Association of arterial blood pressure and vasopressor load with septic shock mortality: a post hoc analysis of a multicenter trial

INTRODUCTION: It is unclear to which level mean arterial blood pressure (MAP) should be increased during septic shock in order to improve outcome. In this study we investigated the association between MAP values of 70 mmHg or higher, vasopressor load, 28-day mortality and disease-related events in septic shock. METHODS: This is a post hoc analysis of data of the control group of a multicenter trial and includes 290 septic shock patients in whom a mean MAP > or = 70 mmHg could be maintained during shock. Demographic and clinical data, MAP, vasopressor requirements during the shock period, disease-related events and 28-day mortality were documented. Logistic regression models adjusted for the geographic region of the study center, age, presence of chronic arterial hypertension, simplified acute physiology score (SAPS) II and the mean vasopressor load during the shock period was calculated to investigate the association between MAP or MAP quartiles > or = 70 mmHg and mortality or the frequency and occurrence of disease-related events. RESULTS: There was no association between MAP or MAP quartiles and mortality or the occurrence of disease-related events. These associations were not influenced by age or pre-existent arterial hypertension (all P > 0.05). The mean vasopressor load was associated with mortality (relative risk (RR), 1.83; confidence interval (CI) 95%, 1.4-2.38; P < 0.001), the number of disease-related events (P < 0.001) and the occurrence of acute circulatory failure (RR, 1.64; CI 95%, 1.28-2.11; P < 0.001), metabolic acidosis (RR, 1.79; CI 95%, 1.38-2.32; P < 0.001), renal failure (RR, 1.49; CI 95%, 1.17-1.89; P = 0.001) and thrombocytopenia (RR, 1.33; CI 95%, 1.06-1.68; P = 0.01). CONCLUSIONS: MAP levels of 70 mmHg or higher do not appear to be associated with improved survival in septic shock. Elevating MAP >70 mmHg by augmenting vasopressor dosages may increase mortality. Future trials are needed to identify the lowest acceptable MAP level to ensure tissue perfusion and avoid unnecessary high catecholamine infusions.

Ridge alterations post-extraction in the esthetic zone: a 3D analysis with CBCT

Dimensional alterations of the facial bone wall following tooth extractions in the esthetic zone have a profound effect on treatment outcomes. This prospective study in 39 patients is the first to investigate three-dimensional (3D) alterations of facial bone in the esthetic zone during the initial 8 wks following flapless tooth extraction. A novel 3D analysis was carried out, based on 2 consecutive cone beam computed tomographies (CBCTs). A risk zone for significant bone resorption was identified in central areas, whereas proximal areas yielded only minor changes. Correlation analysis identified a facial bone wall thickness of ≤ 1 mm as a critical factor associated with the extent of bone resorption. Thin-wall phenotypes displayed pronounced vertical bone resorption, with a median bone loss of 7.5 mm, as compared with thick-wall phenotypes, which decreased by only 1.1 mm. For the first time, 3D analysis has allowed for documentation of dimensional alterations of the facial bone wall in the esthetic zone of humans following extraction. It also characterized a risk zone prone to pronounced bone resorption in thin-wall phenotypes. Vertical bone loss was 3.5 times more severe than findings reported in the existing literature.

Obesity and overweight as a risk factor for pneumonia in polytrauma patients: a retrospective cohort study

BACKGROUND Obesity is a growing problem in western societies. The aim of this retrospective cohort study was to determine the association between the overweight and obese polytrauma patients and pneumonia after injury. METHODS A total of 628 patients with an Injury Severity Score (ISS) of 16 or greater and 16 years or older were included in this retrospective study. The sample was subdivided into three groups as follows: body mass index (BMI) of less than 25 kg/m2; BMI of 25 kg/m2 to 30 kg/m2; and BMI more than 30 kg/m2. The Murray score was assessed at admission and at its maximum during hospitalization to determine pulmonary problems. Pneumonia was defined as bacteriologically positive sputum with appropriate radiologic and laboratory changes (C-reactive protein and interleukin 6). Data are given as mean ± SEM. One-way analysis of variance and the Kruskal-Wallis test were used for the analyses, and the significance level was set at p < 0.05; Bonferroni-Dunn test was performed as post hoc analysis. RESULTS The Abbreviated Injury Scale (AIS) score for the thorax was 3.2 ± 0.1 in the group with a BMI of less than 25 kg/m2, 3.3 ± 0.1 in the group with a BMI of 25 kg/m2 to 30 kg/m2, and 2.8 ± 0.2 in the group with BMI of more than 30 kg/m2 (p = 0.044). The Murray score at admission was elevated with increasing BMI (0.8 ± 0.8 for BMI < 25 kg/m2, 0.9 ± 0.9 for BMI 25–30 kg/m2, and 1.0 ± 0.8 for BMI > 30 kg/m2; p = 0.137); the maximum Murray score during hospitalization revealed significant differences (1.2 ± 0.9 for BMI < 25 kg/m2, 1.6 ± 1.0 for BMI 25–30 kg/m2, and 1.5 ± 0.9 for BMI > 30 kg/m2; p < 0.001). The incidence of pneumonia also increased with increasing BMI (1.6% for BMI < 25 kg/m2, 2.0% for BMI 25–30 kg/m2, and 3.1% for BMI > 30 kg/m2; p = 0.044). CONCLUSION Obesity leads to an increased incidence of pneumonia in a polytrauma situation. LEVEL OF EVIDENCE Prognostic/epidemiologic study, level IV.

Risk Factors and Outcomes for Late Presentation for HIV-Positive Persons in Europe: Results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE)

Background Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality. Methods and Findings LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV diagnosis with a CD4 count <350/mm3 or an AIDS diagnosis within 6 months of HIV diagnosis among persons presenting for care between 1 January 2000 and 30 June 2011. Logistic regression was used to identify factors associated with LP and Poisson regression to explore the impact on AIDS/death. 84,524 individuals from 23 cohorts in 35 countries contributed data; 45,488 were LP (53.8%). LP was highest in heterosexual males (66.1%), Southern European countries (57.0%), and persons originating from Africa (65.1%). LP decreased from 57.3% in 2000 to 51.7% in 2010/2011 (adjusted odds ratio [aOR] 0.96; 95% CI 0.95–0.97). LP decreased over time in both Central and Northern Europe among homosexual men, and male and female heterosexuals, but increased over time for female heterosexuals and male intravenous drug users (IDUs) from Southern Europe and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred during 327,003 person-years of follow-up. In the first year after HIV diagnosis, LP was associated with over a 13-fold increased incidence of AIDS/death in Southern Europe (adjusted incidence rate ratio [aIRR] 13.02; 95% CI 8.19–20.70) and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55–12.43). Conclusions LP has decreased over time across Europe, but remains a significant issue in the region in all HIV exposure groups. LP increased in male IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis, with significant variation across Europe. Earlier and more widespread testing, timely referrals after testing positive, and improved retention in care strategies are required to further reduce the incidence of LP.

Risk of tuberculosis following HIV seroconversion in high-income countries

Background Few data exist on tuberculosis (TB) incidence according to time from HIV seroconversion in high-income countries and whether rates following initiation of a combination of antiretroviral treatments (cARTs) differ from those soon after seroconversion. Methods Data on individuals with well estimated dates of HIV seroconversion were used to analyse post-seroconversion TB rates, ending at the earliest of 1 January 1997, death or last clinic visit. TB rates were also estimated following cART initiation, ending at the earliest of death or last clinic visit. Poisson models were used to examine the effect of current and past level of immunosuppression on TB risk after cART initiation. Results Of 19 815 individuals at risk during 1982–1996, TB incidence increased from 5.89/1000 person-years (PY) (95% CI 3.77 to 8.76) in the first year after seroconversion to 10.56 (4.83 to 20.04, p=0.01) at 10 years. Among 11 178 TB-free individuals initiating cART, the TB rate in the first year after cART initiation was 4.23/1000 PY (3.07 to 5.71) and dropped thereafter, remaining constant from year 2 onwards averaging at 1.64/1000 PY (1.29 to 2.05). Current CD4 count was inversely associated with TB rates, while nadir CD4 count was not associated with TB rates after adjustment for current CD4 count, HIV-RNA at cART initiation. Conclusions TB risk increases with duration of HIV infection in the absence of cART. Following cART initiation, TB incidence rates were lower than levels immediately following seroconversion. Implementation of current recommendations to prevent TB in early HIV infection could be beneficial.

Health care index score and risk of death following tuberculosis diagnosis in HIV-positive patients

OBJECTIVES: To assess health care utilisation for patients co-infected with TB and HIV (TB-HIV), and to develop a weighted health care index (HCI) score based on commonly used interventions and compare it with patient outcome. METHODS: A total of 1061 HIV patients diagnosed with TB in four regions, Central/Northern, Southern and Eastern Europe and Argentina, between January 2004 and December 2006 were enrolled in the TB-HIV study. A weighted HCI score (range 0–5), based on independent prognostic factors identified in multivariable Cox models and the final score, included performance of TB drug susceptibility testing (DST), an initial TB regimen containing a rifamycin, isoniazid and pyrazinamide, and start of combination antiretroviral treatment (cART). RESULTS: The mean HCI score was highest in Central/Northern Europe (3.2, 95%CI 3.1–3.3) and lowest in Eastern Europe (1.6, 95%CI 1.5–1.7). The cumulative probability of death 1 year after TB diagnosis decreased from 39% (95%CI 31–48) among patients with an HCI score of 0, to 9% (95%CI 6–13) among those with a score of ≥4. In an adjusted Cox model, a 1-unit increase in the HCI score was associated with 27% reduced mortality (relative hazard 0.73, 95%CI 0.64–0.84). CONCLUSIONS: Our results suggest that DST, standard anti-tuberculosis treatment and early cART may improve outcome for TB-HIV patients. The proposed HCI score provides a tool for future research and monitoring of the management of TB-HIV patients. The highest HCI score may serve as a benchmark to assess TB-HIV management, encouraging continuous health care improvement.

Economic efficiency analysis of different strategies to control post-weaning multi-systemic wasting syndrome and porcine circovirus type 2 subclinical infection in 3-weekly batch system farms.

The study assessed the economic efficiency of different strategies for the control of post-weaning multi-systemic wasting syndrome (PMWS) and porcine circovirus type 2 subclinical infection (PCV2SI), which have a major economic impact on the pig farming industry worldwide. The control strategies investigated consisted on the combination of up to 5 different control measures. The control measures considered were: (1) PCV2 vaccination of piglets (vac); (2) ensuring age adjusted diet for growers (diets); (3) reduction of stocking density (stock); (4) improvement of biosecurity measures (bios); and (5) total depopulation and repopulation of the farm for the elimination of other major pathogens (DPRP). A model was developed to simulate 5 years production of a pig farm with a 3-weekly batch system and with 100 sows. A PMWS/PCV2SI disease and economic model, based on PMWS severity scores, was linked to the production model in order to assess disease losses. This PMWS severity scores depends on the combination post-weaning mortality, PMWS morbidity in younger pigs and proportion of PCV2 infected pigs observed on farms. The economic analysis investigated eleven different farm scenarios, depending on the number of risk factors present before the intervention. For each strategy, an investment appraisal assessed the extra costs and benefits of reducing a given PMWS severity score to the average score of a slightly affected farm. The net present value obtained for each strategy was then multiplied by the corresponding probability of success to obtain an expected value. A stochastic simulation was performed to account for uncertainty and variability. For moderately affected farms PCV2 vaccination alone was the most cost-efficient strategy, but for highly affected farms it was either PCV2 vaccination alone or in combination with biosecurity measures, with the marginal profitability between 'vac' and 'vac+bios' being small. Other strategies such as 'diets', 'vac+diets' and 'bios+diets' were frequently identified as the second or third best strategy. The mean expected values of the best strategy for a moderately and a highly affected farm were £14,739 and £57,648 after 5 years, respectively. This is the first study to compare economic efficiency of control strategies for PMWS and PCV2SI. The results demonstrate the economic value of PCV2 vaccination, and highlight that on highly affected farms biosecurity measures are required to achieve optimal profitability. The model developed has potential as a farm-level decision support tool for the control of this economically important syndrome.

Edema is a sign of early acute myocardial infarction on post-mortem magnetic resonance imaging

The aim of this study was to investigate if acute myocardial infarction can be detected by post-mortem cardiac magnetic resonance (PMMR) at an earlier stage than by traditional autopsy, i.e., within less than 4 h after onset of ischemia; and if so, to determine the characteristics of PMMR findings in early acute infarcts. Twenty-one ex vivo porcine hearts with acute myocardial infarction underwent T2-weighted cardiac PMMR imaging within 3 h of onset of iatrogenic ischemia. PMMR imaging findings were compared to macroscopic findings. Myocardial edema induced by ischemia and reperfusion was visible on PMMR in all cases. Typical findings of early acute ischemic injury on PMMR consist of a central zone of intermediate signal intensity bordered by a rim of increased signal intensity. Myocardial edema can be detected on cardiac PMMR within the first 3 h after the onset of ischemia in porcine hearts. The size of myocardial edema reflects the area of ischemic injury in early acute (per-acute) myocardial infarction. This study provides evidence that cardiac PMMR is able to detect acute myocardial infarcts at an earlier stage than traditional autopsy and routine histology.

Post-immigration education of adult immigrants in Switzerland

In 2000, 20 per cent of the Swiss resident population was constituted by foreigners (Fibbi and Wanner 2009). As in other European countries, the migrant population in Switzerland can broadly be differentiated into three groups: 1) Migrant groups from less-developed regions with substantially lower educational attainments and an increased risk for unemployment than in the reference population, 2) Migrant groups that are rather more successful, although still somewhat behind the majority population, 3) Migrant groups who even outperform the majority population in terms of educational and employment success (Heath et al. 2008). Given these inequalities – in particular in the first migrant group – participation in further education in the country of destination might contribute to better integrate migrants in the Swiss society in general and the labour market in particular. On the basis of the pooled SAKE data set (1991-2000), patterns of participation in further education of adult migrants are analysed. As the results show, many migrant groups differ from the Swiss reference population regarding participation in further education. While inequalities are often explained by educational attainments and occupational status, in some cases they hold even if controlled for the determinants explaining participation in further education in general. Regarding migrant-specific determinants, type of residence permit proved to be an important indicator explaining the disadvantages in access to further education encountered by migrants originating from Former Yugoslavia.

Smoking, apolipoprotein E genotypes, and mortality (the Ludwigshafen RIsk and Cardiovascular Health study).

AIMS The genetic polymorphism of apolipoprotein E (APOE) has been suggested to modify the effect of smoking on the development of coronary artery disease (CAD) in apparently healthy persons. The interaction of these factors in persons undergoing coronary angiography is not known. METHODS AND RESULTS We analysed the association between the APOE-genotype, smoking, angiographic CAD, and mortality in 3263 participants of the LUdwigshafen RIsk and Cardiovascular Health study. APOE-genotypes were associated with CAD [ε22 or ε23: odds ratio (OR) 0.56, 95% confidence interval (CI) 0.43-0.71; ε24 or ε34 or ε44: OR 1.10, 95% CI 0.89-1.37 compared with ε33] and moderately with cardiovascular mortality [ε22 or ε23: hazard ratio (HR) 0.71, 95% CI 0.51-0.99; ε33: HR 0.92, 95% CI 0.75-1.14 compared with ε24 or ε34 or ε44]. HRs for total mortality were 1.39 (95% CI 0.39-0.1.67), 2.29 (95% CI 1.85-2.83), 2.07 (95% CI 1.64-2.62), and 2.95 (95% CI 2.10-4.17) in ex-smokers, current smokers, current smokers without, or current smokers with one ε4 allele, respectively, compared with never-smokers. Carrying ε4 increased mortality in current, but not in ex-smokers (HR 1.66, 95% CI 1.04-2.64 for interaction). These findings applied to cardiovascular mortality, were robust against adjustment for cardiovascular risk factors, and consistent across subgroups. No interaction of smoking and ε4 was seen regarding non-cardiovascular mortality. Smokers with ε4 had reduced average low-density lipoprotein (LDL) diameters, elevated oxidized LDL, and lipoprotein-associated phospholipase A2. CONCLUSION In persons undergoing coronary angiography, there is a significant interaction between APOE-genotype and smoking. The presence of the ε4 allele in current smokers increases cardiovascular and all-cause mortality.

Childhood Trauma and PTSD symptoms increase the risk of cognitive impairment in a sample of former indetured child laborers in old Age.

A growing body of evidence suggests a link between early childhood trauma, post-traumatic stress disorder (PTSD) and higher risk for dementia in old age. The aim of the present study was to investigate the association between childhood trauma exposure, PTSD and neurocognitive function in a unique cohort of former indentured Swiss child laborers in their late adulthood. To the best of our knowledge this is the first study ever conducted on former indentured child laborers and the first to investigate the relationship between childhood versus adulthood trauma and cognitive function. According to PTSD symptoms and whether they experienced childhood trauma (CT) or adulthood trauma (AT), participants (n = 96) were categorized as belonging to one of four groups: CT/PTSD+, CT/PTSD-, AT/PTSD+, AT/PTSD-. Information on cognitive function was assessed using the Structured Interview for Diagnosis of Dementia of Alzheimer Type, Multi-infarct Dementia and Dementia of other Etiology according to ICD-10 and DSM-III-R, the Mini-Mental State Examination, and a vocabulary test. Depressive symptoms were investigated as a potential mediator for neurocognitive functioning. Individuals screening positively for PTSD symptoms performed worse on all cognitive tasks compared to healthy individuals, independent of whether they reported childhood or adulthood adversity. When controlling for depressive symptoms, the relationship between PTSD symptoms and poor cognitive function became stronger. Overall, results tentatively indicate that PTSD is accompanied by cognitive deficits which appear to be independent of earlier childhood adversity. Our findings suggest that cognitive deficits in old age may be partly a consequence of PTSD or at least be aggravated by it. However, several study limitations need to considered. Consideration of cognitive deficits when treating PTSD patients and victims of lifespan trauma (even without a diagnosis of a psychiatric condition) is crucial. Furthermore, early intervention may prevent long-term deficits in memory function and development of dementia in adulthood.

Comparative therapeutic value of post-remission approaches in patients with acute myeloid leukemia aged 40-60 years.

The preferred type of post-remission therapy (PRT) in patients with acute myeloid leukemia (AML) in first complete remission (CR1) is a subject of continued debate, especially in patients at higher risk of nonrelapse mortality (NRM), including patients >40 years of age. We report results of a time-dependent multivariable analysis of allogenic hematopoietic stem cell transplantation (alloHSCT) (n=337) versus chemotherapy (n=271) or autologous HSCT (autoHSCT) (n=152) in 760 patients aged 40-60 years with AML in CR1. Patients receiving alloHSCT showed improved overall survival (OS) as compared with chemotherapy (respectively, 57±3% vs 40±3% at 5 years, P<0.001). Comparable OS was observed following alloHSCT and autoHSCT in patients with intermediate-risk AML (60±4 vs 54±5%). However, alloHSCT was associated with less relapse (hazard ratio (HR) 0.51, P<0.001) and better relapse-free survival (RFS) (HR 0.74, P=0.029) as compared with autoHSCT in intermediate-risk AMLs. AlloHSCT was applied following myeloablative conditioning (n=157) or reduced intensity conditioning (n=180), resulting in less NRM, but comparable outcome with respect to OS, RFS and relapse. Collectively, these results show that alloHSCT is to be preferred over chemotherapy as PRT in patients with intermediate- and poor-risk AML aged 40-60 years, whereas autoHSCT remains a treatment option to be considered in patients with intermediate-risk AML.Leukemia advance online publication, 23 December 2014; doi:10.1038/leu.2014.332.

HDL Cholesterol, Apolipoproteins, and Cardiovascular Risk in Hemodialysis Patients.

High concentrations of HDL cholesterol are considered to indicate efficient reverse cholesterol transport and to protect from atherosclerosis. However, HDL has been suggested to be dysfunctional in ESRD. Hence, our main objective was to investigate the effect of HDL cholesterol on outcomes in maintenance hemodialysis patients with diabetes. Moreover, we investigated the associations between the major protein components of HDL (apoA1, apoA2, and apoC3) and end points. We performed an exploratory, post hoc analysis with 1255 participants (677 men and 578 women) of the German Diabetes Dialysis study. The mean age was 66.3 years and the mean body mass index was 28.0 kg/m(2). The primary end point was a composite of cardiac death, myocardial infarction, and stroke. The secondary end point included all-cause mortality. The mean duration of follow-up was 3.9 years. A total of 31.3% of the study participants reached the primary end point and 49.1% died from any cause. HDL cholesterol and apoA1 and apoC3 quartiles were not related to end points. However, there was a trend toward an inverse association between apoA2 and all-cause mortality. The hazard ratio for death from any cause in the fourth quartile compared with the first quartile of apoA2 was 0.63 (95% confidence interval, 0.40 to 0.89). The lack of an association between HDL cholesterol and cardiovascular risk may support the concept of dysfunctional HDL in hemodialysis. The possible beneficial effect of apoA2 on survival requires confirmation in future studies.

State-of-the-art of imaging detecting endoleaks post-EVAR with special focus on low-flow endoleaks.

Endovascular aortic repair (EVAR) necessitates lifelong surveillance for the patient, in order to detect complications timely. Endoleaks (ELs) are among the most common complications of EVAR. Especially type II ELs can have a very unpredictable clinical course and this can range from spontaneous sealing to aortic rupture. Subgroups of this type of EL need to be identified in order to make a proper risk stratification. Aim of this review is to describe the existing imaging techniques, including their advantages and disadvantages in the context of post-EVAR surveillance with a particular emphasis on low-flow ELs. Low flow ELs cause pressurization of the aortic aneurysm sac with a low velocity filling, leading to difficulty of detection by routine imaging protocols for EVAR surveillance, e.g. bi- or triphasic multislice computed tomographic angiography, magnetic resonance imaging and contrast enhanced ultrasound. In this article, we review the imaging possibilities of ELs and discuss the different imaging strategies available for depicting low flow ELs.

Evaluation of genome-wide loci of iron metabolism in hereditary hemochromatosis identifies PCSK7 as a host risk factor of liver cirrhosis

Genome-wide association studies (GWAS) have revealed genetic determinants of iron metabolism, but correlation of these with clinical phenotypes is pending. Homozygosity for HFE C282Y is the predominant genetic risk factor for hereditary hemochromatosis (HH) and may cause liver cirrhosis. However, this genotype has a low penetrance. Thus, detection of yet unknown genetic markers that identify patients at risk of developing severe liver disease is necessary for better prevention. Genetic loci associated with iron metabolism (TF, TMPRSS6, PCSK7, TFR2 and Chr2p14) in recent GWAS and liver fibrosis (PNPLA3) in recent meta-analysis were analyzed for association with either liver cirrhosis or advanced fibrosis in 148 German HFE C282Y homozygotes. Replication of associations was sought in additional 499 Austrian/Swiss and 112 HFE C282Y homozygotes from Sweden. Only variant rs236918 in the PCSK7 gene (proprotein convertase subtilisin/kexin type 7) was associated with cirrhosis or advanced fibrosis (P = 1.02 × 10(-5)) in the German cohort with genotypic odds ratios of 3.56 (95% CI 1.29-9.77) for CG heterozygotes and 5.38 (95% CI 2.39-12.10) for C allele carriers. Association between rs236918 and cirrhosis was confirmed in Austrian/Swiss HFE C282Y homozygotes (P = 0.014; ORallelic = 1.82 (95% CI 1.12-2.95) but not in Swedish patients. Post hoc combined analyses of German/Swiss/Austrian patients with available liver histology (N = 244, P = 0.00014, ORallelic = 2.84) and of males only (N = 431, P = 2.17 × 10(-5), ORallelic = 2.54) were consistent with the premier finding. Association between rs236918 and cirrhosis was not confirmed in alcoholic cirrhotics, suggesting specificity of this genetic risk factor for HH. PCSK7 variant rs236918 is a risk factor for cirrhosis in HH patients homozygous for the HFE C282Y mutation.