tbuckley/cabot-search huggingface dataset:
When lecturers need patient consent
Authors: S M Yentis
Journal: BMJ (2006)

M edical ethics places much emphasis on patients' autonomy and the importance of informed consent, exemplified by detailed guidance on consent for clinical treatment or investigation and for research. Consent (or lack of it) is also relevant when students and doctors learn, and when medical journals publish educational case reports. The use of patients' information in medical presentations, however, seems to be largely ignored. For example, of nine royal colleges (of 13 contacted) replying to inquiries I made in preparing this article, only one issued specific guidance to lecturers about showing patients' photographs at its meetings—although one was considering it as a result. A further two colleges referred, on their websites, to the General Medical Council's guidance on audiovisual recordings of patients (www.gmc-uk.org/guidance/library/making_audiovisual.asp), and the website of one college referred to similar guidance issued by the BMA (http://www.bma.org.uk/ap.nsf/AttachmentsByTitle/PDFAVrecordings/$FILE/AV.pdf). None of the three US colleges that replied (of eight contacted) issued guidance to speakers, although all referred to US legislation governing patients' confidentiality (www.hhs.gov/ocr/hipaa).

> Strictly, …
Abstract 2873: A molecular signature predictive of indolent prostate cancer
Authors: Shazia Irshad, Mukesh Bansal, Clementine L. Magnen, Risham Dillon, Mireia Castillo-Martin, Tian Zheng, Alvaro Aytes, Sven Wenske, Paolo Guarnieri, Pavel Sumazin, Mitchell Benson, Michael M. Shen, Andrea Califano, Cory Abate-Shen
Journal: Cancer Research (2014)

Abstract With more than 230,000 estimated new cases in 2013, prostate cancer represents the most commonly diagnosed cancer in American men. While a subgroup of patients will develop an aggressive and lethal prostate cancer, most present with a low-risk form of the disease that requires little or no treatment. It is therefore crucial to distinguish patients whose tumors are likely to progress to aggressive disease from those whose tumors will remain indolent and for whom treatment may be more detrimental than beneficial. In our recent study, we hypothesized that low Gleason score prostate tumors can be distinguished as indolent and aggressive based on expression of genes associated with aging and senescence (1). Using gene set enrichment analyses and a decision tree learning model, we identified a 3-gene panel_FGFR1, PMP22, and CDKN1A_that is enriched in indolent prostate cancers and accurately predicts outcome of low Gleason score tumors at both the RNA and protein levels. In particular, protein expression of this 3-gene panel in biopsy samples correctly distinguished Gleason 6 patients who failed active surveillance over a 10-year period. Following from our initial study, our current efforts are focused on exploiting this 3-gene panel to develop a robust clinical assay for distinguishing indolent and aggressive tumors. We are currently using qRT-PCR, immunofluorescence, and immunohistochemistry assays to assess the most effective way to quantify the simultaneous expression of the 3-gene panel in low Gleason score tumor biopsies/tissues. This quantitative assay will ultimately be applied to a large cohort study assessing the predictive power of the 3-gene signature in patients under active surveillance. We envision that such a prognostic test will significantly improve our ability to predict the outcome of patients with low Gleason score tumors and facilitate appropriate decisions of treatment for men under active surveillance. 1. Irshad S, et al. (2013) A molecular signature predictive of indolent prostate cancer. Science translational medicine 5(202):202ra122. Citation Format: Shazia Irshad, Mukesh Bansal, Clementine Le Magnen, Risham Dillon, Mireia Castillo-Martin, Tian Zheng, Alvaro Aytes, Sven Wenske, Paolo Guarnieri, Pavel Sumazin, Mitchell Benson, Michael M. Shen, Andrea Califano, Cory Abate-Shen. A molecular signature predictive of indolent prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2873. doi:10.1158/1538-7445.AM2014-2873
Abstract 4956: A Risk Stratification Analysis of Predictors of Death or Transplant in Children with Hypertrophic Cardiomyopathy
Authors: Steven E Lipshultz, E J Orav, James D Wilkinson, Jeffrey A Towbin, Jane Messere, April M Lowe, Sarah K Clunie, Gerald F Cox, Paul R Lurie, Daphne T Hsu, Charles E Canter, Steven D Colan
Journal: Circulation (2008)

We previously reported initial results from a univariate analysis of baseline predictors of death or heart transplant in children with hypertrophic cardiomyopathy (HCM). We present here the final multivariate analysis resulting in risk stratification rules for 6 HCM etiologic subgroups in children. The Pediatric Cardiomyopathy Registry collected longitudinal data on 882 children with HCM from 1990 –2003. The primary outcome was the earlier of death or heart transplantation. Cox regression was used to identify the 3 most important risk factors at time of diagnosis for each HCM subgroup; all echo measures were expressed as z-scores. Multivariate analysis revealed that children with idiopathic HCM diagnosed by 1 year were at higher risk of poor outcome if they had CHF, low BSA, or elevated LV mass, while risk factors for children diagnosed after 1 year were female gender, depressed fractional shortening, and elevated wall thickness. Risk factors for children with malformation syndrome were Black race, CHF and increased wall thickness; Black race, younger age, and elevated LV mass for children with inborn errors of metabolism; younger age, CHF, and increased wall thickness for children with mixed restrictive HCM; and decreased weight, family history of heart disease, and increased wall thickness for children with mixed dilated HCM. Children with multiple risk factors present at diagnosis had a significantly worse prognosis compared to those with 0 or 1 risk factors. (Figure ) Based on etiologic subtype and number of risk factors present at diagnosis, clinicians can reliably estimate the risk of death of transplant in children with HCM.
Abstract 2926: PNA as novel targeted cancer therapy for BRAFV600E mutant melanoma
Authors: Jeffrey H. Rothman, Oliver Surriga, Shyamprasad D. Vasudeva, Grazia Ambrosini, Ouathek Ouerfelli, Gary K. Schwartz
Journal: Cancer Research (2014)

Abstract Our aim is to target tumor cells specifically by directly suppressing their oncogenes with peptide nucleic acid (PNA) oligonucleotide analogues. PNA oligonucleotides bind to DNA over 1000-fold more avidly than its native complement, are completely resistant to intra and extra cellular enzymatic degradation, show no nonspecific toxicity at therapeutic levels, and when conjugated to delivery peptides can be made nuclear and cell membrane permeable. We have employed these PNA oligomers to target BRAFV600E which is prevalent in cutaneous melanoma in a sequence-specific complementary manner so as to disrupt transcription by strand invasion. For these studies, we have developed a novel delivery peptide conjugated to PNA modified to increase both cellular delivery and PNA stability towards its target. Our results indicate that exposure of the melanoma cell lines to a modified PNA-peptide conjugate selective for BRAFV600E results in a concentration-dependent inhibition of cell growth that is specific for the BRAFV600E mutant melanoma cell lines with an IC50 range of 250 to 500 nM. Moreover, there is no inhibition of BRAFWT cell growth at these concentrations. This is associated with suppression of BRAFV600E protein over time with no effect on BRAFWT protein levels. Furthermore, BRAFV600E protein expression was suppressed for up to 6 days following initial exposure proving the durability of this type of inhibition. Exposure to this modified PNA-peptide down-regulates BRAFV600E mRNA transcription exclusively in the mutant cell lines. Live cell imaging of BRAFV600E mutant cells confirms localization of fluorescein-labeled PNA-delivery peptide specific to BRAFV600E to the nucleus within 3 hours of treatment. Our results indicate that these PNA-peptide derivatives could represent a novel and promising new therapy for patients with BRAFV600E mutant melanoma, and this technology could be applied to a multitude of other cancers either with specific translocations or mutations differing from wild-type cells even by only a single base pair. Citation Format: Jeffrey H. Rothman, Oliver Surriga, Shyamprasad D. Vasudeva, Grazia Ambrosini, Ouathek Ouerfelli, Gary K. Schwartz. PNA as novel targeted cancer therapy for BRAFV600E mutant melanoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2926. doi:10.1158/1538-7445.AM2014-2926
HTLV-II down-regulates HIV-1 replication in IL-2–stimulated primary PBMC of coinfected individuals through expression of MIP-1α
Authors: Claudio Casoli, Elisa Vicenzi, Andrea Cimarelli, Giacomo Magnani, Paolo Ciancianaini, Ercole Cattaneo, PierPaolo Dall'Aglio, Guido Poli, Umberto Bertazzoni
Journal: Blood (2000)
Abstract 16989: Impaired Systolic Function Assessed by Strain Imaging Predicts Cardiovascular Morbidity and Mortality in Heart Failure with Preserved Ejection Fraction
Authors: Amil M Shah, Brian Claggett, Nancy K Sweitzer, Sanjiv J Shah, Inder S Anand, Li Liu, Bertram Pitt, Marc A Pfeffer, Scott D Solomon
Journal: Circulation (2014)

Introduction: Left ventricular (LV) systolic function by strain imaging is impaired in heart failure with preserved ejection fraction (HFpEF) but its prognostic relevance is not known. Hypothesis: We hypothesized that worse longitudinal strain (LS) is independently associated with adverse outcomes. Methods: LS was assessed by 2D speckle-tracking echocardiography in a blinded core laboratory at baseline in 447 patients with HFpEF (left ventricular ejection fraction [LVEF] ≥45%) enrolled in the Treatment Of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial and was related to the primary composite outcome of cardiovascular (CV) death, HF hospitalization, or aborted cardiac arrest, and its components. Results: At a median follow-up of 2.6 (IQR 1.5-3.9) years, 115 patients experienced the primary outcome. Impaired LS, defined as an absolute LS &lt; 15.8%, was present in 53% of patients and was associated with the composite outcome (adjusted HR 2.14, 95% CI 1.26-3.66; p=0.005), CV death alone (adjusted HR 3.20, 95% CI 1.44-7.12; p=0.004), and HF hospitalization alone (adjusted HR 2.23, 95% CI 1.16-4.28; p=0.016) after adjusting for age, gender, race, randomization strata (prior HF hospitalization vs elevated B-type natriuretic peptide level), region of enrollment (Americas vs Russia or Georgia), randomized treatment assignment, history of atrial fibrillation, heart rate, New York Heart Association class, history of stroke, creatinine, hematocrit, LVEF, mass, end-systolic volume index, and E/E’ ratio. These findings were similar in the subgroup of 354 patients with LVEF ≥55%. Conclusions: Among HFpEF patients enrolled in TOPCAT, impaired LV systolic function, measured by LS, is predictive of adverse CV outcomes independent of clinical and conventional echocardiographic predictors. Impaired LS represents a novel imaging biomarker to identify HFpEF patients at particularly high risk for CV morbidity and mortality.
Abstract 2598: Do Exercise Test Abnormalities Fully Account for the Difference in Risk Between Patients with and without a History of Cardiovascular Disease?
Authors: Thomas G Allison, Jorge R Alegria, Luciano Babuin, Joseph G Murphy, Randal J Thomas
Journal: Circulation (2006)

Poor functional capacity and heart rate and electrocardiographic abnormalities during exercise testing occur more often in patients with cardiovascular disease (CVD), and CVD patients have poorer survival than those free of CVD history. We sought to determine whether the exercise test can accurately establish prognosis independent of history of CVD. Subjects consisted of patients referred for exercise testing during 1986–1991. They were stratified by history of CVD established prior to the exercise test. Mortality was determined by examination of the National Death Index in August, 2005. Cox proportional hazards regression was used to determine the significance of CVD history for all-cause mortality after adjustment for age, sex, beta blocker use, functional capacity, heart rate reserve, and normal exercise ECG. A second age, sex, and beta blocker-adjusted analysis used only subjects with a “good” exercise test result defined as functional capacity ≥ 100% of age- and gender- predicted with heart rate rese...
Dynamic Radiology of the Abdomen. Normal and Pathologic Anatomy.
Authors: Morton A. Meyers
Journal: Annals of Internal Medicine (1977)

General Considerations: Dynamics of Image Analysis.- Clinical Embryology.- Intraperitoneal Spread of Infections.- Intraperitoneal Spread of Malignancies.- Staging of GI Cancers.- Pathways of Lymph Node Metastases in Cancer of GI Hepatobiliary Tracts.- Manifestations of Intraperitoneal Air.- Extraperitoneal Spaces.- Renointestinal Relationships.- Duodenocolic Relationships.- Intestinal Effects of Pancreatitis: Spread Along Mesenteric Planes.- Pathways of Regional Spread in Pancreatic Cancer.- Subperitoneal Space.- Small Bowel.- Colon.- Internal Abdominal Hernias.- Pathways of Extrapelvic Spread of Disease.
Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein
Authors: Jada Lewis, Eileen McGowan, Julia Rockwood, Heather Melrose, Parimala Nacharaju, Marjon Van Slegtenhorst, Katrina Gwinn-Hardy, M. P Murphy, Matt Baker, Xin Yu, Karen Duff, John Hardy, Anthony Corral, Wen-Lang Lin, Shu-Hui Yen, Dennis W. Dickson, Peter Davies, Mike Hutton
Journal: Nature Genetics (2000)
Clinical effect of pirfenidone on incidence of lung carcinoma in chronic interstitial pneumonia
Authors: Yukiko Miura, Takefumi Saito, Yoshiya Tsunoda, Toru Tanaka, Hiroyuki Takoi, Yohei Yatagai, Shih-Yuan Lin, Akimasa Sekine, Kenji Hayashihara, Minoru Inomata, Takahito Nei, Yoshinobu Saito, Akihiko Gemma, Arata Azuma
Journal: European Respiratory Journal (2014)

Introduction  Pirfenidone is the first agent reported to improve progression-free survival in patients with idiopathic pulmonary fibrosis (IPF), and what are now needed are data on overall survival.  Aims  Given poor prognosis, it is difficult to assess overall survival. The investigation of impact of pirfenidone associated with prognosis other than inhibition of declines in vital capacity is required. Lung carcinoma worsens prognosis. Pirfenidone inhibits transforming growth factor-beta and epithelial mesenchymal transition, which promote tumor progression. We assessed whether pirfenidone might suppress carcinogensis.  Methods  We reviewed 384 patients with chronic interstitial pneumonia in Ibarakihigashi hospital and Nippon Medical School from January 2009 to November 2013. We compared the incidence of lung carcinoma between pirfenidone and non-pirfenidone group.  Results  Mean observation time was 27.1±24.1 mo vs. 28.4±32.9 mo. The development of lung carcinoma during follow-up of interstitial pneumonia was significantly lower in the pirfenidone group (1.8% (2/113) vs. 32.5% (88/271), p  Conclusion  The incidence of lung carcinoma was lower in pirfenidone group.  Lung carcinoma had been reported to coexist in 7.1-27.3% in IPF.  The limitations are; 1) A retrospective study conducted at two institutions. 2) We reviewed only inpatients. Most of the patients who have lung carcinoma coexisting with IPF are hospitalized and administered chemotherapy in our institutions, so the incidence of lung carcinoma might be higher.  Since the mortality from lung carcinoma is high, the prevention is important to improve prognosis of IPF. Effect of pirfenidone on lung carcinoma is the next challenging focus.
Hepcidin‐dependent and hepcidin‐independent regulation of erythropoiesis in a mouse model of anemia of chronic inflammation
Authors: Jacqueline M. Langdon, Saiah C. Yates, Laurette K. Femnou, Bryan J. McCranor, Chris Cheadle, Qian‐Li Xue, Sophie Vaulont, Curt I. Civin, Jeremy D. Walston, Cindy N. Roy
Journal: American Journal of Hematology (2014)

Increased hepcidin antimicrobial peptide correlates with hypoferremia and anemia in various disease states, but its requirement for anemia of inflammation has not been adequately demonstrated. Anemia of inflammation is usually described as normocytic and normochromic, while diseases associated with over expression of hepcidin, alone, are often microcytic and hypochromic. These differences in erythrocyte parameters suggest anemia in many inflammatory states may not be fully explained by hepcidin‐mediated iron sequestration. We used turpentine‐induced sterile abscesses to model chronic inflammation in mice with targeted disruption of Hepcidin 1 [Hepc1 (−/−)] or its positive regulator, Interleukin‐6 [IL‐6 (−/−)], to determine whether these genes are required for features characteristic of anemia of inflammation. Although hemoglobin levels did not decline in Hepc1 (−/−) mice with sterile abscesses, erythrocyte numbers were significantly reduced compared to untreated Hepc1 (−/−) mice. In contrast, both hemoglobin concentration and erythrocyte number declined significantly in wild type and IL‐6 (−/−) mice with sterile abscesses. Both Hepc1 (−/−) and IL‐6 (−/−) mice had increased erythrocyte mean cell volume and mean cell hemoglobin following sterile abscesses, while wild types had no change. Thus, IL‐6 (−/−) mice with sterile abscesses exhibit an intermediate phenotype between wild type and Hepc1 (−/−). Our results demonstrate the requirement of Hepc1 for the development of anemia in this rodent model. Simultaneously, our results demonstrate hepcidin‐independent effects of inflammation on the suppression of erythropoiesis. Our results suggest chronic anemia associated with inflammation may benefit from interventions protecting erythrocyte number in addition to anti‐hepcidin interventions aimed at enhancing iron availability. Am. J. Hematol. 89:470–479, 2014. © 2014 Wiley Periodicals, Inc.
Specific macrothrombocytopenia/hemolytic anemia associated with sitosterolemia
Authors: Zhaoyue Wang, Lijuan Cao, Yanhua Su, Gaifeng Wang, Ruijuan Wang, Ziqiang Yu, Xia Bai, Changgeng Ruan
Journal: American Journal of Hematology (2013)

Sitosterolemia (phytosterolemia) is a rare inherited sterol storage disorder, characterized by significantly elevated plasma levels of plant sterols. The clinical features of sitosterolemia are xanthomas, premature atherosclerosis, arthritis, and, occasionally, liver function impair and hematologic abnormalities. This disorder is caused by mutations of ABCG5/ABCG8 genes. We report here the clinical, laboratory, and molecular genetic features of 13 patients with sitosterolemia from eight unrelated families who had specific hematologic problems of macrothrombocytopenia, hemolytic anemia, and splenomegaly besides the major clinical manifestations. The peripheral blood films showed some unique features: large platelets surrounded by a circle of vacuoles, and various abnormal erythrocyte shapes, especially stomatocyte. According to these distinct changes of blood cell morphology, we identified two sitosterolemia patients who lacked the classical clinical phenomena. All the patients had been misdiagnosed with immune thrombocytopenia (ITP), Evans syndrome, or secondary ITP with delay being 28.8 years between symptom onset and correct diagnosis. These results indicate that sitosterolemia is certainly not as rare as originally thought. The phenomena of macrothrombocytopenia/hemolysis might represent a new platelet disorder. Plasma plant sterols and ABCG5/ABCG8 genes should be analyzed when such hematologic abnormalities are unexplained. Am. J. Hematol. 89:320–324, 2014. © 2013 Wiley Periodicals, Inc
Abstract 11689: The Association Between Serum Potassium and Mortality in a Cohort of Patients With Diminished Kidney Function
Authors: Alex Yang, Jiacong Luo, Donna E Jensen, Steven M Brunelli
Journal: Circulation (2014)

Introduction: Serum potassium (K) is tightly regulated by the kidney between 3.5 and 5.0 mEq/L, which is essential for cardiac action potential and normal function. However, due to impaired excretory capacity, patients with chronic kidney disease (CKD) often have elevated serum K that potentially increases morbidity and mortality. Hypothesis: To better understand the burden of hyperkalemia and how this may vary by severity of renal disease, we studied the association of serum K with rates of mortality within narrow strata of estimated glomerular filtration rate (eGFR). Methods: We identified a retrospective cohort of patients with eGFR &lt;60 mL/min/1.73m 2 between Jan-2009 and Jun-2013 (N=55,266). Patients were followed until 30-Jun-2013 or censoring (death, end-stage renal disease, transfer of care). Serum K, eGFR, and 13 covariates including demographics, comorbidities and medication use (beta blockers, centrally acting calcium channel blockers, loop and thiazide diuretics) were considered on a time-varying basis, updated at each K measurement. Death was considered as event per time at-risk. Results: At baseline, 15%, 4%, and 1% of patients had serum K 5.0-5.4, 5.5-5.9, and ≥6.0 mEq/L, respectively; prevalence was greater in lower eGFR strata. In each eGFR stratum, a U-shaped association between serum K and mortality was observed (figure shown for eGFR &lt;30 mL/min/1.73m 2 ). Compared to K 4.5-4.9 mEq/L, adjusted incidence rate ratios (IRRs) for K ≥6.0 mEq/L were 3.08 [95%CI, 2.17-4.37], 2.74 [1.13-6.74], 1.72 [0.76-3.86], and 3.90 [1.23-12.32] in eGFR &lt;30, 30-39, 40-49, and 50-59 mL/min/1.73m 2 strata, respectively. Conclusions: Serum K ≥6.0 mEq/L is potently and independently associated with increased mortality among CKD patients. This association is independent of degree of kidney failure. Future population studies should examine cause-specific mortality according to hyperkalemia strata to identify possible mechanisms of cardiac death.