tbuckley/cabot-search huggingface dataset:
Bariatric Surgery for Patients With Type 2 Diabetes—Reply
Authors: Chih-Cheng Hsu, Wei-Jei Lee
Journal: JAMA Surgery (2015)

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Combined Plasma and Cerebrospinal Fluid Signature for the Prediction of Midterm Progression From Mild Cognitive Impairment to Alzheimer Disease
Authors: Benoit Lehallier, Laurent Essioux, Javier Gayan, Roxana Alexandridis, Tania Nikolcheva, Tony Wyss-Coray, Markus Britschgi
Journal: JAMA Neurology (2015)

A reliable method of detecting Alzheimer disease (AD) in its prodromal state is needed for patient stratification in clinical trials or for personalizing existing or potential upcoming therapies. Current cerebrospinal fluid (CSF)- or imaging-based single biomarkers for AD offer reliable identification of patients with underlying AD but insufficient prediction of the rate of AD progression.To optimize prediction of progression from mild cognitive impairment (MCI) to AD dementia by combining information from diverse patient variables.This cohort study from the Alzheimer Disease Neuroimaging Initiative (ADNI) enrolled 928 patients with MCI at baseline and 249 selected variables available in the ADNI data set. Variables included clinical and demographic data, cognitive scores, magnetic resonance imaging-based brain volumetric data, the apolipoprotein E (APOE) and translocase of outer mitochondrial membrane 40 homolog (TOMM40) genotypes, and analyte levels measured in the CSF and plasma. Data were collected in July 2012 and analyzed from July 1, 2012, to June 1, 2015.Progression from MCI to AD within 1 to 6 years. To determine whether combinations of markers could predict progression from MCI to AD within 1 to 6 years, the elastic net algorithm was used in an iterative resampling of a training- and test-based variable selection and modeling approach.Among the 928 patients with MCI in the ADNI database, 94 had 224 of the required variables available for the modeling. The results showed the contributions of age, Clinical Dementia Rating Sum of Boxes composite test score, hippocampal volume, and multiple plasma and CSF factors in modeling progression to AD. A combination of apolipoprotein A-II and cortisol levels in plasma and fibroblast growth factor 4, heart-type fatty acid binding protein, calcitonin, and tumor necrosis factor-related apoptosis-inducing ligand receptor 3 (TRAIL-R3) in CSF allowed for reliable prediction of disease status 3 years from the time of sample collection (80% classification accuracy, 88% sensitivity, and 70% specificity).These study findings suggest that a combination of markers measured in plasma and CSF, distinct from β-amyloid and tau, could prove useful in predicting midterm progression from MCI to AD dementia. Such a large-scale, multivariable-based analytical approach could be applied to other similar large data sets involving AD and beyond.
Coronary heart disease in women
Authors: H Tunstall-Pedoe, C Morrison, K McGeechan
Journal: BMJ (1994)

EDITOR, - Three papers in the issue of 3 September follow the recent publication of findings in 38 populations worldwide from the World Health Organisation's MONICA project (to monitor the trends in and determinants of cardiovascular diseases).4 Our comparison from the Scottish MONICA project in Glasgow from 1985 to 1991 of 3991 myocardial infarctions and coronary deaths in men with 1551 in women (aged 25-64) gives an added perspective.

The international study (which used standardised criteria monitored from Dundee) shows a negative correlation in women, but not men, between population event rates and case fatality at 28 days. Case fatality among women is highest where coronary disease is uncommon, and non-fatal cases in women may be being missed, but is similar to that among men where coronary event rates are high.4 However, this report (besides incidentally redefining the alleged French paradox5,6 as common to southern Europe) also shows a difference between the sexes in how suddenly and where deaths occur, …
Cancer screening in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS)
Authors: P. C. Nathan, K. K. Ness, M. M. Hudson, M. Mahoney, J. S. Ford, W. Landier, G. Armstrong, T. Henderson, L. L. Robison, K. C. Oeffinger
Journal: Journal of Clinical Oncology (2009)

CRA6501 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. No significant financial relationships to disclose.
Fine-Tuning Risk Stratification for Acute Pulmonary Embolism With Cardiac Biomarkers**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Samuel Z. Goldhaber
Journal: Journal of the American College of Cardiology (2010)

Rapid and accurate risk stratification of acute pulmonary embolism (PE) has focused on the anatomic size of the thrombus as well as the PE's physiological effects on systemic arterial pressure, heart rate, and chest computed tomographic or echocardiographic evidence of right ventricular enlargement
Abstract 17493: Simultaneous High-Density Contact Mapping plus Ablation of the Left Atrium for the Treatment of Atrial Fibrillation: a Novel Multi-Electrode Catheter System
Authors: Hans Kottkamp, Dan Reinders, Saar Moisa, Ashkan Sardari, Daniel Weinkam, Jeff Brewster, Kevin Chaplin
Journal: Circulation (2014)

Introduction:  Current catheter technology for treatment of atrial fibrillation (AF) is limited by several factors, e.g. instability of the ablation electrode, missing options for simultaneous high-density mapping, or pulmonary vein isolation (PVI) only.   Hypothesis:  A novel single-catheter multi-electrode system was developed for “global” treatment of AF, i.e. simultaneous high-density contact mapping (e.g. voltage mapping, rotor mapping) plus radiofrequency (RF) ablation (e.g. PVI, substrate modification).   Methods:  The system consists of an array with 20 ribs containing up to 275 gold electrodes, which can be expanded within the body of the left atrium (LA) to a spherical, partially compliant device that contacts the atrial wall in a stable position. RF energy can be applied simultaneously at multiple electrodes as required for the individually tailored ablation of target tissue. The tracing of the ablation sites and subsequent ablation are done remotely in the control room. RF power output is determined by the system based on electrode contact. The temperature sensors are located 25μm behind each electrode. After extensive in-vitro testing, the catheter was deployed in-vivo in 5 canines for mapping and ablation.   Results:  In in-vitro studies, the mean lesion depth measured 3.2±0.4, 3.7±0.4, 4.1±0.4, 4.8±0.3, and 5.1±0.3mm, respectively, depending on the temperature set point of 53, 55, 57, 59, and 61°C. In in-vivo studies, ablation lesion creation parameters ranged in temperature from 52-59 °C with application times of 60-180 seconds. Successful isolation was achieved in all 5 animals. Continuous “wave mapping” allowed for on-line observation of LA activation spread during ablation and for on-line confirmation of PVI or isolation of other targets (e.g. “box” isolation). Contiguity of lesion lines and lesion transmurality was confirmed by histology.   Conclusions:  This multielectrode array is a completely new catheter concept permitting simultaneous high-density contact mapping of the entire LA plus RF ablation with a single device. Chronically, the lesions were shown to be contiguous, transmural and durable. The first in-human use is planned in a clinical study for Q4 of 2014.
Rituximab Maintenance for a Maximum of 5 Years After Single-Agent Rituximab Induction in Follicular Lymphoma: Results of the Randomized Controlled Phase III Trial SAKK 35/03
Authors: Christian Taverna, Giovanni Martinelli, Felicitas Hitz, Walter Mingrone, Thomas Pabst, Lidija Cevreska, Auro del Giglio, Anna Vanazzi, Daniele Laszlo, Johann Raats, Daniel Rauch, Daniel A. Vorobiof, Andreas Lohri, Christine Biaggi Rudolf, Stéphanie Rondeau, Corinne Rusterholz, Ingmar A.F.M. Heijnen, Emanuele Zucca, Michele Ghielmini
Journal: Journal of Clinical Oncology (2015)

Purpose Rituximab maintenance therapy has been shown to improve progression-free survival in patients with follicular lymphoma; however, the optimal duration of maintenance treatment remains unknown. Patients and Methods Two hundred seventy patients with untreated, relapsed, stable, or chemotherapy-resistant follicular lymphoma were treated with four doses of rituximab monotherapy in weekly intervals (375 mg/m 2 ). Patients achieving at least a partial response were randomly assigned to receive maintenance therapy with one infusion of rituximab every 2 months, either on a short-term schedule (four administrations) or a long-term schedule (maximum of 5 years or until disease progression or unacceptable toxicity). The primary end point was event-free survival (EFS). Progression-free survival, overall survival (OS), and toxicity were secondary end points. Comparisons between the two arms were performed using the log-rank test for survival end points. Results One hundred sixty-five patients were randomly assigned to the short-term (n = 82) or long-term (n = 83) maintenance arms. Because of the low event rate, the final analysis was performed after 95 events had occurred, which was before the targeted event number of 99 had been reached. At a median follow-up period of 6.4 years, the median EFS was 3.4 years (95% CI, 2.1 to 5.3) in the short-term arm and 5.3 years (95% CI, 3.5 to not available) in the long-term arm (P = .14). Patients in the long-term arm experienced more adverse effects than did those in the short-term arm, with 76% v 50% of patients with at least one adverse event (P &lt; .001), five versus one patient with grade 3 and 4 infections, and three versus zero patients discontinuing treatment because of unacceptable toxicity, respectively. There was no difference in OS between the two groups. Conclusion Long-term rituximab maintenance therapy does not improve EFS, which was the primary end point of this trial, or OS, and was associated with increased toxicity.
Phase II trial of 177Lutetium radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 (177Lu- J591) in patients (pts) with metastatic castrate-resistant prostate cancer (metCRPC)
Authors: S. T. Tagawa, M. I. Milowsky, M. J. Morris, S. Vallabhajosula, S. Goldsmith, D. Matulich, J. Kaplan, F. Berger, H. I. Scher, N. H. Bander, D. M. Nanus
Journal: Journal of Clinical Oncology (2008)

5140 Background: A phase 1 trial of 177Lu-J591 in pts with metCRPC demonstrated acceptable toxicity, excellent targeting of met sites and biologic activity. Methods: Two successive cohorts of pts with progressive metCRPC receive one dose of 177Lu -J591: Cohort 1 (65mCi/m2), 15 pts; Cohort 2: (70mCi/m2, phase I MTD), 17 pts. The 1° endpoint is PSA and/or measurable disease response at 12 weeks; 2° endpoint is toxicity. A 177Lu-J591 imaging study was performed to confirm tumor targeting. Results: 30 of 32 planned pts have been treated to date; the final 2 pts are in screening. Median age is 72 (range 51–88), median baseline PSA 81.6 (3.3 - 2184.6). 3 with ECOG PS 0, 25 PS 1, 2 PS 2; 97% had bone mets, 23% extra-osseous visceral mets (2 liver, 5 lung, 1 adrenal). Pts progressed after multiple hormonal therapies and 18 (60%) pts progressed on docetaxel. PSA responses are shown in the table. Overall progression free survival (PFS) was 82 days [95% CI 67.4, 96.6] and overall survival (OS) 357 days [182.8, 531.1]; median OS of pts experiencing PSA declines of >30% was 513 days. 6 pts have PFS >14 weeks (1 > 47 weeks); 2 pts remain on study. Excellent targeting of known sites of PC metastases was seen in 29 of 30 (97%) pts. Toxicity: 9 patients received 1–4 platelet transfusions (median 2); no significant hemorrhagic complications occurred. Of 30 evaluable pts, 27 had return to normal platelet counts; the remaining 3 had progressive disease with marrow involvement. 6 pts in cohort 2 received brief granulocyte growth factor support. No serious drug-related non-hematologic toxicity has occurred. Conclusions: Single dose 177Lu-J591 was generally well tolerated, with reversible myelosuppression, and demonstrates anti-tumor activity in pts with progressive metCRPC. An apparent dose-response relationship exists for both toxicity and activity, with more responses seen at the phase I MTD. PSA Response Best PSA Response Cohort 1 (n; %) Cohort 2 (n; %) TOTAL (n; %) ≥ 50% decline 1 (7%) 2 (13%) 3 (10%) ≥ 30% decline 2 (13%) 7 (47%) 9 (30%) 0–29% decline 5 (33%) 3 (20%) 8 (27%) 1–25% increase 4 (27%) 1 (7%) 5 (17%) >25% increase 4 (27%) 4 (27%) 8 (27%) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration BZL Biologics Inc Pfizer, sanofi-aventis
Endocrine Effects of Inhaled Corticosteroids in Children
Authors: Chirag R. Kapadia, Todd D. Nebesio, Susan E. Myers, Steven Willi, Bradley S. Miller, David B. Allen, Elka Jacobson-Dickman
Journal: JAMA Pediatrics (2015)

Inhaled corticosteroids (ICSs) are widely used as first-line treatment for various chronic respiratory illnesses. Advances in devices and formulations have reduced their local adverse effects. However, as delivery of ICSs to the lungs improves, the systemic absorption increases, and an adverse effect profile similar to, although milder than, oral corticosteroids has emerged. The most serious potential adverse effect is adrenal insufficiency, which can be life threatening. Adrenal insufficiency occurs most in patients taking the highest doses of ICSs but is reported with moderate or even low doses as well. Our recommendations include greater vigilance in testing adrenal function than current standard practice. In patients with diabetes mellitus (types 1 and 2), an increase in glucose levels is likely, and diabetes medication adjustment may be needed when initiating or increasing ICSs. The risk of linear growth attenuation and adverse effects on bone mineral density is generally low but should be considered in the face of additional risk factors. On behalf of the Pediatric Endocrine Society Drugs and Therapeutics Committee, we present a review of the endocrine adverse effects of ICSs in children and offer recommendations relating to testing and referral. Limited data in particular realms diminish the strength of certain recommendations, and clinical judgment continues to be paramount.
Infrequency of isolation of HTLV-III virus from saliva in AIDS [letter]
Authors: Ho Dd, Byington Re, Schooley Rt, Flynn T, Rota Tr, Hirsch Ms
Journal: New England Journal of Medicine (1985)

The acquired immunodeficiency syndrome (AIDS) is a sexually transmitted disease that can also be transmitted through contaminated blood or blood products.  This fact is supported in part by the recovery of human T-cell lymphotropic virus Type III (HTLV-III) the etiologic agent of AIDS from blood and semen.  However the report of HTLV-III isolation from the saliva of infected patients has raised concern about the possible casual transmission of this virus although epidemiologic studies have not supported casual contagion.  In the past 12 months we have attempted to isolate HTLV-III from 83 saliva samples from 71 homosexual men seropositive for HTLV-III who were studied at the Massachusetts General Hospital.  All saliva specimens were cultured within 60 minutes after collection.  In addition blood was also obtained from 50 of the 71 men for virus isolation.  Our results are summarized in Table I.  1 of 83 saliva specimens was positive for HTLV-III whereas 28 of 50 blood cultures (56%) yielded the virus.  The virus-positive saliva (unfiltered) was obtained from a patient with AIDS who had pneumocystis pneumonia candidal esophagitis and thrush.  His saliva culture demonstrated reverse transcriptase activity only after 21 days in culture.  In contrast his blood culture showed reverse transcriptase activity on day 3.  This suggests that the HTLV-III titer of this patients saliva was substantially less than that of his blood.  The infrequent isolation of HTLV-III from saliva reported here is unlikely to be due to improper methods because our isolation rate from the blood of infected persons is comparable to those reported by other laboratories.  In addition we have had little difficulty in recovering the virus from the cerebrospinal fluid and neural tissues of HTLV-III-infected patients with neurologic dynfunction.  Therefore we conclude that HTLV-III is present infrequently in the saliva of infected persons.  When it was detected in the saliva of 1 patient with intraoral disease the amount of virus present was small.  These findings are consistent with epidemiologic data indicating the casual transmission of HTLV-III does not occur even among household members exposed to the saliva of infected persons.  These results may be useful in allaying public concern regarding the casual spread of AIDS and HTLV-III infection.  (full text)
Breast Cancer Risk in Childhood Cancer Survivors Without a History of Chest Radiotherapy: A Report From the Childhood Cancer Survivor Study
Authors: Tara O. Henderson, Chaya S. Moskowitz, Joanne F. Chou, Angela R. Bradbury, Joseph Phillip Neglia, Chau T. Dang, Kenan Onel, Danielle Novetsky Friedman, Smita Bhatia, Louise C. Strong, Marilyn Stovall, Lisa B. Kenney, Dana Barnea, Elena Lorenzi, Sue Hammond, Wendy M. Leisenring, Leslie L. Robison, Gregory T. Armstrong, Lisa R. Diller, Kevin C. Oeffinger
Journal: Journal of Clinical Oncology (2015)

Little is known about the breast cancer risk among childhood cancer survivors who did not receive chest radiotherapy. We sought to determine the magnitude of risk and associated risk factors for breast cancer among these women.We evaluated cumulative breast cancer risk in 3,768 female childhood cancer survivors without a history of chest radiotherapy who were participants in the Childhood Cancer Survivor Study.With median follow up of 25.5 years (range, 8 to 39 years), 47 women developed breast cancer at a median age of 38.0 years (range, 22 to 47 years) and median of 24.0 years (range, 10 to 34 years) from primary cancer to breast cancer. A four-fold increased breast cancer risk (standardized incidence ratio [SIR] = 4.0; 95% CI, 3.0 to 5.3) was observed when compared with the general population. Risk was highest among sarcoma and leukemia survivors (SIR = 5.3; 95% CI, 3.6 to 7.8 and SIR = 4.1; 95% CI, 2.4 to 6.9, respectively). By the age of 45 years, the cumulative incidence of breast cancer in sarcoma and leukemia survivors was 5.8% (95% CI, 3.7 to 8.4) and 6.3% (95% CI, 3.0 to 11.3), respectively. No other primary cancer diagnosis was associated with an elevated risk. Alkylators and anthracyclines were associated with an increased breast cancer risk in a dose-dependent manner (P values from test for trend were both < .01).Women not exposed to chest radiotherapy who survive childhood sarcoma or leukemia have an increased risk of breast cancer at a young age. The data suggest high-dose alkylator and anthracycline chemotherapy increase the risk of breast cancer. This may suggest a possible underlying gene-environment interaction that warrants further study.
Reply
Authors: Kathie Béland, Fernando Alvarez
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. Anti‐CD20 has been successfully administered to autoimmune hepatitis (AIH) patients showing an incomplete response or frequent relapses when under treatment with standard immunosuppression, including prednisone either alone or in association with azathioprine, mycophenolate mofetil, cyclosporine, or tacrolimus.1 Therefore, in these patients, it cannot be excluded that B‐cell depletion could have been induced while the immune system was still affected by previous therapy. However, if and how their immunological status differed from that of naïve patients (or our treatment‐naïve AIH model) are unknown. Pilot studies using anti‐CD20 antibodies as initial treatment for AIH are needed to address this issue. B‐cell depletion can exacerbate colitis in an animal model of cholangitis based on transforming growth factor beta (TGF‐β) receptor II‐dominant negative mice.2 However, in patients with primary biliary cirrhosis showing an incomplete response to ursodeoxycholic acid, anti‐CD20 antibody treatment did not induce colitis.3 These patients showed an increased frequency of regulatory T cells and expression of TGF‐β and decreased expression of tumor necrosis factor alpha (TNF‐α)3; an interesting observation given that current treatments for inflammatory bowel diseases aim at reducing TNF‐α levels. Type 1 regulatory T cells cells, through their capacity to produce high amounts of interleukin‐10, are efficient in suppressing innate immune response.5 However, in the case of an AIH, the adaptive immune system is the main pathway in cause, giving to FoxP3 T‐regulatory cells a central role in the suppression of liver inflammation.4 Altogether, our preclinical data on B‐cell depletion4 and published data in AIH patients1 suggest that prospective studies using anti‐CD20 as initial therapy to induce remission in patients with AIH are indicated. These studies will be able to provide safety profile and design tailored protocols for different subtypes of AIH patients, including those with other comorbidities. Initial therapy should allow a rapid, complete remission of liver inflammation with minimal or no side effects to avoid or diminish the evolution to cirrhosis or recover from liver failure; such is not the case with currently administered immunosuppressive drugs.
Third National Cancer Survey—An Overview of Available Information
Authors: S J Cutler, J Scotto, S S Devesa, R R Connelly
Journal: JNCI Journal of the National Cancer Institute (1974)

Data were collected in the Third National Cancer Survey, which covered nine geographic areas with a combined population of 21 million people. During the 3-year period 1969–71, a total of 181,027 new cancers were diagnosed, excluding in situ carcinomas and nonmelanoma skin cancer. Data are presented on the incidence of cancer by primary site and the variation by sex and race. A special feature of the survey was the detailed classification of histologic information, examples of which are included. Examples of supplementary information collected for a 10% sample are presented, including duration of hospitalization, cost of hospitalization and sources of payment, extent of disease at diagnosis, and treatment. Highlights of a special 6-month survey on the incidence of non melanoma skin cancer are also given.