tbuckley/cabot-search huggingface dataset:
Randomized phase III trial of concurrent chemoradiation with or without neoadjuvant gemcitabine, carboplatin, and paclitaxel in locally advanced nasopharyngeal cancer.
Authors: Terence Tan, Wan-Teck Lim, Kam-Weng Fong, Shie-Lee Cheah, Yoke-Lim Soong, Mei-Kim Ang, Quan Sing Ng, Daniel Shao-Weng Tan, Whee Sze Ong, Sze Huey Tan, Connie Siew Poh Yip, Daniel Quah, Khee Chee Soo, Joseph Wee
Journal: Journal of Clinical Oncology (2014)

6003 Background: The role of neoadjuvant chemotherapy in addition to concurrent chemoradiation (CRT) in locally advanced nasopharyngeal cancer (NPC) is unclear. This trial investigates the overall survival (OS), tumor control, toxicity and quality of life (QOL) in stage III-IVB NPC patients treated with this approach. Methods: Patients were stratified by N-stage and randomized to neoadjuvant GCP (gemcitabine 1000mg/m2, cisplatin AUC 2.5 and paclitaxel 70 mg/m2) on Days 1 and 8 every three weeks for 3 cycles followed by CRT (radiotherapy 69.96 Gy (RT) with weekly 40mg/m2Cisplatin), or CRT alone. The accrual (total 172) was planned to detect a 15% difference in OS with a one-sided 5% significance level and 80% power. Kaplan-Meier survival curves were compared using Peto’s method. Cox regression analyses were performed. Results: Between September 2004 and August 2012, 180 patients were accanded, and 172 (GCP 86, CRT 86; WHO type II 7%, type III 93% ) analyzed by intention to treat. The median follow-up was 3.25 years for GCP and 2.69 years for CRT. There was no significant difference in OS between the two arms: 5-year OS 74.8% (GCP) vs 77.6% (CRT); HR =1.05; one-sided p=0.494. No significant difference was seen in the disease-free survival (HR 0.77, 95% CI 0.44–1.35, p=0.362) and distant metastases-free survival (HR 0.80, 95%CI 0.38 – 1.67, p=0.547). Treatment compliance in the neoadjuvant phase was good with relative dose intensity (RDI) between 83-85% but the RDI for concurrent Cisplatin was significantly lower in the GCP arm (75% vs 84%, p=0.003). 98% of patients received RT by intensity-modulated RT or tomotherapy. All patients completed RT except for 1 CRT patient who died during treatment. Overall, the GCP arm had higher rates of grades 3 and 4 pancytopenia (58% vs 37%), neutropenia (66% vs 12%), thrombocytopenia (14%vs 0%) and fatigue (14% vs 2%) than the CRT arm. The global QOL scores were comparable in both arms. The statistical boundary for futility was crossed at this 5th interim analysis and is being reported early on the recommendation of the DSMC. Conclusions: Neoadjuvant chemotherapy with GCP did not improve survival in locally advanced NPC and concurrent CRT remains the standard of care. Clinical trial information: CDR0000657121.
<i>The BMJ</i>’s Christmas gogglebox
Authors: Alison Tonks, Navjoyt Ladher
Journal: BMJ (2015)

Tune in to Channel BMJ this Christmas and throw away your remote control—we’ve got a strong line-up of festive programming for you.

We start with the cover of our print issue, packed with medical superheroes and supervillains. Casting the cover photo from GP John Burscough’s cabinet of over 300 toys, models, and action figures of doctors was tricky thanks to overwhelming choice (doi:10.1136/bmj.h6890). Viewers of The X-Files , Star Trek , and The Octonauts should spot some familiar faces. Fans of The Doctor will be disappointed—he’s better known for his work as a time lord than a clinician, …
Abstract P035: Respiratory Muscle Trainings as a Way of Physical Rehabilitation for Old Patients With Heart Failure
Authors: Elena Kolesnikova, Gregory Arutyunov, Anna Rylova, Natalia Rylova, Valentina Lobzeva
Journal: Circulation (2014)

Background: Physical exercises are well known to be an important part of comprehensive cardiac rehabilitation(CR), but many protocols of physical exercises are not applicable for the old patients for many reasons. Purpose: To study the possibility of respiratory muscles trainings (RMT) in old patients with heart failure (HF) as a way of physical rehabilitation. Methods: 57 patients 84,4±5,7 years old with NYHA II- III HF were randomized to either an exercise training group (EG)(29pts) or to a control group (CG). The CG patients had standard CR according to the national guidelines. The EG participated additionally in a RMT with gradual increase of inspire and expire resistance. Trainings were held for 20 minutes twice a day for 12 months. Peak oxygen consumption (VO2peak) during 6 minute walking test (6 MWT), maximal inspiratory mouth pressures (PI max) were measured at baseline and in 12 months. Results: After 12 weeks there was significant increase in results of 6 MWT in EG (299,6±19,37 m in EG vs 298,2±18,12 m in CG at baseline, [[Unable to Display Character: &amp;#1088;]]&gt;0,05; after (12 months 342±12,76m vs 297,3±11,85 m [[Unable to Display Character: &amp;#1088;]]&lt;0,05), VO2peak in EG 14,96±1,84ml/kg/min in EG vs 14,99±1,91 ml/kg/min in CG at baseline, [[Unable to Display Character: &amp;#1088;]]&gt;0,05; after 12 months 16,18±1,46 ml/kg/min vs 14,35±1,11 ml/kg/min, [[Unable to Display Character: &amp;#1088;]]&lt;0,01) and PImax in EG (median PI max, 6,4 in both groups [25th-75th percentile range 6,4-6.9 in EG vs 25th-75th percentile range 6,3-6,9 in CG] at baseline, p=0,7), after 12 months EG median PI max, 6,9 in EG [25th-75th percentile range6,9-7,2] vs median PI max, 6,5 [25th-75th percentile range 6,3-6,5] in CG, [[Unable to Display Character: &amp;#1088;]]&lt;0,01). EG patients had significantly less hospitalizations because of HF progression (16,9% in EG vs 27,5% in CG) and pneumonias (14,1% vs 19.3%). There were 7 lethal outcomes in EG vs 12 in CG. Conclusion: RMT in old patients with HF improves physical capacity, maximal inspiratory mouth pressures, e and decrease the number of hospitalizations because of HF progression and pneumonias
Mutations in TP53 and associated genomic abnormalities are dependent on breast cancer estrogen receptor status and patient age
Authors: Vita Fedele, Jane Fridlyand, Ritu Roydasgupta, Stefania Tommasi, Angelo Paradiso, Donna Albertson, Christopher Benz
Journal: Cancer Research (2007)

2962  About 20% of breast cancers possess somatic mutations within the evolutionarily conserved core DNA-binding domain encoded by exons 5-8 of the tumor suppressor gene, TP53. Collectively, these breast cancer mutations are associated with increased genomic instability, altered chemotherapy responsiveness and poor patient prognosis. Observed age-associated differences in breast cancer TP53 status (p53mut, p53wt) and genome instability (assessed by array CGH) may be confounded by their correlation with breast cancer estrogen receptor status (ERneg, ERpos), which is strongly age dependent. To better define the relationship between patient age-at-diagnosis, breast cancer ER and TP53 status and array CGH determined genomic abnormalities, DNA samples were analyzed from 509 primary breast cancers (103 ERneg, 342 ERpos) diagnosed in 140 younger (Y,  69y) age patients. Overall, 13% (64/509) of samples were p53mut: 27% in exon 5, 17% in exon 6, 28% in exon 7, and 28% in exon 8. The p53mut frequency varied significantly (3- to 9-fold) according to patient age and breast cancer ER status, with the greatest difference observed within the O age group in which 35% of ERneg tumors and only 4% of ERpos tumors were p53mut (p
STAT3 Inhibition Promotes Potent Th1 Responses By Down Regulating Pdl-1 Expression On Tumor Cells
Authors: Baldev Vasir, Hasan Rajabi, Heidi Mills, Jacalyn Rosenblatt, Dina Stroopinsky, Katarina Luptakova, Maxwell D Coll, Palmer Kristen, Donald Kufe, David Avigan
Journal: Blood (2013)
Notice of Retraction: Jamal SA, et al. Effect of Nitroglycerin Ointment on Bone Density and Strength in Postmenopausal Women: A Randomized Trial.<i>JAMA</i>. 2011;305(8):800-807.
Authors: Richard Eastell, Celeste J. Hamilton, Steven R. Cummings
Journal: JAMA (2015)

To the Editor We wish to retract the article "Effect of Nitroglycerin Ointment on Bone Density and Strength in Postmenopausal Women: A Randomized Trial,"1 published in the February 23, 2011, issue of JAMA.
Abstract 176: Assessment of Sublingual Microcirculation by Sidestream Darkfield Imaging: A Word of Caution
Authors: Anders B Kildal, Thor A Stenberg, Espen Sanden, Truls Myrmel, Ole-Jakob How
Journal: Circulation (2014)

Introduction:  Intravital videomicroscopy of the sublingual microcirculation is used to monitor critically ill patients. Existing guidelines suggest handheld video recordings of ≥ 20 seconds from 5 areas. We tested if a fixated camera that allowed extension of the observation time could improve sensitivity in microcirculatory assessment.   Methods:  Anesthetized pigs (n=8), which were equally divided to a handheld group where microcirculation was assessed continuously in 1 min in 5 areas, and a group with a fixated camera where observation time was extended to 10 min in one area. The microcirculation was challenged by infusion of arginine vasopressin (AVP). Post ischemic acute heart failure (AHF) was induced by left coronary microembolization and the AVP infusion was repeated. Recordings were divided in 20 seconds sequences and Mean Flow Index (MFI) of small vessels were then scored and averaged for each measurement point.   Results:  When giving 0.003, 0,006 and 0,012 IU/kg/min of AVP, MFI in the fixated 10 min group was significantly more reduced (2,03±0,38, 0,98±0,18, 0,48±0,11) compared to both the first 20 seconds (2,77±0,04, 2,06±0,04, 1,74±0,06) and the total 1 min (2,63±0,09, 1,70±0,07, 1,33±0,16) in the handheld group. Following induction of acute heart failure, cardiac output dropped to half of the pre ischemic values. Interestingly, MFI was further decreased when giving 0,001 and 0,003 IU/kg/min of AVP in AHF (1,62±0,60 and 1,16±0,38) compared to pre-ischemia (2,86±0,09 and 2,03±0,38).   Conclusion:  A fixated camera with extended recording times reveals important microcirculatory changes in shock-states not detected by the guideline approach.
Precise Localization of Occult Gastrointestinal Hemorrhage Using Dynamic SPECT/CT
Authors: Douglas A Murrey, Nathan C Hall, Chadwick L Wright, David A Mankoff
Journal: Clinical Nuclear Medicine (2015)

Active but intermittent gastrointestinal (GI) bleeding can be readily detected with dynamic planar scintigraphic imaging. This is a case of a 48-year-old woman who presented from an outside institution with active GI bleeding on 99mTc-labeled RBC (99mTc-RBC) scintigraphy, but the upper and lower GI evaluations failed to subsequently localize the site of persistent bleeding. Repeat 99mTc-RBC planar scintigraphy identified a focus of active extravasation in the right lower quadrant of the abdomen. Dynamic SPECT/CT imaging was immediately performed and further identified the ileocecal valve region as the precise site of active extravasation, which was confirmed at surgery.
Mass-production of human dendritic cells in accordance with gmp for clinical studies
Authors: Yui Harada, Noriko Yasuda, Yoshikazu Yonemitsu
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Although clinical studies have established that antigen-loaded dendritic cells (DCs) vaccines are safe and promising therapy for various kinds of malignancies, their clinical efficacy remains to be established. Issues that limit the clinical efficacy of DC-based immunotherapy, as
Abstract 18759: N-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity C-Reactive Protein and Infarct Size Measured With Delayed Enhancement Multidetector Computed Tomography
Authors: Doo Sun Sim, Youngkeun Ahn, Yun Hyeon Kim, Hyun Ju Seon, Keun Ho Park, Hyun Ju Yoon, Nam Sik Yoon, Kye Hun Kim, Young Joon Hong, Hyung Wook Park, Ju Han Kim, Myung Ho Jeong, Jeong Gwan Cho, Jong Chun Park
Journal: Circulation (2014)

Background: There is a paucity of information on the time-dependent relationship of cardiac biomarkers to infarct size and left ventricular (LV) remodeling after myocardial infarction (MI). We sought to investigate the relationship between levels high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and indices of infarct size and LV volume after acute MI. Methods: A total of 86 patients with ST-elevation MI within 12 hours after the symptom onset underwent delayed enhancement multi-detector computed tomography (DE MDCT) immediately after percutaneous coronary intervention (PCI) to determine infarct size. LV function and remodeling were assessed by echocardiography. Hs-CRP and NT-proBNP were serially measured at admission, 24 hours, and 2 months. DE MDCT and echocardiography were repeated at 2 months after PCI. Results: Levels of both hs-CRP and NT-proBNP at 24 hours showed positive correlation with infarct size at baseline and at 2 months, and negative correlation with LV ejection fraction at baseline and at 2 months. NT-proBNP at 2 months correlated with infarct size (r=0.561, p=0.007), LV ejection fraction (r= - 0.539, p=0.010), and LV end diastolic and systolic volume indices at 2 months (r=0.796, p=0.032 and r=0.831, p=0.021, respectively). NT-proBNP was higher in patients who developed LV remodeling at 2 months: 929 pg/mL vs. 134 pg/mL, p = 0.002. In contrast, hs-CRP at 2 months showed no relationship to infarct size, LV function, or LV volumes at 2 months. Conclusions: Elevated hs-CRP during active myocardial necrosis was associated with infarct size and LV dysfunction, whereas elevated levels of NT-proBNP early and late after the onset of acute MI were both correlated with infarct size, LV dysfunction, and LV remodeling.
Primary versus acquired multidrug-resistant tuberculosis: Which are the true features of multidrug-resistant tuberculosis itself on thin-section CT
Authors: Inyoung Song, Myung Jin Chung, W. Koh, Chin A. Yi, Kyung Soo Lee
Journal: European Respiratory Journal (2011)

Purpose: We designed this study to compare thin-section CT (TSCT) findings of the primary multidrug-resistant (MDR) TB (MDR- P) and non-primary MDR TB (MDR-A) to those of drug-sensitive (DS) TB.

Materials and methods: We included 37 consecutive patients with MDR-P and 86 MDR-A who underwent TSCT of chest. 123 patients with DS TB selected as a control group. Each DS TB patient was age and gender matched to a MDR TB patient. The frequency of lung lesion patterns in terms of tree-in-bud opacity/micronodules (TIB), nodule, consolidation, cavities, large fibrotic thin-walled cavity, and lobar volume decrease observed at TSCT were compared among DS TB, MDR-P, and MDR-A.

Results: TIB (92%) and consolidations (76%) were most frequent findings of MDR-P. The frequencies of these are similar to those of DS TB (TIB for DS TB = 88%, p=0.561; consolidations = 81%, p=0.527). Cavities were next common findings of MDR-P (70%) and this frequency was similar to that of MDR-A (58%, p=0.260) than DS TB (38%, p<0.001). Volume decrease, large thin walled cavity, and pleural thickening were infrequent findings of MDR-P (22%, 5%, 1%, respectively) but common in MDR- A (56%, 30%, 42%, respectively), which mean chronic fibrotic condition.

Conclusion: Single or multiple cavities as well known typical feature of MDR TB are also common in MDR-P and not significantly different from MDR-A. In addition, MDR-P and DS TB reveal more common acute inflammatory findings (tree-in-bud pattern/micronodules, lobular consolidation, and overall consolidation) than MDR-A which reveal chronic fibrotic findings (thin walled cavity and volume decrease) in TSCT.
Injectable hydrogel promotes early survival of induced pluripotent stem cell-derived oligodendrocytes and attenuates longterm teratoma formation in a spinal cord injury model
Authors: T. Führmann, R.Y. Tam, B. Ballarin, B. Coles, I. Elliott Donaghue, D. van der Kooy, A. Nagy, C.H. Tator, C.M. Morshead, M.S. Shoichet
Journal: Biomaterials (2016)
Sexual behaviour of men
Authors: T J McManus, A P M Coxon
Journal: BMJ (1995)

While screening for medical fitness to drive may seem an attractive idea, it is unrealistic.Not only is there a lack of effective screening tests but recent data suggest that this sort of strategy may be not only ineffective but also harmful.Some European countries have attempted to screen for illness relevant to driving by demanding a doctor's certificate at regular intervals after the age of 70.A comparison of accident rates between Sweden (where there is no medical control) and Finland (where regular medical recertification is required after age 70) showed no reduction in fatalities in motor crashes and an increase in pedestrian and cycle fatalities in Finland.This may be a result of stopping older people driving unnecessarily and forcing them into the much higher risk group of pedestrians and cyclists.'
Tamoxifen-citrate counteracts the antitumor effects of cytotoxic drugs in vitro.
Authors: V Hug, G N Hortobagyi, B Drewinko, M Finders
Journal: Journal of Clinical Oncology (1985)

Hormones and cytotoxic drugs are often combined in the treatment of patients with breast carcinoma to broaden the antitumor spectrum of the therapy. We found that, in vitro, the most commonly used endocrine agent, tamoxifen citrate, attenuates the cytotoxic potential of 5-fluorouracil (5-FU) and of doxorubicin. The effect was observed on estrogen receptor positive and on estrogen receptor negative breast tumor cells. Combinations of growth inhibitory hormones and cytotoxic drugs may therefore be counter-productive. For the treatment of hormone-independent tumors they may even be harmful since in these tumors tamoxifen exerts no independent cell kill that compensates for its modifying effect on the cytotoxicity of drugs.
ESRD due to Multiple Myeloma in the United States, 2001–2010
Authors: Scott Reule, Donal J. Sexton, Craig A. Solid, Shu-Cheng Chen, Robert N. Foley
Journal: Journal of the American Society of Nephrology (2015)

Although management of multiple myeloma has changed substantially in the last decade, it is unknown whether the burden of ESRD due to multiple myeloma has changed, or whether survival of patients with multiple myeloma on RRT has improved. Regarding ESRD due to multiple myeloma necessitating RRT in the United States, we evaluated temporal trends between 2001 and 2010 for demography-adjusted incidence ratios, relative to rates in 2001–2002, and mortality hazards from RRT initiation, relative to hazards in 2001–2002. In this retrospective cohort study, we used the US Renal Data System database ( n =1,069,343), 2001–2010, to identify patients with ESRD due to multiple myeloma treated with RRT ( n =12,703). Demography-adjusted incidence ratios of ESRD from multiple myeloma decreased between 2001–2002 and 2009–2010 in the overall population (demography-adjusted incidence ratio 0.82; 95% confidence interval, 0.79 to 0.86) and in most demographic subgroups examined. Mortality rates were 86.7, 41.4, and 34.4 per 100 person-years in the first 3 years of RRT, respectively, compared with 32.3, 20.6, and 21.3 in matched controls without multiple myeloma. Unadjusted mortality hazards ratios declined monotonically after 2004 to a value of 0.72; 95% confidence interval, 0.67 to 0.77 in 2009–2010, and declines between 2001–2002 and 2008–2009 were observed ( P &lt;0.05) in most demographic subgroups examined. Findings were similar when adjustment was made for demographic characteristics, comorbidity markers, and laboratory test values. These data suggest the incidence of RRT from multiple myeloma in the United States has decreased in the last decade, and clinically meaningful increases in survival have occurred for these patients.
Profiling of Oncogenic Driver Events in Lung Adenocarcinoma Revealed MET Mutation as Independent Prognostic Factor
Authors: Sai F. Yeung, Joanna H.M. Tong, Peggy P.W. Law, Lau Y. Chung, Raymond W.M. Lung, Carol Y.K. Tong, Chit Chow, Anthony W.H. Chan, Innes Y.P. Wan, Tony S.K. Mok, Ka F. To
Journal: Journal of Thoracic Oncology (2015)

Oncogenic driver mutations activating receptor tyrosine kinase pathways are promising predictive markers for targeted treatment. We investigated the mutation profile of an updated driver events list on receptor tyrosine kinase/RAS/PI3K axis and the clinicopathologic implications in a cohort of never-smoker predominated Chinese lung adenocarcinoma.We tested 154 lung adenocarcinomas and adenosquamous carcinomas for EGFR, KRAS, HER2, BRAF, PIK3CA, MET, NRAS, MAP2K1, and RIT1 mutations by polymerase chain reaction-direct sequencing. MET amplification and ALK and ROS1 translocations were assessed by fluorescent in situ hybridizations. MET and thyroid transcription factor-1 protein expressions were investigated by immunohistochemistry.Seventy percent of lung adenocarcinomas carried actionable driver events. Alterations on EGFR (43%), KRAS (11.4%), ALK (6%), and MET (5.4%) were frequently found. ROS1 translocation and mutations involving BRAF, HER2, NRAS, and PIK3CA were also detected. No mutation was observed in RIT1 and MAP2K1. Patients with EGFR mutations had a favorable prognosis, whereas those with MET mutations had poorer overall survival. Multivariate analysis further demonstrated that MET mutation was an independent prognostic factor. Although MET protein expression was detected in 65% of lung adenocarcinoma, only 10% of the MET-immunohistochemistry positive tumors harbor MET DNA alterations that drove protein overexpression. Appropriate predictive biomarker is essential for selecting patients who might benefit from specific targeted therapy.Actionable driver events can be detected in two thirds of lung adenocarcinoma. MET DNA alterations define a subset of patients with aggressive diseases that might potentially benefit from anti-MET targeted therapy. High negative predictive values of thyroid transcription factor-1 and MET expression suggest potential roles as surrogate markers for EGFR and/or MET mutations.
5-year prospective cluster randomised controlled study of a new nasopharyngeal carcinoma screening programme
Authors: Mingfang Ji, Wei Sheng, Weimin Cheng, Jun Zhang, Su Mei Cao, Xia Yu, Songlin Huang, Shuming He, Hanwei Huang, Biaohua Wu, Kuangrong Wei, Xiaodong Liu, Shifeng Lian, Honglin Chen, Yingjie Zheng, Shoujie Huang, Shengxiang Ge, Park S P Ng, Qing Liu, Minghuang Hong, Yi Xin Zeng, Yong Yuan, Ningshao Xia, Mun-Hon Ng
Journal: The Lancet (2015)
Should be properly recognised
Authors: C Brittain, B G Steggles, C J Eaton, P J P Holden, R J Fairhurst
Journal: BMJ (1995)

and a defibrillator as well as my medical bag up five flights of stairs in a block of flats, where the lift is invariably out of order or its floor swimming in urine?What do I do with the equipment while visiting patients who do not require it?If I leave it in the car the possibility of its being stolen is high.Have the authors considered the practical implications of their advice?
Quality of palliative care services
Authors: Kris C. P Vissers, Yvonne Engels, Jeroen Hasselaar, Karen Van Beek, Kathrin Woitha, Ahmed Nisar, Xavier Gomez-Batiste, Birgit Jaspers, Leppert Wojciech, Joannes Menten, Sam Ahmedzai, Jean-Marc Mollard
Journal: Journal of Thoracic Oncology (2011)