tbuckley/cabot-search huggingface dataset:
Disability During the Last Two Years of Life
Authors: Alexander K. Smith, Louise C. Walter, Yinghui Miao, W. John Boscardin, Kenneth E. Covinsky
Journal: JAMA Internal Medicine (2013)

<h3>Importance</h3> Whereas many persons at advanced ages live independently and are free of disability, we know little about how likely older people are to be disabled in the basic activities of daily living that are necessary for independent living as they enter the last years of life. <h3>Objective</h3> To determine national estimates of disability during the last 2 years of life. <h3>Design</h3> Prospective cohort study. <h3>Setting</h3> A nationally representative study of older adults in the United States. <h3>Participants</h3> Participants 50 years and older who died while enrolled in the Health and Retirement Study between 1995 and 2010. Each participant was interviewed once at a varying time point in the last 24 months of life. We used these interviews to calculate national estimates of the prevalence of disability across the 2 years prior to death. We modeled the prevalence of disability in the 2 years prior to death for groups defined by age at death and sex. <h3>Main Outcomes and Measures</h3> Disability was defined as need for help with at least 1 of the following activities of daily living: dressing, bathing, eating, transferring, walking across the room, and using the toilet. <h3>Results</h3> There were 8232 decedents (mean [SD] age at death, 79 [11] years; 52% women). The prevalence of disability increased from 28% (95% CI, 24%-31%) 2 years before death to 56% (95% CI, 52%-60%) in the last month of life. Those who died at the oldest ages were much more likely to have disability 2 years before death (ages 50-69 years, 14%; 70-79 years, 21%; 80-89 years, 32%; 90 years or more, 50%;<i>P</i>for trend, &lt;.001). Disability was more common in women 2 years before death (32% [95% CI, 28%-36%]) than men (21% [95% CI, 18%-25%];<i>P</i> &lt; .001), even after adjustment for older age at death. <h3>Conclusions and Relevance</h3> Those who live to an older age are likely to be disabled, and thus in need of caregiving assistance, many months or years prior to death. Women have a substantially longer period of end-of-life disability than men.
Obstructive Sleep Apnea–Hypopnea and Incident Stroke
Authors: Susan Redline, Gayane Yenokyan, Daniel J. Gottlieb, Eyal Shahar, George T. O'Connor, Helaine E. Resnick, Marie Diener-West, Mark H. Sanders, Philip A. Wolf, Estella M. Geraghty, Tauqeer Ali, Michael Lebowitz, Naresh M. Punjabi
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Although obstructive sleep apnea is associated with physiological perturbations that increase risk of hypertension and are proatherogenic, it is uncertain whether sleep apnea is associated with increased stroke risk in the general population.Objectives: To quantify the incidence of ischemic stroke with sleep apnea in a community-based sample of men and women across a wide range of sleep apnea.Methods: Baseline polysomnography was performed between 1995 and 1998 in a longitudinal cohort study. The primary exposure was the obstructive apnea–hypopnea index (OAHI) and outcome was incident ischemic stroke.Measurements and Main Results: A total of 5,422 participants without a history of stroke at the baseline examination and untreated for sleep apnea were followed for a median of 8.7 years. One hundred ninety-three ischemic strokes were observed. In covariate-adjusted Cox proportional hazard models, a significant positive association between ischemic stroke and OAHI was observed in men (P value for linear trend: P = 0.016). Men in the highest OAHI quartile (>19) had an adjusted hazard ratio of 2.86 (95% confidence interval, 1.1–7.4). In the mild to moderate range (OAHI, 5–25), each one-unit increase in OAHI in men was estimated to increase stroke risk by 6% (95% confidence interval, 2–10%). In women, stroke was not significantly associated with OAHI quartiles, but increased risk was observed at an OAHI greater than 25.Conclusions: The strong adjusted association between ischemic stroke and OAHI in community-dwelling men with mild to moderate sleep apnea suggests that this is an appropriate target for future stroke prevention trials.
Early Enhanced Parenteral Nutrition, Hyperglycemia, and Death Among Extremely Low-Birth-Weight Infants
Authors: Hans Jorgen Stensvold, Kenneth Strommen, Astri M. Lang, Tore G. Abrahamsen, Eline Kjorsvik Steen, Are H. Pripp, Arild E. Ronnestad
Journal: JAMA Pediatrics (2015)

Efforts to optimize early parenteral nutrition (PN) in extremely low-birth-weight (ELBW) infants to promote growth and development may increase hyperglycemia risk. Recent studies have identified an association between early hyperglycemia and adverse outcomes in ELBW infants.To examine the prevalence of early hyperglycemia and clinical outcomes among ELBW infants before (2002-2005) and after (2006-2011) the implementation of an early enhanced PN protocol and to assess the independent effects of early enhanced PN and early hyperglycemia on mortality.Observational cohort study in a level III neonatal intensive care unit. Prospectively collected clinical data in the neonatal intensive care unit's medical database, nutritional information, and blood glucose levels were merged for analysis. All ELBW infants born between January 1, 2002, and December 31, 2011, without lethal malformations and still alive at 12 hours of life were eligible for inclusion in the study.Mortality was the main outcome measure. Severe hyperglycemia was defined as 2 consecutive blood glucose levels exceeding 216 mg/dL at least 3 hours apart. A multivariable logistic regression model was applied to determine the independent effects of early enhanced PN and hyperglycemia on mortality.In total, 343 infants were included in the study, 129 in a historical comparison group before the enhanced PN protocol and 214 in the early enhanced PN group. Baseline characteristics were similar between the study groups. After the introduction of early enhanced PN, the prevalence of severe hyperglycemia during the first week of life was higher in the early enhanced PN group (11.6% [15 of 129] vs 41.6% [89 of 214], P < .001), as was the mortality (10.9% [14 of 129] vs 24.3% [52 of 214], P = .003). When adjusting for background characteristics, treatment, and nutritional data, early severe hyperglycemia remained a strong independent risk factor for death (odds ratio, 4.68; 95% CI, 1.82-12.03), together with gestational age (odds ratio, 0.62; 95% CI, 0.49-0.79).The implementation of an enhanced PN protocol was correlated with an increased prevalence of severe hyperglycemia and higher mortality. In the multivariable analysis, an enhanced PN regimen per se was not predictive of mortality, whereas early severe hyperglycemia remained strongly predictive of death. To avoid detrimental effects on outcomes in ELBW infants, the optimal composition of early PN to avoid postnatal growth failure must be carefully balanced against hyperglycemia risk.
Survivin as a Prognostic Marker for Urothelial Carcinoma of the Bladder: A Multicenter External Validation Study
Authors: Shahrokh F. Shariat, Pierre I. Karakiewicz, Guilherme Godoy, Jose A. Karam, Raheela Ashfaq, Yves Fradet, Hendrik Isbarn, Francesco Montorsi, Claudio Jeldres, Patrick J. Bastian, Matthew E. Nielsen, Stefan C. Mller, Arthur I. Sagalowsky, Yair Lotan
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The aim of the current study was to externally validate the value of survivin as a prognostic marker for bladder cancer in a large multi-institutional cohort of patients treated with radical cystectomy. Methods: The study comprised 726 patients treated with radical cystectomy and bilateral pelvic lymphadenectomy. Survivin staining and scoring were done with automated systems coupled with advanced color detection software. Specimens showing at least 10 reactivity were considered altered. Predictive accuracy was quantified using the concordance index and 200-bootstrap resamples were used to reduce overfit bias. Results: Survivin was an independent predictor of disease recurrence and cancer-specific survival in multivariable analyses that controlled for the effects of standard clinicopathologic features (hazard ratios, 1.6; P values 0.002). In all patients (n = 726), addition of survivin to a model including standard clinicopathologic variables did not improve its predictive accuracy (P = 0.67 for disease recurrence and P = 0.27 for cancer-specific survival). In the subgroup of patients with pT1-3N0M0 disease (n = 398), addition of survivin improved the accuracy of standard clinicopathologic features for prediction of disease recurrence and cancer-specific survival (1.3, P &amp;lt; 0.001 and 1.2, P &amp;lt; 0.001, respectively). Conclusions: Survivin expression improves our accuracy for prediction of cancer recurrence and survival in pT1-3N0M0 patients by a small but statistically significant margin. Our findings support the need for further evaluation of survivin and its signaling pathways as well as survivin-targeted therapies in bladder cancer. (Clin Cancer Res 2009;15(22):70129)
Diagnosing and treating psoriatic arthritis: an update
Authors: W.H. Boehncke, A. Qureshi, J.F. Merola, D. Thaçi, G.G. Krueger, J. Walsh, N. Kim, A.B. Gottlieb
Journal: British Journal of Dermatology (2013)

Journal Article Diagnosing and treating psoriatic arthritis: an update Get access W.H. Boehncke, W.H. Boehncke Geneva University Hospital Rue Gabrielle Perret‐Gentil 4 1211 Geneva 14 Switzerland Search for other works by this author on: Oxford Academic Google Scholar A. Qureshi, A. Qureshi Department of Dermatology Brigham and Women's Hospital 221 Longwood Avenue Boston MA 02115 U.S.A Search for other works by this author on: Oxford Academic Google Scholar J.F. Merola, J.F. Merola Department of Dermatology Brigham and Women's Hospital 221 Longwood Avenue Boston MA 02115 U.S.ADepartment of Dermatology Brigham and Women's Hospital 75 Francis Street Boston MA 02115 U.S.A Search for other works by this author on: Oxford Academic Google Scholar D. Thaçi, D. Thaçi Comprehensive Center for Inflammation Medicine University of Lübeck Ratzeburger Allee 160 23435 Lübeck Germany Search for other works by this author on: Oxford Academic Google Scholar G.G. Krueger, G.G. Krueger Dermatology University Hospital University of Utah Clinic 28 50 North Medical Drive Salt Lake City UT 84132 U.S.A Search for other works by this author on: Oxford Academic Google Scholar J. Walsh, J. Walsh University of Utah 50 North Medical Drive Salt Lake City UT 84132 U.S.A Search for other works by this author on: Oxford Academic Google Scholar N. Kim, N. Kim Tufts Medical Center 800 Washington Street, #231 Boston MA 02111 U.S.A Search for other works by this author on: Oxford Academic Google Scholar A.B. Gottlieb A.B. Gottlieb Tufts Medical Center 800 Washington Street, #114 Boston MA 02111 U.S.A Correspondence Alice B. Gottlieb. E‐mail: agottlieb@tuftsmedicalcenter.org Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 170, Issue 4, 1 April 2014, Pages 772–786, https://doi.org/10.1111/bjd.12748 Published: 01 April 2014
Thyroid Hormone, Thyromimetics, and Metabolic Efficiency
Authors: Einav Yehuda-Shnaidman, Bella Kalderon, Jacob Bar-Tana
Journal: Endocrine Reviews (2013)

Abstract Thyroid hormone (TH) has long been recognized as a major modulator of metabolic efficiency, energy expenditure, and thermogenesis. TH effects in regulating metabolic efficiency are transduced by controlling the coupling of mitochondrial oxidative phosphorylation and the cycling of extramitochondrial substrate/futile cycles. However, despite our present understanding of the genomic and nongenomic modes of action of TH, its control of mitochondrial coupling still remains elusive. This review summarizes historical and up-to-date findings concerned with TH regulation of metabolic energetics, while integrating its genomic and mitochondrial activities. It underscores the role played by TH-induced gating of the mitochondrial permeability transition pore (PTP) in controlling metabolic efficiency. PTP gating may offer a unified target for some TH pleiotropic activities and may serve as a novel target for synthetic functional thyromimetics designed to modulate metabolic efficiency. PTP gating by long-chain fatty acid analogs may serve as a model for such strategy.
The P2X7 Receptor Channel: Recent Developments and the Use of P2X7 Antagonists in Models of Disease
Authors: Rachael Bartlett, Leanne Stokes, Ronald Sluyter
Journal: Pharmacological Reviews (2014)

The P2X7 receptor is a trimeric ATP-gated cation channel found predominantly, but not exclusively, on immune cells. P2X7 activation results in a number of downstream events, including the release of proinflammatory mediators and cell death and proliferation. As such, P2X7 plays important roles in various inflammatory, immune, neurologic and musculoskeletal disorders. This review focuses on the use of P2X7 antagonists in rodent models of neurologic disease and injury, inflammation, and musculoskeletal and other disorders. The cloning and characterization of human, rat, mouse, guinea pig, dog, and Rhesus macaque P2X7, as well as recent observations regarding the gating and permeability of P2X7, are discussed. Furthermore, this review discusses polymorphic and splice variants of P2X7, as well as the generation and use of P2X7 knockout mice. Recent evidence for emerging signaling pathways downstream of P2X7 activation and the growing list of negative and positive modulators of P2X7 activation and expression are also described. In addition, the use of P2X7 antagonists in numerous rodent models of disease is extensively summarized. Finally, the use of P2X7 antagonists in clinical trials in humans and future directions exploring P2X7 as a therapeutic target are described.
Ectopic Production of ACTH by a Minor Salivary Gland Tumor
Authors: ALLAN D. MARKS
Journal: Annals of Internal Medicine (1975)

Letters1 October 1975Ectopic Production of ACTH by a Minor Salivary Gland TumorALLAN D. MARKS, M.D., YOUNG NAM KIM, M.D., HOWARD S. KROOP, M.D.ALLAN D. MARKS, M.D.Search for more papers by this author, YOUNG NAM KIM, M.D.Search for more papers by this author, HOWARD S. KROOP, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-83-4-521 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSince the initial description of adrenocorticotropic hormone (ACTH) production by a nonpituitary tumor, more than 200 examples of "the ectopic ACTH syndrome" have been reported. Of these, a salivary gland (parotid) carcinoma has been suggested as the source of ectopic ACTH in only one previous case (1). In the present report a patient is described in whom a minor salivary gland (palatine) adenocarcinoma was responsible for the ectopic ACTH syndrome.A 62-year-old woman was admitted to Temple University Hospital in September 1973 because of an ulcerating mass lesion at the junction of the hard and soft palates. The patient had...References1. JARRETTLACYKIPNIS LPD: Characterization by immunofluorescence of an ACTH-like substance in nonpituitary tumors from patients with hyperadrenocorticism. J Clin Endocrinol 24:543-549 1964 CrossrefGoogle Scholar2. RATCLIFFEKNIGHTBESSER JRG: Tumor and plasma ACTH concentrations with and without the ectopic ACTH syndrome. Clin Endocrinol 1:27-44, 1972 CrossrefMedlineGoogle Scholar3. AMATRUDA T: Non-endocrine secreting tumors, in Duncan's Diseases of Metabolism, 6th ed., edited by BONDY PK. Philadelphia, W. B. Saunders Company, 1969, pp. 1227-1244 Google Scholar4. WEICHERT R: The neural ectodermal origin of the peptidesecreting endocrine glands. Am J Med 49:232-241, 1970 CrossrefMedlineGoogle Scholar5. LEVINEMETZ RS: A classification of ectopic hormoneproducing tumors. Ann NY Acad Sci 230:533-546, 1974 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Temple University Hospital Philadelphia, Pennsylvania 19140 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByEctopic Cushing Syndrome in Adenocarcinoma of the Lung: Case Report and Literature ReviewEctopic ACTH Production and Cushing’s Syndrome in a Patient with Parotid Acinic Cell Carcinoma with High-Grade Transformation: Tumor Context and Clinical ImplicationsColonic adenocarcinoma associated ectopic ACTH secretion: A case historyThe Ectopic ACTH SyndromeTHE CHARACTERIZATION OF THE ACTH PRODUCED BY A PRIMARY PITUITARY TUMOUR IN A PATIENT WITH CUSHING'S DISEASE 1 October 1975Volume 83, Issue 4Page: 521-522KeywordsAdenocarcinomaAdrenocorticotropic hormoneLesionsSalivary gland tumorsSalivary glandsUlcers Issue Published: 1 October 1975 PDF DownloadLoading ...
Coronary Bypass Graft Patency in Patients With Diabetes in the Bypass Angioplasty Revascularization Investigation (BARI)
Authors: Leonard Schwartz, Kevin E. Kip, Robert L. Frye, Edwin L. Alderman, Hartzell V. Schaff, Katherine M. Detre
Journal: Circulation (2002)

Few studies have compared long-term status of bypass grafts between patients with and without diabetes, and uncertainty exists as to whether diabetes independently predicts poor clinical outcome after CABG.Among 1526 patients in BARI who underwent CABG as initial revascularization, 99 of 292 (34%) with treated diabetes mellitus (TDM) (those on insulin or oral hypoglycemic agents) and 469 of 1234 (38%) without TDM had follow-up angiography. Angiograms with the longest interval from initial surgery and before any percutaneous graft intervention (mean 3.9 years) were reviewed. An average of 3.0 grafts were placed at initial CABG for patients with TDM (n=297; internal mammary artery [IMA], 33%) and 2.9 grafts for patients without TDM (n=1347; IMA, 34%). Patients with TDM were more likely than those without to have small (<1.5 mm) grafted distal vessels (29% versus 22%) and vessels of poor quality (9% versus 6%). On follow-up angiography, 89% of IMA grafts were free of stenoses > or =50% among patients with TDM versus 85% among patients without TDM (P=0.23). For vein grafts, the corresponding percentages were 71% versus 75% (P=0.40). After statistical adjustment, TDM was unrelated to having a graft stenosis > or =50% (adjusted odds ratio, 0.87; 95% CI, 0.58 to 1.32).Despite diabetic patients' having smaller distal vessels and vessels judged to be of poorer quality, diabetes does not appear to adversely affect patency of IMA or vein grafts over an average of 4-year follow-up. Previously observed differences in survival between CABG-treated patients with and without diabetes may be largely a result of differential risk of mortality from noncardiac causes.
Why Most Gene Expression Signatures of Tumors Have Not Been Useful in the Clinic
Authors: Serge Koscielny
Journal: Science Translational Medicine (2010)

Omics technologies are expected to enhance our understanding of a variety of diseases and to open the door to patient-specific personalized medicine. Despite the extensive literature on the use of gene expression arrays to predict prognosis in cancer patients, poor progress has been made in the translation of gene expression signatures for use in the clinics. Breast cancer provides a ripe arena for an analysis of why such signatures have failed to fulfill their promise.
Cutaneous Immunization Rapidly Activates Liver Invariant Vα14 NKT Cells Stimulating B-1 B Cells to Initiate T Cell Recruitment for Elicitation of Contact Sensitivity
Authors: Regis A. Campos, Marian Szczepanik, Atsuko Itakura, Moe Akahira-Azuma, Stephane Sidobre, Mitchell Kronenberg, Philip W. Askenase
Journal: The Journal of Experimental Medicine (2003)

T cell recruitment to elicit contact sensitivity (CS) requires a CS-initiating process mediated by B-1 cells that produce IgM, which activates complement to promote T cell passage into the tissues. We now show that Vα14i NKT cells induce B-1 cell activation likely by releasing IL-4 early postimmunization. The CS initiation process is absent in Jα18−/− and CD1d−/− NKT cell–deficient mice and is reconstituted by populations enriched for Vα14i NKT cells. Transfers are not effective if cells are derived from IL-4−/− mice. Staining with specific tetramers directly showed that hepatic Vα14i NKT cells increase by 30 min and nearly double by 2 h postimmunization. Transfer of immune B-1 cells also reconstitutes CS responses in NKT cell–deficient mice. The B-1 cells act downstream of the Vα14i NKT cells to restore CS initiation. In addition, IL-4 given systemically to Jα18−/− or CD1d−/− NKT cell–deficient mice reconstitutes elicitation of CS. Further, splenocytes from immune Jα18−/− mice produce less antigen (Ag)-specific IgM antibodies compared with sensitized WT mice. Together these findings indicate that very early after skin immunization Vα14i NKT cells are stimulated to produce IL-4, which activates B-1 cells to produce Ag-specific IgM, subsequently needed to recruit effector T cells for elicitation of CS responses.
Cranial Stereotactic Radiosurgery: Current Status of the Initial Paradigm Shifter
Authors: Jason P. Sheehan, Chun-Po Yen, Cheng-Chia Lee, Jay S. Loeffler
Journal: Journal of Clinical Oncology (2014)

The concept of stereotactic radiosurgery (SRS) was first described by Lars Leksell in 1951. It was proposed as a noninvasive alternative to open neurosurgical approaches to manage a variety of conditions. In the following decades, SRS emerged as a unique discipline involving a collegial partnership among neurosurgeons, radiation oncologists, and medical physicists. SRS relies on the precisely guided delivery of high-dose ionizing radiation to an intracranial target. The focused convergence of multiple beams yields a potent therapeutic effect on the target and a steep dose fall-off to surrounding structures, thereby minimizing the risk of collateral damage. SRS is typically administered in a single session but can be given in as many as five sessions or fractions. By providing an ablative effect noninvasively, SRS has altered the treatment paradigms for benign and malignant intracranial tumors, functional disorders, and vascular malformations. Literature on extensive intracranial radiosurgery has unequivocally demonstrated the favorable benefit-to-risk profile that SRS affords for appropriately selected patients. In a departure from conventional radiotherapeutic strategies, radiosurgical principles have recently been extended to extracranial indications such as lung, spine, and liver tumors. The paradigm shift resulting from radiosurgery continues to alter the landscape of related fields.