tbuckley/cabot-search huggingface dataset:
Mortality and Prehospital Blood Pressure in Patients With Major Traumatic Brain Injury
Authors: Daniel W. Spaite, Chengcheng Hu, Bentley J. Bobrow, Vatsal Chikani, Duane Sherrill, Bruce Barnhart, Joshua B. Gaither, Kurt R. Denninghoff, Chad Viscusi, Terry Mullins, P. David Adelson
Journal: JAMA Surgery (2016)

<h3>Importance</h3> Current prehospital traumatic brain injury guidelines use a systolic blood pressure threshold of less than 90 mm Hg for treating hypotension for individuals 10 years and older based on studies showing higher mortality when blood pressure drops below this level. However, the guidelines also acknowledge the weakness of the supporting evidence. <h3>Objective</h3> To evaluate whether any statistically supportable threshold between systolic pressure and mortality emerges from the data a priori, without assuming that a cut point exists. <h3>Design, Setting, and Participants</h3> Observational evaluation of a large prehospital database established as a part of the Excellence in Prehospital Injury Care Traumatic Brain Injury Study. Patients from the preimplementation cohort (January 2007 to March 2014) 10 years and older with moderate or severe traumatic brain injury (Barell Matrix Type 1 classification,<i>International Classification of Diseases, Ninth Revision</i>head region severity score of 3 or greater, and/or Abbreviated Injury Scale head-region severity score of 3 or greater) and a prehospital systolic pressure between 40 and 119 mm Hg were included. The generalized additive model and logistic regression were used to determine the association between systolic pressure and probability of death, adjusting for significant/important confounders. <h3>Main Outcomes and Measures</h3> The main outcome measure was in-hospital mortality. <h3>Results</h3> Among the 3844 included patients, 2565 (66.7%) were male, and the median (range) age was 35 (10-99) years. The model revealed a monotonically decreasing association between systolic pressure and adjusted probability of death across the entire range (ie, from 40 to 119 mm Hg). Each 10-point increase of systolic pressure was associated with a decrease in the adjusted odds of death of 18.8% (adjusted odds ratio, 0.812; 95% CI, 0.748-0.883). Thus, the adjusted odds of mortality increased as much for a drop from 110 to 100 mm Hg as for a drop from 90 to 80 mm Hg, and so on throughout the range. <h3>Conclusions and Relevance</h3> We found a linear association between lowest prehospital systolic blood pressure and severity-adjusted probability of mortality across an exceptionally wide range. There is no identifiable threshold or inflection point between 40 and 119 mm Hg. Thus, in patients with traumatic brain injury, the concept that 90 mm Hg represents a unique or important physiological cut point may be wrong. Furthermore, clinically meaningful hypotension may not be as low as current guidelines suggest. Randomized trials evaluating treatment levels significantly above 90 mm Hg are needed.
Peg-Filgrastim after High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation for Hematological Malignancies: A Matched-Pair Analysis.
Authors: Simona Sica, Nicola Piccirillo, Silvia De Matteis, Luca Laurenti, Patrizia Chiusolo, Serena De Vita, Federica Sorà, Rossana Putzulu, Giovanni Reddiconto, Giuliana Farina, Giuseppe d’Onofrio, Giuseppe Leone
Journal: Blood (2004)
Measurement of gamma-H2AX in circulating tumor cells (CTC) from patients receiving ABT-888 (veliparib) in combination with carboplatin on a phase I dose-escalation study (OSU-10080/NCI8609).
Authors: A. Garcia-Villa
Journal: Journal of Clinical Oncology (2011)

58 Background: Non-invasive methods to accurately measure DNA damage induced by PARP inhibitors in the tumors are crucial in identifying the optimal biological dose and schedule of these novel agents. With the use of an antibody that targets the histone H2AX, which becomes phosphorylated on serine residue 139 (γ-H2AX), it is possible to measure DNA DSB in the cell. But repeated biopsy in patients with metastatic breast cancer is not feasible. We propose here to quantify γ-H2AX in CTCs as a measurement of DNA damage in the tumor in patients receiving veliparib (ABT-888), an oral PARP inhibitor and carboplatin on a phase I study. Methods: CTCs were isolated in 10 mL of peripheral blood using negative selection with immunomagnetic tagging and removal of CD45 positive cells at 3 time points. Immunocytochemical staining for nucleus (DAPI), pan-cytokeratin CD45, and γ-H2AX was completed on available samples. Double staining for nucleus and cytokeratin with high nucleus to cytoplasm ratio defined a CTC. The γ-H2AX foci present in the nucleus of the CTCs will be counted by immunocytochemistry (ICC) analysis. Results: We negatively enriched blood sample from enrolled patients with metastatic breast cancer (n=6). CTCs were observed in all samples (55CTCs/mL of blood - 2000CTCs/mL of blood). Thus far 3 out of 6 patient samples have been analyzed. The number of CTCs per mL of blood after enrichment at baseline has a mean of 293, a median of 140 and a range of (684-140) At time point 1 the mean is 1071.33, the median is 1151 and the range is (1151-63). ICC analysis on the CTCs demonstrated the presence of γ-H2AX positive cells. Conclusions: Our novel negative depletion method for isolating CTCs allows for separation of a wider range of CTCs, since it does not assume presence of epithelial markers before separation. This leads to improved yield and purity allowing better ICC detection of various markers directly on CTCs. Development and validation of the above methodology to determine γ-H2AX foci in CTCs will help in identifying a novel, non-invasive biomarker that can be used to assess the effect of DNA damaging agents during therapy.
Metastatic angiosarcomas (mAS): Identification of treatments that significantly improve the outcome.
Authors: E. Amela, A. Italiano, I. L. Ray-Coquard, L. Chaigneau, C. Delcambre, B. Bui Nguyen, F. Bertucci, N. Isambert, D. Cupissol, E. Bompas, J. Bay, F. Duffaud, C. Guillemet, N. Corradini, P. A. Cassier, C. Chevreau, J. Blay, N. Penel
Journal: Journal of Clinical Oncology (2011)

10085 Background: AS represent about 1% of all soft tissue sarcomas. Few literature data are available and the impact role of the different treatments is debated. Methods: We have conducted a retrospective analysis of 149 pts treated in 14 GSF/GETO centers between August 1996 and December 2009. Prognostic factors (PF) have been identified using Log-rank test and Cox model. After adjustment to independent PF, we have estimated the impact of treatments using Cox Model. Results: The study population consisted of 82 (55%) women and 67 (45%) men, the median age was 60 (range, 8-92). The main primaries were soft tissue (35 pts, 23%), breast (29 pts, 19%), skin/scalp (26 pts, 7%), liver (11 pts, 7%) and heart (9 pts, 6%). 7 patients presented underlying genetic disorders. Thirty one (21%) AS arose in irradiated fields. Performance status was 0 or 1 in 75 cases (63%). 58 AS (62%) were grade 3 tumours. 86 pts (62%) presented synchronous metastasis. The main metastatic sites were lung (70, 48%), bone (38, 26%) and liver (46, 31%). The treatment consisted of weekly paclitaxel (47, 31%), doxorubicin-based regimen (69, 47%), other chemotherapy regimens (13, 8%) and surgery of metastatasis (8, 5%). 13 pts (8%) were treated with exclusive palliative care. The median follow-up and overall survival (OS) were 9 and 11 months. Under univariate analysis, the potential PF: presence of bone metastasis (p=0.0107), presence of other metastasis (p=0.0327), performance status ≥2 (p<0.0001), low level of hemoglobin (p=0.006), low level of albumin (p=0.006) and increasing in LDH level (p<0.0001). The Cox model analysis retained only one independent PF: PS ≥2 (Hazard Ratio=2.49, p<0.0001). After adjustment to PS and compared to pts treated with exclusive palliative care, the following treatments were associated with better OS: doxorubicin-containing regimens (HR=0.38, p=0.0165), weekly-paclitaxel (HR=0.36, p=0.0146) and metastasectomy (HR=0.09, p=0.0221). Conclusions: Doxorubicin-based regimens, weekly paclitaxel and metastasectomy are associated with better outcome in pts with mAS. We plan to extend this database for identifying the patients benefiting from these different treatments.
Circulating Platelet-Leukocyte Aggregates as a Marker of Microvascular Lesions in Diabetic Patients.
Authors: Ismail Elalamy, Tahar Chakroun, Francoise Robert, Chantal Lecrubier, Fabienne Elgrably, Meyer M. Samama, Grigoris T. Gerotziafas, Mohamed T. Hatmi
Journal: Blood (2005)
An Unusual Cause of Intestinal Perforation
Authors: Luise I. M. Pernar, Anne Mongiu, Eric G. Sheu
Journal: JAMA Surgery (2016)

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A phase II trial of gemcitabine (G), carboplatin (C), and sorafenib (S) in patients (pts) with transitional cell carcinoma (TCC): Preliminary safety and outcome.
Authors: J. M. Mehnert, A. Mortazavi, M. N. Stein, A. C. Donadio, D. Zelterman, J. A. McDonough, E. Rowen, C. J. Hoimes, G. Gibney, W. K. Kelly
Journal: Journal of Clinical Oncology (2011)

278 Background: Sorafenib is an oral tyrosine kinase inhibitor with anti-angiogenic properties that may enhance the antitumor activity of GC and when administered as maintenance therapy after GC may delay disease recurrence. This study investigated the safety and clinical outcome of adding S to GC for pts with advanced TCC and the role of S maintenance after GC. Methods: Metastatic/unresectable chemotherapy naive TCC pts ECOG PS 0-1 received G 1,000 mg/m 2 d1, 8 and C AUC = 5 d1 with S 400 mg bid d2-19 q21 d for 6 cycles. Pts with stable disease or PR/CR continued on 400 mg bid of S. The primary endpoint was proportion of pts free of progression at 5 months with secondary endpoint of proportion of pts with PR/CR. A Simon two-stage design would enroll 30 pts; if 8 of the initial 17 followed for 5 months or more post treatment showed disease progression, the trial would terminate. Results: 17 pts enrolled, 14 male, 3 female; median age 64 (47-86); ECOG 0 (7)/1 (10). The median number of cycles of GC + S given was 4.4 with multiple dose reductions in 71%. 7 pts (47%) experienced grade (gr) 3/4 neutropenia and 4 (24%) gr 3/4 anemia during GC + S; no neutropenic fever was seen. Gr 3/4 thrombocytopenia occurred in 59% with 2 events of hematuria, 1 epistaxis, and 1 bleeding colitis. Gr 3 nonhematologic toxicities: hypophosphotemia (29%), diarrhea (6%), fatigue (24%), anorexia (6%), dehydration (6%), hand foot syndrome (6%), rash (12%), hypertension (6%). Responses: 1 CR (6%), 4 PR (24 %), 8 SD (47%); 3 pts with evaluable disease showed tumor shrinkage, including 1 with resolution of bone metastases. 9 (53 %) were progression free at 5 months; 7 (41%) came off trial due to &gt; 3 dose reductions (1 prior to first restaging) and 1 withdrew consent. 7 (41%) that achieved CR, PR or SD after a minimum of 4 cycles GC + S received maintenance S for a median of 8 cycles. Conclusions: GC + S showed clinical activity in advanced TCC similar to GC alone but prolonged progression-free intervals were observed in patients treated with S maintenance. GC + S was associated with increased hematologic toxicity although S maintenance was well tolerated. Further studies exploring the role of S maintenance after chemotherapy are warranted. [Table: see text]
A meta-analysis comparing positive surgical margin and complication rates of 110,016 patients undergoing open retropubic, laparoscopic, and robotic-assisted radical prostatectomy.
Authors: P. Sooriakumaran, D. Bloch, A. Hebert, U. Seshadri-Kreaden, P. Wiklund, A. Tewari
Journal: Journal of Clinical Oncology (2011)

103 Background: There is no clear evidence to support one form of surgical approach over another with regards radical prostatectomy. The aim of this study was to analyze the literature available between 2002 and 2008 and compare positive surgical margin and complication rates for open retropubic, laparoscopic, and robotic radical prostatectomy. Methods: A total of 110,016 patients formed the basis of this meta-analysis, representing the largest compilation of radical prostatectomy patients in the literature. Summary data were abstracted on year of publication, pre-operative patient characteristics, positive surgical margins, estimated blood loss, blood transfusions, conversions, length of hospital stay, and total intra- and peri-operative complications, with a further 21 individual perioperative complications selected a priori for abstraction and analysis. Results: The open and laparoscopic surgical groups had similar overall positive surgical margin rates, with the robotic group having lower rates. Both minimally invasive approaches showed significantly lower estimated blood loss and rate of blood transfusions, and a shorter length of hospital stay when compared to an open approach. A further decrease in these parameters was seen when robotic assistance was used. Total complication rates were highest for the open approach, intermediate for the laparoscopic cohort, and lowest for the robotic group. For the individual complication analysis, the rates for death, readmission, reoperation, ureteral, bladder, and rectal injury, ileus, pneumonia, fistula, and wound infection showed significant differences between groups. Conclusions: Robotic assisted laparoscopic radical prostatectomy has overall lower perioperative morbidity and improved early oncologic outcomes compared to conventional laparoscopic or open approaches. Further studies comparing longer term oncologic and functional outcomes, as well as cost-benefit comparisons are needed before making recommendations for or against a specific type of surgery. [Table: see text]
The combination of capecitabine and vinorelbine as a first-line or a second-line treatment in inoperable breast cancer patients.
Authors: T. Nakagawa, M. Saito, F. Kasumi
Journal: Journal of Clinical Oncology (2011)

e11536 Background: Clinical response of advanced or metastatic cancer can be improved by combination chemotherapy. Recently, the combination of capecitabine (C) and vinorelbine (V) has been expected as a first or a second-line in inoperable breast cancer. Methods: We reviewed the following studies: 1) A prospective observational trial (C: 500 mg/m2 bid, d1-14, V : 60mg/m2 IV, d 1+8; q3w, S. Gampenrieder et al. 2010). 2) An international, open-label, phase II trial (C: 1,000mg/m2 bid, d 1-14, V: 80mg/m2 p.o., days 1+8; q3w; N. Tubiana-Mathieu et al. 2009. 3) An open-label, phase II trial (C: 1,000mg/m2 bid, d1-14, V: 20mg /m2 IV, d 1+8; q3w, n=39; G. Orphanos et al. 2009). 4) An open-label, international, multicenter, phase II trial (C: 1,000mg/m2 bid d 1-14, V: 60mg/m2 p.o., d 1, 8, 15; q3w; A. Jones et al. 2009). Results: In these studies, overall response rate (ORR) were around 20% and 53.9%. Clinical benefit rate/disease control rate (CBR: CR+PR+SD≥6mo/DCR: CR+PR+SD) were around 62.5% and 83.3% (Table). Multiple comparison of Study1-4 showed significant differences in ORR. Regimen in 2 and 3 indicated better response rate than in 4. However, no significant differences were seen in CBR/DCR. Comparing a first-line group and a second-line group, chi-square test showed no significant differences in ORR and CBR/DCR. In Jones et al, they demonstrated that patients classified failure to anthracycline-taxane treatment have an ORR of 40%, with a DCR of 60%. Treatment-related adverse events were generally well tolerated in all these studies. Conclusions: These data suggested that the combination of C+V was effective and safe as both a first-line and a second-line in inoperable breast cancer. We expect this therapy would establish as a second-line treatment effective against anthracycline-taxane resistant breast cancer. Study 1) Gampenrieder et al n=30 2) Tubiana-Mathieu et al n=49 3) Orphanos et al n=39 4) Jones et al n=40 Intervention C: 500mg/m2 V: 60mg/m2 IV C: 1,000mg/m2 V: 80mg/m2 p.o. C: 1,000mg/m2 V: 20mg/m2 IV C: 1,000mg/m2 V: 60mg/m2 p.o. Treatment line First-line n=24 Second-line n=6 First-line Second-line Second-line ORR % 33.3 50 51.0 53.9 20 CBR/DCR % 66.7 (CBR) 83.3 (CBR) 63.3 (CBR) 66.7 (DCR) 62.5 (DCR)
Effect of a therapeutic sphingosine 1-phosphate antibody on intratumoral hypoxia and standard chemotherapy in a preclinical model of prostate cancer.
Authors: Olivier Cuvillier, Isabelle Ader, Pierre Bouquerel, Roger Allen Sabbadini, Bernard Malavaud
Journal: Journal of Clinical Oncology (2012)

223 Background: Hypoxia promotes vascularization, metastasis and resistance to treatments. The activation of HIF-1α is identified as the master mechanism of adaptation to hypoxia. We recently identified the sphingosine kinase 1/sphingosine 1- phosphate (SphK1/S1P) pathway as a new modulator of HIF-1α activity under hypoxia in multiple cancer cell models (Ader et al, Cancer Res, 2008). S1P elicits proliferation, survival, or angiogenesis, and is believed to exert most of its actions as a ligand for a family of specific GPCRs to elicit paracrine or autocrine signaling. We have suggested that inhibiting SphK1/S1P signaling, which is upregulated under hypoxia, may normalize the microenvironment and increase sensitivity to chemotherapy, in the broader concept of «normalization of tumor vessels» as tumor oxygenation is known to enhance response to chemotherapy (Ader et al., Cancer Res, 2009). Methods: Quantitation of hypoxia and angiogenesis, and treatment efficacy using an orthotopic (o.t) xenograft model of fluorescent HRPC cells. Results: We provide in vitro evidence that inhibiting the S1P exogenous signaling, through pharmacological inhibition of its receptors or by taking advantage of a monoclonal antibody neutralizing S1P, blocks HIF-1α accumulation and its activity in prostate cancer cells under hypoxia. Second, using an o.t model of prostate cancer, we show that an anti-S1P antibody inhibits intratumoral hypoxia, modifies vessel architecture and improves tumor perfusion within 5 days of treatment. Third, we demonstrate that an anti-S1P strategy sensitizes to docetaxel, the ’gold standard’ treatment for HRPC. A 5-day anti-S1P antibody pretreatment markedly sensitizes to docetaxel in an o.t. PC-3/GFP model established in nude mice. The combination anti-S1P antibody together with docetaxel was not only accompanied by a smaller primary tumor volume compared to docetaxel alone, but also significantly reduced the occurrence and number of metastases. Conclusions: These data establish the proof-of-concept that blocking the exogenous action of S1P reduces intratumoral hypoxia and sensitizes to chemotherapy in prostate cancer animal model.
Characterization of Post Natal Human Lymphoid Progenitors.
Authors: Emmanuelle Six, Delphine Bonhomme, Kheira Beldjord, Monika Jurkowska, Liliane Dal Cortivo, Marta Monteiro, Alexandrine Garrigue, Alain Fischer, Marina Cavazzana-Calvo, Isabelle Andre-Schmutz
Journal: Blood (2006)
Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial
Authors: Osamu Natsume, Shigenori Kabashima, Junko Nakazato, Kiwako Yamamoto-Hanada, Masami Narita, Mai Kondo, Mayako Saito, Ai Kishino, Tetsuya Takimoto, Eisuke Inoue, Julian Tang, Hiroshi Kido, Gary W K Wong, Kenji Matsumoto, Hirohisa Saito, Yukihiro Ohya
Journal: The Lancet (2016)
Incidence of benign pathologic lesions at nephrectomy for renal masses presumed to be stage I renal cell carcinoma in Japanese patients: Impact of sex, age, and tumor size.
Authors: Y. Fujii, K. Saito, Y. Iimura, Y. Yasuda, F. Koga, H. Masuda, J. Yonese, Y. Ishikawa, I. Fukui, K. Kihara
Journal: Journal of Clinical Oncology (2011)

374 Background: The widespread use of modern imaging techniques has resulted in the increased detection of small, asymptomatic renal tumors. Some recent studies from Western countries have reported that the incidence of benign lesions is approximately 15% in patients undergoing definitive surgery for renal masses presumed to be clinical stage I renal cell carcinoma (RCC). The high level of noncancerous lesions is, to some extent, due to the fact that no imaging feature can accurately distinguish either oncocytoma or lipid-poor angiomyolipma (AML) from RCC. This study attempts to determine the incidence of benign pathologic findings for such renal masses in Asian patients. Methods: Between 1991 and 2009, 711 consecutive patients (218 women and 493 men) underwent partial (n=206) or radical (n=505) nephrectomy for renal masses presumed to be stage T1N0M0 (T1a/T1b= 503/208) sporadic RCC on preoperative imaging in two Japanese centers. The mean size of the lesions was 3.3 cm (range 0.3-7.0). The pathologic features were reviewed by an experienced pathologist. Results: Of the 711 masses, 53 (7.5%) revealed benign pathologic findings. Twenty-two (3.1%) were AMLs, 13 (1.8%) were oncocytomas, 8 (1.1%) were complicated cysts, and 10 were others. Twenty-eight (12.8%) of the 218 females and 25 (5.1%) of the 493 males had benign lesions (p=0.0005). Of the 357 patients aged 60 years or younger, 37 (10.4%) had benign lesions while only 16 (4.5%) of the 354 patients over 60 years did (p=0.024). Forty six (9.2%) of the 503 T1a and 7 (3.4%) of the 203 T1b masses were benign (p=0.0071). A multivariate logistic regression model showed that sex, age and tumor size were all independently predictive of benign histology, particularly of AML. Conclusions: The present incidence (7.5%) of benign lesions in presumed clinical stage T1N0M0 RCC masses at nephrectomy was lower than the incidence of approximately 15% previously reported from Western countries, probably because of the low incidence of oncocytomas in Japanese patients. Female gender, young age and small tumor size are all independently predictive of benign lesions, particularly of AML in Japanese patients. No significant financial relationships to disclose.
Hepcidin Protects Against Extracellular Infections By Eliminating Non-Transferrin-Bound Iron
Authors: Deborah Stefanova, Joao Arezes, Kathryn Michels, Barbara Dillon, Marcus Horwitz, Borna Mehrad, Yonca Bulut, Tomas Ganz, Elizabeta Nemeth
Journal: Blood (2016)