Influence of ADRB1, ADRB2, and COMT Genetic Polymorphisms on Postoperative Outcomes of Patients Undergoing Cardiac Valve Surgery

PurposeThe aim of this study is to prospectively investigate the influence of ADRB and COMT gene polymorphisms on postoperative outcomes of patients undergoing cardiac surgery.MethodsThis prospective cohort study included 223 patients undergoing elective cardiac valve surgery using cardiopulmonary bypass. Demographic information, intraoperative data, postoperative data, and blood samples were collected. Patients were genotyped for single-nucleotide polymorphisms (SNPs) of ADRB1 rs1801253, ADRB2 rs1042713, and COMT rs4680. Major adverse cardiovascular and cerebrovascular events (MACCEs) were used as the primary outcome to evaluate the postoperative prognosis of patients. Secondary outcomes included the duration of mechanical ventilatory support, intensive care unit stay, postoperative hospital stay, and postoperative need of inotropic or vasoactive agents.FindingsThe overall incidence of MACCEs was 15.2%. Among 3 SNP loci, only different genotyped carriers of ADRB2 rs1042713 had statistically significant differences in the incidence of MACCEs (P = 0.005), especially for acute kidney injury (P = 0.023). The proportions of postoperative norepinephrine demand of patients carrying the AA genotype of ADRB2 rs1042713 (P = 0.016) and the AG genotype of COMT rs4680 (P = 0.018) were low. The duration of mechanical ventilatory support (P = 0.034) and postoperative hospital stay (P = 0.045) of patients carrying the AG genotype of COMT rs4680 was shortest. After multiple logistic regression analysis, we found that the G allele carriers of ADRB2 rs1042713 had a higher risk of MACCEs (AG vs AA genotype: odds ratio [OR] = 4.348; 95% CI, 1.529–12.359, P = 0.006; GG vs AA genotype: OR = 3.722; 95% CI, 1.060–13.071; P = 0.040), in particular with acute kidney injury (AG vs AA genotype: OR = 5.273; 95% CI, 1.093–25.451; P = 0.038; GG vs AA genotype: OR = 7.533; 95% CI, 1.275–44.522; P = 0.026). There was no SNP-SNP interaction found among the 3 SNPs with multifactor dimensionality reduction analysis.ImplicationThe ADRB2 rs1042713 polymorphism might be related to prognosis of patients undergoing cardiac surgery. Patients carrying the G allele of ADRB2 rs1042713 had a higher risk of developing MACCEs, especially acute kidney injury. chictr.org.com identifier: ChiCTR1800015105.     

Open surgical embolectomy for cardiogenic cerebral embolism: Technical note and its advantages

Background and importanceIn cardiogenic cerebral embolism, early recanalization is the most important factor for good prognosis. However, endovascular thrombectomy often fails to achieve recanalization. We present an open surgical embolectomy technique and discuss its advantages.Clinical presentationA 79-year-old woman developed right hemiparesis and severe aphasia. Magnetic resonance imaging revealed an acute cerebral infarction caused by left middle cerebral artery (MCA) occlusion. We attempted endovascular thrombectomy but failed because it was impossible to guide the catheter to the occlusion site. Hence, we converted to open surgical embolectomy. Sylvian fissure was widely opened. After confirming the range of thrombosis using indocyanine green videoangiography (ICGVAG), the proximal and distal arteries were secured, and a temporary clip was placed on the distal M2 to prevent distal thrombosis migration. MCA was cut approximately 3 mm from the bifurcation, and thrombosis was removed using micro-forceps. The proximal clip was simultaneously inserted but was not clamped because the thrombus was extruded by proximal vascular flow. Immediately after removing the thrombus, intense bleeding occurred from the proximal flow. An assistant clamped the proximal artery using the prepared clip, and the incised area of MCA was sutured using 9-0 threads. We finally confirmed blood flow after recanalization using ICGVAG. The time from skin incision to recanalization was 27 min. After the procedure, the patient developed slight aphasia but had no hemiparesis and was later transferred to a rehabilitation hospital.ConclusionOpen surgical embolectomy may be a secondary rescue treatment option in the case of endovascular thrombectomy failure.     

川芎嗪逆转脂肪细胞介导的卵巢癌奥沙利铂耐药的作用及机制研究

目的： 研究川芎嗪（Ligustrazine）逆转脂肪细胞介导的卵巢癌奥沙利铂耐药的作用,以及对肿瘤细胞中耐药相关蛋白ABCB1、ABCC1和ABCG2表达的影响。方法： MTS法研究川芎嗪逆转脂肪细胞介导的卵巢癌奥沙利铂耐药的IC₅₀值和逆转耐药系数;流式细胞实验研究川芎嗪对脂肪细胞介导的耐药卵巢癌细胞的凋亡水平的影响;划痕实验研究川芎嗪对脂肪细胞介导的耐药卵巢癌细胞的迁移能力的影响;Western Blot研究川芎嗪对肿瘤细胞中耐药相关蛋白ABCG1、ABCC1和ABCG2表达水平。结果： 川芎嗪能够逆转脂肪细胞介导的卵巢癌奥沙利铂耐药,其逆转耐药系数为2.8;川芎嗪能够增加脂肪细胞和肿瘤细胞共培养体系下肿瘤细胞的凋亡;川芎嗪能够抑制脂肪细胞和肿瘤细胞共培养体系下肿瘤细胞的迁移;川芎嗪能够减少肿瘤细胞中耐药相关蛋白ABCB1、ABCC1和ABCG2的表达。结论： 川芎嗪能够逆转脂肪细胞介导的卵巢癌奥沙利铂耐药的作用且其机制与减少耐药相关蛋白ABCB1、ABCC1和ABCG2的表达有关。     

Occult infection with HBV intergenotypic A2/G recombinant following acute hepatitis B caused by an HBV/A2 isolate

Viral and host factors leading to occult hepatitis B virus (HBV) infection (OBI) are not fully understood. Whether HBV genotype may influence the occurrence and course of OBIs is unknown. Here, we describe the case of a patient infected with HBV genotype A2 who developed symptomatic acute hepatitis and did not seroconvert after loss of HBsAg and HBeAg. The acute phase of hepatitis B was followed by a period of more than 2 years during which the DNA of an intergenotypic HBV/A2/G recombinant was intermittently detected in serum.     

腹腔镜单纯尿道前壁加强法与尿道前后壁加强法(Sandwich法)改善前列腺癌根治术后早期尿控的对比分析

目的 探讨腹腔镜单纯尿道前壁悬吊加强法和尿道前后壁加强法对前列腺癌根治术后早期尿控的疗效。方法 纳入自2014年2月至2019年12月,首都医科大学附属北京朝阳医院泌尿外科收治的99例前列腺癌患者,其中56例采用尿道前后壁加强法治疗,43例采用单纯尿道前壁悬吊加强法治疗,比较两组患者的年龄、体质量指数、前列腺体积、术前前列腺特异性抗原（prostate specific antigen,PSA）,临床分期、手术时间、病理分期、Gleason评分、淋巴结阳性率、术后切缘阳性率及通过电话随访拔除尿管后第2、4、12、24、52周时的尿控恢复情况。结果 两组患者的年龄、体质量指数、前列腺体积、PSA、临床分期、手术时间、病理分期、Gleason评分、淋巴结阳性率、术后切缘阳性率差异均无统计学意义（P>0.05）,拔除尿管后第12周可见单纯尿道前壁悬吊加强法的治疗效果优于尿道前后壁加强法,但各指标差异仍无统计学意义（P=0.058）。结论 腹腔镜前列腺癌根治术中采用前壁加强缝合悬吊法安全易行,与前后壁双重加强的方法相比,疗效接近。     

Osteocyte regulation of phosphate homeostasis and bone mineralization underlies the pathophysiology of the heritable disorders of rickets and osteomalacia

Although recent studies have established that osteocytes function as secretory cells that regulate phosphate metabolism, the biomolecular mechanism(s) underlying these effects remain incompletely defined. However, investigations focusing on the pathogenesis of X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets (ADHR), and autosomal recessive hypophosphatemic rickets (ARHR), heritable disorders characterized by abnormal renal phosphate wasting and bone mineralization, have clearly implicated FGF23 as a central factor in osteocytes underlying renal phosphate wasting, documented new molecular pathways regulating FGF23 production, and revealed complementary abnormalities in osteocytes that regulate bone mineralization. The seminal observations leading to these discoveries were the following: 1) mutations in FGF23 cause ADHR by limiting cleavage of the bioactive intact molecule, at a subtilisin-like protein convertase (SPC) site, resulting in increased circulating FGF23 levels and hypophosphatemia; 2) mutations in DMP1 cause ARHR, not only by increasing serum FGF23, albeit by enhanced production and not limited cleavage, but also by limiting production of the active DMP1 component, the C-terminal fragment, resulting in dysregulated production of DKK1 and β-catenin, which contributes to impaired bone mineralization; and 3) mutations in PHEX cause XLH both by altering FGF23 proteolysis and production and causing dysregulated production of DKK1 and β-catenin, similar to abnormalities in ADHR and ARHR, but secondary to different central pathophysiological events. These discoveries indicate that ADHR, XLH, and ARHR represent three related heritable hypophosphatemic diseases that arise from mutations in, or dysregulation of, a single common gene product, FGF23 and, in ARHR and XLH, complimentary DMP1 and PHEX directed events that contribute to abnormal bone mineralization.This article is part of a Special Issue entitled "The Osteocyte".     

Cross sectional survey of Varicella-Zoster virus and measles seropositivity in people living with HIV in a Parisian suburb and a review of current immunization guidelines

According to evidence-based guidelines, vaccines against measles and varicella are generally recommended to susceptible HIV-positive patients, as long as they are not severely immunocompromised. However, routine screening to determine serologic status is not recommended. We conducted a seroprevalence study of anti-measles and anti-Varicella-Zoster virus (VZV) antibodies in adults living with HIV (PLWHA) consulting at Avicenne University Hospital in a Parisian suburb. Sera were collected in years 2018–2020 and tested by commercial immunoassays in 268 patients. Most of the patients were born in Sub-Saharan Africa (55 %) and only 23 % in Europe. Measles and varicella seropositivity were present respectively in 91.4 % and 96.2 % of patients. One patient in ten was seronegative to at least one of tested diseases. In the univariate analysis, only younger age (p = 0.027) was associated with a higher risk of measles seronegativity, while shorter time since arrival in France (p < 0.001) and shorter time since HIV discovery (p = 0.007) were associated with a higher risk of VZV seronegativity. In multivariate analysis no association was found. This study highlights the absence of specific risk factors for VZV and measles seronegativity in PLWHA and supports the importance of routine screening, in order to increase immunization rates and reduce risk of complications.