, 15, every 28-d for 4 cycles. Pts were randomized using a 1:1 design to bex PO 400 mg/m 2 /d either concurrent (C) from Day 1 or sequential (S) at the completion of chemo, for up to a year. Results: 56 patients were enrolled; median age 62.3 (range 41–86), 48 TNM Stage IV, 38 males, 50 ECOG PS 0–1. Of 51 pts evaluable for response, 30 (58%) achieved PR (C: 15 and S: 15); 16 (31%) showed SD (C: 8 and S: 8), and 5 (9.5%) had PD (C: 3 and S: 2). Thirty-two (63%) patients have expired as of 12/31/05. Based on ITT, 40 evaluable pts showed a median TTP of 169 days (C: 166.5 and S 172); The MS for the entire group is 342 days (11.42 mo (C: 12.8 and S: 10.53). Currently, 10 pts are still alive between 407 to 1036 days from registration on the trial. The treatment was well tolerated; overall, AEs were reported in 48% of pts in the S arm and 51% in the C arm. The incidence of Gr 3–4 AEs, regardless of the treatment arm, was &lt; 5%. There were no treatment-associated deaths. Conclusions: Our data suggests a better ORR, TTP, and improvement in MS, when bex is added to carboplatin/ paclitaxel, regardless of concurrent or sequential administration, compared with chemo alone. ORR was not compromised by bex administration and in fact it was above average reported for similar phase-II &amp; -III studies. Toxicity is easily managed. [Table: see text]
Absence of Human T-Cell Lymphotropic Virus Type I in Cutaneous T-Cell Lymphoma
Authors: Arata Kikuchi, Takeji Nishikawa, Kazunari Yamaguchi
Journal: New England Journal of Medicine (1997)

To the Editor: The cutaneous T-cell lymphomas include mycosis fungoides, the Sezary syndrome, and other sporadic primary T-cell proliferations in the skin.1,2 The human T-cell lymphotropic virus type I (HTLV-I) is a retrovirus that causes adult T-cell leukemia–lymphoma, which can also involve the skin and be difficult to distinguish from a primary cutaneous T-cell lymphoma. Recently, several investigators have found the HTLV-I genome in DNA from primary cutaneous T-cell lymphomas and proposed a causal relation between that retrovirus and such lymphomas.3–5 However, their studies have not always differentiated the diagnosis of cutaneous T-cell lymphoma from that of smoldering . . .
ESAT-6–dependent cytosolic pattern recognition drives noncognate tuberculosis control in vivo
Authors: Andreas Kupz, Ulrike Zedler, Manuela Stäber, Carolina Perdomo, Anca Dorhoi, Roland Brosch, Stefan H.E. Kaufmann
Journal: Journal of Clinical Investigation (2016)

IFN-γ is a critical mediator of host defense against Mycobacterium tuberculosis (Mtb) infection. Antigen-specific CD4+ T cells have long been regarded as the main producer of IFN-γ in tuberculosis (TB), and CD4+ T cell immunity is the main target of current TB vaccine candidates. However, given the recent failures of such a TB vaccine candidate in clinical trials, strategies to harness CD4-independent mechanisms of protection should be included in future vaccine design. Here, we have reported that noncognate IFN-γ production by Mtb antigen-independent memory CD8+ T cells and NK cells is protective during Mtb infection and evaluated the mechanistic regulation of IFN-γ production by these cells in vivo. Transfer of arenavirus- or protein-specific CD8+ T cells or NK cells reduced the mortality and morbidity rates of mice highly susceptible to TB in an IFN-γ-dependent manner. Secretion of IFN-γ by these cell populations required IL-18, sensing of mycobacterial viability, Mtb protein 6-kDa early secretory antigenic target-mediated (ESAT-6-mediated) cytosolic contact, and activation of NLR family pyrin domain-containing protein 3 (NLRP3) inflammasomes in CD11c+ cell subsets. Neutralization of IL-18 abrogated protection in susceptible recipient mice that had received noncognate cells. Moreover, improved Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine-induced protection was lost in the absence of ESAT-6-dependent cytosolic contact. Our findings provide a comprehensive mechanistic framework for antigen-independent IFN-γ secretion in response to Mtb with critical implications for future intervention strategies against TB.
Pretreatment gut microbiome predicts chemotherapy-related bloodstream infection
Authors: Emmanuel Montassier, Gabriel A. Al-Ghalith, Tonya Ward, Stephane Corvec, Thomas Gastinne, Gilles Potel, Philippe Moreau, Marie France de la Cochetiere, Eric Batard, Dan Knights
Journal: Genome Medicine (2016)

Bacteremia, or bloodstream infection (BSI), is a leading cause of death among patients with certain types of cancer. A previous study reported that intestinal domination, defined as occupation of at least 30 % of the microbiota by a single bacterial taxon, is associated with BSI in patients undergoing allo-HSCT. However, the impact of the intestinal microbiome before treatment initiation on the risk of subsequent BSI remains unclear. Our objective was to characterize the fecal microbiome collected before treatment to identify microbes that predict the risk of BSI. We sampled 28 patients with non-Hodgkin lymphoma undergoing allogeneic hematopoietic stem cell transplantation (HSCT) prior to administration of chemotherapy and characterized 16S ribosomal RNA genes using high-throughput DNA sequencing. We quantified bacterial taxa and used techniques from machine learning to identify microbial biomarkers that predicted subsequent BSI. We found that patients who developed subsequent BSI exhibited decreased overall diversity and decreased abundance of taxa including Barnesiellaceae, Coriobacteriaceae, Faecalibacterium, Christensenella, Dehalobacterium, Desulfovibrio, and Sutterella. Using machine-learning methods, we developed a BSI risk index capable of predicting BSI incidence with a sensitivity of 90 % at a specificity of 90 % based only on the pretreatment fecal microbiome. These results suggest that the gut microbiota can identify high-risk patients before HSCT and that manipulation of the gut microbiota for prevention of BSI in high-risk patients may be a useful direction for future research. This approach may inspire the development of similar microbiome-based diagnostic and prognostic models in other diseases.
TCTAP A-025 Efficacy of Long 2nd Generation Drug-Eluting Stent Implantation from Healthy to Healthy Segment Under Intravascular Ultrasound Guidance in Acute Myocardial Infarction
Authors: Shota Ikeda, Takahiro Watanabe, Yuichi Hanaki, Tomoyuki Fukuzawa, Shingo Tanaka, Hajime Aoki, Kazuhiko Yumoto
Journal: Journal of the American College of Cardiology (2016)
Contribution of human metapneumovirus to influenza-like infections in North Greece, 2005-2008
Authors: G Gioula, D Chatzidimitriou, A Melidou, M Exindari, V Kyriazopoulou-Dalaina
Journal: Eurosurveillance (2010)

Following its detection in 2001, human metapneumovirus (hMPV) has repeatedly been reported as a respiratory pathogen, especially in children. This study was aimed at determining the proportion of hMPV infections in patients with influenza-like illness (ILI) during the three influenza seasons 2005-6, 2006-7, 2007-8 in northern Greece. We collected 380 nasopharyngeal swabs or aspirates from ILI patients during the winter seasons 2005-2008 and examined them for influenza viruses and hMPV by one-step real time RT-PCR and nested RT-PCR. Influenza viruses were detected in 151 of the 380 specimens (39.7%) and hMPV in 23 of them (6.05%). Co-infections with hMPV and influenza viruses were observed in seven cases. The majority of the ILI patients (60.5%) were 0-18 years-old. However, the incidence of influenza was slightly higher in the age group of 19-60-year-olds, while the incidence of hMPV infections was higher in the age group of 0-18-year-olds. We conclude that hMPV plays an important role as a contributor in influenza-like infections, especially in children. It circulates in the community during influenza seasons and its clinical appearance can be confused with influenza symptoms. However, further research is needed to elucidate the quantitative and qualitative importance of hMPV infections.
385P Thromboembolic events (TE) in patients with metastatic non small cell lung cancer (NSCLC) EGFR / ALK native treated with first-line platinum-based chemotherapy
Authors: V.E. Castellón Rubio, R. Luque Caro, E. Gonzalez Flores, L. Canosa Ruiz
Journal: Annals of Oncology (2015)
Troubled mental health trust is still putting patients at risk, warns CQC
Authors: Gareth Iacobucci
Journal: BMJ (2016)

A mental health trust in England that was criticised for failing to properly investigate the unexpected deaths of more than 1000 people between 2011 and 2015 is continuing to put patients at risk, the healthcare regulator has warned.

The warning from the Care Quality Commission came after an inspection it carried out at Southern Health NHS Foundation Trust found that the trust had failed to adequately deal with serious concerns about the way it reported and investigated deaths of patients with mental health illness and learning disabilities.1

Jeremy Hunt, the health secretary, ordered the inspection after an independent inquiry found that a “failure of leadership” at the trust …
Benefit of Surveillance for Pancreatic Cancer in High-Risk Individuals: Outcome of Long-Term Prospective Follow-Up Studies From Three European Expert Centers
Authors: Hans Vasen, Isaura Ibrahim, Carmen Guillen Ponce, Emily P. Slater, Elvira Matthäi, Alfredo Carrato, Julie Earl, Kristin Robbers, Anneke M. van Mil, Thomas Potjer, Bert A. Bonsing, Wouter H. de Vos tot Nederveen Cappel, Wilma Bergman, Martin Wasser, Hans Morreau, Günter Klöppel, Christoph Schicker, Martin Steinkamp, Jens Figiel, Irene Esposito, Evelina Mocci, Enrique Vazquez-Sequeiros, Alfonso Sanjuanbenito, Maria Muñoz-Beltran, José Montans, Peter Langer, Volker Fendrich, Detlef K. Bartsch
Journal: Journal of Clinical Oncology (2016)

Purpose Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Hereditary factors play a role in the development of PDAC in 3% to 5% of all patients. Surveillance of high-risk groups, may facilitate detection of PDAC at an early stage. The aim of this study was to assess whether surveillance aids detection of early-stage PDAC or precursor lesions (PRLs) and improves the prognosis. Patients and Methods Screening outcomes were collected from three European centers that conduct prospective screening in high-risk groups including families with clustering of PDAC (familial pancreatic cancer [FPC]) or families with a gene defect that predisposes to PDAC. The surveillance program consisted of annual magnetic resonance imaging, magnetic resonance cholangiopancreatography, and/or endoscopic ultrasound. Results Four hundred eleven asymptomatic individuals participated in the surveillance programs, including 178 CDKN2A mutation carriers, 214 individuals with FPC, and 19 BRCA1/2 or PALB2 mutation carriers. PDAC was detected in 13 (7.3%) of 178 CDKN2A mutation carriers. The resection rate was 75%, and the 5-year survival rate was 24%. Two CDKN2A mutation carriers (1%) underwent surgical resection for low-risk PRL. Two individuals (0.9%) in the FPC cohort had a pancreatic tumor, including one advanced PDAC and one early grade 2 neuroendocrine tumor. Thirteen individuals with FPC (6.1%) underwent surgical resection for a suspected PRL, but only four (1.9%) had high-risk lesions (ie, high-grade intraductal papillary mucinous neoplasms or grade 3 pancreatic intraepithelial neoplasms). One BRCA2 mutation carrier was found to have PDAC, and another BRCA2 mutation carrier and a PALB2 mutation carrier underwent surgery and were found to have low-risk PRL. No serious complications occurred as consequence of the program. Conclusion Surveillance of CDNK2A mutation carriers is relatively successful, detecting most PDACs at a resectable stage. The benefit of surveillance in families with FPC is less evident.
Forecasting US ivacaftor outcomes and cost in cystic fibrosis patients with the G551D mutation
Authors: Piyameth Dilokthornsakul, Ryan N. Hansen, Jonathan D. Campbell
Journal: European Respiratory Journal (2016)

Ivacaftor, a breakthrough treatment for cystic fibrosis (CF) patients with the G551D genetic mutation, lacks long-term clinical and cost projections. This study forecasted outcomes and cost by comparing ivacaftor plus usual care versus usual care alone. A lifetime Markov model was conducted from a US payer perspective. The model consisted of five health states: 1) forced expiratory volume in 1 s (FEV 1 ) % pred ≥70%, 2) 40%≤ FEV 1 % pred &lt;70%, 3) FEV 1 % pred &lt;40%, 4) lung transplantation and 5) death. All inputs were extracted from published literature. Budget impact was also estimated. We estimated ivacaftor's improvement in outcomes compared with a non-CF referent population. Ivacaftor was associated with 18.25 (95% credible interval (CrI) 13.71–22.20) additional life-years and 15.03 (95% CrI 11.13–18.73) additional quality-adjusted life-years (QALYs). Ivacaftor was associated with improvements in survival and QALYs equivalent to 68% and 56%, respectively, for the survival and QALY gaps between CF usual care and their non-CF peers. The incremental lifetime cost was $3 374 584. The budget impact was $0.087 per member per month. Ivacaftor increased life-years and QALYs in CF patients with the G551D mutation, and moved morbidity and mortality closer to that of their non-CF peers. Ivacaftor costs much more than usual care, but comes at a relatively limited budget impact.
A work group report on ultrafine particles (American Academy of Allergy, Asthma &amp; Immunology): Why ambient ultrafine and engineered nanoparticles should receive special attention for possible adverse health outcomes in human subjects
Authors: Ning Li, Steve Georas, Neil Alexis, Patricia Fritz, Tian Xia, Marc A. Williams, Elliott Horner, Andre Nel
Journal: Journal of Allergy and Clinical Immunology (2016)
Two listeria outbreaks caused by smoked fish consumption—using whole-genome sequencing for outbreak investigations
Authors: S. Gillesberg Lassen, S. Ethelberg, J.T. Björkman, T. Jensen, G. Sørensen, A. Kvistholm Jensen, L. Müller, E.M. Nielsen, K. Mølbak
Journal: Clinical Microbiology and Infection (2016)
Abstract MP69: Prevalence of Treatment Resistant Hypertension Among Individuals with Chronic Kidney Disease: Results from the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Rikki M Tanner, David A Calhoun, Emmy K Bell, C. B Bowling, Orlando M Gutiérrez, Marguerite R Irvin, Daniel T Lackland, Suzanne Oparil, David Warnock, Paul Muntner
Journal: Circulation (2013)

Hypertension requiring treatment with multiple antihypertensive medications is common among individuals with chronic kidney disease (CKD). Small clinic-based studies have reported a high prevalence of treatment resistant hypertension (TRH) among patients with CKD. However, the prevalence of TRH has not been estimated for people with CKD in population-based studies. We hypothesized that lower estimated glomerular filtration rate (eGFR) and higher albumin-to-creatinine ratio (ACR) would be associated with a higher prevalence of TRH. We determined the prevalence of TRH among REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants (n=30,239) by eGFR and ACR and evaluated clinical and demographic correlates of TRH in those with CKD. Blood pressure was measured twice, pill bottles were inspected, and serum creatinine and an ACR were measured during an in-home study visit. TRH was defined as systolic/diastolic blood pressure ≥140/90 mmHg with concurrent use of ≥3 antihypertensive medication classes or use of ≥4 antihypertensive medication classes. CKD was defined as an ACR ≥30 mg/g or a CKD-EPI equation-derived eGFR &lt;60 ml/min/1.73m 2 . The mean age of the 11,285 REGARDS participants treated for hypertension was 66.0 (SD=9.0) years, 56.9% were women and 48.8% were black. The prevalence of TRH was 14.5%, 23.5%, and 31.2% for those with an eGFR ≥60, 45-59, and &lt;45 mL/min/1.73m 2 , respectively. The prevalence of TRH was 11.3%, 18.8%, 25.5%, and 44.5% for ACR &lt;10, 10-29, 30-299, and ≥300 mg/g, respectively. A graded association between lower eGFR and higher ACR with TRH remained present after multivariable adjustment (Table 1). Also, after multivariable adjustment, black race, a larger waist circumference, diabetes, and history of myocardial infarction and stroke were associated with TRH among individuals with CKD. In conclusion, individuals with CKD have a high prevalence of TRH. Strategies are needed to improve blood pressure control in this population and reduce cardiovascular disease risk.
Sequential shear-wave elastography of liver and spleen rules out clinically significant portal hypertension in compensated advanced chronic liver disease
Authors: Christian Jansen, Christopher Bogs, Aleksander Krag, Sven Francque, Jonel Trebicka
Journal: Gut (2016)

With interest we read the letter entitled ‘Ruling in and ruling out with elastography in compensated advanced chronic liver disease’ by Agustin et al 1 to our study ‘Algorithm to rule-out clinically significant portal hypertension combining Shear-wave elastography of liver and spleen: a prospective multi-centre study’.2 Indeed, we would like to thank our colleagues for their interest in our study and deciphering the strengths and weaknesses of this study. Besides acknowledging the merits of the study, the colleagues commented on the selection of patients regarding severity and aetiology of advanced chronic liver disease (ACLD), as well as the clinical importance of ruling out or ruling in clinically significant portal hypertension (CSPH).

The criticism about the selection of patients stimulated us to perform new calculations. Even though the algorithm was calculated including patients with decompensated ACLD (dACLD), it performed much better in …
An international discussion is desirable
Authors: H. F L Garretsen, F. Sturmans
Journal: BMJ (1996)

EDITOR,—Richard Smith states that wars on drugs are doomed to fail and asks whether it is time to consider “going Dutch,” referring to the fact that the Netherlands is more willing than other countries to experiment with decriminalisation.1 What considerations must be taken into account in the debate on the availability of hard drugs in the Netherlands?

Many people argue that hard drugs should be freely available. One argument for this is on grounds of “fairness”: why is alcohol freely available …
Epirubicin (E) in combination with cisplatin (CDDP) and capecitabine (C) versus docetaxel (D) combined with 5-fluorouracil (5-FU) by continuous infusion as front-line therapy in patients with advanced gastric cancer (AGC): Preliminary results of a randomized phase II trial of the Gruppo Oncologico Dell'Italia Meridionale.
Authors: E. Maiello, F. De Vita, V. Gebbia, V. Lorusso, S. Cinieri, F. Giuliani, M. Orditura, E. Fistola, G. Filippelli, G. Colucci
Journal: Journal of Clinical Oncology (2011)

97 Background: Combination chemotherapy regimens improve outcome of AGC patients even if there is no accepted global standard regimen. Compared with ECF, D in combination with 5-FU c.i. shown promising efficacy in a phase II randomised study (J Clin Oncol. 23:494;2005). REAL-2 trial demonstrated that C was effective as 5-FU c.i. when used as part of a triple combination regimen turning the treatment into an easier to administer regimen (N Engl J Med. 358: 36; 2008). In the present study we compare DF versus ECX as first-line therapy of AGC. Methods: Patients with previously untreated histologically documented AGC, with at least one measurable disease, age &lt; 18 years, ECOG PS ≤ 2, and age 18-75 years, were randomly assigned to receive E (50 mg/m 2 day 1), CDDP (60 mg/m 2 day 1) and C (625 mg/m 2 bid, days 1-21) (ECX) or D (85 mg/m 2 day 1) and 5-FU (750 mg/m 2 /day c.i., days 1-5) (DF) q 3 weeks. RECIST and NCI criteria were employed to determine the activity and the toxicity of these regimens. Results: The main characteristics in ECX and DF arms were: M/F = 22/14 and 23/8, median age = 58 years (range 39-74 years) and 61 years (range 44-75 years), site of disease = liver in 29 (82.8%) and in 20 (64.5%) patients, lung in 7 (20%) and in 4 (12.9%) patients, lymph-nodes in 26 (74.2%) and in 21 (67.7%) patients, multiple 14 (20%) versus 21 (60%) and 16 (51.6%) versus 14 (48.4%). ORR (CR + PR) was 54.3% in ECX arm and 22.6% in DF arm. Nine PRO were observed in both arms (25.7% and 29.2%, respectively). Main toxicity rate (G3-4) in the evaluable patients assigned to ECX arm were neutropenia (28.5% versus 19.4%), nausea/vomiting (18.2% versus 3.2%), alopecia (22.8% versus 18.3%) and H&amp;F syndrome (5.7% versus 0%). The worst toxicity (G3-4) in DF arm was anaemia (9.6% versus 5.7%). Conclusions: Preliminary results of this study shown an higher ORR of ECX regimen with respect to DF with a favourable toxicity profile. No significant financial relationships to disclose.