Calcaneal BMD Obtained by Dual X-Ray and Laser Predicts Future Hip Fractures—A Prospective Study on 4 398 Swedish Women

The predictive value of dual X-ray and laser (DXL) calcaneal BMD (BMDDXL) on hip fractures was prospectively studied in 4,398 females aged 55 to 99 years. The average follow-up period was 3 years and 11 months with a total of 17,270 person years. Fractures were identified from the national patient register. After inclusion, 130 females sustained a hip fracture. The age adjusted hazard ratio for T-score <−2.5 versus >−2.5 was 2.64. Of all patients who sustained a hip fracture 78% had a T-score of −2.5 or below. The annual hip fracture rate was 0.26% at T-scores ≥−2, but 1.5% at T-scores ≤−2.5. The area under curve for the model including calcaneal BMDDXL, follow-up time, and age to prospectively predict hip fractures was 0.84. Conclusions. Calcaneal BMDDXL obtained by DXL Calscan predicts hip fractures and may therefore be suitable for diagnosing osteoporosis and for predicting fracture risk

A radiomics model based on preoperative gadoxetic acid–enhanced magnetic resonance imaging for predicting post-hepatectomy liver failure in patients with hepatocellular carcinoma

BackgroundPost-hepatectomy liver failure (PHLF) is a fatal complication after liver resection in patients with hepatocellular carcinoma (HCC). It is of clinical importance to estimate the risk of PHLF preoperatively.AimsThis study aimed to develop and validate a prediction model based on preoperative gadoxetic acid–enhanced magnetic resonance imaging to estimate the risk of PHLF in patients with HCC.MethodsA total of 276 patients were retrospectively included and randomly divided into training and test cohorts (194:82). Clinicopathological variables were assessed to identify significant indicators for PHLF prediction. Radiomics features were extracted from the normal liver parenchyma at the hepatobiliary phase and the reproducible, robust and non-redundant ones were filtered for modeling. Prediction models were developed using clinicopathological variables (Clin-model), radiomics features (Rad-model), and their combination.ResultsThe PHLF incidence rate was 24% in the whole cohort. The combined model, consisting of albumin–bilirubin (ALBI) score, indocyanine green retention test at 15 min (ICG-R15), and Rad-score (derived from 16 radiomics features) outperformed the Clin-model and the Rad-model. It yielded an area under the receiver operating characteristic curve (AUC) of 0.84 (95% confidence interval (CI): 0.77–0.90) in the training cohort and 0.82 (95% CI: 0.72–0.91) in the test cohort. The model demonstrated a good consistency by the Hosmer–Lemeshow test and the calibration curve. The combined model was visualized as a nomogram for estimating individual risk of PHLF.ConclusionA model combining clinicopathological risk factors and radiomics signature can be applied to identify patients with high risk of PHLF and serve as a decision aid when planning surgery treatment in patients with HCC

Copeptin is independently associated with vascular calcification in chronic kidney disease stage 5

Background: Vascular calcification (VC) is an independent predictor of cardiovascular disease (CVD) present in 30– 70% of patients with chronic kidney disease (CKD). Copeptin is a sensitive surrogate marker of arginine vasopressin (AVP), which is involved in many pathophysiologic processes in CKD. The aim of the present study was to explore the association of copeptin with VC in CKD stage 5. Methods: Copeptin was investigated in conjunction with living donor kidney transplantation in 149 clinically stable CKD stage 5 patients (CKD5), including 53 non-dialyzed (CKD5-ND) and 96 dialysis patients treated by peritoneal dialysis (PD) (n = 43) or hemodialysis (HD) (n = 53). We analyzed the association of copeptin with presence and extent of VC ascertained both histologically in biopsies from the inferior epigastric artery (n = 137) and by coronary artery calcification (CAC) score measured by computed tomography. Results: Patients with higher copeptin were older, had higher systolic blood pressure, higher prevalence of CVD and their preceding time on chronic dialysis was longer. In Spearman’s rank correlations (Rho), copeptin concentrations were significantly associated with CAC score (Rho = 0.27; p = 0.003) and presence of medial VC (Rho = 0.21; p = 0.016). Multivariate logistic regression analysis showed that 1-SD higher age, male gender, diabetes and 1-SD higher copeptin were significantly associated with the presence of moderate-extensive VC. Conclusions: High circulating levels of copeptin in CKD5 patients are independently associated with the degree of medial calcification ascertained by histology of arterial biopsies. Thus, plasma copeptin may serve as a marker of the uremic calcification process.Baxter HealthcareKarolinska Institutet Diabetes Theme CenterHeart and Lung FoundationNjurfondenWestmans FoundationEuropean Union’s Horizon 2020 research and innovation program, Marie Sklodowska-Curie (grant agreement No 722609)Publishe

Presynaptic actions of 4-Aminopyridine and γ-aminobutyric acid on rat sympathetic ganglia in vitro

Responses to bath-applications of 4-aminopyridine (4-AP) and -aminobutyric acid (GABA) were recorded intracellularly from neurones in the rat isolated superior cervical ganglion. 4-aminopyridine (0.1–1.0 mmol/l) usually induced spontaneous action potentials and excitatory postsynaptic potentials (EPSPs), which were blocked by hexamethonium. Membrane potential was unchanged; spike duration was slightly increased. Vagus nerve B-and C-fibre potentials were prolonged. In 4-AP solution (0.1–0.3 mmol/l), GABA (0.1 mmol/l), 3-aminopropanesulphonic acid or muscimol evoked bursts of spikes and EPSPs in addition to a neuronal depolarization. These bursts, which were not elicited by glycine, glutamate, taurine or (±)-baclofen, were completely antagonised by hexamethonium, tetrodotoxin or bicuculline methochloride. It is concluded that: (a) 4-AP has a potent presynaptic action on sympathetic ganglia; (b) presynaptic actions of GABA can be recorded postsynaptically in the presence of 4-AP; and (c) the presynaptic GABA-receptors revealed in this condition are similar to those on the postsynaptic membrane

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Calcium-Activated Potassium Channels BK and IK1 Are Functionally Expressed in Human Gliomas but Do Not Regulate Cell Proliferation

Gliomas are morbid brain tumors that are extremely resistant to available chemotherapy and radiology treatments. Some studies have suggested that calcium-activated potassium channels contribute to the high proliferative potential of tumor cells, including gliomas. However, other publications demonstrated no role for these channels or even assigned them antitumorogenic properties. In this work we characterized the expression and functional contribution to proliferation of Ca2+-activated K+ channels in human glioblastoma cells. Quantitative RT-PCR detected transcripts for the big conductance (BK), intermediate conductance (IK1), and small conductance (SK2) K+ channels in two glioblastoma-derived cell lines and a surgical sample of glioblastoma multiforme. Functional expression of BK and IK1 in U251 and U87 glioma cell lines and primary glioma cultures was verified using whole-cell electrophysiological recordings. Inhibitors of BK (paxilline and penitrem A) and IK1 channels (clotrimazole and TRAM-34) reduced U251 and U87 proliferation in an additive fashion, while the selective blocker of SK channels UCL1848 had no effect. However, the antiproliferative properties of BK and IK1 inhibitors were seen at concentrations that were higher than those necessary to inhibit channel activity. To verify specificity of pharmacological agents, we downregulated BK and IK1 channels in U251 cells using gene-specific siRNAs. Although siRNA knockdowns caused strong reductions in the BK and IK1 current densities, neither single nor double gene silencing significantly affected rates of proliferation. Taken together, these results suggest that Ca2+-activated K+ channels do not play a critical role in proliferation of glioma cells and that the effects of pharmacological inhibitors occur through their off-target actions