tbuckley/cabot-search huggingface dataset:
Prospective analysis of the early modulation of plasma amphiregulin (AR) during treatment with cetuximab and irinotecan in irinotecan-refractory metastatic colorectal cancer (mCRC) patients (pts).
Authors: Chiara Cremolini, Fotios Loupakis, Carlotta Antoniotti, Anna Fioravanti, Paola Orlandi, Lisa Salvatore, Bastianina Canu, Marta Schirripa, Gianluca Masi, Teresa Di Desidero, Federica Marmorino, Francesca Bergamo, Federica Zoratto, Guido Bocci, Alfredo Falcone
Journal: Journal of Clinical Oncology (2013)

3602 Background: The potential role of AR tissue levels in the prediction of benefit from anti-EGFRs in mCRC pts was suggested by retrospective series. Preclinical and preliminary clinical experiences showed a modulation of plasma EGFR ligands during the treatment with cetuximab. Previous data by our group evidenced that a significant increase of plasma AR occurred one hour after the administration of cetuximab and higher increases were associated with worse clinical outcome in KRAS and BRAFwt irinotecan-refractory mCRC pts receiving cetuximab and irinotecan. Methods: We designed a prospective confirmatory study in the same setting of mCRC pts. To detect a HR for PFS of 2.3 for pts with high AR levels one hour after the administration of cetuximab (1hr-AR) compared to those with low levels, with two-sided a=0.05 and b=0.2, 45 events were required. The median value was adopted as cut-off. Plasma AR levels were assessed by means of validated ELISA kits. Results: Forty-nine KRAS and BRAFwt pts were included. A significant early increase of AR levels was observed (median increase +24.7%; median levels of baseline AR and 1hr-AR: 18.06 and 24.06 pg/mL, respectively; Wilcoxon signed rank test, p&lt;0.0001). At a median follow-up of 20.4 mos, median PFS and OS were 4.6 and 12.1 mos, respectively. No differences in PFS or OS were observed according to 1hr-AR levels (median PFS 5.5 vs 4.6 mos, HR: 0.76 [95%CI:0.40-1.32], p=0.322; median OS: 15.6 vs 13.4 mos, HR:0.77 [95%CI:0.36-1.62], p=0.485). Conclusions: This prospective experience confirms that AR early increases one hour after the administration of cetuximab. Underlying biological mechanisms should be investigated. Nevertheless, this modulation of AR does not predict clinical outcome. Our work underlines the need to prospectively validate retrospective findings in independent series, to assess their reliability. Clinical trial information: 2008-003160-19.
Cardiac CT With Delayed Enhancement in the Characterization of Ventricular Tachycardia Structural Substrate
Authors: Antonio Esposito, Anna Palmisano, Sofia Antunes, Giuseppe Maccabelli, Caterina Colantoni, Paola Maria Vittoria Rancoita, Francesca Baratto, Clelia Di Serio, Giovanna Rizzo, Francesco De Cobelli, Paolo Della Bella, Alessandro Del Maschio
Journal: JACC. Cardiovascular imaging (2016)
Workstation-Based Calculation of CTA-Based FFR for Intermediate Stenosis
Authors: Mariusz Kruk, Łukasz Wardziak, Marcin Demkow, Weronika Pleban, Jerzy Pręgowski, Zofia Dzielińska, Marek Witulski, Adam Witkowski, Witold Rużyłło, Cezary Kępka
Journal: JACC. Cardiovascular imaging (2016)
Effects of denosumab versus zoledronic acid (ZA) on pain in patients (pts) with metastatic breast cancer: Results from a phase III clinical trial.
Authors: A. Stopeck, L. Fallowfield, D. Patrick, C. S. Cleeland, R. H. De Boer, G. G. Steger, Y. Qian, Q. Jiang, R. D. Dansey, K. Chung
Journal: Journal of Clinical Oncology (2010)

1024 Background: Treatment with bisphosphonates in pts with metastatic breast cancer prevents osteoclast-mediated skeletal related events (SREs) and reduces pain. Denosumab, an investigative fully human monoclonal antibody against RANKL, was superior to ZA in delaying and preventing SREs in a recently completed randomized trial of breast cancer pts with bone metastases. Here, we describe pain outcomes from this study. Methods: Eligible breast cancer pts received either subcutaneous denosumab 120 mg or intravenous ZA 4 mg every 4 weeks in a double-bind, double-dummy design. Pts completed the Brief Pain Inventory to assess pain severity and interference with daily functioning at baseline (BL), day 8, and before each monthly visit through end of study. Analyses included all randomized pts (N=2,046) and were performed through week 73, when 30% of pts had dropped out due to death, disease progression, or consent withdrawal. Worst-pain severity ratings were dichotomized to no/mild (0-4) and moderate/severe (5-10). For pain prevention, pts with no/mild pain at BL were analyzed for time to moderate/severe pain. The proportion of pts with moderate/severe pain by study visit was also determined. For pain palliation, time to pain improvement of ≥2-point decrease from BL was analyzed. Results: Pts with scores of no/mild pain at BL (n=1,042) experienced a prolonged median time to development of moderate/severe pain with denosumab (295 days) compared with ZA (176 days; HR 0.78, 95% CI: 0.67–0.92, p=0.0024). The proportion of pts with no/mild pain at BL who reported moderate/severe pain on-study was consistently lower for denosumab than ZA through week 73 (Table). Time to pain improvement was similar between treatment arms (denosumab: median 82 days, ZA: 85 days; HR 1.02; 95% CI: 0.91–1.15; p=0.72). Conclusions: Denosumab significantly extended the length of time that pts had no or mild pain compared with ZA. Among pts with no/mild pain at BL, fewer pts on denosumab experienced worsening of pain than pts on ZA. % of pts with no/mild pain at BL reporting moderate/severe pain by study visit Study week 13 25 37 49 61 73 Denosumab (N=542) 17.3 17.9 15.6 15.6 19.1 14.8 ZA (N=500) 22.1 23.2 27.4 25.6 25.3 26.7 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen, Novartis Amgen Amgen, Novartis Amgen, Novartis
Bendamustine treatment of B-cell lymphoproliferative disorders: A single-institution experience.
Authors: J. L. Knoble, J. Densmore, M. E. Williams
Journal: Journal of Clinical Oncology (2010)

e18542 Background: Bendamustine (B) has been an established treatment of lymphoproliferative disorders (LPD) in Germany for over 30 years. The drug has only recently gained FDA approval, however, and clinical experience with the drug in the United States is limited. The unique drug structure, with both alkylating and antimetabolite features, suggests a unique clinical activity profile including alkylator-resistant LPD. We evaluated B response and toxicity data and compared these outcomes with reported experience. Methods: A retrospective chart review was conducted on patients who received B at our institution for treatment of a LPD, both on or off clinical trials. 30 patients, median age 68.5, received 1 to 7 cycles of therapy from 9/2004 through 7/2009; 17 patients received the drug on clinical trial. B was used as a single agent (n=11) or in combination with rituximab (R) (n=19). All patients were treated previously, 28 with at least one prior R- containing regimen. Dosing ranged from 60 to 120 mg/m2 on days 1 and 2 of each 3 or 4 week cycle. Results: The overall response rate (ORR) was 73%. Complete response (CR/CRu) was 37%, and partial response (PR) was also 37%. Median progression-free survival (PFS) was 17 months. Toxicity was evaluated using the CTCAE v3.0 grading system. Nausea was the most common reported toxicity (grade 1, n=8, grade 2, n=3) . Grade 1 skin rash was reported in 3 patients. Grade 1 thrombocytopenia was reported in 7 patients, and 3 patients required dose reduction/delay due to grade 3 toxicity. 3 patients developed grade 1 neutropenia, and 1 had grade 3 toxicity. There were no treatment-related deaths. Conclusions: B ± R responses correlated with previously reported findings among several individual LPD subtypes, with the exception of a poorer response in MCL patients. Our findings endorse significant clinical activity including patients with relapsed/refractory disease, with an acceptable toxicity profile. LPD subtype n ORR (%) CR (%) PR (%) Median PFS (mo.) Follicular 14 13 (93) 6 (43) 7 (50) 22 Mantle cell 6 3 (50) 0 3 (50) 3.5 CLL/SLL 8 6 (75) 5 (62.5) 1 (12.5) 21 Diffuse large B cell 2 0 0 0 NA Totals 30 22 (73) 11 (37) 11 (37) 17 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Biogen Idec, Cepahlon, Genentech, Keryx Biopharmaceuticals
Diabetes prevention through prevention of hepatitis B
Authors: James Lin, Horng‐Yih Ou, Lee‐Ming Chuang, Ken C. Chiu
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. To the Editor: We read the article by Khalili et al.1 with great interest. The relationship between hepatitis B and diabetes is very intriguing. In this predominantly Asian population with hepatitis B surface antigen‐positive (HBsAg+) serology, the prevalence of diabetes was 12.5%. The authors compared the prevalence of diabetes from the general US population and concluded that diabetes was more prevalent in hepatitis B virus‐infected adults than the general population. Based on a recent report on the US population in 2011‐2012,2 the overall prevalence of diabetes is 14.3% and 20.6% in the Asian subgroup, which is much higher than reported in this study. However, the difference could be due to the definition of diabetes used in this study, based on only history or fasting plasma glucose which could definitely underestimate the prevalence. We recently examined the prevalence of diabetes based on the vaccination history and hepatitis B serology in the adult population from the National Health and Nutrition Examination Survey 2005‐2010.3 The prevalence of diabetes was 11.62% in those who received hepatitis B vaccination, while it was 19.14% in those without vaccination. In the population with serological evidence of immunization (hepatitis B surface antibody+/hepatitis B core antibody−/HBsAg−), the prevalence was 6.72%, while it was 19.01% in those without. In the population with successful vaccination as defined by history of vaccination and serology (hepatitis B surface antibody+/hepatitis B core antibody−/HBsAg−), the prevalence was 5.36%, while it was 18.51% in those without. After adjustment for covariates, hepatitis B vaccination history is not protective for diabetes (odds ratio = 1.08, 95% confidence interval 0.96‐1.23), while successful vaccination of hepatitis B reduces the risk of diabetes by 33% (odds ratio = 0.67, 95% confidence interval 0.52‐0.84). However, we were not able to examine the impact of HBsAg in this population due to a low prevalence (0.13%). With the majority of projected increases in the prevalence of diabetes by 2030 stemming from developing countries4 where hepatitis B is epidemic,5 prevention of hepatitis B by vaccination could provide a unique opportunity to reduce the burden of both hepatitis B and diabetes.
CMS Grants to Address Social Needs of Beneficiaries
Authors: Julie A. Jacob
Journal: JAMA (2016)

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
Risk of Major Adverse Cardiovascular Events and All-Cause Mortality in Patients With Hidradenitis Suppurativa
Authors: Alexander Egeberg, Gunnar. H. Gislason, Peter R. Hansen
Journal: JAMA Dermatology (2016)

Hidradenitis suppurativa (HS) is a common inflammatory skin disease. The disease has been associated with cardiovascular (CV) risk factors, but the risk of CV disease in patients with HS is unknown.To investigate CV risk in patients with HS.A population-based cohort study was conducted from January 1, 1997, to December 31, 2011, using individual-level linkage of nationwide administrative registers. In a study population of 35 368 Danish individuals, 5964 patients aged 18 years or older with a hospital-based diagnosis of HS (cases) were matched 1:5 on age, sex, and calendar time with 29 404 individuals serving as controls.Outcomes were myocardial infarction (MI), stroke, CV-associated death, major adverse CV events (MACEs), and all-cause mortality. Incidence rate ratios (IRRs) were estimated by Poisson regression.The 5964 patients with HS had a mean (SD) age of 37.7 (11.7) years; 4346 (72.9%) were women. In this sample, a total of 62 (42 749.0 person-years) MIs, 74 (42 647.8 person-years) ischemic strokes, 63 (42 941.7 person-years) CV-associated deaths, 169 (42 463.5 person-years) MACEs, and 231 (42 941.7 person-years) all-cause deaths occurred during follow-up. Adjusted (age, sex, socioeconomic status, smoking, comorbidity, and medication) IRRs (95% CIs) were 1.57 (1.14-2.17) for MI, 1.33 (1.01-1.76) for ischemic stroke, 1.95 (1.42-2.67) for CV-associated death, 1.53 (1.27-1.86) for MACEs, and 1.35 (1.15-1.59) for all-cause mortality. When patients with severe psoriasis were used as controls, the adjusted IRRs in patients with HS were 1.00 (0.74-1.35) for MI, 0.93 (0.71-1.22) for ischemic stroke, 1.58 (1.17-2.12) for CV-associated death, 1.08 (0.90-1.29) for MACEs, and 1.09 (0.94-1.28) for all-cause mortality.Hidradenitis suppurativa was associated with a significantly increased risk of adverse CV outcomes and all-cause mortality independent of measured confounders. The risk of CV-associated death was higher in patients with HS compared with the risk in those with severe psoriasis. The results call for increased awareness of this association and for studies of its clinical consequences.
p-Cresyl sulfate is associated with carotid arteriosclerosis in hemodialysis patients and promotes atherogenesis in apoE−/− mice
Authors: Ya J. Jing, Jing W. Ni, Feng H. Ding, Yue H. Fang, Xiao Q. Wang, Hai B. Wang, Xiao N. Chen, Nan Chen, Wei W. Zhan, Lin Lu, Rui Y. Zhang
Journal: Kidney International (2015)
Both age and location predict survival in childhood ependymoma: A SEER study
Authors: C. S. McGuire, K. L. Cobb, P. G. Fisher
Journal: Journal of Clinical Oncology (2007)

9545 Background: Supratentorial (SUP) ependymoma in childhood has been reported in studies with limited samples to carry improved overall survival (OS) compared to infratentorial (INF) tumors, with spinal (SPI) ependymoma having the best outcome. Moreover, radiation therapy (XRT) for INF tumors has been considered standard of care, though there have been case reports of children treated successfully without XRT. Thus, we aimed to examine how age, gender, location, XRT and race influence OS in childhood ependymoma by rigorous analysis of a large registry. Methods: We queried the Surveillance Epidemiology End Results (SEER) registry from 1973 to 2003, strictly defining ependymomas by histology (ICD-O-3: 9391–9394). ICD-0–2 site codes, when available, were used to distinguish SUP, INF, and SPI tumors. OS was compared by age, gender, race, location, and XRT, using Kaplan-Meier analysis with logrank tests in SPSS 12.0 (Chicago, IL). Cox regression incorporated all significant covariates from univariate analysis. A similar analysis was conducted to determine whether findings differed in adults. Results: 635 children &lt;18 years at diagnosis were identified (265 females; 510 whites, 77 blacks; 106 SUP, 193 INF, 55 SPI) with 5-year OS 57.1% ± standard error 2.3%. With univariate analysis, OS did not differ by gender or race. For location, 5-year OS did not differ between SUP 59.5% ± 5.4% and INF 57.1% ± 4.1%, but was significantly better for SPI 86.7% ± 5.2%. With multivariate analysis, location and age remained significant predictors for OS, with younger children having worse outcome. A similar multivariate analysis in 1388 adults again showed age and location to be significant. Adults fared better than children (logrank p &lt;0.0001). XRT of INF tumors was associated with significantly improved OS in children (logrank p &lt;0.018), but did not lead to an OS difference among adults. Conclusions: Age and location directly influence OS in childhood ependymoma. SPI tumors are associated with a significantly better prognosis than other ependymomas. This study could not show a difference in OS between SUP and INF tumors, proposed recently to have different stem cell origins. SPI tumors may represent a distinct biological entity. Curiously, XRT is associated with improved OS in pediatric, but not adult, INF ependymomas. No significant financial relationships to disclose.
New Definitions for Sepsis and Septic Shock
Authors: Edward Abraham
Journal: JAMA (2016)

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
The Role of<i>APOE</i>in the Occurrence of Frontotemporal Dementia in Amyotrophic Lateral Sclerosis
Authors: Adriano Chiò, Maura Brunetti, Marco Barberis, Barbara Iazzolino, Anna Montuschi, Antonio Ilardi, Stefania Cammarosano, Antonio Canosa, Cristina Moglia, Andrea Calvo
Journal: JAMA Neurology (2016)

Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease with a wide spectrum of involvement of cognitive functions. The mechanisms of this heterogeneity are still largely unknown, but genetic variants may account for this variability.To assess the influence of the apolipoprotein E (APOE) and C9ORF72 genotypes on cognitive impairment in a population-based series of Italian patients with ALS.All 504 patients with ALS living in Piemonte, Italy, diagnosed between January 1, 2009, and December 31, 2013, and identified through the Piemonte and Valle d'Aosta register for ALS, were eligible to participate in the study. Controls were 223 age- and sex-matched individuals identified through the patients' general practitioners. Data analysis was performed from June 1 to December 31, 2014.The presence of APOE and C9ORF72 genotypes was assessed. Patients were cognitively classified as having ALS with normal cognition, ALS with frontotemporal dementia (FTD), ALS with executive or nonexecutive impairment, and ALS with behavioral impairment.Of the 504 patients with incident ALS, 357 (70.8%) were included in the study; 154 were women, 203 were men, they had a mean (SD) age at onset of 64.8 (10.2) years, and 37 of them carried a C9ORF72 repeat expansion. Cognitive testing revealed that 184 patients (51.5%) had ALS with normal cognition, 51 (14.3%) had ALS with FTD, 103 (28.9%) had ALS with executive or nonexecutive impairment, and 19 (5.3%) had ALS with behavioral impairment. Distribution of APOE haplotypes did not significantly differ between patients and controls or among patients with different levels of cognitive impairment. According to multivariate logistic regression, the presence of C9ORF72 repeat expansions was the strongest determinant of FTD (odds ratio, 13.08; 95% CI, 4.75-36.02; P < .001); however, the presence of an APOE ε2 allele significantly increased the risk of FTD (odds ratio, 2.61; 95% CI, 1.14-6.10; P = .03). Presence of an APOE ε4 allele was ineffectual.C9ORF72 repeat expansions have a primary role in increasing the risk of cognitive impairment in patients with ALS; the APOE ε2 allele, to a lesser extent, also increases the risk of FTD. These study findings highlight the importance of considering the genetic background of patients with ALS when analyzing the putative effect of genetic modifiers.
EGFR gene copy number, KRAS and BRAF status, PTEN and AKT expression analysis in patients with metastatic colon cancer treated with anti-EGFR monoclonal antibodies ± chemotherapy
Authors: C. Bengala, S. Bettelli, A. Fontana, F. Bertolini, G. Sartori, N. Malavasi, L. Losi, C. Del Giovane, G. Luppi, P. Conte
Journal: Journal of Clinical Oncology (2009)

e15055 Background: Cetuximab and panitumumab have proven to be effective in metastatic colon cancer (mCRC). KRAS mutation has been demonstrated to be a biomarker of resistance to both monoclonal antibodies. However the status and expression of other biomarkers of the RAS-RAF-MAPK signalling pathway can have a crucial role in sensitivity to anti-EGFR monoclonal antibodies. Methods: We have retrospectively analyzed tumor tissue biomarkers including EGFR gene copy number (GCN) by FISH, KRAS and BRAF status by PCR-based sequencing, PTEN and AKT expression by IHC in patients with mCRC treated with cetuximab and panitumumab ±chemotherapy. Response to treatment, TTP and OS were evaluated. Results: Sixty-three patients (pts) have been analyzed. Median age was 59 years (34–80); 53 pts had received cetuximab and 10 pts panitunumab. Concomitatnt chemotherapy was FOLFIRI, CPT-11, FOLFOX4 and Xeliri in 35, 13, 6 and 4 pts respectively. Five pts had received monoclonal antibodies only. Twenty- one pts were treated in 1 st -2 nd line and 42 pts in 3 rd -4 th line. So far EGFR GCN is available on 55 pts, KRAS and BRAF on 63 pts, PTEN in primary tumor (PT) on 36 pts and in metastatic (MTS) site on 24 pts, AKT on 19 pts. EGFR/nuclei ratio was &gt; 2.9 in 31 % of the pts, KRAS and BRAF were mutated in 36.5 % and 3 % of the pts respectively; PTEN was positive in 42 % and 79 % in PT and MTS respectively. Moreover 21.8 % of the pts had EGFR/nuclei &gt; 2.9 and CEP7 Polisomy &gt; 50 %. Four pts achieved a partial remission (6.3 %). Partial response rate was 17 % vs. 2.6 % in pts with high and low EGFR GCN respectively (p: 0.007) and 13 % vs. 2.5 % in pts with WT and mutated KRAS respectively (p: 0.048). Median TTP was 3 months (0.83–32.9). It was 4.2 vs. 2.3 mos in pts with WT and mutated KRAS respectively (p: 0.001). Median OS was 9.7 mos (2.03–49.0) and no statistically significant differences were observed according to the biomarkers status. However a trend was observed for pts with KRAS WT 10.6 vs. 7.8 mos and for PTEN positive in PT: 9.0 vs. 5.67 mos. Conclusions: Our data confirm the predictive role of EGFR gene copy number and KRAS status on the response and survival. Complete biomarker characterization is ongoing and an analysis for interaction will be performed. No significant financial relationships to disclose.