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05). CONCLUSIONS The fixation stability of the trilayer collagen prototype without fibrin glue is lower than of the clinically used bilayer membrane with fibrin glue in chondral defects at the medial and lateral talar shoulder in an experimental human specimen test. Clinical use of trilayer collagen prototype without fibrin glue has to be validated by clinical testing to evaluate if the lower stability of fixation is still sufficient. The cullin-RING E3 ubiquitin ligase CRL4Cdt2 has emerged as a master regulator of genome stability, which targets key cell cycle proteins for proteolysis during S phase and after DNA damage. Recent advances shed light on how it couples ubiquitination to DNA synthesis, offering a new paradigm for substrate recognition Cdt2 binds directly onto proliferating cell nuclear antigen (PCNA) loaded on DNA, which serves as a landing pad for the independent recruitment of the ubiquitin ligase and its substrates. Cyclin-dependent kinases (CDKs) and the ataxia telangiectasia and Rad3-related (ATR) kinase ensure accurate spatiotemporal regulation of CRL4Cdt2 under normal conditions and upon DNA damage. Deregulation of Cdt2 is evident in malignancies and was recently highlighted as a major target of oncogenic viruses, supporting the therapeutic targeting of the ligase as a promising anticancer strategy. PURPOSE To identify risk factors for developing symptomatic brain metastases and evaluate the impact of prophylactic cranial irradiation (PCI) on brain metastasis-free survival (BMFS) and overall survival (OS) in extensive disease small cell lung cancer (ED-SCLC). MATERIALS AND METHODS Among 190 patients diagnosed with ED-SCLC who underwent FDG PET/CT and brain Magnetic Resonance Imaging (MRI) prior to treatment, 53 (27.9%) received PCI while 137 (72.1%) did not. Prognostic index predicting a high risk of symptomatic brain metastases was calculated for the group without receiving PCI (observation group, n = 137) with Cox regression model. RESULTS Median follow-up time was 10.6 months. Bindarit datasheet Multivariate Cox regression showed that the following three factors were associated with a high risk of symptomatic brain metastases the presence of extrathoracic metastases (p = 0.004), hypermetabolism of bone marrow or spleen on FDG PET (p  less then  0.001), and high neutrophil-to-lymphocyte ratio (p = 0.018). PCI significantly improved BMFS in high-risk patients (1-year rate 94.7% vs. 62.1%, p = 0.001), but not in low-risk patients (1-year rate 100.0% vs. 87.7%, p = 0.943). However, PCI did not improve OS in patients at high risk for symptomatic brain metastases (1-year rate 65.2% vs. 50.0%, p = 0.123). CONCLUSION Three prognostic factors (the presence of extrathoracic metastases, hypermetabolism of bone marrow or spleen on FDG PET, and high neutrophil-to-lymphocyte ratio) were associated with a high risk of symptomatic brain metastases in ED-SCLC. PCI was beneficial for patients at a high risk of symptomatic brain metastases in terms of BMFS, but not OS. Thus, selective use of PCI in ED-SCLC according to the risk stratification is recommended. BACKGROUND Increasing evidence has indicated that gut microbiota is closely associated with radiation-induced bowel injury. We aimed to evaluate the safety and efficacy of fecal microbiota transplantation (FMT) in patients with chronic radiation enteritis (CRE). METHODS A pilot study of FMT for CRE was performed. The primary outcomes were safety and response to FMT which was defined as a ≥1-grade reduction in Radiation Therapy Oncology Group (RTOG/EORTC) late toxicity grade from baseline, by 8 weeks post-FMT. The secondary outcomes included a decrease in the severity of four common symptoms (diarrhea, rectal hemorrhage, abdominal/rectal pain and fecal incontinence) in CRE and changes in Karnofsky Performance Status (KPS) score. Microbial analyses were performed by 16S rRNA sequencing. RESULTS Five female patients underwent FMT from January to November 2018 with a median age of 58 (range 45-81) years. The median baseline RTOG/EORTC grade was 2 (range 2-4). Three patients responded to FMT and experienced improvement in diarrhea, rectal hemorrhage, abdominal/rectal pain and fecal incontinence as well as a decrease in KPS score. No FMT-related death and infectious complications occurred. One mild FMT-related AE was observed during a follow-up ranged from 8 to 18 months. 16S rRNA sequencing indicated that FMT altered the composition of gut microbiota of patients. CONCLUSION The present case series first demonstrated that FMT might be safe and effective to improve intestinal symptoms and mucosal injury in patients with CRE for a period of time. Trial registration ID NCT03516461. BACKGROUND Neurocognitive function of adult patients with brain tumours may deteriorate after radiotherapy. Proton beam therapy (PBT) reduces the volume of irradiated healthy brain tissue and could potentially preserve neurocognition and quality of life (QoL). As present data are still limited, the impact of clinical factors and dosimetric parameters on neurocognitive function and QoL during recurrence-free follow-up after PBT is investigated. METHODS The current study includes 62 brain tumour patients treated with PBT between 2015 and 2017. Neurocognition and QoL were assessed at baseline and every 3 months after PBT using the Montreal Cognitive Assessment (MoCA) test together with EORTC-QLQ-C30 and BN20 questionnaires, respectively. Objective and self-reported measures of neurocognitive functions were correlated. During two years of follow-up, the impact of clinical co-factors as well as dosimetric parameters of several brain structures were analysed using a mixed-model approach. RESULTS At baseline, mean Mstudies and comparison to patients treated with photon therapy. BACKGROUND AND PURPOSE No evidence has been presented until now whether recommendations given in recently issued guidelines concerning CIED-bearing patients significantly decrease RT-related complications. MATERIALS AND METHODS 160 RT-cases were prospectively treated with 3D-CRT, IMRT, SBRT using exclusively 6 MV photons (n = 146) and electrons (n = 14) according to the 2015 issued German DEGRO/DGK-guideline for CIED-bearing patients and compared to 40 RT-cases (3D-CRT, 10-23 MV photons (n = 39) and electrons (n = 1)) of CIED-bearing patients which were treated in concordance to the 1994 issued AAPM-guideline. RESULTS With AAPM-recommendations, complications occurred in 7/39 (17.95%) photon-RT cases, one patient experienced inadequate defibrillation therapy. For all patients treated with photon energies between 6 and 23 MV, a relative risk for CIED failure if treated with > 6 MV was calculated to be 9.03 (95% CI 5.24-15.55). After implementation of the DEGRO/DGK guideline, no complications were noted in 147 cases treated with photons, even though CIED-doses were as high as 5.

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