67; 95% CI 1.08-2.58). Comparisons of baseline characteristics between patients with favorable and poor outcome indicated the correlation between CYP2C19 loss-of-function (LOF) allele and poorer clinical outcome in ≤ 60-year-old patients (OR = 4.29; 95% CI 1.68-10.93). The heterogeneity test showed a presence of interaction between age and CYP2C19 LOF (OR = 3.75; 95% CI 1.30-10.81). SKF38393 The logistic analyses further suggested that CYP2C19 LOF predicted poor clinical outcome in ≤ 60-year-old but not in > 60-year-old LAA-associated minor stroke patients receiving clopidogrel for the second prevention. Conclusions Carriage of the CYP2C19 LOF allele may prevent expected clinical outcome during clopidogrel therapy in young LAA-associated minor stroke patients, whereas not in older patients.Dysregulations of the NEK2 and PIM1-3 kinase signaling axes have been implicated in the pathogenesis of several cancers, including those with a neuroendocrine phenotype. However, their impact on bronchopulmonary neuroendocrine neoplasms (BP-NENs) has not been investigated. The aim of this pilot study was to determine mRNA and protein levels of NEK2, PIM1, and PIM3 in a group of 49 patients with BP-NENs 11 typical carcinoids, 5 atypical carcinoids, 11 large cell neuroendocrine carcinomas, 22 small cell lung carcinomas (SCLC). The expression was measured using TaqMan-based RT-PCR and immunohistochemistry. NEK2 and PIM1 mRNA levels were higher in the SCLC patients than in the other BP-NEN groups (p less then 0.001). There was an association between NEK2 mRNA and protein expression (p = 0.023) and elevated NEK2 mRNA levels were related to reduced survival in BP-NEN patients (p = 0.015). Patients with higher PIM1 protein expression had also diminished survival comparing with those with weak or no PIM1 expression (p = 0.037). Elevated NEK2 and PIM1 expression were related to aggressive tumor phenotype and indirectly affected the overall survival of BP-NEN patients. Our pilot study supports the need for future investigation of the biological function of NEK2 and PIM1 in BP-NEN transformation to verify the clinical value of our findings.Background and aims Most patients with multiple sclerosis presenting with a relapsing-remitting disease course at diagnosis transition to secondary progressive multiple sclerosis (SPMS) 1-2 decades after onset. SPMS is characterized by predominant neurodegeneration and atrophy. These pathogenic hallmarks result in unsatisfactory treatment response in SPMS patients. Therefore, early diagnosis of SPMS is necessary for prompt treatment decisions. The aim of this review was to assess neurophysiological and fluid biomarkers that have the potential to monitor disease progression and support early SPMS diagnosis. Methods We performed a systematic review of studies that analyzed the role of neurophysiological techniques and fluid biomarkers in supporting SPMS diagnosis using the preferred reporting items for systematic reviews and meta-analyses statement. Results From our initial search, we selected 24 relevant articles on neurophysiological biomarkers and 55 articles on fluid biomarkers. Conclusion To date, no neurophysiological or fluid biomarker is sufficiently validated to support the early diagnosis of SPMS. Neurophysiological measurements, including short interval intracortical inhibition and somatosensory temporal discrimination threshold, and the neurofilament light chain fluid biomarker seem to be the most promising. Cross-sectional studies on an adequate number of patients followed by longitudinal studies are needed to confirm the diagnostic and prognostic value of these biomarkers. A combination of neurophysiological and fluid biomarkers may be more sensitive in detecting SPMS conversion.Introduction The rate of venous thromboembolism following surgical treatment of proximal humerus fractures is not well established. Methods A retrospective review of all patients undergoing surgical treatment for proximal humerus fractures from September 2011 to May 2017 was performed. Included patients received only mechanoprophylaxis using sequential compression devises. All patients had at least 6 months follow-up. The primary outcome of interest was the rate of postoperative DVT and PE. Results 131 patients underwent 139 surgeries for proximal humerus fracture. After exclusion criteria were applied, 92 patients who underwent 92 surgeries were included. There were 47 females and 45 males. Five (5.4%) were taking Aspirin 81 mg preoperatively. There were 76 cases of open reduction and internal fixation (ORIF), 8 cases of reverse total shoulder arthroplasty, 4 cases of hemiarthroplasty, 3 cases of closed reduction percutaneous pinning (CRPP), 1 case of open reduction without fixation. 53.3% of patients had one or more risk factors for VTE. There were no cases of fatal PE or DVT. There were two cases of symptomatic PE (2.2%) following one ORIF and one CRPP. There was one additional case of asymptomatic PE found incidentally after ORIF. Overall VTE rate was 3.3%. Fisher’s exact test yielded that there was no significant association between the presence of VTE risk factors and prevalence of VTE postoperatively (p = 0.245). Conclusions The incidence of symptomatic VTE after surgery for proximal humerus fractures is low. Chemical VTE prophylaxis in patients after surgical fixation for proximal humerus fractures is not universally indicated. Selective prophylaxis for patients with systemic risk factors may be warranted.Introduction The use of quadriceps tendon-patellar bone (QTB) autograft for anterior cruciate ligament (ACL) reconstruction is gaining momentum. Yet, long-term results that compare this procedure with established methods are lacking. The aim of this study was to report and compare long-term results of ACL reconstruction using QTB autografts versus bone-patellar tendon-bone (BPTB) autografts, both anchored using a hardware-free press-fit fixation technique. Materials and methods 60 athletes (Tegner score ≥6) with primary ACL rupture were prospectively randomized into two groups. 56 patients were evaluated after a mean duration of 12.2 ± 1.9 months (range 10-14) and 43 patients after 10.3 ± 0.2 years (range 10-11). Results On final follow-up, 90% of patients scored very good and good results in the functional Lysholm score (mean 99 ± 7.1, range 74-100 points). Normal or almost normal IKDC score was reported by 84% of the patients (mean 97 ± 9.5, range 60-100 points). The activity level decreased in the Tegner score from median of 7 before injury to 6 after 10 years.