tbuckley/cabot-search huggingface dataset:
Correllation of Proteolytic Matrix Metalloproteases (MMPs) and Inhibitors (TIMPs) with JAK2V617F Mutation and Clinical Phenotype in BCR-ABL Negative Myeloproliferative Neoplasia (MPN).
Authors: C. M. Vadikolia, K. Anagnostopoulos, Despina Pantelidou, G. Tripsianis, Emmanouil Spanoudakis, Ioanna Bazdiara, Athanasios Anastasiadis, Dimitrios Margaritis, A. Kortsaris, C. Tsatalas, Georgios Bourikas
Journal: Blood (2009)
The effect of age on overall survival (OS) in patients with metastatic breast cancer (MBC) treated with capecitabine
Authors: J. L. Blum, X. Hu, D. Odom, B. Sherrill, S. Glück
Journal: Journal of Clinical Oncology (2009)

1097 Background: Both in monotherapy and in combination with a taxane, C has been shown to improve OS in patients with MBC. Since C is often used in older adults because of tolerability and ease of administration (PO vs IV), and lack of alopecia, an exploratory analysis was conducted to see if an association exists between age and OS among patients with MBC treated with C. Methods: Data from the intermittent dose (2510 mg/m 2 ) 2 wks on/1 wk off arms of 5 phase II/III monotherapy or combination therapy with C registration trials involving patients with MBC were analyzed. Intent-to-treat (ITT) was defined as all randomized patients who took at least 1 dose of study medication. Patients were divided into 3 groups by age. A Kaplan-Meier method was used to estimate the age-category specific survival by trial. Next, Cox proportional hazard regression analysis was conducted using pooled data from the 5 trials with stratification by trial and key baseline characteristics. Analyses were conducted at the 95% confidence level. Results: A total of 570 ITT patients were included in the analysis (median age 55.0 years; range, 26–83): 193 (34%) were 18–49 years old; 246 (43%) 50–64 years old; and 131 (23%) ≥65 years old. A baseline Karnofsky score ≥90 was observed in 65.3%, 56.5%, and 50.4% of patients, respectively. The median treatment duration (range) was 93.0 (2–397) days in the 18 to 49-year-old group, 109.5 (2–448) days in the 50 to 64-year-old group, and 80.0 (5–371) days in the ≥65-year-old group. Unadjusted log-rank tests for each of the 5 trials showed no significant differences in OS between age categories. In the pooled analysis, Cox regression did not detect significant differences in survival based on age. Using age ≥65 years as the reference group, the hazard ratios were 1.06 (95% CI 0.81, 1.41) for age 18–49 years and 0.99 (95% CI 0.77, 1.29) for age 50–64 years. The Cox model revealed consistent results after further controlling for the Karnofsky score and number of metastatic sites. Conclusions: No statistically significant effect of age on OS was observed in patients with MBC treated with C. OS outcomes appear comparable across predefined age groups of patients with MBC treated with C. [Table: see text]
Licensing system for doctors
Authors: P. R Bradley
Journal: BMJ (2002)

Editor—I'm sure that the revalidation of doctors in the United Kingdom that Eaton mentions in her news article will proceed.1 This will be mainly because it is driven by politicians and academics, and because, like so many of these things, it seemed like a good idea at the time, but I challenge whether it will make any difference to overall quality of service or care.

We have had this in Australia for 10 years now, yet there is still little hard evidence that it has done anything but introduce yet another layer of bureaucracy. We call it vocational registration (VR), and we have to accumulate a minimum number of points over a triennium. For me it has changed nothing in my work habits, as I always enjoyed doing continuing medical education when I chose those things I most felt I needed to brush up in. Now, the compulsion has removed a lot of the fun of this while no doubt providing a lot of “gainful employment” to the “specialists” retained by the drug companies to lecture, they being only too happy to “sponsor” the meetings because of the great access this gives then to the doctors. The fact that this automatically narrows the scope of subjects to those relevant to the latest (and most expensive) drugs seems bye the bye—you will find the “authorities” remarkably reluctant to put up real money to provide this education, once they have put the requirement in place.

I am convinced one's conscientiousness in keeping up to date is far more a function of one's basic personality, which is decided well before college, let alone medical school, and people who are lazy will still find ways to be so, and people (the vast majority) who are not will just have to jump through all the loops and hoops. Have fun, people—never learn from others' mistakes.
MILD RHEUMATIC VALVULAR HEART DISEASE IS ASSOCIATED WITH INTERSTITIAL MYOCARDIAL FIBROSIS: A T1 MAPPING STUDY
Authors: Carlos G. Santos-Gallego, Yennik Glasgow, Michael Benacerraf, Allen Weiss, Chirag Agarwal, Juan Antonio Requena-Ibanez, Valentin Fuster, Juan Badimon, Angel Sanz Salvo
Journal: Journal of the American College of Cardiology (2017)
Male breast cancer: Looking for prognostic subgroups.
Authors: Miguel Henriques Abreu, Noemia Afonso, Pedro Henriques Abreu, Francisco Menezes, Paula Lopes, Rui Henrique, Deolinda Pereira, Carlos Lopes
Journal: Journal of Clinical Oncology (2015)

e11562 Background: Male Breast Cancer (MBC) remains a poor understood disease. Prognostic factors are not well established and specific prognostic subgroups are warranted as Female’s subgroups seem inadequate to identify the aggressive forms of MBC Methods: Data from 111 MBC cases treated in a single Cancer Center were retrospectively reviewed. Blinded-central pathological revision with additional immunohistochemical (IHQ) staining analysis for estrogen (ER), progesterone (PR) and androgen (AR) receptors, HER2, ki67 and p53 was done. Cox regression model was used for uni/multivariate survival analysis. Two classifications of Female molecular subgroups (based in ER,PR and HER2, classification A, and in ER,PR,HER2 and ki67, classification B) were used to achieve their prognostic value in MBC patients. Hierarchical clustering was performed to define subgroups based on the six-IHQ panel. Results: According to Female classifications, the majority of tumors were luminal A (89.2% and 60.0%) and B (7.2% and 35.8%). Triple negative phenotype was infrequent (2.7% and 3.2%) and HER2 enriched, non-luminal, was rare ( ≤ 1% in both). In multivariate analysis the poor prognostic factors were: tumors > 2cm (HR: 1.8; 95% CI: 1.0-3.4 years, p = 0.049), absence of ER (HR: 4.9; 95% CI: 1.7-14.3 years, p = 0.004) and presence of distant metastasis at diagnosis (HR: 5.3; 95% CI:2.2-3.1, p < 0.001). Female molecular subtypes were also independent prognostic factors (p = 0.009 and p = 0.046), but when analyzed only luminal groups, prognosis did not differ regardless the classification used (p > 0.20). Clustering defined different subgroups that have prognostic value (p < 0.001), with better survival in ER/PR+, AR-, HER2- and ki67/p53 low group (11.5 years 95% CI 6.2-16.8 years), and worst in PR- group (4.5 years 95% CI 1.6-7.8 years). The cluster groups were independent prognostic factors (p = 0.045). Conclusions: Molecular subtypes defined for Female patients do not give the same prognostic information in MBC even in the major groups (luminal). Two prognostic subgroups with distinct profiles (RP- group and ER/PR+, AR-, HER2-, ki67/ p53 low group) were identified in a restricted and routinely six-IHQ marker panel. Future studies must achieve their real prognostic value in these patients.
RACIAL DISPARITY IN AORTIC VALVE REPLACEMENT OUTCOMES: INSIGHT FROM NATIONAL INPATIENT SAMPLE
Authors: Ali Hama Amin, Vinay Badhwar, Fahad Alqahtani, Sami Aljohani, Zakeih Chaker, Ahmed Almustafa, Mohammad Akram Kawsara, Mohamad Alkhouli
Journal: Journal of the American College of Cardiology (2017)
How well do we communicate risk? An evaluation of AJCC version 6 and 7 staging systems for soft tissue sarcomas.
Authors: Robert G. Maki, Cristina R. Antonescu, Meera Hameed, Nicole H. Moraco, Samuel Singer, Murray F. Brennan
Journal: Journal of Clinical Oncology (2012)

10001 Background: Cancer staging systems allow physicians to communicate risks of a particular clinical situation with one another and with patients. Few data have been presented to support the update of a commonly employed staging system for soft tissue sarcoma (STS). We examined American Joint Committee on Cancer (AJCC) versions 6 (2002) and 7 (2010) staging systems for patients with primary STS using a single institution clinically annotated prospective database. Methods: Subsets of the prospectively collected Memorial Sloan-Kettering Cancer Center STS database of 8647 patients from 1982 to 2010 were examined with respect to criteria of the AJCC versions 6 and 7 staging systems. Results: Tumor size does not appear to be adequately addressed in version 6 or 7. Relapse-free survival was statistically worse for increasing size of primary STS &lt;5, 5-10, 10-15, and &gt;15 cm; in comparison, overall survival decreased over three size categories (&lt;5, 5-10, &gt;10 cm). Tumor depth, a statistically significant factor in patient outcomes that is included in version 6, is functionally omitted in version 7. Patients with node involvement without other metastases fare statistically worse than patients with large, high grade tumors without nodal metastasis, as shown previously. Version 6 and 7 criteria do not address effects of primary anatomic site and histology, even for tumors with same FNCLCC grade. Sarcoma subtypes defined after publication of FNCLCC criteria are difficult to incorporate into existing guidelines. Conclusions: Improved prognostication of STS outcomes is better achieved by staging according to anatomic primary site, depth, and a larger number of size categories. Histology-specific nomograms improve prognostic accuracy, such as those for liposarcoma, GIST, or rhabdomyosarcoma. Staging accuracy increases at the cost of portability and simplicity. The increasing difficulties with use of a single STS staging system highlight the potential benefit of newer techniques, such as patient-specific nomograms or Bayesian networks. Staging systems will require significant modifications to incorporate increasingly sophisticated molecular diagnostics.
ATRIAL FIBRILLATION CYCLE LENGTH MEASURED BY TRANSESOPHAGEAL ECHOCARDIOGRAPHY: A PREDICTOR FOR MAINTAINING SINUS RHYTHM AFTER DC CARDIOVERSION
Authors: Dae Sung Lee, Yong Hyun Park, Yeon Seong Kim, Tae Hyun Kim, Soo Yong Lee, Min Ku Chon, Sang Hyun Lee, Ki Won Hwang, Jeong Su Kim, June Hong Kim, Kook Jin Chun
Journal: Journal of the American College of Cardiology (2017)
MORTALITY IN PREGNANT WOMEN WITH CONGENITAL HEART DISEASE: A SUBANALYSIS OF THE CALIFORNIA PREGNANCY-ASSOCIATED MORTALITY REVIEW
Authors: Aarthi Sabanayagam, Anushree Agarwal, Christy MacCain, Elizabeth Lawton, Elliot Main, Afshan Hameed, Ian Harris, Elyse Foster
Journal: Journal of the American College of Cardiology (2017)
THREE-YEAR CLINICAL OUTCOMES OF THE XIENCE/PROMUS COBALT-CHROMIUM EVEROLIMUS-ELUTING STENT IN PATIENTS TREATED WITH IN-STENT RESTENOSIS
Authors: Takashi Hiromasa, Shoichi Kuramitsu, Takashi Morinaga, Yohei Kobayashi, Hiroyuki Jinnouchi, Takenori Domei, Makoto Hyodo, Yoshimitsu Soga, Shinichi Shirai, Kenji Ando
Journal: Journal of the American College of Cardiology (2017)
Prognostic impact of breast cancer (BC) subtype in elderly patients.
Authors: Elisabeth Bergen, Cornelia Tichy, Anna Sophie Berghoff, Margaretha Rudas, Peter Christian Dubsky, Zsuzsanna Bago-Horvath, Robert M Mader, Michael Gnant, Karin Dieckmann, Christoph Zielinski, Guenther G. Steger, Matthias Preusser, Rupert Bartsch
Journal: Journal of Clinical Oncology (2015)

e20536 Background: We aimed to analyze the impact of BC subtypes on the clinical course with special emphasis on the occurrence of brain metastases (BM) and outcome in an elderly breast cancer population. Methods: 571 patients ≥ 65 years receiving treatment for BC from 2007-2011 were identified from a BC database. BC subtypes and clinical characteristics including overall survival (OS) were obtained by chart review. Statistical analysis was performed using the Chi Square test, the log rank test and time depended covariate cox regression model as appropriate. Results: Three-hundred-eighty/571 (63%) were grouped among the young-old (65-74 years), 182/571 (31.9%) among the old-old (75-84 years), and 29/571 (5,1%) among the oldest-old ( ≥ 85 years). 392/571 (68.8%) patients presented with luminal BC, 119/571 (20.8%) with HER2 positive and 59/571 (10.3%) with triple negative BC. After a median follow up of 38 months (range 0-204), 115/571 (20.1%) patients presented with metastatic recurrence. Highest recurrence rate was observed in HER2 positive BC patients (43/119 (36.1%)), followed by triple negative (15/59 (25.4%) and luminal BC (57/392 (14.5%); p < 0.001; Chi Square test). BM occurred significantly more frequently in HER2 positive BC patients (9/119 (7.6%) compared to triple negative (2759 (3.4%) and luminal BC patients (6/392 (1.5%); p = 0.003; Chi Square test). Occurrence of metastases (HR 7.7; 95% CI 5.2-11.4; p < 0.001) as well as development of BM (HR 3.5; 95% CI 1.9-6.4; p < 0.001) had a significant impact on OS prognosis as entered in a time depended covariate cox regression model. Conclusions: In contrast to younger BC patients, HER2 positive BC subtype and not triple negative BC subtype was linked to the most aggressive clinical course including the development of metastatic disease and BM in our elderly cohort.
Efficacy and safety comparison between belotecan and topotecan in patients with recurrent or refractory ovarian cancer: A multi-center, randomized, open-labelled, parallel-group phase IIb trial.
Authors: Hee Seung Kim, Sang-Yoon Park, Chan-Yong Park, Young-Tae Kim, Beob-Jong Kim, Yong Jung Song, Byoung Gie Kim, Yong Beom Kim, Chi-Heum Cho, Jong-Hyeok Kim, Yong Sang Song
Journal: Journal of Clinical Oncology (2015)

5527 Background: Belotecan is a camptothecin derivative with anti-tumor properties. Previous studies suggested the feasibility of belotecan-based chemotherapy for patients with primary or recurrent ovarian cancer. Thus, we conducted a phase IIb trial to compare the efficacy and safety between belotecan and another derivative of camptothecin, topotecan, in patients with recurrent or refractory ovarian cancer. Methods: Patients with recurrent or refractory ovarian cancer were randomized to receive belotecan 0.5 mg/m2 (B-arm) or topotecan 1.5 mg/m2(T-arm) intravenously for 5 consecutive days every 3 weeks till 6 cycles or disease progression. The primary endpoint was overall response rate based on RECIST or GCIG criteria, and secondary endpoints were progression-free survival (PFS), overall survival (OS) and adverse events according to NCI-CTCAE version 4.0. Results: One hundred and forty one patients were randomized from January 2011 to June 2014. Among all patients, 140 were eligible in full analysis (FA) set where patients received at least one dose (B-arm, n = 71; T-arm, n = 69), and 130 were eligible in per protocol (PP) set where patients completed the study protocol (B-arm, n = 66; T-arm, n = 64). Clinico-pathologic characteristics were not different between the two arms. ORR was not different between B- and T-arms in FA and PP sets (29.6% vs. 26.1%, p = 0.645; 30.3% vs. 25%, p = 0.499). Median values of PFS in B- and T-arms were 26.4 vs. 17.3 months in FA (HR = 0.69; 95% CI 0.41-1.16) and PP sets (HR = 0.68; 95% CI 0.39-1.16) without significant difference. However, OS was improved in B- versus T-arm in FA set with marginal significance (median values, 37.1 vs. 21.3 months, log-rank p = 0.053; HR = 0.60; 95% CI 0.35-1.01), and PP set (median values, 37.1 vs. 24.9 months, log-rank p = 0.023; HR = 0.53; 95% CI 0.31-0.93). Grade 3 or 4 adverse events were not different between the two arms. Conclusions: Belotecan may have a similar response and toxicity rates to topotecan in patients with recurrent or refractory ovarian cancer. Moreover, belotecan may prolong OS when compared with topotecan in these patients. Clinical trial information: NCT01630018.
Gene expression profiling to improve prognostic stratification of men with advanced penile squamous cell cancer (PSCC) receiving first-line systemic therapy.
Authors: Amitkumar N. Mehta, Eddy Shih-Hsin Yang, Andrea Necchi, Patrizia Giannatempo, Maurizio Colecchia, Bernhard J. Eigl, Dongquan Chen, Sejong Bae, Gurudatta Naik, Jennifer Gordetsky, Shi Wei, Tiffiny Cooper, Guru Sonpavde
Journal: Journal of Clinical Oncology (2015)

e15633 Background: In patients (pts) with advanced PSCC receiving first-line chemotherapy (CT), visceral metastases (VM) and ECOG performance status (PS) ≥ 1 were reported to be poor prognostic factors for overall survival (OS). We performed tumor gene expression analysis from men with advanced PSCC who received first line platinum-based chemotherapy, to enhance prognostic stratification. Methods: We obtained baseline VM status, PS, clinical stage and formalin-fixed paraffin embedded (FFPE) PSCC tumor samples from men with advanced PSCC who received first-line platinum-based chemotherapy. RNA was extracted from macrodissected tumors using high pure FFPET RNA isolation kit (Roche). Expression of 739 cancer associated genes and 40 housekeeping genes was performed using the nCounter System (Nanostring Technologies). Univariate (UVA) and multivariate analyses (MVA) assess the association of genes and clinical factors with OS. Results: FFPE tumor samples were available from 25 pts who received cisplatin-based CT. All pts had stage 4 disease except one with stage 3 disease. The median OS was 7.4 months (mo). In UVA evaluating genes as continuous variables, upregulated MAML2 (p = 0.004), KITLG (p = < 0.0001) and JAK1 (p = 0.029) were associated with poor survival, and upregulated FANCA was associated with better OS (p = 0.024). p16, a surrogate for HPV, was not associated with OS. In MVA including clinical factors and these 4 genes, only VM (HR = 3.957 (95% CI = 1.333-11.741, p = 0.013)) and KITLG (HR = 1.013 [95% CI = 1.004-1.022, p = 0.006) were significantly associated with poor survival. The presence 0, 1 and both of these poor risk factors (VM present and KITLG ≥ median) was associated with a median OS of 17.0, 6.7 and 3.2 mo, respectively. Conclusions: In men with advanced PSCC receiving first line cisplatin-based CT, the combination of a clinical factor (VM status) and molecular factor (tumor KITLG gene expression) enhanced prognostic stratification. These data warrant validation and may guide drug development in this orphan disease with unmet needs.
PREDICTING CARDIOVASCULAR RISK IN STATIN-TREATED PATIENTS: THE AIM-HIGH (ATHEROTHROMBOSIS INTERVENTION IN METABOLIC SYNDROME WITH LOW HDL/HIGH TRIGLYCERIDES: IMPACT ON GLOBAL HEALTH OUTCOMES) RESIDUAL RISK SCORE
Authors: Philip Chui, Moti Kashyap, Nathan Wong
Journal: Journal of the American College of Cardiology (2017)
IMPELLA OR INTRA-AORTIC BALLOON PUMP SUPPORT IN PATIENTS UNDERGOING HIGH RISK PERCUTANEOUS CORONARY INTERVENTION: A REAL WORLD SINGLE CENTER EXPERIENCE
Authors: Sabato Sorrentino, Usman Baber, Jaya Chandrasekhar, Serdar Farhan, Michela Faggioni, Birgit Vogel, Samantha Sartori, Jason Kovacic, Pedro Moreno, Kesanakurthy Srinivas, Pooja Vijay, Gennaro Giustino, George Dangas, Roxana Mehran, Annapoorna Kini, Samin Sharma
Journal: Journal of the American College of Cardiology (2017)
Detection of somatic mutations in fine needle aspirates of pancreatic cancer with next-generation sequencing.
Authors: Joseph M. Herman, Vicente Valero, Christopher Lee Wolfgang, Christine A Iacobuzio-Donahue
Journal: Journal of Clinical Oncology (2014)

e15225 Background: Fine needle aspiration (FNA) is a common method of diagnosis of advanced stage pancreatic cancer, yet has traditionally been considered inadequate for molecular studies due to the small number of cells removed from the patient. Methods: To determine the extent to which FNAs can be sequenced we performed limiting dilution studies by mixing the human cancer cell line Panc1 with normal fibroblasts and found that mutations present at allele frequencies as low as 0.1% can be detected. In patients with resected pancreatic cancer, sequencing of FNAs taken postoperatively from the resected tissues correctly identified all driver genes present in the carcinoma. Based on these results we sequenced the normal blood and FNAs of 20 patients obtained in the course of diagnosis for an unresectable pancreatic mass. Results: We identified at least one driver gene mutation in the FNAs of 17 of 20 patients including actionable mutations in ATM and MTOR. For one patient with a wild type KRAS gene we also found a potentially deleterious NF1 mutation. Deep sequencing of FNAs is feasible and can be utilized in the course of real-time clinical diagnoses. Conclusions: Routine sequencing of FNAs will afford new opportunities for study of previously uncharacterized patient populations with this disease by bridging cancer genomics with clinical outcomes.
ANGIOGRAPHIC DYE PRIOR TO COMBINED HEART-KIDNEY DONATION DOES NOT APPEAR TO HARM DONOR KIDNEY FUNCTION AFTER TRANSPLANT
Authors: Derek Leong, Tamar Aintablian, Jignesh Patel, Michelle Kittleson, Dael Geft, Lawrence Czer, Jon Kobashigawa
Journal: Journal of the American College of Cardiology (2017)
Subcutaneous or intravenous administration of romiplostim in thrombocytopenic patients with myelodysplastic syndrome (MDS)
Authors: M. Sekeres, H. Kantarjian, P. Fenaux, P. Becker, A. Boruchov, A. Guerci-Bresler, K. Hu, J. Franklin, D. Berger
Journal: Journal of Clinical Oncology (2009)

7009 Background: Thrombocytopenia is common in patients (pts) with MDS, and treatment options are currently limited to platelet (plt) transfusions. Romiplostim is an Fc-peptide fusion protein (peptibody) that stimulates plt production by the same mechanism as thrombopoietin. Methods: This was a phase II, multicenter, single arm, open-label study. Eligibility criteria included IPSS low or intermediate-1 risk MDS and a mean baseline plt count ≤50x10 9 /L. Safety and efficacy of romiplostim were evaluated in pts receiving 750μg romiplostim according to one of 3 schedules: weekly or biweekly subcutaneous injections (QWSC or Q2WSC), or biweekly intravenous injections (Q2WIV). Plt responses were measured per IWG 2006 criteria. Results: Of the 28 pts enrolled, 17 (61%) completed the study; 22 (79%) were male and the mean (±SD) baseline plt count was 29 (±10) x 10 9 /L. The mean age was 71 years and 19 pts (68%) had received plt transfusions in the past year. Mean duration of exposure to romiplostim was 12 (±8) weeks. The most common adverse events (AEs) were fatigue and headache (both 18%). Five pts experienced serious AEs, and there were 2 cases of disease progression to AML: one pt in the QWSC cohort who received romiplostim for 4 weeks and one in the Q2WSC cohort who received romiplostim for 20 weeks. For pts who completed 8 weeks treatment, 15/23 (65%) achieved a plt response, defined by IWG 2006 criteria, and 14/23 (61%) did not require a plt transfusion during this period. The small number of pts limited the ability to compare administration schedules; minor differences were observed in plt responses and plt transfusions, and the incidence of AEs appeared similar among cohorts. Conclusions: IV and SC romiplostim appeared well-tolerated and effective in raising plt counts and avoiding plt transfusions in low and intermediate-1 risk MDS pts. The dose recommendation for future studies is 750μg, given QW or Q2W SC. [Table: see text] [Table: see text]