Expression of the TGF-β–ALK-1 Pathway in Dura and the Outer Membrane of Chronic Subdural Hematomas

Neovascularization of the outer membrane plays a critical role in the development and enlargement of chronic subdural hematomas (CSHs) and vascular endothelial growth factor (VEGF) may promote their progression. However, the precise mechanisms remain to be determined. We focused on the signaling pathway upstream of VEGF, transforming growth factor β (TGF-β), and activin receptor-like kinase 1 (ALK-1) to identify the mechanisms underlying the neovascularization of the outer membrane of CSH. Retrospective comparative study was conducted on 15 consecutive patients diagnosed as CSH with burr-hole drainage. Dura and the outer membrane were collected. We immunohistochemically examined the expression of VEGF, integrin-α, TGF-β, and ALK-1 on the outer membrane and dura of CSH and compared our findings with control samples and the signal intensity of hematomas on computed tomography (CT) scans. VEGF and integrin-α expression was markedly up-regulated in both the dura and outer membrane of CSH, the expression of TGF-β and ALK-1 in the dura was slightly increased in the dura and markedly up-regulated in the outer membrane. There was no significant correlation between their expression and CT density. Here we first report the expression of TGF-β and ALK-1 in the outer membrane and dura mater of CSH. We suggest that the TGF-β–ALK-1 pathway and VEGF affect neovascularization and the progression of CSH.     

Occupational Factors and Problem Drinking among a Japanese Working Population

Problem drinking is a serious public health problem in the workplace. However, few Japanese epidemiological studies have investigated the occupational characteristics of problem drinking. The purpose of this study is to clarify the occupational risk factors for problem drinking among a Japanese working population. We used data from a random-sampling survey about mental health and suicide, conducted among Hamamatsu City residents aged 15 to 79 yr old during May and June in 2008. The relation between occupational factors and problem drinking was analyzed with multiple logistic regression models stratified by gender. CAGE questionnaire was used to assess problem drinking. With regard to employment types, problem drinkers were more prevalent among self-employed women. With regard to occupational types, clerical and service professions had more problem drinkers of either sex, while administrative/managerial and sales professions had more women with such problem. With regard to company size, male problem drinkers were more prevalent in smaller companies than in larger ones. These results indicate that the prevalence of problem drinkers in the workplace depends on where one works. It is necessary to consider these characteristics to provide effective measures to address problem drinking in the workplace.     

Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab

Background Post hoc analyses assessed the prognostic and predictive value of baseline alpha-fetoprotein (AFP), as well as clinical outcomes by AFP response or progression, during treatment in two placebo-controlled trials (REACH, REACH-2).Methods Serum AFP was measured at baseline and every three cycles. The prognostic and predictive value of baseline AFP was assessed by Cox regression models and Subpopulation Treatment Effect Pattern Plot method. Associations between AFP (≥ 20% increase) and radiographic progression and efficacy were assessed.Results Baseline AFP was confirmed as a continuous (REACH, REACH-2; p < 0.0001) and dichotomous (≥400 vs. <400 ng/ml; REACH, p < 0.01) prognostic factor, and was predictive for ramucirumab survival benefit in REACH (p = 0.0042 continuous; p < 0.0001 dichotomous). Time to AFP (hazard ratio [HR] 0.513; p < 0.0001) and radiographic (HR 0.549; p < 0.0001) progression favoured ramucirumab. Association between AFP and radiographic progression was shown for up to 6 (odds ratio [OR] 5.1; p < 0.0001) and 6–12 weeks (OR 1.8; p = 0.0065). AFP response was higher with ramucirumab vs. placebo (p < 0.0001). Survival was longer in patients with an AFP response than patients without (13.6 vs. 5.6 months, HR 0.451; 95% confidence interval, 0.354–0.574; p < 0.0001).Conclusions AFP is an important prognostic factor and a predictive biomarker for ramucirumab survival benefit. AFP ≥ 400 ng/ml is an appropriate selection criterion for ramucirumab.Clinical Trial Registration ClinicalTrials.gov, REACH ({"type":"clinical-trial","attrs":{"text":"NCT01140347","term_id":"NCT01140347"}}NCT01140347) and REACH-2 ({"type":"clinical-trial","attrs":{"text":"NCT02435433","term_id":"NCT02435433"}}NCT02435433).Subject terms: Oncology, Biomarkers     

Oxidative stress and endothelial dysfunction: Clinical evidence and therapeutic implications

An imbalance of nitric oxide (NO) and reactive oxygen species (ROS), so-called “oxidative stress,” may promote endothelial dysfunction, leading to cardiovascular complications. Activation of nicotinamide–adenine dinucleotide phosphate oxidase, xanthine oxidase, cyclooxygenase, and mitochondrial electron transport, inactivation of the antioxidant system, and uncoupling of endothelial NO synthase lead to oxidative stress along with an increase in ROS production and decrease in ROS degradation. Although experimental studies, both in vitro and in vivo, have shown a critical role of oxidative stress in endothelial dysfunction under the condition of excessive oxidative stress, there is little information on whether oxidative stress is really involved in endothelial function in humans. In a clinical setting, we showed an association between oxidative stress and endothelial function, especially in patients with renovascular hypertension as a model of increased oxidative stress and in patients with Gilbert syndrome as a model of decreased oxidative stress, through an increase in the antioxidant property of unconjugated bilirubin.     

Timing of Uterine Artery Embolization for Leiomyoma during the Menstrual Cycle

PurposeTo investigate differences in outcomes of uterine artery embolization (UAE) for leiomyoma when performed during different phases of the menstrual cycle.Materials and MethodsIn this single-institution retrospective analysis, 111 premenopausal patients (median [range] age, 44 [33–52] years) undergoing UAE for symptomatic leiomyoma between June 2014 and February 2020 were included. Twenty-one patients underwent UAE in the menstrual phase (the early follicular phase), 27 in the late follicular phase, and 63 in the luteal phase. Baseline characteristics and technical and peri-procedural outcomes were compared among groups. Leiomyoma infarction on contrast-enhanced magnetic resonance imaging 1 week after UAE and 4-month outcomes, including changes in the Uterine Fibroid Symptom and Quality of Life questionnaire scores, the volume reduction rates of the uterus and largest leiomyoma, follicle stimulating hormone values, adverse events, and amenorrhea, were compared among groups.ResultsA 4-month follow-up was completed for all patients. No significant differences were observed among groups in baseline characteristics or technical and peri-procedural outcomes. There were no significant differences in the multivariate-adjusted 1-week infarction rates of all leiomyoma volumes (P = .161) or multivariate-adjusted 4-month outcomes, including changes in the Uterine Fibroid Symptom and Quality of Life questionnaire symptoms and total scores (P = .864 and P = .798, respectively), the volume reduction rates of the uterus and the largest leiomyoma (P = .865 and P = .965, respectively), and follicle stimulating hormone values (P = .186) among the groups. No significant differences were noted in the 4-month adverse events (P = .260) or amenorrhea (P = .793) among the groups.ConclusionsThe present study demonstrated no significant differences in the outcomes of UAE for leiomyoma when performed during different phases of the menstrual cycle.