tbuckley/cabot-search huggingface dataset:
Role of immunohistochemistry in the diagnosis of poorly differentiated neuroendocrine carcinoma.
Authors: M. H. Bukhari, E. Byron, J. R. Strosberg, N. A. Nasir, E. Henderson-Jackson, M. Bui, F. Khalil, D. Coppola, L. K. Kvols, A. Nasir
Journal: Journal of Clinical Oncology (2010)

e21086 Background: The role of combined histopathologic and immunohistochemical approach in the diagnosis and subclassification of primary poorly differentiated neuroendocrine carcinomas (PDNECAs) was evaluated at a single institution with multidisciplinary expertise in neuroendocrine oncology. Methods: Clinico-pathologic data from 80 adult patients, aged: 25-76 yrs (mean 42 yrs years), Patients: 51 M/29 F, with primary PD-NECA of the lung 42, colon 33, pancreas 19, gall bladder 3, liver 2 and miscellaneous 17 who had undergone biopsy/resection at our institution were included. Data sources were pathology archives, consultation files, tumor registry and social security index. Results: Histopathology was adequate for diagnosing pure small cell (SCCA) and large cell neuroendocrine carcinoma (LC-NECA). Immunohistochemistry was useful in supporting the diagnosis of PDNECA. Overall, chromogranin, synaptophysin, NSE, and CD56 were positive in 44/75 (60%), 72/77 (94%), 24/28 (88%), and 22/25 (88%) cases, respectively. Immunoreactivities for other markers for primary PDNECAs from various organs were as follows: TTF-1-16/24 (67%) pulmonary and of 0% for nonpulmonary; α-fetoprotein (AFP)-2/2 (100%) hepatic vs. 0% non- hepatic; CAM 5.2-16/19 (85%) pancreatic, 5/6 (83%) pulmonary; CK-7-15/19 (79%) pancreatic, 83% Pulmonary vs. 28-50% in non- pancreatic/pulmonary/colonic; CDX2 100% in small intestine primaries and 0% in pancreatic and gall bladder PD-NECAs, CEA-5/5 (100%) colonic; CK20-23/27 (85%) colonic. Ki-67 index ranged from 20-70% (median: 45%). There was a strong correlation between mitotic count and Ki-67 index (r +0.953). Conclusions: Histopathology can be used to subclassify PD-NECA into small-cell, large-cell, and mixed small and large cell subtypes. However, in patients with PD-NECA of unknown origin, a panel of immunohistochemical markers (TTF1, CK7, CK20, and CDX2) may be helpful in pointing toward the primary site, that can then be subjected to more focused radiologic evaluation to detect the primary site. No significant financial relationships to disclose.
Pediatric Tumors
Authors: R. Elhasid, E. Vlodavsky, A. Nachtigal, Z. Keidar, S. Postovsky, M. Weyl Ben Arush
Journal: Journal of Clinical Oncology (2001)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.1.276 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11134225 Pediatric Tumors Case 3. Bone Marrow Involvement in Osteosarcoma R. ElhasidxR. ElhasidSearch for articles by this author , E. VlodavskyxE. VlodavskySearch for articles by this author , A. NachtigalxA. NachtigalSearch for articles by this author , Z. KeidarxZ. KeidarSearch for articles by this author , S. PostovskyxS. PostovskySearch for articles by this author , M. Weyl Ben ArushxM. Weyl Ben ArushSearch for articles by this author Show More Ranbam Medical Center and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel https://doi.org/10.1200/JCO.2001.19.1.276 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
Clinical factors linked with coronary artery disease in chronic obstructive pulmonary disease (COPD)
Authors: J.H. Park, Y.H. Ahn, S.K. Ki, Y.J. Jung, K.S. Lee, W.Y. Jung, S.S. Sheen, K.J. Park
Journal: European Respiratory Journal (2014)

Background: Chronic obstructive pulmonary disease (COPD) is frequently accompanied by coronary artery disease (CAD) and cardiovascular disease is the most common cause of death in COPD. Therefore, this study was performed to identify the clinical factors linked with angiography-proven CAD in COPD.  Methods:We retrospectively reviewed medical records of 406 patients (male : 88.4%, mean age : 68.9  ± 9.3) with COPD who had undergone coronary angiography in Ajou University hospital from Jan. 1997 to Dec. 2012.  Results: Hemoglobin level and serum HDL were lower in COPD with CAD than in COPD without CAD ( p  p  p  p   Conclusion: Our data showed that hypertension, left heart failure, and lower serum HDL level were independent predictors for the presence of CAD in COPD. FEV1 and triple vessel CAD were independently associated with the survival of the patients with COPD.
Sleep apnoea and post-stroke vascular events: is it only due to poor continuous positive airway pressure use?
Authors: Aibek E. Mirrakhimov
Journal: European Respiratory Journal (2012)

Sleep apnoea and post-stroke vascular events: is it only due to poor continuous positive airway pressure use?To the Editors: I read the recent European Respiratory Journal article by MARTI ´NEZ- GARCI ´A et al. [1] with keen interest.The authors analysed 166 patients with recent ischaemic stroke and followed them for 7 yrs to study the impact of obstructive sleep apnoea (OSA) on new cardiovascular events.According to their results, 31 patients did not have OSA, 39 patients had mild-to-moderate OSA and 96 patients had moderate-to-severe OSA.Continuous positive airway pressure (CPAP) was initiated 2 months after an acute cerebrovascular event in patients with moderate-to-severe disease only.However, 68 out of 96 participants in the severe OSA group did not tolerate CPAP.It is noteworthy to emphasise that noncompliant patients with moderate-to-severe OSA were older, and had a higher prevalence of arterial hypertension, previous cerebrovascular disease, atrial fibrillation (AFib), oral anticoagulant use, antihypertensive medication use and diabetes mellitus, but except for age, these variables did not reach statistical significance.After regression analysis adjusted for potential confounders, such as age, sex, stroke severity, previous cerebrovascular disease, AFib, arterial hypertension, previous ischaemic heart disease, hypercholesterolaemia, fibrinogen levels, carotid artery disease, smoking status and body mass index, the authors found that untreated OSA independently increased the nonfatal cardiovascular risk (predominantly cerebrovascular disease) 2.87 times (p50.033).Overall, this study solidifies current knowledge (the first study with such long follow-up) that OSA is a strong cardiovascular risk factor and the speculations about possible protective effects on decreased vascular morbidity and mortality among elderly patients with OSA are of less value, at least for stroke [2].Another key issue highlighted by the study is that clinical questionnaires for excessive daytime sleepiness (EDS) may have decreased sensitivity in stroke patients or these patients may not have EDS at all.I would like to thank and congratulate the authors on this exceptionally important data.However, some issues need to be mentioned.
Respiratory health in Saudi Arabia
Authors: Talha Khan Burki
Journal: The Lancet Respiratory Medicine (2015)

"Before the Kingdom of Saudi Arabia was established in 1932, health care was generally provided by local healers", explains the website for the Saudi Arabian embassy in the USA. "One of King Abdulaziz's first initiatives for his new state was to establish free health care, not just for citizens, but for the pilgrims who come to the Kingdom to visit the Islamic holy sites". According to Bloomberg, Saudi Arabia now has the 16th most efficient health-care system in the world, ahead of countries such as Canada, Germany, Sweden, and the USA.
Cardioprotection and Safety of Dexrazoxane in Patients Treated for Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Advanced-Stage Lymphoblastic Non-Hodgkin Lymphoma: A Report of the Children’s Oncology Group Randomized Trial Pediatric Oncology Group 9404
Authors: Barbara L. Asselin, Meenakshi Devidas, Lu Chen, Vivian I. Franco, Jeanette Pullen, Michael J. Borowitz, Robert E. Hutchison, Yaddanapudi Ravindranath, Saro H. Armenian, Bruce M. Camitta, Steven E. Lipshultz
Journal: Journal of Clinical Oncology (2015)

To determine the oncologic efficacy, cardioprotective effectiveness, and safety of dexrazoxane added to chemotherapy that included a cumulative doxorubicin dose of 360 mg/m(2) to treat children and adolescents with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic non-Hodgkin lymphoma (L-NHL).Patients were treated on Pediatric Oncology Group Protocol POG 9404, which included random assignment to treatment with or without dexrazoxane given as a bolus infusion immediately before every dose of doxorubicin. Cardiac effects were assessed by echocardiographic measurements of left ventricular function and structure.Of 573 enrolled patients, 537 were eligible, evaluable, and randomly assigned to an arm with or without dexrazoxane. The 5-year event-free survival (with standard error) did not differ between groups: 77.2% (2.7%) for the dexrazoxane group versus 76.0% (2.7%) for the doxorubicin-only group (P = .9). The frequencies of severe grade 3 or 4 hematologic toxicity, infection, CNS events, and toxic deaths were similar in both groups (P ranged from .26 to .64). Of 11 second malignancies, eight occurred in patients who received dexrazoxane (P = .17). The mean left ventricular fractional shortening, wall thickness, and thickness-to-dimension ratio z scores measured 3 years after diagnosis were worse in the doxorubicin-alone group (n = 55 per group; P ≤ .01 for all comparisons). Mean fractional shortening z scores measured 3.5 to 6.4 years after diagnosis remained diminished and were lower in the 21 patients who received doxorubicin alone than in the 31 patients who received dexrazoxane (-2.03 v -0.24; P ≤ .001).Dexrazoxane was cardioprotective and did not compromise antitumor efficacy, did not increase the frequencies of toxicities, and was not associated with a significant increase in second malignancies with this doxorubicin-containing chemotherapy regimen. We recommend dexrazoxane as a cardioprotectant for children and adolescents who have malignancies treated with anthracyclines.
Abstract 18974: A Pilot Study of the Effects of Ranolazine on Right Ventricular Structure and Function, Exercise Capacity, and Symptoms in Pulmonary Arterial Hypertension
Authors: Sanjiv J Shah, Michael J Cuttica, Lauren Beussink, Hamorabi Mkrdichian, Roberto Sarnari, Brandon Benefield, Senthil Selvaraj, Jane E DeMatte, Daniel C Lee
Journal: Circulation (2012)

Introduction: Right ventricular (RV) failure is a major cause of death in pulmonary arterial hypertension (PAH). RV ischemia, which is common in PAH, plays a major role in the development of RV failure. We hypothesized that ranolazine, a late Na+ current inhibitor, would be beneficial in patients with PAH by increasing RV perfusion. Methods: We prospectively enrolled 10 patients with World Health Organization (WHO) Group I PAH and symptoms of angina (or anginal equivalent) in an observational, 3-month study of the effects of ranolazine (1000 mg PO BID) in PAH. All patients were on chronic pulmonary vasodilator therapy. At baseline and 3 months, patients underwent functional class assessment, 6-minute walk test, bicycle echocardiography with speckle-tracking for assessment of RV mechanics, right heart catheterization, and adenosine perfusion cardiac MRI. Data was compared at baseline vs. 3-months using paired t-tests. Results: The mean age was 47±13 y, and 80% were female. At baseline, patients had moderate or greater PAH (Table 1) with evidence of RV dysfunction (7/10 patients had reduced RV fractional area change [&lt;0.35], and all patients had septal flattening indicative of RV overload). Ranolazine was well tolerated in 90% of patients (7 patients tolerated the full dose and 2 patients required a dose reduction due to side effects, after which the drug was well tolerated). Ranolazine was discontinued in 1 patient due to a medication interaction. After 3 mo. of ranolazine therapy, symptoms improved, exercise capacity increased, RV size decreased, and tricuspid annular plane systolic excursion (TAPSE) increased (Table 1). There were no changes in invasive hemodynamics, and no major adverse events. Conclusions: Ranolazine is well tolerated and safe in patients with WHO Group I PAH. After 3 mo. of therapy, ranolazine improved RV size and function and resulted in symptomatic improvement. These findings support the development of clinical trials for ranolazine in PAH.
O086 : Budesonide for autoimmune hepatitis: Response rate and limitations in a large real life cohort
Authors: M. Peiseler, T. Liebscher, N. Pannicke, M. Sebode, R. Zenouzi, J. Hartl, H. Ehlken, C. Weiler-Normann, A.W. Lohse, C. Schramm
Journal: Journal of Hepatology (2015)
Pulmonary metastasised extraskeletal osteosarcoma
Authors: Eva M T Bots, Pieter J Wismans, Lennert Slobbe
Journal: Thorax (2015)

A 63- year-old Caucasian man who smoked presented with lower back pain, dyspnoea and weight loss. A chest CT showed multiple bilateral cavitating lesions, consolidations and ground glass lesions (figure 1). Because a CT-guided pulmonary biopsy elsewhere revealed chronic inflammation with caseating granulomas, he had initially been treated with tuberculostatics and subsequently antifungal medication without clinical improvement. Since the patient had also developed …
Lymphatic and vascular invasion patterns in triple-negative breast cancer.
Authors: S. Yaman, B. Gumuskaya, C. Ozkan, S. Aksoy, G. Guler, M. K. Altundag
Journal: Journal of Clinical Oncology (2010)

676 Background: Triple-negative breast cancer (TNBC) comprises of about 15%-20% of all breast cancer cases. Many studies have detected less lymph node metastasis in TNBC than sporadic breast cancers. In this study, we studied capillary and lymphatic invasion in tumors of TNBC patients. Methods: Two experienced pathologists blinded to clinical data evaluated capillary and lymphatic invasion patterns in 39 TNBC patients' tumor samples. Tumor samples were immunohistochemically stained with CD34 (endothelial cell marker) and D2-40 (podoplanin, a membrane protein, specific for lymphatic endothelium). The CD34 positive samples were categorized into two groups depending on their reaction with D2-40: lymphatic (D2-40 positive) and capillary (D2-40 negative) invasion. Results: We have detected vascular invasion in 15 out of 39 samples (38.5%) with CD34. Among those, capillary invasion was found in 14 (35.9%) and lymphatic invasion in 3 (7.7%) and both in 2 (5.1%) tumors. We did not find any significant correlations among capillary invasion, lymphatic invasion, vascular invasion, tumor grade, menopause status, history of cancer, and TNM. Conclusions: Capillary invasion is more commonly observed than lymphatic invasion in TNBC patients. This finding provides an explanation for more hematogenous metastasis (spreading) and less lymph node metastasis seen in TNBC patients. No significant financial relationships to disclose.
Celiac Disease Increases Risk of Thyroid Disease in Patients With Type 1 Diabetes: A Nationwide Cohort Study
Authors: Matthew Kurien, Kaziwe Mollazadegan, David S. Sanders, Jonas F. Ludvigsson
Journal: Diabetes Care (2015)

OBJECTIVE Both type 1 diabetes (T1D) and celiac disease (CD) have been linked to autoimmune thyroid disease (ATD). We examined if individuals with both T1D and CD were at a higher risk of ATD than those with only T1D. RESEARCH DESIGN AND METHODS This study was a nationwide population-based cohort study. We defined T1D as having an inpatient or a hospital-based outpatient diagnosis of T1D at age ≤30 years in the Swedish National Patient Register between 1964 and 2009. Data on CD were obtained through small intestinal biopsy reports showing villous atrophy (Marsh histopathology grade III) between 1969 and 2008 at any of the 28 pathology departments in Sweden. ATD included hyperthyreosis and hypothyreosis, defined according to the Swedish National Patient Register. We identified 947 individuals with T1D and biopsy-verified CD. These were matched to 4,584 control subjects with T1D but no CD diagnosis. Cox regression then estimated the risk of ATD. RESULTS Among T1D, CD was a risk factor for later ATD. During follow-up, 90 T1D+CD patients developed ATD (expected n = 54). Adjusting for sex, age, and calendar period, this corresponded to a hazard ratio (HR) of 1.67 (95% CI 1.32–2.11; P &amp;lt; 0.001). This excess risk was highest in those who had CD for 10 years or more (HR 2.22 [95% CI 1.49–3.23]). Risk increases were seen in both males and females. CD was a risk factor for both hypothyreosis (HR 1.66 [95% CI 1.30–2.12]) and hyperthyreosis (HR 1.72 [95% CI 0.95–3.11]). CONCLUSIONS Among patients with T1D, CD is a risk factor for the later development of ATD.
Homocysteine and folate concentrations in blood from patients treated with hemodialysis.
Authors: T Tamura, K E Johnston, S M Bergman
Journal: Journal of the American Society of Nephrology (1996)

Plasma homocysteine and plasma and erythrocyte folate concentrations before and after hemodialysis were measured in 31 patients with ESRD. Homocysteine and folate were measured by HPLC-fluorometric and microbiological methods, respectively. The mean plasma homocysteine level declined from 36.8 to 24.2 mumol/L during hemodialysis, indicating that homocysteine can be partly removed by hemodialysis (P < 0.0001). Mean plasma folate concentration before hemodialysis was 46.4 nmol/L and decreased to 25.9 nmol/L after hemodialysis (P < 0.0001), whereas mean erythrocyte folate concentration did not change (1295 and 1385 nmol/L before and after hemodialysis, respectively). Plasma folate concentrations showed a significant negative correlation with homocysteine concentrations before and after hemodialysis (r = -0.53, P < 0.003, and r = -0.59, P < 0.001, respectively). Furthermore, there were significant negative correlations between plasma homocysteine and erythrocyte folate concentrations both before (r = -0.60, P < 0.0005) and after hemodialysis (r = -0.49, P < 0.005). All patients had homocysteine concentrations over 12.0 mumol/L before hemodialysis, and only three had homocysteine concentrations lower than 12.0 mumol/L after hemodialysis. Although significant correlations existed between homocysteine and folate concentrations, the majority of the patients in this study appeared to have adequate folate nutriture as assessed by blood folate concentrations. It remains to be determined whether patients with ESRD have an altered homocysteine metabolism.
Withholding sugar review will stifle input to obesity strategy, says MP
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

An MP and former GP has accused England’s health secretary, Jeremy Hunt, of hypocrisy for refusing to publish a review of the evidence on what measures could help to reduce people’s consumption on sugar while claiming that he supports data sharing.

In July Public Health England said that its review on what measures the government could take to reduce the population’s sugar consumption would be published at the end of the summer and would inform the government’s strategy on tackling childhood obesity.1 But this week the Department of Health said that the review and the strategy would be published simultaneously “in the coming months.”

In an article in the Daily Telegraph on 12 October Sarah Wollaston, the Conservative MP for Totnes and chair of the health select committee, called on Duncan Selbie, chief executive of Public Health England, to use his powers to insist that the report be made public.2 She said that when Public Health …
Landscape of gene fusions in epithelial cancers: seq and ye shall find
Authors: Chandan Kumar-Sinha, Shanker Kalyana-Sundaram, Arul M. Chinnaiyan
Journal: Genome Medicine (2015)

Enabled by high-throughput sequencing approaches, epithelial cancers across a range of tissue types are seen to harbor gene fusions as integral to their landscape of somatic aberrations. Although many gene fusions are found at high frequency in several rare solid cancers, apart from fusions involving the ETS family of transcription factors which have been seen in approximately 50 % of prostate cancers, several other common solid cancers have been shown to harbor recurrent gene fusions at low frequencies. On the other hand, many gene fusions involving oncogenes, such as those encoding ALK, RAF or FGFR kinase families, have been detected across multiple different epithelial carcinomas. Tumor-specific gene fusions can serve as diagnostic biomarkers or help define molecular subtypes of tumors; for example, gene fusions involving oncogenes such as ERG, ETV1, TFE3, NUT, POU5F1, NFIB, PLAG1, and PAX8 are diagnostically useful. Tumors with fusions involving therapeutically targetable genes such as ALK, RET, BRAF, RAF1, FGFR1–4, and NOTCH1–3 have immediate implications for precision medicine across tissue types. Thus, ongoing cancer genomic and transcriptomic analyses for clinical sequencing need to delineate the landscape of gene fusions. Prioritization of potential oncogenic "drivers" from "passenger" fusions, and functional characterization of potentially actionable gene fusions across diverse tissue types, will help translate these findings into clinical applications. Here, we review recent advances in gene fusion discovery and the prospects for medicine.
Abstract 15318: Association of Single-Nucleotide Polymorphisms with Left Atrial Scar in Patients with Atrial Fibrillation
Authors: Sanghamitra Mohanty, Amelia W Hall, Prasant Mohanty, Chintan Trivedi, Luigi Di Biase, Rong Bai, Amin Al-Ahmad, Rodney Horton, John D Burkhardt, Javier Sanchez, Jason Zagrodzky, Shane Bailey, Joseph G Gallinghouse, Patrick Hranitzky, Vishwanath R Iyer, Andrea Natale
Journal: Circulation (2014)

Introduction: Earlier studies have demonstrated that some AF patients develop spontaneous atrial scarring that leads to genesis and perpetuation of the arrhythmia. However, it is still unclear why it happens in some and not in others. Therefore, we hypothesized that the atrial scar phenotype is associated with certain specific genetic variants and examined the relationship between AF-related single-nucleotide polymorphisms (SNP) and left atrial scar. Methods: Four hundred AF patients (67% male, 62±12 year, left atrial size 45.3±7 mm, 64% non-paroxysmal) undergoing catheter ablation were prospectively enrolled at our center. DNA extraction and genotyping for 16 AF-associated SNPS identified by GWAS study were performed from the collected blood samples using Qiagen QiaAMP 96 well blood kit and TaqMan assay respectively. Three hundred seventy-two DNA samples were available for genotyping. The Hardy-Weinberg equilibrium was assessed using Chi-square analyses. Multivariable logistic model was utilized to identify predictors of LA scar after adjusting for age, gender, LA size, hypertension and diabetes mellitus and odds ratio (OR) and 95% confidence intervals were computed. Results: Of all 16 SNPs, rs3807989 showed a strong inverse association with LA scar at univariate analysis (0.54 [0.348-0.89] p= 0.014) in the overall population. After adjustment for covariates, the association became highly significant indicating a 50% reduction in scar risk (OR 0.50 (0.30-0.83) p=0.007). When stratified by type of AF, rs3807989 genotype predicted a substantially stronger 69% risk-reduction in the non-PAF population (OR 0.31 (0.15-0.62) p=0.0009). Conclusion: The SNP, rs3807989 on chromosome 7p31, was demonstrated to be associated with reduced risk of left atrial scar formation in AF patients. This genetic variant is located in close proximity to the caveolin-1 gene which is known to have an anti-fibrotic role by inhibiting transforming growth factor-β1, a key mediator in the fibrosis process. Therefore, it can be postulated that by some unknown mechanism the candidate chromosomal variant potentially upregulates caveolin-1 function resulting in attenuation of fibrosis and scar formation.