tbuckley/cabot-search huggingface dataset:
Validation of the Caprini Venous Thromboembolism Risk Assessment Model in Critically Ill Surgical Patients
Authors: Andrea T. Obi, Christopher J. Pannucci, Andrew Nackashi, Newaj Abdullah, Rafael Alvarez, Vinita Bahl, Thomas W. Wakefield, Peter K. Henke
Journal: JAMA Surgery (2015)

Appropriate risk stratification for venous thromboembolism (VTE) is essential to providing appropriate thromboprophylaxis and avoiding morbidity and mortality.To validate the Caprini VTE risk assessment model in a previously unstudied high-risk cohort: critically ill surgical patients.We performed a retrospective cohort study of 4844 adults (≥18 years old) admitted to a 20-bed surgical intensive care unit in a large tertiary care academic hospital during a 5-year period (July 1, 2007, through June 30, 2012).The main study outcome was VTE (defined as patients with deep vein thrombosis or pulmonary embolism) that occurred during the patient's initial hospital admission.The study population was distributed among risk levels as follows: low, 5.3%; moderate, 19.9%; high, 31.6%; highest, 25.4%; and superhigh, 14.9%. The overall incidence of inpatient VTE was 7.5% and increased with risk level: 3.5% in low-risk patients, 5.5% in moderate-risk patients, 6.6% in high-risk patients, 8.6% in highest-risk patients, and 11.5% in superhigh-risk patients. Patients with Caprini scores greater than 8 were significantly more likely to develop inpatient VTE events when compared with patients with Caprini scores of 7 to 8 (odds ratio [OR], 1.37; 95% CI, 1.02-1.85; P = .04), 5 to 6 (OR, 1.35; 95% CI, 1.16-1.57; P < .001), 3 to 4 (OR, 1.30; 95% CI, 1.16-1.47; P < .001), or 0 to 2 (OR, 1.37; 95% CI, 1.16-1.64; P < .001). Similarly, patients with Caprini scores of 7 to 8 were significantly more likely to develop inpatient VTE when compared with patients with Caprini scores of 5 to 6 (OR, 1.33; 95% CI, 1.01-1.75; P = .04), 3 to 4 (OR, 1.27; 95% CI, 1.08-1.51; P = .005), or 0 to 2 (OR, 1.38; 95% CI, 1.10-1.74; P = .006).The Caprini VTE risk assessment model is valid. This study supports the use of individual risk assessment in critically ill surgical patients.
Scaling up of highly active antiretroviral therapy in a rural district of Malawi: an effectiveness assessment
Authors: Laurent Ferradini, Arnaud Jeannin, Loretxu Pinoges, Jacques Izopet, Didakus Odhiambo, Limangeni Mankhambo, Gloria Karungi, Elisabeth Szumilin, Serge Balandine, Gaëlle Fedida, M Patrizia Carrieri, Bruno Spire, Nathan Ford, Jean-Michel Tassie, Philippe J Guerin, Chris Brasher
Journal: The Lancet (2006)
An Angiographic Severity Index for Pulmonary Embolism
Authors: PETER N. WALSH, RICHARD H. GREENSPAN, MORRIS SIMON, ALLAN L. SIMON, THOMAS M. HYERS, PAUL C. WOOSLEY, CHRISTINE M. COLE
Journal: Circulation (1973)

This report has discussed the use of an angiographic severity index for pulmonary embolism in the analysis of pulmonary angiograms from 160 patients admitted to the Urokinase-Pulmonary Embolism Trial. Angiographic studies done before and after treatment with urokinase or heparin were analyzed independently by three radiologists who had no knowledge of treatment assignment. A subjective evaluation and a subsequent objective recording of abnormalities were made. The computation of a severity index was based on a numerical grading system for definite abnormalities specific for pulmonary embolism (intraluminal filling defects and vascular obstructions). The procedure for computing the severity index was simple enough that recorded abnormalities were coded and punched by a statistical clerk and analyzed by computer. Correlations between subjective evaluations and objective severity indices were high. There was excellent agreement among the three radiologists for both subjective and objective methods. Highly significant treatment differences were detected. The angiographic severity index might help to classify patients, predict prognosis, plan clinical studies, and assess treatment effects.
Prevalence and Phenotypes of APC and MUTYH Mutations in Patients With Multiple Colorectal Adenomas
Authors: Shilpa Grover, Fay Kastrinos, Ewout W. Steyerberg, E. Francis Cook, Akriti Dewanwala, Lynn Anne Burbidge, Richard J. Wenstrup, Sapna Syngal
Journal: JAMA (2012)

Patients with multiple colorectal adenomas may carry germline mutations in the APC or MUTYH genes.To determine the prevalence of pathogenic APC and MUTYH mutations in patients with multiple colorectal adenomas who had undergone genetic testing and to compare the prevalence and clinical characteristics of APC and MUTYH mutation carriers.Cross-sectional study conducted among 8676 individuals who had undergone full gene sequencing and large rearrangement analysis of the APC gene and targeted sequence analysis for the 2 most common MUTYH mutations (Y179C and G396D) between 2004 and 2011. Individuals with either mutation underwent full MUTYH gene sequencing. APC and MUTYH mutation prevalence was evaluated by polyp burden; the clinical characteristics associated with a pathogenic mutation were evaluated using logistic regression analyses.Prevalence of pathogenic mutations in APC and MUTYH genes.Colorectal adenomas were reported in 7225 individuals; 1457 with classic polyposis (≥100 adenomas) and 3253 with attenuated polyposis (20-99 adenomas). The prevalence of pathogenic APC and biallelic MUTYH mutations was 95 of 119 (80% [95% CI, 71%-87%]) and 2 of 119 (2% [95% CI, 0.2%-6%]), respectively, among individuals with 1000 or more adenomas, 756 of 1338 (56% [95% CI, 54%-59%]) and 94 of 1338 (7% [95% CI, 6%-8%]) among those with 100 to 999 adenomas, 326 of 3253 (10% [95% CI, 9%-11%]) and 233 of 3253 (7% [95% CI, 6%-8%]) among those with 20 to 99 adenomas, and 50 of 970 (5% [95% CI, 4%-7%]) and 37 of 970 (4% [95% CI, 3%-5%]) among those with 10 to 19 adenomas. Adenoma count was strongly associated with a pathogenic mutation in multivariable analyses.Among patients with multiple colorectal adenomas, pathogenic APC and MUTYH mutation prevalence varied considerably by adenoma count, including within those with a classic polyposis phenotype. APC mutations predominated in patients with classic polyposis, whereas prevalence of APC and MUTYH mutations was similar in attenuated polyposis. These findings require external validation.
THE MODERN TREATMENT OF HERNIA BY TRUSSES
Authors: W. M. Eccles
Journal: BMJ (1928)

THE opeiative treatmen1t of hernia hiasbecome so widespread durling this century that the mechanical retenitioln of viscela withlini the abdomen is likely to become a lost art.Undoubtedly her nia is a-menable to successful treatmiient by oper ation in its ear ly stages in suitable subjects, and the perfection to wlhichl sulch operatioins lhave been brought
Treatment of chronic hepatitis B in children with prednisone followed by alfa-interferon: a controlled randomized study
Authors: Riccardo Utili, Evangelista Sagnelli, Giovanni B. Gaeta, Bruno Galanti, Salvatore Nardiello, Francesca M. Felaco, Giuseppe Pasquale, Aldo Marrone, Lucia Aprea, Teresa Pizzella, Laura Digilio, Giuseppe Cesaro, Carolina Sardaro, Lucio Santarpia, Luigi E. Adinolfi, Augusto Andreana, Michele Russo, Pietro Filippini, Rosa Zampino, Felice Piccinino, Giuseppe Ruggiero, Guiseppe Giusti
Journal: Journal of Hepatology (1994)
Surviving too long in Crohn's disease
Authors: A DI SABATINO
Journal: Gut (2001)

See article on page 35 

Intestinal inflammation results from derangement of those mechanisms of innate and acquired immunity which subtly regulate the local immune response.1 This is the case in Crohn's disease and coeliac disease, both characterised by marked mucosal lymphocyte infiltration, abnormal T cell activation, and upregulation of Th1 cytokines.2 

In recent years another piece has been added to the entangled puzzle of intestinal inflammation. Apoptosis, a highly controlled process of cell death,3 modulates immune and inflammatory responses by limiting expansion of activated T lymphocytes and deleting autoreactive T cell clones.4 5 At the intestinal mucosal level, this process may be of particular relevance ensuring that physiological lamina propria T cell activation, due to chronic exposure to dietary antigens and exogenous pathogens, does not result in inflammatory tissue damage. Otherwise, defective T cell apoptosis may lead to a state of uncontrolled intestinal inflammation, and has been reported in coeliac disease6 and in Crohn's disease.7 8In the former, decreased lymphocyte apoptosis has been found at the level of the epithelial compartment,6 and this defect, favouring expansion of intraepithelial lymphocytes with an abnormal phenotype and a restricted repertoire, may precede the onset of refractory sprue9 or T cell lymphoma.10Unlike coeliac disease, in …
Mometasone and Desloratadine Have an Additive Effect on Eosinophil Survival Induced by Epithelial Cells Culture Supernatants from Nasal Mucosa and Polyps
Authors: J ROCAFERRER, E MENDEZ, M FUENTES, I ALOBID, A VALERO, C PICADO, J MULLOL
Journal: Journal of Allergy and Clinical Immunology (2008)
Reply to: “Do EASL and mRECIST responses have independent effects on survival in hepatocellular carcinoma patients treated with transarterial embolization?”
Authors: Tim Meyer, Amy Kirkwood, Roopinder Gillmore
Journal: Journal of Hepatology (2012)

We thank Wang and colleagues for their critical appraisal of our paper which explores the prognostic importance of early response assessment in patients with hepatocellular cancer (HCC) undergoing transarterial embolisation [1]. Wang et al. correctly point out that the prognosis for HCC patients is determined by many factors, including liver function, and are concerned that Child–Pugh score may have been a confounding factor in our analysis. Of the 83 patients included in the study, 69 had Child–Pugh A liver scores and only 13 had Child–Pugh B.
NK cell activation through the NKG2D ligand MULT-1 is selectively prevented by the glycoprotein encoded by mouse cytomegalovirus gene <i>m145 </i>
Authors: Astrid Krmpotic, Milena Hasan, Andrea Loewendorf, Tanja Saulig, Anne Halenius, Tihana Lenac, Bojan Polic, Ivan Bubic, Anja Kriegeskorte, Ester Pernjak-Pugel, Martin Messerle, Hartmut Hengel, Dirk H. Busch, Ulrich H. Koszinowski, Stipan Jonjic
Journal: The Journal of Experimental Medicine (2005)

The NK cell–activating receptor NKG2D interacts with three different cellular ligands, all of which are regulated by mouse cytomegalovirus (MCMV). We set out to define the viral gene product regulating murine UL16-binding protein-like transcript (MULT)-1, a newly described NKG2D ligand. We show that MCMV infection strongly induces MULT-1 gene expression, but surface expression of this glycoprotein is nevertheless completely abolished by the virus. Screening a panel of MCMV deletion mutants defined the gene m145 as the viral regulator of MULT-1. The MCMV m145-encoded glycoprotein turned out to be necessary and sufficient to regulate MULT-1 by preventing plasma membrane residence of MULT-1. The importance of MULT-1 in NK cell regulation in vivo was confirmed by the attenuating effect of the m145 deletion that was lifted after NK cell depletion. Our findings underline the significance of escaping MULT-1/NKG2D signaling for viral survival and maintenance.
Salmonella typhimurium induces epithelial IL-8 expression via Ca2+-mediated activation of the NF-κB pathway
Authors: Andrew T. Gewirtz, Anjali S. Rao, Peter O. Simon, Didier Merlin, Denice Carnes, James L. Madara, Andrew S. Neish
Journal: Journal of Clinical Investigation (2000)

Interactions between the enteric pathogen Salmonella typhimurium and the luminal surface of the intestine provoke an acute inflammatory response, mediated in part by epithelial cell secretion of the chemokine IL-8 and other proinflammatory molecules. This study investigated the mechanism by which this pathogen induces IL-8 secretion in physiologically polarized model intestinal epithelia. IL-8 secretion induced by both the prototypical proinflammatory cytokine TNF-α and S. typhimurium was NF-κB dependent. However, NF-κB activation and IL-8 secretion induced by S. typhimurium, but not by TNF-α, was preceded by and required an increase in intracellular [Ca2+]. Additionally, agonists that increased intracellular [Ca2+] by receptor-dependent (carbachol) or independent (thapsigargin, ionomycin) means also induced IL-8 secretion. Furthermore, the ability of S. typhimurium mutants to induce IκB-α degradation, NF-κB translocation, and IL-8 transcription and secretion correlated precisely with their ability to induce an intracellular [Ca2+] increase in model intestinal epithelia, but not with their ability to invade these cells. Finally, S. typhimurium, but not TNF-α, induced a Ca2+-dependent phosphorylation of IκB-α. These results indicate that S. typhimurium–induced activation of NF-κB–dependent epithelial inflammatory responses proceeds by a Ca2+-mediated activation of an IκB-α kinase. These observations raise the possibility that pharmacologic intervention of the acute inflammatory response can be selectively matched to the specific class of initiating event.
Indications That Phototherapy Is a Risk Factor for Insulin-Dependent Diabetes
Authors: Gisela Dahlquist, Bengt Källén
Journal: Diabetes Care (2003)

In a previous study (1), we found that the diagnosis of maternal-child blood group incompatibility appeared as a risk factor for type 1 diabetes, but we were not able to disentangle possible treatment effects from that of diagnosis. A European population-based multicenter study confirmed the association of type 1 diabetes with jaundice and blood group immunization (2). Since our previous study, the number of infants recorded in the Swedish Childhood Diabetes Registry has almost doubled. We therefore repeated our study with special stress on the possible risk associated with phototherapy.

The Childhood Diabetes Registry, containing information on 7,343 children with diabetes and born during the period 1973–1997, was linked with the Medical Birth …
Highlighting Crypt Necrosis by Using Confocal Laser Endomicroscopy for the In Vivo and Real-Time Diagnosis of GI Graft-Versus-Host Disease
Authors: Gheorghe Hundorfean, Abbas Agaimy, Mircea T. Chiriac, Wolf Rösler, Andreas Mackensen, Jürgen Siebler, Markus F. Neurath
Journal: Journal of Clinical Oncology (2012)
Radiotherapy-Related Lung Fibrosis Enhanced by Tamoxifen
Authors: S. M. Bentzen, J. Z. Skoczylas, M. Overgaard, J. Overgaard
Journal: JNCI Journal of the National Cancer Institute (1996)

Tamoxifen is an anti-estrogen with proven efficacy and low toxicity in the treatment of breast cancer. However, tamoxifen has been shown to exert a number of nonhormonal as well as hormonal effects. One nonhormonal effect of tamoxifen is the induction of transforming growth factor-beta (TGF-beta) secretion. TGF-beta has been implicated in the pathogenesis of radiation-induced fibrosis.We investigated the development of lung fibrosis in breast cancer patients who were treated after mastectomy with radiotherapy, with or without simultaneous adjuvant treatment with tamoxifen.Data from 196 women were included in the analysis. Eighty-four women were postmenopausal patients who participated in a randomized trial testing tamoxifen as an adjuvant to postmastectomy radiotherapy. The radiotherapy technique employed an 8-MV photon field covering the axillary and the infraclavicular and supraclavicular regions of the affected side of the chest; the chest wall was treated with an abutted electron field. Optical density changes in pretreatment and post-treatment chest x-ray films were used to monitor the development of lung fibrosis; lung reactions were assessed in the photon-irradiated field only. Logistic regression analysis was used to explore relationships between radiation dose and the development of lung fibrosis in patients either receiving or not receiving tamoxifen. All P values are from two-sided tests.Among the 84 women who participated in the randomized trial of radiotherapy plus tamoxifen (n = 38) versus radiotherapy alone (n = 46), there was a significant association between tamoxifen treatment and the incidence of marked lung fibrosis (relative risk = 2.0; 95% confidence interval [CI] = 1.2-3.5; P = .01). When logistic regression analysis was used to evaluate data from all 196 patients, a highly significant relationship was found between the incidence of lung fibrosis and total radiation dose (P = .0005). In the full analysis, an increased risk of marked lung fibrosis was found again for patients who received tamoxifen simultaneously with radiotherapy (with patients receiving radiotherapy alone as the referent, odds ratio = 2.9; 95% CI = 1.3-6.3; P = .007). Patient age and menopausal status did not significantly influence the results.Tamoxifen treatment during postmastectomy radiotherapy enhances the risk of radiation-induced lung fibrosis.In view of pre-existing data, we hypothesize that tamoxifen mediates the enhancement of radiation-induced lung fibrosis through the induction of TGF-beta secretion. If this hypothesis is correct, new strategies might be devised for preventing or reducing radiation-induced fibrosis. Because we studied a relatively small portion of the irradiated lung, we cannot recommend changes in current therapeutic measures; however, we strongly encourage additional studies of lung fibrosis in patients receiving tamoxifen and radiotherapy.
Aberrant Crypt Foci as Precursors of the Dysplasia-Carcinoma Sequence in Patients with Ulcerative Colitis
Authors: Takehiro Kukitsu, Tetsuji Takayama, Koji Miyanishi, Atsushi Nobuoka, Shinichi Katsuki, Yasushi Sato, Rishu Takimoto, Takuya Matsunaga, Junji Kato, Tomoko Sonoda, Sumio Sakamaki, Yoshiro Niitsu
Journal: Clinical Cancer Research (2008)

Long-standing ulcerative colitis (UC) predisposes patients to the development of colorectal cancer, but surveillance of colitis-associated cancer by detecting the precancerous lesion dysplasia is often difficult because of its rare occurrence and normal-looking appearance. In sporadic colorectal cancer, aberrant crypt foci (ACF) have been reported by many investigators to be precursor lesions of the adenoma-carcinoma sequence. In the present study, we analyzed the genetic background of ACF to determine whether they could be precursors for dysplasia, and we examined the usefulness of endoscopic examination of ACF as a surrogate marker for surveillance of colitis-associated cancer.ACF were examined in 28 UC patients (19 patients with UC alone and 9 patients with UC and dysplasia; 2 of those patients with dysplasia also had cancer) using magnifying endoscopy. K-ras, APC, and p53 mutations were analyzed by two-step PCR RFLP, in vitro--synthesized protein assay, and single-strand conformation polymorphism, respectively. Methylation of p16 was analyzed by methylation-specific PCR.ACF that appeared distinct endoscopically and histologically were identified in 27 out of 28 UC patients. They were negative for K-ras, APC, and p53 mutations but were frequently positive for p16 methylation (8 of 11; 73%). In dysplasia, K-ras and APC mutations were negative but p53 mutation (3 of 5; 60%) and p16 methylation (3 of 5; 60%) were positive. There was a significant stepwise increase in the number of ACF from patients with UC alone to patients with dysplasia and to patients with cancer. Univariate and multivariate analyses showed significant correlations between ACF and dysplasia.We have disclosed an ACF-dysplasia-cancer sequence in colitis-associated carcinogenesis similar to the ACF-adenoma-carcinoma sequence in sporadic colon carcinogenesis. This study suggests the use of ACF instead of dysplasia for the surveillance of colitis cancer and warrants further evaluation of ACF as a surveillance marker in large-scale studies.
Economic burden of physical activity–related injuries in Dutch children aged 10–12
Authors: Dorine C M Collard, Evert A L M Verhagen, Willem van Mechelen, Martijn W Heymans, Mai J M Chinapaw
Journal: British Journal of Sports Medicine (2011)

Injuries in children occur most often in physical activity-related activities. A lot of these injuries result in direct and indirect costs. A detailed overview of the economic burden of those injuries in children is lacking.A prospective study was conducted with 996 children in Dutch primary schools to describe the economic burden of injuries that occur during organised sports, leisure time and physical education (PE) class activities. Injuries were continuously monitored by PE teachers during the school year 2006-2007. An injury was recorded if it occurred during PE class, leisure time or organised sports activity and caused the child to at least stop the current activity. If an injury was recorded, parents received a cost diary to report the direct and indirect costs of the child's injury. Costs were collected from a societal perspective.During one school year, a total of 119 injuries were reported by 104 children. The mean total costs as a result of an injury were €188 ± 317. The mean direct costs as a result of an injury were much higher than the mean indirect costs (€131 ± 213 and €57 ± 159, respectively). The highest costs were found for upper extremity and leisure time injuries.Physical activity-related injuries are common in children and result in medical costs. Injuries that lead to the highest costs are those that occur during leisure time activities and upper extremity injuries. Intervention programmes for children to prevent upper extremity injuries and leisure time activity injuries may reduce direct (ie, healthcare) and indirect costs.ISRCTN78846684.
Cooperation and Antagonism among Cancer Genes: The Renal Cancer Paradigm
Authors: Samuel Peña-Llopis, Alana Christie, Xian-Jin Xie, James Brugarolas
Journal: Cancer Research (2013)

Abstract It is poorly understood how driver mutations in cancer genes work together to promote tumor development. Renal cell carcinoma (RCC) offers a unique opportunity to study complex relationships among cancer genes. The four most commonly mutated genes in RCC of clear-cell type (the most common type) are two-hit tumor suppressor genes, and they cluster in a 43-Mb region on chromosome 3p that is deleted in approximately 90% of tumors: VHL (mutated in ∼80%), PBRM1 (∼50%), BAP1 (∼15%), and SETD2 (∼15%). Meta-analyses that we conducted show that mutations in PBRM1 and SETD2 co-occur in tumors at a frequency higher than expected by chance alone, indicating that these mutations may cooperate in tumorigenesis. In contrast, consistent with our previous results, mutations in PBRM1 and BAP1 tend to be mutually exclusive. Mutation exclusivity analyses (often confounded by lack of statistical power) raise the possibility of functional redundancy. However, mutation exclusivity may indicate negative genetic interactions, as proposed herein for PBRM1 and BAP1, and mutations in these genes define RCC with different pathologic features, gene expression profiles, and outcomes. Negative genetic interactions among cancer genes point toward broader context dependencies of cancer gene action beyond tissue dependencies. An enhanced understanding of cancer gene dependencies may help to unravel vulnerabilities that can be exploited therapeutically. Cancer Res; 73(14); 4173–9. ©2013 AACR.
RETRACTED ARTICLE: EGFR and MET receptor tyrosine kinase–altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers
Authors: Michela Garofalo, Giulia Romano, Gianpiero Di Leva, Gerard Nuovo, Young-Jun Jeon, Apollinaire Ngankeu, Jin Sun, Francesca Lovat, Hansjuerg Alder, Gerolama Condorelli, Jeffrey A Engelman, Mayumi Ono, Jin Kyung Rho, Luciano Cascione, Stefano Volinia, Kenneth P Nephew, Carlo M Croce
Journal: Nature Medicine (2011)