tbuckley/cabot-search huggingface dataset:
Association of Bacteremic Sepsis With Long-term Neurocognitive Dysfunction in Pediatric Patients With Acute Lymphoblastic Leukemia
Authors: Yin Ting Cheung, Aaron Eskind, Hiroto Inaba, Melissa M. Hudson, Ching-Hon Pui, Kevin R. Krull, Joshua Wolf
Journal: JAMA Pediatrics (2018)

Results | Coding yes and maybe responses as probable minority SOGI identities, approximately 0.86% (raw, n = 43; weighted, n = 70 952) of children self-identified as gay or bisexual.Nearly a quarter of children (raw, n = 23.8%;weighted, n = 23.7%)indicated that they did not understand the sexual orientation question.By contrast, 6.7% of parents (raw, n = 332; weighted, n = 554 674) indicated their child might be gay.For gender identity, 0.4% (raw, n = 23; weighted, n = 33 575) of children self-identified as transgender; 40.2% did not understand the question (raw, n = 1729; weighted, n = 3 298 558).A total of 1.2% (raw, n = 51; weighted, n = 98 732) of parents indicated that their child might identify as transgender.The 2-step gender identification method identified 0.15% of youth (raw, n = 8; weighted, n = 12 501) whose current gender identity differs from their birth sex.Most children reported that their minority sexual orientation and/or gender identity was not a source of problems with family or school.Parents reported slightly more variance, with 7.0% reporting some problems related to sexual orientation (raw, n = 21; weighted, n = 39 083), and 15.3% reporting some problems with gender identity (raw, n = 7; weighted, n = 15 089).Neither children nor parents reported a lot of problems related to SOGI.Discussion | The ABCD Study data indicate that less than 1% of US youth report minority sexual orientation or gender identities at age 9 to 10 years; youth and parent reports of SOGI information were generally discordant.4][5] The study does not yet include other dimensions of SOGI (eg, same-gender attraction; gender expression) or other sexual orientation identities that youth may report (eg, pansexual) 6 ; future inclusion or availability of such assessments may enhance identification of sexual and gender minority youth.Identifying as a sexual minority typically occurs in midadolescence 4,5 ; thus, more youth in the ABCD Study cohort will likely identify as sexual minorities as the cohort ages.Contrary to prior research on minority stress, 5 parents and youth indicated that minority sexual orientation and gender identity were not sources of substantial familial and school stress.However, this study did not examine SOGI indicators in association with health indicators.Future researchers should analyze the rich data available in the ABCD Study to understand how minority SOGI development is associated with health and resilience across adolescence.
Association of diabetes with colorectal cancer treatment and outcomes.
Authors: Arjun Iyengar, Heather Taffet Gold, Joseph Nicholson, Daniel Jacob Becker
Journal: Journal of Clinical Oncology (2017)

e18112 Background: Diabetes mellitus (DM) is associated with an increased incidence of colorectal cancer, but the impact of diabetes on colorectal cancer (CRC) prognosis and treatment patterns remains unknown. As outcomes in both CRC and DM have improved, appropriate co-management of the two diseases has become a priority to help patients live longer and healthier. Methods: A systematic search of PubMed, Embase, and CINAHL databases was performed to evaluate/assess the association of diabetes with colon cancer treatment patterns and outcomes, including recurrence rates (RR), disease free survival (DFS), colon cancer-specific (CSM) and all-cause mortality (ACM). We included English language peer-reviewed studies through November 2016 following the preferred reporting items of systematic reviews and meta-analyses (PRISMA) method. We applied STROBE quality criteria and conducted a random-effects meta-analysis. An inconsistency index (I2) was used to estimate the heterogeneity between studies. Results: After reviewing 2,611 reports, 35 studies were included that described an association of DM with CRC treatment patterns or outcomes. A meta-analysis of 14 studies that assessed (ACM) among 146,129 patients demonstrated an increased risk for ACM for CRC patients with DM (OR 1.28, 95% CI 1.16-1.42, I2 = 80%, P &lt; .00001). No statistical significance was found in comparing 4 studies that looked at CSM (OR 0.91, 95% CI .72-1.14, I2 = 89%, P = 0.42). Analysis of 4 studies that assessed DFS found lower DFS in patients with DM (OR 1.75, 95% CI 1.33-2.31, I = 3%, P &lt; .0001). Aggregating 3 studies that evaluated RFS demonstrated no clear association of DM and RFS(OR 1.12, CI 95% 0.91-1.38, I = 64%, P = .27). No consistent treatment discrepancies were noted in 6 studies that assessed the impact of DM on various CRC treatment modalities (receipt of surgery, chemotherapy, radiation). Conclusions: CRC patients with diabetes are at a greater risk for ACM and have worse DFS compared to those without DM. Analysis was limited due to study heterogeneity. We did not find consistent evidence that CRC is treated differently in patients with DM. Further study is warranted to clarify the mechanism of poor outcomes in CRC patients with DM and to improve survival.
Longitudinal assessment of patient-reported cumulative symptom burden as an indicator of chronic health conditions in adult survivors of childhood cancer: A joint report of the St. Jude Lifetime Cohort (SJLIFE) and the Childhood Cancer Survivor Study (CCSS).
Authors: I-Chan Huang, Matthew J. Ehrhardt, Chenghong Li, Daniel A. Mulrooney, Wassim Chemaitilly, Deokumar Srivastava, Gregory T. Armstrong, Leslie L. Robison, Melissa M. Hudson, Kevin R. Krull
Journal: Journal of Clinical Oncology (2018)

10571 Background: Adult survivors of childhood cancer experience a high cumulative burden of therapy-related chronic health conditions (CHCs). However, longitudinal evaluation of patient-reported symptoms has not been examined as an indicator of CHCs in this population. Methods: 735 long-term adult survivors of childhood cancer completed three symptom surveys through participation in both SJLIFE and CCSS across 25 years (1992-2016). Surveys included 10 symptom domains: sensory, cardiac, pulmonary, musculoskeletal, memory, pain, fatigue, nausea, anxiety and depression. Domains were classified as present vs. absent at each time point and summated with possible scores ranging from 0 to 30. Cardiac, pulmonary and endocrine CHCs were clinically determined after the last survey and graded using modified CTCAE criteria. Poisson regression identified associations of cumulative symptom burden (dichotomized as high [top quartile of the symptom burden scores] vs. low [bottom three quartiles]) with each organ system-specific CHC (grades 2-4 vs. 0-1) and severe/life-threatening CHCs (any grades 3-4 vs. 0-2), adjusting for age, sex, race and education. Results: Across the three symptom surveys, survivors' mean ages were 27, 36 and 40 years; mean years from diagnosis was 31 years at the final clinical assessment. Survivors were mostly female (51%), Caucasian (90%) and treated for leukemia (46%). Survivors with high cumulative symptom burden had a 30% increased risk of hypertension/dyslipidemia (RR 1.3, 95% CI 1.1 1.6) and endocrine dysfunction (RR 1.3, 95% CI 1.0 1.7), and a 40% increased risk of respiratory disorders (RR 1.4, 95% CI 1.2 1.8) compared to survivors with low symptom burden. High cumulative symptom burden was associated with a 50% increased risk of having severe/life-threatening CHCs (RR 1.5, 95% CI 1.2 1.9) compared to those with low symptom burden. Conclusions: Routine symptom screening may help identify adult survivors of childhood cancer who are at concurrent and/or future risk of hypertension/dyslipidemia, endocrine and respiratory disorders.
The risk of developing hepatocellular carcinoma following non-Hodgkin lymphoma.
Authors: Mahmoud Chaker, Anas M Saad, Muneer J Al-Husseini, Mohamed M Gad, Inas A. Ruhban, Asfar S. Azmi
Journal: Journal of Clinical Oncology (2018)

e16141 Background: Due to lymphoid tissue in the liver parenchyma, non-Hodgkin lymphomas (NHL) in the liver has been well studied. However, studies regarding development of second primary Hepatocellular Carcinoma (HCC) after a diagnosis of NHL are limited. We aim to evaluate the risk of HCC following NHL. Methods: Using the Surveillance Epidemiology and End Results ‘SEER’ program of the National Cancer Institute ‘NCI’, we obtained data of 114,190 patients diagnosed with NHL during 1992-2014. We defined ‘an event’ as the diagnosis of a second primary HCC after a latency period of six months following NHL diagnosis. We followed patients for the development of the event and calculated the Observed/Expected (O/E) ratio to evaluate the risk following NHL when comparing NHL patients’ population to the general US population. A p value less than .05 was considered statistically significant. Results: Patients diagnosed with NHL during 1992-2014, of which 152 patients were later diagnosed with a second primary HCC. The risk of developing HCC increased significantly after a diagnosis of NHL with an O/E of 1.24. The risk was specifically high within the first five years with 77 patients and O/E significantly increased; 1.32. However, after five years of diagnosis the risk of HCC did not increase significantly. When calculated according to sex, risk increased significantly in males with 115 patients, and O/E of 1.22. Whereas, the risk among females did not change. Most patients were between 20 and 64 years old when they were diagnosed with NHL, and the risk of developing HCC increased significantly among this age group with an O/E of 1.47. On the other hand, risk of HCC among patients older than 64 years who developed NHL did not change. Conclusions: Development of HCC following NHL is rare yet significant. In those patients with a second primary HCC after NHL, adjustments to patient management plan should be considered in order to achieve better outcomes and improve patient prognosis. Further studies are required to determine an evidence based treatment for that patient population.
Efficacy and safety of isolated limb perfusion for melanoma in elderly patients.
Authors: Max Fullah Madu, Marion M. Deken, Jos A. Van Der Hage, Katarzyna Józwiak, Michel W.J.M. Wouters, Alexander Christopher Jonathan Van Akkooi
Journal: Journal of Clinical Oncology (2017)

e21549 Background: Data on isolated limb perfusion (ILP) in elderly melanoma patients is scarce. We aimed to evaluate the efficacy and safety of ILP in our institutional cohort of melanoma patients. Methods: Retrospective analysis of AJCC stage IIIB/C melanoma patients who underwent ILP for locally advanced (unresectable) melanoma in-transit metastases of the limb between 2000 and 2016. Normothermic ILP (37-38 °C) was performed with either Melphalan or Melphalan and Tumor Necrosis Factor (TNF). Baseline characteristics, local toxicity (Wieberdink) and systemic toxicity, locoregional progression-free survival (PFS) and melanoma-specific survival (MSS) were assessed and prognostic factors for response to ILP, melanoma recurrence and survival were analyzed using univariable and multivariable analysis. Results: 88 patients were included. The overall response rate to ILP was 81%, with a complete response (CR) rate of 47%. Median overall locoregional PFS was 6 months, while patients with a CR had a median PFS of 16 months. Median overall MSS was 38 months. Two patients (2.3%) suffered Wieberdink IV toxicity (compartment syndrome), while no patients required amputation because of severe toxicity. Based on the median age of 70, we split patients into younger and elderly groups. Toxicity rates, response rates and locoregional PFS did not differ significantly between younger and elderly patients. CR was prognostic for improved locoregional PFS and MSS. Moreover, patients &gt; 70 and patients with stage IIIC disease had a higher risk of melanoma-specific death. Conclusions: ILP has good and potential durable responses, but also less frequent and less severe toxicity than recently developed targeted or immune therapies, which can be reserved for progression to stage IV. This study showed that ILP is an effective and safe procedure for elderly patients ( &gt; 70) with locally advanced melanoma of the limb.
Preclinical development of ciclopirox prodrug for the treatment of non-muscle invasive and muscle invasive bladder cancer.
Authors: Scott James Weir, Robyn Wood, Tammy Ham, Parthasarathy Ranjarajan, Prabhu Ramamoorthy, Lian Rajewski, Kathy Heppert, John Haslam, Karl Schorno, Michael Dalton, Michael J McKenna, Greg Reed, Amanda E Brinker, William McCulloch, Michael Jay Baltezor, Roy A. Jensen, John Arthur Taylor, Shrikant Anant
Journal: Journal of Clinical Oncology (2018)

e14576 Background: Ciclopirox (CPX) is an antifungal agent contained in a number of FDA-approved topical drug products. CPX possesses anticancer activity in a number of in vitro and in vivo preclinical models, however, its clinical utility is limited due to poor oral bioavailability, gastrointestinal toxicity, and poor water solubility. Ciclopirox Prodrug (CPX-POM) is a novel anticancer agent being developed for the treatment of non-muscle invasive (NMIBC) and muscle invasive (MIBC) bladder cancer. Methods: In vitro were conducted in two high grade human bladder cancer (T24, 253JBV) cell lines to characterize the mechanisms of action for CPX. The pharmacokinetics of CPX-POM, CPX and its major, inactive glucuronide metabolite (CPX-G) were characterized in mouse, rat and dog studies. The effect of IP CPX-POM on progression from carcinoma in situ to muscle invasive bladder cancer was characterized in the mouse BBN model of bladder cancer. Preclinical safety of IV CPX-POM was characterized in 28-day GLP toxicology studies in rats and dogs. Results: CPX-POM is completely metabolized in vivo to its active metabolite, CPX. CPX and its major inactive glucuronide metabolite (CPX-G) are extensively eliminated in urine. CPX achieves steady-state urine concentrations exceeding in vitro IC50 values by 15 to 30-fold at well tolerated doses. CPX inhibited cell proliferation, colony formation, and bladdosphere formation in vitro with IC50 values of 2-4 µM. CPX arrested cells at the S and G0/G1 phases, and induced cell death. CPX significantly reduced expression of genes at the mRNA level involved in cancer stem cell signaling pathways including Notch, Wnt, and Hedgehog. In the BBN model, CPX-POM resulted in significant decreases in bladder weight, migration to lower stage tumors, dose-dependent reduction in Ki67 and PCNA staining, across a dose range of 25-200 mg/kg. Dose-dependent decreases in Notch 1, Presenilin 1, and Hey 1 were observed in bladder cancer tissues obtained from CPX-POM treated animals. Conclusions: The safety, dose tolerance, pharmacokinetics and pharmacodynamics of CPX-POM are currently being characterized in a first-in-human trial enrolling patients with advanced solid tumors.
Remission observed from a phase 1 clinical study of CAR-T therapy with safety switch targeting BCMA for patients with relapsed/refractory multiple myeloma.
Authors: Yarong Liu, Zhi Chen, Runhong Wei, Lin Shi, Feng He, Zixiao Shi, Tao Jin, Ronglin Xie, Baofeng Wei, Jing Chen, Hongliang Fang, Bo Zhu, Qi-Jing Li, Pin Wang
Journal: Journal of Clinical Oncology (2018)

8020 Background: Encouraging results are seen from several early phase clinical trials on the cellular immunotherapy based on chimeric antigen receptor (CAR)-engineered T (CAR-T) targeting B cell maturation antigen (BCMA) for the treatment of relapsed/refractory (RR) multiple myeloma (MM). We developed an anti-BCMA CAR-T cell product manufactured via gamma-retrovirus-mediated transduction of activated T cells to express a second-generation CAR with the 4-1BB costimulatory domain along with a truncated epidermal growth factor receptor (tEGFR) as a safety switch. The preclinical study confirmed its high reactivity against MM cells. Methods: A phase 1 clinical trial (NCT03093168) has been launched to evaluate the safety and feasibility of this BCMA CAR-T cell product for treating RRMM. The enrolled RRMM patients had received at least 3 prior treatment regimens, including a proteasome inhibitor and an immunomodulatory agent, or are double-refractory, and have over 20% BCMA expression on plasma cells. Patients were subjected to a lymphodepleting regimen with Cy once (300 mg/m2, d-3) and Flu daily for 3 days (25 mg/m2, d-5 to d-3) prior to the CAR-T infusion (d0) at a dose of 9×106 CAR+ cells/kg. The efficacy was assessed by the International Uniform Response Criteria for Multiple Myeloma, and the toxicity iss graded by CTCAE 4.02. Results: As of December 31, 2017, 10 patients had been infused with this intended dose of the autologous BCMA CAR-T cells, and 7 patients had reached at least 1 month of follow-up. As of this data cut-off, no greater than Grade 1 neurotoxicities or cytokine release syndrome (CRS) had been observed. The overall response rate (ORR) for the 7 evaluable patients was 86%, including 2 sCRs and 2 MRD-negative responses (2 VGPR). The CAR-T cell expansion and persistence were consistently observed throughout these patients. Conclusions: Our result demonstrates the promising efficacy with the infused dose, including 2 sCRs and ongoing clinical responses for more than 12 months, with only mild and manageable CRS to date. These initial data provide strong evidence to support the further development of this anti-myeloma cellular immunotherapy. Clinical trial information: NCT03093168.
Effect of tumor location in metastatic colorectal cancer to response anti-EGFR and anti-VEGF treatment: One center study.
Authors: Metin Ozkan, Ender Dogan, Mahmut Ucar, Teoman Sakalar, Ahmet Alghareeb, Ersin Ozaslan, Mevlude Inanc
Journal: Journal of Clinical Oncology (2017)

e15023 Background: Colorectal cancer is the one of the most common malignancy in western countries. In addition to standart treatment antiEGFR and antiVEGF agents have improved PFS and overall survival. Current studies showed that the colorectal cancers have heterogenous characteristics. The Colon is divided into two parts as a right and left colon according to embrological origin. Recent years supposed that right and left located colorectal tumors may not response samely to anti egfr and anti vegfr therapies. We performed a retrospective study in our clinic to answer this questions. Methods: Study Population and data collection: Between January 2005 and December 2016, all metastatic colorectal cancer patients (n = 285) who received anti-EGFR and anti- VEGF agent with chemotherapy on initial treatment at the Erciyes University Medical Oncology Department were retrospectively reviewed. We included patients with diagnosed metastatic colorectal cancer and who received at least 1 dose of antiEGFR-based or antiVEGFR-based triplet bio-chemotherapy as their first-line treatments. Study population was divided into two groups as right and left colon. Results: A total of 251 patients met the inclusion criteria: 55 patients classified as a right colon cancer (RCC) and 196 patients classified as a left colon cancer (LCC) . 16 patients in RCC group received anti-EGFR-based triplet and 39 patients in RCC group received antiVEGF-based triplet; 76 patients in LCC group received anti-EGFR-based triplet and 120 patients in LCC group received antiVEGF-based triplet as first-line bio-chemotherapy. There were no differences between the patients received antiEGFR and antiVEGF therapy in RCC group (PFS,antiEGFR vs anti VEGF, 7 vs 8 months,P = 0.378; OS, 21 vs 19 months, P = 0.876). There were no differences between the patients received antiEGFR and antiVEGF therapy in LCC group (PFS,antiEGFR vs anti VEGF, 10 vs 10 months,P = 0.202; OS, 27 vs 24 months, P = 0.656). Conclusions: Our study shows that there were no significiant difference between the metastatic colorectal cancer patients received antiEGFR and antiVEGF treatment in LCC and RCC.
Combat lifesaver-trained, first-responder application of junctional tourniquets: a prospective, randomized, crossover trial
Authors: Ismael Flecha, Jason F. Naylor, Steven G. Schauer, Ryan A. Curtis, Cord W. Cunningham
Journal: Military Medical Research (2018)

Junctional hemorrhage surpassed extremity hemorrhage as the leading cause of preventable death after the resurgence of limb tourniquets during the recent conflicts in Afghanistan and Iraq. Junctional tourniquets (JTQs) were developed in response to this injury pattern. Published data for JTQ efficacy are limited and do not incorporate nonmedical, military first responders. We compared the time for effective placement and scores for device satisfaction between two different JTQs, stratified by combat lifesaver (CLS) and combat medics. We performed a prospective, randomized, crossover trial utilizing the SAM® Medical Junctional Tourniquet (SJT) and Junctional Emergency Treatment Tool (JETT™). Investigators simple randomized CLS and combat medics to SJT or JETT for their first JTQ application on mannequins with penetrating inguinal injuries. Then, participants immediately placed the other JTQ on another casualty with the same injury. The primary outcome measured was time of successful application. Success was defined as proper JTQ placement and a pressure reading of at least 180 mmHg. We compared outcomes between CLS and combat medics. Unsuccessful JTQ applications were excluded from the comparative analysis. From June 2015 to August 2015, a total of 227 personnel (133 CLS and 94 combat medics) at Fort Hood, Texas, USA volunteered to participate in the study. Twenty-eight percent (38 of 133) of CLS and 40% (38 of 94) of combat medics placed both JTQs successfully, for a total of 152 applications (76 SJTs and 76 JETTs). We found a significant difference between applications of the JETT between the CLS and combat medics (92.0 ± 37.7 s versus 70.5 ± 20.5 s, P = 0.004). No other subgroup analyses, whether by device or user, demonstrated a significant difference in application time. Both groups preferred the SJT over the JETT. CLS disagreed with combat medics that the JETT could be easily applied by one person (median 3.0 [2.0, 4.0] versus median 4.0 [3.0, 5.0]; P = 0.006). Overall, success rates for both the SJT and JETT were low. Improved training is needed to increase successful application of junctional tourniquets before widespread implementation. Combat lifesavers and combat medics prefer the SJT over the JETT.