tbuckley/cabot-search huggingface dataset:
A randomized phase II trial of concurrent temozolomide (TMZ) and radiotherapy (RT) followed by dose dense compared to metronomic TMZ and maintenance cis-retinoic acid for patients with newly diagnosed glioblastoma multiforme (GBM)
Authors: J. Sul, K. S. Panageas, A. B. Lassman, A. Hormigo, C. Nolan, I. T. Gavrilovic, S. A. Grimm, L. M. DeAngelis, L. E. Abrey
Journal: Journal of Clinical Oncology (2007)

2031 Background: Metronomic and dose dense scheduling are alternatives to conventional TMZ regimens to overcome drug resistance in part by depleting O-6 methylguanine-DNA methyltransferase (MGMT). Furthermore, metronomic TMZ may inhibit endothelial recovery and act as an anti-angiogenic therapy; dose dense TMZ increases the intensity of drug delivery. Objective: To determine the overall (OS) and progression free survival (PFS) of patients with newly diagnosed GBM treated with concurrent TMZ and RT followed by dose dense or metronomic TMZ and maintenance cis-retinoic acid. Methods: Patients with newly diagnosed, histologically confirmed GBM underwent standard RT with TMZ. Upon completion of this treatment, patients were randomized to receive dose-dense TMZ (150mg/m 2 , days 1–7 and 15–21 of a 28 day cycle) or metronomic TMZ (50mg/m 2 daily in 28 day cycles), for 6 cycles. Maintenance cis-retinoic acid was prescribed following the 6 cycles of adjuvant TMZ. OS and PFS were calculated from date of diagnosis. Prospective correlative tissue analysis of MGMT status is planned. A Simon minimax 2-stage design was used for each cohort. If either group has 70% survival probability at 1 year, further evaluation in a phase III trial will be recommended. Results: 51 patients were randomized: 24 to metronomic, and 27 to dose dense. Median age is 57, and median KPS 90. 26 patients have progression of disease (POD), with a median follow up of 5 months. Grade 3/4 hematologic toxicity occurred in 7 patients (14%), 3 in the metronomic and 4 in the dose dense arm. Conclusions: Our patient population is comparable to that of other upfront GBM treatment trials. Metronomic and dose dense TMZ appear to be well tolerated with equivalent toxicities. Early analysis suggests that patients on the dose dense regimen may have better PFS than those on the metronomic arm. [Table: see text] No significant financial relationships to disclose.
A woman with lower back pain
Authors: Tobenna J Oputa, Jamie A’Court
Journal: BMJ (2017)

A 52 year old woman presented with a two day history of lower back pain that was radiating into her left leg with weakness in that leg. She had a history of chronic back pain. Neurological examination revealed reduced power in her left leg of 3/5, but was otherwise normal. Based on a magnetic resonance image (MRI) of her lumbosacral spine (fig 1⇓) what is the most likely cause of this woman’s back pain?



Fig 1  Mid-sagittal T2 weighted lumbosacral spine magnetic resonance imaging scan



Disc prolapse at …
HOSPITAL VARIATION IN TARGETED TEMPERATURE MANAGEMENT FOR ACUTE MYOCARDIAL INFARCTION PATIENTS COMPLICATED BY OUT-OF-HOSPITAL CARDIAC ARREST IN THE U.S.
Authors: Christopher Fordyce, Anita Chen, Tracy Wang, Joseph Lucas, Abhinav Goyal, Graham Wong, Sean Van Diepen, Michael Kontos, Timothy Henry, Christopher Granger, Matthew Roe
Journal: Journal of the American College of Cardiology (2017)
Case 10-2015
Authors: Eric P. Hazen, Nicole A. Sherry, Sareh Parangi, Carlos A. Rabito, Peter M. Sadow
Journal: New England Journal of Medicine (2015)

A 15-year-old girl with Graves' disease was admitted to the hospital because of psychotic symptoms — including depression, hallucination, and suicidal thoughts — that began approximately 2 months after treatment with methimazole had been initiated.
Validation of Genetic Predictors for Stroke In Children with Sickle Cell Anemia
Authors: Jonathan Michael Flanagan, Thad A Howard, Denise M Frohlich, William Herbert Schultz, Catherine Driscoll, Ramamoorthy Nagasubramanian, Nicole A Mortier, Amy C Kimble, Banu Aygun, Robert J Adams, Ronald W Helms, Russell E. Ware
Journal: Blood (2010)
Contribution of <i>P53</i> mutation to high standardized uptake values of <sup>18</sup>F-fluorodeoxyglucose positron emission tomography and impact on survival in patients with breast cancer.
Authors: Sung Gwe Ahn, Hak Min Lee, Seung Ah Lee, Young Hoon Yoo, Joon Jeong, In-Sun Chu
Journal: Journal of Clinical Oncology (2014)

e22071 Background: High rate of glycolysis exhibited by cancer cells plays a crucial role in carcinogenesis and tumor progression. We sought to uncover key molecules contributing to increasing glucose uptake identified by 18F-fluorodeoxy glucose positron emission tomography (FDG-PET), along with an exploration its prognostic value using two breast cancer cohorts. Methods: First cohort consisted of 66 women with FDG-PET and gene-expression profiling (Illumina, San Diego, CA). Clustered analysis by standardized uptake value (SUV) level from FDG-PET and gene network analysis suggested that repression of p53 might be a key determinant associated with elevated SUV level. Second cohort consisted of women with p53 gene sequencing analysis and FDG-PET. Mutational analysis of exons 5-9 of the p53 gene was carried out using polymerase chain reaction-denaturing high performance liquid chromatography. Of these women, to reduce bias and clearly estimate the influence of p53 mutation on SUV and survival, we identified 114 women by propensity-score matching method. Results: Propensity-score matching using 5 clinicopathologic factors generated 2 matched groups, each composed of 57 patients. In these patients, regarding baseline characteristics, there was no significant difference between two groups stratified by p53 mutational status except level of SUV. The mean SUV of p53-mutational group (n=57) was significantly higher than that of wild-type p53-group (7.49 vs. 5.44, P=0.013). Compared with the group with intact p53, recurrence-free survival (RFS) was significantly reduced in the group with p53 mutation (P =0.017). In multivariate analysis, p53 mutational status carried prognostic significance (hazard ratio 3.73, 95% CI 1.15-12.07) independent of tumor size, nodal status, and estrogen receptor status. Conclusions: We found that p53 mutation plays a key role in elevated glucose uptake and adversely affects survival in patients with breast cancer.
AST/GOT1 expression status in primary resection specimen as a prognostic biomarker in human pancreatic ductal adenocarcinoma (PDAC).
Authors: Fenja M Feld, Philipp D Nagel, Stephanie E Weissinger, Claudia Welke, Peter Möller, Jochen K Lennerz
Journal: Journal of Clinical Oncology (2014)

e15245 Background: A novel metabolic link in PDAC has recently been established whereby the mutated KRAS molecule acts as a modulator of the cancer cell’s redox maintenance system via an increase in the Glutamic-Oxalacetic Transaminase 1 (GOT1) expression. The clinical relevance of the metabolic KRAS-GOT link is unknown in primary human patient samples. Here we studied whether the GOT1 expression status (a) correlates with the KRAS mutation status, (b) can be identified via specific clinicopathological phenotypes, and (c) has prognostic relevance. Methods: We analyzed two independent PDAC cohorts: 1. ‘International Cancer Genome Consortium’; (ICGC, 57 patients with whole-exome sequencing, genome wide expression profile, clinicopathological data, follow up) and 2. ‘Ulm’ (122 patients with molecular genetic workup, tissue-microarray, clinicopathological data, follow up). GOT1-overexpression was assessed via RNA level (ICGC) and immunohistochemistry (Ulm). Results: (a) In both cohorts the GOT1 expression status was not predictive of the KRAS mutation status (P=0.2, ICGC; P=0.8, Ulm), indicating that GOT1 assessment cannot serve as a surrogate marker for KRAS mutation testing and that additional modulatory factors at play. (b) Phenotype comparison of each cohort showed that GOT1 high/positive subgroups do not differ by age, sex, T-, N-, M- status, AJCC stage grouping or tumor grading (P=0.08-1.00). (c) Outcome analyses revealed longer overall survival times for patients with GOT1 high-expressing tumors (P=0.093, ICGC; P=0.049, Ulm). After the combination of both cohorts and multivariate testing, the overall survival of GOT1 high-expressing tumors is significantly longer compared to low-expressing tumors (P=0.009) and may serve as an independent prognostic marker in up to 68% of patients. Conclusions: Despite a lack of correlation between the GOT1 expression status and the KRAS mutation, or a specific clinicopathological phenotype, our findings indicate that the GOT1 expression status is a valuable prognostic biomarker in pancreatic ductal adenocarcinoma.
TRANSCATHETER AORTIC VALVE REPLACEMENT IN A PATIENT WITH VERY MOBILE AORTIC VALVE MASS
Authors: Brian Agbor-Etang, Hong Seok Lee, Ashis Mukherjee, Prabhdeep Sethi, Sami Nazzal, Alan Malki, Christopher Gibson, Ramdas Pai
Journal: Journal of the American College of Cardiology (2017)
Abstract 24: Bnip3 Provokes ROS Production and Maladaptive Autophagy by Displacing Uncoupling Protein3 (UCP3) From Cytochrome c Oxidase of Respiration Chain Complex in Cardiotoxicity
Authors: Rimpy Dhingra, Victoria Margulets, Davinder Jassal, Gerald Dorn II, Lorrie A. Kirshenbaum
Journal: Circulation Research (2015)

Doxorubicin is known for its cardiotoxic effects and inducing cardiac failure, however, the underlying mechanisms remain cryptic. Earlier we established the inducible - death protein, Bcl-2-like Nineteen- Kilodalton- Interacting - Protein 3 (Bnip3) to be crucial for disrupting mitochondrial function and inducing cell death of cardiac myocytes. Whether Bnip3 underlies cardiotoxic effects of doxorubicin toxicity is unknown. Herein we demonstrate a novel signaling pathway that functionally links activation and preferential mitochondrial targeting of Bnip3 to the cardiotoxic properties of doxorubicin. Perturbations to mitochondria including increased calcium loading, ROS, loss of αΨm and mPTP opening were observed in cardiac myocytes treated with doxorubicin. In mitochondria, Bnip3 forms strong association with Cytochrome c oxidase subunit1 (COX1) of respiratory chain and displaces uncoupling protein 3 (UCP3) resulting in increased ROS production, decline in maximal and reserved respiration capacity and cell viability. Impaired mitochondrial function was accompanied by an accumulated increase in autophagosomes and necrosis demonstrated by increase release of LDH, cTnT and loss of nuclear High Mobility Group Protein 1 (HMGB-1) immunoreactivity. Interestingly, pharmacological or genetic inhibition of autophagy with 3-methyl adenine (3-MA), or Atg7 knock-down suppressed necrotic cell death induced by doxorubicin. Loss of function of Bnip3 restored UCP3-COX complexes, mitochondrial respiratory integrity and abrogated necrotic cell death induced by doxorubicin. Mice germ-line deficient for Bnip3 were resistant to doxorubicin cardiotoxicity displaying normal mitochondrial morphology, cardiac function and survival rates comparable to vehicle treated mice. The findings of the present study demonstrate that doxorubicin provokes maladaptive autophagy and necrotic cell death of ventricular myocytes that is mutually dependent and obligatorily linked to Bnip3.
Non-Hodgkin's lymphoma (NHL) in elderly patients (pts): Patient-tailored treatment according to a comprehensive geriatric evaluation
Authors: D. Bernardi, I. Milan, M. Balzarotti, A. Giacalone, L. Uziel, L. Siracusano, A. J. M. Ferreri, M. Spina, A. Santoro, U. Tirelli
Journal: Journal of Clinical Oncology (2004)

6678 Background: Elderly patients affected by aggressive NHL are generally not treated in an optimal way. Therefore, we designed a new approach for elderly pts (>70 years) with aggressive NHL, that allows a pt-tailored treatment with the aim of maintaining a balance between the desire of curing the tumor and the need of providing a good quality of life. Methods: The study was started in March 2000. Pts with an ADL and IADL score of at least 5 and whose hepatic and renal function and hemopoietic reserve are sufficiently good, are treated with curative intent. These pts receive CHOP (those with a very good functional status) or CEOP (if mild cardiopathy is present) or CVP (if severe cardiopathy is present) or CEO (if diabetes mellitus is present). Dose reductions of chemotherapy (CT) are also applied according to IADL and ADL. Rituximab is administered if CD20+; G-CSF is administered from day 7 to 12. Results: So far, 61 pts have been enrolled. Median age was 75 years (range: 70–89). Fifty patients are evaluable for response (see table). Hematologic toxicity was evaluated in 42 patients (173 cycles) and G3-G4 toxicity at nadir was registered in 16 cycles (9.2%). Non-hematologic toxicity was evaluated in 56 patients (239 cycles) and was as follows: G3 gastrointestinal in 2 cycles, G3 neurologic in 9 cycles, G3 infection in 4 cycles. Median follow up is 13 months (range 1–43). Five pts relapsed. Thirty-four patients are still in CR. Nine patients died (2 early deaths, 6 PD and 1 respiratory failure in CR one month after the end of CT). Conclusions: Our results demonstrate that this completely new approach is feasible for elderly pts with NHL. We strongly believe that it is highly effective and without significant toxicity. We also believe that a similar approach should be employed for future studies aimed at determining the best treatment for elderly pts affected by any cancer type. No significant financial relationships to disclose.
HEALTH STATUS BENEFITS OF SUCCESSFUL CHRONIC TOTAL OCCLUSION PCI IN PATIENTS WITH DEPRESSED LEFT VENTRICULAR SYSTOLIC FUNCTION: INSIGHTS FROM THE OPEN-CTO REGISTRY
Authors: Sophia Airhart, Yevgeniy Khariton, William Lombardi, Kensey Gosch, James Sapontis, James Grantham, James McCabe
Journal: Journal of the American College of Cardiology (2017)
TRENDS AND OUTCOMES OF MITRAL VALVE REPLACEMENT IN PATIENTS WITH HEPATIC CIRRHOSIS: INSIGHT FROM NATIONAL INPATIENT SAMPLE
Authors: Fahad Alqahtani, Vinay Badhwar, Sami Aljohani, Ahmed Almustafa, Mohammad Akram Kawsara, Ali Hama Amin, Lawrence Wei, J. Scott Rankin, Mohamad Alkhouli
Journal: Journal of the American College of Cardiology (2017)
POOLED COHORT EQUATION AND CORONARY ARTERY CALCIUM IN RETIRED NATIONAL FOOTBALL LEAGUE ATHLETES
Authors: David Carruthers, Parag Joshi, Christopher Maroules, Colby Ayers, James Gentry, Philip Aagaard, Rory Hachamovitch, Reginald Dunn, Andrew Lincoln, Andrew Tucker, Kezia Alexander, Dermot Phelan
Journal: Journal of the American College of Cardiology (2017)
High response to docetaxel (D)/carboplatin (C) based chemotherapy as salvage therapy in patients with docetaxel-resistant metastastic hormone-refractory prostate cancer (HRPC)
Authors: C. Reuter, P. Ivanyi, M. Morgan, A. Ganser, T. Winkler, M. Fenner, V. Grünwald
Journal: Journal of Clinical Oncology (2009)

e16041 Background: Presently, there is no standard treatment for prostate cancer (PC) patients who are resistant to docetaxel therapy. While previous reports support the use of C in combination with D in these patients (pts), the optimal regime is still unknown. Methods: Metastatic HRPC pts with clinical and/or radiographic evidence of progression while on docetaxel were included in our retrospective analysis. Between February 2005 and December 2008, 30 pts received treatment with C AUC 5 q3wks in combination with D 75 mg/m2 q3wks or D 35 mg/m2 d1, d8, d15 q4wks. All pts were assessed for PSA response and clinical outcome. Results: 27 pts were evaluable for response. Median age was 69 years (range 56–77) and median baseline performance status was ECOG 1 (range 0–2). The median number of prior therapies was 1 (range 1–3) with a median of 7 cycles of D therapy (range 3–34) administered. Median PSA at baseline was 297.15 ng/ml (range 12.33–6,446). Serum chromogranin A and neuron-specific enolase (NSE) were elevated in 24/24 and 8/25 cases, respectively. The median follow-up was 8.9 months (range: 0–38) with a median number of 6 cycles DC administered (range: 2–35). PSA declines of ≥50% (= PSA-response) was achieved in 14 of 27 pts (52%, 95% C.I. 0.32, 0.71) and PSA stabilization in 9 pts (33%). 4 pts (15%) progressed without PSA response. 6 PSA responders had a PSA reduction of &gt;90%. The median duration of PSA response was 20.7 wks (95% C.I. 18.4, 59 wks). TTP was significantly longer in PSA responders vs. PSA non-responders (64.7 wks vs 15 wks, p&lt;0.0001). 10 of 16 pts with measureable disease were evaluable for response. 3 of 6 PSA responders had a PR and 3 SD, while 2/4 pts with PSA non-response had PD and 2 SD. At the time of analysis, 2 PSA responders and 7 PSA non-responders have died. Median OS of all patients was 69.7 weeks with 79.9 wks for PSA responders vs. 38 wks for PSA non-responders (p=0.0034). The most common grade 3/4 toxicities were neutropenia in 42%, anemia in 23% and thrombocytopenia in 15% of pts. 17 of 30 pts had blood transfusions due to anemia. Conclusions: This retrospective analysis supports the usefulness of C plus weekly D chemotherapy as ≥second-line chemotherapy in docetaxel-resistant PC patients. No significant financial relationships to disclose.
PROPHYLACTIC DEFIBRILLATOR IMPLANTATION IN PATIENTS WITH NON-ISCHEMIC CARDIOMYOPATHY: AN UPDATED COMPREHENSIVE META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Rahman Shah, Mark Heckle, Abdul Rashid, David Flatt, Teresa Slomka, Beatrix Ramos Bondy, Mohamed Morsy
Journal: Journal of the American College of Cardiology (2017)
Adjuvant aromatase inhibitor adherence based on the Morisky Medication Adherence Scale and identification of predictors to adherence.
Authors: Paula Rosenblatt, Olga G. Goloubeva, Susan Kesmodel, Emily Catherine Bellavance, Saranya Chumsri, Ting Bao, Brian Heiss, Elizabeth M. Nichols, Steven J. Feigenberg, Nancy Tait, Katherine Hanna Tkaczuk
Journal: Journal of Clinical Oncology (2015)

555 Background: Aromatase inhibitors (AI) improve outcomes in hormone receptor positive breast cancer. Unfortunately, adherence to these oral agents remains difficult for many patients. The Morisky Medication Adherence Scale (MMAS) is a validated eight item questionnaire that measures adherence to medication in many chronic conditions. However, the MMAS has not been studied in the oncology setting. The purpose of this study was to identify the level of AI adherence in breast cancer patients based on the MMAS. Secondary objectives were to identify predictors of adherence. Methods: Patients were eligible if they had stage 1-3 hormone receptor positive breast cancer and were being treated at the University of Maryland Marlene and Stewart Greenebaum Cancer Center with AI therapy. Consecutive eligible patients were offered participation on an IRB approved protocol and informed consent was obtained. Participants completed the study questionnaires consisting of the MMAS and demographics. Participants were stratified by duration of AI therapy ≤ 2 years and > 2 years. Results: Between March 2011 and November 2014,100 women were accrued. Median age was 59, 37% were African American, and 62% received chemotherapy. Total adherence was 13% low (MMAS < 6), 37% medium (MMAS 6-7), and 50% high (MMAS = 8). There was no association of duration of AI treatment ≤ 2 yrs vs > 2 yrs and adherence level. The cumulative logit model revealed that possibly race and use of chemotherapy have some predictive ability for adherence, however p-values were only of marginal statistical significance. No association was found between adherence level and age, stage, tumor size, lymph node positivity, type of surgery, use of radiation, education level, marital status, insurance status, or comorbid conditions. Conclusions: Our study shows that only 50% of our patients on adjuvant AI therapy have high adherence based on the MMAS scale. There is a possible association of improved adherence to AI therapy in white patients and those who received adjuvant chemotherapy. Further research is needed to identify predictors to AI adherence in order to develop effective interventions to optimize compliance.
Gemcitabine and ifosfamide (GI) as a second-line systemic chemotherapy for cisplatin-failed advanced urothelial carcinoma (UC)
Authors: Y.-S. Pu, C.-C. Lin, C.-H. Hsu, H.-Y. Keng, C.-Y. Huang, J. Chen, A.-L. Cheng
Journal: Journal of Clinical Oncology (2004)

4739 Background: Cisplatin-based combination chemotherapy is the mainstay treatment for advanced UC. There is no standard salvage regimen for patients who fail cisplatin-based chemotherapy. We evaluated the efficacy and safety of the combination of gemcitabine and ifosfamide as a second-line treatment for advanced UC. Methods: Between Dec. 1998 and Dec. 2003, 15 patients (M:F = 12:3) with a median age 66 (48 - 76) were enrolled. All did not respond to cisplatin-based chemotherapy or progressed from previously cisplatin-sensitive status in less than 6 months (4 with CMV, 5 with P-HDFL [Proc ASCO 2001 abstr 3128], 6 with TP-HDFL [Proc ASCO 2003 abstr 1637]). GI consisted of gemcitabine 800 mg/m2/d IV 30 min on D 1, 8 & 15; ifosfamide 1500 mg/m2/d IV 24 hr on D 8–10; and mesna 800 mg IV bolus before ifosfamide & 1500 mg/m2/d IV 24 hr on D 8 - 11, repeated every 28 days. Results: A total of 48 courses had been given, with an average of 3.4 courses per patient (range: 1–6). Among 14 patients eligible for response evaluation, there were 1 complete response, 4 partial responses, 4 stable diseases and 2 progressive diseases. One patient is still under the protocol treatment now. The overall response rate was 36% (95% C.I. 10–62%) with 7% complete response. The median survival was 6 months (range: 1 to 26+). Fourteen patients were eligible for analysis of toxicity. Grade III/IV leukopenia, anemia, and thrombocytopenia were noted in 6 (14 cycles), 3 (5 cycles), and 6 (11 cycles) patients, respectively. Grade III/IV nausea, vomiting, mucositis, and diarrhea were noted in 0, 1, 3, and 0 patient, respectively. Conclusions: GI is active against cisplatin-failed advanced UC with an acceptable toxicity profile. No significant financial relationships to disclose.
OUTCOMES OF CONCOMITANT ACUTE KIDNEY INJURY AND HOSPITAL ACQUIRED ANEMIA IN PATIENTS WITH MYOCARDIAL INFARCTION: THE TRIUMPH STUDY
Authors: Bhaskar Bhardwaj, Yashashwi Pokharel, Kevin Kennedy, Adam Salisbury, Faraz Kureshi, John Spertus
Journal: Journal of the American College of Cardiology (2017)
ACCURATE SEGMENTAL STRAIN ANALYSIS ON STANDARD CMR CINE IMAGES USING A NOVEL METHOD OF SEGMENT LENGTH TRACKING IN CRT CANDIDATES
Authors: Alwin Zweerink, Cornelis Allaart, Joost P.A. Kuijer, Lina Wu, Aernout Beek, Peter van de Ven, Mathias Meine, Piere Croisille, Patrick Clarysse, Albert van Rossum, Robin Nijveldt
Journal: Journal of the American College of Cardiology (2017)
Usage of HLC-Ratio, FLC-Ratio, Ife, PBMC Infiltration and Isotype Suppression At Best Response Reveals Isotype Suppression As Most Powerful Parameter for Identification of Multiple Myeloma Patients with Long Survival
Authors: Heinz Ludwig, Georg Slavka, Wolfgang Hübl, Hugh Carr-Smith, Dejan Milosavljevic, Richard Hughes, Niklas Zojer, Stephen Harding
Journal: Blood (2012)
PERCUTANEOUS CORONARY INTERVENTION OF CORONARY CHRONIC TOTAL OCCLUSIONS IMPROVES PEAK OXYGEN UPTAKE DURING CARDIOPULMONARY EXERCISE TESTING
Authors: Shuaib Abdullah, Jeffrey Hastings, Suwetha Amsavelu, Francisco Garcia-Morales, Fury Hendrix, Aris Karatasakis, Barbara Danek, Judit Karacsonyi, Bavana Rangan, Michele Roesle, Houman Khalili, Subhash Banerjee, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2017)