Identification and Functional Analysis of APOB Variants in a Cohort of Hypercholesterolemic Patients.

Mutations in APOB are the second most frequent cause of familial hypercholesterolemia (FH). APOB is highly polymorphic, and many variants are benign or of uncertain significance, so functional analysis is necessary to ascertain their pathogenicity. Our aim was to identify and characterize APOB variants in patients with hypercholesterolemia. Index patients (n = 825) with clinically suspected FH were analyzed using next-generation sequencing. In total, 40% of the patients presented a variant in LDLR, APOB, PCSK9 or LDLRAP1, with 12% of the variants in APOB. These variants showed frequencies in the general population lower than 0.5% and were classified as damaging and/or probably damaging by 3 or more predictors of pathogenicity. The variants c.10030A>G;p.(Lys3344Glu) and c.11401T>A;p.(Ser3801Thr) were characterized. The p.(Lys3344Glu) variant co-segregated with high low-density lipoprotein (LDL)-cholesterol in 2 families studied. LDL isolated from apoB p.(Lys3344Glu) heterozygous patients showed reduced ability to compete with fluorescently-labelled LDL for cellular binding and uptake compared with control LDL and was markedly deficient in supporting U937 cell proliferation. LDL that was carrying apoB p.(Ser3801Thr) was not defective in competing with control LDL for cellular binding and uptake. We conclude that the apoB p.(Lys3344Glu) variant is defective in the interaction with the LDL receptor and is causative of FH, whereas the apoB p.(Ser3801Thr) variant is benign.

Primary closure of the midline abdominal wall defect during laparoscopic ventral hernia repair: analysis of risk factors for failure and outcomes at 5 years follow-up.

BACKGROUND: The primary aim of this prospective study is to report bulging and recurrence rates and to analyze the risk factors responsible for failure, after laparoscopic ventral hernia repair (LVHR) with primary closure of defect (PCD) using a running suture and intraperitoneal mesh placement, at 5-year follow-up. The secondary endpoint is to evaluate 30-day postoperative complications, seroma, and pain. METHODS: PCD failure was defined as the presence of postoperative bulging and/or recurrence. Pain was evaluated using a visual analogue scale (VAS). After surgery, fifty-eight patients underwent clinical examination and computed tomography scan to diagnose bulging, recurrence, and seroma (classified according to the Morales-Conde classification). RESULTS: At 60 months follow-up, recurrence was observed in five patients (8.6%), while bulging, not needing a surgical treatment, occurred in fifteen patients (25.9%). Chronic obstructive pulmonary disease (COPD) is the only risk factor responsible for both outcomes together, bulging and recurrences (p = 0.029), while other considered risk factors as gender, age, body mass index, diabetes, smoke habits, primary or incisional hernia and the ratio defect width/transverse abdominal axis did not achieve the statistically significance. Clinical seroma was diagnosed at one month in eight patients (13.8%). Seromas were observed at one year of follow-up. During the follow-up, pain reduction occurred. CONCLUSION: LVHR has evolved toward more anatomical concepts, with the current trend being the abdominal wall anatomical reconstruction to improve its functionality, reducing seroma rates. Based on results obtained, PCD is a reliable technique with excellent recurrence rate at 5 years follow-up, even when the defect closure may generate tension at the midline. On the other hand, this tension could be related with high bulging rate at long-term, particular in case of patients with COPD.

Early Physical Rehabilitation after Sentinel Lymph Node Biopsy in Breast Cancer: Is It Feasible and Safe?

The primary purpose of this research was to investigate the feasibility and safety of delivering an early supervised physical therapy intervention to women after sentinel lymph node biopsy (SLNB); furthermore, we aimed to provide explorative data on its effects. This was a single-site feasibility study. Pre- and post-evaluation was conducted from baseline to follow-up at 6 months. Primary outcomes were participant recruitment, participant retention, compliance with the intervention, and safety. Secondary outcomes were shoulder range of motion, handgrip strength, upper limb pain and disability, scar recovery, quality of life, and the incidence of axillary web syndrome (AWS) and/or lymphoedema. A total of 43 participants (mean age 55.37 years) completed the trial and the follow-up period. A total of 91% of women who met the inclusion criteria agreed to participate, and the adherence rate was 80%. No adverse events were reported. Incidence of AWS was 9.3%, and there was no incidence of lymphoedema at 6 months. Our results support that this intervention is feasible and safe. The results presented in this study also provide preliminary evidence for the use of a rehabilitation program as a supportive intervention after SLNB, but future research on effectiveness is needed.

Effectiveness of virtual reality training for balance and gait rehabilitation in people with multiple sclerosis: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the evidence for the use of virtual reality to treat balance and gait impairments in multiple sclerosis rehabilitation. DESIGN: Systematic review and meta-analysis of randomized controlled trials and quasi-randomized clinical trials. METHODS: An electronic search was conducted using the following databases: MEDLINE (PubMed), Physiotherapy Evidence Database (PEDro), Cochrane Database of Systematic Reviews (CDSR) and (CINHAL). A quality assessment was performed using the PEDro scale. The data were pooled and a meta-analysis was completed. This systematic review was conducted in accordance with the (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) PRISMA guideline statement. It was registered in the PROSPERO database (CRD42016049360). RESULTS: A total of 11 studies were included. The data were pooled, allowing meta-analysis of seven outcomes of interest. A total of 466 participants clinically diagnosed with multiple sclerosis were analysed. Results showed that virtual reality balance training is more effective than no intervention for postural control improvement (standard mean difference (SMD) = -0.64; 95% confidence interval (CI) = -1.05, -0.24; P = 0.002). However, significant overall effect was not showed when compared with conventional training (SMD = -0.04; 95% CI = -0.70, 0.62; P = 0.90). Inconclusive results were also observed for gait rehabilitation. CONCLUSION: Virtual reality training could be considered at least as effective as conventional training and more effective than no intervention to treat balance and gait impairments in multiple sclerosis rehabilitation.