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This study was planned to evaluate the outcome of patients aged ≥80 years undergoing combined conventional aortic valve replacement (AVR) and coronary artery bypass grafting (CABG). This is a systematic review of the literature and meta-analysis of data on patients aged ≥80 years who underwent combined AVR and CABG. The literature search yielded 40 observational studies reporting on 8,975 patients aged ≥80 years. Pooled proportion of immediate postoperative mortality was 9.7% (95% CI 8.4-11.1, 40 studies, 8,975 patients). Immediate mortality was 8.2% (95% CI 6.5-10.0) in 15 studies with a mid-date from 2000 to 2007 and 10.8% (95% CI 9.1-12.7) in 25 studies with a mid-date from 1982 to 1999 (P = .043). Postoperative stroke rate was 3.7% (95% CI 2.8-4.8, 12 studies, 2,770 patients), and postoperative implantation of pacemaker was 4.3% (95% CI 2.6-6.5, 5 studies, 535 patients). The mean length of stay in intensive care unit was 5.3 days (95% CI 3.3-7.3, 5 studies, 490 patients), and the mean length of in-hospital stay was 16.9 days (95% CI 12.4-21.4, 5 studies, 424 patients). One-, 3-, 5- and 10-year pooled survival rates after combined AVR and CABG were 83.2%, 72.9%, 60.8%, and 25.7%, respectively. Conventional AVR and CABG in patients aged ≥80 years are associated with significant operative mortality and morbidity as well as prolonged in-hospital treatment. However, conventional surgery is associated with remarkably good late survival. This suggests that any alternative treatment modality must prove itself of being enough durable also in the very elderly.

The development of isoform selective inhibitors of the carbonic anhydrase (CA; EC 4.2.1.1) enzymes represents the key approach for the successful development of druggable small molecules. Herein we report a series of new benzenesulfamide derivatives (-NH-SO2NH2) bearing the 1-benzhydrylpiperazine tail and connected by means of a β-alanyl or nipecotyl spacer. All compounds 6a–l were investigated in vitro for their ability to inhibit the physiological relevant human (h) CA isoforms such as I, II, IV and IX. Molecular modeling provided further structural support to enzyme inhibition data and structure-activity relationship. In conclusion the hCA I resulted the most inhibited isoform, whereas all the remaining ones showed different inhibition profiles.

IntroductionFetal growth restriction (FGR) includes different conditions in which a fetus fails to reach the own full growth, and accounts for 28%–45% of non-anomalous stillbirths. The management of FGR is based on the prolongation of pregnancy long enough for fetal organs to mature while preventing starvation. As for pharmacological management, most guidelines recommend treatment with low-dose aspirin and/or with heparin, although this approach is still controversial and innovative promising therapies are under investigation. As no firm evidence exists to guide clinicians towards the most effective therapeutic intervention, this protocol describes methods for a systematic review and network meta-analysis (NetMA) of pharmacological treatments for FGR prevention.Methods and analysisWe will search MEDLINE and Embase for clinical trials and observational studies performed on gestating women with clinically diagnosed risk of FGR. Experimental interventions will include heparin and low-molecular-weight heparin, acetylsalicylic acid, antiplatelet agents, phosphodiesterase type 3 and 5 inhibitors, maternal vascular endothelial growth factor gene therapy, nanoparticles, microRNA, statins, nitric oxide donors, hydrogen sulphide, proton pump inhibitors, melatonin, creatine and N-acetylcysteine, and insulin-like growth factors, compared between each other or to placebo or no treatment. Primary efficacy outcome is FGR. Secondary efficacy outcomes will be preterm birth, fetal or neonatal death and neonatal complications. For the safety outcome, all adverse events reported in included studies and experienced by either mothers, fetuses or newborns will be considered. Two review authors will independently screen title, abstract and full paper text, and will independently extract data from included studies. Where possible and appropriate, for primary and secondary efficacy outcomes, a NetMA will be performed using a random-effects model within a frequentist framework. Adverse events will be narratively described.Ethics and disseminationResults will be disseminated through a peer-reviewed scientific journal, and by scientific congresses and meetings.PROSPERO registration numberCRD42019122831.

Background Genetic polymorphisms in genes involved in pain modulation have been reported to be associated to opioid efficacy and safety in different clinical settings. Methods The association between COMT Val158Met polymorphism (rs4680) and the inter-individual differences in the response to opioid analgesic therapy was investigated in a cohort of 87 Italian paediatric patients receiving opioids for cancer pain (STOP Pain study). Furthermore, a systematic review of the association between opioid response in cancer patients and the COMT polymorphism was performed in accordance with the Cochrane Handbook and the Prisma Statement. Results In the 87 paediatric patients, pain intensity (total time needed to reach the lowest possible level) was significantly higher for G/G than A/G and A/A carriers ( p -value = 0.042). In the 60 patients treated only with morphine, the mean of total dose to reach the same pain intensity was significantly higher for G/G than A/G and A/A carriers (p-value = 0.010). Systematic review identified five studies on adults, reporting that opioid dose (mg after 24 h of treatment from the first pain measurement) was higher for G/G compared to A/G and A/A carriers. Conclusions Present research suggests that the A allele in COMT polymorphism could be a marker of opioid sensitivity in paediatric cancer patients (STOP Pain), as well as in adults (Systematic Review), indicating that the polymorphism impact could be not age-dependent in the cancer pain context. Trial registration Registration number: CRD42017057831 .

BackgroundOptimal blood pressure (BP) control can prevent major adverse health events, but target values are still controversial, especially in older patients with comorbidities, frailty and disability.AimsTo evaluate mortality according to BP values in a cohort of older adults enrolled in the Fiesole Misurata Study, after a 6-year follow-up.MethodsLiving status as of December 31, 2016 was obtained in 385 subjects participating in the Fiesole Misurata Study. Patients' characteristics were analysed to detect predictors of mortality. At baseline, all participants had undergone office BP measurement and a comprehensive geriatric assessment.ResultsAfter a 6-year follow-up, 97 participants had died (25.2%). After adjustment for comorbidities and comprehensive geriatric assessment, mortality was significantly lower for SBP 140–159 mmHg as compared with 120–139 mmHg (HR 0.54, 95% CI 0.33–0.89). This result was also confirmed in patients aged 75 + (HR 0.49, 95% CI 0.29–0.85), and in those with disability (HR 0.36, 95% CI 0.15–0.86) or taking antihypertensive medications (HR 0.49, 95% CI 0.28–0.86).DiscussionAn intensive BP control may lead to greater harm than benefit in older adults. Indeed, the European guidelines recommend caution in BP lowering in older patients, especially if functionally compromised, to minimize the risk of hypotension-related adverse events.ConclusionsAfter a 6-year follow-up, mortality risk was lower in participants with SBP 140–159 mmHg as compared with SBP 120–139 mmHg, in the overall population and in the subgroups of subjects aged 75 + , with a disability or taking anti-hypertensive medications.