tbuckley/cabot-search huggingface dataset:
Abstract 13027: Risk of Sudden Cardiac Arrest According to the Time of STEMI Occurrence: the e-MUST Study
Authors: Nicole Karam, Sophie Bataille, Muriel Tafflet, Eloi Marijon, Jean Philippe Empana, Yves Lambert, Christian Spaulding, Xavier Jouven
Journal: Circulation (2015)

Introduction: STEMI mortality decreased drastically during the last decades, and out-of-hospital sudden cardiac arrest (SCA) has become its main mode of death. The risk of out-of-hospital SCA according to the timing of STEMI occurrence has not been assessed. Hypothesis: The risk of SCA, prior to hospital admission, differs according to the timing of STEMI occurrence. Methods: Data were taken from a prospective pre-hospital study (e-MUST study) on all STEMI patients managed by emergency medical services in Paris and its suburbs between January 2006 and December 2010. In this area, emergency calls are routed to the closest dispatch center and regulated by physicians who send, in the field, an ambulance with a physician on board in case of suspected acute myocardial infarction. Pre-hospital EKGs are obtained for all patients and those presenting STEMI are included in the study. We assessed the rate of SCA, prior to hospital admission, according to the timing of STEMI occurrence (4 hours-time intervals starting at midnight). Results: Among the 8,112 STEMI patients enrolled (mean age (SD) 61.6 (14.3) years, 78% males), 452 patients (5.6%) developed out-of-hospital SCA. We observed significant circadian change in the rate of SCA per STEMI, with a progressive increase between 4am and 8pm, followed by a decrease between 8pm and 4am (P=0.0009). The peak rate of SCA per STEMI occurred in the 4pm-8pm time interval (7.7%), while the lowest rate was seen between 4am and 8am (4.2%) (Figure). Conclusions: The risk of STEMI-related SCA is almost 2-fold higher in STEMI occurring in the late afternoon hours. A better understanding of patients’ characteristics, circumstances of occurrence, and pre-hospital care is needed to eventually reduce the risk of SCA promptly after STEMI diagnosis in the field.
Standard of care for MIBC is becoming more standard.
Authors: Kelly LR Miller, Heidar Albandar, David Key, John J. Haluschak
Journal: Journal of Clinical Oncology (2017)

e16011 Background: Despite consensus guideline recommendations, the management of muscle invasive bladder cancer (MIBC) varies dependent on institution setting. The risk of recurrence of localized bladder cancer after cystectomy is substantial and associated with stage. The current standard of care for possibly T2 and certainly T3-T4 MIBC is neoadjuvant cisplatin (NAC) based chemotherapy followed by cystectomy. As recent as 2011, only 12% of patients in this category actually received NAC (Feifer et al. 2011). Similar statistics have been confirmed in the US and Canada. Given there is a 13% reduction in risk of death with use of NAC, the adherence to this recommendation needs to improve. We hypothesize that in a multispecialty community practice where barriers to care are reduced that the percentage of eligible patients receiving NAC is significantly higher than previously reported. Methods: After IRB exemption obtained, patients from 2012-2015 with MIBC who underwent cystectomy were examined. Data collection included age, sex, date of consultation, dates and type of chemotherapy received, eGFR, date of surgery and surgical pathology report staging. Data were analyzed using Kolmogorov-Smirnov, Shapiro-Wilk, Mann-Whittney and Kruskal-Wallis statistical tests. Results: The average patient age was 69 years old with a male predominance. Approximately 54% of patients received neoadjuvant chemotherapy; however, three of those patients did not receive the recommended cisplatin based regimen. Fifty percent of patients received NAC and 57% of cisplatin eligible (age &lt; 80, eGFR &gt; 30) patients received NAC. The average time to cystectomy was 171 days among those receiving NAC, with a decrease in time to cystectomy correlating with age. Conclusions: In a community group practice, adherence to standard of care recommendations for higher stage MIBC patients to receive NAC are significantly higher than recently reported values, 50% vs 12%, respectfully. This was achieved while maintaining acceptable time to cystectomy. This supports our hypothesis that when barriers to care are decreased in a community group practice, high quality standards of care can be effectively delivered. In the future, 5 year overall survival will also be important to evaluate in this population.
Glad to be gay in India
Authors: Jeetha D’Silva
Journal: BMJ (2018)

Aphishek N Chinnappa/Reuters 

A member of India’s lesbian, gay, bisexual, transgender, and queer (LGBTQ) community in Bengaluru (Bangalore) celebrates a landmark judgment that decriminalised homosexuality on Thursday 6 September. The Supreme Court ruling could pave the way to healthcare reforms in a country that has been largely insensitive to the community’s needs. But the process could be arduous, say doctors.

Access to healthcare is a major issue for the gay community, and one raised by Indu Malhotra, one of the five judges in the hearings that led …
A nomogram for predicting post-operative cancer specific survival in AJCC 8th edition stage I NSCLC patients.
Authors: Wenhua Liang, Yuan Zeng, Jianxing He
Journal: Journal of Clinical Oncology (2017)

8540 Background: The AJCC 8 th edition staging system has moved 4-5 cm 7 th edition stage Ib NSCLC to current stage IIa, thus theoretically all current stage I patients are not considered candidates for adjuvant therapy (ad-Tx). This study was to develop a clinical nomogram for predicting cancer specific survival (CSS) of the current stage I resected NSCLC to identify those with higher risk for cancer-related deaths and potentially benefiting from ad-Tx. Methods: NSCLC cases between 1998 and 2013 was extracted from the SEER database and were randomly divided into training (n = 23,496) and validation (n = 7,915) cohorts. We identified and integrated the recurrence-associated factors to build a nomogram. The model was subjected to bootstrap internal validation and independent validation. The predictive accuracy and discriminative ability were illustrated by calibration plots and concordance index (C-index). We determined the cut-off for high-risk group by matching the nomogram-predicted 5-year CSS with that of the current 4-5 cm stage IIa cases. Results: In multivariate analysis, independent factors for CSS were examined lymph node count ( &lt; 16 vs. &gt; = 16), tumor size, resection scope (lobectomy/segmentectomy/wedge resection), differentiation grade, histology (squamous vs. non-squamous vs. former BAC with majority being AIS/MIA) and visceral pleural invasion, which were then integrated into the model (sex and age were not included due to lack of direction to ad-Tx selection). The calibration curves showed excellent agreement between nomogram prediction and actual observation. The C-index of the nomogram was higher than that of staging system (Ia1, Ia2, Ia3, Ib) (training set, 0.60 vs. 0.56, P &lt; 0.01; validation set, 0.60 vs. 0.57, P &lt; 0.01). Specifically, 21.5% stage Ib patients (8.8% of all stage I) were categorized into high risk group (score &gt; 29.5) and had inferior CSS compared with 4-5 cm stage IIa patients. Conclusions: We established a nomogram that can individually predict CSS for 8 th edition stage I NSCLC. By this model, we identified a subset of patients with relatively high risk for recurrence. Further study to determine the impact of postoperative ad-Tx on these high risk patients is undergoing.
Monitoring microsatellite instability (MSI) in circulating tumor DNA by next-generation DNA-seq.
Authors: Adam Deng, Jialiang Yang, Jidong Lang, Zheng Jiang, Weitao Wang, Dawei Yuan, Xishan Wang, Geng Tian
Journal: Journal of Clinical Oncology (2018)

12025 Background: Microsatellite instability (MSI) is a useful predictive biomarker for prognosis of patients with phase II colorectal cancer and clinical benefit from cancer immunotherapy. Conventional MSI testing is commonly performed with tumor tissues by a fluorescent multiplex PCR-based method, consisting of six mononucleotide microsatellite makers. Recently, next generation DNA sequencing (NGS) has been developed for detection of MSI status in tumor tissues. However, we are still curious about whether we could accurately monitor MSI in ctDNA by NGS to achieve the non-invasive diagnosis. Methods: We collected plasma, matched tumor tissue and blood samples from 200 cancer patients. ctDNAs extracted from plasma and genomic DNAs extracted from tumor tissue and blood were used to perform MSI testing by conventional PCR methodand amplicon-based NGS. Six regular mononucleotide microsatellite makers (NR-27, NR-21, BAT-26, BAT-25, NR-24, MONO-27) were analyzed in two methods, and blood was compared as the normal control for MSI evaluation. MSI-H or MSI-L/MSS patients were primarily distinguished by conventional PCR method. Further we performed MSI detection in plasma, matched tumor tissue and blood by NGS and designed an algorithm for evaluating MSI status. Results: In 200 cancer patients, we primarily identified 13 patients with MSI-H (6.5%) and the others with MSS by conventional PCR method. Interestingly, we found that MSI testing in plasma was not performed by conventional PCR assay, namely that MSI could not be precisely monitored by conventional method. However, both MSI testing in plasma and in tumor tissue could be performed well by NGS. Compared the results of MSI testing in tumor tissue by two methods, there was high consistency. Importantly, we found that all 13 MSI-H patients were correctly identified by MSI testing in circulating tumor DNA(ctDNA), in concordance with the results of MSI testing in tumor tissue. The sensitivity of MSI testing was 100%. Conclusions: In our study, the MSI status of cancer patients could be accurately monitored in circulating tumor DNA(ctDNA) by amplicon-based NGS. It provides the possibility of non-invasive MSI testing for cancer patients in clinical diagnosis.
Soluble urokinase plasminogen activator receptor (suPAR) as a novel biomarker in patients undergoing resection of pancreatic adenocarcinoma.
Authors: Sven H Loosen, Marcel Binnebösel, Thomas Longerich, Christoph Roderburg, Christian Trautwein, Ulf Peter Neumann, Tom Luedde
Journal: Journal of Clinical Oncology (2019)

248 Background: Surgical resection represents the only potentially curative therapy for patients with pancreatic adenocarcinoma (PDAC), an aggressive malignancy with a very limited 5-year survival rate. However, even after successful R 0 tumor resection, some patients are still facing an unfavourable prognosis underlining the need for better preoperative stratification algorithms. The soluble urokinase plasminogen activator receptor (suPAR) was recently described as a promising new biomarker for different clinical conditions including cancer. Here, we evaluated the potential role of circulating suPAR as a biomarker in patients undergoing resection of PDAC. Methods: Expression levels of uPAR, the membrane-bound source of circulating suPAR, were analysed in PDAC tissue samples using IHC. Serum levels of suPAR were measured by ELISA in an exploratory as well as a validation cohort comprising a total of 127 PDAC patients and 75 healthy controls. Results were correlated with clinical data. Results: Correlating with a high immunohistochemical expression of uPAR in PDAC tissue samples, serum levels of suPAR were significantly elevated in PDAC patients compared to healthy controls. Importantly, patients with high preoperative suPAR levels above a calculated cut-off value of 5.956 ng/ml showed a significantly reduced overall survival after tumor resection. The prognostic role of suPAR was further corroborated by uni- and multivariate Cox-regression analyses including parameters of systemic inflammation, liver and kidney function as well as clinico-pathological patients’ characteristics. Moreover, high baseline suPAR levels identified those patients particularly susceptible to acute kidney injury after surgery. Conclusions: Our data suggest that circulating suPAR represents a novel prognostic marker in PDAC patients undergoing tumor resection that might be a useful addition to existing preoperative stratification algorithms for identifying patients that particularly benefit from extended tumor resection.
Circular RNA F-circEA-2a derived from EML4-ALK fusion gene promotes cell migration and invasion in non-small cell lung cancer
Authors: Shuangyan Tan, Dan Sun, Wenchen Pu, Qiheng Gou, Chenglin Guo, Youling Gong, Jiao Li, Yu-Quan Wei, Lunxu Liu, Yun Zhao, Yong Peng
Journal: Molecular Cancer (2018)

Oncogenic fusion gene Echinoderm Microtubule-associated protein-Like 4-Anaplastic Lymphoma Kinase (EML4-ALK) contributes to tumorigenesis of a subset of non-small cell lung cancer (NSCLC). Recently, we demonstrated that F-circEA-4a, a tumor-promoting circular RNA (circRNA) generated from the back-splicing of EML4-ALK variant 3b (v3b), is a novel liquid biopsy biomarker for NSCLC. However, circRNAs produced from EML4-ALK gene and their roles in NSCLC are not well-characterized. Here, we identify another EML4-ALK-v3b-derived circRNA, F-circEA-2a, harboring "AA" (rather than "AAAA" in F-circEA-4a) motif at the junction site. F-circEA-2a mainly locates in the cytoplasm and promotes cell migration and invasion, but has little effect on cell proliferation. Moreover, F-circEA-2a exists in tumor, but not in the plasma of NSCLC patients with EML4-ALK fusion gene, further supporting the significant diagnostic value of F-circEA-4a for EML4-ALK-positive NSCLC. This work finds a novel oncogenic circRNA generated from EML4-ALK fusion gene, highlighting the pivotal role of circRNA in EML4-ALK-positive NSCLC development.
Overall survival of intensive care unit patients with hematological malignancies: A 5-year retrospective study.
Authors: Agamenon Quintero, Jorge Racedo, Manuel Gonzalez Fernandez, Joseph Nates, Jesus Vera Aguilera, Heinznel Negrete Perez, Aaron Quintero
Journal: Journal of Clinical Oncology (2018)

e19560 Background: Patients diagnosed with hematological malignancies (HM) can develop acute life-threatening conditions that require intensive care unit (ICU) admission. The aim of this study is to determine the overall survival rate in patients diagnosed with HM who are admitted in the ICU, and to evaluate the predictors of poor outcomes. Methods: A single-center retrospective cohort included 45 critical ill patients with HM admitted to the ICU between January 2010 and December 2015. Data were collected from the ICU records and evaluated in-hospital mortality predictors by multivariate logistic regression analysis. Results: Most of the patients had advance stages of HM (75.0%) and received chemotherapy during the last three months before the ICU admission (69.8%). The most common HM found was non-Hodgkin lymphoma (35.4%), followed by acute lymphocytic leukemia (28.9%) and acute myeloid leukemia (17.8%); other types of HM included chronic myeloid leukemia (6.7%), myelodysplastic syndrome (4.4%), Hodgkin lymphoma (4.4%), and chronic lymphocytic leukemia (2.2%). The median sequential organ failure assessment (SOFA) score calculated at ICU admission was 10.5±4.4. Mortality rate of HM patients hospitalized in the ICU was 50% at sixth day but increased up to 80.0% after a prolonged stay at the ICU. Sepsis (64.4%) and acute respiratory failure (22.2%) were the major reasons for ICU admission. After the stepwise multivariate regression analysis, three independent predictors for mortality in HM patients admitted to the ICU were identified: Eastern Cooperative Oncology Group -ECOG- performance score (odds ratio [OR], 1.5; 95% confidence interval [CI], 0.99-2.31; p = 0.056), arterial hypertension (OR, 4.18; CI, 1.85-12.50; p = 0.0012), and SOFA score at admission (OR, 5.57; CI, 1.08-1.34; p = 0.00082). Conclusions: This study showed a statistically significant impact of arterial hypertension, SOFA score at admission and ECOG performance score in HM patients admitted to ICU. Further studies are necessary to assess the sepsis, nutritional status, other reasons to transfer to the ICU as significant predictors of high-mortality in HM patients admitted to the ICU.
Circulating tumor DNA assessment in patients with diffuse large B-cell lymphoma following CAR-T therapy.
Authors: Saurabh Dahiya, Ryan Le, Nasheed Mohammad Hossain, Matthew Abramian, Lori S. Muffly, David Bernard Miklos
Journal: Journal of Clinical Oncology (2017)

7552 Background: Circulating tumor DNA(CTD) have been used for disease monitoring in Diffuse Large B Cell Lymphoma(DLBCL) (Kurtz ASCO 2016). Role of CTD assessment in DLBCL patients treated with CAR-T therapy has not been studied. We prospectively analyzed CTD of dynamics measured by next generation sequencing(NGS) of BCR using ClonoSeq MRD(Adaptive Biotechnologies), before and after CAR-T therapy to determine feasibility and clinical utility. Methods: At Stanford, 7 patients were enrolled on ZUMA-1 clinical trial NCT02348216, treating chemo-refractory DLBCL patients with anti-CD19, CAR-T. Complete radiologic data and CTD analysis was collected for six subjects. Tumor-DNA was extracted from archival paraffin-embeded tissue &amp; analyzed using the NGS-based assay. PCR amplification of IGH-VDJ, IGH-DJ &amp; IGK regions using universal consensus primers was performed followed by NGS to determine the tumor clonotype(s). Blood collected at day 0,7,14,28,60 &amp; 90 days in relation to CAR-T infusion was used to detect CTD by ClonoSeq quantification of clonotypes. Results: Clonotypes were successfully determined for all 6 subjects, and 30 blood samples for 6 patients were prospectively analyzed. All patients had measurable disease burden pre-CAR-T infusion. CTD dynamics correlated with PET-CT outcomes in 100% of the patients. Increasing CTD temporally preceded progressive disease(PD) before PETCT recognition in 4 of 5 patients and was always increasing when PETCT showed PD. Preceding CTD quantification correlated with disease volume increase. One patient achieved durable KTE-19 complete response(CR) and detectable CTD became undetectable on day 14(and on subsequent samples) following CAR-T infusion, corresponding to 1 &amp; 3 month PETCT CR. Additionally, the burden of disease measured by lymphoma molecules per ml allowed volumetric response assessment in all the patients who experienced massive reduction in tumor volume, but by traditional response definition had partial response. Conclusions: ClonoSeq CTD provides precise total tumor quantification of DLBCL in the CAR-T cell setting. This technology may overcome fundamental limitations of DLBCL imaging(cost, radiation exposure &amp; limited repetition).
Factors influencing pain and efficacy of topical photodynamic therapy: a retrospective study
Authors: E. Lydon, R.S. Dawe, S.H. Ibbotson
Journal: British Journal of Dermatology (2018)

Photodynamic therapy (PDT) is widely used to treat superficial non-melanoma skin cancers and dysplasia. 1Pain may be experienced during irradiation, with one study showing pain intervention was required in 44% of PDT treatments. 2 Other retrospective studies indicated that large treatment areas on head and neck sites, actinic keratoses and strong protoporphyrin IX fluorescence may be predictors of more severe PDT-induced pain, but data were not conclusive. 3,4Excepting nerve blockade or reduction in irradiance, other pain relief methods are relatively ineffective.It is therefore important to identify predictors of PDT-
Abstract 14163: The Single Ventricle Reconstruction (SVR) Trial at 6 Years: Transplant-Free Survival, Catheter Interventions, and Morbidity
Authors: Jane W Newburger, Lynn A Sleeper, J. W Gaynor, Danielle Hollenbeck-Pringle, Peter Frommelt, Jennifer Li, William T Mahle, Ismee A Williams, Andrew M Atz, Kristin M Burns, Shan Chen, James F Cnota, Carolyn Dunbar-Masterson, Nancy S Ghanayem, Caren S Goldberg, Jeffrey P Jacobs, Alan B Lewis, Seema Mital, Christian Pizarro, Aaron W Eckhauser, Paul Stark, Richard G Ohye
Journal: Circulation (2015)

Background: In the SVR trial, 1-year (y) transplant (tx)-free survival was better for the Norwood procedure with right ventricle-to-pulmonary artery shunt (RVPAS) vs modified Blalock-Taussig shunt (MBTS). At 6 y, we compared tx-free survival, unplanned interventions, morbidities, New York Heart Association (NYHA) Class, and RV ejection fraction (RVEF) by assigned shunt. Methods and Results: The SVR trial treated 549 pts. Vital status and medical history were ascertained annually. Tx-free survival in the RVPAS (63.5%) vs MBTS (58.7%) groups did not differ (Figure; log-rank P=.13). Similarly, neither mortality nor tx alone differed by shunt type. By 6 y, RVPAS pts had a higher incidence of any catheter intervention (.38 vs .23/pt-yr, P&lt;.001), balloon angioplasty (P=.014), stent (P=.009), and coiling (P&lt;.001). The % of pts with morbidities by 6 y were similar in the groups, with overall rates: pacemaker 3%, thrombosis 16%, stroke 7%, seizures 13%, protein losing enteropathy 3%, plastic bronchitis 0.5%, and 6-y NYHA Class I 71%, II 21%, III 3%, and IV 5%. Among pre-specified subgroups, worse tx-free survival was associated with low birth weight (&lt;2500 g); worse pre-Norwood tricuspid regurgitation (≥2.5 mm jet width); lower surgeon Norwood volume; preterm birth (&lt;37 wks); and combined aortic atresia and pre-term birth (all P&lt;.01). Subgroup x shunt interaction was significant only for surgeon volume levels (P&lt;.05); in the highest volume group (n &gt;15/y), the MBTS was beneficial (P&lt;.04), and in 3 lower volume groups, the RVPAS was qualitatively better. In 6-y echoes read to date, RVEF was similar in the RVPAS vs MBTS groups (46±7, n=55 vs 46±6%, n=48; P=.9). Conclusions: By 6 y, tx-free survival was an absolute 4.8% higher for pts assigned to the RVPAS vs MBTS group, but the difference no longer reached statistical significance, and they needed more catheter interventions. Rates of death, tx, and morbidities; distribution of NYHA Class; and RVEF were each similar in the shunt groups.
Is esophagectomy indicated after induction therapy in patients with clinical N3 esophageal cancer?
Authors: Shadia Ibrahim Jalal, Fatima Ezzeddine, Kenneth Kesler, Thomas J Birdas
Journal: Journal of Clinical Oncology (2018)

e16073 Background: The benefit of inclusion of esophagectomy after induction therapy in patients with node-positive non-metastatic esophageal cancer is well established. It is unclear if that benefit persists even in patients with high burden of nodal disease at diagnosis. Methods: The National Cancer Database was queried for patients with clinical N3M0 esophageal carcinoma between 2010-2014, excluding those with incomplete records or receiving no therapy. Survival of patients receiving surgery after induction therapy was compared to those receiving definitive chemoradiation, adjusting for patient and tumor factors. As a reference, comparisons were made for cN1 and cN2 patients. Results: A total of 598 cN3M0 patients were identified. Resection was performed in 31.3% (vs 44.5% in cN1 and 39.4% in cN2, p = 0.0001). Surgery was performed more frequently in men (p = 0.03), younger patients (median age 61 vs. 63 years, p = 0.006), white (33.7% vs. 13% in African Americans, p = 0.03), with private insurance (p = 0.003 vs. other insurances) and adenocarcinomas (38.1% vs. 16.7% squamous, p = 0.0001). The 3-year survival was 32.2% vs. 17.9% (p = 0.0001). Median survival for all clinical node-positive stages are shown in the Table. In multivariate analysis, female sex, younger age and surgical resection (all - p < 0.0001) were independent predictors of long-term survival. Conclusions: Inclusion of surgery as part of multimodality therapy in patients with cN3M0 esophageal cancer results in a significant survival advantage, although smaller than in other nodal stages. Careful patient selection for surgical resection is paramount in order to maximize that benefit. Clinical Node status Surgery Median Survival (months) 95% CI P value N1 no 15.8 15.2-16.4 < 0.0001 yes 37.1 34.9- 39.3 N2 no 13.6 12.7-14.4 < 0.0001 yes 31.9 29.1 -34.8 N3 no 12.2 11.2- 13.6 < 0.0001 yes 20.0 15.1 - 24.9