Myocardial Fibrosis and Inflammation by CMR Predict Cardiovascular Outcome in People Living With HIV

ObjectivesThe goal of this study was to examine prognostic relationships between cardiac imaging measures and cardiovascular outcome in people living with human immunodeficiency virus (HIV) (PLWH) on highly active antiretroviral therapy (HAART).BackgroundPLWH have a higher prevalence of cardiovascular disease and heart failure (HF) compared with the noninfected population. The pathophysiological drivers of myocardial dysfunction and worse cardiovascular outcome in HIV remain poorly understood.MethodsThis prospective observational longitudinal study included consecutive PLWH on long-term HAART undergoing cardiac magnetic resonance (CMR) examination for assessment of myocardial volumes and function, T1 and T2 mapping, perfusion, and scar. Time-to-event analysis was performed from the index CMR examination to the first single event per patient. The primary endpoint was an adjudicated adverse cardiovascular event (cardiovascular mortality, nonfatal acute coronary syndrome, an appropriate device discharge, or a documented HF hospitalization).ResultsA total of 156 participants (62% male; age [median, interquartile range]: 50 years [42 to 57 years]) were included. During a median follow-up of 13 months (9 to 19 months), 24 events were observed (4 HF deaths, 1 sudden cardiac death, 2 nonfatal acute myocardial infarction, 1 appropriate device discharge, and 16 HF hospitalizations). Patients with events had higher native T1 (median [interquartile range]: 1,149 ms [1,115 to 1,163 ms] vs. 1,110 ms [1,075 to 1,138 ms]); native T2 (40 ms [38 to 41 ms] vs. 37 ms [36 to 39 ms]); left ventricular (LV) mass index (65 g/m² [49 to 77 g/m²] vs. 57 g/m² [49 to 64 g/m²]), and N-terminal pro–B-type natriuretic peptide (109 pg/l [25 to 337 pg/l] vs. 48 pg/l [23 to 82 pg/l]) (all p < 0.05). In multivariable analyses, native T1 was independently predictive of adverse events (chi-square test, 15.9; p < 0.001; native T1 [10 ms] hazard ratio [95% confidence interval]: 1.20 [1.08 to 1.33]; p = 0.001), followed by a model that also included LV mass (chi-square test, 17.1; p < 0.001). Traditional cardiovascular risk scores were not predictive of the adverse events.ConclusionsOur findings reveal important prognostic associations of diffuse myocardial fibrosis and LV remodeling in PLWH. These results may support development of personalized approaches to screening and early intervention to reduce the burden of HF in PLWH (International T1 Multicenter Outcome Study; NCT03749343).     

内镜下精准食管胃静脉曲张断流术的前瞻性研究（附180例报告）

目的前瞻性研究内镜下精准食管胃静脉曲张断流术的临床疗效及安全性。方法 180例肝硬化伴食管胃静脉曲张行内镜下治疗者纳入前瞻性分析,行内镜下精准食管胃静脉曲张断流术。采用改良的"三明治夹心法",聚桂醇-组织胶-生理盐水,行血管来源支精准断流治疗,观察治疗的显效率、有效率、改善率以及再出血率和并发症发生情况。结果术后1个月,静脉曲张显效率67.8%(122/180),有效率30.0%(54/180),无效率2.2%(4/180),改善率97.8%(176/180)。术后2周内,再出血率3.3%(6/180)。术后3个月内,再出血率7.2%(13/180)。所有患者均无严重并发症发生,总体并发症发生率37.8%(68/180)。结论内镜下精准食管胃静脉曲张断流术疗效及安全性较好,值得推广。     

肿瘤坏死因子受体选择性拮抗剂的研究进展

肿瘤坏死因子(TNF)信号通路是很有价值的治疗靶标,抗TNF药物已成功治疗自身免疫和炎症疾病,但传统的抗TNF药物完全封闭TNF信号通路,导致影响自身的免疫调节和监视功能而增加感染、致癌的风险和产生新的自身免疫疾病。选择性抑制sTNF/TNFR1而保留mTNF/TNFR2传导的信号能减少副作用而不降低治疗效果。该文探讨了选择性抑制TNFR1介导的信号通路对治疗TNF相关疾病的意义,分析TNF识别并激活肿瘤坏死因子受体(TNFR)的作用机制,可能会为设计新药提供新的思路。     

国家免费艾滋病抗病毒药物治疗4年疗效观察

目的 观察国家免费艾滋病抗病毒药物治疗效果。方法 回顾性分析嘉兴市纳入国家免费高效抗病毒治疗的艾滋病病例治疗效果。结果 ①随着治疗时间增加,169例病例CD4⁺T淋巴细胞计数均值和增长值均呈明显上升趋势,均值由基线的(155.36±99.86)μL^-1持续上升至48个月时的(360.98±141.09)μL^-1(b=0.362,F=182.07,P<0.001);增长值由6个月时的(84.43±81.31)μL^-1不断上升至48个月时的(242.88±140.23)μL^-1(b=0.364,F=134.82,P<0.001)。②对基线CD4⁺T淋巴细胞按照≤200 μL^-1和>200~350 μL^-1分组后进行不同治疗阶段抗病毒效果分析发现,2组各治疗阶段CD4⁺T淋巴细胞计数均明显增长(P<0.01),随着治疗时间的增加,2组CD4⁺T淋巴细胞计数增长均呈线性趋势(≤200 μL^-1组,F线性=274.36,P<0.001;>200~350 μL^-1组,F线性=102.25,P<0.001);同一疗程不同基线组分析表明,各疗程不同基线组之间CD4⁺T淋巴细胞增长差异均无统计学意义。③治疗满1,2,3年的HIV病毒抑制率(病毒载量<400 cp·mL^-1)分别为68.55%(109/159)、77.36%(123/159)、87.42%(139/159),抗病毒治疗失败率(病毒载量≥10 000 cp·mL^-1)分别为12.58%(20/159)、8.80%(14/159)、3.77%(6/159)。④抗病毒治疗失败病例中有10例检测出耐药基因。结论 国家免费艾滋病抗病毒药物治疗4年疗效明显,但仍有不足,应采取相应措施改进。     

Adverse effects of vagotomy on ethanol-induced gastric injury in the rat

Truncal vagotomy is known to aggravate the damaging effects of alcohol-induced gastric injury and prevent the occurrence of adaptive cytoprotection against such injury by a mild irritant. This study was undertaken to determine whether aberrations in glutathione (GSH) metabolism were responsible for these vagotomy-induced effects. Fasted rats (6–8/group) were subjected to truncal vagotomy and pyloroplasty or sham vagotomy and pyloroplasty. One week later they were given 2 ml of oral saline or the mild irritant, 25% ethanol (EtOH). Thirty minutes following such treatment, animals were either sacrificed or orally received 2 ml of 100% EtOH and then were sacrificed 5 min later. At sacrifice, in each experimental group, stomachs were removed and either evaluated macroscopically for the degree of injury involving the glandular gastric epithelium or samples of the mucosa were prepared for measurement of total GSH levels or GSH peroxidase (GPX) and GSH reductase (GRT) activity. In nonvagotomized animals, saline treatment prior to 100% EtOH exposure resulted in injury to the glandular epithelium involving approximately 18%. Treatment with 25% EtOH prior to 100% EtOH exposure virtually abolished this injury. In vagotomized animals, 100% EtOH elicited almost three times the amount of injury observed in the nonvagotomized state and the protective effect of 25% EtOH pretreatment was prevented. Effects of the various treatment modalities on GPX and GRT activity were not significantly different from control values. When mucosal GSH results were plotted against the presence or absence of gastric injury among the various groups studied, no significant correlation was apparent. Thus, aberrations in glutathione metabolism do not explain the absence of adaptive cytoprotection following vagotomy or the exacerbation of alcohol-induced damage under conditions of vagal denervation.This work was supported by research grant DK 25838 from the National Institutes of Health.     

获得性免疫缺陷综合征患者胃黏膜组织人类免疫缺陷病毒感染分析

Objective To investigate the distribution and amount of human immunodeficiency virus (HIV) infection in gastric mucosa from untreated acquired immune deficiency syndrome (AIDS) patients and highly active antiretroviral therapy (HAART) treated patients.Methods Thirty-five AIDS patients (14 untreated patients and 21 patients receiving HAART) and 10 HIV-1 seronegative patients with gastrointestinal symptoms were enrolled and examined by upper endoscopy.The labeled HIV-1 double-stranded cDNA probe was a PCR product corresponding to the LTR and gag gene of the HIV-1 genome.HIV in gastric mucosal tissues from AIDS patients was detected using in situ hybridization (ISH) and compared with that in peripheral blood mononuclear cells (PBMC).Results ① No obvious character was found in gastrointestinal symptoms,endoscopy examination and pathology results of AIDS patients.② The expression of HIV gene was mainly detected in the gastric mucosal mononuclear cell (MMC).Other cells were also observed with HIV expression including mucosal epithelial cells,gland epithelial cells and interstitial cells.③There was no difference in HIV expression between sinus ventriculi and gastric body.④ HIV gene expression from AIDS patients was (1.97±3.25)% in gastric mucosa,no difference in HIV gene expression between two groups (P＞0.05).⑤ HIV gene expression in PBMC smear from AIDS patients was (12.38 ± 9.17)%.HIV expreesion in PBMC from patients who had received HAART for 1-4 years were markedly lower than that from patients who had not received HAART (P＜0.05).Conclusions The gastric mueosa is one of HIV infected sites.The potential effect of HAART on the decrease of HIV infected cells in gastric mucosa was unsatisfactory.     

Association of highly active antiretroviral therapy failure with chemokine receptor 5 wild type

OBJECTIVES: Approximately 10% of HIV-infected patients fail to respond properly to highly active antiretroviral therapy (HAART). Among other factors, genetic variants of chemokine receptors have been shown to modify the course and outcome of HIV infection. Our objective was to investigate whether a failure of virological response is associated with polymorphisms of the chemokine receptors or cofactors. METHODS: A total of 256 HIV-infected patients receiving HAART and 221 healthy controls were analysed for the chemokine receptor 5 (CCR5)-Delta32-bp, stromal derived factor 1 (SDF1)-3'A and chemokine receptor 2 (CCR2)-64I polymorphisms. Treatment failure was defined as failure to lower the viral load below 50 HIV-1 RNA copies/mL within the first year of treatment despite good adherence. Genomic DNA was extracted from peripheral blood lymphocytes (PBL) and amplified by polymerase chain reaction (PCR). RESULTS: Successful treatment was associated with heterozygosity for the CCR5-Delta32-bp variant found in 24 of 184 responders (13%) vs. one of 72 nonresponders (1.4%; P=0.004). Eighty-four of 184 responders (45.7%) vs. 25 of 72 nonresponders (34.7%) were heterozygous for the SDF1-3'A allele (P=0.073). The CCR2-64I polymorphism was rare in both groups: 4.9% in responders vs. 1.4% in nonresponders (P=0.175). The odds ratio for successful treatment was 4.7 for individuals who tested positive for at least one variant allele of the three polymorphisms. Comparison of genotype frequencies between HIV-infected and healthy individuals showed highly significant differences (P<0.001). CONCLUSIONS: Chemokine receptor polymorphisms have a modifying effect on the virological response to HAART. Multivariate analysis demonstrated that heterozygosity for the CCR5-Delta32-bp variant is an independent prognostic factor for treatment outcome.     

Management Options for Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is associated with diverse pathophysiologic mechanisms. These mechanisms include increased abnormal colonic motility or transit, intestinal or colorectal sensation, increased colonic bile acid concentration, and superficial colonic mucosal inflammation, as well as epithelial barrier dysfunction, neurohormonal up-regulation, and activation of secretory processes in the epithelial layer. Novel approaches to treatment include lifestyle modification, changes in diet, probiotics, and pharmacotherapy directed to the motility, sensation, and intraluminal milieu of patients with IBS. Despite recent advances, there is a need for development of new treatments to relieve pain in IBS without deleterious central or other adverse effects.     

高度近视白内障患者超声乳化术后视力与黄斑区厚度的相关分析

目的：运用光学相干断层扫描术(OCT)回顾性分析高度近视白内障超声乳化摘除联合人工晶状体植入术后BCVA<0.3组和BCVA≥0.3组黄斑中心凹视网膜厚度,分析其与术后视力的相关性。

方法：本研究为回顾性临床研究,共纳入行白内障超声乳化摘除联合人工晶状体植入的高度近视白内障患者70例70眼,于术后1wk; 1,3mo进行随访,记录最佳校正视力(BCVA),并根据术后1wk BCVA分为BCVA<0.3组和BCVA≥0.3组,两组患者于术后1,3mo行OCT检查,测量黄斑中心凹视网膜厚度。采用相关分析研究术后BCVA恢复情况及其与黄斑中心凹视网膜厚度的相关性。

结果：患者术前,术后1wk; 1,3mo的BCVA<0. 05的眼的比分别为30%,14%,11%,7%。BCVA<0.3组术后1,3mo的黄斑中心凹视网膜厚度均较BCVA≥0.3组明显增加,两组术后3mo黄斑中心凹视网膜厚度均较术后1mo明显降低(P<0.01)。术后3mo BCVA和OCT检查黄斑中心凹视网膜厚度之间存在统计学上显著相关(r=-0.716,P<0.05)。

结论：在本研究中,术后所有患者在3mo的随访时间内视力得到一定程度的提高,且术后OCT检查黄斑中心凹视网膜厚度与术后视力的恢复情况相关。