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The purpose of this systematic review was to produce a best evidence synthesis of the effects of Kinesiology Tape (KT) in the treatment of tendinopathies. An electronic search on five databases (PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, SportDiscus, and Physiotherapy Evidence Database (PEDro)) was conducted. Studies were included if (1) patients suffered from tendinopathy; (2) isolated KT was applied in at least one group; (3) comparisons between other techniques were developed; (4) outcomes based on pain, function, disability, or quality of life were analysed. Two reviewers independently extracted data and assessed methodological quality using the Physiotherapy Evidence Database (PEDro) scale. A total of 13 articles met the eligibility criteria, involving 454 participants. Nine of these studies presented upper extremity tendinopathies, and four explored lower extremity tendinopathies. Selected papers ranged from low to high quality, with an average score of 5 on the PEDro scale. According to our findings, there is limited evidence to support KT alone for the treatment of tendinopathies beyond the short-term. Due to the mixed methodological quality and the insufficient number of clinical trials, larger, long-term, high-quality studies are needed to support the theory that tendinopathies can benefit from KT applications.

Twenty-three scientists met at Krobielowice, Poland to discuss the role of growth, nutrition and economy on body size. Contrasting prevailing concepts, re-analyses of studies in Indonesian and Guatemalan school children with high prevalence of stunting failed to provide evidence for an association between nutritional status and body height. Direct effects of parental education on growth that were not transmitted via nutrition were shown in Indian datasets using network analysis and novel statistical methods (St. Nicolas House Analysis) that translate correlation matrices into network graphs. Data on Polish children suggest significant impact of socioeconomic sensitivity on child growth, with no effect of maternal money satisfaction. Height and maturation tempo affect the position of a child among its peers. Correlations also exist between mood disorders and height. Secular changes in height and weight varied across decades independent of population size. Historic and recent Russian data showed that height of persons whose fathers performed manual work were on average four cm shorter than persons whose fathers were high-degree specialists. Body height, menarcheal age, and body proportions are sensitive to socioeconomic variables. Additional topics included delayed motherhood and its associations with newborn size; geographic and socioeconomic indicators related to low birth weight, prematurity and stillbirth rate; data on anthropometric history of Brazil, 1850-1950; the impact of central nervous system stimulants on the growth of children with attention-deficit/hyperactivity disorder; and pituitary development and growth hormone secretion. Final discussions debated on reverse causality interfering between social position, and adolescent growth and developmental tempo., Facultad de Ciencias Naturales y Museo

Neutrophil extracellular traps (NETs) have been described to be related to the pathogenesis of inflammatory and autoimmune conditions. Endometriosis is currently considered a chronic inflammatory condition. Therefore, we performed a preliminary case-control study to compare the circulating plasma NET levels in patients with surgically confirmed endometriosis (E group, n = 82) and those of patients without surgical findings of endometriosis (C group, n = 35). Venous blood samples were obtained at the time of surgery. Circulating plasma NET levels were assessed as histone-DNA complexes (ie, nucleosomes) by a quantitative sandwich enzyme-linked immunosorbent assay. The results were expressed in arbitrary units. Circulating plasma NET levels were significantly higher in the E group compared with the C group (median [25th; 75th percentiles]): E group: 0.734 [0.484; 1.363]; C group: 0.541 [0.411; 0.653]; P = .005). The subanalysis of E group patients with deep infiltrating endometriosis (DIE group) or without DIE (non-DIE group) showed that plasma NET levels were higher in the DIE group ( P = .02). No differences were observed in NET levels among patients with and without severe pelvic pain or in patients with and without infertility, regardless of the presence of endometriotic lesions. Therefore, our study shows significantly higher NET levels in patients with endometriosis, which seem to be attributed to increased levels in the subgroup of patients with DIE, suggesting that the presence of elevated circulating plasma NET levels may reflect an inflammatory status in this gynecological condition. Further research is warranted to confirm our findings and to assess the exact role of NETs in the pathophysiological mechanisms of endometriosis.

Introduction Cabozantinib and ramucirumab are approved for the treatment of adults with hepatocellular carcinoma (HCC) following prior sorafenib treatment; ramucirumab is restricted to use in patients with serum alpha-fetoprotein (AFP) ≥ 400 ng/mL. This matching-adjusted indirect comparison evaluated the efficacy and safety of both drugs after sorafenib in patients with HCC and AFP ≥ 400 ng/mL. Methods Individual patient data (IPD) from the CELESTIAL trial (cabozantinib) and population-level data from the REACH-2 trial (ramucirumab) were used. To align with REACH-2, the CELESTIAL population was limited to patients who received first-line sorafenib only and had baseline serum AFP ≥ 400 ng/mL. The IPD from CELESTIAL were weighted to balance the distribution of 11 effect-modifying baseline characteristics with those of REACH-2. Overall survival (OS; primary endpoint) and progression-free survival (PFS) were compared for the CELESTIAL (matching-adjusted) and REACH-2 populations using weighted Kaplan-Meier (KM) curves and parametric (OS, Weibull; PFS, log-logistic) modeling. Rates of treatment-related adverse events (TRAEs) and TRAE-related discontinuations were also compared. Results After matching and weighting, baseline characteristics were balanced between populations (REACH-2, N = 292; CELESTIAL, effective sample size = 105). Weighted KM estimates for OS (median [95% CI]) were not significantly different between cabozantinib and ramucirumab (10.6 [9.5–17.3] months versus 8.7 [7.3–10.8] months; p = 0.104), but PFS was significantly longer for cabozantinib than for ramucirumab (5.5 [4.6–7.4] months versus 2.8 [2.7–4.1] months; p = 0.016). Parametric modeling results were consistent with the weighted KM analysis. Rates of some grade 3 or 4 TRAEs were lower with ramucirumab than with cabozantinib; however, TRAE-related discontinuation rates were similar (p = 0.271). Conclusion In this MAIC, cabozantinib significantly prolonged median PFS compared with ramucirumab after prior sorafenib treatment in patients with HCC and AFP ≥ 400 ng/mL; rates of some grade 3 or 4 TRAEs were lower with ramucirumab than cabozantinib but related discontinuation rates were not significantly different between treatments. Trial Registration Clinical trials.gov identifiers: CELESTIAL trial (NCT01908426) and REACH-2 trial (NCT02435433). Graphic abstract These slides can be retrieved under Electronic Supplementary Material. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01700-2.

e16555 Background: Nonclinical and clinical data suggest that cabo with a PD1 inhibitor provides synergistic antitumor activity in patients with mRCC, possibly by a cabo-induced switch to an immunopermissive tumor microenvironment. We used a complementary, unbiased, AI approach to gain a holistic view of the complex interplay between multiple pathways, cells and molecules and identify the mechanisms that may underpin this synergism. Methods: Biological targets associated with mRCC pathophysiology or drug actions were identified from proteomic, genomic and transcriptomic databases and literature. Using systems- and AI-based technology, the data were integrated using machine learning into mathematical models of the human mRCC protein network topology. The combined effects of cabo and a PD1 inhibitor on biological targets were simulated assuming target receptors were fully activated or fully inhibited. Relevant effects on known cancer processes (e.g. angiogenesis, metastasis, cell proliferation, immune evasion) were identified using artificial neural networks. Biologically plausible synergistic mechanisms were described with sampling methods. Results: Inhibition of VEGF/VEGFR and GAS6/TAMR axes by cabo enhanced the known effects of PD1 inhibitors on immune evasion mechanisms by modulating multiple humoral and cellular components of the innate and adaptive immune responses (Table). PD1 inhibitors further enhanced the anti-angiogenic and tumor pro-apoptotic effects of cabo by modulating pro- and anti-angiogenic factors and T cell cytotoxicity. Conclusions: These data provide a mechanistic rationale and further support for the beneficial combination of cabo and a PD1 inhibitor and may guide future nonclinical and clinical research.[Table: see text]

550 Background: In the phase 3 METEOR study (NCT01865747), cabo improved OS (median 21.4 vs 16.5 mo; HR, 0.66; 95% CI, 0.53–0.83), progression-free survival and objective response rate compared with eve in patients (pts) with previously treated advanced RCC (Choueiri 2016). Retrospective studies have shown that early tumour shrinkage (eTS), based on target lesion reduction from baseline to first post-baseline scan, has predictive value for targeted therapies in RCC (Grunwald 2015; Grunwald 2016); here we evaluate its impact on OS in METEOR. Methods: In total, 658 pts were randomized 1:1 to receive cabo (60 mg qd) or eve (10 mg qd), stratified by MSKCC risk group and number of prior VEGFR TKIs. Target lesion size was assessed by independent radiology review using CT/MRI scans at baseline, every 8 wk for the first 12 mo and every 12 wk thereafter. Median OS was estimated for pts with ≥30% eTS, any eTS or no eTS at first post-baseline scan (week 8); data cutoff, 2 October 2016 (Motzer 2018). Results: Median follow-up was 28 mo (IQR 25, 30). Median (range) time to objective response was 1.91 (1.6, 11.0) mo with cabo and 2.14 (1.9, 9.2) mo with eve, and corresponded to the time to the first post-baseline scan. A greater proportion of pts had ≥30% eTS with cabo (20%) than with eve (5%) and the rate of any eTS was higher in the cabo arm (73%) than with eve (47%; Table). Median OS with cabo vs eve for pts with ≥30% eTS was not reached (NR; 95% CI, 23.7–NR) vs 10.2 mo (95% CI, 3.9–NE), respectively (stratified HR, 0.45; 95% CI, 0.21–0.95; p