tbuckley/cabot-search huggingface dataset:
Endoscopic closure of a colonic defect using a novel endoloop system via a single-channel endoscope
Authors: Jiankun Wang, Xiang Wang, Li Liu, Lili Zhao, Min Wang, Zhenzhen Liu, Zhining Fan
Journal: Endoscopy (2016)

Successful closure of postoperative defects is essential for endoscopic resection of early neoplasms. The endoscopic purse-string suture (EPSS) using a double-channel colonoscope has been shown to be safe and effective. This method involves the interaction of the endoloop and the metal clips through two separate endoscope channels [1]. However, single-channel colonoscopes are more popular in clinical practice because of their longer length, more flexible operation, and cheaper price, especially when used in the right colon. We report on a novel endoloop system that was innovatively applied via a single-channel endoscope.
Patterns of Somatic Mutation in Human Cancer Genomes
Authors: Michael Stratton
Journal: Clinical Cancer Research (2007)

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

PL02-05 

All cancers are due to abnormalities in DNA. The availability of the human genome sequence has led to the proposal that resequencing of cancer genomes will reveal the full complement of somatic mutations and hence all the cancer genes. To explore the nature of the information that will be derived from cancer genome sequencing we have sequenced the coding exons of the family of 518 protein kinases, ~1.3Mb DNA per cancer sample, in 210 cancers of diverse histological types. Despite the screen being directed toward the coding regions of a gene family that has previously been strongly implicated in oncogenesis, the results indicate that the majority of somatic mutations detected are “passengers”. There is considerable variation in the number and pattern of these mutations between individual cancers, indicating substantial diversity of processes of molecular evolution between cancers. The imprints of exogenous mutagenic exposures, mutagenic treatment regimes and DNA repair defects can all be seen in the distinctive mutational signatures of individual cancers. This systematic mutation screen and others have previously yielded a number of cancer genes that are frequently mutated in one or more cancer types and which are now anticancer drug targets (for example BRAF , PIK3CA , and EGFR ). However, detailed analyses of the data from our screen additionally suggest that there exist a large number of additional “driver” mutations which are distributed across a substantial number of genes. It therefore appears that cells may be able to utilise mutations in a large repertoire of potential cancer genes to acquire the neoplastic phenotype. However, many of these genes are employed only infrequently. These findings may have implications for future anticancer drug development.
72P Differential expression profile of lung squamous cell carcinoma (LSCC) cell lines as a mean to predict drug interaction effects
Authors: A. Verlicchi, N. Karachaliou, C. Lazzari, C. Codony Servat, I. Chaib, S. Marin, A. Gkountakos, S. Pilotto, J.L. Ramírez Serrano, R. Rosell
Journal: Journal of Thoracic Oncology (2016)
Children born after intracytoplasmic sperm injection
Authors: J M Bland, A. G Sutcliffe, B. Taylor, J. Li, S. Thornton, G. Grudzinskas, B. Lieberman
Journal: BMJ (1999)

Editor—Sutcliffe et al compare babies born through intracytoplasmic sperm injection with control babies (matched for social class, maternal education, region, and sex) born after unassisted conception.1 In their table they give means, standard deviations, and 95% confidence intervals for the two groups separately. These confidence intervals tell us about the estimation of the mean in the population of which the babies are a random sample, which they are not. They tell us nothing about the comparison between the cases and controls.

These controls have been chosen to be similar to the study babies in many ways; they are not a representative sample of babies. It is the difference between the study babies and the control babies that is of interest, and the confidence interval we should have is that for this difference in mean. We cannot work this out from the data given, because this is a paired study and we have unpaired standard deviations. All we have for the comparison is the implication, not actually stated, that the differences are not significant. What we should be given are confidence intervals that tell us how different the cases and controls are.
Abstract 17639: Predictors of Poor Neurocognitive Performance and Neuropsychological Phenotypes in Adolescents and Young Adults With Congenital Heart Disease
Authors: Maria Emilia G Areias, Bruno Peixoto, Ana Carolina Pinheiro, Helena Monteiro, Sara Filipa Araújo, Tânia Carvalho, Stefanie Melo, João Pedro Lopes, Filipa Rodrigues, Ana Catarina Nascimento, Joana Miranda, Filipa Vilacova, Cláudia Moura, Joana Luz Soares, Victor Viana, Jorge Quintas, José Carlos Areias
Journal: Circulation (2015)

Objectives: to determine the predictors of neurocognitive performance (NP) of patients with Congenital Heart Disease (CHD), analysing its relation to parameters of fetal development, as head circumference (HC), weight (W) and length (L) at birth, neonatal parameters (APGAR 1, 5), quality of life (QOL), psychiatric morbidity (PM), psychosocial adjustment (PSA) and traits of personality (TP); to identify different phenotypes of NP in CHD patients. Methods: 337 CHD patients, 189 male, ages 12 to 30 years (mean= 16.34 ± 3.12), 117 cyanotic, and 119 healthy controls (56 males, mean=18.41±3.20) participated. Clinical data were collected. Neuropsychological assessment included Wechsler’s Digit Test (direct and reverse) and Symbol Search, Rey’s Complex Figure, BADS’s Key Searching Test, Color-Word Stroop Test, Trail Making Test (A, B) and Logical Memory Task. Participants were interviewed on social support, family educational style, self-image, physical limitations, completed a psychiatric interview (SADS-L) and self-report questionnaires on QOL (WHOQOL-BREF), PSA (YSR and ASR) and TP (NEOPI-R). HC, W and L and APGAR were collected. Results: CHD patients had a significantly worse NP than healthy controls in all tests, and the cyanotic worse than the acyanotic patients. Several correlations were apparent between fetal parameters (HC, W and L) and neuropsychological abilities in CHD. However, the HC was the main predictor of bad NP later on in CHD patients (R=0.435; R2=0.189; F=14.692; p=0.000; β=0.201; t=2.487; p=0.016). We identified 3 neurocognitive phenotypes in CHD patients, minimally, moderately and globally impaired. The last showed lower HC (p=0.003), W (p=0.022) and L, and a bigger number of retentions in school (p=0.017) than the first. The last reported more aggressive behaviors.than the other 2 (p=0.007; p=0.006) and their caregivers reported more social (p=0.025), thought (p=0.041) and attention problems (p=0.001) in their children than the parents of the other 2. Conclusion: CHD patients have worse NP than controls; small HC at birth was the main predictor of poor NP; We identified 3 patterns of neurocognitive disability among CHD patients: mild, moderate and severely impaired, all showing significant differences compared to controls.
Hematopoietic Stem Cell Niche in Health and Disease
Authors: Jonathan Hoggatt, Youmna Kfoury, David T. Scadden
Journal: Annual Review of Pathology Mechanisms of Disease (2016)

Regulation of stem cells in adult tissues is a key determinant of how well an organism can respond to the stresses of physiological challenge and disease. This is particularly true of the hematopoietic system, where demands on host defenses can call for an acute increase in cell production. Hematopoietic stem cells receive the regulatory signals for cell production in adult mammals in the bone marrow, a tissue with higher-order architectural and functional organization than previously appreciated. Here, we review the data defining particular structural components and heterologous cells in the bone marrow that participate in hematopoietic stem cell function. Further, we explore the case for stromal-hematopoietic cell interactions contributing to neoplastic myeloid disease. As the hematopoietic regulatory networks in the bone marrow are revealed, it is anticipated that strategies will emerge for how to enhance or inhibit production of specific blood cells. In that way, the control of hematopoiesis will enter the domain of therapies to modulate broad aspects of hematopoiesis, both normal and malignant.
Hereditary Hemochromatosis in Adults without Pathogenic Mutations in the Hemochromatosis Gene
Authors: Antonello Pietrangelo, Giuliana Montosi, Angela Totaro, Cinzia Garuti, Dario Conte, Stefano Cassanelli, Mirella Fraquelli, Carla Sardini, Francesco Vasta, Paolo Gasparini
Journal: New England Journal of Medicine (1999)

Hereditary hemochromatosis in adults is usually characterized by mutations in the hemochromatosis (HFE) gene on the short arm of chromosome 6. Most patients have a substitution of tyrosine for cysteine at position 282 (C282Y). We studied a large family from Italy that includes persons who have a hereditary iron-overload condition indistinguishable from hemochromatosis but without apparent pathogenic mutations in the HFE gene. We performed biochemical, histologic, and genetic studies of 53 living members of the family, including microsatellite analysis of chromosome 6 and direct sequencing of the HFE gene.
Epidemics of Diarrhea Caused by a Clindamycin-Resistant Strain of<i>Clostridium difficile</i>in Four Hospitals
Authors: Stuart Johnson, Matthew H. Samore, Kylie A. Farrow, George E. Killgore, Fred C. Tenover, Dena Lyras, Julian I. Rood, Paola DeGirolami, Aldona L. Baltch, Mary Ellen Rafferty, Suzanne M. Pear, Dale N. Gerding
Journal: New England Journal of Medicine (1999)

Large outbreaks of diarrhea caused by a newly recognized strain of Clostridium difficile occurred in four hospitals located in different parts of the United States between 1989 and 1992. Since frequent use of clindamycin was associated with the outbreak in one of the hospitals, we examined the resistance genes of the epidemic-strain isolates and studied the role of clindamycin use in these outbreaks.
Chlorpromazine in Psychiatric Illness
Authors: Willis H. Bower
Journal: New England Journal of Medicine (1954)

THE use of chlorpromazine (10-[3-dimethylaminopropyl]-2-chlorphenothiazine) for the treatment of psychiatric illness was started at the McLean Hospital in September, 1953. At the time of this writing it has been used in 29 cases, which form the basis of this report.The compound is also known as largactil (Poulenc, Limited), or 4560 R.P., and as SKF 2601-A, or Thorazine.‡ It is chemically related to promethazine (Phenergan) and diethazine hydrochloride (Diparcol). It is a Central-nervous-system depressant and has been applied, especially in France, to the treatment of various conditions: manic-depressive psychoses, certain schizophrenias, especially if acute and with excitement or confusion, symptoms . . .
Chronic Pulmonary Coccidioidomycosis
Authors: George A. Sarosi, James D. Parker, Irene L. Doto, Fred E. Tosh
Journal: New England Journal of Medicine (1970)

Of 109 patients with proved coccidioidomycosis 20 had chest films and clinical findings indistinguishable from either chronic pulmonary histoplasmosis or chronic pulmonary tuberculosis. Many were thought to have tuberculosis for years before the fungal etiology of the lung disease was determined. Coccidioides immitis was cultured from sputums of 18 of 19 patients, and coccidioidin complement-fixation tests were positive in 14 of 15. Best therapeutic results were obtained with amphotericin B intravenously in a total dose of 30 mg per kilogram of body weight or more.
Advanced epithelial ovarian cancer: 1998 consensus statements
Authors: J.S. Berek, K. Bertelsen, A. du Bois, M.F. Brady, J. Carmichael, E.A. Eisenhauer, M. Gore, S. Grenman, T.C. Hamilton, S.W. Hansen, P.G. Harper, G. Horvath, S.B. Kaye, H.J. Lück, B. Lund, W.P. McGuire, J.P. Neijt, R.F. Ozols, M.K.B. Parmar, M.J. Piccart-Gebhart, R. van Rijswijk, P. Rosenberg, G.J.S. Rustin, C. Sessa, J.T. Thigpen, C. Tropé, M.K. Tuxen, I. Vergote, J.B. Vermorken, P.H.B. Willemse
Journal: Annals of Oncology (1999)
Changes in Mortality Rates from Leukemia in the First Five Years of Life
Authors: John C. Slocumb, Brian MacMahon
Journal: New England Journal of Medicine (1963)

SEVERAL writers have called attention to a recent change in the shape of the age curve of leukemia mortality under five years of age. Before 1920 in England and Wales and 1940 in the United States this "curve" was an approximately horizontal line. In later periods, in both countries, a peak has appeared in the group from three to four years of age and has become more pronounced with the passage of time. This peak has not appeared in rates for nonwhites in the United States,1 nor is it evident in data from Japan.2 It has been suggested that a . . .
Normal Lower-Esophageal-Sphincter Function after Surgical Treatment of Gastroesophageal Reflux
Authors: W. H. Lipshutz, R. J. Eckert, R. D. Gaskins, D. E. Blanton, W. M. Lukash
Journal: New England Journal of Medicine (1974)

To evaluate operations for gastroesophageal reflux, we studied eight patients who had the Hill and seven who had the Belsey procedure. Of these 15, 12 had hiatus hernia, 11 free gastroesophageal reflux of barium, and 10 peptic esophagitis. Two months to four years after operation all but one of these abnormalities disappeared in 14 patients, who were also asymptomatic. Lower-esophageal-sphincter pressure increased from 5.4 ± 0.4 mm HG (mean ± S.E.M.) to 16.5 ± 1.0 after the Hill repair and 12.2 ± 1.3 after the Belsey repair. The difference between the preoperative and postoperative values is highly significant (p < 0.001). Similar improvement marked the response to abdominal compression; peak sphincter response to pentagastrin increased from 17.2 ± 3.7 mm Hg (mean ± S.E.M.) to 35.5 ± 2.9 after the Hill repair and 41.7 ± 7.9 after the Belsey repair. The values after either procedure differed significantly from those obtained before operation (p < 0.001). Thus, the operations result in both clinical improvement and lower-esophageal-sphincter function that appears essentially normal. (N Engl J Med 291:1107–1110, 1974)
191TiP: MYSTIC: a global, phase 3 study of durvalumab (MEDI4736) plus tremelimumab combination therapy or durvalumab monotherapy versus platinum-based chemotherapy (CT) in the first-line treatment of patients (pts) with advanced stage IV NSCLC
Authors: S. Peters, S. Antonia, S.B. Goldberg, J.V. Heymach, E.S. Kim, K. Nakagawa, V. Papadimitrakopoulou, P. Mukhopadhyay, S. McIntosh, N.A. Rizvi
Journal: Journal of Thoracic Oncology (2016)
Case 36-2000
Authors: John F. Reinus, Rhonda K. Yantiss
Journal: New England Journal of Medicine (2000)

Presentation of CaseA 22-year-old man was admitted to the hospital because of a hepatic mass.The patient had been well until three weeks earlier, when he injured the right side of his chest and shoulder, with subsequent pain that was ascribed to a rib contusion. The pain disappeared after nine days, at which point he consulted a physician for clearance to return to work. Examination showed numerous spider angiomas, which were of unknown duration.For several years, the patient had had difficulty gaining weight, with intermittent night sweats. They had become much more severe during the three nights before . . .
Pretransplantation Burden of Leukemic Progenitor Cells as a Predictor of Relapse after Bone Marrow Transplantation for Acute Lymphoblastic Leukemia
Authors: Fatih M. Uckun, John H. Kersey, Robert Haake, Daniel Weisdorf, Mark E. Nesbit, Norma Ramsay
Journal: New England Journal of Medicine (1993)

We developed a test to discern small numbers of residual leukemic progenitor cells in the bone marrow of patients with acute lymphoblastic leukemia (ALL) in remission. Preliminary studies revealed that before undergoing bone marrow transplantation such patients differed in their burden of leukemic progenitor cells. These observations suggested that the burden of these cells might influence the risk of relapse after transplantation.
P272 Managing suspected pulmonary embolism in an ambulatory setting: the Barking Havering and Redbridge University Hospitals experience
Authors: F Kleidona, A Salehi, C Dunne, A Choudhury, RH Johns
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> There is an increasing national precedent for ambulatory care of selected patients with suspected pulmonary embolism (PE).<sup>1</sup> As part of our ambulatory services we established an ambulatory PE pathway in January 2012 with the intention to reduce hospitalizations and cost without any associated risk. <h3>Methods</h3> We conducted a retrospective review of all 165 patients referred to the ambulatory service for suspected PE between January 2012 and May 2013. We included 122 patients and we reviewed all medical notes, laboratory and radiological investigations. <h3>Results</h3> In 5 patients (4%), PE was confirmed after imaging. The mean age was 50 years with 68.5% female patients. The most common presenting complaint was chest pain followed by dyspnoea. In 59% of cases the Well’s score was not documented. D-Dimer was checked in 94.5% of patients with unnecessary measurement in 11% of these. In 20% of patients who had radiological investigations for PE, D-dimer was negative. ECG and CXR were performed in most of cases with abnormal findings in 11% and 15% respectively. 77% of patients underwent CTPA, 21% had a V/Q scan, and 2% had V/Q scan followed by CTPA. The mean time to scan was 1.5 days with minimum of 1 day and maximum of 4 days. All confirmed PEs were identified by CTPA and were provoked by risk factors such as recent surgery, recent pregnancy, oral contraceptives, previous documented VTE. Domiciliary enoxoparin was administered in 89% of patients pending CTPA or VQ. All confirmed PEs were subsequently treated with warfarin. No complications occurred, including bleeding events, recurrent VTEs, readmissions for anticoagulation related events, or deaths related to PE. <h3>Conclusions</h3> Our experience shows that selected patients with suspected PE can be safely managed as outpatients in our trust. Closer adherence to the pathway may prevent a number of unnecessary scans (i.e. PE can be safely excluded when Wells score low and D-Dimer negative without a scan). Our protocol and pathways are being updated to incorporate PESI criteria to safely identify ambulatory patients, and to use of rivaroxoban in preference to warfarin for confirmed PE. <h3>Reference</h3> 1 Ladwa RM, <i>et al</i>. <i>Thorax</i> 2011;<b>66</b>:A160
Posthepatitic Cirrhosis Clinically Simulating Extrahepatic Biliary Obstruction (So-Called Primary Biliary Cirrhosis)
Authors: Wallace A. Jones, William A. Tisdale
Journal: New England Journal of Medicine (1963)

IT has long been recognized that parenchymal liver disease clinically can simulate obstruction of extrahepatic biliary radicles.1 , 2 Clinical and laboratory manifestations of obstruction are occasionally encountered in postnecrotic and Laennec's cirrhosis,3 hemochromatosis,4 viral5 6 7 and toxic hepatitis,8 9 10 11 12 granulomas,13 lymphoma,13 metastatic carcinoma13 , 14 and amyloidosis.13 In addition, some patients with normal extrahepatic bile ducts and clinical and laboratory evidence of obstructive jaundice have been classified as having a distinctive clinicopathological entity15 16 17 18 19 20 21 that is variously termed "primary biliary cirrhosis,"15 "cholangiolitic cirrhosis,"22 "pericholangiolitic biliary cirrhosis,"16 "chronic obliterating cholangitis,"23 "hypertrophic cirrhosis of Hanot"24 and "xanthomatous biliary cirrhosis."25 The characteristic clinical features of this condition include chronic . . .
Malakoplakia: Evidence for Monocyte Lysosomal Abnormality Correctable by Cholinergic Agonist in Vitro and in Vivo
Authors: Nabih I. Abdou, Chaiyakiati NaPombejara, Akira Sagawa, Charles Ragland, Daniel J. Stechschulte, Ulf Nilsson, William Gourley, Itaru Watanabe, Norma J. Lindsey, Max S. Allen, Barbara Sooley
Journal: New England Journal of Medicine (1977)

We studied monocyte function in a case of malakoplakia in an attempt to characterize the immune defect in this condition. Our patient's intracellular cyclic-GMP levels were abnormally low (mean +/- S.D. of 0.17 +/- 0.05 pmol per 10(7) malakoplakia cells, versus 0.79 +/- 0.12 in normals) p less than 0.001). After phagocytosis, his monocytes failed to release beta-glucuronidase. In the bactericidal assay, incubation of the patient's monocytes with Escherichia coli allowed growth of 542 +/- 46 colonies, normal monocytes allowed 95 +/- 22 (p less than 0.001). The percentage of monocytes with large lysosomal granules was 23 +/- 4 in the patient and 4 +/- 2 in normal controls. After in vitro incubation of the patient's cells or in vivo treatment with bethanechol chloride, the cyclic-GMP levels, bactericidal ability and lysosomal granules of the cells returned to normal levels. Low levels of cyclic-GMP could impair lysosomal function and bacterial killing in this condition. Cholinergic agonists correct the in vitro abnormalities and are beneficial in vivo.
Review: In women ≥ 40 years of age at average risk, breast cancer screening causes some harms
Authors: Steven C. Krager, Allan V. Prochazka
Journal: Annals of Internal Medicine (2016)

Source Citation Nelson HD, Pappas M, Cantor A, et al. Harms of breast cancer screening: systematic review to update the 2009 U.S. Preventive Services Task Force recommendation. Ann Intern Med. 2016;164:256-67. 26756737
P221 Evaluation of exacerbation frequency and re-hospitalisation, and risk for subsequent exacerbations in asthma patients in a UK primary care setting
Authors: RY Suruki, JB Daugherty, N Boudiaf, FC Albers
Journal: Thorax (2015)

<h3>Introduction and objective</h3> Exacerbations occur in all asthma patients but disproportionately impact those with more severe disease. This study aimed to describe the frequency of exacerbations by asthma severity and the risk for future exacerbation. <h3>Methods</h3> In a retrospective cohort of asthma patients in the CPRD (2009–2011), we defined asthma severity based on asthma medication use and exacerbation history; index date was asthma medical code date. Asthma severity was determined by asthma medication use and exacerbation history during the 12 months preceding the index date. Exacerbations were ascertained during the 12-month follow-up period and were defined as an asthma-related accident and emergency (A&amp;E) department visit or hospitalisation, or any oral corticosteroid (OCS) prescription with an asthma medical code recorded within ±2 weeks. A proportional hazard model was developed to evaluate the risk for subsequent exacerbations associated with the type of exacerbation (OCS vs. ED/hospitalisation). <h3>Results</h3> A total of 211,807 patients with asthma were identified in CPRD during the study period. The mean age was 45 years and females made up 58% of the study population. Of these patients, 17,785 (8.4%) and 3,592 (1.7%) experienced ≥1 and ≥2 exacerbations, respectively during the follow-up period. The proportion of patients experiencing ≥1 or ≥2 exacerbations increased with severity and prior exacerbation frequency (Table 1). Among 1,900 patients with an asthma-related hospitalisation, 2.3%, 3.3%, and 3.8% experienced asthma-related readmissions within 30-, 60-, and 90-days, respectively. When limited to patients with more severe disease, the readmission rates increased significantly, up to three times in those with a history of ≥2 exacerbations. Compared to an OCS defined exacerbation, an A&amp;E visit or hospital admission was associated with a 30% greater risk for any subsequent exacerbation (HR = 1.3, 95% CI 1.15–1.44), after adjusting for gender, disease severity, atopy, and exacerbation history. <h3>Conclusion</h3> Asthma exacerbations remain a burden for patients with severe asthma or a history of frequent exacerbations. Additionally, patients should be managed carefully after an asthma exacerbation as they are at higher risk for subsequent exacerbations and readmission. (GSK-funded; WEUSKOP7092).