Risk Of Infection-related Mortality Research Articles

Different impact of hemodialysis vintage on cause-specific mortality in long-term hemodialysis patients.

Although dialysis vintage is associated with increased mortality risk in patients receiving hemodialysis (HD), the association of dialysis vintage with cause-specific mortality is unclear. We conducted a nationwide registry-based retrospective cohort study of 216 246 patients receiving maintenance HD for > 1 year at the end of 2009. The associations of dialysis vintage categories (1 -< 2, 2 -< 5, 5 -< 10, 10 -< 15, 15 -< 20, 20 -< 25, 25 -< 30 and ≥ 30 years) with 1-year all-cause and cause-specific mortality, including cardiovascular diseases (CVDs) and infection-related mortality, were examined using logistic regression models. During the 1-year study period, 18 614 deaths occurred from all causes, including 7263 and 3504 deaths from CVD and infection-related causes. From multivariate analysis, the dialysis vintage was incrementally associated with a higher risk for all-cause mortality, with worse outcome observed in the ≥ 30 years category {odds ratio [OR] = 2.43 (95% confidence interval (CI) 2.13-2.77}. A similar association was apparent between the dialysis vintage and infection-related mortality, with a higher risk than that of all-cause mortality in each vintage category [≥ 30 years, OR = 3.55 (95% CI 2.72-4.66)], while the dialysis vintage was associated with only a modest increase in risk of CVD mortality [≥ 30 years, OR = 1.64 (95% CI 1.30-2.08)]. Dialysis vintage has a different impact on cause-specific mortality, with a higher risk for infection-related mortality than CVD mortality. This impact is most pronounced in long-term HD survivors, to whom much attention should be devoted to prevent infectious complications.

Optimal breastfeeding practices and infant and child mortality: a systematic review and meta-analysis.

To synthesise the evidence for effects of optimal breastfeeding on all-cause and infection-related mortality in infants and children aged 0-23 months. We conducted a systematic review to compare the effect of predominant, partial or nonbreastfeeding versus exclusive breastfeeding on mortality rates in the first six months of life and effect of no versus any breastfeeding on mortality rates between 6 and 23 months of age. A systematic literature search was conducted in PubMed, Cochrane CENTRAL and CABI. The risk of all-cause mortality was higher in predominantly (RR 1.5), partially (RR 4.8) and nonbreastfed (RR14.4) infants compared to exclusively breastfed infants 0-5 months of age. Children 6-11 and 12-23 months of age who were not breastfed had 1.8- and 2.0-fold higher risk of mortality, respectively, when compared to those who were breastfed. Risk of infection-related mortality in 0-5 months was higher in predominantly (RR 1.7), partially (RR 4.56) and nonbreastfed (RR 8.66) infants compared to exclusive breastfed infants. The risk was twofold higher in nonbreastfed children when compared to breastfed children aged 6-23 months. The findings underscore the importance of optimal breastfeeding practices during infancy and early childhood.

Pulse Steroids for Refractory Antisynthetase Syndrome: A Booster Therapy?

SESSION TITLE: Diffuse Lung Disease Student/Resident Case Report Posters SESSION TYPE: Student/Resident Case Report Poster PRESENTED ON: Tuesday, October 27, 2015 at 01:30 PM - 02:30 PM INTRODUCTION: Anti-synthetase syndrome (ASS) is an autoimmune condition characterized by inflammatory myositis and interstitial lung disease. Our case of refractory ASS suggests that administering pulse steroids may enhance standard treatment. CASE PRESENTATION: A 43 year-old woman presented with cough, arthralgias and dyspnea progressive over six months. No fever, rash or muscle weakness. Physical exam revealed hypoxia, bibasilar crackles, and mechanic's hands. Autoimmune serologies including ANA, anti-dsDNA, anti-smith, rheumatoid factor, anti-SSA, anti-SSB, anti-SCl-70, and anti-centromere were negative. Anti-Jo1 antibody was positive (6.7 index). Creatinine kinase (200 U/L) and aldolase (11.9 U/L) were elevated. Chest CT revealed fibrotic changes, consolidation without honeycombing in lower lobes and ground glass opacities (GGO) in upper lobes. Pulmonary function testing demonstrated moderate restriction and severely impaired diffusion (DLCO) at 39% predicted. The diagnosis was antisynthetase syndrome. The patient received 60 mg of prednisone daily with rapid improvement in symptoms and radiographic findings. However, tapering steroids failed and 3 grams of daily mycophenolate was added to her regimen. Six weeks later, she deteriorated further with worsening hypoxia, arthralgias, mechanic's hands, DLCO (32% predicted) and progressive GGO and lower lobe infiltration. We administered solumedrol 1 gram daily for three days with rapid clinical improvement and resumed her regimen of daily prednisone and mycophenolate. Within three weeks, the CT chest showed marked clearing and DLCO improved to 39% predicted. At four months post-pulse steroids, she remains on mycophenolate and prednisone (tapered to 20 mg/day) with resolved hypoxia, minimal CT findings and DLCO improved to 46% predicted. DISCUSSION: Prednisone 1mg/kg/day is first line monotherapy for ASS but is often combined with other immunosuppressants. Up to 25% of cases may be refractory, with reported 45% mortality at 20 months. Rituximab is the common therapy for refractory ASS but may present a high infection-related mortality risk. We suggest that in patients with rapidly deteriorating or refractory ASS, pulse steroids may enhance response to standard therapy as a ‘booster' treatment. The rapid response is advantageous since uncontrolled inflammation may lead to irreversible fibrotic changes. CONCLUSIONS: Refractory ASS often has a poor outcome. Current treatments are based on expert recommendations or case series without strong level of evidence. Pulse steroids may offer an effective adjunct to therapy with acute deterioration of ASS. Reference #1: Marie I et al. Interstitial lung disease in patients with antisynthetase syndrome. Arthritis Care & Research. 2013 May; 65 (5): 800-808 Reference #2: Anderson H et al. Long-term experience with rituximab in ASS-related ILD. Rheumatology (2015) doi; 10.1093/rheumatology/kev004; March 2015 DISCLOSURE: The following authors have nothing to disclose: Marie Rosalette Mortel, Pius Ochieng, Mary Salvatore, Mary O Sullivan No Product/Research Disclosure Information

Serum Ferritin Predicts Mortality Regardless of Inflammatory and Nutritional Status in Patients Starting Dialysis: A Prospective Cohort Study

Background: The impact of serum ferritin on prognosis in patients starting hemodialysis (HD) is not fully elucidated. Methods: A prospective cohort of 946 incident HD patients from 26 dialysis centers in Korea was selected for this study. Patients were divided into tertiles according to natural logarithm (Ln) ferritin concentrations. Results: During a median follow-up of 39 months, 88 (9.3%) patients died. Multivariate Cox proportional hazard analysis demonstrated that Ln ferritin was independently associated with an increase in cardiovascular mortality risk (hazard ratio (HR) 1.604, 95% CI 1.040-2.474, p = 0.033), infection-related mortality risk (HR 1.916, 95% CI 1.056-3.476, p = 0.032), and all-cause mortality risk (HR 1.547, 95% CI 1.156-2.069, p = 0.003). Conclusion: Serum ferritin levels at the time of HD commencement were a significant independent risk factor for mortality regardless of systemic inflammation and nutritional status. Therefore, elevated serum ferritin levels could be an effective indicator for prognosis.

Mortality from infections and malignancies in patients treated with renal replacement therapy: data from the ERA-EDTA registry.

Infections and malignancies are the most common non-cardiovascular causes of death in patients on chronic renal replacement therapy (RRT). Here, we aimed to quantify the mortality risk attributed to infections and malignancies in dialysis patients and kidney transplant recipients when compared with the general population by age group and sex. We followed 168 156 patients included in the ERA-EDTA registry who started RRT in 1993-2007 until 1 January 2012. Age- and cause-specific mortality rates per 1000 person-years (py) and mortality rate ratios (MRRs) compared with the European general population (WHO) were calculated. To identify risk factors, we used Cox regression. Infection-related mortality was increased 82-fold in dialysis patients and 32-fold in transplant recipients compared with the general population. Female sex, diabetes, cancer and multisystem disease were associated with an increased risk of infection-related mortality. The sex difference was most pronounced for dialysis patients aged 0-39 years, with women having a 32% (adjusted HR 1.32 95% CI 1.09-1.60) higher risk of infection-related mortality than men. Mortality from malignancies was 2.9 times higher in dialysis patients and 1.7 times higher in transplant recipients than in the general population. Cancer and multisystem disease as primary causes of end-stage renal disease were associated with higher mortality from malignancies. Infection-related mortality is highly increased in dialysis and kidney transplant patients, while the risk of malignancy-related death is moderately increased. Young women on dialysis may deserve special attention because of their high excess risk of infection-related mortality. Further research into the mechanisms, prevention and optimal treatment of infections in this vulnerable population is required.

Infection-related mortality in children with acute lymphoblastic leukemia: an analysis of infectious deaths on UKALL2003

AbstractAlthough infection is the major cause of treatment-related mortality (TRM) in childhood acute lymphoblastic leukemia, factors associated with infection-related mortality (IRM) are poorly understood. To address this, we report an analysis of all 75 cases of IRM in the United Kingdom Childhood Acute Lymphoblastic Leukaemia Randomised Trial 2003 (UKALL 2003). The 5-year cumulative incidence of IRM was 2.4% (95% confidence interval [CI], 1.9%-3.0%), accounting for 75 (30%) of 249 trial deaths and 75 (64%) of 117 TRM deaths. Risk for IRM as a proportion of TRM was greater in induction than other phases (77% vs 56%; P = .02). Sixty-eight percent of cases were associated with bacterial infection (64% Gram-negative) and 20% with fungal infection. Down syndrome was the most significant risk factor for IRM (odds ratio [OR], 12.08; 95% CI, 6.54-22.32; P < .0001). In addition, there was a trend toward increased IRM in girls (OR, 1.63; 95% CI, 1.02-2.61; P = .04), as well as increasing treatment intensity (regimen B vs A: OR, 2.11 [95% CI, 1.24-3.60]; regimen C vs A: OR, 1.41 [95% CI, 0.76-2.62]; P = .02). Importantly, patients with Down syndrome were at significantly higher risk for IRM during maintenance (P = .048). Our results confirm Down syndrome as a major risk factor for IRM. Enhanced supportive care and prophylactic antibiotics should be considered in high-risk patient groups and during periods of increased risk. This study was registered at http://www.controlled-trials.com/ as #ISRCTN07355119.

Comorbid infections in patients with rheumatoid arthritis

The problem of comorbid infections (CI) in modern rheumatology remains important. The reasons behind it include the presence of an autoimmune rheumatic disease and the need to use immunosuppressant drugs. We discuss some problems of CI under EULAR recommendations (2013) for the management of rheumatoid arthritis (RA). The incidence rates of comorbid infections in patients treated with different disease- modifying anti-rheumatic and biological drugs are analyzed. The significance of measures for preventing CI in management of RA patients is demonstrated. The significance of vaccination (first of all, with anti-influenza and pneumococcal vaccines) of RA patients to reduce the incidence rate of lower respiratory tract infections and the risk of infection-related mortality is emphasized. Vaccination is recommended even if suboptimal outcome is expected.

Infection-related mortality is higher for kidney allograft recipients with pretransplant diabetes mellitus

The risk of infection-related mortality in kidney allograft recipients with pre-existing diabetes mellitus is unknown. We determined the risk of infection-related mortality after kidney transplantation in a population-based cohort stratified by diagnosis of pre-existing diabetes mellitus. We linked data between two national registries (Hospital Episode Statistics and the Office for National Statistics) to select all mortality events after kidney transplantation in England between April 2001 and March 2012. The primary outcome measure was infection-related mortality after transplantation comparing diabetic with non-diabetic recipients. A total of 19,103 kidney allograft recipients were analysed; 2,968 (15.5%) were known to have diabetes before kidney transplantation. After transplantation, 2,085 deaths (10.9%) occurred (median follow-up 4.4 years [interquartile range 2.2-7.3]), with 434 classified as secondary to infection (20.8% of all deaths). Risk of overall (16.0% vs 10.0%, p < 0.001) and infection-related (3.3% vs 2.1%, p < 0.001) mortality after kidney transplantation was higher for diabetic than non-diabetic recipients, respectively. No cytomegalovirus-related deaths occurred in diabetic recipients compared with 5.7% in non-diabetic recipients (p < 0.007), with a trend towards more unspecified sepsis in diabetic recipients (30.6% vs 22.6%, respectively, p = 0.070). Diabetes at the time of transplantation was an independent risk factor predicting infection-related mortality in kidney allograft recipients after transplantation (HR 1.71 [95% CI 1.36, 2.15], p < 0.001). Infection-related mortality is more common in kidney allograft recipients with pre-existing diabetes mellitus. Further work is required to determine whether attenuated immunosuppression is beneficial for diabetic kidney allograft recipients.

High-Efficiency Postdilution Online Hemodiafiltration Reduces All-Cause Mortality in Hemodialysis Patients

Retrospective studies suggest that online hemodiafiltration (OL-HDF) may reduce the risk of mortality compared with standard hemodialysis in patients with ESRD. We conducted a multicenter, open-label, randomized controlled trial in which we assigned 906 chronic hemodialysis patients either to continue hemodialysis (n=450) or to switch to high-efficiency postdilution OL-HDF (n=456). The primary outcome was all-cause mortality, and secondary outcomes included cardiovascular mortality, all-cause hospitalization, treatment tolerability, and laboratory data. Compared with patients who continued on hemodialysis, those assigned to OL-HDF had a 30% lower risk of all-cause mortality (hazard ratio [HR], 0.70; 95% confidence interval [95% CI], 0.53-0.92; P=0.01), a 33% lower risk of cardiovascular mortality (HR, 0.67; 95% CI, 0.44-1.02; P=0.06), and a 55% lower risk of infection-related mortality (HR, 0.45; 95% CI, 0.21-0.96; P=0.03). The estimated number needed to treat suggested that switching eight patients from hemodialysis to OL-HDF may prevent one annual death. The incidence rates of dialysis sessions complicated by hypotension and of all-cause hospitalization were lower in patients assigned to OL-HDF. In conclusion, high-efficiency postdilution OL-HDF reduces all-cause mortality compared with conventional hemodialysis.

Retrospective analysis of fluoroquinolone prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation

Patients undergoing allogeneic hematopoietic stem cell transplant are at a high risk for infection-related mortality in the immediate post-transplantation phase. Prophylaxis with a fluoroquinolone is now recommended to reduce this risk with the stipulation that surveillance for increased fluoroquinolone resistance Clostridium difficile associated diarrhea be conducted. We conducted a retrospective chart review of 48 patients who underwent an allogeneic hematopoietic stem cell transplant and received a fluoroquinolone for prophylaxis and 48 patients who underwent an allogeneic hematopoietic stem cell transplant who did not receive a fluoroquinolone for prophylaxis. All patients received the same standard antifungal, antiviral and anti-pneumocystis prophylaxis. Patients receiving fluoroquinolone prophylaxis had a lower incidence of febrile neutropenia than those not receiving prophylaxis, though the difference was not found to be statistically significant (83% vs. 67%, p = 0.098). Similar non-significant improvements in the number of positive cultures recovered during an episode of febrile neutropenia and antimicrobial days were noted. No significant increase in fluoroquinolone resistance, Clostridium difficile associated diarrhea, or in methicillin resistant Staphylococcus aureus infections were noted. Our single institution experience with fluoroquinolone prophylaxis for allogeneic hematopoietic stem cell transplant patients supports continuation of this practice. Expansion to autologous hematopoietic stem cell transplant patients may be appropriate based on guideline recommendations and our institution-specific experience with fluoroquinolone prophylaxis.

Chronic Kidney Disease and Risk of Death from Infection

Background: Infection, bacteremia and sepsis are major sources of morbidity and mortality in patients with end-stage renal disease. This study sought to determine the association between predialysis chronic kidney disease (CKD) and infection-related mortality. Methods: We analyzed participants in the Third National Health and Nutrition Examination Survey (NHANES III). The study included adults ≧45- years-old without end-stage renal disease. Estimated glomerular filtration rate (eGFR) was categorized as ≧60, 45–59.9 and <45 ml/min per 1.73 m², and urinary albumin-to-creatinine ratio (ACR) as <30, 30–299.9 and ≧300 mg/g. The study identified infection-related mortality, including septicemia, respiratory, abdominal and gastrointestinal, cardiac, kidney and genitourinary, neurologic, and other infections over a median of 13 years using the National Death Index. Results: Of 7,400 participants included in the study, 206 died from infections. Compared to individuals with eGFR ≧60 ml/min per 1.73 m², infection-related mortality was higher for those with lower eGFR [adjusted HR = 1.36 (95% CI: 0.81, 2.30) and 2.36 (1.04, 5.38) for eGFR of 45–59.9 and <45 ml/min per 1.73 m², respectively; p trend = 0.06]. Compared to individuals with ACR <30 mg/g, infection-related mortality was higher for ACR levels of 30–299 and ≧300 mg/g [adjusted HR = 1.68 (95% CI: 0.97, 2.92) and 2.84 (0.92, 8.74), p trend = 0.02]. Conclusions: Reduced eGFR and albuminuria are associated with increased risk for infection-related mortality. Efforts are needed to reduce its incidence and mitigate the effects of infections among individuals with CKD.

Serum Albumin as a Predictor of Mortality in Peritoneal Dialysis: Comparisons With Hemodialysis

Serum albumin level predicts mortality in dialysis patients and is used to assess their health status and the quality of delivered care. Whether the threshold level of serum albumin at which mortality risk increases in peritoneal dialysis (PD) patients is the same as for hemodialysis (HD) patients has not been studied. Observational cohort study of dialysis patients undertaken to determine the survival-predictability of serum albumin level in PD patients and compare it with that in HD patients. 130,052 dialysis patients (PD, 12,171; HD, 117,851) who received treatment in any of the 580 dialysis units owned by DaVita Inc between July 1, 2001, through June 30, 2006, followed up through June 30, 2007. Baseline and time-averaged serum albumin level (assayed using bromcresol green) and change in serum albumin level over 6 months. All-cause, cardiovascular, and infection-related mortality. PD patients with baseline serum albumin level <3.0 g/dL had a more than 3-fold higher adjusted risk of all-cause and cardiovascular mortality and 3.4-fold higher risk of infection-related mortality (reference group: serum albumin, 4.00-4.19 g/dL). Adjusted all-cause mortality was significantly lower in PD patients with a ≥0.3-g/dL increase in serum albumin level over 6 months and significantly higher in those for whom it decreased by ≥0.2 g/dL (reference group: serum albumin change, +0.1 to -0.1 g/dL). A significant increase in death risk was evident for HD patients with serum albumin level <4.0 g/dL, but at <3.8 g/dL for PD patients. For each albumin category, overall death risk for PD patients was lower than for HD patients (reference group: HD patients with serum albumin of 4.00-4.19 g/dL). Study can identify associations only without attribution of causality and residual confounding cannot be excluded. Serum albumin predicts all-cause, cardiovascular, and infection-related mortality in both PD and HD patients. However, the threshold at which risk of death increases varies by dialysis modality, and this difference should be considered by agencies or organizations that set quality standards.

Unrelated Umbilical Cord Blood Transplantation and Immune Reconstitution

This review highlights the unique features of immune reconstitution following unrelated cord blood transplantation (UCBT) that lead to heightened risk of infection-related mortality in the early post-UCBT period. There is no evidence that innate immunity is uniquely compromised after UCBT, but the development of antigen-specific cellular immunity is affected by numerical and qualitative deficits, primarily within the first 100 days. Nevertheless, beyond the first few months after UCBT there is no evidence for reduced graft-versus-leukemia (GVL) or anti-viral immunity compared to other hematopoietic cell therapy (HCT) modalities. Novel cellular therapies that are about to enter the clinical setting in the form of natural killer (NK) cell and T-cell therapies in the form of donor lymphocyte infusion (DLI) are also discussed.

The Significance of Hepatic Iron Overload in Allogenic Stem Cell Transplant Recipients.

Abstract 4313 IntroductionIron overload has increasingly been recognized as a cause of morbidity and mortality among allogenic hematopoietic stem cell transplant (HSCT) recipients. Estimation of liver iron is considered the gold standard method that reflects the overall body iron burden. AimWe attempted to correlate the severity of liver iron overload to various clinical parameters in allogenic HSCT recipients. MethodsWe studied 49 adult allogenic HSCT recipients who had a minimum of one liver biopsy performed after transplant. All patients had been diagnosed, transplanted and followed up in our institution since 1998. Biopsies were performed due to abnormal liver function tests under the initial clinical suspicion of GVHD with a mean of 185 days (range: 23-844 days) post-transplant. Sections from each biopsy were stained with hematoxylin and eosin, Masson trichome and Perl's iron stains. We used the histological semiquantitative grading of liver iron (grade 0-4), evidence of GVHD (score 0-3) and fibrosis (stage 0-4). Iron overload was defined as a score of 2 and above (correlating with hepatic iron concentration >1.4 mg/g dry weight). Various clinical parameters were also assessed including age, sex, underlying malignancy, number of transfusions, source and type of stem cell transplant, liver function tests, clinical grading of GVHD, significant bacteremia, other infections, survival and cause of death. ResultsIn this cohort, 28 of 49 patients had iron overload. The overall prevalence of iron overload was 57% (95% confidence interval, 42%-71%). Iron overload in 7 of the 49 patients (14%) was the only histological explanation of liver dysfunction. The degree of iron overload was directly correlated to the number of transfusions (r=0.69, p<0.001), serum ferritin (r=0.55, p=0.004) and the development of significant bacteremia (r=0.33, p=0.019). The correlation to the histologic liver-GVHD grade was close to statistical significance (p=0.062). 37 of the 49 patients (76%) died after HSCT at a mean of 677.8 days (range: 52-3821 days) post-transplant. The overall mortality did not correlate statistically to the degree of iron overload. The mortality was higher in patients with high serum bilirubin (direct or total) and increasing clinical degree of acute GVHD. Sixteen patients died secondary to infection (bacterial=15, fungal=1). However, there was no significant evidence of increased risk of infection-related mortality with iron overload (Hazard Ratio = 1.16, 95% CI, 0.76-1.77, p = 0.496). ConclusionIron overload is a common adverse effect of allogenic HSCT (57% prevalence). Iron overload occurred in some of our patients after as few as 10 red blood cell units. In this cohort, iron overload statistically correlated to the number of transfusions, development of significant bacteremia and clinical acute GVHD. We did not find a statistically significant association with mortality, likely due to our small sample size and complex clinical picture. Iron overload was the only histological explanation of abnormal liver functions in 14% of our patients. More studies are needed to determine the impact of iron overload in long-term morbidity and mortality in allogenic transplant patients. Disclosures:No relevant conflicts of interest to declare.

Long‐term survival of intensive care and hospital patient cohorts compared with the general Australian population: a relative survival approach

Long-term post-hospital survival of intensive care cohorts has been poorly characterized. The relative survival of septic and non-septic intensive care and general hospital patient cohorts, compared with the Australian population, was determined. A retrospective cohort study in a tertiary-level adult intensive care. Index intensive care admissions, July 1993 to June 1999, with sepsis and surviving hospital, constituted the intensive care sepsis cohort; residual patients, the intensive care non-sepsis cohort. Hospital cohorts, infected and non-infected, and Charlson Comorbidity Score (CCS) were obtained electronically, from ICD-9 codes. Follow-up was until death, or for a minimum of 4.2 years, to a maximum of 9.6 years. Time-to-death was sourced from the State registry. Relative survival was determined using the Esteve method and excess hazard modelled by covariate adjusted generalized linear models. The ICU sepsis (n = 224) and non-sepsis (n = 1798) cohorts were of mean (standard deviation, SD) age of 63.2 (15.6) and 59.8 (18.9) years; with co-morbidity score 1.2 (1.3) and 0.5 (0.9) respectively. Hospitalized infected (n = 8455) and non-infected (n = 51,152) cohorts were of age 56.5 (22.2) and 52.2 (20.9) years; co-morbidity score 0.4 (0.9) and 0.3 (0.9) respectively. Relative survival of all cohorts was less than the Australian population; for the two intensive care cohorts, progressive relative survival decline suggested a perpetuating excess mortality. Both age and CCS increments were associated with progressive increases in excess hazard. There was a reduced hazard for intensive care sepsis versus non-sepsis cohorts; 0.42 [95% confidence interval (CI): 0.25-0.71, P = 0.001] and surgical versus medical patients, 0.64 (95% CI: 0.50-0.84, P = 0.001); and an excess hazard for men, 1.38 (95% CI: 1.08-1.74, P = 0.009). Adverse long-term survival of intensive care and hospital patients was demonstrated. For hospital patients there was additional infection-related mortality risk, not evident for ICU patients after case mix control.

High alkaline phosphatase levels in hemodialysis patients are associated with higher risk of hospitalization and death

We evaluated risks associated with elevated alkaline phosphatase in hemodialysis patients using longitudinal data from the Dialysis Outcomes and Practice Patterns Study, a prospective observational study of hemodialysis patients in 12 countries. Alkaline phosphatase levels were normalized by the upper limit of the laboratory-reported reference range. Cause-specific hospitalization and mortality risks were evaluated using Cox proportional hazards models, stratified by region and adjusted for phosphorus, calcium, albumin, parathyroid hormone, case mix, and numerous comorbidities. The odds of high normalized alkaline phosphatase were increased twofold in the United States in comparison to Japan. Elevations of normalized alkaline phosphatase were significantly associated with several comorbid conditions, increased fractures, parathyroidectomy, risk of hospitalization due to major adverse cardiac events, higher all-cause cardiovascular, and infection-related mortality risk. Our results also show that elevated serum normalized alkaline phosphatase was associated with higher risks of hospitalization and death in hemodialysis patients, independent of calcium, phosphorus, and parathyroid hormone levels.

The effect of statin therapy on infection-related mortality in patients with atherosclerotic diseases*

Statins have pleiotropic effects that are independent of their lipid-lowering ability. We have previously shown that prior statin therapy is associated with a decreased risk of severe sepsis in patients admitted with acute bacterial infection. The aim of this study was to determine whether statin therapy is associated with a decreased risk of infection-related mortality. A prospective, observational, population-based study. Tertiary university medical center. Using a computerized database, 11,490 patients with atherosclerotic diseases were identified and followed for up to 3 yrs. Two groups of patients were compared: those receiving statins in the final month before follow-up termination and those who were not. None. The primary outcome was infection-related mortality. Of the 11,362 patients included in the final analysis, 5,698 (50.1%) belonged to the statin group. Median follow-up was 19.8 months (interquartile range, 14.3-33.3). The risk of infection-related mortality was significantly lower in the statin compared with the no-statin group (0.9% vs. 4.1%), reflecting a relative risk of 0.22 (95% confidence interval, 0.17-0.28). Stepwise Cox proportional hazard survival analysis including a propensity score for receiving statins revealed that the protective effect of statins adjusted for all known potential confounders remained highly significant (hazard ratio, 0.37; 95% confidence interval, 0.27-0.52). Therapy with statins may be associated with a reduced risk of infection-related mortality. This protective effect is independent of all known comorbidities and dissipates when the medication is discontinued. If this finding is supported by prospective controlled trials, statins may play an important role in the primary prevention of infection-related mortality.

Increased Infection-Related Mortality for Children with Down Syndrome (DS) in Contemporary Children's Oncology Group (COG) Acute Lymphoblastic Leukemia (ALL) Clinical Trials.

In prior COG ALL trials, children with DS have had increased treatment-related morbidity without major increases in mortality, when compared to children without DS. Recently, COG opened phase III, randomized trials for the treatment of children with high risk (AALL0232) and standard risk (AALL0331) precursor-B ALL. COG AALL0232 uses an augmented BFM backbone regimen with randomized comparisons of 28 days of prednisone (PDN) 60 mg/m2 vs. 14 days of dexamethasone (DXM) 10 mg/m2 during induction (IND), and high dose methotrexate with leucovorin rescue (HD MTX) vs. escalating IV MTX without rescue plus Peg asparaginase using the Capizzi schedule (CMTX) during a two-month interim maintenance (IM) phase of therapy. Children with DS participated in the induction steroid randomization, but were non-randomly assigned to CMTX arm due to known increased sensitivity to HD MTX. During the first 22 months of accrual to AALL0232, there were 4 deaths among 20 patients with DS, 3 of these 4 deaths occurred in pts receiving DXM in IND yielding an IND mortalaity rate of 15%, which is significantly higher than the 4.3% rate in CCG 1961 (the prior high risk trial). COG AALL0331 utilizes a standard 3-drug IND consisting of DXM 6 mg/m2 for 28 days, vincristine and PEG asparaginase. Post-IND therapy includes a 2 × 2 randomization between intensified vs. standard consolidation, and escalating CMTX combined with augmented delayed intensification (DI) vs. standard IM and DI phases. On AALL0331, there were 6 deaths among 26 children with DS during the first 10 months of accrual. The deaths occurred in IND (3), intensified consolidation (1) and standard DI (2). The IND mortality rate for DS children on AALL0331 is 11.5% compared to 1.3% in CCG 1991 and 0% in CCG 1952 which used identical IND therapy. During DI, patients on CCG 1991 received DXM on days 1–7 and 15–21, whereas those on AALL0331 receive DXM on days 1–21; this difference could contribute to an increased risk of infection in the DS population during the DI phases of the latter trial. The majority of deaths have been due to overwhelming infection with cardiovascular collapse during times of neutropenia. Both COG AALL0232 and AALL0331 suspended enrollment to DS patients pending subsequent therapy changes and expanded supportive care guidelines. This experience emphasizes that children with DS carry a significant risk of infection-related mortality and mandates increased vigilance for early detection and treatment of symptoms suggestive of infection.

Acute Respiratory Viral Infections Aggravate Arterial Endothelial Dysfunction in Children With Type 1 Diabetes

Despite improvements in therapy for children with type 1 diabetes, the prevalence of cardiovascular morbidity in adulthood due to accelerated atherosclerosis remains significant (1). Similar to other cardiovascular risk factors, the diabetic state facilitates arterial endothelial injury, a primary event in the pathogenesis of atherosclerosis (2). Although several pediatric studies have reported an association of diabetes with arterial endothelial dysfunction (3,4), pathogenic animal studies have suggested that even though this disease predisposes to endothelial dysfunction and atherosclerosis, it might not be sufficient to cause them (5). Notably, type 1 diabetes increases the propensity for both chronic and acute infections in part by weakening the immune mechanisms (6). The risk is particularly increased for respiratory tract infections, but other infections have also been associated with diabetes (7). Furthermore, diabetic patients are at greater risk for infection-related mortality (8), and the excess risk appears to be linked to cardiovascular diseases (9). In the present study, we investigated whether viral respiratory tract infections in children with type 1 diabetes might impose an additional burden on the arterial endothelial function. A total of 26 children (aged 6–18 years, mean [±SD] age 14 ± 3 years) with type 1 diabetes (duration 6 ± 3 years) were recruited. Of these, 11 children had a clinically manifested upper respiratory tract infection (body temperature >38°C and flu-like symptoms) 6–8 weeks before the …

Reduced-intensity conditioning reduces the risk of severe infections after allogeneic peripheral blood stem cell transplantation.

We compared the occurrence of severe infections following 71 reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplants (PBSCT) and 123 standard myeloablative PBSCT (MINI and STAND groups, respectively) from HLA-identical siblings. The probability of 1-year infection-related mortality (IRM) was 19% in the STAND group and 10% in the MINI group (log-rank, P = 0.3). On multivariate analysis the only significant variable associated with a higher risk of IRM was the development of moderate-to-severe GVHD (P = 0.005). The probability of developing CMV infection was 39% in the STAND group and 21% in the MINI group (P = 0.03) (43% and 21%, respectively, in seropositive donor/recipient pairs, P = 0.01), and the probability of developing CMV disease was 9.5% and 1%, respectively (P = 0.05) (11% and 1%, respectively, in seropositive donor/recipient pairs, P = 0.03). Multivariate analysis of CMV infection identified four variables associated with a higher risk: CMV positive serostatus (P = 0.05), STAND transplant group (P = 0.02), the development of moderate-to-severe GVHD (P < 0.001) and a dose of CD34(+) cells infused below 6 x 10(6)/kg (P = 0.01). Invasive fungal infections and pneumonias of unknown origin did not differ between groups, and neither did other severe non-CMV viral infections and bacterial infections. Our results suggest that RIC allogeneic PBSCT may decrease the risk of dying from an opportunistic infection and reduces the occurrence of CMV infection and disease. Overall, the development of GVHD (acute or chronic) is an important risk factor for these complications. Other infections continue to pose a significant threat to recipients of RIC allografts, stressing that prophylactic and supportive measures are an important aspect in their care.