tbuckley/cabot-search huggingface dataset:
Use of Contemporary Imaging Techniques for Electrophysiological and Device Implantation Procedures
Authors: Angelo Auricchio, Francesco Fulvio Faletra
Journal: JACC. Cardiovascular imaging (2019)

Recent technological advances in cardiac imaging allow the visualization of anatomic details up to millimeter size in 3-dimensional format. Thus, it is not surprising that electrophysiologists increasingly rely upon cardiac imaging for the diagnosis, treatment, and subsequent management of patients affected by various arrhythmic disorders. Cardiac imaging methods reviewed in the present work involve: 1) the prediction of arrhythmic risk for sudden cardiac death in patients with heart disease; 2) catheter ablation of atrial fibrillation or ventricular tachycardia; and 3) cardiac resynchronization therapy. Future integration of diagnostic and interventional cardiac imaging will further increase the effectiveness of cardiac electrophysiological procedures and will help in delivering patient-specific therapies with ablation and cardiac implantable electronic devices.
Metformin Inhibits Progression of Head and Neck Squamous Cell Carcinoma by Acting Directly on Carcinoma-Initiating Cells
Authors: Xingyu Wu, Huwate Yeerna, Yusuke Goto, Toshinori Ando, Victoria H. Wu, Xuefeng Zhang, Zhiyong Wang, Panomwat Amornphimoltham, Anne N. Murphy, Pablo Tamayo, Qianming Chen, Scott M. Lippman, J. Silvio Gutkind
Journal: Cancer Research (2019)

Abstract Metformin may reduce the progression of head and neck squamous cell carcinoma (HNSCC); however, whether metformin acts by altering the host metabolism or targets cancer-initiating cells remains poorly understood. This gap in knowledge has prevented the stratification of patient populations who are most likely to benefit from metformin treatment. Here, we explored whether metformin acts directly on HNSCC cells to inhibit aberrant cell growth. To investigate the tumor cell autonomous effects of metformin, we engineered representative HPV− and HPV+ HNSCC cells harboring typical genetic alternations to express the yeast mitochondrial NADH dehydrogenase (NDI1) protein, which is insensitive to metformin. NDI1 expression rescued the inhibitory effects of metformin on mitochondrial complex I, abolished the ability of metformin to activate AMP-activated protein kinase, and inhibited mTOR signaling both in vitro and in vivo, and was sufficient to render metformin ineffective to prevent HNSCC tumor growth. This experimental system provided an opportunity to identify metformin-regulated transcriptional programs linked to cancer cell growth inhibition in the tumor microenvironment. Remarkably, computational analysis of the metformin-induced transcriptome revealed that metformin downregulated gene expression signatures associated with cancer stemness and epithelial–mesenchymal transition, concomitant with increased expression of squamous differentiation genes. These findings support that metformin may act directly on cancer-initiating cells to prevent their progression to HNSCC, which may inform the selection of patients at risk of developing HNSCC in future early-stage clinical trials. Significance: Metformin's ability to directly target HNSCC-initiating cells instead of exerting cancer preventive activity based solely on its systemic effects may inform the selection of patients in future precision prevention trials.
<i>Notes from the Field:</i> Hurricane Florence–Related Emergency Department Visits — North Carolina, 2018
Authors: Lauren J. Tanz, Molly N. Hoffman, Dana Dandeneau, Zachary Faigen, Zack Moore, Scott Proescholdbell, Susan M. Kansagra
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

In September 2018, in North Carolina, medication refill emergency department (ED) visits were significantly more prevalent during Hurricane Florence than before or after the hurricane; 31% of ED visits during Hurricane Florence were for medication refills.
Abstract 269: Miofibroblast Tgf-beta Signaling in a Proteotoxic Mouse Model
Authors: Bidur Bhandary, Qinghang Meng, Hanna Osinska, Kritton Shay-Winkler, James Gulick, Shenuarin Bhuiyan Md., Jeffrey Robbins
Journal: Circulation Research (2016)

Introduction: Transforming Growth Factor Beta (TGFβ) is an important cytokine in mediating the fibrogenic response and, in particular, cardiac fibrosis. Extensive fibrosis accompanies the cardiac remodeling that occurs during development of the protein conformation-based disease caused by cardiomyocyte-specific expression of a mutant, small, heat shock-like protein and chaperone, aB crystallin (CryABR120G). During the onset of fibrosis, fibroblasts are activated to the so-called “myofibroblast” state and TGFβ binding is thought to mediate an essential signaling pathway underlying this process. Our central hypothesis is that TGFβ signaling processes that result in significant cardiac fibrosis in a mouse model of proteotoxic heart disease are mediated by cardiac fibroblasts, rather than cardiomyocytes. Here, we have partially ablated TGFβ signaling only in cardiac myofibroblasts to observe if cardiac fibrosis is reduced. Aims and Methods: The objective of this study was to understand the contributions of fibroblast-derived TGFβ signaling to the development of cardiac fibrosis in a proteotoxic mouse model that results in significant cardiac fibrosis. To test the hypothesis we partially deleted the myofibroblast specific canonical and non-canonical signaling by crossing CryAB R120G mice with Tgfbr1 or Tgfbr2 floxed mice. The double transgene containing mice were further crossed with activated myofibroblast specific Cre mice in which Cre expression was driven off the periostin promoter. Echocardiography, Masson’s Trichome staining, PCR arrays, IHC and western blots were performed to characterize the fibrotic progression in CryAB R120G transgenic mice. Results: We observed that myofibroblast-targeted partial knockdown of Tgf βr1 signaling prolonged survival, modestly reducing fibrosis and improving cardiac function . Similarly, Tgf βr2 partial knockdown prolonged survival, modestly reducing fibrosis without improving cardiac function during fibrosis development in CryAB R120G mice. Conclusion: These findings suggest that, in a model of proteotoxic heart disease, myofibroblast based TGFβ signaling in the heart may contribute to cardiac hypertrophy/dysfunction but cannot account entirely for the fibrotic response.
Cellular response to the combined effect of trifluoperazine and ionizing radiation: A molecular study.
Authors: Sudeshna Gangopadhyay, Parimal Karmakar
Journal: Journal of Clinical Oncology (2012)

e13533 Background: It is known that some phenothiazines group of drugs have the potential to modulate ionizing radiation (IR) induced cellular damage. In our previous study, we have shown that Trifluoperazine (TFP), a phenothiazine derivative antipsychotic drug, modulate the effect of IR by inhibiting the IR induced DNA double strand break (DSB) repair, and raising the possibility of using TFP as an adjuvant to radiotherapy. In the present study we tried to explore the mechanism of IR induced DNA damage repair inhibition by TFP. Methods: Effect of TFP and IR on cell viability was determined by MTT assay. Study of possible signaling pathway leading to IR induced cell killing was checked using indirect immunolabeling and transfection. Results: It was observed that the use of TFP (2.5 µg/mL) reduces the LD 50 from 13 Gy to 7.5 Gy. After transfecting the cells with GFP-tagged Ku80 plasmid, we have seen that in the gamma-irradiated cells, Ku80 was completely localized in the nucleus, indicating close association of Ku with the broken DNA ends. However, in the TFP (2.5 μg/mL) treated cells, Ku80 was retained in the cytoplasm after irradiation. Similarly, with indirect immunofluorescence experiments using antibody against DNA-PKcs, the catalytic component of DNA-PK, large bright dots of DNA-PKcs was present in the nucleus when cells were treated with IR alone. But, when the cells were irradiated in the presence of TFP, DNA-PKcs migrated to the nucleus partially, even after 4 h of irradiation. Conclusions: Thus, TFP prevents the trafficking of DNA-PK complex from cytoplasm to nucleus and thereby inhibits the DNA-PK mediated NHEJ. Taken together, our results suggest that TFP sequestered the DNA-PK complex, which is a major player in non homologous end joining (NHEJ) and enhance the effect of IR.
Estimated costs of grade 3–4 all-cause and treatment-related adverse events for stage IV or recurrent non-small cell lung cancer (NSCLC) in the CheckMate 227 (CM-227) trial.
Authors: David D. Stenehjem, Irene Santi, Komal Gupte-Singh, John R. Penrod, Meena Venkatachalam
Journal: Journal of Clinical Oncology (2019)

120 Background: In the ongoing phase 3 CM-227 trial, nivolumab + ipilimumab (N+I) showed significantly longer progression-free survival compared to chemotherapy (C) among patients with NSCLC and tumor mutational burden (TMB) ≥10 mutations/megabase (high) by Foundation One CDx. The frequencies of all-cause (AC) and treatment-related (TR) adverse events (AEs) including grade 3–4 AEs were similar between the N+I and C arms, although the types of AEs differed. This study estimated the costs of managing grade 3–4 ACAEs and TRAEs in the first year after treatment initiation in CM-227 patients with high TMB. Methods: The frequency, grade, and attribution of AEs were extracted from CM-227 patient-level data. Costs of managing each grade 3–4 ACAE and grade 3–4 TRAE were estimated using related codes of the International Classification of Disease, 10th Revision, as well as cost information from the Healthcare Cost and Utilization Project National Inpatient Sample data (2015). A sensitivity analysis accounting for treatment duration and a temporal trends analysis were conducted. Results: In patients treated with N+I (n = 135), 157 grade 3–4 ACAEs and 70 grade 3–4 TRAEs were observed compared to 153 and 74 respectively among the patients treated with C (n = 159). The cost of managing grade 3–4 ACAEs per treated patient for N+I was $19,602 and for C was $16,353 (difference $3,249; 95% CI $1,774–$4,723), while the cost of managing grade 3–4 TRAEs per treated patient was $6,921 and $8,925 for N+I and C, respectively (difference $2,004; 95% CI $878–$3,131). An analysis adjusting for treatment duration yielded lower cost per person-month for N+I compared to C for both grade 3–4 ACAEs ($2,886 and $3,521; difference $634; 95% CI $379–$889) and grade 3–4 TRAEs ($1,019 and $1,921, difference $902; 95% CI $696–$1,109). For both N+I and C, the cost of managing grade 3–4 ACAEs and grade 3–4 TRAEs per person-month was highest in the first 3 months and declined thereafter. Conclusions: The cost of ACAEs was somewhat higher for N+I than for C, while the cost of TRAEs was somewhat lower for N+I than for C. Adjusting for treatment duration, N+I had lower costs for both ACAEs and TRAEs compared to C. Clinical trial information: NCT02477826.
The first 10 years experience with genetic testing (GT) for BRCA1/2 mutations in a publicly funded program at a tertiary care teaching hospital in Ontario, Canada.
Authors: Sherry Athena Doroja Ruste, Andrea Eisen, Kathleen I. Pritchard
Journal: Journal of Clinical Oncology (2013)

1550 Background: Publicly funded testing for BRCA1/2 mutations in Ontario has been available for high-risk individuals since 2000. The criteria are based on personal and/or family cancer history and ethnicity. We reviewed the results of the first 10 yrs of testing at our institution, a regional cancer centre in an academic, tertiary care teaching hospital. Methods: This REB-approved, retrospective study included individuals who had GT from 2001-2011. Sociodemographic, clinical, and GT results were collected. Results: 2,305 individuals met criteria and underwent GT between Jan. 2001and Dec. 2011. Of all tested subjects, 93% were female, median age was 55 yrs., 23% were of Ashkenazi Jewish (AJ) ancestry and 80% lived in an area with family income $50-100K/yr. BRCA1/2 mutations were present in 16%, 8% had unclassified variant (UCV), 76% had normal sequence. We excluded 460 individuals who had predictive GT for a familial mutation, and results are shown in the Table. For each carrier, an average of four additional relatives had GT. The most common criteria for GT was at least three cases of ovarian or breast cancer at any age on the same side of the family. BRCA mutations were most common among those AJ, Italian, Asian Oriental and English ancestry. Wait time for GT result improved from 107 wks. in 2001 to 8 wks. in 2011. Conclusions: In our tested population, the prevalenceof BRCA1/2 mutations was high. Over time wait times improved and more relatives were tested. [Table: see text]
Clinical Applicability of Ultrasound in Systemic Large Vessel Vasculitides
Authors: Alen Brkic, Lene Terslev, Uffe Møller Døhn, Søren Torp‐Pedersen, Wolfgang A. Schmidt, Andreas P. Diamantopoulos
Journal: Arthritis & Rheumatology (2019)

The systemic large vessel vasculitides consist mainly of giant cell arteritis and Takayasu arteritis. Both diseases affect the large blood vessels and can lead to ischemia and end‐organ damage. Ultrasound is an imaging technique that can depict inflammation of the vessel wall in large and medium vessel vasculitis. In this article, we critically review the current evidence for the clinical use of ultrasound for systemic large vessel vasculitides, regarding the clinical applicability, technical requirements, challenges, and cost. A roadmap for the development of a fast‐track ultrasound clinic for giant cell arteritis is also provided.
Characterisation of measles after the introduction of the combined measles-mumps-rubella (MMR) vaccine in 2004 with focus on the laboratory data, 2016 to 2019 outbreak, Romania
Authors: Mihaela Lazar, Aurora Stănescu, Ana Raquel Penedos, Adriana Pistol
Journal: Eurosurveillance (2019)

BackgroundSince January 2016, a resurgence of measles in Romania has led to the third measles epidemic in the past 12 years; 64 deaths have been confirmed so far-the highest number of measles-related deaths since the measles-mumps-rubella (MMR) vaccine was introduced in 2004.AimTo provide an overview on the characterisation on measles in Romania after the introduction of the MMR vaccine with focus on the current outbreak, laboratory and molecular analysis.MethodsWe performed an analysis of measles incidence and mortality after the introduction of MMR vaccination and a retrospective study using serological and molecular data in three consecutive outbreaks with focus on the current outbreak.ResultsIn the current outbreak, 17,533 measles cases were notified to the national surveillance system, 93% were unvaccinated. Measles virus was isolated from 429 samples and 283 were genotyped. Genotype B3 was predominant (n = 269) and sporadic measles cases associated with D8 genotype (n = 9) were also observed; genotype D4 and D8 were identified in the previous two measles outbreaks. The detection of several distinct measles virus B3 genotypes suggests multiple virus importations to Romania.ConclusionThe current outbreak is a consequence of insufficient vaccine coverage. Control measures were implemented to improve uptake of MMR vaccine, including administering the first MMR dose at a younger age (9-11 months) and offering catch-up vaccination to children that have not followed the recommended dosing schedule. More measures are needed to improve the surveillance performance and to achieve high routine MMR vaccination coverage.
Clarification of Reporting of Potential Conflicts of Interest in <i>JAMA</i> Articles
Authors: Victor J. Dzau
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Immune-related adverse events in advanced NSCLC treated with immunotherapy alone or concurrent chemotherapy and immunotherapy.
Authors: John Melson, Daniel Reed, Bethany J. Horton, Margaret Moore, Jacqueline Theresa Brown, Ryan D. Gentzler, Richard Delmar Hall
Journal: Journal of Clinical Oncology (2019)

83 Background: Concurrent chemotherapy (CTX) with checkpoint inhibitors (CPI) has become a new standard of care for treatment naïve stage IV non-small cell lung cancer (NSCLC). Little is known about the timing and pattern of immune-related adverse events (irAEs) when CTX and CPI are combined. We sought to characterize irAEs and determine if combination CTX+CPI affects time to first irAE in comparison to patients (pts) receiving CPI alone. Methods: Advanced NSCLC patients who received at least one dose of a CPI at our institution between 2015 and 2018, either alone or with CTX, were identified. Retrospective review for occurrence of irAEs and clinical outcomes was performed. Proportional hazards models were used to assess time to first irAE for CPI vs CTX+CPI and overall survival (OS) for CPI alone. Results: 149 pts were identified. 112 pts received CPI alone and 37 received CTX+CPI. The proportion of pts with at least 1 irAE was higher in the combination therapy group than the monotherapy group (59% vs 34% of patients). Time to any grade first irAE was shorter with CTX+CPI vs CPI alone (6.0 m vs 36.7 m, HR 1.8, p = 0.0304). Among pts treated with CPI alone, OS was significantly longer with any irAE (38.0 m vs 11.4 m, HR 2.9, p = 0.0026). While there were more irAEs in the CTX+CPI cohort, the frequency of irAEs by organ system was similar to previous reports. Conclusions: For patients receiving CTX+CPI, there is an increased risk of irAEs and a significantly shorter time to first irAE occurrence compared to CPI alone. Among patients receiving CPI alone, the presence of irAE was associated with a 3-fold improvement in OS. Further analysis of OS for the CTX+CPI group is planned with additional follow-up. [Table: see text]
Choice of primary endpoints in first-line phase III trials of HER2-negative or HER2-unknown metastatic breast cancer (MBC).
Authors: Sherko Kümmel, Volkmar Müller, Michael P Lux, Geerd Weyer, Jan P Pintoffl, Christian Jackisch
Journal: Journal of Clinical Oncology (2013)

607 Background: OS is considered the most clinically relevant endpoint in cancer therapy trials, but OS can be confounded by post-trial therapy, particularly in settings with long post-progression survival (PPS). Based on statistical modelling with 50,000 simulated trials, Broglio &amp; Berry [JCNI 2009] suggested the association between improved progression-based endpoints (eg, PFS) and OS is weak in settings with PPS &gt;12 months and can only be shown in very large trials. To test this hypothesis, we analysed efficacy outcomes and choice of primary endpoints in first-line MBC trials. Methods: Data wereanalysed from:randomised, controlled phase III trials comparing systemic chemotherapies and/or targeted agents; enrolling ≥150 pts; published in peer-reviewed journals from 2000–2011. Trials that enrolled only HER2-positive MBC pts or evaluated non-EU approved agents were excluded. Results: Of27 trials, 1 (3.7%) had OS as the primary endpoint, while 18 (66.7%) had progression-based parameters, commonly PFS (9 trials, 33.3%). A significant increase in progression-based parameters was seen in 14 trials (51.9%). All 5 trials (18.5%) showing a significant OS benefit had a PPS &lt;12 months. Mean PPS was considerably longer in trials published in 2006–2011 vs 2000–2005 (14.1 ± 4.0 vs 9.7 ± 2.3 months, respectively), as was mean PFS (8.3 ± 2.2 vs 6.6 ± 1.6 months) and mean OS (25.4 ± 5.6 vs 18.6 ± 3.0 months). A weak correlation was seen between OS and PFS (Pearson’s coefficient r=0.32), but a higher correlation was seen in treatment arms with an OS benefit (r=0.59), as well as in treatment arms with a PPS &lt;12 months (r=0.43) or older studies (r=0.51). Data were insufficient to allow a valid analysis of the effect of further-line therapies or cross-over on OS (16 trials reported further-line therapies; 9 cross-over therapy). Conclusions: In support of the hypothesis by Broglio &amp; Berry, a significant OS advantage was shown exclusively in trials with a PPS &lt;12 months. Due to the weak correlation between PFS and OS, it is difficult to determine the possible surrogacy of PFS for OS. Thus, as an OS benefit might be increasingly difficult to attain, progression-based parameters appear to be valid endpoints in MBC clinical trials.
Psychological Consequences of Admission to the ICU
Authors: Louise Rose, Fiona Muttalib, Neill K. J. Adhikari
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Early progression as a predictor of survival in marginal zone lymphomas: an analysis from the FIL-NF10 study
Authors: Stefano Luminari, Michele Merli, Sara Rattotti, Vittoria Tarantino, Luigi Marcheselli, Federica Cavallo, Marzia Varettoni, Benedetta Bianchi, Francesco Merli, Alessandra Tedeschi, Giuseppina Cabras, Francesca Re, Carlo Visco, Marcia Torresan Delamain, Emanuele Cencini, Michele Spina, Simone Ferrero, Angela Ferrari, Marina Deodato, Donato Mannina, Ombretta Annibali, Angela Rago, Lorella Orsucci, Irene Defrancesco, Marco Frigeni, Marina Cesaretti, Luca Arcaini
Journal: Blood (2019)