Impact of anti-thymocyte globulin dose for graft-versus-host disease prophylaxis in allogeneic hematopoietic cell transplantation from matched unrelated donors: a multicenter experience.

Despite the widespread use of rabbit anti-thymocyte globulin (ATG) to prevent acute and chronic graft-versus-host disease (aGVHD, cGVHD) after allogeneic hematopoietic cell transplantation (allo-HCT), convincing evidence about an optimal dose is lacking. We retrospectively evaluated the clinical impact of two different ATG doses (5 vs 6-7.5 mg/kg) in 395 adult patients undergoing HSCT from matched unrelated donors (MUD) at 3 Italian centers. Cumulative incidence of aGVHD and moderate-severe cGVHD did not differ in the 2 groups. We observed a trend toward prolonged overall survival (OS) and disease-free survival (DFS) with lower ATG dose (5-year OS and DFS 56.6% vs. 46.3%, p=0.052, and 46.8% vs. 38.6%, p=0.051, respectively) and no differences in relapse incidence and non-relapse mortality. However, a significantly increased infection-related mortality (IRM) was observed in patients who received a higher ATG dose (16.7% vs. 8.8% in the lower ATG group, p=0.019). Besides, graft and relapse-free survival (GRFS) was superior in the lower ATG group (5-year GRFS 43.1% vs. 32.4%, p=0.014). The negative impact of higher ATG dose on IRM and GRFS was confirmed by multivariate analysis. Our results suggest that ATG doses higher than 5 mg/kg are not required for MUD allo-HCT and seem associated with worse outcomes.

Iron metabolism imbalance at the time of listing increases overall and infectious mortality after liver transplantation.

BACKGROUND: Liver transplantation (LT) is the best treatment for patients with liver cancer or end stage cirrhosis, but it is still associated with a significant mortality. Therefore identifying factors associated with mortality could help improve patient management. The impact of iron metabolism, which could be a relevant therapeutic target, yield discrepant results in this setting. Previous studies suggest that increased serum ferritin is associated with higher mortality. Surprisingly iron deficiency which is a well described risk factor in critically ill patients has not been considered. AIM: To assess the impact of pre-transplant iron metabolism parameters on post-transplant survival. METHODS: From 2001 to 2011, 553 patients who underwent LT with iron metabolism parameters available at LT evaluation were included. Data were prospectively recorded at the time of evaluation and at the time of LT regarding donor and recipient. Serum ferritin (SF) and transferrin saturation (TS) were studied as continuous and categorical variable. Cox regression analysis was used to determine mortality risks factors. Follow-up data were obtained from the local and national database regarding causes of death. RESULTS: At the end of a 95-mo median follow-up, 196 patients were dead, 38 of them because of infections. In multivariate analysis, overall mortality was significantly associated with TS > 75% [HR: 1.73 (1.14; 2.63)], SF < 100 µg/L [HR: 1.62 (1.12; 2.35)], hepatocellular carcinoma [HR: 1.58 (1.15; 2.26)], estimated glomerular filtration rate (CKD EPI Cystatin C) [HR: 0.99 (0.98; 0.99)], and packed red blood cell transfusion [HR: 1.05 (1.03; 1.08)]. Kaplan Meier curves show that patients with low SF (< 100 µg/L) or high SF (> 400 µg/L) have lower survival rates at 36 mo than patients with normal SF (P = 0.008 and P = 0.016 respectively). Patients with TS higher than 75% had higher mortality at 12 mo (91.4% ± 1.4% vs 84.6% ± 3.1%, P = 0.039). TS > 75% was significantly associated with infection related death [HR: 3.06 (1.13; 8.23)]. CONCLUSION: Our results show that iron metabolism imbalance (either deficiency or overload) is associated with post-transplant overall and infectious mortality. Impact of iron supplementation or depletion should be assessed in prospective study.

Infectious complications and mortality associated with the use of IV iron therapy: a systematic review and meta-analysis.

BACKGROUND: Parental iron is used to optimize hemoglobin and enhance erythropoiesis in end-stage renal disease along with erythropoietin-stimulating agents. Safety of iron has been debated extensively and there is no definite evidence whether parenteral iron increases the risk of infections and mortality. We performed this meta-analysis to evaluate the incidence of infectious complications, hospitalizations and mortality with use of parenteral iron. METHODS: Medical electronic databases [PubMed, EMBASE, Scopus, Web of Science, and cochrane central register for controlled clinical trials (CENTRAL)] were queried for studies that investigated the association between intravenous iron administration and infection in hemodialysis patients. 24 studies (8 Randomized control trials (RCTs) and 16 observational studies) were considered for qualitative and quantitative analysis. RESULTS: All-cause mortality Data from 6 RCTs show that high-dose IV iron conferred 17% less all-cause mortality compared to controls; however, this outcome was not statistically significant (OR = 0.83, CI [0.7, 1.01], p = 0.07). Nine observational studies were pooled under the random effects model due to significant heterogeneity (I2 = 83%, p < 0.001). The overall HR showed increased risk of all-cause mortality in the high-dose group but was statistically non-significant (HR = 1.1, CI [1, 1.22], p = 0.06). Infections Four RCTs with no heterogeneity among their data (I2 = 0%, p = 0.61). Under the fixed effect model, there was no difference in the infection rate between high-dose iron and control group (OR = 0.97, CI [0.82, 1.16], p = 0.77); eight observational studies with significant heterogeneity and utilizing random effects model. Summary HR showed increased yet non-significant risk of infection in the high-dose group (HR = 1.13, CI [0.99, 1.28], p = 0.07) Hospitalization 1 RCT and six observational studies provided data for the rate of all-cause hospitalization. There was marked heterogeneity among observational studies. RCT showed no significant difference between high-dose iron and controls in the rate of hospitalization (OR = 1.03, CI [0.87, 1.23], p = 0.71). Summary HR for observational data showed increased rate of hospitalization in the high-dose group; however, this effect was not statistically significant (HR = 1.11, CI [0.99, 1.24], p = 0.07). Cardiovascular events One RCT compared the rate of adverse cardiovascular events between high-dose and low-dose iron. No significant difference was observed between the two groups (22.3% vs 25.6%, p = 0.12). Six heterogeneous observational studies (I2 = 65%, p < 0.001) reported on the rate of cardiovascular events. No significant difference was observed between high-dose iron and controls (HR = 1.18, CI [0.89, 1.57], p = 0.24). CONCLUSION: High-dose parenteral iron does not seem to be associated with higher risk of infection, all-cause mortality, increased hospitalization or increased cardiovascular events on analysis of RCTs. Observational studies show increased risk for all-cause mortality, infections and hospitalizations that were not statistically significant and were associated with significant heterogeneity.

Impact of Transferrin Saturation on All-Cause Mortality in Patients on Maintenance Hemodialysis.

BACKGROUND: Transferrin saturation (TSAT) is an index that represents the iron-binding capacity of transferrin, which is the main transport protein for iron, and is widely used to evaluate iron status. OBJECTIVE: To evaluate the prognostic importance of TSAT in Japanese patients on maintenance hemodialysis (MHD). METHODS: A total of 398 patients on MHD were recruited and divided into 3 groups on the basis of their baseline TSAT levels (<20, 20-40, and >40%). RESULTS: There was no difference in the proportion of patients on erythropoiesis-stimulating agents or iron supplements between the 3 groups. During a mean follow-up period of 52.2 ± 1 6.3 months, 130 patients died of cardiovascular causes (n = 63, 15.8%) or infection (n = 47, 11.8%). Compared with the reference group (TSAT 20-40%), patients with a TSAT <20% had a significantly higher all-cause mortality rate (6.44 vs. 9.55 events per 100 patient-years, p = 0.0452). Kaplan-Meier analysis showed that all-cause mortality rate was significantly higher in patients with TSAT <20% than in the other 2 groups (p = 0.0353). CONCLUSIONS: Low TSAT was a significant independent risk factor for all-cause mortality in a cohort of Japanese patients on MHD. The findings of this study suggest that the adverse clinical outcomes in patients with low TSAT can be partly attributed to infection-related iron deficiency.

Infection and Malignancy Outweigh Cardiovascular Mortality in Kidney Transplant Recipients: Post Hoc Analysis of the FAVORIT Trial.

OBJECTIVE: Now that long-term survival after successful renal transplantation is no longer limited by excessive cardiovascular risk, the primary care physician should consider that infection and malignancy are leading noncardiovascular causes of death even in the recipient with diabetes. METHODS: We accessed the National Institutes of Health-sponsored Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) study population (4010 renal transplant recipients with elevated homocysteine levels) studied to determine whether folate and B12 supplementation would reduce cardiovascular end points. This trial had a null result. Patients were classified as being nondiabetic or having type 1 or type 2 diabetes. RESULTS: We report an excess (cardiovascular and noncardiovascular) 6-year mortality risk associated with the presence of diabetes mellitus. Two thirds of fatal events in our renal transplant recipients were centrally adjudicated as noncardiovascular. The incidence of noncardiovascular death was 70% higher in the diabetic patient cohort than in the nondiabetic cohort. CONCLUSIONS: These results demonstrate that infection (but not malignancy) risks are far higher in diabetic than nondiabetic immunosuppressed individuals (although noncardiovascular death rate in nondiabetic individuals also exceeded cardiovascular deaths) and may play a larger role in the excess mortality populations than previously thought. Given that follow-up in this study was 4 to 10 years after allograft surgery, there was a lesser degree of acute rejection requiring high-dose immunosuppression than in the initial postallograft years. This unique perspective allows transplant recipients to return to primary physicians when taking low doses of immunosuppressive agents and provides focus for follow-up care.

Long-Term Complications in Patients With Hypoparathyroidism Evaluated by Biochemical Findings: A Case-Control Study.

Hypoparathyroidism (HypoPT) is associated with an increased risk of various complications, but only few data are available on risk factors. Using a case-control design, we assessed associations between biochemical findings and risk of different complications within a subpopulation of our previously identified Danish patients. We retrieved all biochemical data available on 431 (81% women) patients from the Central Region of Denmark, covering approximately 20% of the Danish population. Average age of patients was 41 years at time of diagnosis. Most patients (88%) had HypoPT due to surgery, mainly due to atoxic goiter and more than 95% were on treatment with calcium supplements and activated vitamin D. On average, time-weighted (tw) plasma levels of ionized calcium (Ca2+tw ) was 1.17 mmol/L (interquartile range [IQR], 1.14 to 1.21 mmol/L) and the calcium-phosphate (CaxPtw ) product was 2.80 mmol2 /L2 (IQR, 2.51 to 3.03 mmol2 /L2 ). High phosphatetw levels were associated with increased mortality and risk of any infections, including infections in the upper airways. A high CaxPtw product was associated with an increased mortality and risk of renal disease. Compared to levels around the lower part of the reference interval, lower Ca2+tw levels were associated with an increased risk of cardiovascular diseases. Mortality and risk of infections, cardiovascular diseases, and renal diseases increased with number of episodes of hypercalcemia and with increased disease duration. Treatment with a relatively high dose of active vitamin D was associated with a decreased mortality and risk of renal diseases and infections. In conclusion, risk of complications in HypoPT is closely associated with disturbances in calcium-phosphate homeostasis. © 2018 American Society for Bone and Mineral Research.

Azithromycin to prevent post-discharge morbidity and mortality in Kenyan children: a protocol for a randomised, double-blind, placebo-controlled trial (the Toto Bora trial).

INTRODUCTION: Child mortality due to infectious diseases remains unacceptably high in much of sub-Saharan Africa. Children who are hospitalised represent an accessible population at particularly high risk of death, both during and following hospitalisation. Hospital discharge may be a critical time point at which targeted use of antibiotics could reduce morbidity and mortality in high-risk children. METHODS AND ANALYSIS: In this randomised, double-blind, placebo-controlled trial (Toto Bora Trial), 1400 children aged 1-59 months discharged from hospitals in Western Kenya, in Kisii and Homa Bay, will be randomised to either a 5-day course of azithromycin or placebo to determine whether a short course of azithromycin reduces rates of rehospitalisation and/or death in the subsequent 6-month period. The primary analysis will be modified intention-to-treat and will compare the rates of rehospitalisation or death in children treated with azithromycin or placebo using Cox proportional hazard regression. The trial will also evaluate the effect of a short course of azithromycin on enteric and nasopharyngeal infections and cause-specific morbidities. We will also identify risk factors for postdischarge morbidity and mortality and subpopulations most likely to benefit from postdischarge antibiotic use. Antibiotic resistance in Escherichia coli and Streptococcus pneumoniae among enrolled children and their primary caregivers will also be assessed, and cost-effectiveness analyses will be performed to inform policy decisions. ETHICS AND DISSEMINATION: Study procedures were reviewed and approved by the institutional review boards of the Kenya Medical Research Institute, the University of Washington and the Kenyan Pharmacy and Poisons Board. The study is being externally monitored, and a data safety and monitoring committee has been assembled to monitor patient safety and to evaluate the efficacy of the intervention. The results of this trial will be published in peer-reviewed scientific journals and presented at relevant academic conferences and to key stakeholders. TRIAL REGISTRATION NUMBER: NCT02414399.

Granulocyte transfusion experience in pediatric neutropenic fever: Splitted product can be an alternative?

The granulocyte transfusion (GTX) has been used for a long time due to uncontrolled neutropenic fever with antimicrobial agents. In some cases, the product needs to be splitted for using in the next 12 hours. The aim of this study is to evaluate the efficacy of splitted product and clinical response to GTX. In this study, 15 patients with malignancy with 19 neutropenic fever, who had received 56 GTX, were included. Seventeen of 56 GTX were splitted and used in maximum 12 hours during infections which did not respond to antibacterial and antifungal therapy in 7 days. The patients were divided in to response groups as a complete, partial and progressive. The predictive factors for response group were evaluated. GTX were well tolerated in all patients. The median granulocyte dose was 1.26 (0.38-5.22) × 10(9)/kg. Total response rate was 89.5%. The infection-related mortality rate was 10.5%. Although the granulocyte doses are the same in both of the product groups, an hour later ANC increment of primer product was higher than that of splitted product (p = 0.001). Among the products, 48.7% of primer product and 17.6% of splitted product had induced ≥ 1000/mm(3) ANC increment after an hour (p = 0.039). Granulocyte transfusion is safe and effective in controlling the febrile neutropenia attack. GTX should be applied in a short time to provide effective ANC increment. For now, main granulocyte product instead of splitted product should be preferred in case of uncontrolled neutropenic fever with antibacterial/antifungal agents.

Low Serum Potassium Levels Increase the Infectious-Caused Mortality in Peritoneal Dialysis Patients: A Propensity-Matched Score Study.

BACKGROUND AND OBJECTIVES: Hypokalemia has been consistently associated with high mortality rate in peritoneal dialysis. However, studies investigating if hypokalemia is acting as a surrogate marker of comorbidities or has a direct effect in the risk for mortality have not been studied. Thus, the aim of this study was to analyze the effect of hypokalemia on overall and cause-specific mortality. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: This is an analysis of BRAZPD II, a nationwide prospective cohort study. All patients on PD for longer than 90 days with measured serum potassium levels were used to verify the association of hypokalemia with overall and cause-specific mortality using a propensity match score to reduce selection bias. In addition, competing risks were also taken into account for the analysis of cause-specific mortality. RESULTS: There was a U-shaped relationship between time-averaged serum potassium and all-cause mortality of PD patients. Cardiovascular disease was the main cause of death in the normokalemic group with 133 events (41.8%) followed by PD-non related infections, n=105 (33.0%). Hypokalemia was associated with a 49% increased risk for CV mortality after adjustments for covariates and the presence of competing risks (SHR 1.49; CI95% 1.01-2.21). In contrast, in the group of patients with K <3.5 mEq/L, PD-non related infections were the main cause of death with 43 events (44.3%) followed by cardiovascular disease (n=36; 37.1%). For PD-non related infections the SHR was 2.19 (CI95% 1.52-3.14) while for peritonitis was SHR 1.09 (CI95% 0.47-2.49). CONCLUSIONS: Hypokalemia had a significant impact on overall, cardiovascular and infectious mortality even after adjustments for competing risks. The causative nature of this association suggested by our study raises the need for intervention studies looking at the effect of potassium supplementation on clinical outcomes of PD patients.

Dysregulated iron metabolism in patients on hemodialysis.

The two main causes of death in patients on maintenance hemodialysis (MHD) are cardiovascular disease and infection. In the current report, we discuss the association of the iron-catalyzed Fenton reaction and iron sequestration with complications in MHD patients. In particular, we have studied the deregulation of several iron transport systems of polymorphonuclear leukocytes (PMNLs) and the effects of TNF-α on human umbilical vein endothelial cells or PMNLs obtained from MHD patients and controls, and the following results were obtained. (1) Iron was sequestered in MHD-PMNLs, in which the protein governing iron transport was dysregulated. (2) TNF-α accelerated iron accumulation and oxidative stress in human umbilical vein endothelial cells in a manner similar to that in MHD-PMNLs. (3) An endosomal iron transport protein, or natural resistance-associated macrophage protein 1, was decreased in PMNLs from MHD patients, and TNF-α caused a decline in this protein's expression in control PMNLs. (4) The mitochondrial iron chaperone protein frataxin was decreased in MHD-PMNLs, which was linked to the acceleration of oxidative stress and hypercytokinemia. (5) The index of arterial stiffness was aggravated in MHD patients and was associated with serum hepcidin and TNF-α levels, which could inhibit iron exit from cells. With regard to bacterial infections, iron availability to these intracellular pathogens is critical for their growth. In particular, iron accumulation in cells and endosomes may accelerate the spread of infection. Cardiovascular disease has been shown to be linked to oxidative stress caused by iron sequestration in vascular cells and macrophages as well as by the alteration of iron metabolism in mitochondria, and the observed increase in hepcidin and TNF-α may accelerate these crucial steps of oxidative stress in vascular disease. Thus, because surplus iron in the body may escalate the dysregulation of iron metabolism, as observed in MHD patients, iron supplementation for renal anemia treatment should be prudent.

Nutrition and dietary intake and their association with mortality and hospitalisation in adults with chronic kidney disease treated with haemodialysis: protocol for DIET-HD, a prospective multinational cohort study.

INTRODUCTION: Adults with end-stage kidney disease (ESKD) treated with haemodialysis experience mortality of between 15% and 20% each year. Effective interventions that improve health outcomes for long-term dialysis patients remain unproven. Novel and testable determinants of health in dialysis are needed. Nutrition and dietary patterns are potential factors influencing health in other health settings that warrant exploration in multinational studies in men and women treated with dialysis. We report the protocol of the "DIETary intake, death and hospitalisation in adults with end-stage kidney disease treated with HaemoDialysis (DIET-HD) study," a multinational prospective cohort study. DIET-HD will describe associations of nutrition and dietary patterns with major health outcomes for adults treated with dialysis in several countries. METHODS AND ANALYSIS: DIET-HD will recruit approximately 10,000 adults who have ESKD treated by clinics administered by a single dialysis provider in Argentina, France, Germany, Hungary, Italy, Poland, Portugal, Romania, Spain, Sweden and Turkey. Recruitment will take place between March 2014 and June 2015. The study has currently recruited 8000 participants who have completed baseline data. Nutritional intake and dietary patterns will be measured using the Global Allergy and Asthma European Network (GA(2)LEN) food frequency questionnaire. The primary dietary exposures will be n-3 and n-6 polyunsaturated fatty acid consumption. The primary outcome will be cardiovascular mortality and secondary outcomes will be all-cause mortality, infection-related mortality and hospitalisation. ETHICS AND DISSEMINATION: The study is approved by the relevant Ethics Committees in participating countries. All participants will provide written informed consent and be free to withdraw their data at any time. The findings of the study will be disseminated through peer-reviewed journals, conference presentations and to participants via regular newsletters. We expect that the DIET-HD study will inform large pragmatic trials of nutrition or dietary interventions in the setting of advanced kidney disease.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Infección sistémica por citomegalovirus: influencia del tratamiento con foscarnet en los niveles plasmáticos de calcio y magnesio / Systemic cytomegalovirus infection: Changes in serum calcium and magnesium levels with foscarnet treatment

La infección por citomegalovirus es frecuente en pacientes trasplantados cardiacos. Foscarnet se utiliza, con evidencia limitada, como tratamiento de segunda línea tras el fracaso de ganciclovir en estos pacientes. Presentamos un caso de alteraciones electrolíticas por foscarnet administrado para el tratamiento de infección por citomegalovirus en un paciente pediátrico trasplantado cardiaco. La infección se resolvió tras 6 semanas de tratamiento, apareciendo niveles de calcio iónico bajos durante la infusión del fármaco e hipomagnesemia mantenida tratada con suplementos, que revirtieron al retirar el fármaco

Cytomegalovirus infection is common in cardiac transplant patients. Foscarnet is used, with limited evidence, as second-line treatment after ganciclovir failure in these patients. We describe the case of a paediatric cardiac transplant patient who developed electrolyte disturbances during foscarnet treatment for cytomegalovirus infection. The infection resolved after 6 weeks of treatment. Low ionized calcium and magnesium levels were observed during the drug infusion, which were treated with supplements. The serum levels reverted to normal after drug withdrawal

Infection risk with bolus versus maintenance iron supplementation in hemodialysis patients.

Intravenous iron may promote bacterial growth and impair host defense, but the risk of infection associated with iron supplementation is not well defined. We conducted a retrospective cohort study of hemodialysis patients to compare the safety of bolus dosing, which provides a large amount of iron over a short period of time on an as-needed basis, with maintenance dosing, which provides smaller amounts of iron on a regular schedule to maintain iron repletion. Using clinical data from 117,050 patients of a large US dialysis provider merged with data from Medicare's ESRD program, we estimated the effects of iron dosing patterns during repeated 1-month exposure periods on risks of mortality and infection-related hospitalizations during the subsequent 3 months. Of 776,203 exposure/follow-up pairs, 13% involved bolus dosing, 49% involved maintenance dosing, and 38% did not include exposure to iron. Multivariable additive risk models found that patients receiving bolus versus maintenance iron were at increased risk of infection-related hospitalization (risk difference [RD], 25 additional events/1000 patient-years; 95% confidence interval [CI], 16 to 33) during follow-up. Risks were largest among patients with a catheter (RD, 73 events/1000 patient-years; 95% CI, 48 to 99) and a recent infection (RD, 57 events/1000 patient-years; 95% CI, 19 to 99). We also observed an association between bolus dosing and infection-related mortality. Compared with no iron, maintenance dosing did not associate with increased risks for adverse outcomes. These results suggest that maintenance iron supplementation may result in fewer infections than bolus dosing, particularly among patients with a catheter.

Pre- and perioperative factors affecting infection after living donor liver transplantation.

OBJECTIVE: Infectious complications, including sepsis, that often occur after liver transplantation (LT) comprise the most frequent causes of in-hospital death. This study investigated the predictors of post-transplantation infectious complications to establish a strategy with which to improve short-term outcomes after LT. METHODS: We used univariate and multivariate analyses to assess pre- and perioperative risk factors for post-transplantation infectious complications in 100 consecutive patients who underwent living donor LT from February 2008 through February 2010 at our institute. RESULTS: Multivariate analysis showed that low preoperative body cell mass and the absence of preoperative supplementation with branched-chain amino acids were of prognostic significance for post-transplantation sepsis. In addition, Child-Pugh classification C and massive operative blood loss were independent risk factors for post-transplantation bacteremia, and preoperative low body cell mass was an independent risk factor for in-hospital death from infection. CONCLUSION: Pretransplantation nutritional intervention and decreases in operative blood loss would help prevent post-transplantation infectious complications from developing during living donor LT. Branched-chain amino acid supplementation before LT affects the occurrence of infectious complications.

Vitamin D deficiency is associated with sudden cardiac death, combined cardiovascular events, and mortality in haemodialysis patients.

AIMS: Dialysis patients experience an excess mortality, predominantly of sudden cardiac death (SCD). Accumulating evidence suggests a role of vitamin D for myocardial and overall health. This study investigated the impact of vitamin D status on cardiovascular outcomes and fatal infections in haemodialysis patients. METHODS AND RESULTS: 25-hydroxyvitamin D [25(OH)D] was measured in 1108 diabetic haemodialysis patients who participated in the German Diabetes and Dialysis Study and were followed up for a median of 4 years. By Cox regression analyses, we determined hazard ratios (HR) for pre-specified, adjudicated endpoints according to baseline 25(OH)D levels: SCD (n = 146), myocardial infarction (MI, n = 174), stroke (n = 89), cardiovascular events (CVE, n = 414), death due to heart failure (n = 37), fatal infection (n = 111), and all-cause mortality (n = 545). Patients had a mean age of 66 ± 8 years (54% male) and median 25(OH)D of 39 nmol/L (interquartile range: 28-55). Patients with severe vitamin D deficiency [25(OH)D of ≤ 25 nmol/L] had a 3-fold higher risk of SCD compared with those with sufficient 25(OH)D levels >75 nmol/L [HR: 2.99, 95% confidence interval (CI): 1.39-6.40]. Furthermore, CVE and all-cause mortality were strongly increased (HR: 1.78, 95% CI: 1.18-2.69, and HR: 1.74, 95% CI: 1.22-2.47, respectively), all persisting in multivariate models. There were borderline non-significant associations with stroke and fatal infection while MI and deaths due to heart failure were not meaningfully affected. CONCLUSION: Severe vitamin D deficiency was strongly associated with SCD, CVE, and mortality, and there were borderline associations with stroke and fatal infection. Whether vitamin D supplementation decreases adverse outcomes requires further evaluation.

Does vitamin A supplementation interact with routine vaccinations? An analysis of the Ghana Vitamin A Supplementation Trial.

BACKGROUND: The World Health Organization recommends vitamin A supplementation (VAS) at vaccination contacts after 6 mo of age to reduce mortality. However, it is unknown whether the effect of VAS is independent of vaccinations. One of the original VAS trials from Ghana had collected vaccination information. OBJECTIVE: We reanalyzed the data to explore the hypothesis that VAS reduces mortality in children who had bacille Calmette-Guérin or measles vaccine as their most recent vaccine but increased mortality when diphtheria-tetanus-pertussis vaccine (DTP) was the most recent vaccine. On the basis of previous studies, we expected the effects to be strongest in girls. DESIGN: At enrollment, children aged 6-90 mo were randomly assigned to receive VAS or placebo every 4 mo for 2 y. Vaccination status was assessed at enrollment and after 1 and 2 y by reviewing the children's health cards. Lack of a health card was presumed to mean that the child had not been vaccinated. RESULTS: VAS had a beneficial effect only in children with no record of vaccination at enrollment (n = 5066); the mortality rate ratio (MRR) was 0.64 (95% CI: 0.47, 0.88) compared with 0.95 (95% CI: 0.72, 1.26) in children with one or more vaccinations (n = 6656). Among vaccinated children, the effect of VAS differed between boys (MRR: 0.74; 95% CI: 0.51, 1.08) and girls (MRR: 1.18; 95% CI: 0.84, 1.67) (P = 0.046 for interaction). VAS had a negative effect in measles-vaccinated girls who were missing one or more doses of DTP at enrollment, a group who often received DTP during follow-up (MRR: 2.60; 95% CI: 1.41, 4.80). CONCLUSIONS: The effect of VAS differed by vaccination status. This is potentially problematic because VAS is provided at vaccination contacts.