CDC42 promotes vascular calcification in chronic kidney disease

Vascular calcification is prevalent in patients with chronic kidney disease (CKD) and a major risk factor of cardiovascular disease. Vascular calcification is now recognised as a biological process similar to bone formation involving osteogenic differentiation of vascular smooth muscle cells (VSMCs). Cell division cycle 42 (CDC42), a Rac1 family member GTPase, is essential for cartilage development during endochondral bone formation. However, whether CDC42 affects osteogenic differentiation of VSMCs and vascular calcification remains unknown. In the present study, we observed a significant increase in the expression of CDC42 both in rat VSMCs and in calcified arteries during vascular calcification. Alizarin red staining and calcium content assay revealed that adenovirus-mediated CDC42 overexpression led to an apparent VSMC calcification in the presence of calcifying medium, accompanied with up-regulation of bone-related molecules including RUNX2 and BMP2. By contrast, inhibition of CDC42 by ML141 significantly blocked calcification of VSMCs in vitro and aortic rings ex vivo. Moreover, ML141 markedly attenuated vascular calcification in rats with CKD. Furthermore, pharmacological inhibition of AKT signal was shown to block CDC42-induced VSMC calcification. These findings demonstrate for the first time that CDC42 contributes to vascular calcification through a mechanism involving AKT signalling; this uncovered a new function of CDC42 in regulating vascular calcification. This may provide a potential therapeutic target for the treatment of vascular calcification in the context of CKD. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

The association between body mass index and in-hospital outcome among patients with acute myocardial infarction—Insights from China Acute Myocardial Infarction (CAMI) registry

BackgroundThe relationship between body mass index (BMI) and in-hospital mortality risk among patients with acute myocardial infarction (AMI) remains controversial.Methods and ResultsWe included 35,964 patients diagnosed with AMI in China Acute Myocardial Infarction registry between January 2013 and December 2016. Patients were categorized into 4 groups according to BMI level: BMI <18.5, 18.5–24.9, 25–30, and ≥30 kg/m² for underweight, normal, overweight, and obese groups, respectively. Clinical data were extracted for each patient, and multivariable logistic regression analysis was used to examine the association between BMI level and in-hospital mortality. Compared with normal-weight patients, obese patients were younger, more often current smokers, and more likely to have hypertension, hyperlipidemia, and diabetes. Multivariable regression analysis results demonstrated that compared with normal group, underweight group had significantly higher in-hospital mortality (odds ratio [OR]: 1.34; 95% confidence interval [CI]: 1.06–1.69; p = 0.016), while overweight group (OR: 0.86; 95% CI: 0.77–0.97; p = 0.011) and obese group (OR: 0.65; 95% CI: 0.46–0.91; p = 0.013) had lower mortality. All subgroups showed a trend toward lower in-hospital mortality risk as BMI increased.ConclusionsOur study provided robust evidence supporting “obesity paradox” in a contemporary large-scale cohort of patients with AMI and demonstrated that increased BMI was independently associated with lower in-hospital mortality.     

Hypertensive Crisis during Microwave Ablation of Adrenal Neoplasms: A Retrospective Analysis of Predictive Factors

PurposeTo identify risk factors for hypertensive crisis (HC) during ultrasound-guided percutaneous microwave (MW) ablation of adrenal neoplasms.Materials and MethodsPatients who underwent MW ablation for adrenal tumors between April 2006 and November 2017 were retrospectively identified for this study (51 consecutive patients; 35 males, 16 females; mean age, 55 years; range, 15–85 years). A total of 77 MW ablation treatments were performed for 67 tumors (24 primary [9 pheochromocytomas, 8 adenomas, and 7 cortical carcinomas]; and 43 metastases [22 hepatocellular carcinoma, 8 renal cell carcinoma, 5 non-small cell lung cancer, 4 colorectal cancer, 3 liposarcoma, and 1 malignant fibrous histiocytoma]). The mean diameter of the adrenal tumors was 4.6 cm (range, 1.2–16.2 cm). Information about patient demographics, imaging studies, pathology and laboratory results, procedure records, and clinical outcomes was retrieved and analyzed. Statistical analysis was then performed to determine potential risk factors for HC.ResultsOf the 77 MW ablation procedures, HC occurred in 13 (16.9%). A significantly higher risk of HC was observed in patients with pheochromocytoma (odds ratio [OR], 9.037; 95% confidence interval [CI], 1.731–47.172; P = .009), body mass index <24 kg/m² (OR, 5.167; 95% CI, 1.060–25.194; P = .042), dominant tumor size ≤4.5 cm (OR, 4.023; 95% CI, 1.011–16.005; P = .048), and pre-procedural systolic blood pressure ≥130 mmHg (OR, 0.242; 95% CI, 0.068–0.861; P = .029).ConclusionHC can occur during MW ablation in patients with either primary or metastatic adrenal tumors. Pheochromocytoma, body mass index, tumor size, and pre-procedural systolic blood pressure appear to be significant risk factors for the occurrence of HC.     

Maximal calf circumference reflects calf muscle mass measured using magnetic resonance imaging

BackgroundCalf circumference (CC) has been used as a surrogate for calf muscle mass, which facilitates venous blood return to the heart through active skeletal muscle. However, the correlation between CC and calf muscle mass has not been extensively examined. This study aimed to examine the relationship between CC and calf muscle mass considering differences in sex and physique in elderly individuals.MethodsA total of 124 community-dwelling elderly individuals ≥60 years of age (61 men, mean [±SD] age 74.3 ± 5.7 years) were enrolled. Maximal CC was measured using a tape measure with the subject supine. The cross-sectional area of skeletal muscle tissues was measured using magnetic resonance imaging from the point of greatest calf circumference to 5 cm proximal and distal. Calf muscle mass was calculated by multiplying the area of each slice by slice thickness (5 mm).ResultsCC was strongly correlated with calf muscle mass in male and female subjects (male: r = 0.908, P < 0.001; female: r = 0.892, P < 0.001). Multiple regression analysis revealed that CC and body mass index (BMI) were independent associate factors of calf muscle mass. The following estimation formulae were derived: (male) calf muscle mass (cm³) = 47.82 × CC (cm)−12.50 × BMI (kg/m²) −732.80; (female) calf muscle mass (cm³) = 32.23 × CC (cm) −4.85 × BMI (kg/m²) −429.94.ConclusionsA strong correlation was found between CC and calf muscle mass according to magnetic resonance imaging. Sex differences and BMI should be considered for accurate estimation of calf muscle mass using CC.     

Assessment of volume preservation performed before or after partial nephrectomy accurately predicts postoperative renal function: Results from a prospective multicenter study

Purpose

Partial nephrectomy (PN) is standard for small renal masses, improving renal function by preserving renal parenchyma compared with radical nephrectomy. Recent work demonstrated that postoperative surgeon assessment of volume preservation (SAVP) and 3D imaging measurements agree and correlate with postoperative function. We hypothesize preoperative assessment of volume preservation (PAVP) with PN based on preoperative imaging will reliably indicate postoperative renal function.

Extracapsular extension in oral cavity cancers—predictive factors and impact on recurrence pattern and survival

Extracapsular extension (ECE) has long been considered a poor prognostic factor in oral cavity cancer, the presence of which warrants intensification of adjuvant therapy. This study was done to analyze the survival of patients with ECE who received adjuvant chemoradiation. Patients with pathologically confirmed squamous cell carcinoma of the oral cavity, with a minimum of 2 years of follow-up, who were treated at a tertiary cancer centre in New Delhi, India during the years 2009–2017, were included. On multivariate analysis, ECE was significantly associated with depth of invasion >10 mm and tumour deposit size >5 mm. Among the node-positive group, patients without ECE had a 5-year disease-free survival (DFS) and 5-year overall survival (OS) advantage over ECE-positive patients of 7.8% (63.8% vs. 56.0%) and 16.5% (87.2% vs. 70.7%), respectively. For patients with ECE, the hazard ratio for DFS and OS was 1.3 (95% confidence interval 0.97–1.75, P = 0.078) and 2.30 (95% confidence interval 1.35–3.92, P = 0.002), respectively. ECE remains one of the strongest predictors of recurrence and survival in oral cancer patients, and despite aggressive adjuvant therapy, distant recurrence is still significantly high.     

Gender equity: how do the forensic sciences fare?

ABSTRACT

Females are underrepresented in science, technology, engineering and mathematics (STEM) at all levels of society. Fewer females are completing STEM school subjects, graduating with STEM degrees, being employed as STEM professionals, and holding senior leadership and academic positions in STEM. However, unlike almost every other STEM discipline, the overall ratio of females is higher in many forensic science disciplines. For our sector, rather than having difficulty in attracting females, the bigger issue is how we retain and promote female talent. This complex issue is exacerbated by: gender pay gaps; family role expectations; lack of visible role models or mentors; discrimination and harassment; and bias during recruitment and promotion practices. We discuss barriers relevant for women in the forensic industry and offer potential solutions. These include flexible work arrangements, sponsorship programmes, and fostering and practising an inclusive workplace culture. Gender equity programmes and exemplar STEM organizations focused on a commitment to gender parity will be explored. Harnessing untapped female talent is as much a social justice issue as employing best practices for improving the quality, diversity and output of our forensic science workforce, and research and innovation strategies.