tbuckley/cabot-search huggingface dataset:
Abstract 17411: Change in the Estimated Glomerular Filtration Rate and Blood Pressure After Kidney Transplantation
Authors: Ekamol Tantisattamo, Possawat Vutthikraivit
Journal: Circulation (2017)

Introduction: Chronic kidney disease (CKD) is a risk factor for hypertension (HTN). This association after kidney transplantation is unclear. Hypothesis: We hypothesize that higher eGFR is associated with lower blood pressure (BP). Method: A retrospective closed cohort study of 70 kidney transplant recipients were stratified by renal allograft function at 4 weeks post-transplant into stage 2 to 5 CKD. Change in eGFR every 3 months were correlated with mean SBP and mean DBP at corresponding a 3-month follow-up period until 96 weeks post-transplant. Results: Mean age was 52.66±1.43 years old and 41 patients (58.6%) was male. At 4 week post-transplant, stage 2 and 3 CKD were account to >90% of participants (patients with stage 2 = 19 (27.6%), stage 3 = 46 patients (65.7%)). Since only remaining 5 patients had stage 4 or 5 CKD, there patients were not included in an analysis. Mean eGFR in stage 2 and 3 CKD were 74.21±3.291 and 44.78±1.239, respectively (mean difference 29.428, CI 21.43 to 37.43, p <0.001). In...
DIPG-35. OPEN DIPG INITIATIVE: A PLATFORM FOR ACCELERATING DISCOVERY THROUGH DATA ACCESS, CONSOLIDATION AND HARMONIZATION
Authors: Krutika Gaonkar, Pichai Raman, Madhuri Kambhampati, Chris Jones, Cynthia Hawkins, Sabine Mueller, Adam Resnick, Javad Nazarian
Journal: Neuro-Oncology (2019)

Pediatric brain cancers remain amongst the most lethal childhood cancers with over five decades of failed clinical trials. However, precision based clinical trials incorporating upfront biopsies, postmortem biobanking, along with technological advancements have resulted in a remarkable surge of omics and molecular based tumor classifications as well as a fundamental revision of WHO grading of pediatric brain tumors. However clinical translation of such molecular advancements has yet to impact a broad range of pediatric brain cancers. Major factors contributing to this lag of translation include, data fragmentation across institution, lack of data harmonization, data access, computational limitation, and the paucity of linked clinical and molecular data. To address these obstacles, we set to develop a unique data sharing platform for diffuse intrinsic pontine glioma (DIPG); one of the most devastating childhood brain caners. This initiative, named Project Open DIPG (POP DIPG) intends to consolidate and harmonize DIPG omics across all exiting and newly developed molecular data. Here we report that an international collaboration lead by Children’s Brain Tumor Tissue Consortium (CBTTC) has successfully launched POP DIPG housing the largest OMICs resource for DIPG and midline gliomas to date. Specifically POP DIPG houses the following molecular data: whole genome, whole exome, transcriptome, proteome, methylome of 850 unique subjects, over 1000 specimens and 20 avatar models of the disease. Harmonized and analyzed data are available through PedCBioportal providing the ease of access, rapid queries and hypothesis driven inquiries. Access to raw files is also granted though CBTTC to investigators with defined projects and hypotheses. With the expansion of POP DIPG, preclinical drug testing will be incorporated to accelerate discovery and more importantly to facilitate molecular-driven precision clinical trials. Open DIPG initiative will serve as a model for other challenging childhood cancers by bridging the current gap in bench to bedside translation.
Abstract 01: Supplemental Nutrition Assistance Program (SNAP) Participants Exhibit Higher Rates of Cardiometabolic Mortality Compared to SNAP Eligible Non-participants and SNAP Ineligible Americans
Authors: Zach Conrad, Colin Rehm, Dariush Mozaffarian
Journal: Circulation (2016)

Introduction: The Supplemental Nutrition Assistance Program (SNAP) is the largest food assistance program for low-income Americans. Investigating mortality in this population is crucial to determining what further efforts are needed to reduce health disparities. The National Center for Health Statistics (NCHS) does not provide mortality data by SNAP participation status, so diet-related mortality according to SNAP eligibility and participation is not well established. Objective: To examine cardiometabolic mortality among SNAP participants, SNAP eligible non-participants, and the SNAP ineligible population. Methods: We used data from the National Health Interview Survey for 499,741 US adults age≥25y from 2000-2009 to assess SNAP eligibility and participation. These data were merged with the NCHS Linked Mortality file (2000-2009) to create a nationally representative cohort. Participants were followed until death or through Dec 31, 2011. Survey-weighted Cox-proportional hazards models were used to estimate hazard ratios of cause-specific mortality by SNAP eligibility and participation. Results: Over a mean of 6.8 y of follow-up (maximum 11.9 y), we observed 7408 CHD deaths, 2185 stroke deaths and 1376 diabetes deaths. For all outcomes, in particular diabetes, SNAP participants had highest risk, followed by SNAP eligible non-participants, and then SNAP-ineligible individuals (Figure, panel A). Considerable differences in cause-specific risk of mortality were observed between race/ethnicities among SNAP participants, SNAP eligible non-participants, and the SNAP ineligible population (Figure, panel B). Conclusion: Major health disparities exist between SNAP participants, SNAP eligible non-participants, and SNAP ineligible Americans, as well as by race/ethnicity. Ways to improve health outcomes of SNAP participants, including potential revisions to SNAP programming, are urgently needed to reduce these inequities.
Children should have at least three hours of daily physical activity from age 1, WHO advises
Authors: Gareth Iacobucci
Journal: BMJ (2019)

Young children should engage in at least 180 minutes of physical activity a day from the age of 1 to improve their health, the World Health Organization has recommended.

New global guidelines on physical activity, sedentary behaviour, and sleep for children under 5 also recommend no sedentary screen time for children under the age of 2 and a limit of one hour a day for children aged 2-4.1

This is the first time that WHO has issued guidelines on physical activity for children under 5 and the first time it has specified the length of time that very young children should sit passively watching screen based entertainment such as TVs, computers, and mobile devices.

Children aged 1-2 should spend at least 180 minutes a day in a variety of types of physical activities at any intensity, spread throughout the day, it recommends. …
DIPG-04. TRANSLATION OF DNX-2401 FROM THE BENCH TO THE CLINIC FOR PEDIATRIC HIGH GRADE GLIOMAS INCLUDING DIFFUSE INTRINSIC PONTINE GLIOMAS
Authors: Naiara Martinez-Velez, Marc Garcia-Moure, Virginia Laspidea, Oren Becher, Juan Fueyo, Candelaria Gomez-Manzano, Ana Patiño, Ricardo Diez-Valle, Sonia Tejada-Solis, Marta Alonso
Journal: Neuro-Oncology (2019)

Despite our increased understanding of the genetic make-up and new therapies for pediatric high grade glioma (pHGG) and Diffuse Intrinsic Pontine Glioma (DIPG) the outcome remains grim. Delta-24-RGD (DNX-2401 in the clinic) has been tested for adult glioblastoma presenting a safe profile and promising efficacy. The objective of this study was to evaluate the suitability of DNX-2401 as treatment for pHGG/DIPGs. Our results showed that DNX-2401 exerts a potent antitumor effect in pHGG (n=5) and DIPG (n=6) cell lines in vitro and in vivo. Our clinical trial experience with DNX-2401 in adult glioblastoma underscored the importance of the immune system in durable responses observed in patients. DNX-2401 administration in two DIPG immunocompent models was safe and without toxicity. DNX-2401 prolonged the overall survival, leading 20% to 80% of long-term survivors. Histologic examination showed that DNX-2401 stimulated T-cell infiltration (CD3+, CD4+ and CD8+; p<0.001) within the tumor. Esplenocytes from DNX-2401 treated-mice co-cultured with tumor cells significantly increase the IFNg production (p<0.0001). These outstanding preclinical results allowed us to open a phase I clinical trial for newly diagnosed DIPGs (NCT03178032) where the patients received an intratumoral viral injection followed by standard radiotherapy. Up to date 7 patients have been treated within the trial (3x1010viral particles in 1mL). The procedure was well tolerated and safe. Patients were home 3–4 days after the procedure. All the patients displayed a reduced tumor volume after combined treatment. In the next weeks, we will have information regarding the median survival. We are currently conducting molecular and functional studies to assess the response of the patients to the virus. Information acquired within this clinical study would aid to understand the response of DIPGs to viral therapies therefore to better tailor this strategy to improve the survival and the quality of life of pediatric brain tumor patients.
Abstract 17001: Safety and Efficacy of Balloon Atrial Septostomy for Advanced Pulmonary Hypertension in Patients Failing Prostanoid Therapy
Authors: Brooks T Kuhn, Usman Javed, Thomas W Smith, William J Bommer, Roblee P Allen, Jason H Rogers
Journal: Circulation (2011)

Background: Prostanoid therapy improves quality of life and may increase survival in patients with advanced pulmonary hypertension (PH). Balloon atrial septostomy (BAS) can palliate or a serve as a bridge to transplantation for patients resistant to medical therapy. The safety and efficacy of BAS in the era of prostanoid therapy has not previously been reported. Methods: All patients had progressive symptoms despite prostanoid therapy at the time of their first BAS. Eleven patients who underwent a total of 16 septostomies between 2004-11 were included in this retrospective analysis. Results: Baseline demographics are shown in Table 1. Survival at a mean of 739 days was 73%. No patient died within 24 hours post-procedure. Thirty-day and 1-year survival were both 82%. 4 subjects required repeat BAS due to shunt closure; 3 subjects were successfully bridged to transplant. 9 of 11 patients had improvement by one functional class. Hemodynamic and echocardiographic measurements are presented in Table 2. All non-survivors were male and had higher baseline serum creatinine, mean right atrial pressure, right ventricular (RV) end diastolic pressure and left ventricular filling pressures, and lower RV ejection fraction. Mortality was associated with unchanged post-septostomy cardiac output despite an increase in LVEDP. Tricuspid annular plane systolic excursion (TAPSE) and serum BNP were not different between the two groups. Conclusions: BAS appears to be a promising therapy for select PH patients who have symptomatic progression despite prostanoid therapy. Survival is comparable to prior reports of patients undergoing BAS in the pre-prostanoid era.
Polyp cancers: size matters!
Authors: Pradeep Bhandari
Journal: Endoscopy (2019)

The risk of cancer in a polyp increases with increasing polyp size. The prevalence of cancer in polyps < 5 mm is negligible [1]. This has led to the development of "diagnose-and-leave" and "resect-and-discard" strategies, underpinned by optical biopsy [2]. Attempts have been made to extend these strategies beyond diminutive polyps. The DISCOUNT study group explored optical diagnosis in real time and the implications of extending the practice from diminutive to small polyps. The findings suggested that the Preservation and Incorporation of Valuable Endoscopic Innovations criteria could be met for diminutive as well as small (6 – 9 mm) polyps, resulting in big cost savings [3]. However, the group found that 7/2115 (0.33 %) small polyps harbored cancer and, under the resect-and-discard strategy, these polyps would be discarded leading to inappropriate management of these cancers. Is this risk low enough to be acceptable? The interesting fact is that optical diagnosis could only identify 1 /7 cancers (14 %) before resection, indicating that optical diagnosis works well for differentiating hyperplastic polyps from adenomas but not from cancers. This could be due to the very low prevalence of cancer, as highlighted in the DISCOUNT study, or a lack of training or understanding of cancers. The incidence of polyp cancers stratified by size is useful information for both clinicians and policy makers.
Percutaneous Heart Catheterization in Infants and Children
Authors: MASATO TAKAHASHI, EUGENE L. PETRY, PAUL R. LURIE, STANLEY E. KIRKPATRICK, ROBERT E. STANTON
Journal: Circulation (1970)

This report describes in detail the materials and methods used in the authors' laboratory for percutaneous insertion of catheters and for manipulation of catheters with guide wires in infants and children. A simple thin-walled spinal needle is used to enter femoral vessels initially. Catheter insertion is effected thereafter with the sequential uses of a guide wire, a dilator, and an end-hole catheter. Insertion of two or three catheters into a single vessel may be accomplished. In infants weighing less than 20 pounds, dilation of the vascular puncture wound may be accomplished in stages. Guide wires of different configurations are used for catheter manipulation into various cardiac structures including some which are relatively inaccessible. Guide wires are also used for catheter exchange. Angiograms of high quality may be obtained safely.
Assessment of responsiveness of the musculoskeletal component of SLE-DAS in an independent cohort
Authors: Sabih-Ul Hassan, Khaled Mahmoud, Edward M Vital
Journal: Annals of the Rheumatic Diseases (2019)

We read with interest the report by Jesus et al on the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS).1 We agree that the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) in its original form has limitations as a disease activity tool. Since each organ manifestation can only be graded as present or absent, it is unable to differentiate between mild, moderate or severe disease activity, nor partial response in any feature.

Our group is researching outcome measures in musculoskeletal SLE. We published a previous study of responsiveness of various musculoskeletal outcome measures in patients treated with glucocorticoids.2 As expected, the musculoskeletal component of the SLEDAI-2K was less responsive than the physician visual …
THER-03. REPURPOSING MEFLOQUINE AND ANALOGUES FOR DIPG THERAPY
Authors: Jian Teng, Bakhos Tannous
Journal: Neuro-Oncology (2019)

Diffuse intrinsic pontine gliomas (DIPG) is the leading cause of pediatric death by brain tumors with a median survival after diagnosis of only 9 months, and 5-year survival less than 1%. Despite intensive multimodality treatment, refractory disease and relapses are frequent events in these tumors. We performed a repurposing drug screen aiming at evaluating the potential of recycling of old known drugs for DIPG therapy using patient-derived DIPG stem-like cells. Repurposing of drugs already approved to treat certain conditions to see if they are safe and effective for treating other diseases provides quicker translation from bench to bedside. We identified that a subset of quinoline class of anti-malaria agents to have significant DIPG killing properties. Among them, we selected the FDA-approved compound mefloquine due to its efficacy and potency in killing DIPG cells, with an IC50less than 0.5 µM in all the tested cultures. Mefloquine is the drug of choice for U.S military deployed overseas and travelers. However, mefloquine causes adverse central nervous system effects, including posttraumatic stress disorder-like syndromes, suggesting that this compound accumulates in the brain at a relatively high concentrations, which compromises its use. We took advantage of this unique characteristic of mefloquine and showed that low dose (2.5 - 7.5mg/kg in mouse) of this compound achieve enough amounts in the brain and target the infiltrative DIPG reservoir, leading to tumor shrinkage, while avoiding the neurological side effects. We selected several commercially available mefloquine analogues and found that two of them have an enhanced effect with an IC50 <50 nM on DIPG cell cultures. These results warrant further investigation of these compounds in a clinical setting.
MEDU-01. HDACi AND PLK1i ACT SYNERGISTICALLY IN MYC-AMPLIFIED MEDULLOBLASTOMA
Authors: Gintvile Valinciute, Jonas Ecker, Thomas Hielscher, Christin Schmidt, Marc Remke, Gianluca Sigismondo, Jeroen Krijgsveld, Stefan Pfister, Olaf Witt, Till Milde
Journal: Neuro-Oncology (2019)

Medulloblastoma (MB) is the most common malignant brain tumor in children. Patients with MYC-amplified Group 3 MBs exhibit particularly poor survival rates even after intensive therapy, and surviving patients often suffer from long-term sequelae. Poor survival rates and sequelae call for new therapeutic strategies, such as targeted therapy options. We have previously shown that MYC-amplified MBs are sensitive to class I histone deacetylase (HDAC) inhibition. Here we investigate possible combinatorial treatment with HDACi and PLK1i. We evaluated the metabolic activity of MYC-amplified and non-amplified MB, high grade glioma (HGG) and neuroblastoma (NB) cell lines after single and combinatorial treatments with HDACi and PLK1i. The interaction effect was determined by combination index (CI) calculation using the Chou-Talalay method. On-target activity was examined by immunoblotting for pTCTP and H3K27ac. The findings were validated in an inducible MYC cell line. The gene expression profile in the MYC-amplified HD-MB03 cell line was analyzed after MS-275, volasertib or combination treatment. We show that the MYC target gene PLK1 is significantly downregulated upon HDACi treatment. We hypothesized that inhibition of both, HDACs and PLK1 could have synergistic effects. MYC-amplified cell lines were more sensitive than non-amplified cell lines to PLK1i showing 3–10 times lower IC50. PLK1i and HDACi interacted synergistically (CI below 0.9) in lower concentrations in MYC-amplified compared with non-amplified cell lines. Similar results were obtained for MYC or N-MYC-amplified HGG and NB cell lines. MYC target genes were significantly downregulated in the MYC-amplified cell line HD-MB03 after treatment with PLK1i and HDACi. Our data suggests that MYC-amplification is a predictive marker for PLK1i treatment in MB and other entities. The combination of HDACi and PLKi could be a candidate therapy for MYC-amplified group 3 MB, and possibly other tumors harboring MYC amplification, in future clinical trials. Studies investigating the mechanism of action are ongoing.
Cost‐savings in hidradenitis suppurativa
Authors: M. Argyropoulou, T. Kanni, M. Kyprianou, N. Melachroinopoulos, E. J. Giamarellos‐Bourboulis
Journal: British Journal of Dermatology (2019)

Hidradenitis suppurativa (HS) is a common skin disorder that affects almost 1% of people in Europe. HS causes boils to form in areas of the skin with several sweat glands such as the armpit, breast, groin and the buttocks. The disease is characterized by periods in which the symptoms worsen and boils progressively enlarge and rupture with the production of pus and blood. This study, undertaken at the ATTIKON University Hospital of Athens, Greece, focuses on the treatment efficacy of HS with agents that block tumour necrosis factor protein (herein anti‐TNFs). In 2015, one anti‐TNF compound, adalimumab, was licensed for moderate to severe HS. The authors analyzed 250 patients with moderate to severe HS under long‐term follow‐up and they investigated the impact of anti‐TNFs on preventing exacerbations (worsening of the symptoms) and on the cost of treating HS. The authors found that treatment with anti‐TNFs decreased the frequency of exacerbations by 38%; this was achieved both in moderate and severe HS. The authors calculated the cost of patient‐visits separately when under other therapies and separately under treatment with anti‐TNFs. After subtracting the cost of each injection, the authors found that the cost‐saving achieved with anti‐TNFs was €178.92 per visit. The mean year cost for the most severe patients was €8309.6 under other therapies and €3262.2 under anti‐TNFs. These cost findings are for adalimumab, the cost of which was used for the calculations. The results of this study therefore suggest that adalimumab could be a cost‐effective and efficient treatment for HS.
Treatment-Related Adverse Events of PD-1 and PD-L1 Inhibitors in Clinical Trials
Authors: Yucai Wang, Shouhao Zhou, Fang Yang, Xinyue Qi, Xin Wang, Xiaoxiang Guan, Chan Shen, Narjust Duma, Jesus Vera Aguilera, Ashish Chintakuntlawar, Katharine A. Price, Julian R. Molina, Lance C. Pagliaro, Thorvardur R. Halfdanarson, Axel Grothey, Svetomir N. Markovic, Grzegorz S. Nowakowski, Stephen M. Ansell, Michael L. Wang
Journal: JAMA Oncology (2019)

Programmed cell death (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in cancer therapy. Understanding the treatment-related adverse events of these drugs is critical for clinical practice.To evaluate the incidences of treatment-related adverse events of PD-1 and PD-L1 inhibitors and the differences between different drugs and cancer types.PubMed, Web of Science, Embase, and Scopus were searched from October 1, 2017, through December 15, 2018.Published clinical trials on single-agent PD-1 and PD-L1 inhibitors with tabulated data on treatment-related adverse events were included.Trial name, phase, cancer type, PD-1 and PD-L1 inhibitor used, dose escalation, dosing schedule, number of patients, number of all adverse events, and criteria for adverse event reporting data were extracted from each included study, and bayesian multilevel regression models were applied for data analysis.Incidences of treatment-related adverse events and differences between different drugs and cancer types.This systematic review and meta-analysis included 125 clinical trials involving 20 128 patients; 12 277 (66.0%) of 18 610 patients from 106 studies developed at least 1 adverse event of any grade (severity), and 2627 (14.0%) of 18 715 patients from 110 studies developed at least 1 adverse event of grade 3 or higher severity. The most common all-grade adverse events were fatigue (18.26%; 95% CI, 16.49%-20.11%), pruritus (10.61%; 95% CI, 9.46%-11.83%), and diarrhea (9.47%; 95% CI, 8.43%-10.58%). The most common grade 3 or higher adverse events were fatigue (0.89%; 95% CI, 0.69%-1.14%), anemia (0.78%; 95% CI, 0.59%-1.02%), and aspartate aminotransferase increase (0.75%; 95% CI, 0.56%-0.99%). Hypothyroidism (6.07%; 95% CI, 5.35%-6.85%) and hyperthyroidism (2.82%; 95% CI, 2.40%-3.29%) were the most frequent all-grade endocrine immune-related adverse events. Nivolumab was associated with higher mean incidences of all-grade adverse events compared with pembrolizumab (odds ratio [OR], 1.28; 95% CI, 0.97-1.79) and grade 3 or higher adverse events (OR, 1.30; 95% CI, 0.89-2.00). PD-1 inhibitors were associated with a higher mean incidence of grade 3 or higher adverse events compared with PD-L1 inhibitors (OR, 1.58; 95% CI, 1.00-2.54).Different PD-1 and PD-L1 inhibitors appear to have varying treatment-related adverse events; a comprehensive summary of the incidences of treatment-related adverse events in clinical trials provides an important guide for clinicians.