tbuckley/cabot-search huggingface dataset:
Kashmir communications blackout is putting patients at risk, doctors warn
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Doctors have warned that the current situation in Indian administered Kashmir, where the government has imposed a security lockdown and communications blackout, is preventing people from seeking medical help.

In a rapid response sent to The BMJ ,1 a group of 18 doctors from across India warned that the “grim” situation had led to a “blatant denial of the right to healthcare.”

In the letter, which has been coordinated by Ramani Atkuri, a public health consultant in Madhya Pradesh, the doctors called for …
Role of the lysyl oxidase enzyme family in cardiac function and disease
Authors: Doa’a Al-u’datt, Bruce G Allen, Stanley Nattel
Journal: Cardiovascular Research (2019)

Heart diseases are a major cause of morbidity and mortality world-wide. Lysyl oxidase (LOX) and related LOX-like (LOXL) isoforms play a vital role in remodelling the extracellular matrix (ECM). The LOX family controls ECM formation by cross-linking collagen and elastin chains. LOX/LOXL proteins are copper-dependent amine oxidases that catalyse the oxidation of lysine, causing cross-linking between the lysine moieties of lysine-rich proteins. Dynamic changes in LOX and LOXL protein-expression occur in a variety of cardiac pathologies; these changes are believed to be central to the associated tissue-fibrosis. An awareness of the potential pathophysiological importance of LOX has led to the evaluation of interventions that target LOX/LOXL proteins for heart-disease therapy. The purposes of this review article are: (i) to summarize the basic biochemistry and enzyme function of LOX and LOXL proteins; (ii) to consider their tissue and species distribution; and (iii) to review the results of experimental studies of the roles of LOX and LOXL proteins in heart disease, addressing involvement in the mechanisms, pathophysiology and therapeutic responses based on observations in patient samples and relevant animal models. Therapeutic targeting of LOX family enzymes has shown promising results in animal models, but small-molecule approaches have been limited by non-specificity and off-target effects. Biological approaches show potential promise but are in their infancy. While there is strong evidence for LOX-family protein participation in heart failure, myocardial infarction, cardiac hypertrophy, dilated cardiomyopathy, atrial fibrillation and hypertension, as well as potential interest as therapeutic targets, the precise involvement of LOX-family proteins in heart disease requires further investigation.
Vaping: CDC investigates severe lung injuries
Authors: Janice Hopkins Tanne
Journal: BMJ (2019)

The US Centers for Disease Control and Prevention (CDC) is investigating nearly 100 cases of severe lung injury related to the use of electronic cigarettes, or “vaping.”

The cases have occurred in five states—Wisconsin, Illinois, California, Indiana, and Minnesota. Most of the people affected have been young adults. The CDC is also investigating unconfirmed cases in other states including New York, Indiana, and Utah.1

From 18 June to 15 August, 14 states reported 94 cases of severe lung injury associated with vaping. Thirty cases occurred in the upper Midwest state of Wisconsin, and nearby Illinois reported 24 possible cases.

All patients reported “vaping,” …
Effect of Recombinant Activated Coagulation Factor VII on Hemorrhage Expansion Among Patients With Spot Sign–Positive Acute Intracerebral Hemorrhage
Authors: David J. Gladstone, Richard I. Aviv, Andrew M. Demchuk, Michael D. Hill, Kevin E. Thorpe, Jane C. Khoury, Heidi J. Sucharew, Fahad Al-Ajlan, Ken Butcher, Dar Dowlatshahi, Gord Gubitz, Stephanie De Masi, Judith Hall, David Gregg, Muhammad Mamdani, Michel Shamy, Richard H. Swartz, C. Martin del Campo, Brett Cucchiara, Peter Panagos, Joshua N. Goldstein, Janice Carrozzella, Edward C. Jauch, Joseph P. Broderick, Matthew L. Flaherty
Journal: JAMA Neurology (2019)

Intracerebral hemorrhage (ICH) is a devastating stroke type that lacks effective treatments. An imaging biomarker of ICH expansion-the computed tomography (CT) angiography spot sign-may identify a subgroup that could benefit from hemostatic therapy.To investigate whether recombinant activated coagulation factor VII (rFVIIa) reduces hemorrhage expansion among patients with spot sign-positive ICH.In parallel investigator-initiated, multicenter, double-blind, placebo-controlled randomized clinical trials in Canada ("Spot Sign" Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy [SPOTLIGHT]) and the United States (The Spot Sign for Predicting and Treating ICH Growth Study [STOP-IT]) with harmonized protocols and a preplanned individual patient-level pooled analysis, patients presenting to the emergency department with an acute primary spontaneous ICH and a spot sign on CT angiography were recruited. Data were collected from November 2010 to May 2016. Data were analyzed from November 2016 to May 2017.Eligible patients were randomly assigned 80 μg/kg of intravenous rFVIIa or placebo as soon as possible within 6.5 hours of stroke onset.Head CT at 24 hours assessed parenchymal ICH volume expansion from baseline (primary outcome) and total (ie, parenchymal plus intraventricular) hemorrhage volume expansion (secondary outcome). The pooled analysis compared hemorrhage expansion between groups by analyzing 24-hour volumes in a linear regression model adjusted for baseline volumes, time from stroke onset to treatment, and trial.Of the 69 included patients, 35 (51%) were male, and the median (interquartile range [IQR]) age was 70 (59-80) years. Baseline median (IQR) ICH volumes were 16.3 (9.6-39.2) mL in the rFVIIa group and 20.4 (8.6-32.6) mL in the placebo group. Median (IQR) time from CT to treatment was 71 (57-96) minutes, and the median (IQR) time from stroke onset to treatment was 178 (138-197) minutes. The median (IQR) increase in ICH volume from baseline to 24 hours was small in both the rFVIIa group (2.5 [0-10.2] mL) and placebo group (2.6 [0-6.6] mL). After adjustment, there was no difference between groups on measures of ICH or total hemorrhage expansion. At 90 days, 9 of 30 patients in the rFVIIa group and 13 of 34 in the placebo group had died or were severely disabled (P = .60).Among patients with spot sign-positive ICH treated a median of about 3 hours from stroke onset, rFVIIa did not significantly improve radiographic or clinical outcomes.ClinicalTrials.gov identifier: NCT01359202 and NCT00810888.
Refractory Generalized Granuloma Annulare Treated With Oral Apremilast
Authors: Anuradha Bishnoi, Dinesh Raj, Keshavamurthy Vinay, Sunil Dogra
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
ICD-11 and gender incongruence of childhood: a rethink is needed
Authors: Sam Winter, Diane Ehrensaft, Michelle Telfer, Guy T'Sjoen, Jun Koh, Simon Pickstone-Taylor, Alicia Kruger, Lisa Griffin, Maya Foigel, Griet De Cuypere, Dan Karasic
Journal: The Lancet Child & Adolescent Health (2019)
The Cancer Genome Atlas: Integrated analysis of genome alterations in squamous cell carcinoma of the head and neck.
Authors: David N. Hayes, Jennifer R. Grandis, Adel K. El-Naggar
Journal: Journal of Clinical Oncology (2013)

6009 Background: Head and neck squamous cell carcinoma (HNSCC) is a leading cause of cancer death in worldwide. Methods: The Cancer Genome Atlas (TCGA) is conducting DNA, RNA and miRNA sequencing along with DNA copy number profiling, quantification of mRNA expression, promoter methylation, and reverse-phase protein arrays on surgically resected samples from previously untreated patients with HNSCC. We report for the first time the integrated genomic alterations for 279 HNSCC patients. Results: The demographics of 279 patients enrolled in the study show a median age of 61 years (range: 19-90); 27% female, and history of tobacco smoking in 80%. Over 30 sites of significant somatic copy number alteration were identified as well as 15 significantly mutated genes at the false fiscovery rate of &lt;0.01, including: CDKN2A, TP53, PIK3CA, FAT1, MLL2, TGFBR2, HLA-A, NOTCH1, HRAS, NFE2L2, and CASP8. Evidence of the human papilloma virus (HPV) was observed by sequencing in up to 25% of samples. Integrated genomics data supported expected patterns including the predominant role of HPV type 16 infection in nonsmoking patients with tumors of the oropharynx which are wild-type for the tumor suppressor genes p16, Rb, and p53. In addition, striking atypical cases and viral infections will be presented as well as novel anti-correlation of HPV infection with focal copy number alterations including EGFR amplification and chromosome 11q. By contrast co-occurrence of HPV with focal deletions of TRAF3 and mutations of the oncogene PIK3CA will be described. Integrated tumor subtypes defined by gene expression, methylation, and miRNA will be presented in conjunction with associated mutations exclusive to tumor subtypes. For example, alterations of the “antioxidant response elements” transcription activators NFE2L2 and KEAP1 will be documented in association with the “classical” expression subtype of HNSCC, as has been shown in lung squamous cell carcinoma. By contrast, co-occurrence of CASP8 and HRAS will be documented in the “Basal” subtype. Conclusions: While, HNSCC is a heterogeneous tumor, coordinated tumor alterations are observed, including potentially targetable genes and pathways. Results presented on behalf of TCGA.
Quantifying the Association Between Psychotherapy Content and Clinical Outcomes Using Deep Learning
Authors: Michael P. Ewbank, Ronan Cummins, Valentin Tablan, Sarah Bateup, Ana Catarino, Alan J. Martin, Andrew D. Blackwell
Journal: JAMA Psychiatry (2019)

Compared with the treatment of physical conditions, the quality of care of mental health disorders remains poor and the rate of improvement in treatment is slow, a primary reason being the lack of objective and systematic methods for measuring the delivery of psychotherapy.
Advanced epithelioid haemangioendotelioma: Fever, pain, and pleural effusion predict a worse outcome.
Authors: Bruno Vincenzi, Anna Maria Frezza, Antonella Brunello, Lorenzo D'Ambrosio, Giacomo G. Baldi, Giuseppe Badalamenti, Giovanni Grignani, Andrea Napolitano, Sergio Valeri, Luca Improta, Mariella Spalato Ceruso, Marianna Silletta, Angelo Paolo Dei Tos, Alessandro Gronchi, Silvia Stacchiotti
Journal: Journal of Clinical Oncology (2019)

e22540 Background: Epithelioid hemangioendothelioma (EHE) is an exceedingly rare soft tissue sarcoma subtype. EHE often presents as a multifocal/ multivisceral disease and its clinical behavior is highly unpredictable from indolent to very aggressive forms. A common choice in advanced patients is a close, active surveillance (AS), considering a treatment only in case of disease progression. Our retrospective study aimed to identify clinical features associated with a more aggressive behavior. Methods: Patients affected by advanced EHE treated in 6 centers of the Italian Rare Cancer Network were retrospectively reviewed. Diagnosis was confirmed by a sarcoma expert pathologist and molecular analysis was performed. Baseline clinical features were evaluated, including the presence of systemic symptoms (fever, weight loss, anorexia) and/or tumor related pain. Number of organs involved (1 vs &gt; 1 and 1-2 vs &gt; 2, mitotic index (&lt; 2 vs ≥= 2 mitosis/10 high power fields - HPF). Results: 74 patients were identified (M:F = 42:32; mean age = 44 yrs - range = 16-81, median number of mitosis/10 HPF = 2 - range 0/8, systemic simptoms Y:N = 30:44; fever Y:N = 21:53; tumor related pain Y:N = 23:51; pleural effusion Y:N = 11:63). All patients had metastatic disease; 29 showed the involvement of one organ while 45 had multivisceral disease (18 of them &gt; 2 viscera). At the time of diagnosis, all patients were naive from any systemic therapy and underwent exclusive AS. At a median FU of 32 months (range: 3-212), 48 (65%) patients progressed while 26 (35%) remained stable. No spontaneous regressions were observed. Median PFS was 30 months (range 2-115). Median OS was 54 months (range 3-151). Age, gender, mitotic index, number of involved organs, anorexia and weight loss did not correlate with median PFS (m-PFS). Fever correlated with shorter m-PFS (8 vs 45 months, P= 0.004), as well as pain (10 vs 42 months, P= 0.02) and the presence of pleural effusion (5 vs 46 months, P= 0.0001). In addition, fever and pleural effusion correlated with a shorter m-OS, respectively 29 vs 60 months (P = 0.03) and 11 vs 77 months (P &lt; 0.001). The presence of pain corresponded to a not significant worse m-OS (39 vs 54 months, P= 0.16). Conclusions: Despite the small number of cases, this retrospective study suggests that in advanced EHE patients the presence of fever and/or tumor related pain and/or of pleural effusion can be associated with a more aggressive clinical behavior. Pleural effusion seems to be associated with the worse outcome, with a m-OS of 12 months. These data are worth confirming on a larger patient population.
Reduced 90-day postoperative mortality through geriatric comanagement after cancer surgery.
Authors: Armin Shahrokni, Amy Tin, Saman Sarraf, Koshy Alexander, Soo Jung Kim, Heidi Yulico, Sincere McMillan, Robert J. Downey, Andrew Vickers, Beatriz Korc-Grodzicki
Journal: Journal of Clinical Oncology (2019)

11512 Background: We explored the association between geriatric comanagement and 90-day postoperative mortality of cancer patients aged 75 or older. Methods: A retrospective review of a prospectively maintained database was performed on patients over 75 years old who underwent elective surgery with hospital length of stay of ≥1 day at Memorial Sloan Kettering Cancer Center from 2015-2018. Geriatric comanagement group (GCG) patients had geriatric preoperative evaluation and inpatient geriatric comanagement. Patients in the surgical management group (SMG) did not have geriatric preoperative evaluation or postoperative geriatric comanagement. We utilized a multivariable logistic regression model with 90-day mortality as the outcome, geriatric co-management as the predictor, and adjusted for age, gender, American Society of Anesthesiology score, Memorial Sloan Kettering Frailty Index, preoperative albumin level, operation time, and estimated blood loss. The same logistic model was used to assess the association between adverse surgical events within 30-days (any major complication, readmission, or urgent care center visit) and geriatric comanagement. Results: Of 1,855 patients (median age 80), 1,009 patients (54%) were co-managed by geriatricians. GCG patients were slightly older, less likely to be male, had longer operation time, and stayed in the hospital longer. Adjusted rates of 90-day mortality was lower in GCG vs. SMG (4.3% and 9.2%, respectively; 95% CI around difference -7.3%, -2.5%; p-value &lt; 0.0001). We did not find evidence of a difference in adverse surgical events between groups (OR 0.96, p-value = 0.8). A greater proportion of GCG patients received inpatient physical therapy (80% vs. 64%) and occupational therapy (37% vs. 25%) compared to SMG patients. Conclusions: Our study shows that geriatric comanagement is associated with reduced 90-day postoperative mortality in cancer patients aged ≥75. A randomized trial study is needed to confirm this finding.
Circulating tumor cells (CTCs) and molecular subtypes (MST) in a treatment algorithm for metastatic breast cancer (MBC).
Authors: Mark Graham, Natanya Fleming, Susan Blumenthal, Brittani Boehlke, Eric Schuur
Journal: Journal of Clinical Oncology (2012)

e21022 Background: We measured CTC s and MST of MBC [ER+, HER2- (HR+); HER2+ (H2+); or Triple Negative (TN)] in all MBC pts in our practice and used these in an algorithm to treat MBC. Methods: CTC’s were measured in 156 pts whether beginning Rx with 1st MBC (97), or under way with Rx (59). Pts had CTC s measured over 61 mo. from 11/20/06 thr. 12/31/11; 66 of the pts had died as of 12/31/11. Pts were Rx’d with an algorithm using CTC’s and MST: Pts with ≥ 5 CTC s were Rx’d with chemoRx, usually doublet ChemoRx, but accounting for pt preferences. When CTC’s improved to &lt; 5 for a sustained 3-4 mo. period, or if initially &lt; 5m we sought less morbid therapies: hormonal if ER+, or single agent ChemoRx +/- biologics if ER- or hormone refractory. In a detailed statistical analysis of variables affecting Disease Specific Survival (DSS) in the first 140 pts thr. 6/30/11, with median f/u of 24.0 mo., highest CTC level (max CTC) observed during f/u was used for analysis: CTC Low (max &lt;5, n=60); CTC Moderate (max 5-99; n=55); and CTC High (max ≥ 100; n=25). Results: We reported the distribution of pts and death rates for the 3 MST and the 3 max CTC groupings earlier (Graham, ASCO 2010); the conclusions are similar with 156 pts and longer f/u. Each MST has 40% of pts with 0-4 CTC’s at all time points. Each MST has a smaller group with CTC’s ≥ 100, 16% of all pts. 33% of deaths (22 of 66) occurred in the ≥ 100 CTC pts. 88% with ≥ 100 CTC’s died; these are early deaths. Only 13 of 66 (20%) died if CTC’s &lt; 5, and 31 of 65 (48%) ifh 5-99 CTC’s. In the first 140 pt analyzed thr. 6/30/11, the median DSS from date of highest CTC is not reached for the CTC Low (max. f/u 54 mo.), vs. 35.8 mo. in the CTC Moderate and 3.3 mo. in the CTC High. DSS was signif. longer for the CTC Low and CTC Moderate vs. the CTC High (P&lt;0.001 for both comparisons). DSS was also signif. greater in the CTC Low vs. the CTC Moderate (P = 0.04). Cox multivariate analysis showed that the Max CTC group (HR 4.8, 95% CI 3.1 - 7.6, p &lt; 0.001), age ≥ 55 at time of max CTC (HR 4.0, 95% CI 2.7 - 7.9, p &lt; 0.001), and MST (HR 2.1, 95% CI 1.4 – 3.1, p &lt; 0.001) were predictive of DSS. Conclusions: a. A treatment algorithm of CTC’s and MST in MBC finds subgroups of MBC with long, intermediate and very short DSS; b. Effective treatments are short-lived in pts with CTC max ≥ 100.
Randomized, open-label, phase II study comparing the efficacy and the safety of cabazitaxel versus weekly paclitaxel given as neoadjuvant treatment in patients with operable triple-negative or luminal b/HER2 normal breast cancer (GENEVIEVE).
Authors: Stefan Paepke, Sherko Kümmel, Jens U. Blohmer, Serban Dan Costa, Holger Eidtmann, Wolfgang Eiermann, Bernd Gerber, Claus Hanusch, Joern Hilfrich, Jens Bodo Huober, Christian Jackisch, Andreas Schneeweiss, Carsten Denkert, Keyur Mehta, Sibylle Loibl, Gunter Von Minckwitz
Journal: Journal of Clinical Oncology (2013)

TPS1138 Background: Cabazitaxel is a new taxoid promoting the tubulin assembly in vitro and stabilizing microtubules against cold-induced depolymerization as efficiently as docetaxel. It has shown superior survival against mitoxantrone plus prednisone in docetaxel pre-treated hormone refractory metastatic prostate cancer pts leading to its registration. It showed a favorable toxicity profile with a low rate of alopecia. In the GENEVIEVE study it will be compared to weekly paclitaxel, which is currently most widely used in breast cancer (BC) pts. Methods: This is a prospective multicenter, randomized, open label study investigating efficacy and safety of cabazitaxel. Pts with uni- or bilateral primary BC (stage cT3/T2/T1c and cN+/T1c and pNSLN+), tumor lesion ≥ 2cm (palpation) or ≥ 1cm (sonography) and centrally confirmed TNBC or luminal B/HER2- can be included. Pts will be randomized to four q3w cabazitaxel (25mg/m² i.v.) vs. 12 q1w paclitaxel (80mg/m² i.v.). Randomization will be stratified by nodal status and subtype. Treatment will be given until surgery, disease progression, unacceptable toxicity or withdrawal of consent. The primary objective is pathologic complete response (pCR) (ypT0/is ypN0/+). Secondary objectives are pCR in stratified subgroups and by other definitions, objective response rate, pCR and local recurrence free survival in pts with clinical complete response and neg. core biopsy before surgery, breast conservation rate, toxicity, compliance, survival rates, biomarkers predicting response. Assuming 15% pCR in controls and targeting a smallest clinical improvement of 10% (i.e. pCR = 25% in experimental arm), a total of 326 pts (163/arm) are required for the one-sided proportion comparison test (α=0.1) with 80% power. The trial is registered under NCT01779479. Results: Recruitment is planned for 12 mths in 45 (+10 back-up) sites in Germany. 1 st pt in is planned for Feb 2013. Conclusion: GENEVIEVE will rapidly and precisely compare efficacy and tolerability of cabacitaxel vs. paclitaxel to decide if further development in BC is reasonable. Clinical trial information: NCT01779479.