tbuckley/cabot-search huggingface dataset:
Long term outcomes of patients with anaplastic oligodendroglioma treated in a tertiary care centre in India.
Authors: Subhash Gupta, Haresh Kunhiparambath, Rony Benson, Supriya Mallick, Ajeet K Gandhi, Dayanand Sharma, Pramod Kumar Julka, Goura Kishor Rath
Journal: Journal of Clinical Oncology (2016)

e13517 Background: Optimal management for anaplastic oligodendroglioma (ODG) is evolving through adjuvant radiation (RT) to adjuvant chemoradiation. We analyzed demography, treatment and survival outcome data of 56 patients of ODG registered in our institute from 2000 to 2013. Methods: All patients (Pts) underwent maximal safe surgical resection followed by adjuvant RT 60 Gy in 30 fractions. After 2004, pts underwent chemoradiation with daily Temozolomide TMZ) (75 mg/m2) and maintenance TMZ (150-200 mg/m2 D1-D5) for a total of six cycles. An event was described as death for overall survival, progression/ recurrence of disease, or neuro-deterioration for progression free survival. Log-rank test was used to compare event-free survival (EFS) distribution. Results: Median age at diagnosis was 38 years (range-19-77). 39 patients were male and 17 patients were female with a male: female ratio of 2.3:1. Headache was the commonest symptom seen in 56.4% patients followed by seizures (53.8%) and motor deficit (12.8%).Median duration of symptoms was 8.5 months. Frontal location was most common in 66% of the patients followed by temporal and parietal location (12.5% each). 46(82.1%) patients had pure anaplastic ODG histology while 10(17.9%) patients had mixed anaplastic oligodendroglial tumor. 29(51.8%) patients underwent a gross total excision while others underwent a subtotal resection or a biopsy only. All patients except one underwent adjuvant RT with a median dose of 60 Gy (range 40-60 Gy). 38(67.9%) patients had recieved concurrent chemotherapy and 31(55.4%) patients also recieved adjuvant chemotherapy. The median number of adjuvant cycles was 6. The estimated 5 year overall survival was 83.5%.The median progression free survival (PFS) was 5.2 years and the 5 year PFS was 55.1%. Age, sex, extend of surgery, use of chemotherapy, tumor location were not found to be significant factors affecting PFS on univariate analysis. Conclusions: The use of adjuvant RT and chemotherapy in patients with anaplastic ODG is associated with a good 5 year OS of 83.5% and a 5 year PFS of 55.1%. Age, gender, extend of surgery, use of chemotherapy, tumor location were not significantly correlated with PFS.
A cellular platform to enable targeted brain delivery of T cells to glioblastoma.
Authors: Heba Samaha, Antonella Pignata, Kristen Fousek, Tiara Byrd, Fong Lam, Fabio Stossi, Sean Marelli, Thomas Shum, Sujith Joseph, Meenakshi Hegde, Nabil M. Ahmed
Journal: Journal of Clinical Oncology (2017)

2053 Background: Poor T cell homing hinders the development of effective cell therapy for central nervous system (CNS) malignancies. Lessons learnt from inflammatory brain diseases can give insight into how to overcome the blood brain barrier (BBB) blockade created by cancer. Activated Leukocyte Cell Adhesion Molecule (ALCAM; CD166) is a pathological adhesion molecule upregulated in the endothelium of a number of inflammatory/infiltrative CNS diseases, such as multiple sclerosis. Antibodies blocking ALCAM decrease leukocyte access to the brain and are currently being tested in a clinical trial for MS. Methods: We studied the difference in the dynamic signature of adhesion molecules in the “anergic” brain tumor endothelium and that of infiltrative brain conditions. Consequently, we mapped the ALCAM minimal binding region to domain 3 (D3) of CD6 and created an artificial molecule with the intent of creating a novel cellular platform to reverse endothelial anergy, through ALCAM specific binding. Results: GBM endothelium fails to launch the second wave of adhesion molecules necessary for firm T leukocyte capture and effective BBB transmigration. Engineered D3 on the T cell crosslinked to ALCAM on endothelial cells in proximity ligation assays (PLA; &lt; 40nm) during TEM. Under shear stress, D3 T cells showed a global improved ALCAM specific trafficking kinetics: higher capture on ALCAM+ endothelium, rolling with slower velocity, and better TEM. In an ex vivo model of BBB, D3 T cells exhibited higher transmigratory ability. We discovered that signaling through the D3 endodomain phosphorylated pZAp70 recruiting Talin that enables LFA-1 (ICAM-ligand) open confirmation, mediating effective TEM. Lastly, in an orthotopic model of GBM, D3 T cells homed more and accumulated at the tumor site compared to NT controls. And, testing Her2 CAR T cells on D3 platform showed an advantageous homing after IV administration which was reflected in tumor control and better survival. Conclusions: We created a cellular platform that enables targeted brain delivery of T cells. This platform serves as a gateway to the effective cellular therapeutics for brain malignancies but potentially as a delivery system for complex biologics for other pathological conditions.
Incidence and Predictors of Opioid Prescription at Discharge After Traumatic Injury
Authors: Muhammad Ali Chaudhary, Andrew J. Schoenfeld, Alyssa F. Harlow, Anju Ranjit, Rebecca Scully, Ritam Chowdhury, Meesha Sharma, Stephanie Nitzschke, Tracey Koehlmoos, Adil H. Haider
Journal: JAMA Surgery (2017)

In the current health care environment with increased scrutiny and growing concern regarding opioid use and abuse, there has been a push toward greater regulation over prescriptions of opioids. Trauma patients represent a population that may be affected by this regulation, as the incidence of pain at hospital discharge is greater than 95%, and opioids are considered the first line of treatment for pain management. However, the use of opioid prescriptions in trauma patients at hospital discharge has not been explored.To study the incidence and predictors of opioid prescription in trauma patients at discharge in a large national cohort.Analysis of adult (18-64 years), opioid-naive trauma patients who were beneficiaries of Military Health Insurance (military personnel and their dependents) treated at both military health care facilities and civilian trauma centers and hospitals between January 1, 2006, and December 31, 2013, was conducted. Patients with burns, foreign body injury, toxic effects, or late complications of trauma were excluded. Prior diagnosis of trauma within 1 year and in-hospital death were also grounds for exclusion. Injury mechanism and severity, comorbid conditions, mental health disorders, and demographic factors were considered covariates. The Drug Enforcement Administration's list of scheduled narcotics was used to query opioid use. Unadjusted and adjusted logistic regression models were used to determine the predictors of opioid prescription. Data analysis was performed from June 7 to August 21, 2016.Injury mechanism and severity, comorbid conditions, mental health disorders, and demographic factors.Prescription of opioid analgesics at discharge.Among the 33 762 patients included in the study (26 997 [80.0%] men; mean [SD] age, 32.9 [13.3] years), 18 338 (54.3%) received an opioid prescription at discharge. In risk-adjusted models, older age (45-64 vs 18-24 years: odds ratio [OR], 1.28; 95% CI, 1.13-1.44), marriage (OR, 1.26; 95% CI, 1.20-1.34), and higher Injury Severity Score (≥9 vs <9: OR, 1.40; 95% CI, 1.32-1.48) were associated with a higher likelihood of opioid prescription at discharge. Male sex (OR, 0.76; 95% CI, 0.69-0.83) and anxiety (OR, 0.82; 95% CI, 0.73-0.93) were associated with a decreased likelihood of opioid prescription at discharge.The incidence of opioid prescription at discharge (54.3%) closely matches the incidence of moderate to severe pain in trauma patients, indicating appropriate prescribing practices. We advocate that injury severity and level of pain-not arbitrary regulations-should inform the decision to prescribe opioids.
Screening with low-dose computed tomography (LDCT) of asbestos-exposed subjects and lung cancer (LC) mortality.
Authors: Gianpiero Fasola, Francesco Grossi, Ornella Belvedere, Alessandro Follador, Tina Zanin, Paolo Cassetti, Stefano Meduri, Monica Cattaneo, Marco Giavarra, Giacomo Pelizzari, Manuela Giangreco, Federica Edith Pisa, Valentina Rosolen, Fabiano Barbiero, Fabio Barbone
Journal: Journal of Clinical Oncology (2016)

1554 Background: Our prospective non-randomized ATOM002 study showed that LDCT screening of asbestos-exposed subjects can identify LC at an earlier, potentially more curable, stage than chest radiographs (CXR) (Fasola et al, The Oncologist 2007). The ATOM002 cohort was selected from subjects enrolled in a surveillance program with annual CXR for asbestos exposed workers at the Monfalcone Occupational Health Unit, in the Friuli Venezia Giulia (FVG) region, Italy. Here, we report a cohort mortality study of asbestos exposed subjects from that surveillance program, comparing outcomes in the ATOM002 participants (P) and contemporary nonparticipants (NP). Methods: Within a cohort of 2,433 asbestos-exposed subjects, we compared mortality between the ATOM study P (who had additional baseline and 1 year LDCT) and NP (n = 926 and 1,507, respectively). The follow-up period spanned the years 2002-2011. We performed Cox models to assess survival for all causes, all cancers, LC and malignant pleural mesothelioma. Final models estimating mortality hazard ratios (HR) were adjusted for smoking habits, age, level of asbestos exposure and Charlson-Quan comorbidity index. For external comparison, we estimated the standardized mortality rate ratio (SMR) using FVG regional standard rates. Results: There was a significant 59.3% (95%CI: 3.9-82.8) reduction in adjusted mortality for LC among ATOM002 P vs. NP. LC crude mortality was 99.4 per 100,000 person-year in P (8 LC deaths) compared to 430.4 per 100,000 person-year in NP (50 LC deaths). Mortality was also reduced for all causes (HR = 0.61; 95%CI 0.44-0.84), but not for all cancers (HR = 0.97; 95%CI 0.62-1.50) or malignant pleural mesothelioma (HR = 0.86; 95%CI 0.31-2.41). Compared with regional mortality rates, a trend towards reduced mortality for LC was found among ATOM study P (SMR = 0.55; 95%CI 0.24-1.09), in contrast to a statistically significant increase in the NP (SMR = 2.07; 95%CI 1.53-2.73). Conclusions: Participation in the LDCT screening was associated with reduced LC mortality compared to CXR-based surveillance. To our knowledge, this is the first report suggesting reduction in mortality from LC with LDCT screening in an asbestos-exposed population.
Association of clinical phenotype and treatment history with survival in adult brainstem glioblastoma.
Authors: Jooyeon Nam, Rebecca A. Harrison, Shiao-Pei S. Weathers, Clement Pillainayagam, John Frederick De Groot, Carlos Kamiya-Matsuoka, Monica Elena Loghin, Marta Penas-Prado, W. K. Alfred Yung, Jing Li, Sherise D. Ferguson, Barbara Jane O'Brien
Journal: Journal of Clinical Oncology (2017)

e13539 Background: Brainstem gliomas are rare, comprising 1-2% of malignant primary brain tumors. Brainstem glioblastoma (bGBM) often poses a therapeutic challenge due to scarcity of evidence guiding treatment, and the high rate of neurologic morbidity. We examined bGBM cases at MD Anderson Cancer Center (MDACC) to characterize the salient clinical features of bGBM, and the impact of therapy on patient survival. Methods: Adult patients with pathologically-confirmed bGBM (N = 34) treated at MDACC between June 2005 and June 2015 were identified from the neurosurgical database. Patients’ clinical, radiographic, and treatment data were extracted from the medical record. Descriptive statistics and Kaplan-Meier analyses were performed. Results: Mean age was 52.5 years (SD = 12.1) and median KPS was 80 (SD = 14.2) at time of diagnosis. Initial surgical intervention included biopsy (82.4%) and resection (17.6%). Most patients were treated with concurrent chemoradiation (N = 18, 52.9%) or sequential radiation followed by chemotherapy (N = 8, 23.5%), and the remainder had no documented post-operative anti-tumor therapy. At the time of this analysis, 82.4% of the cohort had died. Median progression free survival (PFS) was 5.8 months (SD = 6.7) and overall survival (OS) was 8.9 months (SD = 19.6). On univariate analysis, gait abnormality (p = .02), incoordination (p = .002), dysphagia (p = .04), or facial numbness (p = .01) at presentation was associated with shorter OS. KPS of ≥70 at diagnosis was significantly associated with better OS (15.6 vs 3 months, p = .001), and the patients with good functional status were more likely to receive concurrent chemoradiation. Bevacizumab was given as concurrent or adjuvant treatment in 2 and 3 cases, respectively, and did not affect OS (p = .82). Conclusions: This retrospective analysis demonstrates a significant and complex relationship between presenting clinical features, functional status and variable treatments in bGBM and survival outcomes. This evidence contributes to our understanding of bGBM, and highlights areas for further study in this malignant condition.
Contemporary prevalence, in-hospital outcomes, and prognostic determinants of triple valve surgery: National database review involving 5,234 patients
Authors: Lucas B. Ohmes, Luke Kim, Dmitriy N. Feldman, Christopher Lau, Monica Munjal, Antonino Di Franco, Fawad Hameedi, Ivancarmine Gambardella, Leonard N. Girardi, Mario Gaudino
Journal: International Journal of Surgery (2017)
Genome wide association study for anthracycline-induced congestive heart failure.
Authors: Laura Gardner, Fei Shen, Milan Radovich, Lang Li, Kathy Miller, Guanglong Jiang, Dongbing Lai, Anne M. O'Neill, Joseph A. Sparano, Nancy E. Davidson, David A. Cameron, Irmina Gradus-Pizlo, Ronald Mastouri, Thomas M. Suter, Tatiana Foroud, George W. Sledge, Bryan P. Schneider
Journal: Journal of Clinical Oncology (2016)

1017 Background: Anthracycline-induced congestive heart failure (CHF) is a rare but serious toxicity associated with this commonly employed anti-cancer therapy. The ability to predict which patients might be at increased risk prior to exposure would be valuable to optimally counsel risk to benefit ratio for each patient. Herein we present a genome wide approach for biomarker discovery with two validation cohorts to predict CHF from adult patients planning to receive an anthracycline. Methods: We performed a genome wide association study (GWAS) in 3431 patients from the randomized phase III adjuvant breast cancer trial E5103 to identify SNP genotypes associated with an increased risk of anthracycline-induced CHF. We further attempted candidate validation in two independent phase III adjuvant trials, E1199 and BEATRICE. Results: When evaluating for cardiologist adjudicated CHF, 11 SNPs had a p-value <10-5 of which 9 independent chromosomal regions were associated with increased risk. Validation of the 2 top SNPs in E1199 revealed one SNP, rs28714259 that demonstrated a borderline increased CHF risk (p=0.04, OR=1.9). rs28714259 was subsequently tested in BEATRICE and was significantly associated with a decreased left ventricular ejection fraction (p=0.018, OR=4.2). Combining results from these independent studies provided further evidence of a significant association between rs28714259 and cardiac damage (p=7.4 x10-9). Conclusions: rs28714259 represents a validated SNP that is associated with anthracycline-induced CHF in three independent, phase III adjuvant breast cancer clinical trials.
A phase 1 trial of TRC102 (methoxyamine HCl) with temozolomide (TMZ) in patients with solid tumors and lymphomas.
Authors: Robert S. Meehan, Alice P. Chen, Geraldine Helen O'Sullivan Coyne, Jerry M. Collins, Shivaani Kummar, Larry Anderson, Kazusa Ishii, Jennifer Zlott, Larry Rubinstein, Yvonne Horneffer, Lamin Juwara, Woondong Jeong, Naoko Takebe, Robert J. Kinders, Ralph E. Parchment, James H. Doroshow
Journal: Journal of Clinical Oncology (2016)

2556 Background: The base excision repair (BER) pathway has been shown to promote resistance to both alkylating agents and antimetabolite chemotherapy. TRC102 inhibits BER by binding to chemotherapy-induced abasic sites; it potentiates the activity of alkylating agents including TMZ in murine models. In human xenograft studies, TRC102 efficiently enhanced the antitumor effect of TMZ regardless of cell line genetic characteristics, including O6-methylguanine DNA-methyltransferase (MGMT), mismatch repair (MMR), or p53 status. Methods: We conducted a phase 1 trial of TRC102 in combination with TMZ to determine the safety, tolerability, and maximum tolerated dose (MTD) of the combination in patients (pts) with refractory solid tumors. Eligibility criteria included adults with histologically-confirmed malignancies that had progressed on standard therapy, ECOG PS of 0-2, and adequate organ function. We followed a standard 3+3 design. Oral TRC102 and TMZ were administered daily, days 1-5, in 28-day cycles. We also evaluated the pharmacokinetic profile of TRC102 with TMZ. Antitumor responses were determined using RECIST criteria. Results: The escalation phase accrued between August 2013 and August 2015. MTD was reached at DL7 (TRC102 150mg PO D1-5, TMZ 150mg/m2 PO D1-5). The DLT at DL8 was hematologic. A total of 37 pts were enrolled, of whom 4 had a partial response (PR) (NSCLC, ovarian(2), and colon); one further PR occurred in a pt with colon cancer but was unconfirmed due to concurrent illness; 11 pts had stable disease (SD), 16 progressive disease (PD), and 5 were not evaluable. Three of the PR pts remain on study (20, 7, 5 months). Grade 3/4 adverse events included neutropenia (11%), anemia (8%), thrombocytopenia (5%), hemolysis (3%) or hypophosphatemia (3%). The half-life of TMZ was 2 hours, which was similar to reported monotherapy values; TRC102 half-life was 24 hours and its plasma concentrations increased with dose. Conclusions: The observation of 4 PRs and 11 SDs demonstrates that this combination is active and the side effect profile is manageable. The expansion phase of the trial is in progress. MGMT status, γH2Ax, caspase 3, and Ki67 will be evaluated in tumor biopsies from the ongoing expansion cohort. Clinical trial information: NCT01851369.
Evaluation of faecal incontinence scores
Authors: S Brophy, J Deasy, DA McNamara
Journal: Endoscopy (2006)

Aims: Clinical severity is the main determinant of treatment outcome in faecal incontinence, however embarrassment may prevent accurate assessment of symptomatology. We compared patient-administered and physician-administered faecal incontinence questionnaires to estimate the effect of mode of administration on results.
An in vitro study on the efficacy of removing calcium hydroxide from curved root canal systems in root canal therapy
Authors: Ying Wang, Li-Yang Guo, Hong-Zhi Fang, Wen-Ling Zou, Ying-Ming Yang, Yuan Gao, Hui Yang, Tao Hu
Journal: International Journal of Oral Science (2017)

To compare the efficacy of various irrigants (citric acid, ethylenediaminetetraacetic acid (EDTA) and NaOCl) and techniques in removing Ca(OH)2 in two types of curved root canal systems, simulated root canals with specific curvatures were used to investigate the effects of different irrigants and instruments on Ca(OH)2 removal. The optimal methods were verified on extracted human teeth. Simulated root canals were assigned to one of two groups based on the irrigation solution: 10% citric acid or 2.5% NaOCl. Each group was divided into four subgroups according to the technique used to remove Ca(OH)2. The percentage of Ca(OH)2 removal in different sections of root canals was calculated. On the basis of the results obtained for the simulated canals, 10% citric acid and 17% EDTA were applied to remove Ca(OH)2 from the extracted human teeth with curved root canal systems. The teeth were scanned by micro computed tomography to calculate the percentage of Ca(OH)2 removal in the canals. In simulated root canals, we found that 10% citric acid removed more Ca(OH)2 than 2.5% NaOCl in the 0–1 mm group from the apex level (P<0.05). Ultrasonic and EndoActivator activation significantly removed more Ca(OH)2 than a size 30 K file in the apical third (P<0.05). However, there were no significant differences in any sections of the canals for 10% citric acid or 17% EDTA in removing Ca(OH)2 in extracted human teeth. We concluded that it was effective to remove residual Ca(OH)2 using the decalcifying solution with EndoActivator or Passive Ultrasonic Irrigation in a curved root canal system. A protocol for Ca(OH)2 removal was provided based on the conclusions of this study and the methods recommended in previous studies. Using citric acid in combination with ultrasonic rinsing helps flush out root canals prior to completing treatment. Calcium hydroxide, Ca(OH)2, is used to eliminate microbes from root canals during treatment. However, residual Ca(OH)2 left behind once treatment is complete can reduce the effectiveness of sealants and weaken dentin bonds. Hui Yang and Tao Hu at Sichuan University in Chengdu, China, and co- trialled novel ways of removing Ca(OH)2 from curved root canal systems. Using synthetic root canal models and extracted human teeth, the team used different rinsing chemicals and techniques to clean root canals of different shapes. They found that citric acid was most effective, particularly when combined with ultrasonic rinsing. This technique agitated and loosened residues left in the root canal wall, allowing for a cleaner finish.
Concurrent smoking effects the reduced incidence of colorectal cancer associated with hormone replacement therapy
Authors: D Debnath, RK Choudhary, KA Gunning
Journal: Endoscopy (2006)

Aims: Although intake of hormone replacement therapy (HRT) is beneficially associated with reduced incidence of colorectal cancer (CRC), little is known about the effect of concomitant smoking on such beneficial effect of HRT. We aimed to assess the association between concurrent smoking and HRT intake, and the incidence of CRC.
Prevalence of triple negative breast cancer in India – systematic review and meta analysis.
Authors: Gurprataap Sandhu, Sebhat Erqou, Heidi Patterson, Aju Mathew
Journal: Journal of Clinical Oncology (2016)

e12561 Background: The prevalence of triple negative breast cancer (TNBC) is reported to be higher in India than observed in western population. There is substantial variation in prevalence rates between studies. We performed a systematic review and literature-based meta-analysis of studies to estimate the prevalence of TNBC in India. Methods: A systematic search of Medline, Scopus, EMBASE and Web of science data bases for studies published between Jan 1, 1999 and December 31, 2015 was conducted. Studies were eligible for inclusion if it provided data on patients with breast cancer in India, and described the prevalence of triple negative tumor subtype in the study population. Combinations of MESH and free text words - triple negative; breast cancer; India were used to search databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for article search and reporting. We pooled study specific estimates using random-effects meta-analysis. Results: Data was obtained from 17 studies. 7,237 patients with breast cancer were included in the analysis. Overall pooled prevalence of TNBC was 31% (95% CI: 27-35%). There was high degree of heterogeneity with an I2 of 91.2% (95% CI: 88%-94%, p < 0.001). The mean age of the patients was 49.7 years, 41.2% of the study population were premenopausal, 24% had tumor size > 5 cm, and 57% had positive axillary lymph nodes. There was no regional variation in the summary estimate of prevalence of TNBC. The definition of HER2 positivity and ER positivity was variable across studies. However, it did not account for the heterogeneity (p > 0.05 by meta-regression). Meta-regression did not identify significant differences in prevalence estimates based on age of study population, proportion of women with premenopausal status, grade 3 disease or tumor size. There was no evidence of publication bias (Begg’s test; p = 0.239). Conclusions: Prevalence of TNBC in India is 31% (95% CI: 27-35%), and is considerably higher compared to that seen in western population.