tbuckley/cabot-search huggingface dataset:
Streamlining universal screening for lynch syndrome (LS): Towards improved yield of genetic counseling (GC).
Authors: Stefania Sciallero, Azzurra Damiani, Simonetta Zupo, Linda Battistuzzi, Alberto Puccini, Carla Bruzzone, Edoardo Gonella, Viviana Gismondi, Mariella Dono, Luca Mastracci, Alberto F. Sobrero, Liliana Varesco, Federica Grillo
Journal: Journal of Clinical Oncology (2019)

503 Background: LS is largely underdiagnosed although Universal Screening (US) in colorectal cancer (CRC) patients through MisMatch Repair deficiency (MMR-d) testing is widely endorsed. Low adherence to guidelines among oncologists may be partly due to a lack of consensus on whether all MMR-d patients should be referred to GC/Genetic Testing (GT). As BRAF mutation rules out LS, we estimated the increased yield of LS diagnosis from GC /GT which could be obtained by selecting candidates for GC through BRAF testing. Methods: From 2011 to 2016, 1447 consecutive stage I-IV CRC surgical patients at a single institution, underwent immunohistochemistry (IHC) for LS using anti MLH1, MSH2, MSH6 and PMS2 antibodies. Oncologists were invited to refer all MMR-d patients to GC/GT. BRAFV600E testing was carried out only in case of MLH1 protein loss at IHC. Results: MMR-d was found in 194 patients (13%), with 171 showing loss of MLH1 expression (88%). Oncologists referred 27 (16%) to GC. Among the 21 who underwent GC, BRAF testing and GT, 9 were BRAF wild type (wt) (43%) and none had LS. Among the 23 MMR-d patients with loss of expression of MSH2, MSH6 or PMS2 (≠MLH1), oncologists referred 9 to GC (39%): 7 underwent GC / GT and 3 carried LS (43%) at GT. Median age was 76 years (range 30-97) in the MMR-d group, 78 (range 41-97) in the MLH1 group and 63 (range 30-86) in the ≠MLH1 group. Overall, LS was diagnosed in 3 of the 28 MMR-d patients (11%) who underwent GC /GT, possibly an underestimate due to the advanced median age of our MLH1 loss patients. Had we only offered GC to the 9 BRAF wt patients among the 21 with MLH1 loss, we could have avoided 12 (57%) of the GC sessions conducted, increasing the yield of LS diagnosis from 3/28 (11%) to 3/16 (19%) (75% increase). Conclusions: When US for LS is adopted, a GC referral rate reduction of 57% among MLH1 loss patients, and an overall increase in the yield of GC of about 75% can be obtained by testing for BRAF mutation before oncologist referral to GC rather than after. As multistep selection of patients by oncologists may be unfeasible, CRC pathology reports with combined MMR-d and BRAF testing (for MLH1 loss at IHC) and an ‘LS suspicion alert’ could improve oncologists’ awareness of LS and compliance with guidelines.
An Open-Label Phase I/II Study of Carfilzomib, Bendamustine and Dexamethasone (CBD) in Newly Diagnosed Multiple Myeloma Patients
Authors: Siyang Leng, Shahzad Raza, Amer Assal, Gregory Baliko, Julia Gould, Rachel K Shields, Markus Y Mapara, Suzanne Lentzsch
Journal: Blood (2017)
Successful Simultaneous Screening of Sickle Cell Disease, HIV and Tuberculosis in Rural Guinea Bissau, West Africa through Rapid Tests and a Standardized Clinical Questionnaire: An Outreach Program Due to a Public-Private Partnership
Authors: Federica Menzato, Luca Bosa, Armando Sifna, Luisa Da Silva, Elena Gasperoni, Maddalena Martella, Mamadu Saliu Sanha, Alfa Mustik, Liviana Da Dalt, Fabio Riccardi, Raffaella Colombatti
Journal: Blood (2018)
Potential for Digital Behavioral Measurement Tools to Transform the Detection and Diagnosis of Autism Spectrum Disorder
Authors: Geraldine Dawson, Guillermo Sapiro
Journal: JAMA Pediatrics (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Aspiration of Airway Dead Space
Authors: EDOARDO DE ROBERTIS, SIGURDUR E. SIGURDSSON, BJÖRN DREFELDT, BJÖRN JONSON
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Alveolar ventilation and CO2 elimination during mechanical ventilation can be enhanced by reducing dead-space ventilation. Aspiration of gas from the dead space (ASPIDS) is a new principle, according to which gas rich in CO2 during late expiration is aspirated through a channel ending at the distal end of the tracheal tube. Simultaneously, fresh gas injected into the inspiratory line fills the airway down to the same site. We hypothesized that ASPIDS would allow a reduction of tidal volume (Vt) and airway pressure (Paw). To test our hypothesis we studied six anaesthetized and mechanically ventilated pigs (24 ± 4 kg). The intention was to decrease Vt while keeping PaCO2 constant by using ASPIDS. Vt was reduced by decreasing the minute ventilation (V˙ e) in two steps, of 1.8 L/min (V˙ e − 1.8) and 2.2 L/min (V˙ e − 2.2), respectively, and by increasing respiratory rate (RR) from 20 to 46 breaths/min. At ASPIDS, peak Paw was reduced by 35% at V˙ e − 1.8 and at V˙ e − 2.2 (p < 0.001), and by 20% at an RR of 46 (p < 0.01). PaCO2 was maintained or reduced at ASPIDS. No intrinsic positive end-expiratory pressure developed. Arterial blood pressure and heart rate were unaffected. The results show that ASPIDS allows a reduction in Vt and Paw while PaCO2 is kept constant. ASPIDS does not lead to problems associated with jet streams of gas or with gas humidification, and can be developed as a safe technique.
Abstract 20072: Prognostic Value of Baseline Right Ventricular Dysfunction in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Islam Abdelkarim, Wei Han, Floyd Thoma, Andrew D Althouse, William E Katz, Frederick W Crock, Matthew E Harinstein, Dustin E Kliner, Forozan Navid, Thomas G Gleason, Joon S Lee, John T Schindler, Joao L Cavalcante
Journal: Circulation (2016)

Introduction: The prevalence of right ventricular dysfunction (RVD) and its relationship with all-cause mortality in severe aortic stenosis patients treated with transcatheter aortic valve replacement (TAVR) is unknown. Hypothesis: Presence of baseline RVD in patients treated with TAVR is associated with increased all-cause mortality. Methods: We assessed RV function in 237 patients who underwent TAVR from July 2011 through July 2015. Tricuspid annular plane systolic excursion (TAPSE) was measured in the apical 4-chamber view. RVD is defined as TAPSE  40 clinical parameters and risk factors, was calculated. Notably, the STS-PROM score does not account for RVD. Kaplan-Meier curves and Cox models were used to quantify the effect of RVD on mortality; the Akaike Information Criterion (AIC) was used to select the TAPSE threshold most strongly associated with all-cause mortality. Results...
Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
Authors: Domenico Corrado, Guy Fontaine, Frank I. Marcus, William J. McKenna, Andrea Nava, Gaetano Thiene, Thomas Wichter
Journal: Circulation (2000)

Abstract —Arrhythmogenic right ventricular (RV) dysplasia/cardiomyopathy (ARVD/C) is a heart muscle disease characterized by peculiar RV involvement and electrical instability that precipitates ventricular arrhythmias and sudden death. The purpose of the present consensus report of the Study Group on ARVD/C of the Working Groups on Myocardial and Pericardial Disease and Arrhythmias of the European Society of Cardiology and of the Scientific Council on Cardiomyopathies of the World Heart Federation is to review the considerable progress in our understanding of the etiopathogenesis, morbid anatomy, and clinical presentation of ARVD/C since it first was described in 1977. The present article focuses on important but still unanswered issues, mostly regarding risk stratification, clinical outcome, and management of affected patients. Because ARVD/C is relatively uncommon and any one center may have experience with only a few patients, an international registry is being established to accumulate information and enhance the numbers of patients that can be analyzed and thus answer pending questions. The registry also will facilitate pathological, molecular, and genetics research on the causes and pathogenesis of the ARVD/C. Furthermore, availability of an international database will enhance awareness of this largely unrecognized condition among the medical community. Physicians are encouraged to enroll patients in the International Registry of ARVD/C.
Pre-Transplant and Peri-d100 Gastrointestinal Dysbiosis Is Associated with the Subsequent Development of Chronic Graft-Versus-Host Disease
Authors: Kate A Markey, Antonio LC Gomes, Eric R. Littmann, Sean M Devlin, Ann E. Slingerland, John B. Slingerland, Annelie Clurman, Gillian Moore, Samira A Fatmi, Molly Maloy, Eric G. Pamer, Ying Taur, Sergio Giralt, Miguel-Angel Perales, Doris Ponce, Jonathan U. Peled, Marcel R.M. van den Brink
Journal: Blood (2018)
A miRNA Expression Signature in Breast Tumor Tissue Is Associated with Risk of Distant Metastasis
Authors: Thomas E. Rohan, Tao Wang, Sheila Weinmann, Yihong Wang, Juan Lin, Mindy Ginsberg, Olivier Loudig
Journal: Cancer Research (2019)

Abstract Dysregulation of miRNA expression may influence breast cancer progression, and experimental evidence suggests that miRNA silencing might suppress breast cancer metastasis. However, the relationship between miRNA and metastasis must be confirmed before this approach can be applied in the clinic. To this end, we conducted a two-stage study in a cohort of 3,760 patients with breast cancer to first identify and then validate the association between miRNA expression and risk of distant metastasis. The first stage (discovery) entailed miRNA sequencing of 126 case–control pairs; qPCR was used to validate the findings in a separate set of 80 case–control pairs. The 13 miRNAs most differentially expressed between cases and controls were combined into an miRNA score that was significantly associated with risk of distant metastasis in a logistic regression model that also included clinical variables (tumor size and number of positive lymph nodes) (ORper unit increase in score = 1.30; 95% confidence interval, 1.03–1.66). The results of this study suggest that in women with invasive breast cancer, a miRNA score that incorporates both clinical variables and miRNA expression levels in breast tumor tissue is moderately predictive of risk of subsequent distant metastasis. Significance: A novel predictive scoring system for patients with breast cancer includes clinical variables and the expression levels of 13 miRNAs and may help to identify those at increased risk of distant metastasis.
Blue rubber bleb nevus syndrome: endoscopic treatment with sclerotherapy during double-balloon enteroscopy in a 9-year-old boy
Authors: Maria Carolina Malafaia, Sophie Heissat, Philippe Jacob, Catherine Le Gall, Mathias Ruiz, Jean-Christophe Saurin, Mathieu Pioche
Journal: Endoscopy (2019)

Blue rubber bleb nevus syndrome (BRBNS), also called Bean syndrome, is a rare disease associated with multiple venous malformations essentially in the skin and the gastrointestinal (GI) tract [1] [2]. It commonly presents with anemia and patients respond to supportive measures, but severe symptoms may be treated by surgical resection, endoscopic sclerotherapy, and laser photocoagulation [3] [4].
Abstract B069: Drug response variability between luminal and basal prostate cancer tumors
Authors: Robert Den, Jonathan Lehrer, Mandeep Takhar, Mohammed Alshalalfa, Nicholas Erho, Elai Davicioni, Felix Feng
Journal: Cancer Research (2018)

Abstract Introduction: Prostate cancer (PCa) is a genomically heterogeneous disease that has been subtyped into molecularly distinct subtypes. Over the past several years, multiple drugs have demonstrated improvements in overall survival in men with advanced prostate cancer, prompting further investigations of these drugs. However, characterizing drug response in the localized disease setting and in the context of PCa molecular subtypes needs further investigation. Here in a large prospective cohort of men with adverse pathology we explore the heterogeneity of patient drug response between basal, luminal, and neuroendocrine prostate cancer subtypes. Methods: Whole-transcriptome RNA expression profiles of 9,640 radical prostatectomy (RP) samples from prospective use of the Decipher test were obtained from the GRID registry database. Patients were subtyped into basal, luminal A, luminal B, and neuroendocrine subtypes using the PAM50 and small cell gene expression signatures. Drug response scores (DRS) predicting patient sensitivity for 89 oncology drugs were determined using in vitro drug sensitivity and microarray data from the NCI-60 panel. Pearson’s chi squared test was used to determine significant differences in drug sensitivity among PCa subtypes. Results: Applying the subtype signatures to the cohort, we classified 43% of samples as basal, 26% as luminal A, 30% as luminal B, and 2% as neuroendocrine. DRS was highly variable across the subtypes. Basal tumors showed a distinct drug response profile where basal tumors were more sensitive to kinase inhibitors (e.g., cabozantanib, dasatnib, erlotinib), mTOR inhibitors (e.g., everolimus, temsirolumus), DNA repair inhibitors (e.g., olaparib, mitoxantrone), and alkylating (e.g., cisplatin, carboplatin) chemotherapy. Luminal A and B were more sensitive to steroid inhibition (e.g., abiraterone, tamoxifen) and anti-microtuble (e.g., docetaxel, paclitaxel, vinorelbine) chemotherapy, whereas neuroendocrine had highest DRS for antiproliferative agents (e.g., mitomycin, cytabarine, carmustine, topotecan), Significant differences in average DRS scores in subtypes were observed for all 89 drugs (p&amp;lt;0.001). Conclusion: Prostate cancer subtypes in the localized disease setting have distinct drug response profiles, suggesting that subtyping and DRS scores may be useful for selecting candidates for systemic therapy trials. Citation Format: Robert Den, Jonathan Lehrer, Mandeep Takhar, Mohammed Alshalalfa, Nicholas Erho, Elai Davicioni, Felix Feng. Drug response variability between luminal and basal prostate cancer tumors [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B069.
Further Consideration of the Pigmented Lesion Assay
Authors: Meghan Beatson, Martin A. Weinstock
Journal: JAMA Dermatology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Patrolling Monocytes Scavenge Endothelial Adherent Sickle Red Blood Cells in Sickle Cell Disease
Authors: Yunfeng Liu, Hui Zhong, Weili Bao, Avital Mendelson, Xiuli An, Patricia Shi, Stella T. Chou, Deepa Manwani, Karina Yazdanbakhsh
Journal: Blood (2018)
Impaired Cytomegalovirus Immunity in Idiopathic Pulmonary Fibrosis Lung Transplant Recipients with Short Telomeres
Authors: Iulia Popescu, Hannah Mannem, Spencer A. Winters, Aki Hoji, Fernanda Silveira, Emily McNally, Matthew R. Pipeling, Elizabeth A. Lendermon, Matthew R. Morrell, Joseph M. Pilewski, Vidya Sagar Hanumanthu, Yingze Zhang, Swati Gulati, Pali D. Shah, Carlo J. Iasella, Christopher R. Ensor, Mary Armanios, John F. McDyer
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Cytomegalovirus (CMV)-related morbidities remain one of the most common complications after lung transplantation and have been linked to allograft dysfunction, but the factors that predict high risk for CMV complications and effective immunity are incompletely understood.To determine if short telomeres in idiopathic pulmonary fibrosis (IPF) lung transplant recipients (LTRs) predict the risk for CMV-specific T-cell immunity and viral control.We studied IPF-LTRs (n = 42) and age-matched non-IPF-LTRs (n = 42) and assessed CMV outcomes. We measured lymphocyte telomere length and DNA sequencing, and assessed CMV-specific T-cell immunity in LTRs at high risk for CMV events, using flow cytometry and fluorescence in situ hybridization.We identified a high prevalence of relapsing CMV viremia in IPF-LTRs compared with non-IPF-LTRs (69% vs. 31%; odds ratio, 4.98; 95% confidence interval, 1.95-12.50; P < 0.001). Within this subset, IPF-LTRs who had short telomeres had the highest risk of CMV complications (P < 0.01) including relapsing-viremia episodes, end-organ disease, and CMV resistance to therapy, as well as shorter time to viremia versus age-matched non-IPF control subjects (P < 0.001). The short telomere defect in IPF-LTRs was associated with significantly impaired CMV-specific proliferative responses, T-cell effector functions, and induction of the major type-1 transcription factor T-bet (T-box 21;TBX21).Because the short telomere defect has been linked to the pathogenesis of IPF in some cases, our data indicate that impaired CMV immunity may be a systemic manifestation of telomere-mediated disease in these patients. Identifying this high-risk subset of LTRs has implications for risk assessment, management, and potential strategies for averting post-transplant CMV morbidities.
Should oral immunotherapy be contraindicated in patients with eosinophilic esophagitis if IgE-mediated food allergy develops after dietary elimination to treat EoE?
Authors: Stephanie C. Erdle, Hannah Roberts, Lianne Soller, Vishal Avinashi, Elaine Wardley, Jocelyn Jia, Edmond S. Chan
Journal: Journal of Allergy and Clinical Immunology (2019)
β-catenin and plakoglobin as prognostic markers in anal cancer.
Authors: Mette Pernille Myklebust, Havjin Jacob, Jon Espen Dale, Olav Dahl
Journal: Journal of Clinical Oncology (2015)

e14503 Background: β-catenin and plakoglobin are members of the catenin protein family and localize to adherens junctions and desmosomes, respectively. In this study, we evaluated the prognostic value in carcinoma of the anal region of these highly similar proteins with dual functions in cell-cell adhesion and gene regulation. Methods: Expression of b-catenin and plakoglobin was determined by immunohistochemistry in a TMA containing 62 paraffin-embedded biopsies from primary, non-metastatic carcinomas of the anal region. The staining was scored as fraction (%) of positive tumor cells. Cutpoints for dichotomization of variables were based on ROC analyses. Most patients received treatment with radiotherapy and FuMi with or without surgery, while a few were treated with surgery alone (N = 4). Statistical analyses of relapse-free survival (RFS) in association to dichotomized b-catenin and plakoglobin expression were performed using Kaplan-Meier analyses (KM) and Cox regression. Results: Of 62 biopsies, 56 were successfully stained and scored. β-catenin and plakoglobin localized to the plasma membrane, in addition to varying cytoplasmic staining. Nuclear staining was not detected. Survival analyses identified patients with low membranous β-catenin and high membranous plakoglobin to have poor prognosis (5-year RFS was 25 % for low vs 76% for high b-catenin, P < .001, while 5-year RFS was 25% for high vs 66% for low plakoglobin, P < .001). Multivariate Cox analysis identified both low β-catenin (HR = 4.20, 95% CI 1.36-13.00, P = .013) and high plakoglobin (HR 3.63, 95% CI 1.19-11.03, P = .023) as independent markers for poor survival when adjusted for treatment, stage and MCM7-staining. Membranous β-catenin and plakoglobin expression combined into one variable was an even stronger determinant of prognosis (Table 1), and the variable remained significant in multivariate analysis (P = .002). Table 1: KM-analysis of β-catenin and plakoglobin as one combined variable. Conclusions: We demonstrate β-catenin and plakoglobin as strong prognostic markers in anal cancer. Category 5-year RFS (%) P-value Low plakoglobin + high β-catenin 87 < .001 High plakoglobin + high β-catenin 43 Low plakoglobin + low β-catenin 38 High plakoglobin + low β-catenin 11