tbuckley/cabot-search huggingface dataset:
Outcomes of hematopoietic stem cell transplant recipients admitted to the medical intensive care unit.
Authors: Duc Quang Tran, Amelia A. Langston, Edmund K. Waller, Melanie Simon, Charise Gleason, Daniela Casbourne, Micah Fisher, Jonathan L. Kaufman, Christopher Flowers, Sagar Lonial, Ajay K. Nooka
Journal: Journal of Clinical Oncology (2013)

7035 Background: Outcome results for hematopoietic stem cell transplant (HSCT) patients admitted to intensive care unit (ICU) and prognosis is infrequently reported during recent years, especially in view of increasing use of unrelated donors, increasing use of transplant maneuver in older patients using reduced intensity conditioning regimens and improvement in supportive care. We assessed our institutional survival outcomes and evaluated predictors of mortality in HSCT recipients admitted to ICU. Methods: Among the 390 HSCTs performed from March 2011 until July 2012, we retrospectively evaluated 34 HSCT patients admitted to ICU. 22 patients received mechanical ventilation (MV) or vasopressor support and were analyzed separately. All previously defined predictors of mortality were evaluated. SPSS version 20 was used for statistical analysis. Results: 9% of all HSCT patients were admitted to ICU. 65% of patients received allogeneic transplants. Major underlying hematological malignancies were AML/MDS (29%) and myeloma (24%). 41% were admitted for respiratory failure and 23.5% for sepsis. Median age was 55.5 (range: 27-76). Median length of ICU stay was 7 days (0-42) and median APACHE II score was 20 (9-39). 30 day and 60 day mortality rates are 47% and 62% among all patients; 54% and 68% among MV patients or receiving vasopressors. Predictors for day 30 mortality on univariate analysis among all patients were APACHE II score ≥26 (p=0.05). Predictors for day 60 mortality were APACHE II score ≥31 (p=0.001) and multiorgan failure (p=0.009). Among patients receiving MV or vasopressors, APACHE II score ≥31 is the only significant predictor of mortality (p=0.011). On multivariate analysis, APACHE II score ≥31 at day 30 hazards ratio (HR) 3.777 (95%CI 1.041-13.69; p=0.043) and at day 60 HR 3.789 (95%CI 1.07-13.45; p=0.039) are significant predictors of mortality. Conclusions: Significant predictors identified on multivariate analyses were APACHE II score ≥31 at day 30 and day 60. Interestingly, type of transplant is not a significant predictor of mortality. Future studies with larger patient samples and longer follow up are required for further understanding of prognosis in these patients.
FIRST-IN-HUMAN VISONE HEART FAILURE STUDY: ASYMPTOMATIC DIAPHRAGMATIC STIMULATION FOR CHRONIC HEART FAILURE WITH REDUCED EJECTION FRACTION: CASE REPORT
Authors: Ana Jorbenadze, Nikoloz Shaburishvili, Michael Mirro, Michel Zuber, Paul Erne, Tamaz Shaburishvili
Journal: Journal of the American College of Cardiology (2020)
HSR20-113: Diabetes Complications and Risks of Breast Cancer Recurrence Among Older Women
Authors: Jifang Zhou, Alemseged A. Asfaw, Nadia A. Nabulsi, Nita A. Mukand, Inyoung Lee, Naomi Y. Ko, Denise M. Boudreau, Gregory S. Calip
Journal: Journal of the National Comprehensive Cancer Network (2020)
Effect of pretreatment clinical consultation on oncologist prescribing behavior in the initial treatment of NSCLC.
Authors: Marc L. Fishman, Akhil Kumar, William S. Shimp, Laura Rose Bobolts, James Edward Krook, Val Fishman, Sharon Davis, Robert Walton, Dinah Huff, William J. Hrushesky
Journal: Journal of Clinical Oncology (2013)

e19130 Background: Oncology Analytics (OA) promotes evidence-based treatments, based upon objective assessments of efficacy and safety. ASCO guidelines and FDA approval recommend bevacizumab only in combination with carboplatin/paclitaxel, based on E4599 which showed improved OS. NCCN guidelines allow bevacizumab with virtually any approved 1st line chemotherapy (2A). Board certified OA oncologists perform real-time clinical consultations if bevacizumab usage in 1st line is not per level 1 evidence. More recently, those conversations include the Phase III Pointbreak Trial’s failure to show OS advantage with carboplatin/pemetrexed/bevacizumab. Methods: All bevacizumab requests with doublet chemotherapy were tabulated, from 2010 through 2012, and the outcome of pre-treatment clinical consultations were retrospectively analyzed. Results: Bevacizumab with a platinum doublet was requested in 91 patients with non-squamous NSCLC. Of these, 53% (48/91) of requests were for carboplatin/paclitaxel/bevacizumab, consistent with level one evidence, FDA approval and ASCO guidelines. All were approved after confirmation of histology and absence of relative contraindications. Approximately half (47%; 43/91) of the requests were not consistent with level 1 evidence, though compliant with non-evidence-based NCCN guidelines. After clinical consultation, 20 of 43 requests (46%) were revised to evidence-based protocols. Conclusions: These data suggest that nearly half of bevacizumab requests in NSCLC are not in accordance with published level 1 evidence. Pre-treatment clinical consultations can promote evidence based care while reducing costs. National guidelines should be evidence based, especially in common cancers where level 1 evidence is available, since practicing physicians may rely on these guidelines when planning treatment. [Table: see text]
A randomised phase II study comparing irinotecan (IRI) plus leucovorin (LV) and 5-fluorouracil (5FU) versus IRI-LV-5FU followed be oxaliplatin (OXA) plus LV-5FU in patients with previously untreated metastatic colorectal cancer (CRC)
Authors: H. P. Kalofonos, P. Papakostas, G. Aravantinos, C. Papadimitriou, G. Pentheroudakis, I. Varthalitis, D. Tsavdaridis, K. Syrigos, P. Kosmidis, G. Fountzilas
Journal: Journal of Clinical Oncology (2006)

3583 Background: IRI and OXA are both effective in the treatment of CRC. A theoretical framework supports the hypothesis that sequential administration of cytotoxic drugs at adequate doses can maximize the cell kill and overcome drug resistance. The aim of the study was to compare the response rate (RR), the time to tumor progression (TTP), the overall survival (OS) and to assess the toxicity profile of previously untreated patients with advanced CRC randomly assigned between IRI-LV-5FU (arm A) versus IRI-LV-5FU followed by OXA-LV-5FU (arm B). Methods: Intent to treat analysis was performed on 429 patients (219 in arm A and 210 in arm B) who were randomized from 31/10/2001 to 21/10/2004. The treatment schedules consisted of weekly IRI, 80 mg/m 2 or OXA, 45 mg/m 2 plus LV 200 mg/m 2 followed immediately by intravenous bolus 5FU, 450 mg/m 2 for 6 weeks followed by a 2-week rest period. Treatment was continued for 4 cycles, patients in arm B were treated initially with IRI-LV-5FU for 2 cycles followed by sequential administration of 2 cycles of OXA-LV-5FU. Results: The study failed to show any superiority of the sequential regimen. There were no significant differences between the two arms in the overall RR (26% versus 28%, p=0.631), TTP (Median, 7.8 versus 8.4 months, p=0.149). Toxicity profiles (grade III and IV) were equally frequent in both arms (diarrhea 13% versus 13.5%, febrile neutropenia 2% versus 1.5%, neurotoxicity 0% versus 0.5%). Conclusions: IRI-LV-5FU or IRI-LV-5FU followed by QXA-LV-5FU show equally substantial activities with manageable toxicity profile in advanced CRC. No significant financial relationships to disclose.
Critical Care Utilization for the COVID-19 Outbreak in Lombardy, Italy
Authors: Giacomo Grasselli, Antonio Pesenti, Maurizio Cecconi
Journal: JAMA (2020)

Yan Bai, MD; Lingsheng Yao, MD; Tao Wei, MD; Fei Tian, MD; Dong-Yan Jin, PhD; Lijuan Chen, PhD; Meiyun Wang, MD, PhD
Risk factors for gastrointestinal perforations in patients with metastatic colorectal cancer receiving bevacizumab plus chemotherapy
Authors: M. Sugrue, M. Kozloff, J. Hainsworth, S. Badarinath, A. Cohn, P. Flynn, R. Steis, W. Dong, S. Sarkar, A. Grothey
Journal: Journal of Clinical Oncology (2006)

3535 Background: Bevacizumab (BV) prolongs overall survival and progression-free survival when added to standard chemotherapy in patients (pts) with metastatic colorectal cancer (mCRC). BRiTE is a large, community-based observational registry of pts with mCRC receiving BV plus first-line chemotherapy (CT). Incidence rate, temporal pattern, and potential risk factors associated with gastrointestinal perforation (GIP) were explored. Methods: Baseline patient characteristics (BC), including prospectively identified potential risk factors for GIP, were collected at study entry. Safety data were collected every 3 months (mo). Logistic regression models, adjusted and unadjusted for treatment assignment, were used to identify BC potentially associated with GIP. Results: 1968 pts were enrolled between Feb 2004 and Jun 2005. Median study follow-up was 10 mo as of Nov 4, 2005. GIPs were observed in 34 pts (1.7%). For pts with GIP, median time to first event was 2.1 mo; the majority of events were non-fatal and occurred within the first 3 mo after starting BV. BC including GI medical history (chronic aspirin or NSAID use, peptic ulcer disease, diverticulosis) were similar in pts with or without GIP and with earlier or later GIP onset (≤ or &gt;3 mo from start of BV). Although adjusted models did not show any significant BC, GIP rates were numerically higher in pts with primary tumor intact (2.6%) vs. resected (1.6%). Furthermore, univariate analyses revealed a significant difference between intact (2.3%) and resected (0.8%) primary tumor for earlier GIP (≤3 mo from start of BV). The majority of pts with GIP had at least one of the following: acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, tumor at GIP site, abdominal carcinomatosis, prior abdominal or pelvic radiation therapy. Conclusions: Preliminary analyses indicate the incidence of GIP in this large, community-based observational registry is similar to that previously reported in phase III mCRC trials with BV. No associations between specific BCs and an increased risk of GIP were identified. Patients with primary tumor intact were more likely to incur a GIP within the first 3 mo of starting BV and CT. [Table: see text]
Ovarian cancer distribution of histology, stage, and screening performance.
Authors: Lua R Eiriksson, Clare J Reade, Genevieve Lennox, Golnessa Mojtahedi, Joan Murphy, Sarah E Ferguson, Marcus Q Bernardini
Journal: Journal of Clinical Oncology (2013)

5543 Background: Survival in women with ovarian cancer is strongly influenced by stage of disease at diagnosis. As such, strategies have been investigated to identify biomarkers for early detection. This premise assumes a progression of disease from early to late stage. Varying histologic subtypes in ovarian cancer have distinct etiologies. It is likely that early detection strategies will need to be subtype specific. This study sought to evaluate histologic subtypes, stage of disease, and screening performance in a cohort of women diagnosed with ovarian cancer. Methods: This analysis was performed as an REB approved sub-study of a single institution ovarian cancer tumor banking protocol for which all patients presenting with suspected ovarian cancer, since February 2011, were eligible. This analysis included all patients with confirmed ovarian cancer. Patients were identified and tracked prospectively. Results: There were 135 patients with ovarian cancer (mean age 57 ± 12 years). 67% were post-menopausal. The distribution of histologic subtypes was 42% high-grade serous (HGS), 18% endometrioid, 12% clear cell, 6% low-grade serous (LGS), 6% sex-cord stromal, 5% germ cell, 3% mucinous, 3% mixed, 3% carcinosarcoma, and 2% other. 64 (47%) women presented with advanced disease with a median CA 125 of 260 (range 14 – 21 782), of whom 43 (68%) were found to have HGS histology. 46 (34%) patients presented with stage I disease with a median CA 125 of 41 (range 3 – 9305). Of these, the distribution of histologic subtypes included 13 (28%) endometrioid, 9 (20%) clear cell, 5 (11%) sex-cord stromal, 5 (11%) HGS, 3 (7%) mucinous and 23% other. Risk of Malignancy Index (RMI) scoring for women with stage I disease (N = 35) revealed a false negative rate of 31%, including 4 clear cell, 2 LGS, 2 endometrioid and 1 each of HGS, mucinous, and mixed (clear cell and endometrioid) histologies. Conclusions: Stage I ovarian cancer consists primarily of non-serous histologies, which are not reliably detected using CA 125 and ultrasound markers. Current approaches to screening for early stage disease may require the identification of biomarkers unique to clear cell and endometrioid histologies and novel strategies for the identification of patients at risk for HGS carcinomas.
ACUTE OUTCOMES AFTER CORONARY ORBITAL ATHERECTOMY AT CENTERS WITHOUT ON-SITE SURGICAL BACKUP: DIABETICS VERSUS NON-DIABETICS AND IMPACT OF ACCESS SITE
Authors: Lakshmi G. Rao, Anila Rao, Zsuzsanna Igyarto, Brad Martinsen, Surya Rao
Journal: Journal of the American College of Cardiology (2020)
CAN THE SEQUENTIAL ORGAN FAILURE ASSESSMENT (SOFA) SCORE BE USED FOR RISK STRATIFICATION IN A TERTIARY CARDIAC INTENSIVE CARE UNIT POPULATION?
Authors: Anika Raja, Ankit Vyas, Aaron Jacob Bagnola, Scott Barnett, Carolyn Rosner, Behnam Tehrani, Alexander George Truesdell, Abdulla Damluji, Robert Cole, Lauren Cooper, Shashank Desai, Hala Moukhachen, Mitchell Psotka, Palak Shah, Stephanie Garofalo, Wayne B. Batchelor, Christopher R. DeFilippi, Shashank Sinha
Journal: Journal of the American College of Cardiology (2020)
Abstract P6-04-20: Proteogenomic analysis of estrogen modulated breast cancer metastasis
Authors: Anran Chen, Purba Singh, Beom-Jun Kim, Lacey E Dobrolecki, Alana L Welm, Michael T Lewis, Matthew J Ellis
Journal: Cancer Research (2020)

Abstract Background: Estrogen Receptor (ER) positive breast cancer is the most common subtype (70%) and associated with the most deaths from the disease. Almost all deaths from breast cancer are caused by metastasis. While metastatic ER-positive breast cancer is a leading cause of cancer-related death, metastasis studies have largely focused on ER-negative breast cancer. A major reason for such imbalance is the lack of physiologically relevant mice models for studying ER-positive breast cancer. The patient derived xenograft (PDX) technique provides us with a powerful means to study highly clinically relevant human ER-positive breast cancer in mice, but most studies using PDX models still focus on orthotopic rather than metastatic tumor growth. Here we describe studies of the metastatic process using PDX models to more comprehensively understand the value of these PDX lines for therapeutic modelling. These findings will empower us to develop therapeutics designed to control systemic disease, not just orthotopic tumor growth. Experimental design and methods: We have studied 14 ER positive PDX lines in ovariectomized SCID beige mice with and without estradiol supplementation. We have analyzed both orthotopic tumor and a variety of metastatic sites including liver, lung, brain and bone. Data is being generated using next-generation DNA and RNA sequencing, mass spectrometry-based proteomics. We use integrated bioinformatics pipelines to shed light on the metastatic process. Results: We have generated macro-metastatic maps that record sites with observable metastatic nodules of each PDX line in mice. IHC of Liver, bone, brain, lung of each mouse also generated micro-metastatic maps. The most common organ of metastasis in mice is the lung. In some PDX lines, the sites of metastasis differ between groups with and without estradiol supply. The ongoing proteogenomic profiling of orthotopic and metastatic tumors reveals potential molecular drivers of metastasis in ER+ breast cancer. Conclusion: Here, we describe an approach to the systematic investigation of the ER+ breast cancer metastasis process. This approach will allow us to identify druggable targets that may interrupt the metastatic process and/or inhibit tumor growth at metastatic sites. Citation Format: Anran Chen, Purba Singh, Beom-Jun Kim, Lacey E Dobrolecki, Alana L Welm, Michael T Lewis, Matthew J Ellis. Proteogenomic analysis of estrogen modulated breast cancer metastasis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-04-20.
Advanced ovarian carcinoma: Which place for neoadjuvant chemotherapy?
Authors: G. Bousquet, F. Narducci, A. Lesoin, S. Taieb, C. Fournier, D. Querleu, E. Leblanc
Journal: Journal of Clinical Oncology (2006)

5071 Background: Most patients with ovarian carcinoma are diagnosed at an advanced stage. The ability to surgically resect tumor to microscopic residual disease remains a major prognostic factor. The use of a preoperative chemotherapy for patients with bulky disease is still debated. The objective of this study was to evaluate this therapeutic sequence. Methods: We retrospectively collected data from 207 stage III ovarian cancer patients between January 1998 and August 2004. 127 patients were considered as poor surgical candidates and received neoadjuvant chemotherapy. After 3 courses of a platinum-based chemotherapy, 51 patients who showed a good response by CA125 and CT scan underwent an interval debulking surgery (Group A). For the 43 patients with a partial response or stable disease, 3 other cycles of the same protocol were administered, followed by a secondary surgery (Group B). The remaining 33 patients progressed and had no surgery (GroupC). Results: Optimal tumor debulking (residuum &lt;1 mm) was achieved in 90% and 81% of group A and B patients respectively. Node involvement was not different between the two groups (62%). After a median follow-up of 20.8 months, 98 patients had relapsed and 54 had died. Median OS was 42 months, 37.2 months and 14.4 months for group A, B and C respectively. Three-year OS was 76.7% for group A vs. 50.9% for group B (p = 0.11). Two-year disease free survival was not statistically different for groups A and B (17.3% and 18.5%). In the combined A and B sub-group, univariate analysis for OS showed non-optimal staging according to EORTC criteria (p = 0.005), post-surgical residuum (p = 0.02) and lack of lymphadenectomy (p = 0.01) as adverse prognostic factors. On multivariate analysis, only non-optimal staging remained significant. Conclusions: Neoadjuvant chemotherapy is feasible. We believe the difference in overall survival between groups A and B was likely due to a higher chemosensitivity for group A. Our results support the importance of an optimal surgical staging and the possible therapeutic role of routine lymphadenectomy. No significant financial relationships to disclose.
Results from a phase Ib study of trastuzumab emtansine (T-DM1), paclitaxel (T), and pertuzumab (P) in patients with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab.
Authors: Shanu Modi, Anthony D. Elias, Patricia LoRusso, Meghna Samant, Ellie Guardino, Betsy Althaus, Ian E. Krop
Journal: Journal of Clinical Oncology (2012)

528 Background: The antibody–drug conjugate T-DM1 has shown single-agent activity in phase II studies in patients (pts) with HER2–positive MBC. Preclinical data suggest synergy for T-DM1 combined with taxanes and with P. Methods: TDM4652g is a phase Ib, open-label, dose-escalation study evaluating the safety and tolerability of T-DM1 (qw and q3w) + T (qw) ± P (q3w) in pts with HER2-positive MBC previously treated with trastuzumab. A 3+3 dose-escalation scheme is used for T-DM1 + T to determine the maximum tolerated dose (MTD); P is added at this MTD. Initial restrictive dose-limiting toxicity (DLT) criteria were modified to establish a more clinically relevant MTD. Results: We report interim results with T-DM1 (qw and q3w) + T (+ P) using modified DLT criteria. 24 pts have been enrolled in these cohorts; median age was 53 yrs (range, 23–69)*; median number of prior systemic therapies in MBC was 7 (range, 2–15)*. See table below. Conclusions: Data support combining T-DM1 + T ± P at the MTD for future clinical trials. The MTD for weekly T-DM1 + T is 2.4 mg/kg + 80 mg/m 2 qw; MTD for weekly T-DM1 + T + P is 2.4 mg/kg + 80 mg/m 2 qw + 840 mg LD, 420 mg q3w. Updated results will be presented, including the MTD for T-DM1 q3w + T qw ± P q3w, outcomes from pts with prolonged follow-up, and duration of response from an extension trial. [Table: see text]
Anti-carbamylated proteins antibody repertoire in rheumatoid arthritis: evidence of a new autoantibody linked to interstitial lung disease
Authors: Raul Castellanos-Moreira, Sebastian Cruz Rodríguez-García, Maria Jose Gomara, Virginia Ruiz-Esquide, Andrea Cuervo, Ivette Casafont-Solé, Julio Ramírez, Susana Holgado, Jose A Gómez-Puerta, Juan D Cañete, Isabel Haro, Raimon Sanmarti
Journal: Annals of the Rheumatic Diseases (2020)

To analyse the association between anti-carbamylated protein antibodies (Anti-CarP) and interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients.Cross-sectional study including RA patients fulfilling the 2010 ACR/EULAR criteria. The main population comprised two groups: (1) RA patients diagnosed with RA-ILD (RA-ILD group); (2) RA patients without ILD (non-ILD RA group). Non-ILD RA patients in whom ILD was suspected underwent a diagnostic work-up and, if ILD was diagnosed, were switched to the RA-ILD group. ILD was diagnosed by high-resolution computed tomography and confirmed by a multidisciplinary committee. An independent replication sample was also obtained. Three Anti-CarP IgG autoantibodies against fetal calf serum (Anti-FCS), fibrinogen (Anti-Fib) and chimeric fibrine/filagrine homocitrullinated peptide (Anti-CFFHP) and one Anti-CarP IgA against FCS (Anti-FCS-IgA) were determined by home-made ELISA. Associations between Anti-CarP and ILD were analysed using multivariable logistic regression adjusted by smoking, sex, age, RA disease duration, rheumatoid factor and anticitrullinated protein antibodies.We enrolled 179 patients: 37 (21%) were finally diagnosed with RA-ILD. Anti-CarP specificities were more frequent in RA-ILD patients (Anti-FCS 70% vs 43%; Anti-Fib 73% vs 51%; Anti-CFFHP 38% vs 19%; Anti-CarP-IgA 51% vs 20%, p<0.05 for all comparisons). Serum titers of Anti-CarP were significantly higher in RA-ILD patients. Anti-CarP specificities showed a robust effect towards increasing the odds of ILD in the multivariate analysis (Anti-FCS (OR: 3.42; 95% CI: 1.13 to 10.40), Anti-Fib (OR: 2.85; 95% CI: 0.83 to 9.70), Anti-CFFHP (OR: 3.11; 95% CI: 1.06 to 9.14) and Anti-FCS-IgA (OR: 4.30; 95% CI: 1.41 to 13.04)). Similar findings were observed in the replication sample.Anti-CarP were strongly associated with ILD. The role of homocitrullination in RA-ILD merits further investigation.