tbuckley/cabot-search huggingface dataset:
The Risk for Sudden Cardiac Death Among Patients Living With Heart Failure and Human Immunodeficiency Virus
Authors: Raza M. Alvi, Anne M. Neilan, Noor Tariq, Malek O. Hassan, Magid Awadalla, Lili Zhang, Maryam Afshar, Adam Rokicki, Connor P. Mulligan, Virginia A. Triant, Markella V. Zanni, Tomas G. Neilan
Journal: JACC Heart Failure (2019)
Abstract 16456: Is Trisomy 21 a Risk Factor for Rapid Progression of Pulmonary Arteriopathy? -Revisit Histopathological Characteristics Based on 282 Lung Biopsy Specimens
Authors: Naoki Masaki, Yuriko Saiki, Masato Endo, Kay Maeda, Koyu Watanabe, Shingo Takahara, Ko Sakatsume, Katsuhiro Hosoyama, Yukihiro Hayatsu, Satoshi Kawatsu, Ichiro Yoshioka, Shinya Masuda, Kiichiro Kumagai, Osamu Adachi, Masatoshi Akiyama, Shunsuke Kawamoto, Yoshikatsu Saiki
Journal: Circulation (2016)

Background: Pulmonary hypertension (PH) is clinically known to be more progressive in trisomy 21 patients than non-trisomy 21, the same seems to be applicable to pulmonary arteriopathy. However, pu...
The Role of the Microbiome in Drug Response
Authors: Rosina Pryor, Daniel Martinez-Martinez, Leonor Quintaneiro, Filipe Cabreiro
Journal: The Annual Review of Pharmacology and Toxicology (2019)

The microbiome is known to regulate many aspects of host health and disease and is increasingly being recognized as a key mediator of drug action. However, investigating the complex multidirectional relationships between drugs, the microbiota, and the host is a challenging endeavor, and the biological mechanisms that underpin these interactions are often not well understood. In this review, we outline the current evidence that supports a role for the microbiota as a contributor to both the therapeutic benefits and side effects of drugs, with a particular focus on those used to treat mental disorders, type 2 diabetes, and cancer. We also provide a snapshot of the experimental and computational tools that are currently available for the dissection of drug-microbiota-host interactions. The advancement of knowledge in this area may ultimately pave the way for the development of novel microbiota-based strategies that can be used to improve treatment outcomes.
Early pubertal maturation and risk of childhood asthma: A Mendelian randomization and longitudinal study
Authors: Yang‐Ching Chen, Hsien‐Yu Fan, Chen Yang, Yungling L. Lee
Journal: Allergy (2019)

Abstract Background Studies on early puberty and incident asthma have reported inconsistent results and are mainly performed in females. In this longitudinal study, we investigated the causal relationship between pubertal maturation and asthma through Mendelian randomization ( MR ) and explored the joint effect of overweightness and early pubertal maturation on asthma. Methods We used data from the Taiwan Children Health Study with longitudinal follow‐ups of 2991 children aged 11‐17 years. Six puberty‐related single‐nucleotide polymorphisms (combined into a weighted allelic score) were used to yield genetic instrumental variables for early puberty. Early pubertal maturation was defined as reaching a certain pubertal stage earlier than the median age for that stage. Incident asthma cases were calculated by excluding children with a history of asthma prior to that age. Results The results of MR analysis revealed that early pubertal maturation was associated with active asthma ( OR = 1.18; 95% CI : 1.08‐1.28); this effect was significant in male children. Early pubertal maturation significantly increased the risk of incident asthma outcomes at 12 and 17 years of age in both sexes (hazard ratio = 2.15; 95% CI : 1.21‐3.84). Taking non‐overweight and non–early puberty children as the reference group, we observed a synergistic effect of overweightness and early pubertal maturation on asthma risk ( OR = 1.08; 95% CI : 1.04‐1.11) in children of both sexes. Conclusions Early screening and intervention for obesity are recommended to prevent future early pubertal onset and asthma occurrence.
Interobserver correlation of morphometric data obtained from routine preoperative abdominal CT scans in pancreatic surgery.
Authors: Tiffani Dawn Shelton, Jan Franko, Charles David Goldman, Shawna Grimm
Journal: Journal of Clinical Oncology (2013)

e20714 Background: Quantification of frailty is necessary for estimation of therapy tolerance. Sarcopenia is a recognized measure of frailty and predicts long-term survival in both non-surgical and surgical cohorts. Here we set to evaluate interobserver agreement for certain sarcopenia parameters on routine abdominal CT scans among patients undergoing Whipple procedure for suspicion of neoplasm. Methods: Two observers using a standardized protocol for measurements of linear and surface morphometric parameters independently reviewed thirty abdominal CT scans. Results: Mean morphometric data for the entire group were: total psoas area 2237±868 mm 2 , mean psoas muscle density 46±9 HU, mean psoas antero-posterior diameter 40±8mm, mean psoas latero-lateral diameter 36±8 mm, mean rectus muscle thickness 9.2±2.6 mm, mean distance between anterior vertebral L4 surface and linea alba 115±28 mm (L4-alba distance), mean subcutaneous fat thickness 23.7 ±11.5mm, mean L4 vertebra antero-posterior diameter 37.6±5.2 mm. Excellent inter-observer correlation was observed for total psoas area is R 2 =0.788, p&lt;0.001. Similarly good correlation was detected between observers for rectus muscle thickness (R 2 =0.6019, p&lt;0.001), subcutaneous fat thickness (R 2 =0.731, p&lt;0.001), and L4-alba distance (R 2 =0.601, p&lt;0.001). Poor correlation was observed for L4 diameter (R 2 =0.392,p=0.0014). No interobserver correlation was observed for psoas muscle density (R 2 =0.005, p=0.743). Conclusions: Excellent degree of interobserver correlation was observed for the following morphometric data obtained from abdominal CT scans: Total psoas muscle area, L4-alba distance, rectus muscle and subcutaneous fat thickness. Further studies are needed to evaluate utility of morphometric parameters for prediction of surgical outcomes.
Longitudinal evaluation of fine motor deficits in children with leukemia
Authors: M. J. Hockenberry, K. Krull, I. M. Moore, A. Pasvogel, M. Gregurich, K. Kaemingk
Journal: Journal of Clinical Oncology (2006)

8559 Background: Fine motor assessments are important tools to use in screening children undergoing treatment for acute lymphoblastic leukemia (ALL) that may provide decisive data that can reveal subtle changes in neurodevelopment over time. Methods: Fine motor and visual-motor skills were assessed longitudinally in a group of 83 children receiving treatment for ALL. Children in this study had the first fine motor assessment at an average of 8 weeks into treatment and had already received several doses of Vincristine. Fine motor and visual-motor skills assessments were repeated at years 1 and 2 into therapy. The mean age at time of first assessment was 7.2 years and 58% were female. Results: Fine motor speed deficits were evident at the first assessment, and for many, continued to be problematic at Years 1 and 2. In addition to fine motor speed deficits, a significant decline in visual motor integration skills was noted from the baseline level (p = 0.019). Visual motor integration skills observed at Years 1 and 2 were predicted by the baseline performance on the Purdue Pegboard test. Our results indicate that the factors underlying these declines in higher-level skills begin within six months of the onset of chemotherapy. Conclusions: Early reductions in fine motor speed, possibly due to Vincristine, steroids and/or acute Methotrexate toxicity, may lead to reduced visual motor integration and construction abilities. The reduced fine motor skills, which predict eventual declines in visual motor integration, may be part of the underlying process for reduced perceptual abilities and nonverbal intellect often reported in long-term follow-up studies. For children with ALL, motor and sensory-perceptual examinations during treatment may identify those most at risk for significant long-term effects interfering with integration of visual spatial construction. These basic processing skills are necessary elements to the development of higher-level cognitive abilities, including nonverbal intelligence and academic achievement, particularly in arithmetic and written language. Early identification of reduced processing skills can provide an opportunity to identify at risk patients and intervene prior to reduction in these higher-level skills. Supported by NIH/NICHD RO-1 Funding: Grant number HD 37816 No significant financial relationships to disclose.
Abstract 13776: Interaction of Baseline Left Ventricular Volume and Dyssynchrony on Long Term Prognosis After Cardiac Resynchronization Therapy
Authors: Bhupendar Tayal, Antonia Delgado-Montero, Akiko Goda, Samir Saba, Niels Risum, Peter Sogaard, John Gorcsan
Journal: Circulation (2015)

Background: Baseline dyssynchrony by radial strain (≥130 ms) has been associated with favorable outcome after cardiac resynchronization therapy (CRT) in heart failure (HF) patients with widened QRS. Because LV dilatation is associated with more advanced disease that is less responsive to CRT, we hypothesized that dyssynchrony has less prognistic value in patients with severely dilated LVs. Methods: We prospectively studied consecutive 260 CRT patients with class II-IV HF, LV EF ≤35%, and QRS≥120 ms. Assessment of dyssynchrony was done at mid-LV level by radial strain. Patients were divided into two groups based on the median value of end diastolic volume (EDV). Outcome events were death, LV assist device or transplantation over 4 years after CRT. Results: Out of 260 patients studied, 20 (8%) had poor image quality and 3 (1%) were lost to follow-up. Based on a median EDV of 180 ml: 121 (51%) had EDV≥180ml and 116 (49%) had EDV &lt;180ml. Patients with EDV≥180ml were more often male, with lower LVEF and were younger (p&lt;0.05). Baseline dyssynchrony by radial strain was detected with a higher percentage in EDV≥180ml group (p=0.02). There were 87 (37%) outcome events over 4 years. In the group with EDV&lt;180 ml, absence of dyssynchrony at baseline was associated with a significantly higher risk for events with adjusted hazard ratio 2.09, 95% confidence interval 1.05 to 4.17 (p=0.03) after adjusting for QRS duration, LBBB, ischemia and baseline LV EF. Dyssynchrony was not associated with events in those with more dilated LVs EDV≥180 ml (p=0.8). Conclusions: Significant baseline mechanical dyssynchony was of prognostic significance in CRT patients who had less LV dilatation. In contrast, baseline dyssynchony was not associated with outcomes after CRT in those with more severely dilated LVs, which may represent more advanced LV disease that is less responsive to CRT.
Resistance Training Increases Muscle Strength and Muscle Size in Patients With Liver Cirrhosis
Authors: Luise Aamann, Gitte Dam, Mette Borre, Aska Drljevic-Nielsen, Kristian Overgaard, Henning Andersen, Hendrik Vilstrup, Niels Kristian Aagaard
Journal: Clinical Gastroenterology and Hepatology (2019)
Phase I study of safety and pharmacokinetics of fruquintinib, a selective inhibitor of VEGF receptor-1, -2, and -3 tyrosine kinases in patients with advanced solid tumors.
Authors: Jin Li, Junning Cao, Jian Zhang, Songhua Fan, Yang Sai, Hua MU
Journal: Journal of Clinical Oncology (2012)

3038 Background: Fruquintinib is a novel oral small molecule compound discovered and developed by Hutchison MediPharma that selectively inhibits vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 and has demonstrated potent inhibitory effects on multiple human tumor xenografts. This first-in-human study is conducted to assess the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), safety and tolerability, pharmacokinetics (PK), and preliminary anti-tumor activity of fruquintinib. Methods: This phase I study used the 3+3 design for dose-escalation of fruquintinib given once daily (QD) in 28-day cycles in patients with solid tumors who had failed standard therapies. Endpoints included safety, PK, and preliminary efficacy measurements. Results: To date 16 patients were enrolled in 5 dose cohorts of 1-6 mg QD, with age 42-69 yr, 44% male, ECOG 0-1 and all heavily pretreated. Tumor types included 9 colorectal, 3 lung, 3 breast, and 2 gastric (one patient with bi-primary carcinoma of breast and colon). The most common adverse events included hypertension (50%), proteinuria (43.8%), hand-foot syndrome (HFS 43.8%), diarrhea (31.2%), and hoarseness (25%). Grade 3/4 AEs were diarrhea (25%), HFS (12.5%), thrombocytopenia (6.2%), and hyperbilirubinemia (6.2%). Three DLTs were observed: 2 grade 3 HFS both at 6mg and 1 grade 3 hyperbilirubinemia at 4mg. PK analysis showed good and rapid absorption followed by slow terminal elimination with a half-life of approximately 37 hours which was consistent across all dose groups. Both C max and AUC exhibited good dose proportionality over the studied dose range with low inter-patient variability following single and multiple doses. Among 8 evaluable patients, 2 (1 colorectal and 1 gastric) had confirmed partial response for more than 4 months; 5 had stable disease, including 3 SDs of 3-8 months. Conclusions: Fruquintinib was well tolerated at doses up to 4 mg QD to date and demonstrated excellent pharmacokinetic properties. Encouraging clinical activity was observed. Further clinical studies are warranted and under planning.
Prevalence of BRAF gene mutation in Thai sporadic colorectal cancer patients.
Authors: Krittiya Korphaisarn, Ekkapong Roothumnong, Akarin Nimmannit, Chanin Limwongse, Ananya Manuyakorn, Wipawi Klaisuban, Charuwan Akewanlop
Journal: Journal of Clinical Oncology (2012)

e14051 Background: The role of BRAF gene mutation has been studied for its association with prognosis of colorectal cancer (CRC). The prevalence was reported 10-15% in Caucasian patients. However, there is no existing data in Thai patients. This study aimed to determine the prevalence of BRAF V600E mutation, association with various clinicopathological features and outcome in Thai sporadic CRC patients. Methods: DNA was extracted from randomly selected formalin-fixed paraffin-embedded tumor blocks of CRC patients with stage I-IV receiving surgery of the primary tumors at Siriraj Hospital between 2006 and 2007. BRAF V600E mutation was performed by two-round allele-specific PCR and analysis using high sensitivity DHPLC. The association between patient characteristics and BRAF status with overall survival (OS) and disease free survival (DFS) were explored by Kaplan-Meier estimation and log-rank test together with Cox’s proportional hazard regression. Results: BRAF V600E mutation was identified in 7 out of 188 patients (3.7%). Four patients were female. There were more likely to found in tumors on the left side (n=4) compared with right side (n=2) and rectum (n=1). All patients with mutation had stage I-III diseases; one with stage I and 3 with stage II and III each. Four had moderately differentiated tumors. Six patients had neither lymphovascular nor perineural invasion. Patients with mutation seemed to have better survival. In multivariate analysis, BRAF mutation did not have major prognostic value regarding DFS or OS. Conclusions: The prevalence of BRAF V600E mutation in Thai sporadic CRC was 3.7% which was lower than what reported in Caucasian patients. Further study with larger number of patients is warranted to determine whether BRAF mutation has significant prognostic value.
External validation of somatic copy number alteration (SCNA) at chromosome 1q23.3 in advanced urothelial carcinoma (UC).
Authors: Markus Riester, Lillian Werner, Joaquim Bellmunt Molins, Shamini Selvarajah, Barbara Weir, Edward C. Stack, Rachel S. Park, Robert O'Brien, Fabio Augusto Barros Schutz, Toni K. Choueiri, Sabina Signoretti, Enrique Gallardo, Federico Rojo, Josep Lloreta Trull, Luigi Marchionni, William C Hahn, David Monty Berman, Philip W. Kantoff, Franziska Michor, Jonathan E. Rosenberg
Journal: Journal of Clinical Oncology (2012)

4585 Background: Advanced UC is associated with multiple SNCAs. To identify SCNA predictors of poor survival in advanced UC, we evaluated SCNAs in two cohorts of high-risk urothelial carcinoma of the bladder. Methods: We obtained DNA copy number data from bladder cancer patients in two independent cohorts [Spanish cohort (n= 93, Agilent aCGH 180k array) and Brigham and Women’s/Dana-Farber (BW/DF) cohort (n = 48, Affymetrix OncoScan FFPE Express 2.0)]. For the BW/DF cohort, we acquired copy number information from 30 primary tumors and 33 metastases. For 12 patients, both primary and matched metastases were available. The GISTIC method was used on GLAD segmented data to identify driver copy number lesions, and the NBC algorithm to identify recurrent breakpoints. Cox proportional hazards models were used to estimate the effect of the identified SCNAs on overall survival, defined as time from start of chemotherapy for metastatic disease (Spanish) or from metastatic recurrence (BW/DF). Copy numbers were incorporated in the Cox models as continuous measures. Statistical significance of optimal cutpoints was estimated with permutation tests. Copy number profiles of primary tumors and metastases were compared with hierarchical clustering. Results: Amplification of 1q23.3 was independently associated with overall survival in both cohorts (Spanish cohort: HR 3.98; 95% 1.64-9.67; p &lt; 0.03; C-statistic 0.54, 95% 0.45-0.65. BW/DF cohort: HR 6.28; 95% 1.84-21.4; p &lt; 0.042; C-statistic 0.62, 95% 0.48-0.76). Amplifications at 22q12.2 were enriched in patients who developed metastasis (p &lt; 0.05). A breakpoint analysis identified possible truncations of ITPR1 (Spanish: 15%; BW/DF: 25%) and PRIM2 (Spanish: 31% BW/DF: 12.5%) in large numbers of samples. For primary tumors with matched metastases, we observed that metastases clustered together with their primary tumors. Conclusions: External validation of the 1q23.3 amplification demonstrates the association of this SCNA with poor outcomes in advanced UC; the identification of the target of this copy number gain is ongoing. Gene truncations and their biological significance require further experimental investigation.
Cytokeratin 19 fragment (CYFRA21-1) to predict the efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in non-small cell lung cancer (NSCLC) harboring EGFR mutation.
Authors: Kosuke Tanaka, Akito Hata, Reiko Kaji, Shiro Fujita, Jumpei Takeshita, Takeshi Matsumoto, Kazuya Monden, Kazuma Nagata, Kyoko Otsuka, Shigeki Nanjo, Ryo Tachikawa, Kojiro Otsuka, Michio Hayashi, Keisuke Tomii, Nobuyuki Katakami
Journal: Journal of Clinical Oncology (2012)

10610 Background: EGFR mutation is independently associated with a favorable response in NSCLC patients receiving EGFR-TKIs, regardless of gender or smoking history. However, recent reports have indicated that squamous cell carcinoma patients harboring EGFR mutations show a worse response to EGFR-TKIs than adenocarcinoma patients. We hypothesized that serum CYFRA21-1 is a predictive marker in EGFR mutated patients treated with EGFR-TKIs. Methods: We retrospectively screened 160 NSCLC patients harboring EGFR mutations (exon 19 deletions, L858R in exon 21, or other minor mutations) who received either gefitinib or erlotinib between 1992 and 2011. Patients were screened for histology, sex, age, smoking status, efficacy of EGFR-TKI and tumor markers (CEA/CYFRA21-1) at initial diagnosis. Results: Out of 160 eligible patients treated with EGFR-TKIs, 77 patients with high CYFRA21-1 level (&gt;2 ng/ml) showed statistically shorter progression-free survival (PFS) than 83 patients with normal CYFRA21-1 level (median PFS 7.5 vs 14.0 months, p=0.006). No significant difference in PFS was observed between high CEA group (&gt;5 ng/ml) and normal CEA group (median PFS 8.6 vs 11.2 months, p=0.2423). Multivariate analysis revealed that high CYFRA21-1 level is independently associated with PFS (HR 1.35; p=0.002) as well as squamous cell carcinoma (HR 1.40; p=0.020) and performance status 2-4 (HR 2.63; p=0.003). No statistically significant difference in overall survival (OS) was observed between high CYFRA21-1 group and normal group (median OS 24.8 vs 39.1 months, p=0.104). Conclusions: High CYFRA level patients have significantly shorter PFS, which may indicate that this subgroup has a larger squamous component and thus less response to EGFR-TKIs. Serum CYFRA21-1 level is a predictive marker of EGFR-TKIs efficacy and EGFR mutated patients can be divided into two subgroups according to CYFRA21-1 level at initial diagnosis.
Prevalence of Mental Health Disorders Among Adults With Cerebral Palsy
Authors: Daniel G. Whitney, Seth A. Warschausky, Sophia Ng, Edward A. Hurvitz, Neil S. Kamdar, Mark D. Peterson
Journal: Annals of Internal Medicine (2019)

Persons with cerebral palsy (CP) have an increased risk for secondary chronic conditions during childhood, including mental health disorders. However, little is known about how these disorders affect adults with CP.To determine the prevalence of mental health disorders among adults with CP compared with those without CP.Cross-sectional.2016 Optum Clinformatics Data Mart.8.7 million adults (including 7348 adults with CP).Other neurodevelopmental comorbid conditions (intellectual disabilities, autism spectrum disorders, epilepsy) and 37 mental health disorders (as 6 categories) were identified on the basis of diagnosis codes. Direct age-standardized prevalence of the mental health disorder categories was estimated by sex for adults with CP alone, adults with CP and neurodevelopmental disorders, and adults without CP.Men with CP alone had higher age-standardized prevalence than men without CP for schizophrenic disorders (2.8% [95% CI, 2.2% to 3.4%] vs. 0.7%), mood affective disorders (19.5% [CI, 18.0% to 21.0%] vs. 8.1%), anxiety disorders (19.5% [CI, 18.0% to 21.0%] vs. 11.1%), disorders of adult personality and behavior (1.2% [CI, 0.8% to 1.6%] vs. 0.3%), and alcohol- and opioid-related disorders (4.7% [CI, 3.9% to 5.5%] vs. 3.0%). The same pattern was observed for women. Compared with adults with CP alone, those with CP and neurodevelopmental disorders had similar or higher age-standardized prevalence of the 6 mental health disorder categories, except for the lower prevalence of alcohol- and opioid-related disorders in men.Single claims code was used to define the cohort of interest. Information on the severity of CP was not available.Compared with adults without CP, those with CP have an elevated prevalence of mental health disorders, some of which may be more pronounced in patients with comorbid neurodevelopmental disorders.National Institute on Disability, Independent Living, and Rehabilitation Research.