tbuckley/cabot-search huggingface dataset:
Diet, Serum Cholesterol, and Death from Coronary Heart Disease
Authors: Richard B. Shekelle, Anne MacMillan Shryock, Oglesby Paul, Mark Lepper, Jeremiah Stamler, Shuguey Liu, William J. Raynor
Journal: New England Journal of Medicine (1981)

Over twenty years ago, we evaluated diet, serum cholesterol, and other variables in 1900 middle-aged men and repeated the evaluation one year later. No therapeutic suggestions were made. Vital status was determined at the 20th anniversary of the initial examination. Scores summarizing each participant's dietary intake of cholesterol, saturated fatty acids, and polyunsaturated fatty acids were calculated according to the formulas of Keys and Hegsted and their coworkers. The two scores were highly correlated, and results were similar for both: there was a positive association between diet score and serum cholesterol concentration at the initial examination, a positive association between change in diet score and change in serum cholesterol concentration from the initial to the second examination, and a positive association prospectively between mean base-line diet score and the 19-year risk of death from coronary heart disease. These associations persisted after adjustment for potentially confounding factors. The results support the conclusion that lipid composition of the diet affects serum cholesterol concentration and risk of coronary death in middle-aged American men. (N Engl J Med. 1981; 304:65–70.)
FRI0570 At Pre-Clinical Stage; Connective Tissue Disease is Indistinguishable from Other Inflammatory Arthritis on Ultrasound in Ccp-Negative Early Arthritis Patients:
Authors: A.S. Zayat, A. Aleyan, E.M. Hensor, P. Emery, E.M. Vital
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> ANA positivity is a common finding in patients presenting with inflammatory joints symptoms without connective tissue disease (CTD) features. These patients can be seropositive (i.e. CCP and RF) or sero-negative. A group of these patients may not have enough findings to meet the RA classification criteria. There are limited data on long-term prognosis (i.e. disease progression) on this subgroup of patients. <h3>Objectives</h3> To assess if musculoskeletal ultrasound (US) can predict future diagnosis of CTD in ANA-positive CCP negative arthralgia. <h3>Methods</h3> Patients with new inflammatory joint symptoms presented to early arthritis clinic where recruited into Inflammatory Arthritis Continuum (IACON) study. These patients neither satisfied OA nor CTD diagnosis at presentation. Patients had a baseline clinical and imaging assessment and were followed up over 1-4 years for determination of ultimate diagnosis at endpoint. US imaging of hands, wrists, elbows, knees, feet and ankle was performed. Synovitis and erosions were assessed using OMERACT definitions and scoring. The analysis focused on ANA positive patients. To compare baseline US between endpoint diagnosis groups, Kruskal-Wallis tests were used. <h3>Results</h3> A total of 151 ANA positive patients were recruited; 73 (48.3%) were CCP negative, of whom 17 (23%) satisfied the RA classification criteria at presentation, 45 (61%) were diagnosed as undifferentiated inflammatory arthritis (UA) and 11 (15%) had other diagnoses. Of the 45 UA patients, after 1-4 years of follow up, 10 (22%) were ultimately diagnosed as CTD (4 SLE, 2 systemic sclerosis, 3 primary Sjogren9s syndrome and one undifferentiated CTD). The remaining 35 satisfied other diagnostic criteria or remained undifferentiated. After 12 months, 9/10 patients with an endpoint diagnosis of CTD had persistent ANA positivity compared to 13.4% of the other patients. In those with UA at baseline, 33.3% of endpoint CTD patients had ultrasound synovitis (GS ≥2 and/or PD≥1) at baseline in comparison to 45% of endpoint inflammatory arthritis (IA), 50% of endpoint UA and 44% of other non-inflammatory diagnoses. GS and PD scores at baseline did not differ between endpoint diagnoses (Table 1). <h3>Conclusions</h3> In absence of CCP, patients with ANA-positive early onset inflammatory arthritis that were ultimately diagnosed as a CTD were clinically and sonographically indistinguishable from those were ultimately diagnosed as seronegative RA or SpA. Although PD appears to be present in third of CTDs in the early pre-diagnosis phases, this cannot in its own predict the CTD development. Similarly, presence of PD synovitis did not mean development of specific IA such as RA. <h3>Disclosure of Interest</h3> None declared
Pain, Hurt, and Harm -- The Ethics of Pain Control in Infants and Children
Authors: Gary A. Walco, Robert C. Cassidy, Neil L. Schechter
Journal: New England Journal of Medicine (1994)

It has long been recognized that patients receive less relief from pain than they should1,2. A recent review concluded that pain can be relieved effectively in 90 percent of patients but is not relieved effectively in 80 percent of patients3. The tendency toward undermedication for pain is even more pronounced in children than in adults4. There are large discrepancies between the amounts of postoperative analgesia ordered for and administered to adults and those ordered for and administered to children who have the same diagnoses and have undergone the same procedures5,6.Interest in pain control . . .
A Study of Urinary and Serum Lysozyme in Patients with Renal Disease
Authors: Darwin J. Prockop, Warren D. Davidson
Journal: New England Journal of Medicine (1964)

LYSOZYME, a bacteriolytic enzyme discovered in 1922 by Sir Alexander Fleming,2 is found in a number of biologic fluids. The enzyme is a basic protein of low molecular weight that lyses susceptible bacteria by a reaction with cell-wall mucopolysaccharides releasing N-acetyl amino sugars and N-acetyl amino sugar-peptide complexes.3 Kidney contains more lysozyme activity than any other mammalian tissue,4 but little, if any, lysozyme activity is found in normal urine.5 , 6 Lysozymuria has been reported in some children with nephrotic syndrome7 and in some adults with renal disease,6 but no definitive evidence of the source of urinary lysozyme is available.In the . . .
Association of<i>BIM</i>Deletion Polymorphism With Intrinsic Resistance to EGFR Tyrosine Kinase Inhibitors in Patients With Lung Adenocarcinoma
Authors: Shang-Gin Wu, Yi-Nan Liu, Chong-Jen Yu, Pan-Chyr Yang, Jin-Yuan Shih
Journal: JAMA Oncology (2016)

This study explores the impact of BIM polymorphism on treatment outcome of patients with advanced adenocarcinoma, comparing those who experienced primary resistance with those who had partial response after treatment with epidermal growth factor receptor tyrosine kinase inhibitors.
S57 Short-term clinically important deterioration predicts long-term clinical outcome in COPD patients: A post-hoc analysis of the TORCH trial
Authors: I Naya, L Tombs, P Jones
Journal: Thorax (2015)

<h3>Background</h3> COPD is a progressive disease leading to adverse outcomes such as exacerbations and death. Numerous predictors of these outcomes have been identified, based on observations at single time points, but little is known about disease trajectory as a predictor of long-term outcome. We hypothesised that the occurrence of a composite measure of clinically important deterioration (CID) made up of moderate/severe exacerbations, worsening of FEV<sub>1</sub> or St George’s Respiratory Questionnaire (SGRQ) total score measured over 6 months may predict future long-term adverse outcomes. <h3>Method</h3> A <i>post hoc</i> analysis of the TORCH data, in all four treatment arms, was performed in 5292 (86.5%) of the 6112 COPD patients in the study at 6-months (day 182). CID was defined as: decrease of ≥100 mL in post-bronchodilator FEV<sub>1</sub>, or increase of ≥4 units in the SGRQ, or a moderate/severe exacerbation. Using day 182 status, we tested the association between the occurrence of any CID type at or before 6 months and outcomes over the next 30 months including: sustained deterioration in FEV<sub>1</sub> and SGRQ scores, moderate/severe exacerbations and mortality. A Cox’s proportional hazards model used day 182 deterioration status with covariates collected at day 182, smoking status and geographical region to estimate future risk. <h3>Results</h3> By day 182, 2870 [54%] patients had experienced a CID (CID+) and 2422 [46%] had not (CID-). 30 months later, the CID- group had a LS mean post-bronchodilator FEV<sub>1 </sub>117 ml (95% CL 100,134; p &lt; 0.001) higher compared to the CID+ group and the SGRQ total score was 6.4 units (95% CL 5.4, 7.5; p &lt; 0.001) better. Over the same period, post CID+ patients had a 61% (95% CL 50, 72%; p &lt; 0.001) increased risk of a new moderate/severe exacerbation and a 41% (95% CL 15, 72%; p &lt; 0.001) increased risk of all-cause death vs. the CID- group (see Figure 1). <h3>Conclusion</h3> Patients experiencing a clinically important deterioration early in the TORCH trial appeared to be set on a clinical path of sustained deterioration in both health status and FEV<sub>1 </sub>with an increased medium/long-term future risk of exacerbations and all-cause death.
Fate of Chromatin of Interphase Nuclei Subjected to “Prophasing” in Virus-Fused Cells2
Authors: Sei-ichi Matsui, Herbert Weinfeld, Avery A. Sandberg
Journal: JNCI Journal of the National Cancer Institute (1972)

The fate of chromatin of interphase nuclei (G1, S, or G2) of cells fused by means of Sendai virus with metaphase cells has been studied in a Chinese hamstercell line (DON). “Prephasing” of such interphase nuclei was differentiated from the metaphase chromosomes by 3H-thymidine labeling of their DNA before cell fusion. After prophasing reached its peak, Colcemid was removed from the culture to permit the binucleate cells to enter a G1 state. Interphase S or G1 chromatin became randomly distributed to daughter cells, when metaphase chromosomes underwent karyokinesis or subsequent cytokinesis, and persisted either as nuclear fragments or micronuclei. In a subsequent nuclear division, Sand G1 chromatin again were subject to prophasing and emerged again as “pulverized” chromatin, an indication of continuousasynchrony with the original metaphase nucleus. This contrasts with the behavior of G2 chromatin. The latter amalgamated with the metaphase chromatin to form a nucleus-like structure. In subsequent mitoses, most G2 chromatin was reorganized as intact metaphase chromosomes among those representative of the original metaphase cell. In this case, the G2 chromatin became synchronized with the original metaphase chromatin. Thus, providing the interphase nucleus is in G2, prophasing in a binucleate cell containing a metaphase set of chromosomes can be followed by events simulating metaphase as well. It is concluded that the metaphase cell contains factors capable of inducing many events of a normal mitosis.
Avoiding Bias in the Conduct and Reporting of Cost-Effectiveness Research Sponsored by Pharmaceutical Companies
Authors: Alan L. Hillman, John M. Eisenberg, Mark V. Pauly, Bernard S. Bloom, Henry Click, Bruce Kinosian, J. Sanford Schwartz
Journal: New England Journal of Medicine (1991)

Because of the growing focus on containing health care costs, pharmaceutical companies are trying to demonstrate the cost effectiveness of their products relative to alternatives. In Europe and Australia, economic analyses are often required for government approval and pricing of new pharmaceuticals. In the United States, such analyses are increasingly being used for marketing and to obtain formulary approval. Because of the corporate need for timely results and confidentiality about a new drug in the period before marketing begins and because other financial support is limited, pharmaceutical companies themselves sponsor most academic research into the cost effectiveness of pharmaceuticals. The . . .
Association of Androgen Deprivation Therapy With Depression in Localized Prostate Cancer
Authors: Kathryn T. Dinh, Gally Reznor, Vinayak Muralidhar, Brandon A. Mahal, Michelle D. Nezolosky, Toni K. Choueiri, Karen E. Hoffman, Jim C. Hu, Christopher J. Sweeney, Quoc-Dien Trinh, Paul L. Nguyen
Journal: Journal of Clinical Oncology (2016)

Purpose Androgen deprivation therapy (ADT) may contribute to depression, yet several studies have not demonstrated a link. We aimed to determine whether receipt of any ADT or longer duration of ADT for prostate cancer (PCa) is associated with an increased risk of depression. Methods We identified 78,552 men older than age 65 years with stage I to III PCa using the SEER-Medicare–linked database from 1992 to 2006, excluding patients with psychiatric diagnoses within the prior year. Our primary analysis was the association between pharmacologic ADT and the diagnosis of depression or receipt of inpatient or outpatient psychiatric treatment using Cox proportional hazards regression. Drug data for treatment of depression were not available. Our secondary analysis investigated the association between duration of ADT and each end point. Results Overall, 43% of patients (n = 33,882) who received ADT, compared with patients who did not receive ADT, had higher 3-year cumulative incidences of depression (7.1% v 5.2%, respectively), inpatient psychiatric treatment (2.8% v 1.9%, respectively), and outpatient psychiatric treatment (3.4% v 2.5%, respectively; all P &lt; .001). Adjusted Cox analyses demonstrated that patients with ADT had a 23% increased risk of depression (adjusted hazard ratio [AHR], 1.23; 95% CI, 1.15 to 1.31), 29% increased risk of inpatient psychiatric treatment (AHR, 1.29; 95% CI, 1.17 to 1.41), and a nonsignificant 7% increased risk of outpatient psychiatric treatment (AHR, 1.07; 95% CI, 0.97 to 1.17) compared with patients without ADT. The risk of depression increased with duration of ADT, from 12% with ≤ 6 months of treatment, 26% with 7 to 11 months of treatment, to 37% with ≥ 12 months of treatment (P trend &lt; .001). A similar duration effect was seen for inpatient (P trend &lt; .001) and outpatient psychiatric treatment (P trend &lt; .001). Conclusion Pharmacologic ADT increased the risk of depression and inpatient psychiatric treatment in this large study of elderly men with localized PCa. This risk increased with longer duration of ADT. The possible psychiatric effects of ADT should be recognized by physicians and discussed with patients before initiating treatment.
Replacement of the Aortic Root with a Pulmonary Autograft in Children and Young Adults with Aortic-Valve Disease
Authors: Nicholas T. Kouchoukos, Victor G. Davila-Roman, Thomas L. Spray, Suzan F. Murphy, Johanna B. Perrillo
Journal: New England Journal of Medicine (1994)

The optimal substitute for severely diseased aortic valves in children and young adults is unknown. The use of a mechanical prosthesis requires permanent treatment of the patient with anticoagulants and is associated with thromboembolic and hemorrhagic complications. Aortic-valve allografts and porcine bioprostheses, which do not necessitate anticoagulant therapy, may deteriorate and have limited durability.
HER-2/Neu overepression in gastric cancer
Authors: R. Vergara, I. Torrazza, O. Castillo Fernandez
Journal: Journal of Clinical Oncology (2009)

e15679 Background: Gastric cancer is one of the most frequent causes of cancer-related deaths in the world.Overexpression of human epidermal growth factor receptor 2 (HER-2) has been shown to be a significant negative prognostic variable, with estimates ranging from 6- 35%. This is the first study done in our country regarding HER-2 overexpresion in gastric cancer. Methods: 90 cases with histologic diagnosis of gastric cancer were reviewed, in the period between October 2007 and July 2008. Formalin-fixed paraffin- embedded gastric cancer specimens were tested for HER-2 status using Herceptest (Dako). They were analyzed with HER-2 scores for gastric cancer. Other parameters evaluated were: demographic, clinical, histological characteristics, and treatment administrared. Results: The average age of our patients was 60.3 ± 15.8 years, with similar gender distribution. The more frequent symptoms of presentation were loss of weight (68.9%) and dyspepsia (58.9%). The most frequent anatomical location was the antrum (32%). HER-2 overexpression was 5.6% (four cases of intestinal type and one case of diffuse type). 63.3% of the patients presented with clinical stage IV, which is associated with worse survival (p&lt; 0.001). 40% of the patients underwent complete surgical excision of the neoplasia, from which 44% received adjuvant chemotherapy and radiotherapy. 52.2% of the patients had already died when developing this study. Conclusions: The majority of our patients presented with advange stage at the time of diagnosis, HER-2 overexpression was 5.6%. There was no statistical significance when comparing it with the histological type, nor survival (p= 0.086). No significant financial relationships to disclose.
Impact of Donor Epstein-Barr Virus Serostatus on the Incidence of Graft-Versus-Host Disease in Patients With Acute Leukemia After Hematopoietic Stem-Cell Transplantation: A Study From the Acute Leukemia and Infectious Diseases Working Parties of the European Society for Blood and Marrow Transplantation
Authors: Jan Styczynski, Gloria Tridello, Lidia Gil, Per Ljungman, Jennifer Hoek, Simona Iacobelli, Katherine N. Ward, Catherine Cordonnier, Hermann Einsele, Gerard Socie, Noel Milpied, Hendrik Veelken, Patrice Chevallier, Ibrahim Yakoub-Agha, Johan Maertens, Didier Blaise, Jan Cornelissen, Mauricette Michallet, Etienne Daguindau, Eefke Petersen, Jakob Passweg, Hildegard Greinix, Rafael F. Duarte, Nicolaus Kröger, Peter Dreger, Mohamad Mohty, Arnon Nagler, Simone Cesaro
Journal: Journal of Clinical Oncology (2016)

Purpose We investigated the effect of Epstein-Barr virus (EBV) serostatus on the overall outcome of allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Patients and Methods The study included 11,364 patients who underwent allogeneic peripheral-blood or bone marrow transplantation for acute leukemia between 1997 and 2012. We analyzed the impact of donor and recipient EBV serologic status on overall survival, relapse-free survival, relapse incidence, nonrelapse mortality, and incidence of graft-versus-host disease (GVHD) after allo-HSCT. Results Patients receiving grafts from EBV-seropositive donors had the same overall survival as patients who received grafts from EBV-seronegative donors (hazard ratio [HR], 1.05; 95% CI, 0.97 to 1.12; P = .23). Seropositive donors also had no influence on relapse-free survival (HR, 1.04; 95% CI, 0.97 to 1.11; P = 0.31), relapse incidence (HR, 1.03; 95% CI, 0.94 to 1.12; P = .58), and nonrelapse mortality (HR, 1.05; 95% CI, 0.94 to 1.17; P = .37). However, in univariate analysis, recipients receiving grafts from seropositive donors had a higher risk of chronic GVHD than those with seronegative donors (40.8% v 31.0%, respectively; P &lt; .001; HR, 1.42; 95% CI, 1.30 to 1.56). When adjusting for confounders, higher risk was identified for both acute and chronic GVHD. In seronegative patients with seropositive donors, the HR for chronic GVHD was 1.30 (95% CI, 1.06 to 1.59; P = .039). In seropositive patients with seropositive donors, the HR was 1.24 (95% CI, 1.07 to 1.45; P = .016) for acute GVHD and 1.43 (95% CI, 1.23 to 1.67; P &lt; .001) for chronic GVHD. Seropositive patients with seronegative donors did not have an increased risk of GVHD. Conclusion Our data suggest that donor EBV status significantly influences development of acute and chronic GVHD after allo-HSCT.
P22 Derangements in energy, amino-acid and gut microbial metabolism in hepatic encephalopathy: a metabolomic approach
Authors: J Bajaj, N Patel, D Heuman, A Sanyal, D Bell
Journal: Gut (2010)

Introduction  Hepatic encephalopathy (HE) pathogenesis is related to gut microbial products, which lead to deranged cerebral bioenergetics. Biofluid MR spectroscopy (MRS) can be used to determine changes in bioenergetics, gut microbial products, amino acid and lipid metabolites. Lactulose is used as a first-line HE Rx despite a poor evidence basis.  Aim  To evaluate the clinical and metabolic consequences of lactulose withdrawal in HE.  Method  Patients with cirrhosis on lactulose for precipitated HE underwent cognitive testing with inhibitory control (ICT), urine and serum collection for MRS and inflammatory markers while on lactulose. Lactulose was then withdrawn and patients followed for 30 days with visits at day 2, 14 and 30; ICT, serum and urine testing were repeated at every visit. Relapse of HE was defined clinically. Multivariate analysis of urine and serum metabolites involved principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA). Univariate analysis was applied to hypothesis-driven metabolites, multivariate-driven metabolites and inflammatory marker concentrations.  Results  7 cirrhotic men (age 53±7 years, 5 HCV, 2 alcohol) on lactulose for 6±5 months for precipitated HE (5 GI bleed, 2 infections) were included. Three patients clinically relapsed 38±6 days post-withdrawal; all 3 had >15 ICT lures while on lactulose. None of those who scored  15 as a cut-off for HE relapse, MRS distinguished with a sensitivity and specificity of 70.0%/63.6% using urine and 100%/100% using serum on PLS-DA. Urine PLS-DA: In relapsers, urine TMAO was reduced indicating altered gut bacterial metabolism while malonic acid and citrate were higher demonstrating impaired energetics. Glycine and phenylalanine, associated with false neuro-transmitters, were also increased in relapsers along with creatinine. Serum PLS-DA: Relapsers had higher choline and its metabolite, dimethylglycine levels which is associated with extrusion of choline after astrocyte swelling in HE as well as higher levels of lipids. Univariate analysis confirmed that relapsers had lower TMAO (p=0.00280) and higher choline (p=0.0414), LDL (0.0265) and creatinine (p=0.00970). Inflammation was depressed in relapsers compared to others evidenced by decreased endotoxin (p=0.03), IFN-γ (p=0.045), IL-4 (0.0002) and TNF-α (p=0.0013) suggesting a compensatory anti-inflammatory response syndrome.  Conclusion  HE relapse post-lactulose withdrawal is associated with derangements in bioenergetics, amino-acid, lipid and gut microbial metabolism as well as depression of the inflammatory response.
Case 18-2006
Authors: William J. Triggs, Robert H. Brown, Daniel L. Menkes
Journal: New England Journal of Medicine (2006)

A 57-year-old woman had had progressive numbness and weakness of the feet and legs since her early 30s. She had had dilated, fixed, and unequal pupils since adolescence. Her father had similar symptoms with his feet and legs, as well as dilated pupils and impotence. Two of her brothers, her son, and her daughter had neuropathy, dilated pupils, or both. A diagnostic procedure was performed.
Withholding and withdrawal of life-sustaining treatments in low-middle-income versus high-income Asian countries and regions
Authors: Jason Phua, Gavin M. Joynt, Masaji Nishimura, Yiyun Deng, Sheila Nainan Myatra, Yiong Huak Chan, Nguyen Gia Binh, Cheng Cheng Tan, Mohammad Omar Faruq, Yaseen M. Arabi, Bambang Wahjuprajitno, Shih-Feng Liu, Seyed Mohammad Reza Hashemian, Waqar Kashif, Dusit Staworn, Jose Emmanuel Palo, Younsuck Koh
Journal: Intensive Care Medicine (2016)