tbuckley/cabot-search huggingface dataset:
Dissection of DLBCL microenvironment provides a gene expression-based predictor of survival applicable to formalin-fixed paraffin-embedded tissue
Authors: S. Ciavarella, M.C. Vegliante, M. Fabbri, S. De Summa, F. Melle, G. Motta, V. De Iuliis, G. Opinto, A. Enjuanes, S. Rega, A. Gulino, C. Agostinelli, A. Scattone, S. Tommasi, A. Mangia, F. Mele, G. Simone, A.F. Zito, G. Ingravallo, U. Vitolo, A. Chiappella, C. Tarella, A.M. Gianni, A. Rambaldi, P.L. Zinzani, B. Casadei, E. Derenzini, G. Loseto, A. Pileri, V. Tabanelli, S. Fiori, A. Rivas-Delgado, A. López-Guillermo, T. Venesio, A. Sapino, E. Campo, C. Tripodo, A. Guarini, S.A. Pileri
Journal: Annals of Oncology (2019)

Ann Oncol 2018; 29: 2363–2370 (doi: 10.1093/annonc/mdy450) The affiliations of authors T. Venesio and A. Sapino were originally incorrect. These have now been corrected as per the author listing above. Dissection of DLBCL microenvironment provides a gene expression-based predictor of survival applicable to formalin-fixed paraffin-embedded tissueAnnals of OncologyVol. 29Issue 12PreviewGene expression profiling (GEP) studies recognized a prognostic role for tumor microenvironment (TME) in diffuse large B-cell lymphoma (DLBCL), but the routinely adoption of prognostic stromal signatures remains limited. Full-Text PDF Open Access
Abstract 45: The Association of Cumulative Systolic Blood Pressure With Cardiovascular Disease: Findings From the Lifetime Risk Pooling Project Cohorts
Authors: Orna Reges, Hongyan Ning, John T Wilkins, Donald M Lloyd-jones, Norrina B Allen
Journal: Circulation (2020)

Background: Blood pressure (BP) is a known risk factor for cardiovascular disease (CVD), but prior studies have predominantly focused on single measurements of BP. Previous studies which have examined longitudinal BP have been mostly limited to a single cohort and have examined BP during older age. Objective: To assess the association of cumulative systolic BP (SBP) in middle age with CVD using individual-level pooled data from 5 US community-based cardiovascular disease cohorts. Methods: Among participants from the Lifetime Risk Pooling Project, we defined the index date as the earliest SBP measurement taken within 45-65 yr of age with ≥2 previous SBP measurements during the prior 5 years. Multivariate Cox proportional hazards models, with and without current SBP, were used to assess the association of cumulative 5-years SBP (Cum5ySBP, defined as 4 quarters {q1to q4} of SBP mm Hg-years) with any CVD, coronary heart disease, stroke, and heart failure. Models were adjusted for age, sex, race, education, BMI, smoking status, diabetes, total cholesterol level, and use of hypertensive medications as well as index SBP. Results: The association of Cum5ySBP with CVD over an average of 12.9 years was assessed for 13,957 individuals (54.6% women; mean age: 59.6 yr). Cum5ySBP was significantly associated with CVD incidence, with higher risk as the Cum5ySBP increased {Cum5ySBP: HRq2: 1.34 (1.20-1.48), HRq3: 1.71 (1.55-1.90), and HRq4: 2.16 (1.95-2.40)} (Figure 1A). The Cum5ySBP remained significant even when index SBP was incorporated into the model {Cum5ySBP: HRq2: 1.12 (1.01-1.25), HRq3: 1.24 (1.10-1.39), and HRq4: 1.19 (1.03-1.37)} (Figure 1B), as well as when evaluated separately for each type of CVD event. Conclusions: Cum5ySBP is a significant risk factor of CVD, above and beyond current BP. The risk for any CVD component increased with increases in cumulative SBP. These findings emphasize the importance of early treatment for individuals with high BP in order to reduce the cumulative burden of SBP and ultimately prevent CVD outcomes.
A phase III trial of topotecan and whole brain radiation (WBRT) therapy for patients with CNS metastases due to lung cancer
Authors: Y. Ko, T. Neuhaus, R. Müller, G. Grabenbauer, J. Hedde, H. Schüller, M. Kocher, S. Stier, R. Ullrich, R. Fietkau
Journal: Journal of Clinical Oncology (2007)

2049 Background: Brain metastases represent an important cause of morbidity in patients (pts) with lung cancer and are associated with a mean survival of less than 6 months. Thus studies to improve outcome are urgently needed. Methods: Based on promising data raised in a phase I/II trial, in which WBRT was combined with topotecan (ASCO #444, 2003), we initiated an open, randomized, prospective, multicentric phase III trial, comparing WBRT (20 x 2 Gy; arm A) alone with WBRT + topotecan (0.4 mg/m 2 /d x 20; arm B). 320 pts with CNS-metastases due to SCLC or NSCLC were projected. Primary endpoint was overall survival (OS), secondary endpoints were local response and progression-free survival (PFS). However, since until the cut off date of study completion (i.e. a study duration of 34 months) only a total of 96 (A: 49, B: 47) pts have been recruited, an interim analysis was performed at that time point. Results: The demographic data (ø age 59 (34–75), 64% male, 66% NSCLC, mainly (64%) ECOG 0–1, extracerebral metastases in 75% and more than 4 cerebral lesions in 26% of pts) were evenly distributed in the two groups. Also the rate of grade 3/4 toxicities (besides alopecia 115 non-hematological (A/B: 60/55) and 43 hematological events (18/25)) did not differ remarkably between the arms. Early deaths (within 6 weeks after recruitment) occurred in 24% of the patients (A/B: 30%/18%), mainly due to tumor progression. Local response, evaluated 2 weeks after treatment, was assessable in 44 (A/B: 21/23) pts, showing CR in 8 (5/3), PR in 17 (6/11), SD in 14 (6/8) and PD in 5 (4/1) pts (all differences n.s.). Neither PFS (median A/B; days: 76/97, range, 24–251/20–428) nor OS (median A/B; days: 95/87, range 4–433/3–752) differed significantly (Cox-Mantel test; p=0.82 and 0.43, respectively). Conclusions: The available data, gained from the only phase III trial regarding concurrent WBRT and topotecan, show no significant advantage for concurrent radiochemotherapy for patients with lung cancer, however due to the limited number of recruited patients a possible small advantage of a combined treatment could not be demonstrated. Based on these results and the slow recruitment a continuation of the study did not seem reasonable. No significant financial relationships to disclose.
The role of IL-22 in intestinal health and disease
Authors: Mary E. Keir, Tangsheng Yi, Timothy T. Lu, Nico Ghilardi
Journal: The Journal of Experimental Medicine (2020)

The cytokine interleukin-22 (IL-22) is a critical regulator of epithelial homeostasis. It has been implicated in multiple aspects of epithelial barrier function, including regulation of epithelial cell growth and permeability, production of mucus and antimicrobial proteins (AMPs), and complement production. In this review, we focus specifically on the role of IL-22 in the intestinal epithelium. We summarize recent advances in our understanding of how IL-22 regulates homeostasis and host defense, and we discuss the IL-22 pathway as a therapeutic target in diseases of the intestine, including inflammatory bowel disease (IBD), graft-versus-host disease (GVHD), and cancer.
Distinctive characteristics of non-small cell lung cancer in younger patients: A national cancer database (NCDB) analysis of patients under 40 years old (1998–2003)
Authors: V. Velcheti, B. Goodgame, D. Morgensztern, F. Gao, M. Baggstrom, R. Govindan
Journal: Journal of Clinical Oncology (2007)

18035 Background: Non-small cell lung cancer (NSCLC) is disease of the elderly and is rare in younger adults. NSCLC in younger patients may be biologically different and have a different presentation and natural history. Methods: We identified in the National Cancer Data Base (NCDB), all patients diagnosed with NSCLC from 1998 to 2003. NCDB is a cancer database maintained by the American College of Surgeons. The NCDB data is obtained from the cancer programs participating in the Commission on Cancer NCDB annual call for data. Data on gender, race, stage and histology were obtained from the NCDB. The characteristics of patients with NSCLC from 16–39 years of age were compared to the entire group. Results: In the NCDB, 551248 patients with NSCLC diagnosed from 1998- 2003 were identified. Of these 4093 were in the age group 16–39. We compared the characteristics of NSCLC in younger group to the entire cohort (Table). Younger patients were more likely to be women, 52% vs 42% (p&lt;0.001), and more likely to present with distant disease (stage 3 &amp; 4) 75% vs 61% (p&lt;0.001). Adenocarcinoma was more common in younger patients, 48% respectively, vs. 38%. Squamous cell carcinoma was far less common in younger patients, 12% vs 28% (p&lt;0.001). Conclusions: Patients with NSCLC who are &lt; 40 years old at diagnosis are more likely to be women and have adenocarcinoma histology. Younger patients present with advanced stage more often than those who are older than 40 years at diagnosis. Table: Characteristics of younger patients with NSCLC [Table: see text] No significant financial relationships to disclose.
Club Cell TRPV4 Serves as a Damage Sensor Driving Lung Allergic Inflammation
Authors: Darin L. Wiesner, Richard M. Merkhofer, Carole Ober, Gregory C. Kujoth, Mengyao Niu, Nancy P. Keller, James E. Gern, Rebecca A. Brockman-Schneider, Michael D. Evans, Daniel J. Jackson, Thomas Warner, Nizar N. Jarjour, Stephane J. Esnault, Michael B. Feldman, Matthew Freeman, Hongmei Mou, Jatin M. Vyas, Bruce S. Klein
Journal: Cell Host & Microbe (2020)
Can we improve the outcome of patients with advanced non-seminomatous germ cell tumors (NSGCT): 16 years experience of a single institution
Authors: A. Tryakin, S. Tjulandin, M. Fedyanin, D. Titov, A. Bulanov, A. Garin, K. Figurin, D. Kanagavel, J. Sergeev, T. Zakharova
Journal: Journal of Clinical Oncology (2007)

5092 Background: We performed an analysis to review the outcome of patients (pts) with advanced NSGCT treated in Russian Cancer Research Center, since the introduction of modern chemotherapy (CT) at 1987. Moreover, we analyzed whether the results had improved over the last 6 years. Methods: 589 CT-naive pts with advanced NSGCT received induction etoposide- and cisplatin-based CT from 1987 to 2003. 534 (91%) pts had primary testicular tumor. Most commonly used CT regimens were EP (36%), BEP (52%), and C-BOP-3BEP (9%). Median follow-up was 60 months (range, 2–210) for the pts who survived. Pts survival was compared in accordance with two treatment periods, ‘before 1997’ and ‘after 1997’. Results: Survival rate differed significantly among the IGCCCG prognostic groups. There was a trend toward improved results over the last 6-year period (see table ). The poor prognostic group attained the most pronounced improvement in both PFS and OS (absolute benefit 14%). This fact could be explained by CT intensification (decrease in the number of reasons for treatment delay or dose-reduction on next cycle of CT) and by increase in the rate of post-CT resections of residual tumors. Conclusions: Despite the absence of major changes in advanced NSGCT treatment during the last two decades, there still exists opportunity to improve the outcome of the pts. [Table: see text] No significant financial relationships to disclose.
Abstract 12230: Impact of Hyperuricemia on Clinical Outcomes After Percutaneous Coronary Intervention for In-stent Restenosis
Authors: Hyung Joon Joo, Han Saem Jeong, Hyungdon Kook, Seung Hun Lee, Jae Hyoung Park, Soon Jun Hong, Cheol Woong Yu, Do-Sun Lim
Journal: Circulation (2017)

Introduction: Pathophysiologically, in-stent restenosis (ISR) is considered to be an intrinsic cellular and biologic response after stent implantation. Inflammation has been thought to be involved ...
Laminin Drives Survival Signals To Promote A Contractile Smooth Muscle Phenotype And Airway Hyperreactivity
Authors: T Tran, C Teoh, J Tam, Y Qiao, C Chin, O Chong, AG Stewart, T Harris, W Wong, S Guan, B Leung, WT Gerthoffer, H Unruh, AJ Halayko
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Increased airway smooth muscle (ASM) mass is believed to underlie the relatively fixed airway hyperresponsiveness (AHR) in asthma. Developments of therapeutic approaches to reverse airway remodeling are impeded by our lack of insight on the mechanisms behind the increase in mass of contractile ASM cells. Increased expression of laminin, an extracellular matrix protein, is associated with asthma. Our studies investigate the role of laminin-induced ASM survival signals in the development of increased ASM and AHR. Antagonizing laminin integrin binding using the laminin-selective competing peptide, YIGSR, and mimicking laminin with exogenous α2-chain laminin, we show that laminin is both necessary and sufficient to induce ASM cell survival, concomitant with the induction of ASM contractile phenotype. Using siRNA, we show that the laminin-binding integrin α7β1 mediates this process. Moreover, in laminin-211-deficient mice, allergen-induced AHR was not observed. Notably, ASM cells from asthmatic airways express a higher abundance of intracellular cell survival proteins, consistent with a role for reduced rates of cell apoptosis in development of ASM hyperplasia. Targeting the laminin-integrin α7β1 signaling pathway may offer new avenues for the development of therapies to reduce the increase in mass of contractile phenotype ASM cells that underlie AHR in asthma.
Fedratinib in patients with myelofibrosis previously treated with ruxolitinib: An updated analysis of the <scp>JAKARTA2</scp> study using stringent criteria for ruxolitinib failure
Authors: Claire N. Harrison, Nicolaas Schaap, Alessandro M. Vannucchi, Jean‐Jacques Kiladjian, Eric Jourdan, Richard T. Silver, Harry C. Schouten, Francesco Passamonti, Sonja Zweegman, Moshe Talpaz, Srdan Verstovsek, Shelonitda Rose, Juan Shen, Tymara Berry, Carrie Brownstein, Ruben A. Mesa
Journal: American Journal of Hematology (2020)

Fedratinib is an oral, selective Janus kinase 2 (JAK2) inhibitor. The phase II JAKARTA2 study assessed fedratinib in patients with intermediate- or high-risk myelofibrosis (MF) who were resistant or intolerant to prior ruxolitinib per investigator assessment. Patients received fedratinib 400 mg/day in 28-day cycles. The JAKARTA2 outcomes were initially reported using a last-observation-carried forward (LOCF) analysis in a "Per Protocol" population. This updated analysis of JAKARTA2 employs intention-to-treat analysis principles without LOCF for all treated patients (ITT Population; N = 97), and for a patient subgroup who met more stringent definitions of prior ruxolitinib failure (Stringent Criteria Cohort; n = 79). Median duration of prior ruxolitinib exposure was 10.7 months. The primary endpoint was spleen volume response rate (SVRR; ≥35% spleen volume decrease from baseline to end of cycle 6 [EOC6]). The SVRR was 31% in the ITT Population and 30% in the Stringent Criteria Cohort. Median duration of spleen volume response was not reached. Symptom response rate (≥50% reduction from baseline to EOC6 in total symptom score [TSS] on the modified Myelofibrosis Symptom Assessment Form [MFSAF]) was 27%. Grade 3-4 anemia and thrombocytopenia rates were 38% and 22%, respectively. Patients with advanced MF substantially pretreated with ruxolitinib attained robust spleen responses and reduced symptom burden with fedratinib.
Abstract P109: Consistency of Self-reported Prior Diagnosis of Atrial Fibrillation and Medicare Claims Diagnoses: The Reasons for Geographic and Racial Differences in Stroke
Authors: Oluseun O Akinyele, Elsayed Z Soliman, Ligong Chen, Hooman Kamel, Emily B Levitan
Journal: Circulation (2020)

Introduction: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Although self-reported prior diagnosis is a widely used method for ascertainment of AF in population studies, recall bias may impact the accuracy of this method. Objective: To examine the consistency of self-reported AF as compared to diagnoses recorded in Medicare claims. Methods: Among 30,239 black and white adults aged 45 years and older who enrolled in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study, 8,588 participants aged 65 years and older with a minimum of 6 months of Medicare fee-for-service coverage at the time of enrollment were included in this analysis. Using AF diagnosis codes from Medicare claims as the “gold standard”, we calculated sensitivity, specificity, positive predictive value (PPV), and negative predicted value (NPV) of self-reported prior diagnosis of AF by a physician or other health professional. Results: The average age of the study population was 73.4 years, 50.5% were women, 31.6% were black, and 10.1% reported a prior diagnosis of AF. The prevalence of Medicare claims diagnoses for AF ranged from 28.6% to 32.5% depending on definition ( Table ). Compared to Medicare claims, self-reported prior diagnosis of AF had 22.4-24.5% sensitivity, 95.6-95.7% specificity, 68.8-71.5% PPV, and 71.9-76.0% NPV. Results were consistent across strata defined by age, gender, race, and cognitive status. Conclusion: Compared to Medicare claims, self-reported prior diagnosis by a physician or other health professional had low sensitivity but high specificity to detect AF. This suggests that an approach utilizing only self-report to detect AF would not be ideal. However, most participants who reported a prior diagnosis of AF had Medicare claims supporting this diagnosis.
Abstract MP41: Cost-related Medication Nonadherence by Psychological Distress Status Among Adults With Hypertension in the US
Authors: Giujing Wang, Jing Fang, Chanhyun Park
Journal: Circulation (2020)

Objectives: Medication adherence is a major factor determining the effectiveness of hypertension management. Financial cost and psychological distress (PD) may influence medication adherence, but research in this field is lacking. This study investigated cost-related medication nonadherence (CRMN) and cost-reduction strategies (CRS) by PD status in US adults with hypertension. Methods: The study population included adults aged 18 years and older with self-reported hypertension (n=15,778) from the 2017 and 2018 National Health Interview Survey, a nationally representative health survey. CRMN was defined as persons having skipped medication, taking less medication than prescribed, or delaying a medication refill in the past 12 months to save money. CRS was defined as persons having asked a doctor for lower cost medication, bought prescription drugs from another country, or used alternative therapies in the past 12 months to save money. PD was based on a 6-item scale of the Kessler Psychological Distress Scale classified as no/low, mild/moderate, and severe distress. We calculated adjusted percentages of CRMN and CRS for each PD level. We calculated adjusted odds ratios (AOR) of both CRMN and CRS by PD status for overall and sub-population groups by age and sex. We controlled for race/ethnicity, education level, insurance status, household income, and cardiovascular risk factors. Results: Among the adults with hypertension, 10.4% reported CRMN, 24.0% reported CRS, 11.9% had mild/moderate and 6.0% had severe PD. Adjusted percentage of CRMN increased from 7.3% for no/low to 19.0% for mild/moderate and 28.7% for severe PD status (p&lt;0.001); and adjusted percentage of CRS increased from 21.1% to 35.0% and 39.8%, respectively (p&lt;0.001). These patterns hold for age and sex group with a higher percentage for younger (18-64 years) than for older (65 and older) age groups. Compared with patients with no/low PD, patients with mild/moderate and severe PD were more likely to report CRMN with an AOR of 2.81 (95% CI: 2.34-3.37) and 5.12 (4.17-6.30), respectively; and for CRS, the AOR was 1.93 (1.70-2.19) and 2.30 (1.91-2.76), respectively. These patterns were consistent for each age and sex group while the younger age group and women experienced more CRMN and CRS. Conclusions: The positive relationships between CRMN and PD, as well as CRS and PD suggest that uncontrolled PD could play a disruptive role in hypertension management. Addressing behavioral health among adults with hypertension may be important to achieving hypertension control goals.
Abstract P214: Emotional Intelligence Increases During 10-Day Intensive Lifestyle Program
Authors: Francisco E Ramirez, EDWIN RENCK, Neil Nedley
Journal: Circulation (2020)

Background: Emotional intelligence (EQ) has been linked with success in life. Previous studies have shown that EQ can be improved. EQ could be negatively affected by depression and/or anxiety. We document the effect that a multi lifestyle intervention together with cognitive behavioral therapy (CBT) can have on patients in 10 days. Healthy lifestyles that improve heart health could improve mental health. Methods: During the 10-day medical residential program that took place in the Sierra mountains in northern California, patients received are seen by a board certified physician which prescribes a custom plan for the 10 days. Patients stayed in the facilities during the 10 days. Each patient received CBT by a licensed clinical psychologist and chaplaincy with an emphasis in improving thinking patterns. The program included physical exercise sessions, buffet like whole foods plant-based meals rich in omega-3, bright light therapy, hydrotherapy, classical music therapy, improving circadian rhythm, among other prescriptions. All of the participants activities were monitored on a strict schedule, this included time for meals, activities, therapy, rest, and other activities. At the start and end of the program every participant filled out a 85-item questionnaire which included a standardized mini EQ test, and demographics. Results: The average age of the n=186 study participants was 44 years, with a minimum of 12 and maximum of 97. Patients from various countries participated. EQ was measured at the beginning and end of the program. The mean EQ value at start was 95.1, SD 15.0, median 94, and mode 92. The mean EQ at the end of the program was 118.4, SD 16.0, median 120, mode 120. On average a participant increased their EQ by 23 points, the change showed statistical significance (p&lt;0.001, one-tailed t-test). Conclusions: It seems the lifestyle program increases EQ in 10 days, a follow up is necessary to evaluate if this increase in EQ remain long-term.