tbuckley/cabot-search huggingface dataset:
Phase II study of preoperative radiation with concurrent capecitabine, oxaliplatin, and bevacizumab followed by surgery and postoperative 5-FU, leucovorin, oxaliplatin (FOLFOX), and bevacizumab in patients with locally advanced rectal cancer: A trial of the Eastern Cooperative Oncology Group (E3204).
Authors: Steven J. Cohen, Yang Feng, Jerome Carl Landry, Charles A. Staley, Richard Whittington, Elin R. Sigurdson, Halla Sayed Nimeiri, Udit N. Verma, Al Bowen Benson
Journal: Journal of Clinical Oncology (2012)

3605 Background: Oxaliplatin and bevacizumab potentiate the antitumor activity of fluoroyprimidines and radiotherapy in preclinical and clinical studies of colorectal cancer. This phase II trial evaluated the efficacy of the preoperative combination of capecitabine, oxaliplatin, and bevacizumab with radiotherapy in rectal cancer. Methods: Eligibility: resectable T3/T4 adenocarcinoma of the rectum ≤ 12 cm. from anal verge. Preoperative treatment was capecitabine (825 mg/m² bid M-F), oxaliplatin (50 mg/m² weekly), bevacizumab (5 mg/kg D1,15,29), and pelvic external beam radiotherapy (50.4 Gy/28 fractions). Surgery was performed within 6-8 weeks. Within 12 weeks of surgery, patients received 12 cycles of FOLFOX + bevacizumab (5 mg/kg) Q2 weeks. Pathologic complete response (path CR) was the primary endpoint. Secondary endpoints included resection rate and toxicity. Results: Fifty-seven patients (pts) enrolled from 7/06 to 5/10 and 54 were eligible. Clinical staging: T3/4 (50/4), NX0/1/2 (2/16/31/5). Most common grade 3/4 non-hematologic toxicities during treatment were rectal pain (9), fatigue (8), and diarrhea (7). Two patients died of aspiration. Nine pts had early postsurgical complications (9 wound infections, 6 dehiscence, 1 abscess) and 23 had late surgical complications (23 non-healing wounds, 12 dehiscence, 5 bowel obstruction/ileus, 2 abscess). Pathologic staging: T0/1/2/3 (11/3/15/19), N0/1/2 (32/10/7). Nine pts had path CRs (17%, 90% CI:[9%-27%]. Surgery was LAR (38) and APR (11). Twenty-two pts did not receive postoperative chemotherapy (39%), 16 due to adverse events. Five local recurrences have been reported. RFS and OS data are immature. Conclusions: The addition of oxaliplatin and bevacizumab to capecitabine and radiotherapy for locally advanced rectal cancer resulted in downstaging for the majority of pts but did not improve the pathologic complete response rate compared to historical controls. The combination resulted in significant early and late postsurgical complications.
Practitioner feedback on clinical practice guidelines developed by Cancer Care Ontario's Lung Disease Site Group: Extending the circle of involvement
Authors: W. K. Evans, D. Cameron, J. Mackay, N. Lloyd, M. Brouwers
Journal: Journal of Clinical Oncology (2004)

6031 Background: Clinical practice guidelines (CPGs) are developed in Ontario through the disease site groups of Cancer Care Ontario's Program in Evidence-based Care. The Lung DSG consists of medical, radiation and surgical oncologists, methodologists, nurses and two consumer representatives. Guideline topics are selected by the DSG members and researched by specially trained research coordinators, who collate the evidence from the medical literature for review by the DSG. Since 1995, 10 CPGs have been published and 4 others have been completed in draft form. Methods: Completed CPGs are sent to practitioners for their feedback (PF) as part of the CPG development cycle. The CPG is accompanied by a survey instrument that asks about the acceptability and usefulness of the CPG to the practitioner. Results: 1198 questionnaires have been sent with the 14 CPGs to medical oncologists (52.3% of total questionnaires), radiation oncologists (16.3%), surgeons (15.9%), respirologists (13.7%) and other specialists (1.8%). The majority of questionnaires went to community-based practitioners (60%) and most practitioners surveyed were not members of the DSG (83.1%). Surveys were completed by 62.8% of those surveyed and 80% of those responding indicated that the CPG was relevant to their practice. Respondents indicated that they agreed or strongly agreed with the need for the CPG topic in 86.9% of cases, with the acceptability of the evidence summary (91.9%) and with the guideline recommendation as stated (86.1%). Overall, 77.1% indicated that they were likely to use the CPG in their practice. Practitioners frequently commented on issues of guideline clarity and adoption, or suggested wording edits. Explicit responses to these comments are included in the final CPG. Conclusions: PF enables a greater number of practitioners to participate in CPG development and review, obtains important feedback on the quality of the CPG document and the feasibility of CPG use in practice. By self-report, the majority of practitioners indicate that they would adopt CPG recommendations from the provincial Lung DSG. No significant financial relationships to disclose.
DNA Methylation Profiling of Sorted Cells from Myelofibrosis Patients reveals Aberrant Epigenetic Regulation of Immune Pathways and identifies Early MPN Driver Genes
Authors: Hans Carl Hasselbalch, Helene Myrtue Nielsen, Fazila Asmar, Christen Lykkegaard Andersen, Lasse Sommer Kristensen, Kruse A Torben, Mads Thomassen, Thomas Stauffer Larsen, Vibe Skov, Caroline Riley, Lise Lotte Hansen, Morten K. Jensen, Ole Weis Bjerrum, Vasu Punj, Kirsten Grønbæk
Journal: Blood (2014)
Physical Violence During the 12 Months Preceding Childbirth—Alaska, Maine, Oklahoma, and West Virginia, 1990-1991
Journal: JAMA (1994)

This study examined the prevalence of physical violence against women during the 12 months preceding childbirth and its relation to maternal characteristics in Alaska Maine Oklahoma and West Virginia.  Using the 1990 and the 1991 data from the Pregnancy Risk Assessment Monitoring System varied percentages of women reporting physical abuse among the four states were noted: from 3.8% in Maine to 6.9% in Oklahoma.  Overall the report indicated that in each state higher rates of physical violence were associated with low educational attainment race marital status age living conditions participation in prenatal care and unintended pregnancy.  In addition this article cites recommendations for health care providers to be aware of the risk among all pregnant women; for efforts to effectively identify victims; for evaluations of intervention programs; and for further examinations of the patterns of violence during pregnancy.
Survey ranks Indian cities on cleanliness
Authors: Cheryl Travasso
Journal: BMJ (2016)

Mysuru, Chandigarh, and Tiruchirapalli have come top—while Itanagar, Asansol, and Dhanbad have finished last—in a survey1 that ranked 73 Indian cities on cleanliness and sanitation.

The survey, Swachh Survekshan (Clean Survey) 2016, is part of a programme to improve the cleanliness of Indian cities. Led by the Quality Council of India, a joint organisation representing the Indian government and three industry associations, teams of trained assessors visited state capitals and cities …
Application of intrathecal trastuzumab for treatment of meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer
Authors: K. Shojima, E. Suzuki, K. Saito, S. Sekine, D. Kitagawa, T. Aruga, S. Saji, K. Kuroi
Journal: Journal of Clinical Oncology (2008)

1138 Background: When the humanized anti-HER2 monoclonal antibody trastuzumab is given intravenously, very little reaches the cerebrospinal fluid (CSF). Thus, carcinomatous meningitis may occur in patients with complete systemic remission induced by trastuzumab therapy. Intracerebral injections in rats with meningeal carcinomatosis have shown an increase in survival without clinical or histologic toxic effects. Three cases of meningeal dissemination from breast cancer treated with intrathecally administered trastuzumab have been reported clinically without any significant adverse events. Here we report a case of a 66-year-old woman with HER2-overexpressing metastatic breast cancer who suffered from meningeal carcinomatosis and was treated with intrathecal trastuzumab. Results: The patient developed invasive apocrine carcinomas (six involved nodes, hormone receptor-negative and HER2 3+) in her right breast and was initially treated with mastectomy and axillary nodal dissection followed by chemotherapy (CEF; cyclophosphamide, doxorubicine, and 5-fluorouracil followed by docetaxel) and radiotherapy (50 Gy). Two years later, the patient had episodes of vertigo and headaches. MRI and CSF analysis indicated brain metastasis and meningeal carcinomatosis without any metastatic lesions other than these metastatic sites. An Ommaya reservoir for intrathecal treatment with methotrexate and cytarabine was placed surgically, and the patient was treated with intrathecal chemotherapy and whole-brain radiotherapy (40Gy). Meningeal enhancement and brain tumor on MRI and tumor cell counts in CSF still remained after the maximal treatment cycle. As the next choice of treatment, intrathecal therapy with weekly trastuzumab (25 mg/body) was begun after approval of IRB. After 6 injections of trastuzumab, malignant cells in CSF disappeared and interestingly the brain tumor shrank. The patient still continues intrathecal trastuzumab without any clinical toxic effects. Conclusions: Considering the few options for treatment of meningeal dissemination in MBC, this approach might be a viable method of treatment for meningeal dissemination of HER2-positive MBC patients through appropriate clinical trials. No significant financial relationships to disclose.
Duration of anticoagulation after isolated pulmonary embolism
Authors: Gualtiero Palareti, Benilde Cosmi, Emilia Antonucci, Cristina Legnani, Nicoletta Erba, Angelo Ghirarduzzi, Daniela Poli, Sophie Testa, Alberto Tosetto, Vittorio Pengo, Paolo Prandoni
Journal: European Respiratory Journal (2016)

In the D-dimer and ULtrasonography in Combination Italian Study (DULCIS), serial D-dimer measurement in combination with assessment of residual thrombosis (in patients with deep vein thrombosis (DVT)) identified patients who safely discontinued anticoagulation after an unprovoked venous thromboembolism (VTE). In this subgroup analysis, the value of D-dimer tests was assessed in patients with isolated pulmonary embolism (PE) compared with those with DVT, with or without PE (DVT/PE). The DULCIS database was reanalysed in relation to this target. 26.8% of the DULCIS patients had isolated PE as the index event; this was more prevalent in females (34.1%) than in males (21.1%; p&lt;0.0001). The rate of positive D-dimer was similar in isolated PE and DVT/PE. The rate of recurrences was not different in isolated PE or DVT/PE patients (4.8% ppy versus 3.8% ppy; nonsignificant) who stopped anticoagulation for negative D-dimer, but it was markedly high (11.2% ppy; p&lt;0.0001) in those with isolated PE who remained without anticoagulation despite positive D-dimer. Recurrences were more frequently new isolated PE in patients with isolated PE than with DVT/PE (six (46.2%) out of 13 versus two (7.4%) out of 27; p=0.0085). Serial D-dimer assessment can inform on the risk of recurrent VTE and help determine the duration of anticoagulation in patients with isolated PE.
Weekly administration of 5-fluorouracil (5-FU), folinic acid (FA), oxaliplatin (L-OHP) and irinotecan (CPT-11) [FUFOXIRI] for patients with metastatic gastric or colorectal cancer
Authors: A. Harba, S. Peinert, W. Grothe, K. Jordan, T. Kegel, L. P. Mueller, R. Behrens, A. Grothey, D. Arnold, H.-J. Schmoll
Journal: Journal of Clinical Oncology (2005)

3719 Background: Combination schedules with 5-FU, FA, L-OHP and CPT-11 have shown high efficacy in patients (pts) with metastatic colorectal cancer (CRC). However, significant toxicities jeopardize therapeutic success. As a result of a preceding phase I study, we evaluated the FUFOXIRI regimen with weekly infusional 5-FU/FA, OHP and CPT-11 to define a regimen with improved tolerability and high efficacy. Methods: FUFOXIRI was administered with weekly CPT-11 [80 mg/m2; 1h] followed by a 2h-infusion of OHP (50mg/m2) and FA (500 mg/m2)/2000 mg 5-FU [24h]. All agents were given on days 1, 8, 15, 22; q d 36. Results: 24 pts with metastatic colorectal (n=14) or gastric (n=10) cancer were enrolled: 14/10 m/f, median age 54 yrs [26–64], median Karnofsky PS 90% [70–100]. 5 pts (3 colorectal /2 gastric) had prior chemotherapy. Median duration of treatment was 3 cycles [1–7]. 21 pts. were evaluable for toxicity: No grade 4 toxicity occurred. Main grade 3 toxicities were diarrhea (23%), nausea/vomiting (14%), leukopenia (14%) and neuropathy (9.5%). In 53 % of pts with >1cycle dose-reductions were required, mainly on day 15 and 22. Efficacy analysis of 19 pts. showed PR in 47% of all pts and 58% of CRC pts. Another 53% of all pts and 42% of CRC pts achieved SD. No disease progression was observed. Median PFS was 8 [1–26] mos for all and 8.5 [1–26] mos for CRC pts, respectively. Median OS was 13 [1–54] mos for all and 15.5 [1–54] mos for CRC pts. Conclusions: FUFOXIRI is an effective regimen for pts with both gastric and colorectal cancer. The favorable toxicity profile is remarkable but was achieved by dose modifications in the majority of pts. Therefore, a further refinement of the administration schedule (d 1 and 8 q d 22) has been initiated in a subsequent trial. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche, sanofi-aventis sanofi-aventis sanofi-aventis
Efficacy and safety of denileukin diftitox (Dd) in a phase III, double-blind, placebo-controlled study of CD25+ patients with cutaneous T-cell lymphoma (CTCL)
Authors: A. Negro-Vilar, Z. Dziewanowska, E. S. Groves, V. Stevens, J. K. Zhang, M. Prince, A. Martin, W. Sterry
Journal: Journal of Clinical Oncology (2007)

8026 Background: ONTAK®(Dd), a genetically engineered fusion protein combines the enzymatically active domain of diphtheria toxin with the sequence of interleukin-2 (IL-2), designed to target IL-2 receptor expressing malignancies. Dd received FDA accelerated approval for the treatment of CTCL in patients with the CD25 component of the IL-2 receptor. Methods: The confirmatory placebo- controlled L4389–11 phase III trial evaluated 9 and 18μg/kg/d Dd in 144 patients with CD25(+) CTCL. Patients (=3 prior treatments, stages Ia - III) received Dd or placebo IV for up to 8 cycles, consisting of Dd once daily for 5 days every 3 weeks. Tumor burden in skin, blood and lymph nodes and a physician's global (PGA) were assessed relative to baseline and before every treatment cycle beginning with cycle 2. Confirmation of tumor response required two more consecutive cycles (3 observations). Investigator assessments were ratified by an independent Drug Evaluation Review Committee. Results: Initial analysis of activity and benefit shown below. Both Dd treatment arms were greatly superior to placebo in a dose dependent fashion. Population demographics were the same across treatment arms (median age 59 years, 55% male). Randomization was stratified by disease status at baseline, 67% were = stage IIa, 33% were =stage IIb. Response between stage groups within each arm did not differ significantly. Many responses were confirmed after 5 or more cycles. AEs were similar to those in previous Dd studies. The only significantly different Grade 3/4 adverse event was nausea (2% in Placebo and 15% in 18μg/kg/d). No differences in serious adverse events among treatment arms were observed. The frequency of AEs and SAEs markedly decrease after the first two cycles of treatment. Conclusions: This is the largest randomized, placebo controlled trial conducted in CTCL, providing clear evidence for efficacy and clinical benefit for Dd. No significant financial relationships to disclose. [Table: see text]
FGF23 signaling impairs neutrophil recruitment and host defense during CKD
Authors: Jan Rossaint, Jessica Oehmichen, Hugo Van Aken, Stefan Reuter, Hermann J. Pavenstädt, Melanie Meersch, Mark Unruh, Alexander Zarbock
Journal: Journal of Clinical Investigation (2016)

Chronic kidney disease (CKD) has been associated with impaired host response and increased susceptibility to infections. Leukocyte recruitment during inflammation must be tightly regulated to protect the host against pathogens. FGF23 levels are increased in blood during CKD, and levels of this hormone have been associated with a variety of adverse effects in CKD patients. Here, we have shown that CKD impairs leukocyte recruitment into inflamed tissue and host defense in mice and humans. FGF23 neutralization during CKD in murine models restored leukocyte recruitment and host defense. Intravital microscopy of animals with chronic kidney failure showed that FGF23 inhibits chemokine-activated leukocyte arrest on the endothelium, and downregulation of FGF receptor 2 (FGFR2) on PMNs rescued host defense in these mice. In vitro, FGF23 inhibited PMN adhesion, arrest under flow, and transendothelial migration. Mechanistically, FGF23 binding to FGFR2 counteracted selectin- and chemokine-triggered β2 integrin activation on PMNs by activating protein kinase A (PKA) and inhibiting activation of the small GTPase Rap1. Moreover, knockdown of PKA abolished the inhibitory effect of FGF23 on integrin activation. Together, our data reveal that FGF23 acts directly on PMNs and dampens host defense by direct interference with chemokine signaling and integrin activation.
The Pooled Cohort Risk Equations—Black Risk Matters
Authors: David C. Goff, Donald M. Lloyd-Jones
Journal: JAMA Cardiology (2016)

Ervin R. Fox, MD, MPH; Tandaw E. Samdarshi, MD, MPH; Solomon K. Musani, PhD; Michael J. Pencina, PhD; Jung Hye Sung, ScD; Alain G. Bertoni, MD, MPH; Vanessa Xanthakis, PhD; Pelbreton C. Balfour Jr, MD, ScM; Satya S. Shreenivas, MD; Carolyn Covington, PhD, RN; Philip R. Liebson, MD; Daniel F. Sarpong, PhD; Kenneth R. Butler, PhD; Thomas H. Mosley, PhD; Wayne D. Rosamond, PhD; Aaron R. Folsom, MD; David M. Herrington, MD; Ramachandran S. Vasan, MD, MPH; Herman A. Taylor, MD, MPH
Abstract 182: Prehospital Intravenous Epinephrine May Boost Survival of Patients with Traumatic Cardiopulmonary Arrest
Authors: Shi-Yi Chen, Yen-Pin Chen, Wen-Chu Chiang, Patrick Chow-In Ko, Hui-Chih Wang, Chih-Wei Yang, Edward Pei-Chuan Huang, Kah-Meng Chong, Sot Shih-Hung Liu, Wei-Ting Chen, Jiun-Wei Chen, Yi-Chia Lee, Ming-Ju Hsieh, Matthew Huei-Ming Ma
Journal: Circulation (2014)

Background: Prehospital resuscitation for patients with major trauma emphasized load-and-go principle. However, for those with traumatic cardiopulmonary arrest (TCPA), the role of prehospital intravenous epinephrine (PIE) remained unclear. This study aimed to evaluate the effectiveness of PIE in patients with TCPA. Method: We analyzed data from an Utstein registry for out-of-hospital cardiac arrest in Taipei to test the association between PIE and outcomes of TCPAs. Enrollees were adult patients (≧18 year-old) with TCPA. Patients with signs of obvious death like decapitation or rigor mortis, or with existing do-not-resuscitation order were excluded. Primary outcome was survival to admission, and secondary outcome was survival to discharge. A subgroup analysis was performed by stratified total prehospital time. Result: From Jun 1, 2010 to May 31, 2013 there were total 514 cases enrolled. PIE was administrated in 43 (8.4%) cases. Patients who received PIE were more likely with witnessed collapse, initial shockable rhythm, placement of advanced airway, longer total prehospital time and less blunt injury. Patient number with survival to admission and survival to discharge was 101 (19.6%) and 20 (3.9%), respectively. In parsimonious models, the adjusted odds ratios (AOR) of PIE was 2.57 (95% confidence interval (CI) 1.24-5.31) on primary outcome (Figure 1), and 3.53 (95%CI 0.84-15.47) on secondary outcome. Subgroup analysis showed increased ORs of PIE in cases with longer prehospital time (Figure 2). Conclusion: Among patients with TCPA, PIE was associated with increased survival to admission in an Asian metropolitan area, especially for those with longer prehospital time.
Single-agent activity of GCS-100, a first-in-class galectin-3 antagonist, in elderly patients with relapsed chronic lymphocytic leukemia
Authors: F. Cotter, D. A. Smith, T. E. Boyd, D. A. Richards, C. Alemany, D. Loesch, G. Salogub, G. F. Tidmarsh, G. M. Gammon, J. Gribben
Journal: Journal of Clinical Oncology (2009)

7006 Background: GCS-100 is a polysaccharide antagonist of galectin-3, a protein whose overexpression on certain tumor cells is associated with poor prognosis in cancer patients. GCS-100 has been shown to induce apoptosis of patient CLL cells ex vivo. In addition, GCS-100 potentiates the in vitro activity of other agents commonly used to treat CLL, including rituximab. This phase II clinical trial evaluated the potential of GCS-100 as a novel single-agent therapeutic for relapsed CLL. Methods: Patients with Rai Stage II or higher CLL who had relapsed after one or two prior therapies were eligible. Prior therapies included a range of chemotherapy combinations including FCR, cyclophosphamide/vincristine/rituximab, and chlorambucil/prednisone. Patients received GCS-100 i.v. at 160 mg/m 2 for 5 days every 21 days until disease progression. Peripheral blood was collected on study days 1, 4, and 8 of each cycle to assess peripheral leukocyte counts and apoptosis. CD38 and Zap70 expression were assessed where possible. Results: 24 pts were enrolled;16 men and 8 women (median age 67 years, range 40–86 years, 15/24 pts were over 65 years). GCS-100 was well-tolerated. There were no cases of drug-related grade 3 or 4 hematological toxicity or other serious AE. Two patients discontinued treatment due to rash, which resolved with cessation of treatment and which has been shown to be responsive to steroids. Six (25%) patients experienced PR, including 4 patients with &gt;50% shrinkage of lymph node lesions. Currently 6 patients remain on study with a median duration of 5 months (range 4.5–9 months). In addition, apoptosis of peripheral leukocytes was confirmed by caspase activation and by DNA fragmentation. Conclusions: GCS-100 has significant single-agent activity in relapsed CLL. Its lack of myelosuppression and potential synergy with other agents makes GCS-100 a strong candidate for further development in CLL, particularly for elderly patients for whom there is a major need for less toxic agents. [Table: see text]