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1.
Safety of Intravenous Iron in Dialysis: A Systematic Review and Meta-Analysis.
Hougen, I, Collister, D, Bourrier, M, Ferguson, T, Hochheim, L, Komenda, P, Rigatto, C, Tangri, N
Clinical journal of the American Society of Nephrology : CJASN. 2018;(3):457-467
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Abstract
BACKGROUND AND OBJECTIVES The safety of intravenous iron dosing in dialysis is uncertain. Higher-dose intravenous iron may be associated with a higher risk of infections, cardiovascular events, hospitalizations, and mortality. This systematic review aimed to determine the safety of higher-dose versus lower-dose intravenous iron, oral iron, or no iron supplementation in adult patients treated with dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We searched Medline, EMBASE, Cochrane library, and CINAHL from inception to January 6, 2017 for randomized, controlled trials and observational studies comparing higher-dose intravenous iron with lower-dose intravenous iron, oral iron, or no iron in patients treated with dialysis that had all-cause mortality, infection, cardiovascular events, or hospitalizations as outcomes. RESULTS Of the 2231 eligible studies, seven randomized, controlled trials and 15 observational studies met inclusion criteria. The randomized, controlled trials showed no association between higher-dose intravenous iron (>400 mg/mo for most studies) and mortality (six studies; n=970; pooled relative risk, 0.93; 95% confidence interval, 0.47 to 1.84; follow-up ranging from 35 days to 26 months) or infection (four studies; n=743; relative risk, 1.02; 95% confidence interval, 0.74 to 1.41). The observational studies showed no association between higher-dose intravenous iron (>200 mg/mo for most studies) and mortality (eight studies; n=241,408; hazard ratio, 1.09; 95% confidence interval, 0.98 to 1.21; follow-up ranging from 3 to 24 months), infection (eight studies; n=135,532; pooled hazard ratio, 1.13; 95% confidence interval, 0.99 to 1.28), cardiovascular events (seven studies; n=135,675; hazard ratio, 1.18; 95% confidence interval, 0.90 to 1.56), or hospitalizations (five studies; n=134,324; hazard ratio, 1.08; 95% confidence interval, 0.97 to 1.19). CONCLUSIONS Higher-dose intravenous iron does not seem to be associated with higher risk of mortality, infection, cardiovascular events, or hospitalizations in adult patients on dialysis. Strength of this finding is limited by small numbers of participants and events in the randomized, controlled trials and statistical heterogeneity in observational studies.
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Gut microbes as future therapeutics in treating inflammatory and infectious diseases: Lessons from recent findings.
Mukherjee, S, Joardar, N, Sengupta, S, Sinha Babu, SP
The Journal of nutritional biochemistry. 2018;:111-128
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Abstract
The human gut microbiota has been the interest of extensive research in recent years and our knowledge on using the potential capacity of these microbes are growing rapidly. Microorganisms colonized throughout the gastrointestinal tract of human are coevolved through symbiotic relationship and can influence physiology, metabolism, nutrition and immune functions of an individual. The gut microbes are directly involved in conferring protection against pathogen colonization by inducing direct killing, competing with nutrients and enhancing the response of the gut-associated immune repertoire. Damage in the microbiome (dysbiosis) is linked with several life-threatening outcomes viz. inflammatory bowel disease, cancer, obesity, allergy, and auto-immune disorders. Therefore, the manipulation of human gut microbiota came out as a potential choice for therapeutic intervention of the several human diseases. Herein, we review significant studies emphasizing the influence of the gut microbiota on the regulation of host responses in combating infectious and inflammatory diseases alongside describing the promises of gut microbes as future therapeutics.
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Syzygium Cordatum Hochst. ex Krauss: An Overview of Its Ethnobotany, Phytochemistry and Pharmacological Properties.
Maroyi, A
Molecules (Basel, Switzerland). 2018;(5)
Abstract
Syzygium cordatum is a valuable medicinal plant in the materia medica of east and southern Africa. The aim of this study was to review the botany, medicinal uses, phytochemistry and ethnopharmacological properties of S. cordatum. Relevant literature search was carried out using internet sources such as ACS, Web of Science, Wiley, SpringerLink, Scopus, Mendeley, Google Scholar, Pubmed, SciFinder, BioMed Central, Science Direct and Elsevier. Other literature sources were conference papers, book chapters, books, theses and websites. The leaves, roots, bark and fruits of S. cordatum are used as ethnomedicines against 24 human diseases such as gastro-intestinal disorders, burns, sores, wounds, colds, cough, respiratory complaints, sexually transmitted infections (STIs), tuberculosis, fever and malaria. Several phytochemical compounds including alkaloids, anthocyanidin, essential oils, flavonoids, leucoanthocyanidin, phenols, phytosterols, saponins, simple sugars, terpenoids and triterpenoid have been identified from S. cordatum. Pharmacological evaluations revealed that S. cordatum is characterized by several biological activities including antibacterial, antifungal, antidiarrheal, anti-sexually transmitted infections, antidiabetic, anticholinesterase, anti-inflammatory, antileishmanial, antioxidant, antiplasmodial and anti-proteus. These pharmacological findings lend credence to the traditional ethnomedicinal uses and ethnopharmacological importance of S. cordatum. Future research on the species should identify the biological compounds, their mode of action and physiological pathways and clinical relevance.
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Cdc42 - A tryst between host cholesterol metabolism and infection.
Sviridov, D, Mukhamedova, N
Small GTPases. 2018;(3):237-241
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Abstract
Emerging evidence points to an important connection between pathogenesis of intracellular infections and host cholesterol metabolism. In our study we demonstrated that human cytomegalovirus exploits host small GTPase Cdc42 to hijack cellular cholesterol efflux pathway. It appears that the virus uses host machinery to stimulate cholesterol efflux by modifying lipid rafts and altering properties of plasma membrane, but the altered pathway is controlled by the viral protein US28 instead of the host ATP binding cassette transporter A1. We speculate that virus-controlled remodeling of plasma membrane facilitates immune evasion, exocytosis of viral proteins and cell-to-cell transmission of human cytomegalovirus. These mechanisms may be not unique for the cytomegalovirus and subverting reverse cholesterol transport pathway may be a generic mechanism used by pathogens to alter properties of host plasma membrane adapting it for their purposes-to hide and disseminate.
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Infection and Malignancy Outweigh Cardiovascular Mortality in Kidney Transplant Recipients: Post Hoc Analysis of the FAVORIT Trial.
Weinrauch, LA, D'Elia, JA, Weir, MR, Bunnapradist, S, Finn, PV, Liu, J, Claggett, B, Monaco, AP
The American journal of medicine. 2018;(2):165-172
Abstract
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.
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Intrauterine infection, immune system and premature birth.
Helmo, FR, Alves, EAR, Moreira, RAA, Severino, VO, Rocha, LP, Monteiro, MLGDR, Reis, MAD, Etchebehere, RM, Machado, JR, Corrêa, RRM
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2018;(9):1227-1233
Abstract
Preterm birth accounts for nearly one million deaths among children under five years of age, and although its etiopathogenesis is not fully elucidated, ascending intrauterine infection and fetal inflammatory response seem to be the main triggers. The intense inflammatory response mediated by IL-1β, TNF-α, PAF, IFN-γ and IL-6, PGE2 and MMP-1 and MMP-9 causes fetal membrane damage and rupture, increased uterine contractions and biochemical and structural changes in the cervix. Furthermore, preterm neonates have deficient innate and adaptive immune responses characterized by reduced levels of IgG, opsonization and phagocytosis, as well as increased activation of Th1 cells in relation to Th2 cells. Therefore, this triad is favors the occurrence of neonatal complications, such as respiratory distress syndrome, necrotizing enterocolitis, retinopathy of prematurity and bronchopulmonary dysplasia. Due to serious maternal and child health complications of intrauterine infection, several studies have tried to identify biomarkers for the early diagnosis of this entity. This literature review aims to discuss the main scientific findings regarding the association between ascending intrauterine infection, immune system and preterm birth.
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Validation of two multiplex platforms to quantify circulating markers of inflammation and endothelial injury in severe infection.
Leligdowicz, A, Conroy, AL, Hawkes, M, Zhong, K, Lebovic, G, Matthay, MA, Kain, KC
PloS one. 2017;(4):e0175130
Abstract
Biomarkers can prognosticate outcome and enable risk-stratification. In severe infection, focusing on multiple markers reflecting pathophysiological mechanisms of organ injury could enhance management and pathway-directed therapeutics. Limited data exist on the performance of multiplex biomarker platforms. Our goal was to compare endothelial and immune activation biomarkers in severe pediatric infections using two multiplex platforms. Frozen plasma from 410 children presenting to the Jinja Regional Hospital in Uganda with suspected infection was used to measure biomarkers of endothelial (Angiopoietin-2, sFlt-1, sVCAM-1, sICAM-1) and immune (IL-6, IP-10, sTNFR-1, CHI3L1) activation. Two multiplex platforms (Luminex®, EllaTM) based on monoclonal antibody sandwich immunoassays using biotin-streptavidin conjugate chemistry were selected with reagents from R&D Systems. The two platforms differed in ease and time of completion, number of samples per assay, and dynamic concentration range. Intra-assay variability assessed using a coefficient of variation (CV%) was 2.2-3.4 for Luminex® and 1.2-2.9 for EllaTM. Correlations for biomarker concentrations within dynamic range of both platforms were best for IL-6 (ρ = 0.96, p<0.0001), IP-10 (ρ = 0.94, p<0.0001) and sFlt-1 (ρ = 0.94, p<0.0001). Agreement between concentrations obtained by both methods assessed by the Bland-Altman test varied, with best agreement for CHI3L1. Our data suggest that biomarkers of endothelial and immune activation can be readily measured with multiplex platforms. Luminex® and EllaTM produced reliable results with excellent CV% values. The EllaTM platform was more automated and completed in 75 minutes, potentially compatible with near-patient use. Trends in concentrations obtained by these methods were highly correlated, although absolute values varied, suggesting caution is required when comparing data from different multiplex platforms.
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Infections: A Possible Risk Factor for Type 2 Diabetes.
Chakraborty, S, Bhattacharyya, R, Banerjee, D
Advances in clinical chemistry. 2017;:227-251
Abstract
Diabetes mellitus is one of the biggest challenges to human health globally, with an estimated 95% of the global diabetic population having type 2 diabetes. Classical causes for type 2 diabetes, such as genetics and obesity, do not account for the high incidence of the disease. Recent data suggest that infections may precipitate insulin resistance via multiple mechanisms, such as the proinflammatory cytokine response, the acute-phase response, and the alteration of the nutrient status. Even pathogen products, such as lipopolysaccharide and peptidoglycans, can be diabetogenic. Therefore, we argue that infections that are known to contribute to insulin resistance should be considered as risk factors for type 2 diabetes.
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The Metabolic Response to Stress and Infection in Critically Ill Children: The Opportunity of an Individualized Approach.
De Cosmi, V, Milani, GP, Mazzocchi, A, D'Oria, V, Silano, M, Calderini, E, Agostoni, C
Nutrients. 2017;(9)
Abstract
The metabolic response to stress and infection is closely related to the corresponding requirements of energy and nutrients. On a general level, the response is driven by a complex endocrine network and related to the nature and severity of the insult. On an individual level, the effects of nutritional interventions are highly variable and a possible source of complications. This narrative review aims to discuss the metabolic changes in critically-ill children and the potential of developing personalized nutritional interventions. Through a literature search strategy, we have investigated the importance of blood glucose levels, the nutritional aspects of the different phases of acute stress response, and the reliability of the available tools to assess the energy expenditure. The dynamics of metabolism during stressful events reveals the difficult balance between risk of hypo- or hyperglycemia and under- or overfeeding. Within this context, individualized and accurate measurement of energy expenditure may help in defining the metabolic needs of patients. Given the variability of the metabolic response in critical conditions, randomized clinical studies in ill children are needed to evaluate the effect of individualized nutritional intervention on health outcomes.
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Survival Rates and Mortality Risk Factors of Thai Patients with Type 2 Diabetes Mellitus.
Krairittichai, U, Potisat, S
Journal of the Medical Association of Thailand = Chotmaihet thangphaet. 2017;:S8-15
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is a common public health problem due to both its micro- and macro-vascular chronic complications. Data on survival rates and mortality risk factors of T2DM in Thailand need to be investigated and updated. OBJECTIVE To assess the survival rate and mortality risk factors in T2DM patients. MATERIAL AND METHOD This study is a part of the Thai DMS Diabetes Complications project which is a prospective observational 4-year study of Thai T2DM patients. All patients were recruited from out-patient departments of seven public hospitals and received standard treatment from their doctors. Their clinical and laboratory status were evaluated annually over 4 years, with particular emphasis on diabetic nephropathy, retinopathy and neuropathy. Outcomes at the end of the four-year study were expressed as survival or death, and causes of mortality were identified. RESULTS 1,097 from 1,120 stable T2DM patients were enrolled. After 4 years of follow-up, 80 patients (7.3%) had died. Causes of death were: cardiovascular disease (20 cases, 25.0%); infection (20 cases, 25.0%); malignancy (10 cases, 12.5%); end-stage renal disease (4 cases, 5.0%); and other causes (26 cases, 32.5%). Survival rates at 1, 2, 3, and 4 years were 98.9, 97.5, 96.2 and 92.7% respectively. Hazard ratios (95% CI) of all-cause mortality were being over 60 years old 1.84 (1.15-2.94) and having diabetic nephropathy 1.75 (1.12-2.75). Survival rates from cardiovascular mortality at 1, 2, 3, and 4 years were 99.2, 98.4, 97.4 and 94.5% respectively. Hazard ratios (95% CI) of cardiovascular mortality were: female gender 1.75 (1.05-2.94); diabetic nephropathy 1.72 (1.03-2.88); and diabetic retinopathy 1.74 (1.02-2.94). CONCLUSION The survival rate of Thai patients with T2DM over the 4 years was 92.7%. Being over 60 years old and having diabetic nephropathy were associated with all-cause mortality. Female gender, diabetic nephropathy and diabetic retinopathy were associated with cardiovascular mortality.