tbuckley/cabot-search huggingface dataset:
Unmet needs of chronic hepatitis C in the era of direct-acting antiviral therapy
Authors: Chung-Feng Huang, Ming-Lung Yu
Journal: Clinical and Molecular Hepatology (2020)

The treatment of chronic hepatitis C (CHC) has been revolutionized in an era of all-oral direct-acting antivirals (DAAs) since 2014. Satisfactory treatment efficacy and tolerability can be provided by novel DAAs. Nevertheless, there are still some unmet needs and emerging issues in the treatment of CHC in the DAA era. Certain hard-to-cure populations are prone to have inferior treatment responses, including patients with severe liver decompensation, active hepatocellular carcinoma (HCC), and hepatitis C virus (HCV) genotype 3 (HCV-3) infection and those who experience multiple DAA treatment failures. Hepatitis B virus (HBV) reactivation during and after DAA treatment has raised concern regarding the use of prophylactic antivirals against HBV throughout DAA treatment. However, the standard strategy for the use of prophylactic antivirals is not uniform across regional guidelines. In the post-sustained virological response (SVR) period, HCC still occurs in a substantial proportion of patients. Due to the relatively short follow-up period, the net benefit of the achievement of an SVR by DAAs in the reduction of extrahepatic manifestations has not yet been determined. Attention must also be paid to HCV reinfection, particularly in high-risk populations. The most critical and unmet need for HCV elimination is the large gap in the HCV care cascade at the population level. To accomplish the World Health Organization (WHO)’s goal for HCV elimination by 2030, the expansion of access to HCV care requires a continuous effort to overcome practical and political challenges.
Small bowel adenocarcinoma phenotyping and prognostic factors.
Authors: Thomas Aparicio, Magali Svrcek, Anais Laforest, Aziz Zaanan, Kanean Beohou, Pauline Afchain, Emmanuel Mitry, Julien Taïeb, Frédéric Di Fiore, Jean-Marc Gornet, Anne Thirot-Bidault, Iradj Sobhani, David Malka, Thierry Lecomte, Christophe Locher, Franck Bonnetain, Pierre Laurent-Puig
Journal: Journal of Clinical Oncology (2013)

3585 Background: SBA is a rare tumor with poor prognosis. Data regarding SBA molecular alterations are lacking. Methods: We searched for several candidate oncogenic alterations and characterised the immunophenotype according to the primary tumour location in pts with SBA (all stages; ampullary tumours excluded) treated in 11 centres from 1996 to 2008. Tissue microarrays were constructed from tumour samples, and DNA was extracted from formalin-fixed, paraffin-embedded samples. HER2, β-catenin, TP53, and mismatch repair (MMR) protein expression was assessed by immunohistochemistry. A molecular analysis assessed microsatellite instability, KRAS mutation and BRAFV600E mutation. Results: We obtained samples from 63 SBA pts (median age, 58 years; tumour stage: I-II, n=19 (30%); III, n=22 (35%); IV, n=20 (32%); locally advanced, n=2 (3%)). HER2 overexpression (3+) was observed in 2/62 (3%) pts. Overexpression of TP53 was observed in 26/62 (42%) pts. Abnormal expression of β-catenin was observed in 12/62 (19%) pts. MMR deficiency (dMMR) was observed in 14/61 (23%) pts, consistent with Lynch syndrome in 7/14 (50%) pts. All of the dMMR tumours were in duodenum or jejunum. Only one of dMMR tumour was stage IV. A KRAS mutation was observed in 21/49 (43%) pts. BRAFV600E mutation was observed in only 1/40 pt. Median overall survival (OS) was 36.6 months (95% confidence interval [CI], 26.9-72.2). In univariate analysis, stage I-II (p&lt;0.001) and dMMR phenotype (p=0.02) were significantly associated with longer OS. In multivariate analysis, only disease stage independently predicted longer OS (p&lt;0.001). For stage IV pts, median OS was 17.9 months (CI, 12.6-36.6). For stage I-III pts median recurrence-free survival (RFS) was 26.7 months (CI: 14.6-42.4). A trend for a better RFS was observed if tumour was dMMR HR: 0.39 (CI, 0.10-1.44], p=0.15. Conclusions: This large study suggests that molecular alterations in SBA are closer to those in colorectal cancer (CRC) than those in gastric cancer, with low levels of HER 2 overexpression and high rates of KRAS mutations. The seemingly higher rate of dMMR than in CRC may be explained by the higher frequency of Lynch syndrome in SBA in pts. A trend for good prognosis was associated with dMMR.
A NOVEL ECHOCARDIOGRAPHIC INDEX DEMONSTRATING REDUCED RELATIVE VALVE LOAD IN PATIENTS WITH PARADOXICAL LOW-FLOW COMPARED TO NORMAL-FLOW SEVERE AORTIC STENOSIS WITH PRESERVED LEFT VENTRICULAR EJECTION FRACTION
Authors: Nicholas Ngiam, Nicholas Chew, Ching-Hui Sia, Hui Wen Sim, Yong-Qiang Benjamin Tan, William K.F. Kong, Tiong-Cheng Yeo, Kian Keong Poh
Journal: Journal of the American College of Cardiology (2020)
BPI20-012: Relative Risk of Various Endocrinopathies Associated With the Use of Immune Checkpoint Inhibitors in the First-Line Treatment of Advanced Renal Cell Carcinoma: a Systematic Review and Meta-Analysis
Authors: Nusrat Jahan, Francis Mogollon-Duffo, Miguel Quirch, Somedeb Ball, Fred Hardwicke, Lukman Tijani, Shabnam Rehman
Journal: Journal of the National Comprehensive Cancer Network (2020)

"BPI20-012: Relative Risk of Various Endocrinopathies Associated With the Use of Immune Checkpoint Inhibitors in the First-Line Treatment of Advanced Renal Cell Carcinoma: a Systematic Review and Meta-Analysis" published on 20 Mar 2020 by National Comprehensive Cancer Network.
FDA Takes on Agricultural Biotech
Authors: Rebecca Voelker, Rebecca Voelker
Journal: JAMA (2020)

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
Reactive arthritis and other musculoskeletal symptoms associated with acquisition of diarrhoeagenic <i>Escherichia coli</i> (DEC)
Authors: Riitta Tuompo, Tinja Lääveri, Timo Hannu, Sari H Pakkanen, Juha Kirveskari, Marjatta Leirisalo-Repo, Anu Kantele
Journal: Annals of the Rheumatic Diseases (2020)

Using a prospective research design, we evaluated the association between acquisition of diarrhoeagenic Escherichia coli (DEC) and development of reactive arthritis (ReA) and other reactive musculoskeletal (MSK) symptoms among international travellers.A total of 526 study participants were asked to provide pretravel and post-travel stool samples and fill in questionnaires (pretravel, post-travel and 3-week follow-up). A multiplex quantitative PCR assay was deployed to detect five DEC comprising enteroaggregative E. coli, enteropathogenic E. coli, enterotoxigenic E. coli, enterohaemorrhagic E. coli and enteroinvasive E. coli and Salmonella, Shigella, Campylobacter, Yersinia, and Vibrio cholerae. Multivariate analysis was employed to identify factors predisposing to MSK symptoms. New post-travel MSK symptoms reported by participants with DEC were assessed by phone interviews and, if needed, clinically confirmed.From among the total of 224 volunteers who returned all questionnaires and stool specimens, 38 (17.0%) reported MSK symptoms. Multivariate analysis revealed that acquisition of DEC was associated with MSK symptoms (OR 3.9; 95% CI 1.2 to 13.3). Of the 151 with only-DEC, four (2.6%) had ReA, two (1.3%) reactive tendinitis and three (2.0%) reactive arthralgia. ReA was mostly mild, and all patients with ReA were negative for human leucocyte antigen B27. Antibiotic treatment of travellers' diarrhoea did not prevent development of MSK symptoms.A total of 17% of volunteers reported post-travel MSK symptoms. DEC acquisition was associated with an increased risk of developing them, yet the ReA incidence remained low and the clinical picture mild. Antibiotic treatment did not protect against development of MSK symptoms.
Interleukin-10 promoter gene polymorphism (-819*C) associated with poor treatment outcome in DLBCL patients treated with 8 cycles of R-CHOP as a first line
Authors: Y. K. Kim, H. N. Kim, J. J. Lee, D. H. Yang, J. S. Ahn, S. H. Cho, I. J. Chung, M. R. Park, H. J. Kim
Journal: Journal of Clinical Oncology (2006)

7575 Background: IL-10 is an anti-inflammatory cytokine inhibiting T h1 functions, which may facilitate tumor escape from the immune response. Among the various IL-10 promoter genes, the IL-10–1082G, -819C and -592C alleles were reported to be associated with high serum IL-10 level. Methods: In present study, we studied the frequency of these 3 alleles and their influence to the clinical outcome in 50 DLBCL patients treated with 8 cycles of R (Rituximab, 375 mg/m 2 on day 1 of each cycle)-CHOP every 3 weeks. Results: 50 patients with newly diagnosed DLBCL were included and all of them represented CD20 positivity. At diagnosis, median age was 60 (19∼85) and 24 (48%), 14 (28%), 8 (16%) and 4 (8%) patients belonged to the low, low-intermediate, high-intermediate and high risk group according to IPI reports, retrospectively. Of 50 patients, 8 (16%), 19 (38%) and 22 (44%) were found to carry IL-10–1082G, -819C and -592C alleles, retrospectively. As compared with -1082AA genotype, -1082G allele (GA/GG) failed to show better outcome (eg. higher CR or longer progression-free survival, PFS) after 8 cycles of R-CHOP. Further, patients with -819C or -592C alleles were not able to affect the response rates (CR or PR) compared with -819TT or -592AA genotype. On the other hand, the PFS was significantly shorter in patients carrying -819C allele than TT genotype (13.9 vs 26.9 ms, p&lt;0.01). PFS also decreased in -592C allele compared with AA genotype (15.2 vs 26.5 ms, p&lt;0.05). Of 30 patients with bcl 2 positivity, patients carrying -819C alleles also showed significant lower PFS than TT genotype (12.4 vs 16.1 ms, p&lt;0.05). In multivariate analysis including IPI, stage, IL-10–1082G, -819C and -592C allele frequencies, -819C allele remained as an independent prognostic factor predicting shorter PFS (RR=3.6, p&lt;0.05). In a haplotype analysis, patients carrying ATA/ATA showed significant longer PFS than in other haplotypes (p&lt;0.05). Conclusions: It is still a matter of debate to manage the DLBCL patients with refractory or progressive disease. This study suggests that the detection of IL-10 gene promoter polymorphism such as -819C allele helps us to predict the patients with poor prognosis and to establish a stratified treatment plan in DLBCL patients. No significant financial relationships to disclose.
Abstract 15671: High-throughput Single-RNA Molecule Imaging Analysis Reveals Spatial Heterogeneity of Cardiomyocytes in Stress Response
Authors: Masahiro Satoh, Seitaro Nomura, Takanori Fujita, Toshiyuki Ko, Takashige Tobita, Masamichi Ito, Kanna Fujita, Hiroyuki Aburatani, Yoshio Kobayashi, Issei Komuro
Journal: Circulation (2017)

Introduction: The heart responds to various mechanical stresses by altering its gene expression profile, however, it remains elusive whether this stress response coincides with spatial heterogeneit...
Cardiac Ultrasound Uses Artificial Intelligence to Produce Images
Authors: Rebecca Voelker
Journal: JAMA (2020)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Obesity, Hypertension, and Cardiac Dysfunction
Authors: Alan J. Mouton, Xuan Li, Michael E. Hall, John E. Hall
Journal: Circulation Research (2020)

Obesity and hypertension, which often coexist, are major risk factors for heart failure and are characterized by chronic, low-grade inflammation, which promotes adverse cardiac remodeling. While macrophages play a key role in cardiac remodeling, dysregulation of macrophage polarization between the proinflammatory M1 and anti-inflammatory M2 phenotypes promotes excessive inflammation and cardiac injury. Metabolic shifting between glycolysis and mitochondrial oxidative phosphorylation has been implicated in macrophage polarization. M1 macrophages primarily rely on glycolysis, whereas M2 macrophages rely on the tricarboxylic acid cycle and oxidative phosphorylation; thus, factors that affect macrophage metabolism may disrupt M1/M2 homeostasis and exacerbate inflammation. The mechanisms by which obesity and hypertension may synergistically induce macrophage metabolic dysfunction, particularly during cardiac remodeling, are not fully understood. We propose that obesity and hypertension induce M1 macrophage polarization via mechanisms that directly target macrophage metabolism, including changes in circulating glucose and fatty acid substrates, lipotoxicity, and tissue hypoxia. We discuss canonical and novel proinflammatory roles of macrophages during obesity-hypertension-induced cardiac injury, including diastolic dysfunction and impaired calcium handling. Finally, we discuss the current status of potential therapies to target macrophage metabolism during heart failure, including antidiabetic therapies, anti-inflammatory therapies, and novel immunometabolic agents.
Role of gemcitabine along with dendritic cell therapy in advanced-stage pancreatic cancers: Phase I/II trial results in 26 patients from India.
Authors: Jamal Anono Khan
Journal: Journal of Clinical Oncology (2012)

e13071^ Background: Pancreatic cancer is the leading cause of cancer deaths worldwide with a very poor survival rate. No adequate therapy allows the patient to have a longer life of even 1 year. Methods: Dendritic cell(DC) based immunotherapy along with gemcitabine chemotherapy is planned to do phase I/II trial in 26 patients of advanced stage adenocarcinoma of pancreas. Inclusion criteria was defined as unresectable disease, ECOG performance status of not more than 2, Blood chemistry and hematocrit within normal range and of all age groups. Peripheral blood mononuclear cells are cultured in GM-CSF/IL-4 in RPMI. At 6 th day of culture, the immature dendritic cells are exposed to antigens previously isolated from fresh excised tissue and further matured for 2 days. The cells along with medium are harvested and 1 million mature DC are infused IV by mixing them in 100 ml of dextrose normal saline with ondasnetron 4mg injection. Gemcitabine was given on day 1 and on day 8 th and DC on day 15 th . The cycle is repeated every month for 3 months followed by DC therapy alone at every 23 days interval till patient survives. The primary end point was overall survival and the secondary end point was improvement in quality quotient. Results: 6 patients survived for 24 months, 10 for 12 months and 3 for 6 months, with radiological improvement in only 4 patients with 25% reduction of disease. The quality quotient of 14 patients improved by second dose of dc therapy with improved appetite and decreased pain in abdomen including cheerfulness in 13 patients. Conclusions: Gemcitabine and DC immunotherapy is a good option for advanced stage pancreas cancer patients.
Localization of Macrophages in the Human Lung via Design-based Stereology
Authors: Patrick S. Hume, Sophie L. Gibbings, Claudia V. Jakubzick, Rubin M. Tuder, Douglas Curran-Everett, Peter M. Henson, Bradford J. Smith, William J. Janssen
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Interstitial macrophages (IMs) and airspace macrophages (AMs) play critical roles in lung homeostasis and host defense, and are central to the pathogenesis of a number of lung diseases. However, the absolute numbers of macrophages and the precise anatomic locations they occupy in the healthy human lung have not been quantified.Objectives: To determine the precise number and anatomic location of human pulmonary macrophages in nondiseased lungs and to quantify how this is altered in chronic cigarette smokers.Methods: Whole right upper lobes from 12 human donors without pulmonary disease (6 smokers and 6 nonsmokers) were evaluated using design-based stereology. CD206 (cluster of differentiation 206)-positive/CD43+ AMs and CD206+/CD43- IMs were counted in five distinct anatomical locations using the optical disector probe.Measurements and Main Results: An average of 2.1 × 109 IMs and 1.4 × 109 AMs were estimated per right upper lobe. Of the AMs, 95% were contained in diffusing airspaces and 5% in airways. Of the IMs, 78% were located within the alveolar septa, 14% around small vessels, and 7% around the airways. The local density of IMs was greater in the alveolar septa than in the connective tissue surrounding the airways or vessels. The total number and density of IMs was 36% to 56% greater in the lungs of cigarette smokers versus nonsmokers.Conclusions: The precise locations occupied by pulmonary macrophages were defined in nondiseased human lungs from smokers and nonsmokers. IM density was greatest in the alveolar septa. Lungs from chronic smokers had increased IM numbers and overall density, supporting a role for IMs in smoking-related disease.
Characterization of Philadelphia-negative myeloproliferative neoplasm patients with chromosome 12 abnormalities.
Authors: Christopher Brent Benton, Maria Florencia Tanaka, Sherry Pierce, Lingsha Zhou, Jorge E. Cortes, Hagop M. Kantarjian, Srdan Verstovsek
Journal: Journal of Clinical Oncology (2013)

7112 Background: Chromosome 12 (Chr 12) abnormalities have been reported as infrequent events in myelofibrosis (MF). Structural abnormalities at 12q13-15 and 12q24 have been reported in primary MF (PMF), and understanding genes at these loci, such as Hmga2 and Lnk may help in the treatment of Philadelphia-negative (Ph-neg) myeloproliferative neoplasms (MPN). We sought to better characterize Ph-neg MPN patients (pts) with Chr 12 aberrations. Methods: We queried a database of pts with any Ph-neg MPN who were referred to MD Anderson Cancer Center from 1985 to 2012. We identified pts with Chr 12 abnormalities and reviewed available clinical information. We compared characteristics and outcomes of pts who had Chr 12 abnormalities with pts who had no Chr 12 abnormality. Results: Of 1,787 pts with Ph-neg MPN, 36 pts (2%) were found to have a Chr 12 abnormality. Of these, 31 (86%) had MF, 1 (3%) had polycythemia vera (PV), 3 (8%) had hypereosinophilic syndrome, and 1 (3%) had unspecified MPN. Fourteen pts (39%) had successive biopsies demonstrating evolving cytogenetic abnormalities. The percentage of pts with MF was significantly higher among patients with Chr 12 abnormalities (86% vs. 54%, p-value &lt; 0.001). A larger fraction of MF pts with Chr 12 abnormalities had post-PV MF (PPMF) (31% vs. 14%, p-value &lt; 0.001). Age, JAK2 status, and incidence and rate of leukemic transformation from MF were not significantly different between the two groups. Of the 31 Chr 12 pts with MF, 12 (39%) had an abnormality at 12q13, 8 (26%) at 12q24, 6 (19%) had trisomy 12, 5 (16%) at 12q15, and 6 (19%) had another Chr 12 abnormality. Four pts (13%) had a structural abnormality at &gt;1 site along the long arm of Chr 12. Survival of Chr 12 MF pts as a whole or subdivided by chromosomal abnormality was not significantly different than MF pts without Chr 12 abnormalities. Conclusions: Our investigation into pts with Ph-neg MPN harboring Chr 12 abnormalities is the largest of its kind, and shows 3% of MF pts possessed some type of Chr 12 abnormality, most frequently at 12q13. We found that Chr 12 Ph-neg MPN pts were more likely to have MF and PPMF. Further investigation into the functional significance of these structural abnormalities is warranted.
LEFT ATRIAL STIFFNESS INDEX IS A DETECTIVE MARKER FOR THE PROGRESSION OF TARGET ORGAN DAMAGE IN HYPERTENSION
Authors: Yan Liu, Yixiao Zhao, Qiaobing Sun, Yan Lu, Ying Zhang, Wei Song, Yunpeng Cheng, Tao Cong, Yinong Jiang
Journal: Journal of the American College of Cardiology (2020)
CLINICAL SIGNIFICANCE OF THE PERIAORTIC ADIPOSE TISSUE INFLAMMATION IN PATIENTS WITH ABDOMINAL AORTIC ANEURYSMS
Authors: Masao Yamaguchi, Masahiro Hoshino, Kai Nogami, Hiroki Ueno, Hidenori Hirano, Masahiro Hada, Yohei Sumino, Toru Misawa, Yoshihisa Kanaji, Tomoyo Sugiyama, Taishi Yonetsu, Tsunekazu Kakuta
Journal: Journal of the American College of Cardiology (2020)
Tips for success in pulmonary hypertension treatment: progress in isolating endothelial cells from pulmonary artery catheters
Authors: Andrea L. Frump, Tim Lahm
Journal: European Respiratory Journal (2020)

<b>The paucity of patient-derived pulmonary cells has been a limiting factor in the study of pulmonary hypertension; however, new advances have the potential to increase scientific translatability and identify novel mechanisms driving early disease</b>http://bit.ly/2U1AUEw