Helicobacter pylori infection in patients with Hepatitis C Virus positive chronic liver diseases

BACKGROUND AND GOALS: One-third of patients with liver cirrhosis suffers from acute peptic ulcer, a disease strongly correlated with Helicobacter pylori (H. pylori) infection. We report the seroprevalence of antibodies to H. pylori in 179 patients with Hepatitis C Virus (HCV)-related chronic active hepatitis and cirrhosis. MATERIALS AND METHODS: Among patients, 135 (86 males and 49 females, mean age 51.2 +/- 13.28, range 27-77 years) had chronic active hepatitis (CAH) and 44 cirrhosis (28 males and 16 females, mean age 62.4 +/- 9.2, range 37-77 years). Serum antibodies to H. pylori were tested using a commercial enzyme immunosorbent assay. The control population consisted of 619 consecutive blood donors (523 males, 96 females, mean age 47 +/- 5.3 years, range 18-65). RESULTS: The overall prevalence of antibodies to H. pylori was 73.1% (131/179) among patients and 47% (291/619) among blood donors (p<0.0001; OR 3.08 [95%CI, 2.10-4.51]). 70.5% (24/34) of patients aged less than 40 years were seropositive for H. pylori versus 34.2% (90/263) of controls (p<0.0001; OR 4.61[95%CI, 2.0-10.85]). Among cirrhosis patients, the prevalence of antibodies to H. pylori was 79.5% (35/44) versus 47% (291/619) of controls (p<0.0001; OR 4.38 [95%CI, 1.98-9.98]). Overall seroprevalence among CAH patients was 71.1% (96/135) versus 47% (291/619) of blood donors (p<0.0001; OR 2.77 [95%CI, 1.82-4.24]). CONCLUSIONS: The high seroprevalence of antibodies to H. pylori in patients with HCV-positive liver diseases explains the elevated incidence of peptic ulcer, and warrants studies on the pathogenic role in human liver diseases of Helicobacter spp which is known to cause chronic hepatitis and hepatocellular carcinoma in mice.     

Association of the ABCA1 gene polymorphisms with type 2 DM in a Japanese population

To examine the association of the ATP-binding cassette transporter 1 (ABCA1) gene with type 2 diabetes (DM), we studied genetic polymorphisms of the ABCA1 gene including its linkage disequilibrium (LD) and haplotype analyses using a Japanese population. A sample set (DM:72, IGT:75, and NGT:227) was genotyped with 34 SNPs distributed from the promoter region to the last exon of the ABCA1 gene. LD between SNPs was assessed in pairwise manner. Among 13 LD blocks constructed, an LD block at the 5'-region showed a significant difference in the haplotype distribution between the study groups (NGT vs. IGT + DM: overall p = 0.0180; NGT vs. DM: 0.0001). Fisher's exact probability test (NGT vs. DM) showed a significant association of the haplotype 2 of the LD block (p = 0.0001), with an odds ratio (OR) of 2.53 (95%CI:1.62-4.12). Diplotype analysis also showed a significant association of the diplotypes with the haplotype 2 (OR:2.59, 95%CI:1.48-4.54, p = 0.0013).     

Predictors of postoperative atrial fibrillation after coronary artery bypass graft surgery

Objectives

The present study was aimed to identify the preoperative, intraoperative, and postoperative predictors of AF in a pure cohort of the patients with coronary artery disease who underwent CABG surgery.

Methods

Between November 2005 and May 2006, 302 consecutive patients were included in this prospective study. All the relevant clinical, electrocardiographic, echocardiographic, and laboratory data were gathered in the included patients and they were also monitored for development of post-CABG AF.

Results

Postoperative AF occurred in 46 (15%) of patients. By univariate analysis, older age, P-wave abnormality in ECG, presence of mitral regurgitation, larger left atrium (LA), left main coronary artery involvement, failure to graft right coronary artery (RCA), and adrenergic use in ICU were significantly associated with occurrence of post-CABG AF (all P< 0.05). However, in the logistic regression model, age (OR: 1.067, 95%CI: 1.02-1.116, P=0.005), LA dimension (OR: 1.102, 95%CI: 1.017-1.1936, P=0.017), P-wave morphology (OR: 12.07, 95%CI: 3.35-48.22, P=0.0001), failure to graft RCA (OR: 3.57, 95%CI: 1.20-10.64, P=0.022), and postoperative adrenergic use (OR: 0.35, 95%CI: 0.13-0.93, P=0.036) remained independently predictive of postoperative AF.

Conclusion

The present study suggested that age, P-wave morphology, LA dimension, failure to graft right coronary artery, and postoperative adrenergic use were independent predictors of post-CABG AF. Therefore, clinical data, ECG and echocardiography may be useful in preoperative risk stratification of the surgical patients for the occurrence of post-CABG AF.     

自噬通路基因多态性与晚期非小细胞肺癌含铂化疗疗效的相关性分析

对晚期非小细胞肺癌患者采用含铂化疗是肺癌临床治疗中非常重要的方法,然而不同患者对含铂化疗的敏感性却存在着明显的个体差异,这提示发现潜在的分子标志物对预测临床中含铂化疗疗效具有关键作用。本研究旨在探索自噬通路基因多态性与晚期非小细胞肺癌含铂化疗疗效之间的相关性,以期寻找可能影响含铂化疗药物敏感性的分子标记。本研究纳入了1004例接受含铂化疗的晚期非小细胞肺癌患者,分析了自噬通路中13个基因上的99个SNP位点与含铂化疗临床获益、无疾病进展时间及总生存时间之间的相关性。研究发现,位于ULK1基因的位点rs7953348(G>A) (P=0.017, OR:0.67, 95%CI:0.49~0.93)和rs12303764(A>C) (P=0.009, OR:0.63, 95%CI:0.45-0.89)及位于ATG14基因上的位点rs17742719(C>A) (P=0.002, OR:1.83, 95%CI:1.26~2.66)、rs8003279(A>G) (P=0.006, OR:1.65, 95%CI:1.16~2.35)和rs1009647(G>A) (P=0.002, OR:1.70, 95%CI:1.22~2.37)与临床获益存在显著关联,位于DRAM基因上的位点rs7955890(G>A) (P=0.004, HR:0.63; 95%CI:0.46~0.86)和rs17032060(G>A) (P=0.006, HR:0.65, 95%CI:0.48~0.88)及位于ATG3基因上的位点rs13082005(G>A) (P=0.012, HR:1.27,95%CI:1.05~1.53)与含铂化疗的无疾病进展时间显著相关,位于ULK1基因的位点rs7953348(G>A) (P=0.011, HR:0.74, 95%CI:0.58~0.93)和位于ATG10基因上的位点rs1864183(G>A) (P=0.016, HR:0.42, 95%CI:0.21~0.85)对含铂化疗的总生存时间有着显著影响。研究结果提示自噬通路在含铂化疗敏感性中发挥着重要作用,自噬通路基因多态性可能是预测含铂化疗疗效的潜在分子标志物,这可能为临床上肺癌的个体化医疗提供一定的理论基础。     

The insulin polymorphism -23Hph increases the risk for type 1 diabetes mellitus in the Romanian population

The insulin -23Hph and IGF2 Apa polymorphisms were genotyped in Romanian patients with T1DM (n = 204), T2DM (n = 215) or obesity (n = 200) and normoponderal healthy subjects (n = 750). The genotypes of both polymorphisms were distributed in concordance with Hardy-Weinberg equilibrium in all groups. The -23Hph AA genotype increased the risk for T1DM (OR: 3.22, 95%CI: 2.09-4.98, p < 0,0001), especially in patients without macroalbuminuria (OR: 4.32, 95%CI: 2.54-7.45, p < 0,0001). No other significant association between the alleles or genotypes of insulin -23Hph and IGF2 Apa and diabetes or obesity was identified.     

Lack of an association between -308G>A polymorphism of the TNF-α gene and liver cirrhosis risk based on a meta-analysis

TNF-α is a potential proinflammatory cytokine that plays an important role in the pathogenesis of liver cirrhosis. We investigated a possible association between TNF-α -308G>A polymorphism and liver cirrhosis risk by conducting a meta-analysis. Publications addressing the association between TNF-α -308G>A and liver cirrhosis risk were selected from the Pubmed and Embase databases. Data were extracted from the studies by two independent reviewers; odds ratio (OR) with a 95% confidence interval (CI) was calculated from these data. The meta-analysis was performed by Review Manager Version 5.0.24 and STATA Version 9.2. Eleven studies were retrieved, reporting a total of 1796 liver cirrhosis cases and 2113 healthy controls. A meta-analysis of these 11 studies identified no significant association between TNF-α -308G>A polymorphism and liver cirrhosis risk in all comparisons of G vs A allele; GG vs GA + AA; GG + GA vs AA; GG vs AA; GG vs GA (OR = 1.14, 95%CI = 0.85-1.55, P = 0.38; OR = 1.24, 95%CI = 0.87- 1.77, P = 0.24; OR = 0.90, 95%CI = 0.62-1.30, P = 0.57; OR = 1.03, 95%CI = 0.56-1.89, P = 0.92; OR = 1.30, 95%CI = 0.90-1.88, P = 0.17; respectively). In conclusion, we found no association between TNF-α -308G>A polymorphism and liver cirrhosis risk, both in Caucasian and Asian populations.     

Association of TNF-α promoter polymorphisms with the outcome of persistent HBV infection in a northeast Chinese Han population

Tumor necrosis factor-α (TNF-α) plays an important role in the pathogenesis and clinical outcome of chronic hepatitis B virus (HBV) infection. The objective of this study was to evaluate the relationship between functional polymorphisms of TNF-α and different outcomes of persistent HBV infection in a northeast Chinese Han population. Here 189 HBV spontaneously recovered subjects (SR), 571 HBV-infected patients including 180 chronic hepatitis B (CHB), 196 liver cirrhosis (LC), and 195 hepatocellular carcinoma (HCC) individuals were enrolled in this study. All the samples were genotyped for TNF-α -857C/T and -863C/A using the polymerase chain reaction-restriction fragment length polymorphism method. The frequency of -857CC genotype was significantly higher in CHB and LC individuals compared with that of SR subjects (P= 0.03, OR = 1.57, 95% CI 1.04-2.39 and P= 0.03, OR = 1.57, 95% CI 1.04-2.35, respectively). A significant difference in the distribution of the allele -857C was observed for both CHB vs. SR (P= 0.01, OR = 1.52, 95% CI 1.08-2.13) and LC vs. SR (P= 0.02, OR = 1.47, 95% CI 1.06-2.04) cohorts. In addition, the frequency of -863AA genotype was significantly higher in CHB and LC patients than that of SR subjects (P= 0.01, OR = 3.90, 95% CI 1.35-11.23 and P= 0.01, OR = 3.83, 95% CI 1.34-10.96, respectively), and allele -863A frequency was significantly more common in CHB, LC, and HCC cohorts than that of SR controls (P= 0.004, OR = 1.72, 95% CI 1.19-2.50; P= 0.001, OR = 1.81, 95% CI 1.26-2.61 and P= 0.001, OR = 1.90, 95% CI 1.33-2.73, respectively). Our data also revealed that haplotype CA was strongly associated with persistent HBV infection. These results suggest an association between the TNF-α promoter variants and different outcomes of persistent HBV infection in the studied population.     

Interleukin-10 gene polymorphisms and chronic/aggressive periodontitis susceptibility: A meta-analysis based on 14 case-control studies

Interleukin-10 (IL-10) has been described as an anti-inflammatory cytokine and IL-10 gene polymorphisms was associated with altered interleukin-10 levels, therefore, we aimed to conduct a meta-analysis assessing the association of IL-10 genetic polymorphisms with the risk of both chronic periodontitis (CP) and aggressive periodontitis (AgP). Electronic databases were acquired from PubMed, Embase, the Sinomed and WANFANG. Fourteen studies with 1438 patients and 1303 control subjects investigated the association of the three single-nucleotide polymorphisms (SNPs) of IL-10 (-1082A>G, -819C>T, -592C>A) and chronic/aggressive periodontitis risk were brought into this study. We found that there was no association between IL-10 -1082 gene polymorphism and periodontitis risk (either CP or AgP), even when we separately investigated sub-group analysis among Caucasians. The -819 polymorphism seemed to be a genetic risk factor to CP among Caucasians (T allele vs. C allele: OR=1.55, 95%CI=1.07-2.24; CT vs. CC: OR=1.64, 95%CI=1.00-2.67). When excluding one study deviated from HWE, the results showed that the T allele carriers had a significantly risk of CP in overall population (T allele vs. C allele: OR=1.23, 95%CI=1.03-1.48). Furthermore, the results of this meta-analysis showed that -592 polymorphism was associated with a significantly increased risk of CP (A allele vs. C allele: OR=1.38, 95%CI=1.04-1.85; AA vs. CA+CC: OR=1.39, 95%CI=1.05-1.85 for overall analysis; A allele vs. C allele: OR=1.97, 95%CI=1.36-3.86; AA vs. CC: OR=3.70, 95%CI=1.32-10.39; CA vs. CC: OR=2.22, 95%CI=1.36-3.64, AA+CA vs. CC: OR=2.35, 95%CI=1.46-3.79 for Caucasian descent analysis). This meta-analysis suggested that IL-10 -819 and -592 gene polymorphisms were associated with CP, especially among Caucasians. Further research is needed to assess possible gene-gene or gene-environment-lifestyle interactions on periodontal disease..     

代谢正常肥胖个体发生非酒精性脂肪性肝病的相关性研究

目的:探讨代谢正常肥胖(Metabolically healthy obese,MHO)个体与非酒精性脂肪性肝病(Nonalcoholic fatty liver disease,NAFLD)发生的相关性。方法:选择2006年4月～2010年1月来湖南省人民医院体检中心体检人群共4076例,排除过量饮酒者、乙肝标志物阳性者及相关资料不全者共2830例纳入本研究。其中1367例在1～3年后再次体检。记录受检者身高、体重、血压、血脂、空腹血糖、腹部B超结果。NAFLD采用2010年中华医学会肝病学分会诊断标准中影像学诊断定义,行腹部B超检查进行诊断。结果:1.我院体检人群中MHO合并NAFLD者占51.34%,明显高于正常对照组(P=0.000),MHO组发生NAFLD的OR值为19.967(95%CI,12.646-31.533;P=0.000)。2.随访1～3年后,MHO中NAFLD发病率高于正常对照组(44.44%vs 7.02%,OR=10.600,95%CI,4.873-23.058;P=0.000)。结论:MHO个体合并NAFLD比例较正常对照者升高,MHO个体增加NAFLD患病风险。     

Tumour necrosis factor alpha (TNF-α) genetic polymorphisms and the risk of autoimmune liver disease: a meta-analysis

Epidemiological studies have evaluated the association between tumour necrosis factor alpha (TNF-α)-308G/A and (TNF-α)-238G/A polymorphisms, and the risk of autoimmune liver disease (AILD), yet the results are conflicting. To derive a more precise estimation of the relationship, we performed this meta-analysis. A systematic review was conducted to identify all eligible studies of TNF-α polymorphisms and AILD risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association between the two TNF-α polymorphisms and AILD risk. A total of 15 eligible studies were identified. Overall, positive associations of -308G/A polymorphism with AILD risk were found (A vs G allele: OR = 1.45, 95%CI = 1.13–1.86; AA vs GG: OR = 2.74, 95%CI = 1.51–4.96; GA vs GG: OR = 1.46, 95%CI = 1.11–1.92; dominant model: OR = 1.57, 95%CI = 1.18–2.10; recessive model: OR = 2.22, 95%CI = 1.31–3.76). In subgroup analysis by ethnicity, a significantly higher risk was found in Caucasians. In subgroup analysis by AILD category, significant association was observed in autoimmune hepatitis and primary sclerosing cholangitis, especially in Caucasians. Patients carrying TNF-α-238A allele had a slightly decreased risk of developing AILD (OR = 0.65, 95%CI = 0.48–0.87). However, we found both TNF-α polymorphisms were not associated with primary biliary cirrhosis risk, even in subgroup analysis. Our meta-analysis suggests that the TNF-α-308G/A and -238G/A polymorphisms may contribute to AILD susceptibility in Caucasians, especially for autoimmune hepatitis and primary sclerosing cholangitis. Nevertheless, we found both TNF-α polymorphisms were unlikely to be associated with the risk of primary biliary cirrhosis.     

单胎妊娠早产胎膜早破呼吸窘迫综合征的危险因素分析

目的:探讨单胎妊娠早产胎膜早破发生新生儿呼吸窘迫综合征(respiratory distress syndrome,RDS)的危险因素。方法:选择2017年5月至2019年5月在我院产科分娩的2810例产妇为研究对象,其中97例(3.45%)符合未足月胎膜早破(Preterm premature rupture of membranes,pPROM)标准,包括53例RDS。收集以下信息:PROM潜伏期、出生时胎龄、脐动脉搏动指数(Umbilical artery pulsatility index,UAPI)、大脑中动脉搏动指数(Middle cerebral artery pulsation index,MCAPI)、胎儿窘迫、产前使用类固醇、新生儿实验室参数、性别、体重、Apgar评分、分娩类型、妊娠高血压疾病、妊娠期糖耐量异常或糖尿病等信息,通过Logistic回归分析研究变量对RDS的影响。结果:Logistic回归分析结果显示,以下变量与RDS密切相关:新生儿性别女性(OR=0.517;95%CI:0.312-0.107;P=0.042),产前使用类固醇(OR=0.467;95%CI:0.355-0.698;P0.001),异常UAPI(OR=2.830;95%CI:1.783-6.234;P=0.002),异常MCA PI(OR=2.136;95%CI:1.120-4.017;P=0.032),胎儿窘迫(OR=2.420;95%CI:1.287-4.824;P=0.017),母体HGB(OR=0.689;95%CI:0.511-1.013;P=0.221),新生儿HGB(OR=0.752;95%CI:0.645-0.891;P0.001),新生儿RBC(OR=0.311;95%CI:0.201-0.565;P0.001)。结论:单胎妊娠早产胎膜早破发生RDS危险因素主要是性别、胎儿胎盘循环异常和胎儿窘迫。     

Association of cytotoxic T-lymphocyte associated antigen 4 gene polymorphism with type 1 diabetes mellitus: A meta-analysis

To evaluate the association between costimulatory molecule cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) gene polymorphism and type 1 diabetes mellitus(T1DM), sixty-three published studies before December, 2011 were included. Meta-analysis was performed for each genotype in a random/fixed effect model. The combined odds ratio (OR) with 95% confidence interval (95%CI) was calculated to estimate the strength of the association. Overall, significant correlation was noted between CTLA-4 gene polymorphism (i.e. +49A/G, CT60A/G in a per-allele model) and the risk of T1DM (for +49A/G: OR=1.47, 95%CI=1.36-1.60, P<0.001; for CT60A/G: OR=1.31, 95%CI=1.18-1.45, P<0.001). However, no significant association was noted between C(-318)T polymorphism and T1DM. In the subgroup analysis, for +49A/G and CT60A/G, the statistically significant associations were also demonstrated in diverse racial descents (Caucasian and Asian) and age of onset (<20years and >20years). In conclusion, our results suggest that CTLA-4 polymorphism contributes to the susceptibility of T1DM.     

N-acetyltransferase 2 polymorphism in patients with diabetes mellitus

The arylamine N-acetyltransferases (NATs) are a unique family of enzymes that catalyse the transfer of an acetyl group from acetyl-CoA to the terminal nitrogen of hydrazine and arylamine drugs and carcinogens. Human arylamine NATs are known to exist as two isoenzymes, NAT1 and NAT2. The objective of this study was to identify whether the genetic polymorphism of NAT2 plays a role in susceptibility to Diabetes Mellitus (DM). Ninety-seven patients with DM and 104 healthy controls were enrolled in the study. NAT2*5A, NAT2*6A, NAT2*7A/B and NAT2*14A polymorphisms were detected by using real time PCR with LightCycler (Roche Diagnostics GmbH, Mannheim, Germany). According to our data, the NAT2*5A and NAT2*6A mutant genotypes and NAT2*14A heterozygous genotype were associated with an increased risk of development of DM (OR = 47.06; 95%CI: 10.55-209.77 for NAT 2*5A, OR = 18.48; 95%CI: 3.83-89.11 for NAT2*6A and OR = 18.22; 95%CI: 6.29-52.76 for NAT2*14A). However, the NAT2*7A/B gene polymorphism carried no increased risk for developing DM disease. After grouping according to phenotypes as either slow or fast acetylators, NAT2*6A slow acetylator was found to be a significant risk factor for DM (OR = 6.09; 95%CI: 1.99-18.6, p = 0.02). The results indicate that NAT2 slow acetylator genotypes may be an important genetic determinant for DM in the Turkish population.     

Quantifying Cancer Absolute Risk and Cancer Mortality in the Presence of Competing Events after a Myotonic Dystrophy Diagnosis

Recent studies show that patients with myotonic dystrophy (DM) have an increased risk of specific malignancies, but estimates of absolute cancer risk accounting for competing events are lacking. Using the Swedish Patient Registry, we identified 1,081 patients with an inpatient and/or outpatient diagnosis of DM between 1987 and 2007. Date and cause of death and date of cancer diagnosis were extracted from the Swedish Cause of Death and Cancer Registries. We calculated non-parametric estimates of absolute cancer risk and cancer mortality accounting for the high non-cancer competing mortality associated with DM. Absolute cancer risk after DM diagnosis was 1.6% (95% CI=0.4-4%), 5% (95% CI=3-9%) and 9% (95% CI=6-13%) at ages 40, 50 and 60 years, respectively. Females had a higher absolute risk of all cancers combined than males: 9% (95% CI=4-14), and 13% (95% CI=9-20) vs. 2% (95%CI= 0.7-6) and 4% (95%CI=2-8) by ages 50 and 60 years, respectively) and developed cancer at younger ages (median age =51 years, range=22-74 vs. 57, range=43-84, respectively, p=0.02). Cancer deaths accounted for 10% of all deaths, with an absolute cancer mortality risk of 2% (95%CI=1-4.5%), 4% (95%CI=2-6%), and 6% (95%CI=4-9%) by ages 50, 60, and 70 years, respectively. No gender difference in cancer-specific mortality was observed (p=0.6). In conclusion, cancer significantly contributes to morbidity and mortality in DM patients, even after accounting for high competing DM mortality from non-neoplastic causes. It is important to apply population-appropriate, validated cancer screening strategies in DM patients.     

XRCC1 and ERCC1 variants modify malignant mesothelioma risk: a case-control study

Malignant pleural mesothelioma (MPM) is a rare aggressive tumor associated with asbestos exposure. The possible role of genetic factors has also been suggested and MPM has been associated with single nucleotide polymorphisms (SNPs) of xenobiotic and oxidative metabolism enzymes. We have identified an association of the DNA repair gene XRCC1 with MPM in the population of Casale Monferrato, a town exposed to high asbestos pollution. To extend this observation we examined 35 SNPs in 15 genes that could be involved in MPM carcinogenicity in 220 MPM patients and 296 controls from two case-control studies conducted in Casale (151 patients, 252 controls) and Turin (69 patients, 44 controls), respectively. Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Two DNA repair genes were associated with MPM, i.e. XRCC1 and ERCC1. Considering asbestos-exposed only, the risk increased with the increasing number of XRCC1-399Q alleles (Casale: OR=1.44, 95%CI 1.02-2.03; Casale+Turin: OR=1.34, 95%CI 0.98-1.84) or XRCC1 -77T alleles (Casale+Turin: OR=1.33, 95%CI 0.97-1.81). The XRCC1-TGGGGGAACAGA haplotype was significantly associated with MPM (Casale: OR=1.76, 95%CI 1.04-2.96). Patients heterozygotes for ERCC1 N118N showed an increased OR in all subjects (OR=1.66, 95%CI 1.06-2.60) and in asbestos-exposed only (OR=1.59, 95%CI 1.01-2.50). When the dominant model was considered (i.e. ERCC1 heterozygotes CT plus homozygotes CC versus homozygotes TT) the risk was statistically significant both in all subjects (OR=1.61, 95%CI 1.06-2.47) and in asbestos-exposed only (OR=1.56, 95%CI 1.02-2.40). The combination of ERCC1 N118N and XRCC1 R399Q was statistically significant (Casale: OR=2.02, 95%CI 1.01-4.05; Casale+Turin: OR=2.39, 95%CI 1.29-4.43). The association of MPM with DNA repair genes support the hypothesis that an increased susceptibility to DNA damage may favour asbestos carcinogenicity.     

Risk Factors for Death from Influenza A(H1N1)pdm09, State of S?o Paulo,Brazil, 2009

This case-control study aimed to assess the risk factors for death from influenza A(H1N1)pdm09 in patients with laboratory confirmation, who had severe acute respiratory illness-SARI and were hospitalized between June 28^th and August 29^th 2009, in the metropolitan regions of São Paulo and Campinas, Brazil. Medical charts of all the 193 patients who died (cases) and the 386 randomly selected patients who recovered (controls) were investigated in 177 hospitals. Household interviews were conducted with those who had survived and the closest relative of those who had died. 73.6% of cases and 38.1% of controls were at risk of developing influenza-related complications. The 18-to-59-year age group (OR = 2.31, 95%CI: 1.31–4.10 (reference up to 18 years of age)), presence of risk conditions for severity of influenza (OR = 1.99, 95%CI: 1.11–3.57, if one or OR = 6.05, 95%CI: 2.76–13.28, if more than one), obesity (OR = 2.73, 95%CI: 1.28–5.83), immunosuppression (OR = 3.43, 95%CI: 1.28–9.19), and search for previous care associated with the hospitalization (OR = 3.35, 95%CI: 1.75–6.40) were risk factors for death. Antiviral treatment performed within 72 hours of the onset of symptoms (OR = 0.17, 95%CI: 0.08–0.37, if within 48hours, and OR = 0.30, 95%CI: 0.11–0.81, if between 48 and 72 hours) was protective against death. The identification of high-risk patients and early treatment are important factors for reducing morbi-mortality from influenza.     

Interleukin-28B polymorphisms on the SVR in the treatment of naïve chronic hepatitis C with pegylated interferon-α plus ribavirin: A meta-analysis

There are accurate but inconclusive data on the association between single nucleotide polymorphisms (SNPs) of interleukin (IL)-28B and sustained virological response (SVR) in chronic hepatitis C (CHC). This meta-analysis aimed to derive a more precise estimation of the effects of IL-28B SNPs locus (rs12979860 and rs8099917) on SVR in naïve CHC patients receiving pegylated interferon alpha (PEG-IFN-α) plus ribavirin. Literature search was conducted up to June, 2011, in PubMed, EMBASE and Cochrane Database of Systematic Reviews. A total of 36 studies involving 10912 cases with CHC receiving PEG-IFN-α plus ribavirin met the inclusion criteria. Analyses were stratified either by ethnicity or genotype of hepatitis C virus. In genotype 1/4 patients, rs12979860 CC was associated with high SVR in CHC patients (Caucasian: odds ratio (OR), 4.567; 95% confidence interval (CI), 3.826–5.452; Asian: OR, 4.033; 95%CI, 3.050–5.333; African American: OR, 4.297; 95%CI, 2.168–8.515; Hispanics: OR, 4.350; 95%CI, 2.817–6.717) but had no effect in genotype 2/3. In Caucasian (genotype 1/4: OR, 2.542; 95%CI, 2.108–3.065; genotype 2/3: OR, 1.363; 95%CI, 1.020–1.820) and Asian (genotype 1/4: OR, 5.214; 95%CI, 3.694–7.360; genotype 2/3: OR, 1.785; 95%CI, 1.095–2.910), rs8099917 TT was associated with high SVR in both genotype 1/4 and 2/3. Meta-regression showed that in Caucasians with CHC genotype 1/4, gender male might contribute to the effect of rs12979860 on SVR but advanced fibrosis might weaken this effect. Furthermore, in Asians with CHC genotype 1/4, high baseline viral load and advanced fibrosis might also undermine the effect of rs8099917 on SVR. This meta-analysis suggested that IL-28B rs12979860 CC and rs8099917 TT were associated with high SVR rate in CHC genotype 1/4. In CHC genotype 2/3, rs8099917 TT carriers also had higher SVR.     

Adjunctive steroid in HIV-negative patients with severe Pneumocystis pneumonia

Background

High-dose steroid therapy has been proven effective in AIDS-related Pneumocystis pneumonia (PCP) but not in non-AIDS-related cases. We evaluated the effects on survival of steroids in HIV-negative patients with PCP.

Methods

Retrospective study patients admitted to the ICU with hypoxemic PCP. We compared patients receiving HDS (≥1 mg/Kg/day prednisone equivalent), low-dose steroids (LDS group, <1 mg/Kg/day prednisone equivalent), and no steroids (NS group). Variables independently associated with ICU mortality were identified.

Results

139 HIV-negative patients with PCP were included. Median age was 48 [40–60] years. The main underlying conditions were hematological malignancies (n=55, 39.6%), cancer (n=11, 7.9%), and solid organ transplantation (n=73, 52.2%). ICU mortality was 26% (36 deaths). The HDS group had 72 (51.8%) patients, the LDS group 35 (25%) patients, and the NS group 32 (23%) patients. Independent predictors of ICU mortality were SAPS II at ICU admission (odds ratio [OR], 1.04/point; [95%CI], 1.01-1.08, P=0.01), non-hematological disease (OR, 4.06; [95%CI], 1.19-13.09, P=0.03), vasopressor use (OR, 20.31; 95%CI, 6.45-63.9, P<0.001), and HDS (OR, 9.33; 95%CI, 1.97-44.3, P=0.02). HDS was not associated with the rate of ICU-acquired infections.

Conclusions

HDS were associated with increased mortality in HIV-negative patients with PCP via a mechanism independent from an increased risk of infection.