Knorpeltrauma und post-traumatische Inflammationsreaktion

A trauma of articular cartilage is often associated with an inflammatory reaction and results in many cases in the development of post-traumatic osteoarthritis. The pathogenetic connection between inflammatory processes and cartilage degeneration is not clear so far. One of the pivotal signaling kinases in these degrading mechanisms is the p38 MAPK. In order to investigate the post-traumatic reactions, an in vitro model was developed. Human cartilage explants were mechanically impacted by using a drop-tower. Additionally to the mechanical stress a group was either stimulated with IL-1ß (IL) or C5a. Another group was stimulated with IL and the p38 MAPK-inhibitor SB203580. The post-traumatic effects were measured in terms of cell survival, gene expression and the release of mediators. A human in vitro co-culture system of cartilage explants with synovial fibroblasts (SF) was established to elucidate the role of the synovial tissue regarding inflammatory and catabolic reactions post trauma. A significant decrease in chondrocyte viability after trauma, but no additional effect of IL was detected. For the first time an elevated release of PGD2 by human articular cartilage in response to a single mechanical impact was demonstrated. Various other mediators (e.g. PGE2, NO, IL-6) were released in response to trauma ± IL stimulation. ACAN and COL2A1 gene expression was reduced after trauma + IL stimulation whereas MMP-1, -3, and -13 gene expression was elevated. Stimulation with C5a showed no effects concerning post-traumatic inflammatory and catabolic reactions. SB203580 had a tendency to improve cell survival and to reduce the release of proinflammatory mediators as well as the mRNA expression level of matrix-catabolic genes after impact in an inflammatory environment. Co-cultivation of cartilage explants with SF resulted in mutual effects post trauma including a decreased amount of viable chondrocytes and an increased release of prostaglandins and IL-6 after trauma

Improving Chemotherapy-Induced Peripheral Neuropathy in Patients with Breast or Colon Cancer after End of (Neo)adjuvant Therapy: Results from the Observational Study STEFANO

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect persisting after completion of neurotoxic chemotherapies. This observational study was designed to evaluate the effectiveness of the dietary supplement OnLife (R) (patented mixture of specific fatty acids and palmitoylethanolamide) in improving symptoms of CIPN in breast and colon cancer patients. Methods: Improvement of CIPN was evaluated in adult patients, previously treated with (neo)adjuvant paclitaxel- (breast cancer) or oxaliplatin-based (colon cancer) therapies, receiving OnLife (R) for 3 months after completion of chemotherapy. The primary endpoint was to compare the severity of peripheral sensory neuropathy (PSN) and peripheral motor neuropathy (PMN) before and at the end of OnLife (R) treatment. Secondary endpoints included the assessment of patient-reported quality of life and CIPN symptoms as assessed by questionnaires. Results: 146 patients (n = 75 breast cancer patients and n = 71 colon cancer patients) qualified for analysis; 31.1% and 37.5% of breast cancer patients had an improvement of PSN and PMN, respectively. In colon cancer patients, PSN and PMN improved in 16.9% and 20.0% of patients, respectively. According to patient-reported outcomes, 45.9% and 37.5% of patients with paclitaxel-induced PSN and PMN, and 23.9% and 22.0% of patients with oxaliplatin-induced PSN and PMN experienced a reduction of CIPN symptoms, respectively. Conclusion: OnLife (R) treatment confirmed to be beneficial in reducing CIPN severity and in limiting the progression of neuropathy, more markedly in paclitaxel-treated patients and also in patients with oxaliplatin-induced CIPN

First‐line pazopanib in intermediate‐ and poor‐risk patients with metastatic renal cell carcinoma: Final results of the FLIPPER

Temsirolimus has long been the only approved first-line standard of care (SOC) with overall survival (OS) benefit in poor-risk patients with advanced or metastatic renal cell cancer (mRCC). However, tyrosine kinase inhibitors are also commonly used in clinical practice. Pazopanib is an SOC for first-line mRCC treatment, but for poor-risk patients data are scarce. The FLIPPER (First-Line Pazopanib in Poor-Risk Patients with Metastatic Renal Cell Carcinoma) study aimed to assess efficacy and safety of first-line pazopanib in poor-risk mRCC patients. FLIPPER was a single-arm, multicenter, Phase IV trial. Key inclusion criteria were treatment-naive clear cell, inoperable advanced or mRCC, poor-risk according to MSKCC with slight modification, Karnofsky performance status (KPS) >= 60% and adequate organ function. Oral pazopanib 800 mg was given daily. Primary endpoint was the 6-month progression-free survival rate (PFS6). Secondary endpoints included PFS, OS, overall response rate (ORR), duration of response (DOR) and safety. For analysis, descriptive statistics were used. Between 2012 and 2016, 60 patients had been included. Forty-three patients qualified for safety analyses, 34 for efficacy. Median age was 66 years, 64.7% of patients were poor-risk, 82.4% had a KPS <= 70%. PFS6 was 35.3% (95% CI, 19.7-53.5). Median PFS and OS were 4.5 months (95% CI, 3.6-7.8) and 9.3 months (95% CI, 6.6-22.2), respectively. ORR was 32.4% (95% CI, 17.4-50.5), median DOR 9.7 months (95% CI, 1.8-12.4). The most common treatment-related grade 3/4 adverse event reported in 4.7% of patients was hypertension. No treatment-related death occurred. Since pazopanib is active and well tolerated in poor-risk patients with clear cell mRCC, our results support its use as first-line treatment in this setting