Aims Brugada syndrome (BrS) is characterized by a unique electrocardiogram (ECG) pattern and life-threatening arrhythmias. However, the Type 1 Brugada ECG pattern is often transient, and a genetic cause is only identified in <25% of patients. We sought to identify an additional biomarker for this rare condition. As myocardial inflammation may be present in BrS, we evaluated whether myocardial autoantibodies can be detected in these patients. Methods and results For antibody (Ab) discovery, normal human ventricular myocardial proteins were solubilized and separated by isoelectric focusing (IEF) and molecular weight on two-dimensional (2D) gels and used to discover Abs by plating with sera from patients with BrS and control subjects. Target proteins were identified by mass spectrometry (MS). Brugada syndrome subjects were defined based on a consensus clinical scoring system. We assessed discovery and validation cohorts by 2D gels, western blots, and ELISA. We performed immunohistochemistry on myocardium from BrS subjects (vs. control). All (3/3) 2D gels exposed to sera from BrS patients demonstrated specific Abs to four proteins, confirmed by MS to be α-cardiac actin, α-skeletal actin, keratin, and connexin-43, vs. 0/8 control subjects. All (18/18) BrS subjects from our validation cohorts demonstrated the same Abs, confirmed by western blots, vs. 0/24 additional controls. ELISA optical densities for all Abs were elevated in all BrS subjects compared to controls. In myocardium obtained from BrS subjects, each protein, as well as SCN5A, demonstrated abnormal protein expression in aggregates. Conclusion A biomarker profile of autoantibodies against four cardiac proteins, namely α-cardiac actin, α-skeletal actin, keratin, and connexin-43, can be identified from sera of BrS patients and is highly sensitive and specific, irrespective of genetic cause for BrS. The four involved proteins, along with the SCN5A-encoded Nav1.5 alpha subunit are expressed abnormally in the myocardium of patients with BrS.

Clinical and radiological related outcomes have been reported for Chevron osteotomy as correction for mild to moderate hallux valgus, but only for relatively small patient series. Moreover, evaluation of the patient's point of view has mostly been conducted by means of more physician-based outcome measures. The goal of this study was to evaluate the effect of the Chevron osteotomy for hallux valgus on patients' daily lives using the Foot and Ankle Outcome Score (FAOS) as a validated and a hallux valgus specific patient reported outcome measure (PROM). Secondary outcome measures were radiological correction, complication rate, and re-operations. All 438 Chevron procedures (336 patients), at two surgical hospital sites in the period between January 2010 and October 2014, were retrospectively evaluated with a follow-up of at least 6 months. Patients were invited to fill in a cross-sectional online FAOS. For the FAOS, a total response of 60% was achieved. The FAOS ranged between 71 and 88 with a follow-up of on average 36 months. Patients with an undercorrection of their hallux valgus (11.6% of the procedures) scored significantly lower on three subscales of the FAOS (range between 61 and 77 versus 72-84). Patients who had a reoperation (12.6% of the procedures) also scored significantly lower on four subscales: 58-100 versus 73-89. Postoperative radiological measurements improved significantly with a mean difference of 6.1 (5.9; 6.4) degrees for the intermetatarsal angle and 13.7 (13.0; 14.5) degrees for the hallux valgus angle. In this large study cohort, Chevron osteotomy for hallux valgus offers good PROM scores on FAOS. These scores were significantly lower in patients with radiological undercorrection or with a reoperation. Results of the FAOS appear to modulate with physician based outcomes and therapeutic incidents. Improvement of outcome may therefore well be possible by increased attention on these surgical details.

Rotation of the femoral component in total knee arthroplasty (TKA) is of high importance in respect of the balancing of the knee and the patellofemoral joint. Though it is shown that computer assisted surgery (CAOS) improves the anteroposterior (AP) alignment in TKA, it is still unknown whether navigation helps in finding the accurate rotation or even improving rotation. Therefore the aim of our study was to evaluate the postoperative femoral component rotation on computed tomography (CT) with the intraoperative data of the navigation system. In 20 navigated TKAs the difference between the intraoperative stored rotation data of the femoral component and the postoperative rotation on CT was measured using the condylar twist angle (CTA). This is the angle between the epicondylar axis and the posterior condylar axis. Statistical analysis consisted of the intraclass correlation coefficient (ICC) and Bland-Altman plot. The mean intraoperative rotation CTA based on CAOS was 3.5° (range 2.4–8.6°). The postoperative CT scan showed a mean CTA of 4.0° (1.7–7.2). The ICC between the two observers was 0.81, and within observers this was 0.84 and 0.82, respectively. However, the ICC of the CAOS CTA versus the postoperative CT CTA was only 0.38. Though CAOS is being used for optimising the position of a TKA, this study shows that the (virtual) individual rotational position of the femoral component using a CAOS system is significantly different from the position on a postoperative CT scan.

Obesity is associated with diseases such as dyslipidemia, type 2 diabetes, and cardiovascular disease (CVD). The accumulation of lipids in numerous tissues is accompanied by increased infl ammatory processes such as macrophage infi ltration and production of infl ammatory mediators in Abstract Low-grade infl ammation in different tissues, including activation of the nuclear factor B pathway in liver, is involved in metabolic disorders such as type 2 diabetes and cardiovascular diseases (CVDs). In this study, we investigated the relation between chronic hepatocyte-specifi c overexpression of IkB kinase (IKK)-␤ and hypertriglyceridemia, an important risk factor for CVD, by evaluating whether activation of IKK-␤ only in the hepatocyte affects VLDL-triglyceride (TG) metabolism directly. Transgenic overexpression of constitutively active human IKK-␤ specifi cally in hepatocytes of hyperlipidemic APOE*3-Leiden mice clearly induced hypertriglyceridemia. Mechanistic in vivo studies revealed that the hypertriglyceridemia was caused by increased hepatic VLDL-TG production rather than a change in plasma VLDL-TG clearance. Studies in primary hepatocytes showed that IKK-␤ overexpression also enhances TG secretion in vitro, indicating a direct relation between IKK-␤ activation and TG production within the hepatocyte. Hepatic lipid analysis and hepatic gene expression analysis of pathways involved in lipid metabolism suggested that hepatocyte-specifi c IKK-␤ overexpression increases VLDL production not by increased steatosis or decreased FA oxidation, but most likely by carbohydrate-responsive element binding protein-mediated upregulation of Fas expression. These fi ndings implicate that specifi c activation of infl ammatory pathways exclusively within hepatocytes induces hypertriglyceridemia. Furthermore, we identify the hepatocytic IKK-␤ pathway as a possible target to treat hypertriglyceridemia. Abbreviations: Abcg5 , ATP-binding cassette sub-family G member 5; Abcg8 , ATP-binding cassette sub-family G member 8; Acox1 , acylCoenzyme A oxidase 1; apo, apolipoprotein; ChREBP, carbohydrateresponsive element binding protein; Cidea , cell death activator CIDE-A; Cidec , fat-specifi c protein FSP27; Cpt1a , carnitine palmitoyltransferase 1a; CVD, cardiovascular disease; Cyclo , cyclophilin; Cyp27a1 , cholesterol 27 hydroxylase; Cyp7a1 , cholesterol 7 alpha hydroxylase; Cyp8b1 , sterol 12 alpha-hydrolase; Dgat1 , acyl:diacylglycerol transferase 1; E3L, APOE*3-Leiden; FAME, fatty acid methyl ester; Fas , fatty acid synthase; FPLC, fast-performance liquid chromatography; Gapdh , glyceraldehyde-3-phosphate dehydrogenase; Hmgcr , HMG-CoA reductase; I B, inhibitor of B; IKK-␤ , I B kinase ␤ ; LIKK, liver-specifi c IKK-␤ overexpression; Mttp , microsomal triglyceride transfer protein; NF-B, nuclear factor-B; Nr1 h3 , liver X receptor alpha; Nr1 h4 , farnesoid X activated receptor; Pklr, liver-type pyruvate kinase; PL, phospholipid; Plin2 , perilipin 2; Plin5 , perilipin 5; Ppara , peroxisome proliferator activated receptor alpha; Ppargc...