tbuckley/cabot-search huggingface dataset:
Abstract P414: The Interrelations Between Serum Uric Acid, Silent Myocardial Infarction and Mortality in the General Population
Authors: Muhammad Imtiaz Ahmad, Abhishek Dutta, Muhammad Ali Anees, Elsayed Z Soliman
Journal: Circulation (2019)

Background: Whether elevated uric acid (UA) is associated with silent myocardial infarction (SMI) or whether their joint association predicts an increased risk of mortality has not been explored. Methods: This analysis included 6,323 participants (58.4±13.1 years, 53.9% women, and 49.7% Non-Hispanic whites) without clinical cardiovascular disease (CVD) from the Third National Health and Nutrition Examination Survey (NHANES-III). SMI was defined as electrocardiographic evidence of myocardial infarction (MI) without a history of MI. Multivariable logistic regression model was used to examine the cross-sectional association between baseline UA and SMI. Cox-proportional hazard analysis was used to calculate hazard ratio (HR) with 95% confidence interval (CI) for the risk of all-cause and CVD mortality with UA in the absence and presence of SMI. Results: Higher baseline level of UA was associated with higher odds of baseline SMI. The prevalence of SMI was 0.79%, 1.18%, 1.59% and 2.27% across the UA quartiles respectively; multivariable-adjusted OR (95% CI): 2.53 (1.19-5.37) comparing the upper with lower quartile. During a median follow up of 14 years, there were 1916 all-cause death of whom 774 were CVD deaths. Compared to participants with the lowest UA quartile values and without SMI, those with highest UA had a 34% increased the risk of all-cause mortality (multivariable-adjusted HR: (95%CI): 1.34 (1.15-1.56)). This risk increased by 112% in the presence of SMI (multivariable-adjusted HR (95%CI): 2.12(1.41-3.70)). Similar results were observed for CVD mortality. SMI carried an increased risk of all-cause and CVD mortality only in higher quartiles of UA. Conclusion: The strong association of UA with SMI and the additive effect of UA and SMI on mortality further support the potential role of UA as a marker of poor outcomes. Both UA and electrocardiogram are simple, inexpensive markers which can potentially be used in risk stratification and identification of high-risk individuals.
The Evidence Supporting Cardiovascular Guidelines
Authors: Robert O. Bonow, Eugene Braunwald
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 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
A prospective phase II clinical study of concurrent chemoradiotherapy for 92 cases cervical esophageal squamous cell carcinoma.
Authors: Hongxuan Li, Changxing LV, Jun Liu, Xiaolong Fu
Journal: Journal of Clinical Oncology (2015)

e15072 Background: A single center prospective clinical phase II study to evaluate survival conditions of patients with cervical esophageal squamous cell carcinoma(CESCC) who underwent concurrent chemoradiotherapy (CCRT ) and toxicities. Methods: Eligibility criteria: CESCC pathologically confirmed, no distant metastasis, 18 to 75 years old, PS:0-2, and tolerable to the treatment of CCRT. Radiotherapy: GTV covered the gross tumor and positive lymph nodes. CTV covered GTV with an additional radial margin of at least 1 cm and longitudinal margins of at least 3 cm. Regions of lymph nodes between the upper and lower bounds were included in CTV. PTV-C, PTV-G covered the CTV, GTV with a margin of 0.5-0.8cm respectively; 3D-CRT or IMRT was used. A total dose of 50Gy/25 fractions/5 weeks was given to PTV-C, and 60Gy/30 fractions/6 weeks was given to PTV-G. Chemotherapy: All patients were treated with platinum-based doublet chemotherapeutic regimens. Responders with intolerable toxicities in the first cycle only accepted one cycle of concurrent chemotherapy. Two to three cycles of consolidation chemotherapy followed CCRT. Endpoints: progression free survival (PFS), overall survival (OS), and toxicities. Results: Ninety-two patients were enrolled from March 2007 to July 2014. The median follow-up time was 29 months. In all the patients, 27 cases (29.3%) received two cycles concurrent chemotherapy, 68 cases (73.9%) received at least 2 cycles consolidation chemotherapy, and 81 cases (88%) received 60Gy radiotherapy. The median total dose of radiotherapy was 60Gy (Range: 50 to 63Gy). One-year, 2-year, and 3-year PFS were: 76.7％、52.1％、42.7％ respectively (the median PFS: 25 ±5.316months), One-year, 2-year, and 3-year OS respectively were 89％、65.7％、52.3％(the median OS:40 ±9.116 months). Toxicities: Grade III and IV radiation esophagitis occurred in 51 cases (55.4%) and 3 cases (3.3%) respectively; grade III and, IV myelosuppression occurred in 21 cases (22.8%) and 4 cases (4.3%) respectively. Four cases died of severe toxicities (4.3%), among whom 3 cases had esophageal fistula and 1 case had Laryngeal edema. Conclusions: Efficacy of CCRT for CESCC is satisfying, and toxicities are tolerable.
Apolipoprotein E is a concentration-dependent pulmonary danger signal that activates the NLRP3 inflammasome and IL-1β secretion by bronchoalveolar fluid macrophages from asthmatic subjects
Authors: Elizabeth M. Gordon, Xianglan Yao, Haitao Xu, William Karkowsky, Maryann Kaler, Or Kalchiem-Dekel, Amisha V. Barochia, Meixia Gao, Karen J. Keeran, Kenneth R. Jeffries, Stewart J. Levine
Journal: Journal of Allergy and Clinical Immunology (2019)
Clinical relevance of HEp-2 indirect immunofluorescent patterns: the International Consensus on ANA patterns (ICAP) perspective
Authors: Jan Damoiseaux, Luis Eduardo Coelho Andrade, Orlando Gabriel Carballo, Karsten Conrad, Paulo Luiz Carvalho Francescantonio, Marvin J Fritzler, Ignacio Garcia de la Torre, Manfred Herold, Werner Klotz, Wilson de Melo Cruvinel, Tsuneyo Mimori, Carlos von Muhlen, Minoru Satoh, Edward K Chan
Journal: Annals of the Rheumatic Diseases (2019)

The indirect immunofluorescence assay (IIFA) on HEp-2 cells is widely used for detection of antinuclear antibodies (ANA). The dichotomous outcome, negative or positive, is integrated in diagnostic and classification criteria for several systemic autoimmune diseases. However, the HEp-2 IIFA test has much more to offer: besides the titre or fluorescence intensity, it also provides fluorescence pattern(s). The latter include the nucleus and the cytoplasm of interphase cells as well as patterns associated with mitotic cells. The International Consensus on ANA Patterns (ICAP) initiative has previously reached consensus on the nomenclature and definitions of HEp-2 IIFA patterns. In the current paper, the ICAP consensus is presented on the clinical relevance of the 29 distinct HEp-2 IIFA patterns. This clinical relevance is primarily defined within the context of the suspected disease and includes recommendations for follow-up testing. The discussion includes how this information may benefit the clinicians in daily practice and how the knowledge can be used to further improve diagnostic and classification criteria.
Abstract P249: Central Obesity and Systemic Inflammation Predict Subsequent Levels of Procollagen Type III N-Terminal Peptide in Framingham Offspring Study Adults
Authors: Richard T Pickering, Martha R Singer, Vanessa Xanthakis, Vasan S Ramachandran, Lynn L Moore
Journal: Circulation (2019)

Background: Fibrosis is a process that, in healthy individuals, is characterized by deposition of extracellular matrix (ECM) components. However, in pathological states, such as the low-grade inflammation associated with obesity, excessive tissue ECM production is associated with dysfunction of various organs such as liver, kidney, and adipose tissue. Procollagen Type III N-terminal peptide (P3NP) is produced during collagen synthesis and is linked to adverse outcomes including cardiovascular events. Few studies have examined the relationship between systemic inflammation or body fat distribution and P3NP. Methods: Data from the prospective Framingham Offspring study were used to examine the link between systemic inflammation, body fat distribution and P3NP. Of the 944 individuals with P3NP measured at exam 6, 737 had CRP measured at exam 2 and 859 had waist circumference measured at exam 4, along with potential confounders including sex, age, smoking, and body mass index (BMI). Levels of serum CRP at exam 2 were classified into 3 groups (≤1.0, 1.0 to ≤3.0, &gt;3.0 mg/L) and waist circumference was divided in sex specific quintiles. Due to non-normality, levels of P3NP were log transformed. Multivariable general linear models were used to assess the associations between both CRP and waist circumference and P3NP. Age, sex, smoking status, physical activity and BMI were assessed as potential confounders. Results: Compared with individuals with the lowest levels of CRP at exam 2 (≤1mg/L) those with intermediate or high levels (CRP: 1.0 to ≤3.0, and &gt;3.0) had statistically significantly higher levels of plasma P3NP at exam 6 (3.8 ± 0.2, 4.2 ± 0.3, and 4.3 ± 0.3 mg/L, from lowest to highest category, respectively, p-trend&lt;0.001). Additionally, men in the two highest quintiles of waist circumference at exam 4 had statistically significantly (p&lt;0.05) higher plasma P3NP levels than those in the lowest quintile (4.6 ± 0.4, 4.5 ± 0.4 vs. 3.7 ± 0.4 mg/L for quintiles 5 and 4 vs. 1, respectively). No effect was seen in women. Conclusions: These results suggest a link between both systemic inflammation and waist size (a simple indicator of central adiposity) and circulating markers of fibrosis. These findings may suggest that adverse health outcomes associated with visceral adiposity and systemic inflammation may be linked with development of fibrosis.
Preclinical efficacy studies using HuMax-Axl-ADC, a novel antibody-drug conjugate targeting Axl-expressing solid cancers.
Authors: Esther CW Breij, Sandra Verploegen, Andreas Lingnau, Edward N van den Brink, Maarten Janmaat, Mischa Houtkamp, Wim Bleeker, David Satijn, Paul Parren
Journal: Journal of Clinical Oncology (2015)

3066 Background: HuMax-Axl-ADC is an antibody-drug conjugate (ADC) that specifically targets Axl-expressing tumor cells. Aberrant expression of Axl, a receptor tyrosine kinase, has been described in solid and hematological malignancies, in both primary tumors and metastasis. Expression and activation of Axl is associated with poor clinical prognosis in cancers of the lung, pancreas, esophagus and breast. Moreover, Axl expression has been implicated in resistance to both chemotherapy and targeted therapy. Although the mechanism behind Axl activation in cancer is not fully understood, activation through the Axl ligand Gas6 has been implicated in at least some cancers. At the cellular level, Axl is involved in tumor cell adherence, migration and epithelial-to-mesenchymal transition. Methods: A panel of Axl-specific ADCs was generated by conjugating human Axl antibodies with the microtubule disrupting agent monomethyl auristatin E (MMAE), through a protease-cleavable linker. Axl-ADCs were functionally characterized in vitro, and the anti-tumor activity was tested in vivo using xenograft models. Results: Axl-ADCs demonstrated high affinity binding to Axl and efficiently induced cytotoxicity in vitro, which was dependent on both Axl expression and conjugation with MMAE. In a lung cancer xenograft model, Axl ADCs were shown to have potent anti-tumor activity in vivo. The most potent Axl-ADCs, including HuMax-Axl-ADC, induced complete tumor regression upon treatment with a single dose of 1 mg/kg. HuMax-Axl-ADC also strongly inhibited tumor growth in a xenograft model that showed high endogenous expression of Gas6. This is in line with our observation that HuMax-Axl-ADC does not compete with Gas6 for Axl binding. Importantly HuMax-Axl-ADC was able to induce tumor regression in PDX models that, similar to many human tumor biopsies, showed Axl expression in only a subpopulation of tumor cells Conclusions: HuMax-Axl-ADC is a novel ADC that shows potent anti-tumor activity in solid cancer xenograft models. The results obtained in preclinical studies support further development of HuMax-Axl-ADC for the treatment of solid cancers.
Role of adjuvant chemotherapy in advanced stage upper urinary tract urothelial carcinoma after radical nephroureterectomy: A competing risk analysis.
Authors: Minyong Kang, Hyung Suk Kim, Jae Young Joung, Yong Ho Shin, Byong Chang Jeong, Tae Jin Kim
Journal: Journal of Clinical Oncology (2019)

367 Background: To determine whether adjuvant chemotherapy (ACH) influences cancer-specific mortality, bladder cancer-specific mortality, and other-cause mortality in patients with locally advanced upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU) through the use of competing risk analysis. Methods: Among 785 patients with UTUC who underwent RNU from 1994 through 2015, we analyzed 338 individuals with locally advanced UTUC (pathologic T3–T4 and/or positive lymph nodes) without distant metastases. Patients were classified into two groups according to receipt of ACH. The study endpoints were UTUC-, bladder cancer- and other cause-specific survivals. The association of potential risk factors with outcome was tested with the Fine and Gray regression model. Results: Overall, 42.6% (n = 144) received ACH following RNU. During a median follow-up duration of 31.5 months, rates of UTUC-, bladder cancer-, and other cause-mortalities were 32.5% (n = 110), 5.0% (n = 17), and 4.1% (n = 14), respectively. Of note, there were no significant differences in overall survival between the observation and ACH groups according to the competing risks of death (UTUC, bladder cancer, and other causes of death). Multivariate analysis showed that only older age at surgery (≥ 65 years; hazard ratio [HR] = 1.71) and positive resection margin (HR = 7.25) remained as poor predictors of UTUC-specific and bladder cancer-specific survival, respectively. Additionally, no factors were identified as independent predictors of other causes of death. Conclusions: In summary, through competing risk analysis, we demonstrated that postoperative chemotherapy did not improve UTUC-specific and bladder-cancer specific survival, nor other cause-specific survival, in patients with locally advanced UTUC who underwent RNU. These results can offer practical information for clinicians regarding treatment decision making in these patients, who are at high risk of death due to competing causes.
Effect of prevention of mother-to-child transmission strategies on antiretroviral therapy coverage in pregnant women in Zambia: analysis using routinely collected data (2010–15)
Authors: Sehlulekile Gumede-Moyo, Jim Todd, Ab Schaap, Paul Mee, Suzanne Filteau
Journal: The Lancet Global Health (2019)

BackgroundThe WHO recommendation for lifelong antiretroviral therapy (ART) for all pregnant and lactating women (Option B+) has been adopted by nearly all countries with the highest HIV burdens. In January, 2013, Zambia announced that it would revise its guidelines on prevention of mother-to-child transmission (PMTCT) and adopt Option B+. Accurate estimates of coverage of PMTCT services in pregnant women with HIV are vital for monitoring progress towards HIV elimination targets. We aimed to show trends in the coverage of PMTCT services in Zambia from 2010 to 2015. We describe the proportion of women attending antenatal care who are HIV positive, the proportion of HIV-positive pregnant women who started ART, the proportion of HIV-infected women already on ART, and time to treatment initiation.MethodsThis was a retrospective cohort study using routinely collected data from SmartCare, an electronic health record system. We included data from all pregnant women who attended antenatal care in the 889 health facilities using the SmartCare database in Zambia.FindingsWe included data for 104 155 pregnant women who attended antenatal services in SmartCare facilities between Jan 1, 2010, and Dec 31, 2015. Of these women, 9% (9262) tested HIV-positive during antenatal visits and 43% (44 387) had missing HIV test results. Almost half (47%, [4375]) the pregnant women who tested HIV-positive in their antenatal visit were recorded in 2010. Among HIV-positive women, there was an increase in those already on ART at first antenatal visit from 9% (40) in 2011 to 74% (1 155) in 2015. In our study, 65% (983/1501) of the women who started ART after testing HIV-positive during antenatal care were documented after the adoption of Option B+ (2013–15). Mean time lag between starting antenatal care and ART initiation was 7 months over the 6 year study period, but there were notable variations between provinces and years.InterpretationThe implementation of WHO PMTCT guidelines introduced after 2010 in Zambia has resulted in an increase in the proportion of HIV-infected pregnant women attending antenatal care who are already on ART. The SmartCare database could enable Zambian health policy makers to act on urgent PMTCT interventions and improve health-care quality and outcomes for mothers and their infants. However, there is a need first to improve procedures for data collection and entry. The number of missing data observations indicate the need for further qualitative research on why so many records were missing from the database.FundingSEARCH (Sustainable Evaluation through Analysis of Routinely Collected HIV data) and the Bill & Melinda Gates Foundation (grant number OPP1084472).
Early Use of Laser for Port-Wine Stains
Authors: Erin F. Mathes, Ilona J. Frieden
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
Economic burden of select adverse events (AEs) in patients (Pts) with advanced urothelial cancer (aUC) treated with first-line (1L) systemic therapy.
Authors: Petros Grivas, François Laliberté, Yunes Doleh, Cristi O'Connor, Mei Sheng Duh, Rahul Shenolikar
Journal: Journal of Clinical Oncology (2019)

363 Background: Limited information on costs related to incident AEs in pts with aUC in the real-world setting is available. Methods: Pts with aUC treated with 1L systemic therapy (94% chemotherapy, 6% immune checkpoint inhibitor) between 1/2012-9/2017 (first therapy administration defined the index date) were identified using IQVIA Real-World Data Adjudicated Claims – US database. Pts with continuous enrollment for ≥6 months pre- and ≥3 months post-index and ≥1 UC diagnosis code were included. Proportions of pts with febrile neutropenia (FN), dehydration, acute kidney injury (AKI), sepsis, colitis, hepatitis, adrenal insufficiency, and pneumonitis (select AEs), and per-pt-per month (PPPM) healthcare costs were assessed. Incident AEs during 1L therapy were identified using outpatient/inpatient claims and a subgroup of severe AEs (identified using only inpatient claims) was analyzed separately. Incremental costs of AEs were calculated as cost differences (CDs) between pts with and without AEs using multivariate linear regression to adjust for baseline differences. Results: Pts with (n = 666) and without (n = 569) select AEs had similar median age of 62 years; pts with select AE had more women (34.4% vs. 29.0%) and chemotherapy-treated pts than pts without select AEs (96.1% vs. 91.0%) (both p &lt; 0.05). Baseline characteristics were similar in pts with (n = 290) and without (n = 1,290) severe AEs. FN (28.0%; severe 6.3%), dehydration (26.5%; severe 8.3%), AKI (11.3%; severe 8.8%), and sepsis (8.8%; severe 8.0%) occurred most frequently during 1L therapy (median duration: 15 weeks). Adjusted PPPM CDs between pts with and without AEs were $1,716 overall and $6,130 for severe AEs, with the greatest CDs observed for pneumonitis ($14,400; severe $20,242), sepsis ($8,581; severe $9,490) and AKI ($7,977; severe $8,843) (all p &lt; 0.05). Inpatient costs had the largest impact on CDs. Conclusions: Costs of AEs, especially severe, during 1L treatment of aUC can cause substantial burden to healthcare system. Biomarker-based therapy selection, education/awareness early recognition and management of AEs may reduce hospitalizations and healthcare costs, and may impact care quality.
James Arthur Nicholson
Authors: Andrea R G Sheel, Amy J Thomas
Journal: BMJ (2019)

James Arthur Nicholson—or “Jimbob,” as he liked to be called—was originally from Stockton on Tees. After qualifying he moved to Mersey Deanery to complete his surgical training and made Liverpool his home. He completed a research fellowship and dedicated his short but exceptional research career to pancreatic cancer. In 2017 he successfully defended his PhD thesis on …