Combining proteins with n-3 PUFAs (EPA + DHA) and their inflammation pro-resolution mediators for preservation of skeletal muscle mass.

The optimal feeding strategy for critically ill patients is still debated, but feeding must be adapted to individual patient needs. Critically ill patients are at risk of muscle catabolism, leading to loss of muscle mass and its consequent clinical impacts. Timing of introduction of feeding and protein targets have been explored in recent trials. These suggest that "moderate" protein provision (maximum 1.2 g/kg/day) is best during the initial stages of illness. Unresolved inflammation may be a key factor in driving muscle catabolism. The omega-3 (n-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are substrates for synthesis of mediators termed specialized pro-resolving mediators or SPMs that actively resolve inflammation. There is evidence from other settings that high-dose oral EPA + DHA increases muscle protein synthesis, decreases muscle protein breakdown, and maintains muscle mass. SPMs may be responsible for some of these effects, especially upon muscle protein breakdown. Given these findings, provision of EPA and DHA as part of medical nutritional therapy in critically ill patients at risk of loss of muscle mass seems to be a strategy to prevent the persistence of inflammation and the related anabolic resistance and muscle loss.

Guidance for assessment of the inflammation etiologic criterion for the GLIM diagnosis of malnutrition: A modified Delphi approach.

BACKGROUND: The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation, and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation. METHODS: A GLIM-constituted working group with 36 participants developed consensus-based guidance through a modified Delphi review. A multiround review and revision process served to develop seven guidance statements. RESULTS: The final round of review was highly favorable, with 99% overall "agree" or "strongly agree" responses. The presence of acute or chronic disease, infection, or injury that is usually associated with inflammatory activity may be used to fulfill the GLIM disease burden/inflammation criterion, without the need for laboratory confirmation. However, we recommend that recognition of underlying medical conditions commonly associated with inflammation be supported by C-reactive protein (CRP) measurements when the contribution of inflammatory components is uncertain. Interpretation of CRP requires that consideration be given to the method, reference values, and units (milligrams per deciliter or milligram per liter) for the clinical laboratory that is being used. CONCLUSION: Confirmation of inflammation should be guided by clinical judgment based on underlying diagnosis or condition, clinical signs, or CRP.

Guidance for assessment of the inflammation etiologic criterion for the GLIM diagnosis of malnutrition: A modified Delphi approach.

BACKGROUND & AIMS: The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation in support of the etiologic criterion for inflammation. METHODS: A GLIM-constituted working group with 36 participants developed consensus-based guidance through a modified-Delphi review. A multi-round review and revision process served to develop seven guidance statements. RESULTS: The final round of review was highly favorable with 99 % overall "agree" or "strongly agree" responses. The presence of acute or chronic disease, infection or injury that is usually associated with inflammatory activity may be used to fulfill the GLIM disease burden/inflammation criterion, without the need for laboratory confirmation. However, we recommend that recognition of underlying medical conditions commonly associated with inflammation be supported by C-reactive protein (CRP) measurements when the contribution of inflammatory components is uncertain. Interpretation of CRP requires that consideration be given to the method, reference values, and units (mg/dL or mg/L) for the clinical laboratory that is being used. CONCLUSION: Confirmation of inflammation should be guided by clinical judgement based upon underlying diagnosis or condition, clinical signs, or CRP.

The relationship between nutrient intake and executive function in adults with post-traumatic stress disorder.

BACKGROUND: Executive function (EF) deficits are common in adults with post-traumatic stress disorder (PTSD). Macro- and micronutrient intake are potential modifiable factors that may influence EF in PTSD. OBJECTIVES: To explore the relationship between the daily dietary intake of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs), vitamin C, vitamin E, vitamin D, vitamin B12 and folate, and EF in adults with PTSD. METHODS: This was a cross-sectional observational study of adults with PTSD who completed neurocognitive assessments (n = 201). Digit span backwards, spatial span backwards, Stroop test and the Ruff Figural Fluency Task were used to assess EF. FoodFinder nutrient intake based on 24-h dietary recalls was used to calculate average daily nutrient intake. Multivariable linear regression models were used to regress EF on the nutrient variables. RESULTS: Intake of vitamin E, ω-3 PUFAs, and ω-6 PUFAs were all positively associated with planning and set-shifting, with vitamin E (adjusted ß = 0.20, p = 0.004) and ω-6 (adjusted ß = 0.17, p = 0.01) remaining significant after adjustment for age; sex; education and body mass index. Vitamin D intake was negatively associated with interference (adjusted ß = -0.21, p = 0.01). Vitamin C, vitamin B12 and folate intake were not associated with EF. LIMITATIONS: 24-h dietary recall data is limited by recall bias. Circulating nutrient levels were not measured. CONCLUSIONS: Dietary intake of vitamins E, ω-3 and ω-6 may be important modifiable factors affecting EF in adults with PTSD. Randomised controlled trials are needed to investigate whether micro- and macronutrient interventions can improve EF and other outcomes in PTSD.

Associations of HIV and iron status with gut microbiota composition, gut inflammation and gut integrity in South African school-age children: a two-way factorial case-control study.

BACKGROUND: Human immunodeficiency virus (HIV) and iron deficiency (ID) affect many African children. Both HIV and iron status interact with gut microbiota composition and related biomarkers. The study's aim was to determine the associations of HIV and iron status with gut microbiota composition, gut inflammation and gut integrity in South African school-age children. METHODS: In this two-way factorial case-control study, 8- to 13-year-old children were enrolled into four groups based on their HIV and iron status: (1) With HIV (HIV+) and ID (n = 43), (2) HIV+ and iron-sufficient nonanaemic (n = 41), (3) without HIV (HIV-) and ID (n = 44) and (4) HIV- and iron-sufficient nonanaemic (n = 38). HIV+ children were virally suppressed (<50 HIV RNA copies/ml) on antiretroviral therapy (ART). Microbial composition of faecal samples (16S rRNA sequencing) and markers of gut inflammation (faecal calprotectin) and gut integrity (plasma intestinal fatty acid-binding protein [I-FABP]) were assessed. RESULTS: Faecal calprotectin was higher in ID versus iron-sufficient nonanaemic children (p = 0.007). I-FABP did not significantly differ by HIV or iron status. ART-treated HIV (redundancy analysis [RDA] R2 = 0.009, p = 0.029) and age (RDA R2 = 0.013 p = 0.004) explained the variance in the gut microbiota across the four groups. Probabilistic models showed that the relative abundance of the butyrate-producing genera Anaerostipes and Anaerotruncus was lower in ID versus iron-sufficient children. Fusicatenibacter was lower in HIV+ and in ID children versus their respective counterparts. The prevalence of the inflammation-associated genus Megamonas was 42% higher in children with both HIV and ID versus HIV- and iron-sufficient nonanaemic counterparts. CONCLUSIONS: In our sample of 8- to 13-year-old virally suppressed HIV+ and HIV- children with or without ID, ID was associated with increased gut inflammation and changes in the relative abundance of specific microbiota. Moreover, in HIV+ children, ID had a cumulative effect that further shifted the gut microbiota to an unfavourable composition.

The Effect of ß-Glucan Prebiotic on Kidney Function, Uremic Toxins and Gut Microbiome in Stage 3 to 5 Chronic Kidney Disease (CKD) Predialysis Participants: A Randomized Controlled Trial.

There is growing evidence that gut dysbiosis contributes to the progression of chronic kidney disease (CKD) owing to several mechanisms, including microbiota-derived uremic toxins, diet and immune-mediated factors. The aim of this study was to investigate the effect of a ß-glucan prebiotic on kidney function, uremic toxins and the gut microbiome in stage 3 to 5 CKD participants. Fifty-nine participants were randomized to either the ß-glucan prebiotic intervention group (n = 30) or the control group (n = 29). The primary outcomes were to assess kidney function (urea, creatinine and glomerular filtration rate), plasma levels of total and free levels of uremic toxins (p-cresyl sulfate (pCS), indoxyl-sulfate (IxS), p-cresyl glucuronide (pCG) and indoxyl 3-acetic acid (IAA) and gut microbiota using 16S rRNA sequencing at baseline, week 8 and week 14. The intervention group (age 40.6 ± 11.4 y) and the control group (age 41.3 ± 12.0 y) did not differ in age or any other socio-demographic variables at baseline. There were no significant changes in kidney function over 14 weeks. There was a significant reduction in uremic toxin levels at different time points, in free IxS at 8 weeks (p = 0.003) and 14 weeks (p < 0.001), free pCS (p = 0.006) at 14 weeks and total and free pCG (p < 0.001, p < 0.001, respectively) and at 14 weeks. There were no differences in relative abundances of genera between groups. Enterotyping revealed that the population consisted of only two of the four enterotypes: Bacteroides 2 and Prevotella. The redundancy analysis showed a few factors significantly affected the gut microbiome: these included triglyceride levels (p < 0.001), body mass index (p = 0.002), high- density lipoprotein (p < 0.001) and the prebiotic intervention (p = 0.002). The ß-glucan prebiotic significantly altered uremic toxin levels of intestinal origin and favorably affected the gut microbiome.

The effect of oral iron supplementation on the gut microbiota, gut inflammation, and iron status in iron-depleted South African school-age children with virally suppressed HIV and without HIV.

PURPOSE: Both HIV and oral iron interventions may alter gut microbiota composition and increase gut inflammation. We determined the effect of oral iron supplementation on gut microbiota composition, gut inflammation, and iron status in iron-depleted South Africa school-aged children living with HIV (HIV+) but virally suppressed on antiretroviral therapy and children without HIV (HIV-ve). METHODS: In this before-after intervention study with case-control comparisons, we provided 55 mg elemental iron from ferrous sulphate, once daily for 3 months, to 33 virally suppressed (< 50 HIV RNA copies/mL) HIV+ and 31 HIV-ve children. At baseline and endpoint, we assessed microbial composition of faecal samples (16S rRNA sequencing), and markers of gut inflammation (faecal calprotectin), anaemia (haemoglobin) and iron status (plasma ferritin, soluble transferrin receptor). This study was nested within a larger trial registered at clinicaltrials.gov as NCT03572010. RESULTS: HIV+ (11.3y SD ± 1.8, 46% male) and HIV-ve (11.1y SD ± 1.7, 52% male) groups did not significantly differ in age or sex ratio. Following iron supplementation, improvements were observed in haemoglobin (HIV+ : 118 to 124 g/L, P = 0.003; HIV-ve: 120 to 124 g/L, P = 0.003), plasma ferritin (HIV+ : 15 to 34 µg/L, P < 0.001; HIV-ve: 18 to 37 µg/L, P < 0.001), and soluble transferrin receptor (HIV+ : 7.1 to 5.9 mg/L, P < 0.001; HIV-ve: 6.6 to 5.7 mg/L, P < 0.001), with no significant change in the relative abundance of any genera, alpha diversity of the gut microbiota (HIV+ : P = 0.37; HIV-ve: P = 0.77), or faecal calprotectin (HIV+ : P = 0.42; HIV-ve: P = 0.80). CONCLUSION: Our findings suggest that oral iron supplementation can significantly improve haemoglobin and iron status without increasing pathogenic gut microbial taxa or gut inflammation in iron-depleted virally suppressed HIV+ and HIV-ve school-age children.

n-3 long-chain PUFA promote antibacterial and inflammation-resolving effects in Mycobacterium tuberculosis-infected C3HeB/FeJ mice, dependent on fatty acid status.

Non-resolving inflammation is characteristic of tuberculosis (TB). Given their inflammation-resolving properties, n-3 long-chain PUFA (n-3 LCPUFA) may support TB treatment. This research aimed to investigate the effects of n-3 LCPUFA on clinical and inflammatory outcomes of Mycobacterium tuberculosis-infected C3HeB/FeJ mice with either normal or low n-3 PUFA status before infection. Using a two-by-two design, uninfected mice were conditioned on either an n-3 PUFA-sufficient (n-3FAS) or -deficient (n-3FAD) diet for 6 weeks. One week post-infection, mice were randomised to either n-3 LCPUFA supplemented (n-3FAS/n-3+ and n-3FAD/n-3+) or continued on n-3FAS or n-3FAD diets for 3 weeks. Mice were euthanised and fatty acid status, lung bacterial load and pathology, cytokine, lipid mediator and immune cell phenotype analysed. n-3 LCPUFA supplementation in n-3FAS mice lowered lung bacterial loads (P = 0·003), T cells (P = 0·019), CD4+ T cells (P = 0·014) and interferon (IFN)-γ (P < 0·001) and promoted a pro-resolving lung lipid mediator profile. Compared with n-3FAS mice, the n-3FAD group had lower bacterial loads (P = 0·037), significantly higher immune cell recruitment and a more pro-inflammatory lipid mediator profile, however, significantly lower lung IFN-γ, IL-1α, IL-1ß and IL-17, and supplementation in the n-3FAD group provided no beneficial effect on lung bacterial load or inflammation. Our study provides the first evidence that n-3 LCPUFA supplementation has antibacterial and inflammation-resolving benefits in TB when provided 1 week after infection in the context of a sufficient n-3 PUFA status, whilst a low n-3 PUFA status may promote better bacterial control and lower lung inflammation not benefiting from n-3 LCPUFA supplementation.

Adjunct n-3 Long-Chain Polyunsaturated Fatty Acid Treatment in Tuberculosis Reduces Inflammation and Improves Anemia of Infection More in C3HeB/FeJ Mice With Low n-3 Fatty Acid Status Than Sufficient n-3 Fatty Acid Status.

Populations at risk for tuberculosis (TB) may have a low n-3 polyunsaturated fatty acid (PUFA) status. Our research previously showed that post-infection supplementation of n-3 long-chain PUFA (LCPUFA) in TB without TB medication was beneficial in n-3 PUFA sufficient but not in low-status C3HeB/FeJ mice. In this study, we investigated the effect of n-3 LCPUFA adjunct to TB medication in TB mice with a low compared to a sufficient n-3 PUFA status. Mice were conditioned on an n-3 PUFA-deficient (n-3FAD) or n-3 PUFA-sufficient (n-3FAS) diet for 6 weeks before TB infection. Post-infection at 2 weeks, both groups were switched to an n-3 LCPUFA [eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA)] supplemented diet and euthanized at 4- and 14- days post-treatment. Iron and anemia status, bacterial loads, lung pathology, lung cytokines/chemokines, and lung lipid mediators were measured. Following 14 days of treatment, hemoglobin (Hb) was higher in the n-3FAD than the untreated n-3FAS group (p = 0.022), whereas the n-3FAS (drug) treated control and n-3FAS groups were not. Pro-inflammatory lung cytokines; interleukin-6 (IL-6) (p = 0.011), IL-1α (p = 0.039), MCP1 (p = 0.003), MIP1- α (p = 0.043), and RANTES (p = 0.034); were lower, and the anti-inflammatory cytokine IL-4 (p = 0.002) and growth factor GMCSF (p = 0.007) were higher in the n-3FAD compared with the n-3FAS mice after 14 days. These results suggest that n-3 LCPUFA therapy in TB-infected mice, in combination with TB medication, may improve anemia of infection more in low n-3 fatty acid status than sufficient status mice. Furthermore, the low n-3 fatty acid status TB mice supplemented with n-3 LCPUFA showed comparatively lower cytokine-mediated inflammation despite presenting with lower pro-resolving lipid mediators.

Beneficial effect of long-chain n-3 polyunsaturated fatty acid supplementation on tuberculosis in mice.

Intakes of the omega-3 essential fatty acids (n-3 EFAs) are low in the general adult population, with high n-6/n-3 polyunsaturated fatty acid (PUFA) ratios and the accompanying suboptimal n-3 PUFA status. Eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) have antibacterial and inflammation-resolving effects in tuberculosis (TB). However, whether switching to a diet with optimum n-3 EFA intake after the infection has comparable benefits has not been investigated. We aimed to compare the effects of a diet with sufficient n-3 EFA content in an acceptable n-6/n-3 PUFA ratio for rodents ((n-3)eFAS group) with those on the same diet supplemented with EPA and DHA (EPA/DHA group) in Mycobacterium tuberculosis (Mtb)-infected C3HeB/FeJ mice with a low n-3 PUFA status. Mice were conditioned on an n-3 PUFA-deficient diet with a high n-6/n-3 PUFA ratio for 6 weeks before Mtb infection and randomized to either (n-3)eFAS or EPA/DHA diets 1 week post-infection for 3 weeks. At endpoint, EPA and DHA compositions were higher and arachidonic acid, osbond acid, and total n-6 LCPUFAs lower in all lipid pools measured in the EPA/DHA group (all P < 0.001). Percentage body weight gain was higher (P = 0.017) and lung bacterial load lower (P < 0.001) in the EPA/DHA group. Additionally, the EPA/DHA group had a more pro-resolving lung lipid mediator profile and lower lung in IL-1α and IL-1ß concentrations (P = 0.023, P = 0.049). Inverse correlations were found between the lung and peripheral blood mononuclear cell EPA and DHA and selected pro-inflammatory cytokines. These are the first findings that indicate that EPA/DHA supplementation provides benefits superior to a diet with sufficient n-3 EFAs concerning bacterial killing, weight gain and lung inflammation resolution in Mtb-infected mice with a low n-3 PUFA status. Therefore, EPA and DHA may be worth considering as adjunct TB treatment.

Longer-Term Omega-3 LCPUFA More Effective Adjunct Therapy for Tuberculosis Than Ibuprofen in a C3HeB/FeJ Tuberculosis Mouse Model.

Advancement in the understanding of inflammation regulation during tuberculosis (TB) treatment has led to novel therapeutic approaches being proposed. The use of immune mediators like anti-inflammatory and pro-resolving molecules for such, merits attention. Drug repurposing is a widely used strategy that seeks to identify new targets to treat or manage diseases. The widely explored nonsteroidal anti-inflammatory drug (NSAID) ibuprofen and a more recently explored pharmaconutrition therapy using omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs), have the potential to modulate the immune system and are thus considered potential repurposed drugs in this context. These approaches may be beneficial as supportive therapy to the already existing treatment regimen to improve clinical outcomes. Here, we applied adjunct ibuprofen and n-3 LCPUFA therapy, respectively, with standard anti-TB treatment, in a C3HeB/FeJ murine model of TB. Bacterial loads, lung pathology, lung cytokines/chemokines and lung lipid mediators were measured as outcomes. Lung bacterial load on day 14 post-treatment (PT) was lower in the n-3 LCPUFA, compared to the ibuprofen group (p = 0.039), but was higher in the ibuprofen group than the treated control group (p = 0.0315). Treated control and ibuprofen groups had more free alveolar space initially as compared to the n-3 LCPUFA group (4 days PT, p= 0.0114 and p= 0.002, respectively); however, significantly more alveolar space was present in the n-3 LCPUFA group as compared to the ibuprofen group by end of treatment (14 days PT, p = 0.035). Interleukin 6 (IL-6) was lower in the ibuprofen group as compared to the treated control, EPA/DHA and untreated control groups at 4 days PT (p = 0.019, p = 0.019 and p = 0.002, respectively). Importantly, pro-resolving EPA derived 9-HEPE, 11-HEPE, 12-HEPE and 18-HEPE lipid mediators (LMs) were significantly higher in the EPA/DHA group as compared to the ibuprofen and treated control groups. This suggests that n-3 LCPUFAs do improve pro-resolving and anti-inflammatory properties in TB, and it may be safe and effective to co-administer as adjunct therapy with standard TB treatment, particularly longer-term. Also, our results show host benefits upon short-term co-administration of ibuprofen, but not throughout the entire TB treatment course.

Examining Associations of HIV and Iron Status with Nutritional and Inflammatory Status, Anemia, and Dietary Intake in South African Schoolchildren.

The etiology of multifactorial morbidities such as undernutrition and anemia in children living with the human immunodeficiency virus (HIV) (HIV+) on antiretroviral therapy (ART) is poorly understood. Our objective was to examine associations of HIV and iron status with nutritional and inflammatory status, anemia, and dietary intake in school-aged South African children. Using a two-way factorial case-control design, we compared four groups of 8 to 13-year-old South African schoolchildren: (1) HIV+ and low iron stores (inflammation-unadjusted serum ferritin ≤ 40 µg/L), n = 43; (2) HIV+ and iron sufficient non-anemic (inflammation-unadjusted serum ferritin > 40 µg/L, hemoglobin ≥ 115 g/L), n = 41; (3) children without HIV (HIV-ve) and low iron stores, n = 45; and (4) HIV-ve and iron sufficient non-anemic, n = 45. We assessed height, weight, plasma ferritin (PF), soluble transferrin receptor (sTfR), plasma retinol-binding protein, plasma zinc, C-reactive protein (CRP), α-1-acid glycoprotein (AGP), hemoglobin, mean corpuscular volume, and selected nutrient intakes. Both HIV and low iron stores were associated with lower height-for-age Z-scores (HAZ, p < 0.001 and p = 0.02, respectively), while both HIV and sufficient iron stores were associated with significantly higher CRP and AGP concentrations. HIV+ children with low iron stores had significantly lower HAZ, significantly higher sTfR concentrations, and significantly higher prevalence of subclinical inflammation (CRP 0.05 to 4.99 mg/L) (54%) than both HIV-ve groups. HIV was associated with 2.5-fold higher odds of iron deficient erythropoiesis (sTfR > 8.3 mg/L) (95% CI: 1.03-5.8, p = 0.04), 2.7-fold higher odds of subclinical inflammation (95% CI: 1.4-5.3, p = 0.004), and 12-fold higher odds of macrocytosis (95% CI: 6-27, p < 0.001). Compared to HIV-ve counterparts, HIV+ children reported significantly lower daily intake of animal protein, muscle protein, heme iron, calcium, riboflavin, and vitamin B12, and significantly higher proportions of HIV+ children did not meet vitamin A and fiber requirements. Compared to iron sufficient non-anemic counterparts, children with low iron stores reported significantly higher daily intake of plant protein, lower daily intake of vitamin A, and lower proportions of inadequate fiber intake. Along with best treatment practices for HIV, optimizing dietary intake in HIV+ children could improve nutritional status and anemia in this vulnerable population. This study was registered at clinicaltrials.gov as NCT03572010.

The Development of a Quantified Food Frequency Questionnaire for Assessing Iron Nutrition in Schoolchildren from Resource-Limited Settings in Cape Town, South Africa.

Children are vulnerable to developing iron deficiency anemia, especially in resource-limited settings. Information on habitual dietary intake informs dietary interventions aimed at improving iron deficiency. Dietary assessment in school-aged children is challenging and requires concerted efforts to mitigate the pitfalls of long complex methods. Nested within an intervention trial, we aimed to obtain dietary intake information to assess iron nutrition in 8 to 13-year-old children from resource-limited settings in Cape Town, South Africa. Following careful consideration of the study objective, participant characteristics, research setting, available resources, and features of the different dietary intake assessment methods, we identified an iron quantified food frequency questionnaire (QFFQ) as the best method to obtain the information. The QFFQ reflected the study population's habitual intake and the nutrients of interest (protein, iron, vitamin A, vitamin C, calcium, zinc, and fiber). In addition, strategies such as interview-administration of the QFFQ, interviewing the child participant and caregiver together, simplifying frequency reporting, a strategic food list order and a variety of interesting portion size estimation aids collectively supported dietary intake assessment in this young study population. Using a methodical, multiphase approach and strategies that promote participant engagement, we developed the QFFQ, achieved interview success, and obtained comparable data.

Obesity and Other Nutrition Related Abnormalities in Pre-Dialysis Chronic Kidney Disease (CKD) Participants.

Chronic kidney disease (CKD) is increasing in sub-Saharan Africa. Undernutrition has been prevalent amongst end stage CKD patients, with limited data on the prevalence of obesity. The aim of this study was to assess the nutritional status of CKD patients using various methods sensitive to over and under-nutrition. Stage 3 to 5 CKD patients (glomerular filtration rate (GFR) < 60 mL/min/1.73 m2) attending a pre-dialysis clinic in Cape Town, were enrolled. Exclusion criteria included infectious and autoimmune conditions. Sociodemographic, clinical and biochemical data were collected, and anthropometric measurements were performed. Dietary intake was measured with a quantified food frequency questionnaire (FFQ). Statistical Package for the Social Sciences (SPSS) version 26 was used for statistical analysis. Seventy participants, with mean age of 41.8 ± 11.8 years, 52.9% females and 47.1% males were enrolled. Participants enrolled mainly had stage 5 kidney failure. Thirty percent were overweight (21) and 25 (36%) were obese, 22 (60%) of females were overweight and obese, while 13 (39.4%) of males were predominantly normal weight. Abdominal obesity was found in 42 (60%) of participants, mainly in females. Undernutrition prevalence was low at 3%. Dietary assessment showed a high sugar and protein intake. There was a high prevalence of overweight, obesity and abdominal obesity in CKD stage 35 patients, with unhealthy dietary intake and other nutritional abnormalities.

Omega-3 Fatty Acid and Iron Supplementation Alone, but Not in Combination, Lower Inflammation and Anemia of Infection in Mycobacterium tuberculosis-Infected Mice.

Progressive inflammation and anemia are common in tuberculosis (TB) and linked to poor clinical outcomes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have inflammation-resolving properties, whereas iron supplementation in TB may have limited efficacy and enhance bacterial growth. We investigated effects of iron and EPA/DHA supplementation, alone and in combination, on inflammation, anemia, iron status markers and clinical outcomes in Mycobacterium tuberculosis-infected C3HeB/FeJ mice. One week post-infection, mice received the AIN-93 diet without (control) or with supplemental iron (Fe), EPA/DHA, or Fe+EPA/DHA for 3 weeks. Mice supplemented with Fe or EPA/DHA had lower soluble transferrin receptor, ferritin and hepcidin than controls, but these effects were attenuated in Fe+EPA/DHA mice. EPA/DHA increased inflammation-resolving lipid mediators and lowered lung IL-1α, IFN-γ, plasma IL-1ß, and TNF-α. Fe lowered lung IL-1α, IL-1ß, plasma IL-1ß, TNF-α, and IL-6. However, the cytokine-lowering effects in the lungs were attenuated with Fe+EPA/DHA. Mice supplemented with EPA/DHA had lower lung bacterial loads than controls, but this effect was attenuated in Fe+EPA/DHA mice. Thus, individually, post-infection EPA/DHA and iron supplementation lowered systemic and lung inflammation and mitigated anemia of infection in TB, but not when combined. EPA/DHA also enhanced bactericidal effects and could support inflammation resolution and management of anemia.

The effects of anti-inflammatory agents as host-directed adjunct treatment of tuberculosis in humans: a systematic review and meta-analysis.

BACKGROUND: The potential role of adjunctive anti-inflammatory therapy to enhance tuberculosis (TB) treatment has recently received increasing interest. There is, therefore, a need to broadly examine current host-directed therapies (HDTs) that could accelerate treatment response and improve TB outcomes. METHODS: This systematic review and meta-analysis included randomised controlled trials of vitamin D and other HDT agents in patients receiving antibiotic treatment for pulmonary TB. Sputum smear conversion rate at 4-8 weeks was the primary outcome. Secondary outcomes included blood indices associated with infectivity and inflammation, chest radiology and incidence of adverse events. RESULTS: Fifty-five studies were screened for eligibility after the initial search, which yielded more than 1000 records. Of the 2540 participants in the 15 trials included in the meta-analysis, 1898 (74.7%) were male, and the age at entry ranged from 18 to 70 years. There was a 38% significantly (RR 1.38, 95% CI = 1.03-1.84) increased sputum smear negativity in patients administered with vitamin D in addition to standard TB treatment than those receiving only the TB treatment. Patients treated with other HDT anti-inflammatory agents in addition to TB treatment also had a 29% significantly increased sputum smear conversion rate (RR 1.29, 95% CI = 1.09-1.563). Lymphocyte to monocyte ratio was significantly higher in the vitamin D treatment groups compared to the controls (3.52 vs 2.70, 95% CI for difference 0.16-1.11, p = 0.009) and (adjusted mean difference 0.4, 95% CI 0.2 -- 0.6; p = 0.001); whilst tumour necrosis factor-alpha (TNF-α) showed a trend towards a reduction in prednisolone (p < 0.001) and pentoxifylline (p = 0.27) treatment groups. Vitamin D and N-acetylcysteine also accelerated radiographic resolution in treatment compared to placebo at 8 weeks. No differences were observed in the occurrence of adverse events among all HDT treatments. CONCLUSIONS: Vitamin D and other anti-inflammatory HDT medications used as adjunct TB treatment may be well tolerated and effective. They significantly improved sputum smear conversion rate and chest radiological appearance, and also exhibited an inflammation resolution effect.

Plasma Glutamine Levels in Relation to Intensive Care Unit Patient Outcome.

Low and high plasma glutamine levels are associated with increased mortality. This study aimed to measure glutamine levels in critically ill patients admitted to the intensive care unit (ICU) , correlate the glutamine values with clinical outcomes, and identify proxy indicators of abnormal glutamine levels. Patients were enrolled from three ICUs in South Africa, provided they met the inclusion criteria. Clinical and biochemical data were collected. Plasma glutamine was categorized as low (<420 µmol/L), normal (420-700 µmol/L), or high (>700 µmol/L). Three hundred and thirty patients (median age 46.8 years, 56.4% male) were enrolled (median APACHE II score) 18.0 and SOFA) score 7.0). On admission, 58.5% had low (median 299.5 µmol/L) and 14.2% high (median 898.9 µmol/L) plasma glutamine levels. Patients with a diagnosis of polytrauma and sepsis on ICU admission presented with the lowest, and those with liver failure had the highest glutamine levels. Admission low plasma glutamine was associated with higher APACHE II scores (p = 0.003), SOFA scores (p = 0.003), C-reactive protein (CRP) values (p < 0.001), serum urea (p = 0.008), and serum creatinine (p = 0.023) and lower serum albumin (p < 0.001). Low plasma glutamine was also associated with requiring mechanical ventilation and receiving nutritional support. However, it was not significantly associated with length of stay or mortality. ROC curve analysis revealed a CRP threshold value of 87.9 mg/L to be indicative of low plasma glutamine levels (area under the curve (AUC) 0.7, p < 0.001). Fifty-nine percent of ICU patients had low plasma glutamine on admission, with significant differences found between diagnostic groupings. Markers of infection and disease severity were significant indicators of low plasma glutamine.

The Problem of Hospital Malnutrition in the African Continent.

This study aims to determine the prevalence of risk of malnutrition on admission and discharge in African hospitals, and to identify the association with selected indicators. In this multi-center prospective cohort study, adult patients from hospitals in South Africa, Kenya, and Ghana were screened on admission and discharge and contacted 3 months post-discharge. Relevant morbidity and mortality outcomes were assessed. At risk of malnutrition was indicated if NRS-2002 score ≥3. Adult patients (n = 2126; 43.11 years, IQR: 31.95-55.60; 52.2% female) were screened on admission and 61% were identified as at risk of malnutrition. The proportion of at-risk patients for the three hospitals in Kenya and Ghana (66.2%) were significantly higher than that of the three South African hospitals (53.7%) (Chi2 = 31.0; p < 0.001). Discharge risk of malnutrition was 71.2% (n = 394). Mean length of stay (LOS) was 6.46 ± 5.63 days. During hospitalization, 20.6% lost ≥5% body weight, 18.8% were referred for nutrition support, and discharge BMI (23.87 ± 7.38 kg/m2) was significantly lower than admission BMI (24.3 ± 7.3 kg/m2) (p < 0.001). Admission nutrition risk was associated with lower admission and discharge BMI (p < 0.001), longer LOS (p < 0.001), increased 3-month re-admission rates (Chi2 = 1.35; p = 0.245) and increased mortality (Chi2 = 21.68; p < 0.001). Nearly two-thirds of patients were at risk of malnutrition on admission. This was associated with longer LOS and greater hospital mortality. The nutritional status of patients deteriorated during hospitalization. Routine screening practices with appropriate nutrition support action should be implemented as a matter of urgency.

Parenteral Provision of Micronutrients to Adult Patients: An Expert Consensus Paper.

BACKGROUND: Micronutrients, an umbrella term used to collectively describe vitamins and trace elements, are essential components of nutrition. Those requiring alternative forms of nutrition support are dependent on the prescribed nutrition regimen for their micronutrient provision. The purpose of this paper is to assist clinicians to bridge the gap between the available guidelines' recommendations and their practical application in the provision of micronutrients via the parenteral route to adult patients. METHODS: Based on the available evidenced-based literature and existing guidelines, a panel of multidisciplinary healthcare professionals with significant experience in the provision of parenteral nutrition (PN) and intravenous micronutrients developed this international consensus paper. RESULTS: The paper addresses 14 clinically relevant questions regarding the importance and use of micronutrients in various clinical conditions. Practical orientation on how micronutrients should be prescribed, administered, and monitored is provided. CONCLUSION: Micronutrients are a critical component to nutrition provision and PN provided without them pose a considerable risk to nutrition status. Obstacles to their daily provision-including voluntary omission, partial provision, and supply issues-must be overcome to allow safe and responsible nutrition practice.

GLIM Criteria for the Diagnosis of Malnutrition: A Consensus Report From the Global Clinical Nutrition Community.

BACKGROUND: This initiative aims to build a global consensus around core diagnostic criteria for malnutrition in adults in clinical settings. METHODS: The Global Leadership Initiative on Malnutrition (GLIM) was convened by several of the major global clinical nutrition societies. Empirical consensus was reached through a series of face-to-face meetings, telephone conferences, and e-mail communications. RESULTS: A 2-step approach for the malnutrition diagnosis was selected, that is, first screening to identify at risk status by the use of any validated screening tool, and second, assessment for diagnosis and grading the severity of malnutrition. The malnutrition criteria for consideration were retrieved from existing approaches for screening and assessment. Potential criteria were subjected to a ballot among GLIM participants that selected 3 phenotypic criteria (non-volitional weight loss, low body mass index, and reduced muscle mass) and 2 etiologic criteria (reduced food intake or assimilation, and inflammation or disease burden). To diagnose malnutrition at least 1 phenotypic criterion and 1 etiologic criterion should be present. Phenotypic metrics for grading severity are proposed. It is recommended that the etiologic criteria be used to guide intervention and anticipated outcomes. The recommended approach supports classification of malnutrition into four etiology-related diagnosis categories. CONCLUSIONS: A consensus scheme for diagnosing malnutrition in adults in clinical settings on a global scale is proposed. Next steps are to secure endorsements from leading nutrition professional societies, to identify overlaps with syndromes like cachexia and sarcopenia, and to promote dissemination, validation studies, and feedback. The construct should be re-considered every 3-5 years.