All-cause Infection Research Articles

Pathogen colonization of the gastrointestinal microbiome at intensive care unit admission and risk for subsequent death or infection.

Loss of colonization resistance within the gastrointestinal microbiome facilitates the expansion of pathogens and has been associated with death and infection in select populations. We tested whether gut microbiome features at the time of intensive care unit (ICU) admission predict death or infection. This was a prospective cohort study of medical ICU adults. Rectal surveillance swabs were performed at admission, selectively cultured for vancomycin-resistant Enterococcus (VRE), and assessed using 16S rRNA gene sequencing. Patients were followed for 30days for death or culture-proven bacterial infection. Of 301 patients, 123 (41%) developed culture-proven infections and 76 (25%) died. Fecal biodiversity (Shannon index) did not differ based on death or infection (p = 0.49). The presence of specific pathogens at ICU admission was associated with subsequent infection with the same organism for Escherichia coli, Pseudomonas spp., Klebsiella spp., and Clostridium difficile, and VRE at admission was associated with subsequent Enterococcus infection. In a multivariable model adjusting for severity of illness, VRE colonization and Enterococcus domination (≥ 30% 16S reads) were both associated with death or all-cause infection (aHR 1.46, 95% CI 1.06-2.00 and aHR 1.47, 95% CI 1.00-2.19, respectively); among patients without VRE colonization, Enterococcus domination was associated with excess risk of death or infection (aHR 2.13, 95% CI 1.06-4.29). Enterococcus status at ICU admission was associated with risk for death or all-cause infection, and rectal carriage of common ICU pathogens predicted specific infections. The gastrointestinal microbiome may have a role in risk stratification and early diagnosis of ICU infections.

Burden of illness and costs among paediatric haemophilia patients with and without central venous access devices treated in US hospitals.

Central venous access devices (CVADs) facilitate repeated or urgent treatments for paediatric haemophilia patients, but are associated with complications. This study examined the burden of illness, healthcare utilization and costs for CVADs in a real-world hospital setting. This study included haemophilia patients ages ≤18years with discharges during 2006-2014 in the US Premier Healthcare Database. Haemophilia was identified using ICD-9 diagnosis codes and CVAD exposure using billing information. After matching haemophilia patients with and without CVADs on demographic and clinical characteristics, we compared infection, thrombosis, length of stay (LOS), inflation-adjusted hospital cost (2014 $USD) and readmission outcomes using generalized estimating equation models adjusted for hospital teaching status. Among 4793 paediatric haemophilia patients treated at one of 548 hospitals, a total of 197 patients were identified with CVAD exposure. The matched sample included 310 haemophilia patients (155 CVAD and 155 non-CVAD). CVAD cases had greater frequencies of all-cause infections (29% vs 17%, P=.01) and thrombosis (6% vs 1%, P=.06), longer adjusted mean LOS (9.5 vs 4.7days, P=.002), higher adjusted mean inpatient total hospitalization costs ($47200 vs $25389, P=.02) as well as more inpatient and outpatient visits at 30-, 60- and 90-days (P<.05 for all differences) compared with non-CVAD patients. Paediatric haemophilia patients with CVADs experienced greater infection rates, healthcare utilization and higher hospitalization costs compared with non-CVAD patients. The results of this study may inform further research efforts to understand the costs and benefits of novel treatment alternatives for young haemophilia patients requiring CVADs.

Incidence Rate of Post-Kidney Transplant Infection: A Retrospective Cohort Study Examining Infection Rates at a Large Canadian Multicenter Tertiary-Care Facility.

Background:Reducing post-operative infections among kidney transplant patients is critical to improve long-term outcomes. With shifting disease demographics and implementation of new transplantation protocols, frequent evaluation of infection rate and type is necessary.Objective:Our objectives were to assess the incidence and types of post-operative infections in kidney transplant recipients at a large tertiary-care facility and determine sample sizes needed for future intervention trials.Design:Retrospective cohort study.Setting:The Ottawa Hospital, Ottawa, Ontario.Patients:Adult kidney transplant patients, N = 142.Measurements:Demographic data, transplant protocol, infections up to 2 years following transplantation.Methods:Infections within 2 years following transplantation in all kidney transplant recipients between January 2011 and December 2012 were reviewed. Sample sizes were determined using all-cause infection rates and infection-free survival data.Results:Of 142 patients, 44 (31.0%) had at least one infection. The incidence of infection was 36.2 per 100 patient-years by 2 years post-transplant. A total of 32 (22.5%) patients had 56 infection-related hospitalizations with 73.2% occurring in the first year. In the first 2 years, urinary tract infections had the highest incidence (18.1 per 100 patient-years) followed by skin (3.9 per 100 patient-years), cytomegalovirus (3.9 per 100 patient-years), and bacteremia (3.9 per 100 patient-years). Results indicate that 206 patients per study arm would be needed to show a 30% reduction in the 2-year incidence of infection post-transplantation.Limitations:Infection rates may be slightly underestimated due to the relatively short 2-year follow-up; however, the highest infection-risk period was captured within this time frame.Conclusions:Infections post-kidney transplant are still common, particularly urinary tract infections. They are associated with significant morbidity and hospitalization. Given the feasible sample sizes calculated in this study, intervention trials are indicated to further reduce infection rates within the first 2 years post-kidney transplantation.

Invited commentary

Infections after placement of a prosthetic graft, for either aortic or peripheral arterial reconstruction, are feared and potentially devastating complications. These infections can have significant morbidity and can also lead to subsequent infections. In this issue of the Journal of Vascular Surgery, Fariñas et al report their experience with postoperative infectious complications after placement of prosthetic grafts for both lower extremity and aortic reconstruction. Their all-cause infection rate was 27.2%. The majority of infections were surgical site infections, and only two graft infections were noted. The authors identified preoperative active lower extremity soft tissue infection as an independent risk factor for infectious complications after both aortic and lower extremity operations. Although active lower extremity infection may not be able to be resolved for patients with advanced critical limb ischemia or those who undergo emergent aortic surgery, efforts should be undertaken to treat soft tissue infection before elective aortic aneurysm repair. Prolonged mechanical ventilation was noted to be a predictor for infectious complications after aortic surgery, once again emphasizing the importance of expeditious extubation in the immediate postoperative period, although it is unclear whether this is a marker of overall illness. There are several lessons to be learned from this analysis. Studies of postoperative infectious complications should not combine very different procedures together as “vascular surgery procedures.” To correctly identify high-risk patients and to set in place systems for improvement, each specific type of intervention and indication needs to be closely examined. Leg bypass and aortic surgery are very different from one another with regard to a number of issues. For example, postoperative nasogastric tubes are often used after aortic procedures and seldom after leg bypass. Prolonged intubation with postoperative tracheostomy placement is less of an issue for lower extremity bypass as it is for major open abdominal surgery. Finally, for aortic surgery, an operation performed for aneurysmal disease is very different from one executed to treat occlusive disease, and a ruptured aneurysm is much different from an elective aneurysm repair. To decrease these rates of postoperative infections, risks identification and interventions should be tailored for specific scenarios. Studies need to be optimally designed to answer the questions that they set up to ask. Future prospective work is needed as granular details are needed, including surgical and preparation technique. Risks factors identified in this study, such as poor glucose control, anemia, and prolonged ventilation, can also be analyzed and teased out to see if they are really factors that predict a poor outcome or merely markers for ill and sick patients with more advanced disease. As such, risk reduction methods should focus specifically on each procedure and indication. The opinions or views expressed in this commentary are those of the authors and do not necessarily reflect the opinions or recommendations of the Journal of Vascular Surgery or the Society for Vascular Surgery. Risk factors and outcomes for nosocomial infection after prosthetic vascular graftsJournal of Vascular SurgeryVol. 66Issue 5PreviewThe objective of this study was to determine risk factors for nosocomial infections (NIs) and predictors of mortality in patients with prosthetic vascular grafts (PVGs). Full-Text PDF Open Archive

Transposed brachio-basilic arterio-venous fistulae versus prosthetic arteriovenous grafts; mid-term results and a review of literature

Introduction With increasing prevalence of chronic kidney disease worldwide, the demand for long-term renal replacement therapy is on the incline. Apart from renal transplantation, this includes sustainable vascular access for long-term haemodialysis, often requiring secondary and tertiary access. Objective To assess the place of Transposed Brachio-Basilic Arterio- Venous Fistula (TBB-AVF) as a second line access compared to prosthetic Aretrio Venous Grafts (AVG), with emphasis on functional patency and access related morbidity and mortality. Study Design A prospective cohort study (January 2014 to March 2016) comparing TBB-AVF and AVG, at the National Institute of Nephrology Dialysis and Transplantation, Colombo, Sri Lanka. All patients where venous mapping revealed no suitable cephalic vein were included. Those who preferentially opted for a central venous catheter, those requiring urgent initiation of dialysis or considered unfit for TBB-AVF or AVG creation were excluded. TBB-AVF was performed where the basilica vein was patent and >2 mm. AVG was used when it was Results 459 patients were enrolled; 382(83%) TBB-AVF and 77(17%) AVG. Mean follow-up was 11(± 4.8) months. There were 9 deaths, all >4 weeks from access creation and not directly related to the access. The all-cause mortality rate was 5/382 (1.3%) TBB-AVF and 4/77 (5.2%) AVG; p=0.02. Surgical site infections were seen in 24 (6.4%) TBB-AVFs and 10 (13.7%) AVGs; p=0.03. The overall functional patency at six months was 307/375 (81.9%) in TBB-AVF and 57/73 (78.1%) in AVGs; p=0.45. Conclusion TBB-AVF provide comparable medium term functional patency to AVG and are associated with a significantly less incidence of all-cause mortality and surgical site infection.

Outcome of HIV-associated lymphoma in a resource-limited setting of Jos, Nigeria

BackgroundLymphoma is a leading cause of cancer-related death among human immunodeficiency virus (HIV)-infected individuals in the current era of potent anti-retroviral therapy (ART). Globally, mortality after HIV-associated lymphoma has profound regional variation. Little is known about HIV-associated lymphoma mortality in Nigeria and other resource-limited setting in sub-Saharan Africa. Therefore, we evaluated the all-cause mortality after lymphoma and associated risk factors including HIV at the Jos University Teaching Hospital (JUTH) Nigeria.MethodsWe conducted a ten-year retrospective cohort study of lymphoma patients managed in JUTH. The main outcome measured was all-cause mortality and HIV infection was the main exposure variable. Overall death rate was estimated using the total number of death events and cumulative follow up time from lymphoma diagnosis to death. Cox proportional hazard regression was used to assess factors associated with mortality after lymphoma diagnosis.ResultsOut of 40 lymphoma patients evaluated, 8(20.0%) were HIV positive and 32(80.0%) were HIV negative. After 127.63 person- years of follow-up, there were 16 deaths leading to a crude mortality rate of 40.0 per 100 person-years. The 2-year probability of survival was 30% for HIV-infected patients and 74% for HIV-uninfected. Median survival probability for HIV-infected patients was 2.1 years and 7.6 years for those without HIV. Unadjusted hazard of death was associated with late stage, HR 11.33(95% CI 2.55, 50.26,p = 0.001); low cumulative cycles of chemotherapy, HR 6.43(95% CI 1.80, 22.89,p = 0.004); greater age, HR 5.12(95% CI 1.45,18.08,p = 0.01); presence of comorbidity, HR 3.43(95% CI 1.10,10.78,p = 0.03); and HIV-infection, HR 3.32(95% CI 1.05, 10.51,p = 0.04). In an adjusted model only stage was significantly associated with death, AHR 5.45(1.14–26.06, p = 0.03).ConclusionOur findings suggest that HIV- infection accounted for three times probability of death in lymphoma patients compared to their HIV-uninfected counterparts due to late stage of lymphoma presentation in this population. Also initiation of chemotherapy was associated with lower probability of death among lymphoma patients managed at JUTH, Nigeria. Earlier stage at lymphoma diagnosis and prompt therapeutic intervention is likely to improve survival in these patients. Future research should undertake collaborative studies to obtain comprehensive regional data and identify unique risk factors of poor outcomes among HIV-infected patients with lymphoma in Nigeria.

Polyclonal and monoclonal antibodies for induction therapy in kidney transplant recipients.

Polyclonal and monoclonal antibodies for induction therapy in kidney transplant recipients.

Project CLEAR (Changing Lives by Eradicating Antibiotic Resistance) Randomized Controlled Trial (RCT): Serial Decolonization of Recently Hospitalized Methicillin-Resistant Staphylococcus aureus (MRSA) Carriers Reduces Risks of MRSA Infections and All-Cause Infections in the 1-Year Post-Hospitalization

Project CLEAR (Changing Lives by Eradicating Antibiotic Resistance) Randomized Controlled Trial (RCT): Serial Decolonization of Recently Hospitalized Methicillin-Resistant Staphylococcus aureus (MRSA) Carriers Reduces Risks of MRSA Infections and All-Cause Infections in the 1-Year Post-Hospitalization

Burden of Illness Among Pediatric Hemophilia Patients with and without Central Venous Access Devices Treated in U.S. Hospitals

Introduction: Central venous access devices (CVADs) are valuable tools to facilitate repeated or urgent treatments for hemophilia patients. However, CVADs may increase the risk for local and systemic infection, as well as thrombosis. There is limited real-world information on the use of CVADs among the pediatric hemophilia population treated in a hospital setting. The aim of this study was to describe and compare the characteristics and burden of illness of the hemophilia population with and without CVADs.Methods: This observational study used data from the Premier research database and included inpatients and outpatients who were age ≤ 18 years at the time of index admission and discharged during 2006-2014 from one of 548 U.S. hospitals. We identified hemophilia patients using principal or secondary ICD-9 diagnosis codes 286.0x or 286.1x, and CVAD exposure using billing information that represented the procedure with or without a corresponding ICD-9 procedure code of 86.07. We matched CVAD to non-CVAD exposed patients using a 1:1 matching scheme based on age (+/- 1 year), Factor-VIII therapy (yes/no), Factor-IX therapy (yes/no), number of prior HCP encounters in previous 365 days (+/- 5), previous hospitalization for infection in previous 365 days (yes/no), and geography (9 census region categories). Comparisons of outcomes including infections, thrombosis, revisit rates, and length of stay between groups were made using Wilcoxon signed rank tests for medians and generalized linear models for categorical variables to account for correlation between matched pairs, stratified by inpatients and outpatients.Results: There were a total of 4,793 eligible pediatric hemophilia patients during the study period. Of these, 197 (4.1%) had CVAD exposure according to our criteria. The matched sample included 163 CVAD cases and 163 controls (142 inpatients and 184 outpatients).The inpatient hemophilia population was median age 5 years, primarily male (93%), white (55%), treated in urban hospitals (94%) in the south region (46%), and had Medicaid as the primary payer (47%). Compared with the non-CVAD group, patients with CVAD exposure in the pre-matched group were more often male (98% vs. 92%), younger (3 vs. 5 years), and treated in urban (98% vs. 94%), teaching hospitals (79% vs. 64%). Among the inpatient matched sample, CVAD cases compared with controls experienced a greater frequency of all-cause 30-day (24% vs. 11%, p=0.03), 60-day (31% % vs. 13%, p=0.01), and 90-day (33% vs. 17%, p=0.02) outpatient revisits, and more all-cause infections (12% vs. 2%, p=0.02), but no notable difference in the frequency of thrombosis (4% vs. 2%, p=0.48) or inpatient revisits. The median hospital length of stay for inpatients was greater for CVAD cases compared with controls (4 vs. 3 days, p=0.01).The outpatient hemophilia population was slightly older (median age 9 years) and less often male (82%) or treated in urban hospitals (82%), but otherwise had similar demographic characteristics to the inpatient population; 58% white, with 49% in the South and 45% having Medicaid as the primary payer. Compared with the non-CVAD group, outpatients with CVAD exposure in the pre-matched group were more often male (97% vs. 82%), younger (4 vs. 9 years), and treated in urban (92% vs 82%), teaching hospitals (61% vs. 39%). Among the outpatient matched sample, CVAD cases compared with controls had greater frequencies of subsequent inpatient and outpatient visits at 30-, 60-, and 90-days (all p< 0.05), as well as all-cause infections (24% vs. 3%, p=0.0001) and thrombosis (9% vs. 0.9%, p=0.03).Conclusions: CVAD exposure was associated with a greater frequency of infections, thrombosis, and inpatient and outpatient revisit rates, as well as longer length of stay, among pediatric hemophilia patients treated in U.S. hospitals. The results of this study may inform research efforts for novel treatments best suited to the unique needs of hemophilia patients with CVADs. DisclosuresBuckley:Biogen: Employment. Dreyfus:Premier, Inc.: Employment, Equity Ownership, Other: Premier received funding from Biogen to conduct the study. Prasad:MCPHS University: Employment; Biogen: Other: Contracted employment with MCPHS University. Gayle:Premier, Inc.: Employment, Equity Ownership, Other: Premier received funding from Biogen to conduct the study. Kendter:Biogen: Employment. Hall:Biogen: Employment.

The burden of infection in severely injured trauma patients and the relationship with admission shock severity

Infection following severe injury is common and has a major impact on patient outcomes. The relationship between patient, injury, and physiologic characteristics with subsequent infections is not clearly defined. The objective of this study was to characterize the drivers and burden of all-cause infection in critical care trauma patients. A prospective cohort study of severely injured adult patients admitted to critical care was conducted. Data were collected prospectively on patient and injury characteristics, baseline physiology, coagulation profiles, and blood product use. Patients were followed up daily for infectious episodes and other adverse outcomes while in the hospital. Three hundred patients (Injury Severity Score [ISS] >15) were recruited. In 48 hours or less, 29 patients (10%) died, leaving a cohort of 271. One hundred forty-one patients (52%) developed at least one infection. Three hundred four infections were diagnosed overall. Infection and noninfection groups were matched for age, sex, mechanism, and ISS. Infection rates were greater with any degree of admission shock and threefold higher in the most severely shocked cohort (p < 0.01). In multivariate analysis, base deficit (odds ratio [OR], 1.78, 95% confidence interval [CI], 1.48-1.94; p < 0.001) and lactate (OR, 1.36; 95% CI, 1.10-1.69; p = 0.05) were independently associated with the development of infection. Outcomes were significantly worse for the patients with infection. In multivariate logistic regression, infection was the only factor independently associated with multiple-organ failure (p < 0.001; OR, 15.4; 95% CI, 8.2-28.9; r = 0.402), ventilator-free days (p < 0.001; β, -4.48; 95% CI, -6.7 to -2.1; r = 0.245), critical care length of stay (p < 0.001; β, 13.2; 95% CI, 10.0-16.4; r = 0.466), and hospital length of stay (p < 0.001; β, 31.1; 95% CI, 24.0-38.2; r = 0.492). Infectious complications are a burden for severely injured patients and occur early in the critical care stay. Severity of admission shock was predictive of infection and represents an opportunity for interventions to improve infectious outcomes. The incidence of infection may also have utility as an end point for clinical trials in trauma hemorrhage given the relationship with patient-experienced outcomes. Prognostic/epidemiologic study, level II.

Benefits and Risks of Maintaining Normothermia during Cardiopulmonary Bypass in Adult Cardiac Surgery: A Systematic Review

Cardiopulmonary bypass is associated with significant morbidities, and the ideal temperature management during cardiopulmonary bypass remains uncertain. This review assessed the benefits and risks of maintaining normothermia during cardiopulmonary bypass in adult cardiac surgery. A total of 6,731 patients from 44 randomized controlled trials in 14 countries, comparing normothermic (> 34°C) and hypothermic (≤34°C) cardiopulmonary bypass in cardiac surgery (>18 years of age), were identified from MEDLINE (1966 to August 10, 2009), EMBASE (1988 to August 10, 2009), and Cochrane controlled trials register and subject to meta-analysis. Two investigators examined all studies and extracted the data independently. Mortality after normothermic and hypothermic bypass was not significantly different (1.4% vs. 1.9% respectively, relative risk [RR] 1.38, 95% confidence interval [CI] 0.94-2.04, I(2) = 0%, P = 0.10). Hypothermic bypass was, however, associated with an increased risk of allogeneic red blood cells (RR 1.19, 95% CI 1.07-1.34, I(2) = 0%, P = 0.002), fresh frozen plasma (RR 1.54, 95% CI 1.06-2.24, I(2) = 7.7%, P = 0.02), and platelet transfusion (RR 2.53, 95% CI 1.26-5.06, I(2) = 44%, P = 0.009). The risk of stroke, cognitive decline, atrial fibrillation, use of inotropic support or intra-aortic balloon pump, myocardial infarction, all-cause infections, and acute kidney injury after cardiac surgery was not significantly different between the two groups. The differences in the bypass time and targeted perfusion temperature were not significantly related to the risk of mortality and stroke. The current evidence suggests that maintaining normothermia during cardiopulmonary bypass in adult cardiac surgery is as safe as that of hypothermic surgery, and associated with a reduced risk of allogeneic blood transfusion.

Sitagliptin treatment of patients with type 2 diabetes does not affect CD4+ T-cell activation

Dipeptidyl peptidase IV (DPP4) inhibitors have recently become widely used for treating type 2 diabetes, but in meta-analyses are associated with a mildly increased risk of all-cause infections. CD26 is a cell-surface form of DPP4 which can costimulate T-cell proliferation, raising the possibility that DPP4 inhibitors might adversely affect immune function. To address this issue in an observational study, two groups of 20 subjects each were recruited from a private endocrinology practice; one group consisted of type 2 diabetes patients treated for at least 6 months with the DPP4 inhibitor, sitagliptin, whereas patients in the other group had never been treated with this agent. The groups were similar with regard to sex and racial composition, body mass index, hemoglobin A 1c, and use of other medications for diabetes, but the sitagliptin group was slightly older. A blood sample from each patient was analyzed for CD4+ T-cell activation in response to phytohemagglutinin using adenosine triphosphate (ATP)-stimulated bioluminescence. There was not a significant difference in T-cell activation between the treatment groups (median, 419 and 481 ng/ml ATP in the groups that were and were not treated with sitagliptin, respectively). Thus the observed increased rate of infection in diabetic patients treated with sitagliptin cannot be explained by a major effect on T-cell activation. Randomized studies, preferably using several assays of immune function, should be performed to confirm and extend these findings.

Percutaneous Creation of a Venous Anastomosis in a Native Hemodialysis Fistula

The advantages of autogenous fistulas over grafts and catheters for vascular access in hemodialysis are well recognized and include lower rates of all-cause mortality and infection and significantly decreased total access costs. However, a substantial number of fistulas will never mature and are eventually abandoned. Percutaneous techniques are increasingly used to salvage fistulas to enable maturation and use. The authors report on a patient with a thrombosed immature brachiocephalic dialysis fistula with an occluded outflow vein, in whom fistula function was salvaged through creation of a percutaneous vein-to-vein anastomosis. This technique adds to the growing armamentarium of interventional therapies for occluded venous outflow in hemodialysis access sites.

Dipeptidyl Peptidase-4 (CD26): Knowing the Function before Inhibiting the Enzyme

Dipeptidyl peptidase-4 (DPP4) or adenosine deaminase complexing protein 2 (ADCP 2) or T-cell activation antigen CD26 (EC 3.4.14.5.) is a serine exopeptidase belonging to the S9B protein family that cleaves X-proline dipeptides from the N-terminus of polypeptides, such as chemokines, neuropeptides, and peptide hormones. The enzyme is a type II transmembrane glycoprotein, expressed on the surface of many cell types, whose physiological functions are largely unknown. Protein dimerisation should be required for catalytic activity and glycosylation of the enzyme could impact on its physiological functions. The dimeric glycoprotein ADCP has been found linked to adenosine deaminase (ADA) whose relationship with lymphocyte maturation-differentiation is well-established. Since implicated in the regulation of the biological activity of hormones and chemokines, such as glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, DPP4 inhibition offers a new potential therapeutic approach for type 2 diabetes mellitus, as monotherapy and adjunct therapy to other oral agents. The clinical use of presently available orally active inhibitors of DPP4, however, has been associated with side effects that have been in part attributed to the inhibition of related serine proteases, such as DPP8 and DPP9. Indeed, it is noteworthy that CD26 has a key role in immune regulation as a T cell activation molecule and in immune-mediated disorder. All-cause infections were increased after sitagliptin treatment. It is noteworthy that the effects of DPP4 inhibition on the immune system have not been extensively investigated. So far, only routine laboratory safety variables have been measured in published randomised controlled trials. The review summarises present knowledge in the field and suggests some potential directions of future research.

Benefits and Risks of Corticosteroid Prophylaxis in Adult Cardiac Surgery

Cardiopulmonary bypass and cardiac surgery are associated with a significant systemic inflammatory response that may increase postoperative complications. This meta-analysis assessed whether the benefits and risks of corticosteroid use were dose dependent in adult cardiac surgery. Randomized controlled trials of the use of corticosteroid prophylaxis in adult cardiac surgery (>18 years of age) requiring cardiopulmonary bypass were selected from MEDLINE (1966 to August 1, 2008), EMBASE (1988 to August 1, 2008), and the Cochrane controlled trials register without any language restrictions. A total of 3323 patients from 50 randomized controlled trials were identified and subject to meta-analysis. Corticosteroid prophylaxis reduced the risk of atrial fibrillation (25.1% versus 35.1%; number needed to treat, 10; relative risk, 0.74; 95% confidence interval [CI], 0.63 to 0.86; P<0.01) and length of stay in the intensive care unit (weighted mean difference, -0.37 days; 95% CI, -0.21 to -0.52; P<0.01) and hospital (weighted mean difference, -0.66 days; 95% CI, -0.77 to -1.25; P=0.03) compared with placebo. The use of corticosteroid was not associated with an increased risk of all-cause infection (relative risk, 0.93; 95% CI, 0.61 to 1.41; P=0.73), but hyperglycemia requiring insulin infusion after corticosteroid prophylaxis was common (28.2%; relative risk, 1.49; 95% CI, 1.11 to 2.01; P<0.01). No additional benefits were found on all outcomes beyond a total dose of 1000 mg hydrocortisone, and very high doses of corticosteroid were associated with prolonged mechanical ventilation. Evidence suggests that low-dose corticosteroid is as effective as high-dose corticosteroid in reducing the risk of atrial fibrillation and duration of mechanical ventilation but with fewer potential side effects in adult cardiac surgery.

Emerging role of dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes

In type 2 diabetes mellitus (T2DM) there is a progressive loss of beta-cell function. One new approach yielding promising results is the use of the orally active dipeptidyl peptidase-4 (DPP-4) inhibitors. However, every new compound for T2DM has to prove long-term safety especially on cardiovascular outcomes. Systematic review and meta-analysis of the effects of sitagliptin and vildagliptin therapy on main efficacy parameters and safety. SELECTION CRITERIA, DATA COLLECTION, AND ANALYSIS: Randomized controlled clinical studies of at least 12 weeks' duration in T2DM. DPP-4 inhibitors versus placebo showed glycosylated hemoglobin A1c (A1c) improvements of 0.7% versus placebo but not compared to monotherapy with other hypoglycemic agents (0.3% in favor of controls). The overall risk profile of DPP-4 inhibitors was low, however a 34% relative risk increase (95% confidence interval 10% to 64%, P = 0.004) was noted for all-cause infection associated with sitagliptin use. No data on immune function, health-related quality of life and diabetic complications could be extracted. DPP-4 inhibitors have some theoretical advantages over existing therapies with oral antidiabetic compounds but should currently be restricted to individual patients. Long-term data on cardiovascular outcomes and safety are needed before widespread use of these new agents.

Dipeptidyl peptidase-4 (DPP-4) inhibitors for type 2 diabetes mellitus.

In type 2 diabetes mellitus there is a progressive loss of beta-cell function. One new approach yielding promising results is the use of the orally active dipeptidyl peptidase-4 (DPP-4) inhibitors like sitagliptin and vildagliptin. To assess the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors for type 2 diabetes mellitus. Studies were obtained from computerised searches of MEDLINE, EMBASE and The Cochrane Library. Studies were included if they were randomised controlled trials in adult people with type 2 diabetes mellitus and had a trial duration of at least 12 weeks. Two authors independently assessed risk of bias and extracted data. Pooling of studies was performed by means of fixed-effect meta-analysis. Twenty-five studies of good quality were identified, 11 trials evaluated sitagliptin and 14 trials vildagliptin treatment. Altogether, 6743 patients were randomised in sitagliptin and 6121 patients in vildagliptin studies, respectively. Sitagliptin and vildagliptin studies ranged from 12 to 52 weeks duration. No data were published on mortality, diabetic complications, costs of treatment and health-related quality of life. Sitagliptin and vildagliptin therapy in comparison with placebo resulted in an HbA1c reduction of approximately 0.7% and 0.6%, respectively. Data on comparisons with active comparators were limited but indicated no improved metabolic control following DPP-4 intervention in contrast to other hypoglycaemic agents. Sitagliptin and vildagliptin therapy did not result in weight gain but weight loss was more pronounced following placebo interventions. No definite conclusions could be drawn from published data on sitagliptin and vildagliptin effects on measurements of beta-cell function. Overall, sitagliptin and vildagliptin were well tolerated, no severe hypoglycaemia was reported in patients taking sitagliptin or vildagliptin. All-cause infections increased significantly after sitagliptin treatment but did not reach statistical significance following vildagliptin therapy. All published randomised controlled trials of at least 12 weeks treatment with sitagliptin and vildagliptin only reported routine laboratory safety measurements DPP-4 inhibitors have some theoretical advantages over existing therapies with oral antidiabetic compounds but should currently be restricted to individual patients. Long-term data especially on cardiovascular outcomes and safety are urgently needed before widespread use of these new agents. More information on the benefit-risk ratio of DPP-4 inhibitor treatment is necessary especially analysing adverse effects on parameters of immune function. Also, long-term data are needed investigating patient-oriented parameters like health-related quality of life, diabetic complications and all-cause mortality.

Relation of Depression, Natural Killer Cell Function, and Infections after Coronary Artery Bypass in Women

After hospital discharge for coronary artery bypass grafting (CABG), infection is a common cause of morbidity. Although depression has been associated with immune dysfunction, its role in post-CABG infection is unknown. The purpose of this study was to: 1) compare natural killer cell cytotoxicity (NKCC) and post-hospitalization infections in depressed and non-depressed women after CABG; and 2) test whether NKCC mediated the relationship between post-discharge depression and infections. Sixty-seven women recovering from CABG were assessed for depression prior to hospital discharge and followed for six months. Major depression was identified by a structured clinical interview. Infections were identified by patient report using the Modified Health Review and by medical chart audit. Compared to non-depressed women after CABG, women with major depression had reduced NKCC, more all-cause infections, and more self-reported illnesses. Although NKCC did not mediate the relationship between depression and wound (i.e. incisional) infections after CABG, it did mediate the relationship between depression and non-wound infections, including pneumonias and upper respiratory infections. For the first six months after CABG, women with major depression are at increased risk for infections. Natural killer cell cytotoxicity may be related to this phenomenon, particularly to non-wound infections.