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Priya S. Shankarappa Cody J. Peer Arman Odabas Cynthia L. McCully Rafael C. Garcia William D. Figg Katherine E. Warren 《Cancer chemotherapy and pharmacology》2020,85(5):1003-1007
Pexidartinib (PLX3397) is a colony-stimulating factor-1 receptor (CSF-1R) inhibitor under clinical evaluation for potential CNS tumor treatment. This study aims to evaluate plasma pharmacokinetic parameters and estimate CNS penetrance of pexidartinib in a non-human primate (NHP) cerebrospinal fluid (CSF) reservoir model. Five male rhesus macaques, each with a previously implanted subcutaneous CSF ventricular reservoir and central venous lines, were used. NHPs received a single dose of 40 mg/kg pexidartinib (human equivalent dose of 800 mg/m2), administered orally as 200 mg tablets. Serial paired samples of blood and CSF were collected at 0–8, 24, 48, and 72 h. Pexidartinib concentrations were assayed by Integrated Analytical Solutions, Inc. (Berkeley, CA, USA) using HPLC/MS/MS. Pharmacokinetic (PK) analysis was performed using noncompartmental methods. Samples from four NHPs were evaluable. Average (± SD) plasma PK parameters were as follows: Cmax = 16.50 (± 6.67) μg/mL; Tmax = 5.00 (± 2.58) h; AUClast = 250.25 (± 103.76) h*μg/mL; CL = 0.18 (± 0.10) L/h/kg. In CSF, pexidartinib was either quantifiable (n = 2), with Cmax values of 16.1 and 10.1 ng/mL achieved 2–4 h after plasma Tmax, or undetected at all time points (n = 2, LLOQCSF = 5 ng/mL). Pexidartinib was well-tolerated in NHPs, with no Grade 3 or Grade 4 toxicities. The CSF penetration of pexidartinib after single-dose oral administration to NHPs was limited. 相似文献
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Phantana-angkool April Voci Amy E. Warren Yancey E. Livasy Chad A. Beasley Lakesha M. Robinson Myra M. Hadzikadic-Gusic Lejla Sarantou Terry Forster Meghan R. Sarma Deba White Richard L. 《Annals of surgical oncology》2019,26(12):3874-3882
Annals of Surgical Oncology - The role of sentinel lymph node biopsy (SLNB) when ductal carcinoma in situ with microinvasion (DCISM) is identified on core biopsy is unclear. Our aim was to assess... 相似文献
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Ngai-Yin Chan Chi-Chung Choy Ho-Chuen Yuen Hoi-Fan Chow Ho-Fai Fong 《The Canadian journal of cardiology》2019,35(4):396-404
Background
Persistent iatrogenic atrial septal defect (iASD) is a common but poorly characterized complication after cryoballoon (CB) pulmonary vein isolation (PVI) procedures. We therefore investigate its prevalence, evolution, risk factors, and clinical outcomes in a prospective longitudinal study.Methods
A total of 108 patients (41 women, mean age 57 ± 11.3) underwent CB PVI for AF. Serial transesophageal echocardiography (TEE) was performed 9 months and then annually until 6 years after the procedure to study the characteristics of persistent iASD.Results
Persistent iASD occurred in 33 (30.6%) patients 9 months after CB PVI. Spontaneous closure of iASD was found in 6 (22.2%) and 3 (15.8%) patients 2 and 3 years after the procedures, respectively. No spontaneous closure was observed on 4, 5, and 6-year TEE follow-up. The projected long-term persistence rate of iASD after CB PVI was therefore 20% (30.6% × 0.778 × 0.842). Using multivariate logistic regression, a higher number of cryoapplications (≥ 2 minutes) was the only independent predictor of persistent iASD 9 months after CB PVI (odds ratio [OR] 1.207; 95% confidence interval [CI], 1.033-1.411, P = 0.018). Two (1.9%) patients with significantly larger iASD size than the others (long diameter 12.6 ± 0.8 vs 3.7 ± 1.5 mm, P < 0.001; short diameter 10.9 ± 0.2 vs 3 ± 1.1 mm, P < 0.001) required percutaneous closure because of exertional dyspnea and right ventricular enlargement. Over 129.7 patient-years follow-up, during which iASD persisted, there was no occurrence of neurologic events.Conclusions
Approximately one fifth of patients undergoing CB PVI will have permanently persistent iASD. Patients with defect sizes of greater than 10 mm may need percutaneous closure due to significant left-to-right shunting. 相似文献5.
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Hongxu Xian Yuan Liu Alexandra Rundberg Nilsson Raphaella Gatchalian Timothy R. Crother Warren G. Tourtellotte Yi Zhang German R. Aleman-Muench Gavin Lewis Weixuan Chen Sarah Kang Melissa Luevanos Dorit Trudler Stuart A. Lipton Pejman Soroosh John Teijaro Juan Carlos de la Torre Moshe Arditi Elsa Sanchez-Lopez 《Immunity》2021,54(7):1463-1477.e11
7.
Few studies have examined the effects of parental incarceration (PI) on outcomes above and beyond other risk and adverse childhood experiences (ACEs). The objectives of this study were to (1) the associations between PI and mental health problems (attention, externalizing, internalizing, and total behavioral problems) and (2) the mediating role of current socioeconomic status and cumulative ACEs. An observational and cross-sectional design was employed. Analyses included hierarchical multivariable linear regression modeling. The analytic sample included 613 adolescents (11–17?years). On average, youth exposed to PI experienced three times as many ACEs compared with youth unexposed. Youth exposed to PI were more likely to have behavioral problems than their unexposed peers. The main effect for all models was attenuated by current economic hardship as well as exposure to increasing numbers of ACEs. Exposure to PI can be viewed as a marker of accumulative risk for intervention since youth impacted by PI are more likely to experience behavioral difficulties and associated adverse childhood experiences. Due to the associated adversity that impact youth exposed to PI, mental health providers need to be able to identify and screen for symptoms associated with trauma. 相似文献
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Sarah E. R. Bailey Gary A. Abel Alex Atkins Rachel Byford Sarah-Jane Davies Joe Mays Timothy J. McDonald Jon Miller Catherine Neck John Renninson Paul Thomas Fiona M. Walter Sarah Warren Willie Hamilton 《British journal of cancer》2021,124(7):1231
Background The faecal immunochemical test (FIT) was introduced to triage patients with low-risk symptoms of possible colorectal cancer in English primary care in 2017, underpinned by little primary care evidence.Methods All healthcare providers in the South West of England (population 4 million) participated in this evaluation. 3890 patients aged ≥50 years presenting in primary care with low-risk symptoms of colorectal cancer had a FIT from 01/06/2018 to 31/12/2018. A threshold of 10 μg Hb/g faeces defined a positive test.Results Six hundred and eighteen (15.9%) patients tested positive; 458 (74.1%) had an urgent referral to specialist lower gastrointestinal (GI) services within three months. Forty-three were diagnosed with colorectal cancer within 12 months. 3272 tested negative; 324 (9.9%) had an urgent referral within three months. Eight were diagnosed with colorectal cancer within 12 months. Positive predictive value was 7.0% (95% CI 5.1–9.3%). Negative predictive value was 99.8% (CI 99.5–99.9%). Sensitivity was 84.3% (CI 71.4–93.0%), specificity 85.0% (CI 83.8–86.1%). The area under the ROC curve was 0.92 (CI 0.86–0.96). A threshold of 37 μg Hb/g faeces would identify patients with an individual 3% risk of cancer.Conclusions FIT performs exceptionally well to triage patients with low-risk symptoms of colorectal cancer in primary care; a higher threshold may be appropriate in the wake of the COVID-19 crisis.Subject terms: Digestive signs and symptoms, Diagnostic markers, Gastrointestinal cancer 相似文献
10.
Warren Clements Joseph Mathew Mark C. Fitzgerald Jim Koukounaras 《Journal of vascular and interventional radiology : JVIR》2021,32(4):586-592
Patients treated with splenic artery embolization (SAE) >48 hours after a blunt injury for a delayed splenic rupture (DSR) were assessed for the need for a subsequent splenectomy. Thirty-four patients underwent SAE for DSR over 10 years at our level 1 trauma center, performed at a median of 4.5 days after the injury (interquartile range = 5.5), and the patients were followed up for a median of 11 months (interquartile range = 31). There were 3 occurrences of rebleeds, and 2 patients required splenectomy (5.9%). This study showed that treatment with SAE after DSR results in splenic salvage in 94.1% of patients. 相似文献