tbuckley/cabot-search huggingface dataset:
Abstract 16939: Scar/EF Assessed by Delayed Hyperenhancement Cardiac MRI is a Novel Viability Index Which Independently Predicts Survival in Patients with Severe Ischemic Cardiomyopathy
Authors: Deborah H Kwon, Rory Hachamovitch, Zoran B Popovic, Randall C Starling, Milind Y Desai, Scott D Flamm, Thomas Marwick
Journal: Circulation (2011)

Introduction: Myocardial scar burden (MSB) is an independent predictor of mortality in ischemic cardiomyopathy (ICM). However, the integration of MSB with resultant EF has not previously been assessed as a predictor of outcomes in severe ischemic cardiomyopathy. Purpose: We sought to compare the association of scar/EF and other traditional viability indexes with outcomes in severe ICM. Methods: 335 patients with &gt; 70% stenosis in ≥1 epicardial coronary artery (75% men, median age 64 years, median LV ejection fraction (EF) 22 %, median ESVi 109cc) underwent delayed hyperenhancement(DHE)-MRI between 2003-2007. Scar was defined as &gt; 2 SD above normal myocardium. . LV scar score (summed segmental scar score per patient divided by 17) was recorded as: 0 = none, 1 = 1-25%, 2 = 26-50%, 3 = 51-75%, and 4 = &gt; 75%. LV volumes and LV ejection fraction were calculated Scar/EF was defined as scar score/EF. Cox proportional hazards survival modeling of a composite end-point (CE; cardiac transplantation, all-cause mortality) was used to risk-adjust comparisons. Results: Over a follow-up of up to 8 years[mean 5.5 years], 131 events occurred (126 deaths, 5 cardiac transplantations). Revascularization within 90 days after testing (REV) occurred in 168 patients and was modeled with logistic regression to develop a propensity score. Survival analysis revealed that after adjusting for prior CABG/PCI, sex, diabetes, age, use of CRT, ICD, mitral valve or aortic valve procedures, scar/EF( χ 2 18.4, Global χ 2 53), scar score( χ 2 9, Global χ 2 44.9), EF( χ 2 4.5, Global χ 2 40), ESVi ( χ 2 4.5, Global χ 2 40) were predictors of CE. However, scar/EF was the most powerful, independent predictor of CE in the global model. For each of these models, only the addition of scar/EF further increased the χ 2 power . Conclusions: Scar/EF assessed by DHE-MRI is a novel powerful incremental prognostic viability index in patients with severe ICM and has superior prognostic power compared to traditional viability indexes.
Use of prescription drugs is common during pregnancy, US study finds
Authors: Michael McCarthy
Journal: BMJ (2015)

Four in five pregnant women in the United States have a prescription drug dispensed, and nearly half are given drugs that may be harmful to the fetus, a study of Medicaid records has found.

In the study Kristin Palmsten, of the University of California, San Diego and colleagues reviewed outpatient pharmacy records from 2000 to 2007 on 1 106 757 pregnant women who were covered by Medicaid, the health insurance plan …
Fibrin Gel Investment Associated With Line 1 and Line 10 Solid Tumor Growth, Angiogenesis, and Fibroplasia in Guinea Pigs. Role of Cellular Immunity, Myofibroblasts, Microvascular Damage, and Infarction in Line 1 Tumor Regression&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Harold F. Dvorak, Ann M. Dvorak, Eleanor J. Manseau, Linnea Wiberg, W. Hallowell Churchill
Journal: JNCI Journal of the National Cancer Institute (1979)

Line 1 and line 10 tumors became invested in a fibrin-gel cocoon within hours after transplantation to the subcutaneous spaces of unsensitized syngeneic inbred Sewall Wright strain 2 guinea pigs. The fibrin gel comprised more than 80% of the line 1 tumor mass and, after day 3, became organized and was subsequently replaced by fibrous connective tissue, which gave the tumor the appearance of a scirrhous carcinoma. A cellular infiltrate of lymphocytes and basophils developed at the periphery of line 1 tumors after day 8, and tumors regressed by day 13. The fibrin gel investing the highly malignant line 10 tumors accounted for less than 10% of the tumor mass and persisted without fibrous organization as a tumor grew progressively and invaded adjacent tissues. These data provide new and potentially important insights into the biology of solid tumor growth and the mechanisms of immunologic tumor rejection. Envelopment of tumors in a fibrin gel created an anatomic barrier separating the tumors from the host. Neovascularization mimicking that about line 1 and line 10 tumors was induced by sc fibrin implants; these data suggest that activation of the clotting and/or fibrinolytic systems by tumor cells may itself provide sufficient stimulus for induction of tumor angiogenesis without requiring a separate tumor angiogenesis factor. The scirrhous pattern of growth characteristic of line 1 tumors apparently was achieved by organization of an abundant fibrin gel. Line 1 tumor regression did not for the most part involve direct contacts between tumor cells and any type of inflammatory cell, including macrophages; rather, tumor destruction was effected by ischemic necrosis secondary to widespread microvascular injury. The mechanisms of such injury are uncertain, but tumor rejection was correlated with evidence of developing cellular immunity and anatomic associations between lymphocytes and myofibroblasts. Further experiments will be necessary before these findings can be generalized to other tumor systems.
A Study of the First Year of the End-of-Life Clinic for Physician-Assisted Dying in the Netherlands
Authors: Marianne C. Snijdewind, Dick L. Willems, Luc Deliens, Bregje D. Onwuteaka-Philipsen, Kenneth Chambaere
Journal: JAMA Internal Medicine (2015)

<h3>Importance</h3> Right to Die NL, an organization in the Netherlands that advocates for the option of euthanasia, founded the End-of-Life Clinic in 2012 to provide euthanasia or physician-assisted suicide for patients who meet all legal requirements but whose regular physicians rejected their request. Many patients whose requests are rejected have less common situations, such as a psychiatric or psychological condition, dementia, or being tired of living. <h3>Objective</h3> To study outcomes of requests for euthanasia or physician-assisted suicide received by the clinic and factors associated with granting or rejecting requests. <h3>Design</h3> Analysis of application forms and registration files from March 1, 2012, to March 1, 2013, the clinic's first year of operation, for 645 patients who applied to the clinic with a request for euthanasia or physician-assisted suicide and whose cases were concluded during the study period. <h3>Main Outcomes and Measures</h3> A request could be granted, rejected, or withdrawn or the patient could have died before a final decision was reached. We analyzed bivariate and multivariate associations with medical conditions, type of suffering, and sociodemographic variables. <h3>Results</h3> Of the 645 requests made by patients, 162 requests (25.1%) were granted, 300 requests (46.5%) were refused, 124 patients (19.2%) died before the request could be assessed, and 59 patients (9.1%) withdrew their requests. Patients with a somatic condition (113 of 344 [32.8%]) or with cognitive decline (21 of 56 [37.5%]) had the highest percentage of granted requests. Patients with a psychological condition had the smallest percentage of granted requests. Six (5.0%) of 121 requests from patients with a psychological condition were granted, as were 11 (27.5%) of 40 requests from patients who were tired of living. <h3>Conclusions and Relevance</h3> Physicians in the Netherlands have more reservations about less common reasons that patients request euthanasia and physician-assisted suicide, such as psychological conditions and being tired of living, than the medical staff working for the End-of-Life Clinic. The physicians and nurses employed by the clinic, however, often confirmed the assessment of the physician who previously cared for the patient; they rejected nearly half of the requests for euthanasia and physician-assisted suicide, possibly because the legal due care criteria had not been met.
Complication rate of EUS-FNA and EBUS-TBNA in mediastinal nodal aspiration: A meta-analysis
Authors: Arda van Breda, Bob von Bartheld, Jouke Annema
Journal: European Respiratory Journal (2011)

Introduction:  Esophageal and endobronchial ultrasound-guided fine needle aspiration (EUS-FNA/EBUS-TBNA) are rapidly spreading minimally-invasive techniques for the diagnosis and staging of lung cancer and sarcoidosis. Generally, endosonographic procedures are considered to be safe although several severe complications have been reported in case reports. We performed a meta-analysis to assess the morbidity of EUS and EBUS for mediastinal nodal analysis.   Methods:  A Pubmed and Embase search was performed including all original studies (1999 - October 2010) using EUS and EBUS for mediastinal nodal analysis. Case-reports and studies not mentioning procedure morbidity were excluded from analysis.   Results:  353 studies (118 EUS; 74 EBUS; 10 both) were reviewed of which 151 were excluded form analysis. The other 202 studies consisted of 17200 patients (EUS: 7504 patients, EBUS: 8742, both 954). In those patients, 72 complications (0.42%) were reported of which 36 severe (0.21%) (pneumothorax, n=9; thoracal bleeding, n=5; esophageal rupture, n=5; mediastinitis, n=4) and 36 minor (0.21%) (minor pain, n=10; sore throat, n=9; hemoptysis, n=4; fever, n=2). Of the severe complications 20 occurred at EUS (0.27%) and 12 at EBUS (0.14%). No procedure-related deaths were reported.   Conclusions:  The morbidity of mediastinal nodal endosonography is low and mortality has not been reported. The complication rate might well be an underestimated due to underreporting, publication and performer bias. Further prospective evaluation is warranted to determine the actual complication rate of endosonography and identify possible subsets of patients that are at risk for complications.
Characterisation of COPD patients with long length of stay in our Acute District General Hospital
Authors: Anita Saigal, Yasser Madani, Juno Sunny, Leila Morris, Robin Johns
Journal: European Respiratory Journal (2014)

Introduction: Treating exacerbation accounts for the bulk of COPD healthcare expenditure. Published features associated with long Length of Stay (LoS) following admission include old age (1), extent of co-morbidity and socio-economic deprivation (2).

Aims and Methods: We aimed to identify factors associated with a long LoS at Queens Hospital. According to coding data, 499 patients had a COPD admission from Dec 2012 to May 2013. Median LoS was 5 days and the 90th percentile was 14 days. Data was compared from 46 patients with a LoS around 5 days (short LoS) and 52 patients with a LoS above 14 days (long LoS).

Results: In comparison to short LoS, long LoS was associated with: a higher PaCO2 (7.2 vs 5.6 kPa, p<0.01), higher HCO3 (29 vs 25 mM, p=0.01), higher WCC (13 vs 11 x 109/L, p=0.05), higher CRP (71 vs 41, p=0.05), lower albumin (36 vs 38 g/L, p=0.05), and lower Braden score (18 vs 20, p=0.04). In addition, Long LoS patients more frequently had carers at home prior to admission (40% vs 26%), and required new social care or care home placement on discharge (28% vs 6%).

Discussion: Although differences in biochemical and physiological parameters are associated with long LoS, other very important associations are the need for social support prior to admission and for new social support on discharge. Our hospital COPD population is elderly (Mean age 78 vs 71 in the UK COPD national audit (1)), with extensive co-morbidity, and high levels of socio-economic deprivation. Complex discharge planning will increasingly be a key aspect of hospital COPD management for all as the population ages.

(1) Price LC et al, Thorax 2006, 61: 837-842; (2) Agboado G et al, BMJ Open 2012, 2: e000869.
Granulocytic sarcoma is associated with the 8;21 translocation in acute myeloid leukemia.
Authors: M S Tallman, D Hakimian, J M Shaw, G S Lissner, E J Russell, D Variakojis
Journal: Journal of Clinical Oncology (1993)

PURPOSE Since the only three cases of granulocytic sarcoma among patients with acute myeloid leukemia (AML) seen at our institution during the last 12 years were each associated with the 8;21 translocation [t(8;21)], we sought to determine if this association is specific and more frequent than previously recognized. PATIENTS AND METHODS We report three patients with AML and t(8;21) who developed granulocytic sarcomas, and review the world literature. RESULTS Between 1980 and 1992, 53 cases of AML French-American-British (FAB) M2 were identified at our institution. Eight (15%) patients had t(8;21). Three of these eight patients (38%) developed granulocytic sarcoma. All three of our patients received conventional intensive antileukemic chemotherapy yet had short relapse-free survival durations. Several series of patients with t(8;21) report that granulocytic sarcomas occur in approximately 18% of this population, which is four times the expected incidence in AML. Thirty-seven cases have been previously reported. Although karyotype analyses were not reported in many cases of granulocytic sarcoma in the literature, the vast majority of abnormal karyotypes in patients with AML involved t(8;21). Recent work with a cell line derived from a patient with t(8;21) indicates that such cells are unusually adherent to culture bottles and are aggregable CONCLUSION Our data suggest that this association is more common than generally recognized and may be specific. Patients with t(8;21) should be observed closely for signs and symptoms of granulocytic sarcoma. These patients may have a less favorable prognosis than other patients with t(8;21). Cooperative oncology groups should retrospectively identify patients with AML and t(8;21) who had a poor outcome to determine if they had a disproportionate incidence of granulocytic sarcoma. If so, aggressive therapy such as bone marrow transplantation may be warranted early in the therapeutic strategy.
Tumor Selection In Vivo for Reduced Sensitivity to Natural Resistance and Natural Antibodies&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: D A Chow
Journal: JNCI Journal of the National Cancer Institute (1984)

The contribution of natural antibodies (NAb) to the selective elimination of tumor variants in vivo was studied to further support the hypothesis that NAb participate in host-mediated natural resistance (NR) against neoplasia. Tumors obtained after the sc, ip, or iv inoculation of the natural killer cell-resistant, natural antibody-sensitive L5178Y-F9 tumor clone into syngeneic DBA/2 mice were tested for their sensitivity to NR in the [131l]5-iodo-2′-deoxyuridine elimination assay and to serum NAb in the presence of complement. Cells removed from the ip or sc sites of tumor inoculation exhibited a reduced susceptibility to syngeneic NR and to syngeneic but not to allogeneic NAb. Tumors recovered from the spleen, brain, and lungs after iv inoculation also expressed a decreased sensitivity to both syngeneic NR and NAb. These data suggest that NR against tumors is widely disseminated and support the hypothesis that NAb participate in this antitumor defense, including the control of metastatic spread of disease. Tumors previously selected in vivo also exhibited reduced sensitivity to complement-mediated lysis by NAb acquired in the peritoneum. The correlation observed between this sensitivity to complement and the recovery of tumor cells after the ip injection of L5178Y-F9 contribute to the evidence that NAb acts in vivo.
Metformin and lifestyle modification in polycystic ovary syndrome: systematic review and meta-analysis
Authors: Negar Naderpoor, Soulmaz Shorakae, Barbora de Courten, Marie L. Misso, Lisa J. Moran, Helena J. Teede
Journal: Human Reproduction Update (2016)

Background  Polycystic ovary syndrome (PCOS) is a common endocrine disorder with diverse reproductive and metabolic features. It is underpinned by insulin resistance that is exacerbated by obesity. Lifestyle modification is the first line treatment in PCOS, but it is associated with low adherence and sustainability. In small studies, metformin improves outcomes such as hyperinsulinaemia, ovulation and menstrual cyclicity. We conducted a systematic review and meta-analysis to compare the effect of lifestyle modification + metformin with lifestyle modification ± placebo, and of metformin alone with lifestyle modification ± placebo in PCOS on anthropometric, metabolic, reproductive and psychological outcomes.  Methods  Databases including MEDLINE, EMBASE, Pubmed, Scopus, Cochrane, PsycINFO, CINAHL, Clinical Trials registry and ANZCTR were searched for RCTs conducted on humans and published in English up to August 2014. Inclusion criteria were diagnosis of PCOS based on Rotterdam criteria (inclusive of National Institutes of Health criteria) at any age and with any BMI. Interventions of interest included lifestyle + metformin (with any dose and any duration) or metformin alone compared with lifestyle ± placebo.  Results  Of 2372 identified studies, 12 RCTs were included for analysis comprising 608 women with PCOS. Lifestyle + metformin were associated with lower BMI (mean difference (MD) -0.73 kg/m(2), 95% confidence intervals (CI) -1.14, -0.32, P = 0.0005) and subcutaneous adipose tissue (MD -92.49 cm(2), 95% CI -164.14, -20.84, P = 0.01) and increased number of menstrual cycles (MD 1.06, 95% CI 0.30, 1.82, P = 0.006) after 6 months compared with lifestyle ± placebo. There were no differences in other anthropometric, metabolic (surrogate markers of insulin resistance, fasting and area under the curve glucose, lipids and blood pressure), reproductive (clinical and biochemical hyperandrogenism), and psychological (quality of life) outcomes after 6 months between lifestyle + metformin compared with lifestyle ± placebo. With metformin alone compared with lifestyle ± placebo, weight and BMI were similar after 6 months, but testosterone was lower with metformin.  Conclusions  Lifestyle + metformin is associated with lower BMI and subcutaneous adipose tissue and improved menstruation in women with PCOS compared with lifestyle ± placebo over 6 months. Metformin alone compared with lifestyle showed similar BMI at 6 months. These results suggest the combination of lifestyle with metformin has a role to play in weight management: a key concern for women with PCOS. Existing study limitations include small sample sizes, short durations and risk of bias. With international guidelines now acknowledging that lifestyle and pharmacotherapy are required for weight loss and maintenance in obesity, future studies of appropriate size and duration are vital to clarify the role of metformin in PCOS management.
Long-Range Optical Coherence Tomography of the Neonatal Upper Airway for Early Diagnosis of Intubation-related Subglottic Injury
Authors: Giriraj K. Sharma, Gurpreet S. Ahuja, Maximilian Wiedmann, Kathryn E. Osann, Erica Su, Andrew E. Heidari, Joseph C. Jing, Yueqiao Qu, Frances Lazarow, Alex Wang, Lidek Chou, Cherry C. Uy, Vijay Dhar, John P. Cleary, Nguyen Pham, Kevin Huoh, Zhongping Chen, Brian J.-F. Wong
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Subglottic edema and acquired subglottic stenosis are potentially airway-compromising sequelae in neonates following endotracheal intubation. At present, no imaging modality is capable of in vivo diagnosis of subepithelial airway wall pathology as signs of intubation-related injury.Objectives: To use Fourier domain long-range optical coherence tomography (LR-OCT) to acquire micrometer-resolution images of the airway wall of intubated neonates in a neonatal intensive care unit setting and to analyze images for histopathology and airway wall thickness.Methods: LR-OCT of the neonatal laryngotracheal airway was performed a total of 94 times on 72 subjects (age, 1–175 d; total intubation, 1–104 d). LR-OCT images of the airway wall were analyzed in MATLAB. Medical records were reviewed retrospectively for extubation outcome.Measurements and Main Results: Backward stepwise regression analysis demonstrated a statistically significant association between log(duration of intubation) and both laryngeal (P < 0.001; multiple r2 = 0.44) and subglottic (P < 0.001; multiple r2 = 0.55) airway wall thickness. Subjects with positive histopathology on LR-OCT images had a higher likelihood of extubation failure (odds ratio, 5.9; P = 0.007). Longer intubation time was found to be significantly associated with extubation failure.Conclusions: LR-OCT allows for high-resolution evaluation and measurement of the airway wall in intubated neonates. Our data demonstrate a positive correlation between laryngeal and subglottic wall thickness and duration of intubation, suggestive of progressive soft tissue injury. LR-OCT may ultimately aid in the early diagnosis of postintubation subglottic injury and help reduce the incidences of failed extubation caused by subglottic edema or acquired subglottic stenosis in neonates.Clinical trial registered with www.clinicaltrials.gov (NCT 00544427).
Extracellular component hyaluronic acid and its receptor Hmmr are required for epicardial EMT during heart regeneration
Authors: Maria A. Missinato, Kimimasa Tobita, Nicla Romano, James A. Carroll, Michael Tsang
Journal: Cardiovascular Research (2015)

After injury, the adult zebrafish can regenerate the heart. This requires the activation of the endocardium and epicardium as well as the proliferation of pre-existing cardiomyocytes to replace the lost tissue. However, the molecular mechanisms involved in this process are not completely resolved. In this work, we aim to identify the proteins involved in zebrafish heart regeneration and to explore their function.Using a proteomic approach, we identified Hyaluronan-mediated motility receptor (Hmmr), a hyaluronic acid (HA) receptor, to be expressed following ventricular resection in zebrafish. Moreover, enzymes that produce HA, hyaluronic acid synthases (has), were also expressed following injury, suggesting that this pathway may serve important functions in the regenerating heart. Indeed, suppression of HA production, as well as depletion of Hmmr, blocked cardiac regeneration. Mechanistically, HA and Hmmr are required for epicardial cell epithelial-mesenchymal transition (EMT) and their subsequent migration into the regenerating ventricle. Furthermore, chemical inhibition of Focal Adhesion Kinase (FAK) or inhibition of Src kinases, downstream effectors of Hmmr, also prevented epicardial cell migration, implicating a HA/Hmmr/FAK/Src pathway in this process. In a rat model of myocardial infarction, both HA and HMMR were up-regulated and localized in the infarct area within the first few days following damage, suggesting that this pathway may also play an important role in cardiac repair in mammals.HA and Hmmr are required for activated epicardial cell EMT and migration involving the FAK/Src pathway for proper heart regeneration.