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PURPOSE The purpose of this study was to evaluate and compare knee kinematics and kinetics following either single bundle, modified triangular or double-bundle reconstruction of the superficial medial collateral ligament (sMCL) with single bundle anatomic ACL reconstruction. METHODS Using a cadaveric model (n = 10), the knee kinematics and kinetics following three MCL reconstructions (single-bundle (SB), double-bundle (DB), modified triangular) with single bundle anatomic ACL reconstruction were compared with the intact and deficient knee state. The knees were tested under (1) an 89-N anterior tibial load, (2) 5 N-m internal and external rotational tibial torques, and (3) a 7 N-m valgus torque. RESULTS Anatomic ACL reconstruction with SB MCL reconstruction was able to restore anterior tibial translation and external rotation to intact knee values but failed to the internal and valgus rotatory stability. Anatomical DB MCL reconstruction (with SB ACL reconstruction) and the modified triangular MCL reconstruction (with SB ACL reconstruction) restored all knee kinematics to the intact value. CONCLUSION This study shows that clinical presentation with combined ACL and severe sMCL injury, single-bundle MCL with single-bundle ACL reconstruction does not restore knee kinematics. Anatomical double-bundle MCL reconstruction may produce slightly better biomechanical stability than the modified triangular MCL reconstruction, but the modified triangular reconstruction might be more clinically practical with the advantages of being less invasive and technically simpler while at the same time can restore a nearly normal knee joint.Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) is increased in inflammatory bowel disease (IBD) patients, and its serum levels correlate with a worse prognosis. In the present manuscript, we show that eNAMPT serum levels are increased in IBD patients that fail to respond to anti-TNFα therapy (infliximab or adalimumab) and that its levels drop in patients that are responsive to these therapies, with values comparable with healthy subjects. Furthermore, eNAMPT administration in dinitrobenzene sulfonic acid (DNBS)-treated mice exacerbates the symptoms of colitis, suggesting a causative role of this protein in IBD. To determine the druggability of this cytokine, we developed a novel monoclonal antibody (C269) that neutralizes in vitro the cytokine-like action of eNAMPT and that reduces its serum levels in rodents. Of note, this newly generated antibody is able to significantly reduce acute and chronic colitis in both DNBS- and dextran sulfate sodium (DSS)-induced colitis. Importantly, C269 ameliorates the symptoms by reducing pro-inflammatory cytokines. Specifically, in the lamina propria, a reduced number of inflammatory monocytes, neutrophils, Th1, and cytotoxic T lymphocytes are found upon C269 treatment. Our data demonstrate that eNAMPT participates in IBD and, more importantly, that eNAMPT-neutralizing antibodies are endowed with a therapeutic potential in IBD. KEY MESSAGES What are the new findings? Higher serum eNAMPT levels in IBD patients might decrease response to anti-TNF therapy. The cytokine-like activity of eNAMPT may be neutralized with a monoclonal antibody. Neutralization of eNAMPT ameliorates acute and chronic experimental colitis. Neutralization of eNAMPT limits the expression of IBD inflammatory signature. Neutralization of eNAMPT impairs immune cell infiltration in lamina propria.PURPOSE We aimed to investigate the role of FDG-PET/CT in monitoring of response and immune-related adverse events (irAEs) following first-line combination-immune checkpoint inhibitor (combination-ICI) therapy for advanced melanoma. METHODS We retrospectively reviewed outcomes in patients who had (1) first-line nivolumab plus ipilimumab; (2) pre- and post-treatment FDG-PET/CT scans (pre-FDG-PET/CT and post-FDG-PET/CT) within 2 and 4 months of starting ICI, respectively; and (3) at least one lesion assessable by PET response criteria in solid tumors (PERCIST). Extracranial response was monitored by 3 monthly FDG-PET/CT. Whole-body metabolic tumor volume (wbMTV) was measured pre- and post-treatment and correlated with outcome. FDG-PET/CT manifestations of irAE were defined as new increased non-tumoral uptake on post-FDG-PET/CT and were correlated with clinical presentation. RESULTS Thirty-one consecutive patients, median age 60 years (range, 30-78), were identified from 2016 to 2018. The median number of combins. Long-term treatment response monitoring for detection of extracranial secondary progression is feasible by FDG-PET/CT. Beyond response assessment, FDG-PET/CT frequently detects clinically relevant irAEs, which may involve multiple systems contemporaneously or at various time-points and may precede clinical diagnosis.PURPOSE In this review, we discuss how the approach should be throughout the symptomatic and diagnostic process of recurrent bladder cystitis. METHODS AND RESULTS The available literature regarding recurrent bladder cystitis in the PubMed database has been reviewed. While urinary tract infections (UTIs) are amongst the most commonly seen diseases in society, the probability of having a UTI in women within a year is 15%. Within a lifetime, it is above 50%. In addition to the related comorbidities and decreased quality of life, the resulting cost constitutes a serious burden on national economies. Recurrent UTI (rUTI) refers to a group of patients who have suffered from a UTI at least three times in the last 12 months or at least two times during the previous 6 months and have diminished quality of life. During this chronic and bothersome process, it is also complicated as to who is going to make the diagnosis of patients and by whom treatment or follow-up will be provided. https://www.selleckchem.com/products/apcin.html CONCLUSION Although there is no clear answer to this issue in the literature, the urologist might be the moderator of this chronic process as the physician who most frequently faces this condition in daily practice, is most aware of the uroanatomy as well as the pathophysiology and performs relevant operations in cases of necessity. At this point, rather than limiting the evaluation and treatment to a single specialty, it is crucial to solve the problem by using a multidisciplinary approach.
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