tbuckley/cabot-search huggingface dataset:
10-y Risks of Death and Emergency Re-admission in Adolescents Hospitalised with Violent, Drug- or Alcohol-Related, or Self-Inflicted Injury: A Population-Based Cohort Study
Authors: Annie Herbert, Ruth Gilbert, Arturo González-Izquierdo, Alexandra Pitman, Leah Li
Journal: PLoS Medicine (2015)

Background Hospitalisation for adversity-related injury (violent, drug/alcohol-related, or self-inflicted injury) has been described as a "teachable moment", when intervention may reduce risks of further harm. Which adolescents are likely to benefit most from intervention strongly depends on their long-term risks of harm. We compared 10-y risks of mortality and re-admission after adversity-related injury with risks after accident-related injury. Methods and Findings We analysed National Health Service admissions data for England (1 April 1997–31 March 2012) for 10–19 y olds with emergency admissions for adversity-related injury (violent, drug/alcohol-related, or self-inflicted injury; n = 333,009) or for accident-related injury (n = 649,818). We used Kaplan–Meier estimates and Cox regression to estimate and compare 10-y post-discharge risks of death and emergency re-admission. Among adolescents discharged after adversity-related injury, one in 137 girls and one in 64 boys died within 10 y, and 54.2% of girls and 40.5% of boys had an emergency re-admission, with rates being highest for 18–19 y olds. Risks of death were higher than in adolescents discharged after accident-related injury (girls: age-adjusted hazard ratio 1.61, 95% CI 1.43–1.82; boys: 2.13, 95% CI 1.98–2.29), as were risks of re-admission (girls: 1.76, 95% CI 1.74–1.79; boys: 1.41, 95% CI 1.39–1.43). Risks of death and re-admission were increased after all combinations of violent, drug/alcohol-related, and self-inflicted injury, but particularly after any drug/alcohol-related or self-inflicted injury (i.e., with/without violent injury), for which age-adjusted hazard ratios for death in boys ranged from 1.67 to 5.35, compared with 1.25 following violent injury alone (girls: 1.09 to 3.25, compared with 1.27). The main limitation of the study was under-recording of adversity-related injuries and misclassification of these cases as accident-related injuries. This misclassification would attenuate the relative risks of death and re-admission for adversity-related compared with accident-related injury. Conclusions Adolescents discharged after an admission for violent, drug/alcohol-related, or self-inflicted injury have increased risks of subsequent harm up to a decade later. Introduction of preventive strategies for reducing subsequent harm after admission should be considered for all types of adversity-related injury, particularly for older adolescents.
ADAMTS13 Endopeptidase Protects against Vascular Endothelial Growth Factor Inhibitor–Induced Thrombotic Microangiopathy
Authors: Luise Erpenbeck, Melanie Demers, Zsuzsanna K. Zsengellér, Maureen Gallant, Stephen M. Cifuni, Isaac E. Stillman, S. Ananth Karumanchi, Denisa D. Wagner
Journal: Journal of the American Society of Nephrology (2015)

Thrombotic microangiopathy (TMA) is a life-threatening condition that affects some, but not all, recipients of vascular endothelial growth factor (VEGF) inhibitors given as part of chemotherapy. TMA is also a complication of preeclampsia, a disease characterized by excess production of the VEGF-scavenging soluble VEGF receptor 1 (soluble fms-like tyrosine kinase 1; sFlt-1). Risk factors for VEGF inhibitor-related TMA remain unknown. We hypothesized that deficiency of the VWF-cleaving ADAMTS13 endopeptidase contributes to the development of VEGF inhibitor-related TMA. ADAMTS13(-/-) mice overexpressing sFlt-1 presented all hallmarks of TMA, including thrombocytopenia, schistocytosis, anemia, and VWF-positive microthrombi in multiple organs. Similar to VEGF inhibitor-related TMA in humans, these mice exhibited severely impaired kidney function and hypertension. In contrast, wild-type mice overexpressing sFlt-1 developed modest hypertension but no other features of TMA. Recombinant ADAMTS13 therapy ameliorated all symptoms of TMA in ADAMTS13(-/-) mice overexpressing sFlt-1 and normalized BP in wild-type mice. ADAMTS13 activity may thus be a critical determinant for the development of TMA secondary to VEGF inhibition. Administration of recombinant ADAMTS13 may serve as a therapeutic approach to treat or prevent thrombotic complications of VEGF inhibition.
O035 : CCR9 and CCL25 are early pro-inflammatory mediators in acute liver injury
Authors: R. Parker, C. Weston, L.A. Possamai, G.S. Petts, E. Triantafyllou, C. Bersmeier, W. Khamri, J. Wendon, C.G. Antoniades, D.H. Adams
Journal: Journal of Hepatology (2015)
Lymph node retrieval in a randomized trial on western-type versus Japanese-type surgery in gastric cancer.
Authors: A M Bunt, J Hermans, C J van de Velde, M Sasako, F A Hoefsloot, G Fleuren, J A Bruijn
Journal: Journal of Clinical Oncology (1996)

PURPOSE In the tumor-node-metastasis (TNM) staging system, no recommendations are provided on what lymph node retrieval technique is to be used to determine lymph node status, which leads to variability in nodal status assessment and TNM staging. PATIENT AND METHODS Lymph node retrieval was quantitated using data from 237 curatively resected gastric cancer patients, from a prospective, randomized trial that compared the Western resection with limited (D1) and the Japanese resection with extended lymphadenectomy (D2), and compared data from the literature. Moreover, the efficacy of different lymph node retrieval techniques was determined. RESULTS The mean yield of lymph nodes was 15 in D1 and 30 in D2, which is similar to results from German investigators, but substantially lower than results from Japanese investigators (60 in D2). Use of a fat-clearance technique significantly increased (P = .01) nodal yields compared with conventional retrieval. Significantly higher yields (P &lt; .001) were obtained by a Japanese surgeon using conventional retrieval directly postoperatively. Experience of surgicopathologic teams with processing resection specimens did not influence nodal yields. Further analysis showed that reference values for nodal yields per anatomically defined station as reported in the literature were contradicted by our results and indicated the ambiguity of such standards. CONCLUSION Despite some anatomical variability in the distribution of lymph nodes, advice on the number of nodes to examine per N level, feasible in all patients, should be incorporated into the TNM classification to standardize nodal status assessment. Based on our findings, we advocate retrieval of nodes immediately postoperatively by the surgeon.
Sequential chemotherapy with gemcitabine plus carboplatin, followed by additional docetaxel for aged patients with advanced upper-tract urothelial cancer.
Authors: Takahiro Yoneyama, Yuki Tobisawa, Tohru Yoneyama, Hayato Yamamoto, Atsushi Imai, Kazuyuki Mori, Shingo Hatakeyama, Yasuhiro Hashimoto, Takuya Koie, Chikara Ohyama
Journal: Journal of Clinical Oncology (2015)

344 Background: Gemcitabine + cisplatin may be a promising regimen for advanced upper-tract urothelial carcinoma (UTUC) as well as for advanced bladder cancer. However, cisplatin is proved to be too toxic for the patients with impaired renal function and aged patients. Majority of aged patients with UTUC have impaired renal function. There is no standard regimen for such patients. We assessed the effectiveness and adverse events (AEs) of a sequential chemotherapy with Gemcitabine plus carboplatin(GCarbo) followed by GCcarbo plus docetaxel (GCarboD) for advanced UTUC. Methods: We treated 86 patients with advanced UTUC at our clinic between August 2004 and December 2013. 45 patients (31 men and 14 women) with the age of 65 years or older were enrolled. Mean age was 73.0 (65–89), and mean Ccr was 47.9 (11.6–99.2) ml/minute. Mean observation period was 22.9 (3–87.2) months. The therapeutic regimen consisted of 2 lines: GCarbo therapy as the first line, with two courses as a set; GCarboD therapy as the second line if the response in the first line was insufficient. If this regimen was effective, another 2 courses of GCarbo was performed. If this regimen did not induce any tumor size reduction, we switched to GCarboD. Results: GCarbo regimen yielded 1 cases (2.2%) of CR, 20 (44.4%) of PR, and the mean duration of response of 11.0(3–51) months. GCarboD treatment was administered in 12cases, and yielded one (8.3%) PR and a duration of response was 7.0 months. The median survival period was 14.0 months with GCcarbo/GCarboD regimens. As for ARs with GCcarbo regimen, there were 23 (52.2%) of G3/4 blood toxicity. In GCarboD regimen, there were 11 (91.7%) of blood toxicity and 7 (58.3%) of gastrointestinal AEs. Conclusions: Although the present study is small and preliminary, the present sequential chemotherapy is safe and active for advanced UTUC of the patients sixty-five years or older. GCarbo regimen achieved relatively high response rate (46.6%) in advanced UTUC. The median overall survival of 14.0 months is acceptable when average age of 73.0 year for the subjects is took into consideration. However, GCarboD had limited effectiveness for non-responder of GCarbo.
Next-Generation Sequencing to Guide Clinical Trials
Authors: Lillian L. Siu, Barbara A. Conley, Scott Boerner, Patricia M. LoRusso
Journal: Clinical Cancer Research (2015)

Abstract Rapidly accruing knowledge of the mutational landscape of malignant neoplasms, the increasing facility of massively parallel genomic sequencing, and the availability of drugs targeting many “driver” molecular abnormalities have spurred the oncologic community to consider how to use these new tools to improve cancer treatment. In order to assure that assignment of patients to a particular targeted treatment is likely to be beneficial to the patient, it will be necessary to conduct appropriate clinical research. It is clear that clinical (histology and stage) eligibility criteria are not sufficient for most clinical trials using agents that target mutations that are present in only a minority of patients. Recently, several clinical trial designs have been suggested to test the benefit of targeted treatment in molecular and/or clinical subgroups of patients. However, challenges remain in the implementation of such trials, including choice of assay, levels of evidence regarding gene variants, tumor heterogeneity, identifying resistance mechanisms, the necessity of screening large numbers of patients, infrastructure needs, and collaboration of investigators and industry. This article reviews current trial designs and discusses some of the considerations, advantages, and drawbacks of designing clinical trials that depend on particular molecular variants as eligibility criteria. Clin Cancer Res; 21(20); 4536–44. ©2015 AACR. See all articles in this CCR Focus section, “Innovations to Speed Drug Development.”
Impact of annual hospital volume of high dose interleukin-2 infusions on in-patient mortality in patients with melanoma and renal cell carcinoma
Authors: Kathan Mehta, Leonard Appleman, Hong Wang, Ahmad Tarhini, Rahul Parikh
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The 2014 expert consensus on high dose interleukin-2 (HD-IL-2) states that, “Treating a minimum number of patients per year is important, as quality depends upon familiarity and repetition” [1]. The minimum annual volume of HD-IL-2 associated with relatively worse outcomes is
Early-Warning Signs of Violence: Is a Triad Enough?
Authors: Blair Justice, Rita Justice, Irvin A. Kraft
Journal: American Journal of Psychiatry (1974)

While noting that a triad of childhood symptoms—enuresis, firesetting, and cruelty to animals—has been accepted as predictive of violence in adulthood, the authors believe that other symptoms may serve as even more useful predictors. On the basis of a literature search, interviews with many persons who had had contact with troubled youth, and in-depth interviews with eight convicts who had shown behavior problems as children, ther identified four symptoms-fighting, temper tantrums, school problems and truancy, and interpersonal difficullies—as early-warning signs that may indicate serious emotional disturbance which is likely to result in violent behavior.
Detection of Deep Venous Thrombosis Using a Pocket-Size Ultrasound Examination Device
Authors: Koki Nakanishi, Shota Fukuda, Hajime Yamashita, Takuto Uetsuhara, Akiko Sakamoto, Koji Yamasaki, Michihiko Kosaka, Naoya Shirai, Hiroko Uono, Junichi Yoshikawa, Yutaka Otsuji, Kenei Shimada
Journal: JACC. Cardiovascular imaging (2015)
Effects of CPAP therapy withdrawal on exhaled breath pattern in obstructive sleep apnoea
Authors: Esther I Schwarz, Pablo Martinez-Lozano Sinues, Lukas Bregy, Thomas Gaisl, Diego Garcia Gomez, Martin T Gaugg, Yannick Suter, Nina Stebler, Yvonne Nussbaumer-Ochsner, Konrad E Bloch, John R Stradling, Renato Zenobi, Malcolm Kohler
Journal: Thorax (2015)

<h3>Background</h3> Obstructive sleep apnoea (OSA) is highly prevalent and associated with cardiovascular and metabolic changes. OSA is usually diagnosed by polysomnography which is time-consuming and provides little information on the patient9s phenotype thus limiting a personalised treatment approach. Exhaled breath contains information on metabolism which can be analysed by mass spectrometry within minutes. The objective of this study was to identify a breath profile in OSA recurrence by use of secondary-electrospray-ionization-mass spectrometry (SESI-MS). <h3>Methods</h3> Patients with OSA effectively treated with CPAP were randomised to either withdraw treatment (subtherapeutic CPAP) or continue therapeutic CPAP for 2 weeks. Exhaled breath analysis by untargeted SESI-MS was performed at baseline and 2 weeks after randomisation. The primary outcome was the change in exhaled molecular breath pattern. <h3>Results</h3> 30 patients with OSA were randomised and 26 completed the trial according to the protocol. CPAP withdrawal led to a recurrence of OSA (mean difference in change of oxygen desaturation index between groups +30.3/h; 95% CI 19.8/h,40.7/h, p&lt;0.001) which was accompanied by a significant change in 62 exhaled features (16 metabolites identified). The panel of discriminating mass-spectral features allowed differentiation between treated and untreated OSA with a sensitivity of 92.9% and a specificity of 84.6%. <h3>Conclusion</h3> Exhaled breath analysis by SESI-MS allows rapid and accurate detection of OSA recurrence. The technique has the potential to characterise an individual9s metabolic response to OSA and thus makes a comprehensible phenotyping of OSA possible. <h3>Trial registration number</h3> NCT02050425 (registered at ClinicalTrials.gov).
Epstein-Barr Virus Genome Studies in Burkitt's and Non-Burkitt's Lymphomas in Uganda 2
Authors: Charles L. M. Olweny, Isaac Atine, Albert Kaddu-Mukasa, Raphael Owor, Maria Andersson-Anvret, George Klein, W. Henle, G. de-Thé
Journal: JNCI Journal of the National Cancer Institute (1977)

Burkitt's lymphoma (BL) has been widely investigated and has attracted attention because of the possible etiologic role of the Epstein-Barr virus (EBV). To further determine the role of EBV in the causation of this tumor, we measured EBV-specific nuclear antigen (EBNA) and EBV DNA using immunofluorescence and nucleic acid hybridization techniques, respectively. Of 34 BL biopsies, 27 tissues (79%) were EBNA-positive, whereas none of the 25 non-BL biopsy tissues were EBNA-positive. Of 15 BL tumors tested, 14 (93%) were EBV DNA-positive with a mean of 39 (range, 8–86) EBV genome equivalents per cell. Each of the 15 non-BL biopsy specimens subjected to nucleic acid hybridization had less than two virus genome equivalents per cell, although all had serologic evidence of past EBV infection. The findings further supported the possible etiologic role of EBV in African BL and negated the passenger hypothesis. The EBV genome could, therefore, be used as a separating marker between African BL and non-BL lymphomas.
ZOOM: A prospective, randomized trial of zoledronic acid (ZOL; q 4 wk vs q 12 wk) for long-term treatment in patients with bone-metastatic breast cancer (BC) after 1 yr of standard ZOL treatment.
Authors: Dino Amadori, Massimo Aglietta, Barbara Alessi, Lorenzo Gianni, Toni Ibrahim, Gabriella Farina, Fernando Gaion, Francesco Bertoldo, Daniele Santini, Roberta Rondena, Paola Bogani, Carla Ripamonti
Journal: Journal of Clinical Oncology (2012)

9005 Background: ZOL (4 mg q 4 wk) is an established therapy for reducing the risk of debilitating skeletal-related events (SREs) in patients (pts) with bone metastases (mets) from BC. As BC treatments continue to improve pt survival, long-term SRE-reduction is increasingly important, and evaluation of modified ZOL dosing to retain efficacy with reduced adverse events (AEs) is warranted. Methods: ZOOM, a phase III prospective, randomized, open-label, multicenter study, assessed the safety and efficacy of quarterly (4 mg q 12 wk; Arm 1) vs monthly (4 mg q 4 wk; Arm 2) ZOL for ~1 yr in pts with BC who have ≥ 1 bone met, and have received ~1 yr of prior ZOL treatment (9 to 12 doses over ≤ 15 months; last dose ≤ 3 months prior). The primary endpoint was skeletal morbidity rate (SMR; number of SREs/pt/yr). Sample size to detect non-inferiority with 80% power (1-sided a = 0.025) was 420 pts. Secondary endpoints included time to first SRE, bone pain, bone marker (N-telopeptide of type I collagen; NTX) levels, and safety. Results: 425 pts were enrolled (209 in Arm 1; 216 in Arm 2); arms were well balanced for pt and disease characteristics, and anticancer therapies. SMR was similar between arms: 0.26 (95% confidence interval [CI] = 0.15, 0.37) in Arm 1 vs 0.22 (95% CI = 0.14, 0.29) in Arm 2; between-arms difference = 0.04 (upper limit of 1-tailed 97.5% CI = 0.17). Despite the proximity of 0.17 to the adjusted non-inferiority margin (0.19), the non-inferiority of Arm 1 vs 2 remains statistically significant. Safety analyses showed that ZOL was well tolerated. Renal AEs were reported in similar proportions of pts in both arms; 7 cases of osteonecrosis of the jaw were reported (1.65% overall; 4 cases in Arm 1 vs 3 in Arm 2). Conclusions: ZOOM is the first randomized trial to compare ZOL q 12 wk vs ZOL q 4 wk in BC pts after 1 yr of standard ZOL therapy. SMR was similar between arms. Limitations in study design suggest the need to confirm non-inferiority of ZOL q 12 wk in other ongoing phase III trials.
Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia: Time to Move Toward a Minimal Residual Disease–Based Definition of Complete Remission?
Authors: Daisuke Araki, Brent L. Wood, Megan Othus, Jerald P. Radich, Anna B. Halpern, Yi Zhou, Marco Mielcarek, Elihu H. Estey, Frederick R. Appelbaum, Roland B. Walter
Journal: Journal of Clinical Oncology (2015)

Purpose Patients with acute myeloid leukemia (AML) who are in morphologic complete remission are typically considered separately from patients with active disease (ie, ≥ 5% marrow blasts by morphology) in treatment algorithms for allogeneic hematopoietic cell transplantation (HCT), which implies distinct outcomes for these two groups. It is well recognized that the presence of minimal residual disease (MRD) at the time of transplantation is associated with adverse post-HCT outcome for those patients in morphologic remission. This effect of pre-HCT MRD prompted us to compare outcomes in consecutive patients in MRD-positive remission with patients with active AML who underwent myeloablative allogeneic HCT at our institution. Patients and Methods We retrospectively studied 359 consecutive adults with AML who underwent myeloablative allogeneic HCT from a peripheral blood or bone marrow donor between 2006 and 2014. Pre-HCT disease staging included 10-color multiparametric flow cytometry on bone marrow aspirates in all patients. Any level of residual disease was considered to be MRD positive. Results Three-year relapse estimates were 67% in 76 patients in MRD-positive morphologic remission and 65% in 48 patients with active AML compared with 22% in 235 patients in MRD-negative remission. Three-year overall survival estimates were 26%, 23%, and 73% in these three groups, respectively. After multivariable adjustment, MRD-negative remission status remained statistically significantly associated with longer overall and progression-free survival as well as lower risk of relapse compared with MRD-positive morphologic remission status or having active disease, with similar outcomes between the latter two groups. Conclusion The similarities in outcomes between patients in MRD-positive morphologic remission and those with active disease at the time of HCT support the use of treatment algorithms that use MRD- rather than morphology-based disease assessments.
Survivorship in Non–Small Cell Lung Cancer: Challenges Faced and Steps Forward
Authors: Namrata Vijayvergia, Prashant C Shah, Crystal S Denlinger
Journal: Journal of the National Comprehensive Cancer Network (2015)

Improvements in curative therapies and the advent of screening have led to increased numbers of non–small cell lung cancer (NSCLC) survivors. Most survivors have undergone invasive treatment (surgery, radiation therapy, and/or chemotherapy) and carry a higher comorbidity burden than survivors of other cancers. Overall quality of life (QOL) and health-related quality of life (HRQOL) suffer during the treatment phase, with the potential for long-term decline, and both clinical characteristics and treatment impact these measures. Physical and mental components of HRQOL seem to be most at risk for decline. The issues faced by survivors include physical symptoms such as respiratory issues, fatigue, hearing loss, neuropathy, and postsurgical pain; psychological distress leading to depression, financial issues, and poor compliance with recommended guidelines; and fear or risk of recurrence and secondary malignancies. This article summarizes the major issues faced by NSCLC survivors and suggests appropriate management. Future collaborative efforts are needed to further elucidate the complex issues that affect overall QOL and HRQOL in NSCLC survivors and to develop appropriate interventions in this large and diverse survivor population.