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ve patients.Introduction Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease, characterized by the production of autoantibodies. Numerous mechanisms contribute to the pathogenesis and autoimmunity in SLE. One of the most important mechanisms is the defective function of the early complement components that are involved in clearing the immune-complexes and apoptotic debris. Major evidence supporting this hypothesis is the development of severe lupus in individuals with monogenic defects in any one of the early complement components such as C1q, C1 s, C1 r, C2, or C4.Areas covered In this review, we discuss hereditary defects in classical complement components and their clinical manifestations, acquired defects of complements in lupus, the role of complements in the pathogenesis of antiphospholipid antibody syndrome and lupus nephritis, and laboratory assessment of complement components and their functions. Articles from the last 20 years were retrieved from PubMed for this purpose.Expert opinion Complements have a dual role in the pathogenesis of SLE. On one hand, deficiency of complement components predisposes to lupus, while, on the other, excess complement activation plays a role in the organ damage. Understanding the intricacies of the role of complements in SLE can pave way for the development of targeted therapies.Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder, of unknown etiology, that affects 2.5% of the population. An appropriate therapeutic response to conventional treatment is seen. Some studies use augmentative treatment by antipsychotics, glutamatergic, lithium, buspirone, and others agents to improve the therapeutic response. In this study, we aimed to evaluate the efficacy and tolerability of aripiprazole and quetiapine as augmentative treatments in patients with selective serotonin reuptake inhibitor (SSRI) refractory OCD. The OCD patients were initially treated for 12 weeks with a SSRI. If after 12 weeks their Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score was more than 16, they were randomly assigned to either the aripiprazole or the quetiapine augmentation group for an additional 12 weeks. There were no significant differences in age, sex, education, marital status, or score of Y-BOCS and Clinical Global Impression-Severity Scale (CGI-S) between groups (p > 0.05) at the outset of the study. Significant differences were noted after 1 month when compared with results at 2, 3, and 4 months in both groups (p less then 0.001). Both quetiapine and aripiprazole may be effective and well-tolerated augmentative agents in the treatment of SSRI-refractory OCD. Because of positive results, aripiprazole may be considered more effective and may have a more rapid onset in terms of therapeutic response.Introduction Despite an increasingly older pulmonary hypertension (PH) population, data on PH treatments in these patients are limited because there exist no clinical studies dedicated to geriatric groups. cis-diamminedichloroplatinum II Furthermore, elderly patients with comorbidities have been systematically excluded from clinical trials, limiting the evidence base for drugs approved for pulmonary arterial hypertension (PAH).Areas covered This review is focused on the diagnosis and treatment of pulmonary hypertension (PH) in the elderly, which is a hot topic today. Areas covered by the authors include current changes in demographics, clinical characteristics, diagnoses, and risk assessment in the geriatric PAH population. A central part of this review is dedicated to the therapeutic challenges in elderly patients with PAH. The literature search is focused on sorting out post-capillary conditions in the elderly, and on current treatment strategies for PAH and for chronic thromboembolic pulmonary hypertension (CTEPH).Expert opinion Current data indicate that despite more severe disease in elderly patients, the concept of hit hard and early is less used. For example, double upfront oral combination, a common strategy for younger patients, or early parenteral prostacyclins, are less used in the elderly, purporting worse outcomes for these patients.Background. Hallux valgus is a complex deformity of the first ray of the foot, and a significant number of adolescents develop this deformity. link2 More than 130 surgical procedures have been described to treat hallux valgus, but there is no compelling evidence to prefer one method over another. Minimal invasive techniques have been proposed and reported to be successful and cost-effective. The objective of this study was to describe the clinical course of adolescent patients treated with percutaneous distal metatarsal osteotomy. Methods. A retrospective study included patients who had a percutaneous hallux valgus correction during the years 2008 to 2015. The following measurements were compared before surgery up to last follow-up AOFAS Hallux-Metatarsophalangeal-Interphalangeal questionnaire and radiological measurements (HVA, IMA, DMAA). Any postoperative complications were extracted from the medical records. Results. The procedure was performed on 32 feet (27 patients). link3 All patients were less then 18 years of age. There were 10 male patients (12 feet) and 17 female patients (20 feet). Average age at surgery was 15.8 years (range = 13-18 years). Average follow-up time was 43 months (range= 24-94 months). The average AOFAS score before surgery was 66, and after surgery, at last follow-up was 96. This difference was significant (P value less then .0001). Most patients were pain free after the procedure and returned to appropriate age functioning. Significant improvement was noted in all radiological criteria. Conclusions. Percutaneous distal metatarsal osteotomy is safe, reliable, and effective for the correction of mild to moderate symptomatic hallux valgus in adolescents. Levels of Evidence Level IV.Introduction Transforming Growth Factor-Beta (TGF-β) is a master regulator of numerous cellular functions including cellular immunity. In cancer, TGF-β can function as a tumor promoter via several mechanisms including immunosuppression. Since the immune checkpoint pathways are co-opted in cancer to induce T cell tolerance, this review posits that TGF-β is a master checkpoint in cancer, whose negative regulatory influence overrides and controls that of other immune checkpoints.Areas Covered This review examines therapeutic agents that target TGF-β and its signaling pathways for the treatment of cancer which may be classifiable as checkpoint inhibitors in the broadest sense. This concept is supported by the observations that 1) only a subset of patients benefit from current checkpoint inhibitor therapies, 2) the presence of TGF-β in the tumor microenvironment is associated with excluded or cold tumors, and resistance to checkpoint inhibitors, and 3) existing biomarkers such as PD-1, PD-L1, microsatellite instability and tumor mutational burden are inadequate to reliably and adequately identify immuno-responsive patients. By contrast, TGF-β overexpression is a widespread and profoundly negative molecular hallmark in multiple tumor types.Expert Opinion TGF-β status may serve as a biomarker to predict responsiveness and as a therapeutic target to increase the activity of immunotherapies.INTRODUCTION Peripherally inserted central catheters are very common devices for short, medium and long-term therapies. Their performance is strictly dependent on the correct tip location, at the junction between the upper caval vein and the right atrium. It is very important to obtain an estimated measure of the catheter, in order to reach the cavo-atrial junction and optimize the catheter length. Estimated measures are often obtained using cutaneous landmarks. OBJECTIVE Evaluate the reliability of cutaneous landmark-based length estimation during catheter insertion. Identify any patient's related factors that may affect cutaneous landmarks reliability. METHODS We used two distinct techniques and collected data about cutaneous landmark-based length estimation, electrocardiographic guided intravascular length, age, weight and height. We studied the reliability of possible correcting factors, balancing the error average by regression models, and we found and tested two different models of prediction. RESULTS A total number of 519 patients were studied. The average bias, between the two studied length assessment by cutaneous landmarks and electrocardiographic guided catheter length, were 3.77 ± 2.44 cm and 3.28 ± 2.57 cm, respectively. The analysed prediction models (deviance explained 43.5%, Akaike information criterion = 1313.67% and 43.4%, Akaike information criterion = 1313.92), fitted on the validation set, showed a root mean square error of 3.07 and 3.06. CONCLUSION Landmark-based length estimation for preventive catheter length assessment seems to be unreliable, when associated with post-procedural tip location. They are useful for distal trimming catheters to optimize the 'out of skin' portion when associated with electrocardiographic tip location. Models identified for balancing bias are probably not useful.Objective Carbapenemase-producing Klebsiella pneumoniae (CPKp) infections are increasing worldwide. We investigated the in vitro synergistic activity of fosfomycin (FOS) with meropenem (MRP), amikacin (AMK) and colistin (COL) against OXA-48 and/or New Delhi metallo-beta-lactamase (NDM)-producing Kp blood isolates. Materials and Methods Seventeen CPKp blood isolates were studied. The broth microdilution method was used for COL, MRP and AMK susceptibilities, while agar dilution for FOS. Synergy was tested by agar dilution chequerboard technique and also was confirmed by a time-kill assay for FOS/MRP and FOS/COL using three representative isolates that were found to be synergistic. Results FOS in combination with MRP was found to be the most synergistic (15/17 strains, 88%), while 29% and 41% with AMK and COL, respectively. Antagonism was only determined in 2 isolates with the COL/FOS. Conclusions The MRP/FOS combination demonstrated synergistic activity against CRKp, especially against the two common enzyme-producing isolates in Turkey (OXA-48 and NDM).Time perspective, which refers to a mechanism of automatically assigning experiences into temporal categories (as past, present, and future), is argued to be a fundamental dimension in the construction of psychological time in addition to acting as a vulnerability factor for psychological disorders. Negative urgency is another vulnerability factor for psychological disorders that are characterized by engaging in impulsive actions when one is under the influence of negative emotions. The current study aimed to examine how the interaction of different dimensions of time perspective and negative urgency are connected with anxiety and depression. Data were gathered from 404 (255 women) individuals between ages 18 and 65 through measures of time perspective, negative urgency, anxiety, and depression. The results showed that while the interaction of negative urgency with past negative time perspective was associated with depression, a similar pattern was not observed for other dimensions of time perspective. Particularly, negative urgency appeared to boost the negative impact of being past-oriented. Similarly, only the interaction of future time perspective with negative urgency was associated with anxiety, indicating that tending to focus on the events that are likely to take place in the future is associated with elevated levels of anxiety in individuals with high levels of negative urgency.