Tolerance to ischemia and hypoxia is reduced in aged human myocardium

BACKGROUND: Recovery of cardiac function after cardiac surgery and other interventional cardiac procedures in elderly patients is inferior to that in younger patients, suggesting that the aged myocardium is more sensitive to ischemia and other stresses. Although convincing data from animal studies of senescence now exist, there is a dearth of controlled in vitro studies that examine the specific response of aged human myocardium to the stress of hypoxia or ischemia. OBJECTIVE: We sought to determine the effect of age on the capacity of human atrial trabeculae to recover contractile function after in vitro hypoxic or ischemic stress. METHODS: Atrial pectinate trabeculae were dissected from the tip of 58 right atrial appendages harvested during an operation in patients aged between 34 and 89 years and electrically stimulated at 1 Hz in oxygenated Ringer's solution at 37 degrees C. Tissues experienced 30 minutes of either hypoxia (N(2) and perfusate) or simulated ischemia (humidified N(2) without perfusate) and were returned to normoxia for recovery of function for 30 minutes. Developed force and other contractile variables were determined during each period. RESULTS: Under normoxic conditions, no significant age difference was observed for any contractile function variable. However, after hypoxia, the old (70-89 years) and intermediate age groups (60-69 years) showed reduced recovery of developed force (48.5% +/- 22.2% [n = 11] and 44.9% +/- 19% [n = 12], respectively) compared with that found (66.4% +/- 19.7% [n = 15]) in the younger (34-59 years) group (mean +/- SD, P =.02). Similarly, after simulated ischemia, the groups of 70- to 89-year-old and 60- to 69-year-old subjects showed reduced recovery of developed force (35.7% +/- 17% [n = 5] and 51.1% +/- 11.8% [n = 9], respectively) compared with that found (68.2% +/- 10.4% [n = 6]) in the group of 34- to 59-year-old subjects (P =.01). Multivariable analysis, comparing 20 factors of surgical patient characteristics and recovery of developed force, found that only age (P =.01) and hypertension (P =.01) were predictors of reduced recovery of developed force after either hypoxia or simulated ischemia. CONCLUSIONS: In aged human atrial myocardium, the capacity to recover contractile function after in vitro hypoxia or simulated ischemia is reduced compared with the younger myocardium of mature adults. These findings suggest that enhanced myocardial protective strategies may be indicated for elderly patients undergoing cardiac surgery.     

香菇多糖联合抗生素治疗恶性肿瘤围化疗期肺部感染120例临床观察

目的：本文观察香菇多糖对恶性肿瘤患者围化疗期肺部感染抗生素治疗的增效作用。方法：120例围化疗期发生肺部感染恶性肿瘤患者在接受抗生素治疗的同时，随机分成加用香菇多糖针和不加香菇多糖针静脉滴注两组。每组各60例。结果：接受抗生素及香菇多糖联合治疗的患者的有效率显著提高（P〈0．05）．临床症状、体征与X光胸部片改善时间大幅缩短。结论：香菇多糖对恶性肿瘤患者围化疗期肺部感染抗生素治疗有明显增效作用。     

Pharmacokinetics of tacrolimus and mycophenolic acid are altered, but recover at different times during hepatic regeneration in rats.

Hepatic regeneration is very critical to the success of living donor liver transplantation, which allows a reduced size liver to grow in size to accommodate the requirements of both the donor and the recipient. The objectives of this study were to evaluate 1) the hepatic metabolism of the two immunosuppressive drugs, tacrolimus and mycophenolic acid (MPA), and 2) the pharmacokinetics of tacrolimus and mycophenolic acid at various time points after initiation of hepatic regeneration by partial hepatectomy in rats. The hepatic intrinsic clearance of tacrolimus was decreased to 70% and 51% of the control level at the 24th h and the 6th day, respectively, but returned to normal level by day 14. The total body clearance of tacrolimus was reduced transiently but recovered completely by day 18. The hepatic intrinsic clearance of MPA was decreased to 52% and 51% of that in control rats at the 24th h and the 6th day, respectively, but recovered to normal level by day 14. The total body clearance of MPA was reduced at the 24th h but recovered by day 6. The magnitude of reduction in the clearance of tacrolimus and MPA was much smaller than what was predicted from in vitro data. The elimination clearance of MPA glucuronide was also impaired during hepatic regeneration but recovered to normal level with time. In conclusion, the pharmacokinetics of tacrolimus and mycophenolic acid were altered during hepatic regeneration but recovered completely at different rates over time. Caution must be exercised in extrapolating in vitro data to in vivo conditions during hepatic regeneration.     

波依定与洛汀新治疗不同中医证型高血压疗效比较

目的:观察波依定与洛汀新对不同中医证型高血压的疗效是否具有中草药的某些特征,能否按中医辨证选择抗高血压药.方法:按照WHO的标准明确高血压诊断与分级,根据<中药新药临床研究指导原则>分为4型.216例患者随机分为两组,分别给予波依定与洛汀新治疗,疗程4周.分析对总体血压和不同证型血压的影响,以及对不同症状的疗效有无差异.结果:两种药物降低患者总体血压的幅度基本相同;但分层研究,对4种中医证型患者的血压的降低程度明显不同,洛汀新对肝火亢盛型血压降低幅度更明显,波依定对痰湿壅盛型比其它三型降压更好;对阴虚阳亢型和阴阳两虚型两组之间差异无显著性.对各种证型症状的改善作用也显示同样的结果.结论:抗高血压药对不同中医证型高血压的疗效不同,表明西药也同样具有中草药的某些特性,可以根据中医辨证选择抗高血压药.     

Ferric citrate for the treatment of hyperphosphatemia and anemia in patients with chronic kidney disease: a meta-analysis of randomized clinical trials

BackgroundHyperphosphatemia and anemia, which are common complications of chronic kidney disease (CKD), can independently contribute to cardiovascular events. Several previous studies have found that the iron-based phosphate binder, ferric citrate (FC), could be beneficial to both hyperphosphatemia and anemia.MethodsRelevant literature from PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials (CCRCT) and MEDLINE databases were searched up to 21 February 2022, in order to conduct a meta-analysis to investigate the efficacy, safety and economic benefits of ferric citrate treatment in CKD patients with hyperphosphatemia and anemia. The meta-analysis was conducted independently by two reviewers using the RevMan software (version 5.3).ResultsIn total, this study included 16 randomized clinical trials (RCT) involving 1754 participants. The meta-analysis showed that ferric citrate could significantly reduce the serum phosphorus in CKD patients compared to the placebo control groups (MD −1.76 mg/dL, 95% CI (−2.78, −0.75); p = 0.0007). In contrast, the difference between ferric citrate treatment and active controls, such as non-iron-based phosphate binders, sevelamer, calcium carbonate, lanthanum carbonate and sodium ferrous citrate, was not statistically significant (MD − 0.09 mg/dL, 95% CI (−0.35, 0.17); p = 0.51). However, ferric citrate could effectively improve hemoglobin levels when compared to the active drug (MD 0.43 g/dL, 95% CI (0.04, 0.82); p = 0.03) and placebo groups (MD 0.39 g/dL, 95% CI (0.04, 0.73); p = 0.03). According to eight studies, ferric citrate was found to be cost-effective treatment in comparison to control drugs. Most of the adverse events (AE) following ferric citrate treatment were mild at most.ConclusionCollectively, our review suggests that iron-based phosphate binder, ferric citrate is an effective and safe treatment option for CKD patients with hyperphosphatemia and anemia. More importantly, this alternative treatment may also less expensive. Nevertheless, more scientific studies are warranted to validate our findings.     

Neonatal clavicular fracture: clinical analysis of incidence, predisposing factors, diagnosis, and outcome

The objective of this study is to identify maternal, perinatal, and fetal risk factors for clavicular fracture in a single institution. We performed a prospective study of all deliveries during a 14-month period to identify confirmed cases of neonatal clavicular fracture. The control group consisted of the deliveries immediately preceding and following the index cases. Fifty-three cases of clavicular fracture were identified among the 4789 deliveries from October 1995 through November 1996 for an incidence of 1.11%. Three neonates in the clavicular fracture group were delivered through cesarean section. Neonates with fracture were significantly heavier at birth than those without (3564 vs. 3283 g, p <0.001), and had a lower mean head-to-abdominal circumference ratio (0.93 vs. 1.08, p <0.001), history of giving birth to a macrosomia (21 vs. 4%, p <0.05). The anterior shoulder was the predominant site of fracture (30/53). Fracture was detected mostly during the first 3 days of neonatal life (46/53). The outcome was benign, with complete recovery in all cases and no associated neurological sequelae. Neonatal clavicular fracture tended to be associated with neonatal somatometric characteristics and difficult deliveries. Considering the benign nature of this birth trauma, more invasive intrapartum management to lower its incidence is not advised.     

Elucidating the mechanism of nucleation inhibition of pathology crystallization of gout based on the evidence from amorphous form and in solution

The first gout attack in a hyperuricaemic patient may be regarded as a nucleation event which is caused by monosodium urate monohydrate (MSUM) deposition in the synovial fluid. The effect of Tailor-Made Inhibition (TMI) may be effective as drugs for the prevention of aberrant nucleation and crystallization. Therefore, the understanding of the underlying mechanisms in inhibiting the MSUM nucleation by TMI has proven to be of great significance. Yet most of the published studies about nucleation inhibition have tended to focus on simpler molecular models with a hydrogen-bonded acceptor and donor, which may be not suitable for the uric acid molecule with multiple hydrogen-bonded acceptors and donors under physiological conditions. Herein, the mechanisms of nucleation inhibition of MSUM were explored in a simulated biological environment (0.15 M Na⁺ and pH 7.40) in the presence and absence of TMI. And the evidence of nucleation inhibition by TMI in solution and the amorphous form of MSUM was investigated by HNMR, IR, Raman, PXRD, Dynamic light scattering (DLS), induction time measurements, and density functional theory (DFT) calculations. Results showed that the inhibition comes from a combination of kinetic and thermodynamic effects, with an impact of kinetics as the TMI inhibition effects far exceeded what could be accounted for by changes in usual factors of classical nucleation theory. The data demonstrated that the complex between urate and TMI disturbed the formation of two-dimensional sheets of sodion and purine rings parallel to the (011) plane and further impeded the formation of a three-dimensional structure with aromatic stacking interactions in solution. To our knowledge, the nucleation inhibition of TMI is achieved by suppressing interplanar stacking, which is a mechanism proposed for the first time.

Xanthine, a tailor-made inhibitor, could suppress nucleation in the crystallization of gout pathology by blocking the dominant interplanar accumulation in a solution.     

Hypertension and Associated Risk Factors among Children with Intellectual Disability: A Cross-Sectional Study

To investigate the prevalence of hypertension and associated risk factors in Chinese children with intellectual disability, a cross-sectional study was conducted in a sample of 558 children with intellectual disability aged 6–18 years in Hong Kong, and 452 (81.0%) with valid data were included in the data analysis. Blood pressure was measured according to a standard protocol. Hypertension was defined using the age-, gender-, and height-specific classification criteria recommended by the 2018 Chinese Guidelines for Children. Multivariate and hierarchical logistic regression was fitted to examine the associations of hypertension with potential risk factors. Overall, 31.4% of the participants were classified as having hypertension. Obese children were more likely to develop hypertension than non-obese children (adjusted OR = 2.77, 95% CI: 1.28, 5.99, p = 0.010). A paternal education of college or above and a paternal occupation of clerks, sales representatives, and workers were also associated with an increased risk of hypertension. The prevalence of hypertension is high among Chinese children with intellectual disability. Obesity was the strongest risk factor. Further longitudinal studies are warranted to confirm our findings. Nevertheless, preventions against obesity are promising to receive doubled benefits in reducing both obesity and hypertension, given its strong relationship with hypertension in this special population.     

The impact of alfentanil supplementation on the sedation of bronchoscopy: A meta-analysis of randomized controlled trials

Background:The efficacy of alfentanil supplementation for the sedation of bronchoscopy remains controversial. We conduct a systematic review and meta-analysis to explore the influence of alfentanil supplementation on the sedation during bronchoscopy.Methods:We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through December 2019 for randomized controlled trials (RCTs) assessing the effect of alfentanil supplementation versus placebo for the sedation during bronchoscopy. This meta-analysis is performed using the random-effect model.Results:Five RCTs are included in the meta-analysis. Overall, compared with control group for bronchoscopy, alfentanyl supplementation is associated with significantly reduced coughing scores (Std. MD = –0.55; 95% CI = –0.96 to –0.14; P = 0.009) and dose of propofol (Std. MD = –0.34; 95% CI = –0.64 to –0.04; P = 0.03), but reveals the increase in hypoxemia (RR = 1.56; 95% CI = 1.17 to 2.08; P = 0.002).Conclusions:Alfentanyl supplementation benefits to reduce coughing scores and dose of propofol for bronchoscopy, but increases the incidence of hypoxemia. The use of alfentanyl supplementation for bronchoscopy should be with caution.