Moorerobles6309

The development of CDK 4/6 inhibitors has dramatically changed the therapeutic management of hormone receptor-positive (HR+) and HER2 negative metastatic breast cancer (MBC). In combination with fulvestrant, palbociclib, ribociclib and abemaciclib have each been approved for HR+/HER2- MBC following the results of randomized Phase III studies (PALOMA-3, MONALEESA-3, MONARCH-2) and shown a significant advantage in PFS. Data from clinical trials support the combination with aromatase inhibitors in the first line setting and with fulvestrant in the second line. Each agent is well tolerated, and most of the toxicities observed with this class of drugs are generally easily manageable and free from particular complications. The latest evidence from MONARCH-2 and MONALEESA-3 trials shows benefits in terms of overall survival (OS), suggesting an option of using fulvestrant in combination with CDK 4/6 inhibitors in the first line setting. Additional research is needed to determine optimal treatment sequencing, understand the mechanisms of resistance, and develop novel therapeutic strategies to overcome clinical resistance and further improve the outcomes of patients with HR+/HER- MBC. Key questions in the field include the further impact on progression-free survival, overall survival, and the role of continuing CDK 4/6 blockade beyond progression. The purpose of this review is to describe the clinical relevance of fulvestrant in combination with CDK 4/6 inhibitors in HR+/HER2- MBC patients, as well as to discuss the current controversies and evolving research areas. © 2020 Iorfida et al.Objective Chronic shoulder pain (CSP) is a common health problem associated with shoulder dysfunction and persistent pain for many different reasons. However, the studies of pain-related functional brain regions in CSP have been poorly investigated. The main purpose of our study was to observe whether there are abnormal functional changes in brain regions in patients with CSP by using functional magnetic resonance imaging (fMRI). Patients and Methods We compared the differences of brain regions between 37 patients with CSP and 24 healthy controls (HC) using regional homogeneity (ReHo) method. The patients with chronic shoulder pain and healthy controls were matched for age and gender. Brain regions which had abnormal ReHo values were defined as seed region of interests. The approach of seed-based functional connectivity (FC) was further performed to analyze the connectivity between the seeds and whole brain regions. The relationship between abnormal regions and current clinical pain was also evaluated. Results Compared to healthy controls, the patients with CSP showed increased ReHo values in the left middle temporal gyrus and decreased ReHo values in right orbitofrontal cortex (OFC). The seed-based analyses demonstrated decreased connectivity between the right OFC and right rectus, superior frontal gyrus in patients with chronic shoulder pain. However, a correlation between ReHo values and clinical characteristics in CSP patients was not found. Conclusion The observed results indicate that there are abnormal ReHo values in brain regions of patients with CSP, especially in the OFC and middle temporal gyrus. Our findings demonstrate that the experience of CSP patients may be mainly associated with cognitive-affective pain processing, rather than nociception. © 2020 Li et al.Background Although ultrasound-guided transversus abdominis plane block (TAPB) is widely used in multimodal analgesia after cesarean delivery (CD), the complications of TAPB during analgesia after CD have rarely been reported. Methods A total of 84 cases of CD were randomly assigned to either a ropivacaine group (R group) or ropivacaine + dexamethasone group (RD group) in this double-blind trial. The pain site and pain degree at rest and during activity at 2 h, 6 h, 10 h, 12 h, 14 h, 16 h, 20 h, and 24 h after maternal surgery were recorded. The consumption of opioids at 24h, postoperative nausea, vomiting, exhaustion, and other adverse reactions were recorded. Results A total of 80 patients were included in the analysis of results. A total of 19 patients developed ISP, 14 in the R group and 5 in the RD group. The incidence of ISP in the R and RD groups was 35% and 12.5%, respectively. The results described above showed that combining dexamethasone with ropivacaine reduced the incidence of ISP, and the difference was statistically significant (P less then 0.05). Two groups of women with positive ISP had higher values of opioid consumption than women with negative ISP, but the difference was not significant. Conclusion Dexamethasone as an adjuvant for ropivacaine can effectively relieve the ISP of ultrasound-guided TAPB after CD, and can enhance the analgesic effect of ropivacaine. © 2020 Liu et al.Purpose This study aimed to compare the analgesic outcomes between primary and repeated cesarean delivery. Patients and Methods We performed a retrospective analysis based on the medical records of a teaching hospital in China from January 2018 to March 2019. We collected data on demographic characteristics, perioperative complications, anesthesia, and surgical factors for cesarean delivery patients. We also recorded the postoperative analgesic strategy, pain intensity (assessed by the number rating scale) during the first 48 hrs after surgery, hospital cost, and hospital stay. Postoperative inadequate analgesia was defined by a score of ≥ 4 in the number rating scale. Analgesic outcomes after cesarean delivery between primiparas and multiparas were compared using propensity score matching analysis. Moreover, subgroup logistic analysis for different age groups (≥ 35 and less then 35 years) was performed to investigate the effect of the maternal category on postoperative inadequate analgesia. Results A total of 1543 patients were included in the analysis and 571 pairs (1142 patients) were matched in the primiparas and multiparaparas group according to their propensity score. In both the non-matched and matched cohort, the incidence of inadequate analgesia in the primiparas group was lower than that in the multiparas group (16.7% vs. 24.0%, P less then 0.001 and 16.1% vs. 23.5%, P = 0.002; respectively). The multiparas group was identified as being at risk of inadequate analgesia after cesarean delivery in both age groups (age ≥ 35 years, odds ratio 2.18, 95% confidence interval 1.20-3.95; age less then 35 years, odds ratio 1.43, 95% confidence interval 1.08-1.89). Conclusion Multiparas that undergo a repeat cesarean delivery had a significantly higher risk of inadequate postoperative pain treatment than primiparas. The maternal category should be considered when formulating the postoperative analgesia strategy after cesarean delivery. © 2020 Yang et al.The complexity of orphan diseases, which are those that do not have an effective treatment, together with the high dimensionality of the genetic data used for their analysis and the high degree of uncertainty in the understanding of the mechanisms and genetic pathways which are involved in their development, motivate the use of advanced techniques of artificial intelligence and in-depth knowledge of molecular biology, which is crucial in order to find plausible solutions in drug design, including drug repositioning. Particularly, we show that the use of robust deep sampling methodologies of the altered genetics serves to obtain meaningful results and dramatically decreases the cost of research and development in drug design, influencing very positively the use of precision medicine and the outcomes in patients. The target-centric approach and the use of strong prior hypotheses that are not matched against reality (disease genetic data) are undoubtedly the cause of the high number of drug design failures and attrition rates. Sampling and prediction under uncertain conditions cannot be avoided in the development of precision medicine. © 2020 Álvarez-Machancoses et al.Asthma is a chronic respiratory disease that affects 339 million people worldwide and has a considerable impact on the pediatric population. Asthma symptoms can be controlled by pharmacological treatment. However, some patients do not respond to therapy and continue suffering from symptoms, which impair the quality of life of patients and limit their daily activity. Genetic variation has been shown to have a role in treatment response. The aim of this review is to update the main findings described in pharmacogenetic studies of pediatric asthma published from January 1, 2018 to December 31, 2019. During this period, the response to short-acting beta-agonists and inhaled corticosteroids in childhood asthma has been evaluated by eleven candidate-gene studies, one meta-analysis of a candidate gene, and six pharmacogenomic studies. The findings have allowed validating the association of genes previously related to asthma treatment response (ADRB2, GSDMB, FCER2, VEGFA, SPAT2SL, ASB3, and COL2A1), and identifying novel associations (PRKG1, DNAH5, IL1RL1, CRISPLD2, MMP9, APOBEC3B-APOBEC3C, EDDM3B, and BBS9). However, some results are not consistent across studies, highlighting the need to conduct larger studies in diverse populations with more homogeneous definitions of treatment response. Once stronger evidence was established, genetic variants will have the potential to be applied in clinical practice as biomarkers of treatment response enhancing asthma management and improving the quality of life of asthma patients. © 2020 Perez-Garcia et al.Background Several studies have reported the relationship of diabetes mellitus (DM) and obesity with bone mineral density (BMD), but the conclusions remain unclear. Infigratinib supplier This study aimed to provide more information for the relationship of plasma glucose and abdominal visceral fat (AVF) with BMD and bone mineral content (BMC) in women with different glucose metabolism status. Methods Patients were screened by oral glucose tolerance test (OGTT) and were divided into three groups normal glucose tolerance (NGT, n=132), pre-diabetes mellitus (pre-DM, n=28) and newly diagnosed type 2 DM (T2DM, n=27) groups. Plasma glucose concentrations, anthropometric measurements, body composition, and BMD were measured. Analysis of variance (ANOVA), pearson correlation, and multiple linear regression models were used to evaluate the relationship between BMD, plasma glucose, AVF, and other variables. Results The percentage of subjects with osteoporosis or low BMD was 29.9%, and 66.7% subjects in T2DM group were significantly higher than that in the pre-DM (28.6%) and NGT (22.7%) groups (p=0.005 and p less then 0.001, respectively). Both BMD at femoral neck (FN) and lumbar spine (LS) of T2DM group were lower than those in NGT group (p=0.009 and p=0.003, respectively), and BMC of T2DM group was lower than those of NGT and pre-DM groups (p less then 0.001). The results of statistical analysis revealed that both two-hour plasma glucose (2-h PG) and age showed negative correlation with BMC, FN BMD, and LS BMD. AVF showed positive correlation with BMC and LS BMD. Furthermore, the lean mass (LM) showed independent positive effects on BMC. Conclusion Our findings suggest that 1) Age is a strong negative predictor of bone mass. 2) A direct negative effect of increasing 2-h PG might be more prominent at bone mass in women. 3) A moderate increase in AVF is beneficial to bone mass, while excessive increase might be harmful. 4) LM is a positive predictor of BMC. © 2020 Jia et al.