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EDX exhibited minor copper radiation for Co-ZOP, none for ZOP. In vitro fungal adhesion to Co-ZOP was significantly higher than to ZOP; in vitro streptococcal adhesion, cytotoxicity, and in vivo biofilm formation were not significantly different. CONCLUSIONS Co-ZOP showed low surface allocations of copper with no improved antimicrobial properties compared with conventional ZOP in vitro or in vivo. CLINICAL RELEVANCE Antimicrobial effects and low cytotoxicity of biomaterials are important for the clinical outcome. Based on our in vitro and in vivo results, no clinical recommendation can be given for the tested Co-ZOP.The aortic pathologies are well recognized on imaging. However, conventionally cardiac and proximal aortic abnormalities were only seen on dedicated cardiac or aortic studies due to need for ECG gating. Advances in CT technology have allowed motionless imaging of the chest and abdomen, leading to an increased visualization of cardiac and aortic root diseases on non-ECG-gated imaging. The advances are mostly driven by high pitch due to faster gantry rotation and table speed. The high-pitch scans are being increasingly used for variety of clinical indications because the images are free of motion artifact (both breathing and pulsation) as well as decreased radiation dose. Recognition of aortic root pathologies may be challenging due to lack of familiarity of radiologists with disease spectrum and their imaging appearance. It is important to recognize some of these conditions as early diagnosis and intervention is key to improving prognosis. We present a comprehensive review of proximal aortic anatomy, pathologies commonly seen at the aortic root, and their imaging appearances to familiarize radiologists with the diseases of this location.BACKGROUND To find out the physiological method for evaluating the severity of central autonomic dysfunction, we performed detailed evaluation of cutaneous vasomotor neural function in a comparatively large sample of multiple system atrophy (MSA). METHODS We evaluated cutaneous vasomotor neural function in 24 MSA patients. Skin sympathetic nerve activity (SSNA) and sympathetic skin response (SSR) and skin blood flow (skin vasomotor reflex [SVR]) were recorded at rest, as well as reflex changes after electrical stimulation. The parameters investigated were SSNA frequency at rest, reflex latency and amplitude of SSNA reflex bursts, absolute decrease and percent reduction of SVR, recovery time, and spontaneous SVR and SSR frequency. RESULTS There were negative correlations between resting SSNA and disease duration or the SCOPA-AUT score, but these were not significant. SSNA reflex latency displayed significant positive correlations with disease duration and SCOPA-AUT score (p  less then  0.001 and p  less then  0.01, respectively). In all five patients who underwent the same examination twice, SSNA reflex latency was significantly longer at the second examination than at the first examination (p  less then  0.005). A significant positive correlation was identified between recovery time of skin blood flow and SCOPA-AUT score or reflex latency (p  less then  0.05). Significant correlations were not observed between SCOPA-AUT score or disease duration and other parameters. CONCLUSIONS These results suggest that some MSA patients with a comparatively short duration of disease potentially have impaired thermoregulatory function. Measurement of sympathetic outflow to the skin is potentially a useful tool for predicting the severity of central autonomic dysfunction in MSA.OBJECTIVE Aim of the research was to define the quality of life of Italian neurologists and nurses' professional caring for multiple sclerosis, to understand their living the clinical practice and identify possible signals of compassion fatigue. MATERIAL AND METHODS One hundred five neurologists and nurses from 30 Italian multiple sclerosis centres were involved in an online quali-quantitative survey on the organization of care, combined with the Satisfaction and Compassion Fatigue Test and a collection of narratives. Descriptive statistics of the quantitative data were integrated with the results obtained by the narrative medicine methods of analysis. RESULTS Most of the practitioners were neurologists, 46 average years old, 69% women, 43% part time dedicated to multiple sclerosis. An increased number of patients in the last 3 years were referred in 29 centres. Differences were found between neurologists and nurses. Physicians showed higher risks of burnout, reporting intensive working paces, lack of medical personnel, and anxiety caused by the precarious employment conditions. Nurses appeared more satisfied, although the reference to the lack of spaces, and the cross professional roles risk of compassion fatigue. Both positive and negative relationships of care were depicted as influencing the professional quality of life. CONCLUSION The interviewed neurological teams need to limit the risk of compassion fatigue, which appeared from the first years of the career. The prevalence of the risk among neurologists suggests more awareness among scientific societies and health care managers on the risk for this category, as first step to prevent it.PURPOSE Free flaps have become the standard option in reconstructive surgery of the head and neck. Even though many authors have outlined the reliability of free transplants, there is an ongoing discussion about treatment options for patients bearing particular risks as previous irradiation treatment. In this analysis, we aim to address these patients with particular risk profiles by comparing different flap entity outcome parameters. METHODS We retrospectively analyzed a cohort of 494 patients who underwent flap surgery between 2009 and 2018 in our department. Focusing on free microvascular transplants, we additionally analyzed the pectoralis major myocutaneous flap as the most frequently used vascular pedicled flap. Data analysis was performed by uni- and multivariate statistics. RESULTS Overall flap success rate was 90%, with the radial forearm flap occurring to be most reliable (93%) in head and neck reconstruction. Previous radiation therapy (RT) and intraoperative revision of vascular anastomosis during primary surgery significantly resulted in impaired transplant outcome with a success rate of 91.8% (no RT) vs. 83.7% (RT), respectively. There was a negative linear correlation between incision to suture time and number of flaps per year (R2 = 0.67). CONCLUSIONS Preoperative radiation therapy and intraoperative revision of anastomosis significantly impair outcome of microvascular flaps in the head and neck and oral cavity, whereas patient's age is not a predictor of flap failure. Increasing case number and experience reduces time of flap surgery as well as rate of complications and flap failure.PURPOSE OF REVIEW While anti-PD-1 antibodies have been a breakthrough in the treatment of patients with advanced melanoma, a substantial proportion of patients are still refractory to or progress after treatment with anti-PD-1 immunotherapy. U0126 clinical trial Here, we review the post anti-PD-1 therapy alternatives that may be possible for patients with unresectable or metastatic stage 3 or 4 melanoma. RECENT FINDINGS Currently available treatment options include BRAF-targeted and MEK inhibitor-targeted therapies for those with BRAFV600 mutant melanoma, while for patients with BRAF-WT melanoma or those who have already received prior BRAF-targeted therapy, options include anti-CTLA-4 therapy, alone or in combination with anti-PD-1 therapy, or for selected patients, clinical trials that may incorporate other immune checkpoint inhibitors or co-stimulatory agonists, oncolytic virotherapies, adoptive cellular therapies, or other novel agents. Participation in clinical trials is critical in order to delineate what more effective treatment options are and which group of patients after receiving prior anti-PD-1 therapy.Primary glandular bladder tumours (bladder adenocarcinoma [BAC], urachal adenocarcinoma [UAC], urothelial carcinoma with glandular differentiation [UCg]) are rare malignancies with histological resemblance to colorectal adenocarcinoma (CORAD) in the majority of this subgroup. Definite case numbers are very low, molecular data are limited and the pathogenesis remains poorly understood. Therefore, this study was designed to complement current knowledge by in depth analysis of BAC (n = 12), UAC (n = 13), UCg (n = 11) and non-invasive glandular lesions (n = 19). In BAC, in addition to known alterations in TP53, Wnt, MAP kinase and MTOR pathway, mutations in SMAD4, ARID1A and BRAF were identified. Compared to published data on muscle invasive bladder cancer (BLCA) and CORAD, UCg exhibited frequent "urothelial" like alterations while BAC and UAC were characterised by a more "colorectal" like mutational pattern. Immunohistochemically, there was no evidence of DNA mismatch repair deficiency or PD-L1 tumour cell positivity in any sample. Depending on the used antibody 0-45% of BAC, 0-30% of UCg and 0% UAC cases exhibited PD-L1 expressing tumour associated immune cells. A single BAC (9%, 1/11) showed evidence of ARID1A protein loss, and two cases of UCg (20%, 2/10) showed loss of SMARCA1 and PBRM1, respectively. Taken together, our data suggest at least in part involvement of similar pathways driving tumourigenesis of adenocarcinomas like BAC, UAC and CORAD independent of their tissue origin. Alterations of TERT and FBXW7 in single cases of intestinal metaplasia further point towards a possible precancerous character in line with previous reports.This open-label first-in-human study evaluated JPH203, which is a novel selective L-type amino acid transporter 1 inhibitor. We also evaluated the association between the N-acetyltransferase 2 phenotype and outcomes. Japanese patients with advanced solid tumors received daily intravenous JPH203 treatment for 7 days, followed by a 21-day rest period, at escalating doses of 12-85 mg/m2. Dose-limiting toxicities were evaluated during the first cycle using a 3 + 3 design. The study enrolled 17 patients, although grade 3 liver dysfunction was detected in one of six patients receiving 60 mg/m2 and in the first patient to receive 85 mg/m2. Further enrollment was terminated and the maximum tolerated dose was defined as 60 mg/m2. The AUC∞ increased between 12 mg/m2 and 25 mg/m2, although no differences were observed at 25-40 mg/m2. Partial response was observed for one patient with biliary tract cancer (BTC) at the 12 mg/m2 dose, and disease control was achieved by 3 of 6 patients at the 12 mg/m2 and 25 mg/m2 dose levels. Based on these results, we recommend a phase II dose of 25 mg/m2. The disease control rate for BTC was 60%. Two patients with grade 3 liver dysfunction had the rapid N-acetyltransferase 2 phenotype, and disease control was more common for the non-rapid phenotype (50% vs. 12.5%). It appears that JPH203 was well-tolerated and provided promising activity against BTC. The N-acetyltransferase 2 phenotype might help predict the safety and efficacy of JPH203. Clinical trial registration UMIN000016546.Administration of chemotherapeutics as direct injections into tumors offers increased anti-tumor activity and reduced systemic toxicity. In this study, the Renca syngeneic murine xenograft model of renal cancer was used to evaluate the effects of intratumoral (IT) submicron particle docetaxel (NanoDoce®) on tumor growth and immunomodulation. Tumor volume (TV) was compared to controls, including intravenous (IV) chemotherapy. Flow cytometry of peripheral bloods and tumors was used to evaluate immune cell populations. Groups of animals were inoculated with a second Renca tumor at a site distant from the primary tumor. IT NanoDoce significantly reduced primary TV and reduced the growth rates of untreated secondary tumors. CD4+, CD8+ and Treg populations were increased in peripheral bloods from animals administered IT NanoDoce. Additional evaluation of the effect of IT NanoDoce on peripheral and local immune cell populations as well as the impact on sites of distant tumor growth are warranted.