tbuckley/cabot-search huggingface dataset:
Variation in the Incidence and Magnitude of Tumor-Infiltrating Lymphocytes in Breast Cancer Subtypes
Authors: Sasha E. Stanton, Sylvia Adams, Mary L. Disis
Journal: JAMA Oncology (2016)

The presence of tumor-infiltrating lymphocytes (TILs) is a favorable prognostic factor in breast cancer, and TILs may synergize with chemotherapy and immune checkpoint inhibitor therapy for improved clinical response. A more detailed understanding of the variation in lymphocytic infiltration in breast cancer may aid in identifying subtypes more amenable to immunomodulation.To determine the median percentage of patients with breast cancer with no, intermediate, or high levels of TIL and assess variations in lymphocytic cell subsets across breast cancer subtypes.Eligible studies (PubMed, 1990-2015) analyzed tumor lymphocytic, CD8+, and FOXP3+ cellular infiltrates, and used multivariable analyses and quantitative methods for enumerating cell populations. Selection of of studies was performed in accordance with PRISMA guidelines and evaluated by 2 independent appraisers.Fifteen studies (n = 13 914) met prespecified criteria and were reviewed in December 2015. A median of 11% (range, 5%-26%) of breast cancers demonstrate lymphocyte-predominant breast cancer (LPBC), with approximately 16% of cancers showing no evidence of TILs. Triple-negative (TN) breast cancers demonstrated the highest incidence of LPBC (20%; range, 4%-37%). This incidence is similar to that of breast cancers that are human epidermal growth factor 2 positive and either hormone receptor positive or negative (HER2+) at 16% (range 11%-24%). Hormone receptor positive/HER2- (HR+) breast cancer showed the lowest incidence of LPBC at 6% (range, 3%-12%). CD8+ T-cell infiltrates, indicative of type I immunity, were found in 48% of all breast cancers (range, 32%-80%) with similar levels observed in TN (60%; range, 40%-91%) and HER2+ disease (61%; range, 40%-83%). Fewer HR+ tumors demonstrated CD8+ TIL (43%; range, 30%-73%). The highest levels of FOXP3+ cells were observed in TN (70%; range, 65%-76%) and HER2+ disease (67%; range, 61%-74%). A minority of HR+ breast cancers demonstrated high levels of tumor-infiltrating FOXP3+ cells (38%; range, 35%-41%).The magnitude of TIL is variable within and between breast cancer subtypes. Levels of lymphocytic subpopulations may identify breast cancers more amenable to immunomodulation and indicate additional strategies to enhance immunity in patients with low to moderate levels of TILs.
Smoking and ulcerative colitis
Authors: R Logan, M. J S Langman
Journal: BMJ (1984)

eseeneven inthose patients whosurvived foronlyshort periods. Itseems unlikely, therefore, thatfailure toformmetastases isdueto surveillance bytheimmunesystem. Inconclusion, ourobservations provide otherwise unobtainableinformation on mechanisms ofmetastasis inman and confirm that peritoneovenous shunting formalignant ascites does notcarrythehazard ofpromoting clinically important metastasis.
Depressive symptoms and the diagnosis of affective disorder in a clinic population of low socioeconomic status
Authors: P N Wold, A G Rosenfield, K Dwight
Journal: American Journal of Psychiatry (1982)

The authors used the Center for Epidemiological Studies Depression Scale to measure the level of depressive symptoms in a self-referred clinic population whose socioeconomic status was low. They found that the population suffered a high degree of depression and that the diagnosis of major affective syndrome predominated. The depression scale used was found to be a good indicator of probable depression in this population. The authors suggest further investigation of the linkage between socioeconomic status and affective disorder.
Anticancer drug candidate CBL0137, which inhibits histone chaperone FACT, is efficacious in preclinical orthotopic models of temozolomide-responsive and -resistant glioblastoma
Authors: Tara A. Barone, Catherine A. Burkhart, Alfiya Safina, Gary Haderski, Katerina V. Gurova, Andrei A. Purmal, Andrei V. Gudkov, Robert J. Plunkett
Journal: Neuro-Oncology (2016)

The survival rate for patients with glioblastoma (GBM) remains dismal. New therapies targeting molecular pathways dysregulated in GBM are needed. One such clinical-stage drug candidate, CBL0137, is a curaxin, small molecules which simultaneously downregulate nuclear factor-kappaB (NF-ĸB) and activate p53 by inactivating the chromatin remodeling complex, Facilitates Chromatin Transcription (FACT). We used publicly available databases to establish levels of FACT subunit expression in GBM. In vitro, we evaluated the toxicity and effect of CBL0137 on FACT, p53, and NF-ĸB on U87MG and A1207 human GBM cells. In vivo, we implanted the cells orthotopically in nude mice and administered CBL0137 in various dosing regimens to assess brain and tumor accumulation of CBL0137, its effect on tumor cell proliferation and apoptosis, and on survival of mice with and without temozolomide (TMZ). FACT subunit expression was elevated in GBM compared with normal brain. CBL0137 induced loss of chromatin-unbound FACT, activated p53, inhibited NF-ĸB–dependent transcription, and was toxic to GBM cells. The drug penetrated the blood–brain barrier and accumulated in orthotopic tumors significantly more than normal brain tissue. It increased apoptosis and suppressed proliferation in both U87MG and A1207 tumors. Intravenous administration of CBL0137 significantly increased survival in models of early- through late-stage TMZ-responsive and -resistant GBM, with a trend toward significantly increasing the effect of TMZ in TMZ-responsive U87MG tumors. CBL0137 targets GBM according to its proposed mechanism of action, crosses the blood–brain barrier, and is efficacious in both TMZ-responsive and -resistant orthotopic models, making it an attractive new therapy for GBM.
Differences in Clinical Manifestations of Hemochromatosis in Hfe C282Y Homozygotes with Extreme High and Low Iron Phenotypes
Authors: G. D. McLaren, L. W. Powell, P. D. Phatak, J. C. Barton, P. C. Adams, V. N. Subramaniam, L. C. Gurrin, J. D. Phillips, C. Parker, K. J. Allen, W-P Chen, M. J. Emond, D. A. Nickerson, G. A. Ramm, G. J. Anderson, C. E. McLaren
Journal: American Journal of Hematology (2016)
Nasal High-Flow Therapy for Primary Respiratory Support in Preterm Infants
Authors: Calum T. Roberts, Louise S. Owen, Brett J. Manley, Dag H. Frøisland, Susan M. Donath, Kim M. Dalziel, Margo A. Pritchard, David W. Cartwright, Clare L. Collins, Atul Malhotra, Peter G. Davis
Journal: New England Journal of Medicine (2016)

Treatment with nasal high-flow therapy has efficacy similar to that of nasal continuous positive airway pressure (CPAP) when used as postextubation support in neonates. The efficacy of high-flow therapy as the primary means of respiratory support for preterm infants with respiratory distress has not been proved.
D5-04: Global expression profile in NSCLC surgical samples predicts response to pemetrexed
Authors: Rosario Perona, Javier De-Castro-Carpeño, Rosario Machado-Pinilla, Cristobal Belda-Iniesta, Vanesa Rodriguez-Fanjul, Inmaculada Ibanez De Caceres, Enrique Casado, Paloma Cejas, Javier Sanchez-Garcia, Manuel Gonzalez-Baron
Journal: Journal of Thoracic Oncology (2007)
Risk of Bleeding and Thrombosis in Patients 70 Years or Older Using Vitamin K Antagonists
Authors: Hilde A. M. Kooistra, Agneta H. Calf, Margriet Piersma-Wichers, Hanneke C. Kluin-Nelemans, Gerbrand J. Izaks, Nic J. G. M. Veeger, Karina Meijer
Journal: JAMA Internal Medicine (2016)

Previous studies have shown that, despite the higher risk of bleeding, the elderly still benefit from taking anticoagulants if they have a stringent indication. However, owing to the relatively low number of patients older than 90 years in these studies, it is unknown whether this benefit is also seen with the eldest patients.To determine how the risk of bleeding and thrombosis is associated with age in patients older than 70 years who were treated with a vitamin K antagonist (VKA).A matched cohort study was conducted of patients at a thrombosis service who were treated with a VKA between January 21, 2009, and June 30, 2012. All 1109 patients 90 years or older who were treated with a VKA were randomly matched 1:1:1 with 1100 patients aged 80 to 89 years and 1104 patients aged 70 to 79 years based on duration of VKA treatment. Data analysis was conducted from April 2015 to April 2016.The primary outcome was a composite of clinically relevant nonmajor and major bleeding. Secondary outcomes included thromboses and quality of VKA control.During 6419 observation-years, 713 of the 3313 patients (1394 men and 1919 women) had 1050 bleeding events. The risk of bleeding was not significantly increased in patients aged 80 to 89 years (event rate per 100 patient-years [ER], 16.7; hazard ratio [HR], 1.07; 95% CI, 0.89-1.27) and mildly increased in patients 90 years or older (ER, 18.1; HR, 1.26; 95% CI, 1.05-1.50) compared with patients aged 70 to 79 years (ER, 14.8). The point estimates for major bleeding (including fatal) were comparable for patients aged 80 to 89 years (ER, 1.0; HR, 1.09; 95% CI, 0.60-1.98) and those 90 years or older (ER, 1.1; HR, 1.20; 95% CI, 0.65-2.22) compared with those aged 70 to 79 years (ER, 0.9). The increase in bleeding risk was sharper in men than in women. Eighty-five patients (2.6%) developed a thrombotic event. Risk of thrombosis was higher for patients in their 90s (HR, 2.14; 95% CI, 1.22-3.75) and 80s (HR, 1.75; 95% CI, 1.002-3.05) than for patients in their 70s. Vitamin K antagonist control became significantly poorer with rising age, which partly explained the increased bleeding risk in patients 90 years or older, but most of the increased risk of thrombosis was not mediated by VKA control.These clinical practice data of patients considered eligible for anticoagulation show that the bleeding risk with a VKA only mildly increases after the age of 80 years, while there is a sharp increase in the risk of thrombosis in the same age group.
P1055 : The macrophage activation marker soluble CD163 is independently associated with the severity of NAFLD in morbid obesity and reduced by bariatric surgery
Authors: K. Kazankov, J. Tordjman, H.J. Møller, H. Vilstrup, C. Poitou, P. Bedossa, J.-L. Bouillot, K. Clement, H. Grønbæk
Journal: Journal of Hepatology (2015)
PD4-1-8: Prognostic impact of total tumor volume in stage III non-small-cell lung cancer treated with concurrent chemoradiotherapy
Authors: Hideyuki Harada, Nobuyuki Yamamoto, Toshiaki Takahashi, Hirofumi Asakura, Takayuki Hashimoto, Koichi Hirakawa, Masashi Mizumoto, Hiroshi Fuji, Shigeyuki Murayama, Tetsuo Nishimura
Journal: Journal of Thoracic Oncology (2007)
Development of Leukemia in Rats With Tumors Induced by Chicken Sarcoma Virus
Authors: F. Svec, E. Hlavay, P. Kossey, J. Matoška, M. Hladká
Journal: JNCI Journal of the National Cancer Institute (1974)

RBA myeloid leukemia developed in Sprague-Dawley rats inoculated with chicken sarcoma virus. At the site of inoculation, RSA rat sarcoma (RBA-Sa) tumors appeared; besides the sarcomatous tissue, they contained foci of leukemic cells. RBA-Sa, when transplanted subcutaneously gave rise, at the site of inoculation, to sarcomas containing disseminated leukemic cells and generalized leukemia (RBA-Le). RBA leukemic liver and spleen cells, transplanted intraperitoneally into rats of all ages, produced leukemia only. In tissue culture, the sarcoma cells were separated and, when transplanted into rats, gave rise to sarcomas only. RBA-Sa released virus and induced sarcomas in chickens. Virus preparations from leukemic organs induced leukemia in 11% of the rats. In chickens the same virus preparations caused tumors which, except for 2, regressed within 2 weeks. Of rats inoculated with virus preparations from leukemic organs, about 50% died of hepatitis. Another remarkable observation was the increased incidence in female rats of mammary fibroadenomas.
Modeled Perfluorooctanoic Acid (PFOA) Exposure and Liver Function in a Mid-Ohio Valley Community
Authors: Lyndsey A. Darrow, Alyx C. Groth, Andrea Winquist, Hyeong-Moo Shin, Scott M. Bartell, Kyle Steenland
Journal: Environmental Health Perspectives (2016)

Perfluorooctanoic acid (PFOA or C8) has hepatotoxic effects in animals. Cross-sectional epidemiologic studies suggest PFOA is associated with liver injury biomarkers.We estimated associations between modeled historical PFOA exposures and liver injury biomarkers and medically validated liver disease.Participants completed surveys during 2008-2011 reporting demographic, medical, and residential history information. Self-reported liver disease, including hepatitis, fatty liver, enlarged liver and cirrhosis, was validated with healthcare providers. Alanine aminotransferase (ALT), γ-glutamyltransferase (GGT) and direct bilirubin, markers of liver toxicity, were obtained from blood samples collected in the C8 Health Project (2005-2006). Historically modeled PFOA exposure, estimated using environmental fate and transport models and participant residential histories, was analyzed in relation to liver biomarkers (n = 30,723, including 1,892 workers) and liver disease (n = 32,254, including 3,713 workers).Modeled cumulative serum PFOA was positively associated with ALT levels (p for trend < 0.0001), indicating possible liver toxicity. An increase from the first to the fifth quintile of cumulative PFOA exposure was associated with a 6% increase in ALT levels (95% CI: 4, 8%) and a 16% increased odds of having above-normal ALT (95% CI: odds ratio: 1.02, 1.33%). There was no indication of association with either elevated direct bilirubin or GGT; however, PFOA was associated with decreased direct bilirubin. We observed no evidence of an effect of cumulative exposure (with or without a 10-year lag) on all liver disease (n = 647 cases), nor on enlarged liver, fatty liver, and cirrhosis only (n = 427 cases).Results are consistent with previous cross-sectional studies showing association between PFOA and ALT, a marker of hepatocellular damage. We did not observe evidence that PFOA increases the risk of clinically diagnosed liver disease.Darrow LA, Groth AC, Winquist A, Shin HM, Bartell SM, Steenland K. 2016. Modeled perfluorooctanoic acid (PFOA) exposure and liver function in a Mid-Ohio Valley community. Environ Health Perspect 124:1227-1233; http://dx.doi.org/10.1289/ehp.1510391.
Assessment and initial management of major trauma: summary of NICE guidance
Authors: Jessica Glen, Margaret Constanti, Karim Brohi
Journal: BMJ (2016)

#### What you need to know

Trauma is a major contributor to the global burden of disease. Those who experience major trauma have serious and often multiple injuries associated with a strong possibility of death or disability. Nationally there are around 20 000 cases of major trauma per year in England, and over a quarter of these result in deaths.1 Trauma care is a developing field, and recent civilian and military research has led to changes in the assessment and management of severely injured patients. This article summarises the most recent recommendations from the National Institute for Health and Care Excellence (NICE) on the assessment and initial management of major trauma. These guidelines sit as part of a suite of trauma guidelines2 3 4 5 6 and alongside the previously published guidelines on head injury.7 They are written in the context of the NHS, where trauma care was reorganised into major trauma networks in 2012. Here we focus on two central themes of the guidelines—the assessment of a patient with major trauma and the management of patients who are actively bleeding.

#### What’s new in this guidance?

#### Other topics covered in the NICE major trauma guideline

While this article summarises the two central themes of the guideline (streamlined assessment of the major trauma patient in hospital and the management of patients who are actively bleeding), the guideline also …
PTH-237 Differing risk of small bowel necrosis in patients undergoing oesophagectomy and total gastrfectomy with feeding jejunostomy placement: Abstract PTH-237 Table 1
Authors: OS Al-Taan, M Nyasvajjala, M Paul, D Sharpe, S Ubhi, D Bowrey
Journal: Gut (2015)

<h3>Introduction</h3> Placement of feeding jejunostomy at the time of oesophagectomy or total gastrectomy has become standard of care at most UK centres. Review of the literature reveals isolated reports of small bowel necrosis, although the frequency of this problem is unclear. Further, it is unclear whether the risk of small bowel problems is similar for patients after gastrectomy as those after oesophagectomy. The aim of this study was to ascertain the frequency of small bowel problems in a cohort of patients undergoing oesophagogastric surgery. <h3>Method</h3> Retrospective review of patients undergoing oesophagogastric resection for cancer during the years 2009–2014. <h3>Results</h3> The study population comprised 325 patients undergoing oesophagogastric resection with jejunostomy placement (255 oesophagectomy, 70 total gastrectomy). Five patients undergoing total gastrectomy developed small bowel necrosis (5/70, 7%), while this was not observed in any patient undergoing oesophagectomy (0/255, 0%). The table details the time of this complication and the associated factors. All five patients developed small bowel necrosis after initial discharge from intensive care unit to the surgical ward. All patients required laparotomy with small bowel resection with double barrel stoma formation, parenteral nutrition and subsequent reconstruction (6–8 weeks later). Only one patient had a leukocytosis on the day of diagnosis. No laboratory abnormalities were identified in the preceding 24 hr in the other four patients. One patient dies from multi-organ failure, the remaining four were discharged home. <h3>Conclusion</h3> Small bowel necrosis and perforation is a serious and life threatening complication of feeding jejunostomy. In our cohort, it was observed exclusively in patients who had undergone total gastrectomy. There were very few antecedent signs of a problem. All patients required laparotomy and small bowel resection. <h3>Disclosure of interest</h3> None Declared.
Schizophrenia research
Authors: H REUTER
Journal: American Journal of Psychiatry (1993)

The aim of the study was to investigate whether there is any structural evidence for the model of 'cognitive dysmetria' in schizophrenia if an automatic whole-brain analysis method is used.High-resolution magnetic resonance scans were obtained for 75 schizophrenic patients and 75 controls.These data were analysed using the recently developed deformation-based morphometry allowing the assessment of volumetric differences without a priori definition of regions of interest.When compared with controls, we found reduced volumes in patients with schizophrenia in the frontal lobe (gyrus frontalis superior, medius and medialis), the temporal lobe (gyrus temporalis superior and inferior), the thalamus, the left cerebellar hemisphere and the right cerebellar vermis.There was an increase in volume in the right putamen.To date, this is the first structural magnetic resonance imaging study to demonstrate that the three key-elements of the model of cognitive dysmetria -frontal lobe, thalamus, and cerebellum -are reduced in volume in schizophrenic patients.This highlights the importance of this concept for future investigations.
Do Hematopoietic Cell Transplant Patients Treated on a Clinical Trial Do Better? Comparison of Characteristics and Outcomes of Patients Enrolled Versus Not Enrolled on Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) 0201 Trial
Authors: Nandita Khera, Navneet S. Majhail, Ruta Brazauskas, Zhiwei Wang, Mahmoud Aljurf, Görgün Akpek, Yoshiko Atsuta, Sara Beattie, Christopher N. Bredeson, Linda J. Burns, Allen R. Chen, Jason Dehn, César O Freytes, Vikas Gupta, Gregory A. Hale, Yoshihiro Inamoto, Hillard M. Lazarus, Charles F. LeMaistre, Jeanne M. Palmer, Kristjan Paulson, Raquel M. Schears, Amir Steinberg, David Szwajcer, John R. Wingard, Baldeep Wirk, William A. Wood, Steven Joffe, Theresa Hahn, Fausto R. Loberiza, Stephanie J. Lee
Journal: Blood (2014)
Prognostic factors of survival in patients with metastatic castration resistant prostate cancer (mCRPC) treated with cabazitaxel: Sequencing might matter.
Authors: Antoine Angelergues, Denis Maillet, Aude Flechon, Mustafa Ozguroglu, Florence Mercier, Aline Guillot, Sylvestre Le Moulec, Gwenaelle Gravis, Philippe Beuzeboc, Christophe Massard, Thibault De La Motte Rouge, Reza-Thierry Elaidi, Stephane Oudard
Journal: Journal of Clinical Oncology (2013)

5063 Background: Recently, several new drugs have demonstrated an overall survival (OS) benefit in patients (pts) with mCRPC. Their use must be optimized to maximize patient outcomes. We evaluated prognostic factors of OS in mCRPC pts treated with cabazitaxel (C), a new taxane developed to overcome docetaxel (D) resistance. Methods: Records of 125 consecutive mCRPC pts (median 67 yrs) treated with C (after D) were retrospectively collected in 9 centers (France, n=8; Turkey, n=1). Baseline characteristics, disease history, PSA response, OS and radiological and/or clinical progression-free survival (PFS) were collected. The influence of selected variables on OS was analyzed by multivariate logistic regression. Results: At C initiation, 83.3% of pts were ECOG 0-1, 50.8% had an initial Gleason score of 8-10, 62.9% had pain and 84.8% had radiological or clinical progression. Median duration of response to first-line androgen deprivation therapy was 20 months (mo) and 22% received ≥2 prior D lines. New hormonal agents (abiraterone or enzalutamide) were given before C in 33% of pts and after C in 16%. Median number of C cycles received was 6 (range 2-14). A PSA decrease of ≥50% and ≥30% was reached in 41.3% and 48.8% of patients treated with C. Median OS from first C cycle was 13.3 mo and median clinical and/or radiological PFS was 6.5 mo. In multivariate analysis, OS was significantly reduced in pts with ECOG 2 (HR: 6.05), alkaline phosphatase ≥1.5 ULN (HR: 2.64), lymph node involvement (HR: 1.89). Conversely, OS was significantly prolonged in pts with ≥2 prior D lines (HR: 0.35), prior curative therapy (HR: 0.55), a PSA decrease ≥30% with C (HR: 0.21) and in pts treated with abiraterone/enzalutamide after C (HR: 0.37). Median OS from the first D dose was 65 mo in pts treated with abiraterone or enzalutamide after C versus 39 mo in pts receiving these agents before C. Conclusions: Patients with ≥ 2 prior D lines, PSA response ≥30% with C and treated with new hormonal agents after C experienced a prolonged OS. Conversely, intake of new hormonal agents before C rather than after was associated with a reduced OS from the first D dose. Prospective randomized trials are needed to confirm these results.