Micronutrients as immunomodulatory tools for COVID-19 management.

COVID-19 rapidly turned to a global pandemic posing lethal threats to overwhelming health care capabilities, despite its relatively low mortality rate. The clinical respiratory symptoms include dry cough, fever, anosmia, breathing difficulties, and subsequent respiratory failure. No known cure is available for COVID-19. Apart from the anti-viral strategy, the supports of immune effectors and modulation of immunosuppressive mechanisms is the rationale immunomodulation approach in COVID-19 management. Diet and nutrition are essential for healthy immunity. However, a group of micronutrients plays a dominant role in immunomodulation. The deficiency of most nutrients increases the individual susceptibility to virus infection with a tendency for severe clinical presentation. Despite a shred of evidence, the supplementation of a single nutrient is not promising in the general population. Individuals at high-risk for specific nutrient deficiencies likely benefit from supplementation. The individual dietary and nutritional status assessments are critical for determining the comprehensive actions in COVID-19.

Fever and systemic inflammatory response syndrome after retrograde intrarenal surgery: Risk factors and predictive model.

This paper investigates the characteristics of patients who underwent retrograde intrarenal surgery (RIRS) to determine the predictive factors for post-operative fever and systemic inflammatory response syndrome (SIRS) and to construct a predictive nomogram to help with risk-stratification. A retrospective study of 337 patients who underwent RIRS was performed. Fever and SIRS were defined according to a previous consensus. Multivariate logistic regression coefficients were used to generate nomograms. Post-operative fever was found in 59 patients (17.5%), and SIRS was found in 22 patients (6.5%). Septic shock developed in 2 patients (0.6%). Three patients (0.9%) suffered from obstructive hydronephrosis. By multivariate analysis, concomitant diabetes mellitus (p = 0.015), high pre-operative C-reactive protein (CRP) (p = 0.015), long surgical times (p = 0.007), high stone burden (p = 0.004) and positive stone culture (p = 0.003) were independent risk factors for fever. Only high pre-operative CRP (p = 0.001), long surgical times (p = 0.001) and high stone burden (p = 0.001) were found to significantly affect the occurrence of SIRS. Predictive nomograms were built for fever and SIRS and the c-statistics for the two predictive models were 0.766 and 0.887, respectively. All patients recovered well after proper treatment, which included antipyretics, antibiotics, and inotropic support and nephrostomy when needed. In conclusion, high stone burden, long surgical time, positive stone culture, high pre-operative CRP and the presence of diabetes mellitus was could increase the risk of fever or SIRS after RIRS for kidney stone. The constructed nomograms could help clinicians in evaluating the risk for post-operative infectious complications.

The Efficacy of an Oral Elemental Diet in Patients Undergoing Hematopoietic Stem Cell Transplantation.

Objective Conditioning regimens for hematopoietic stem cell transplantation (HSCT) are well known to cause severe gastrointestinal toxicities that often disturb the oral intake of the patients followed by poor nutrition and life-threatening infection. An oral elemental diet (ED) is an easily consumed and assimilated form of liquid nutrients mainly composed of amino acids. It alleviates the digestive loading from the intestine and is mainly used for enteral nutritional support in patients with Crohn's disease. We herein report, for the first time, the efficacy of ED for patients undergoing HSCT. Methods We evaluated the efficacy of ED in a prospective cohort study. The primary endpoint for this study was the hospitalization period. The secondary endpoint was the occurrence of oral mucositis, nausea, diarrhea and fever. Patients A total of 73 patients were consecutively enrolled between March 2011 and March 2013. Twenty-three patients underwent autologous HSCT and 50 patients underwent allogeneic HSCT. The first 21 patients did not receive ED (non-ED group; NEG) while in the successive 52 patients (ED group; EG), oral ED was started before conditioning and was continued until 28 days after transplantation. Results The patient characteristics were similar between the two groups. The mean duration of ED administration for EG was 28.7 days (range, 3-37 days), and the mean total-dose of ED administration was 1904 g (range, 240-2,960 g). The median hospitalization period was significantly shorter in EG compared to NEG, (34 days vs. 50 days; p=0.007). Grade 3-4 oral mucositis occurred less in EG than NEG (25% vs. 48%; p=0.06). Conclusion Oral ED may promote an early mucosal recovery and thereby shorten the duration of hospitalization.

Low bacterial diet versus control diet to prevent infection in cancer patients treated with chemotherapy causing episodes of neutropenia.

BACKGROUND: Neutropenia is a potentially serious side effect of chemotherapy and a major risk factor for infection, which can be life-threatening. It has been hypothesised that a low bacterial diet (LBD) can prevent infection and (infection-related) mortality in cancer patients receiving chemotherapy that causes episodes of neutropenia, but much remains unclear. This review is an update of a previously published Cochrane review. OBJECTIVES: The primary objective of this review was to determine the efficacy of an LBD versus a control diet in preventing infection and in decreasing (infection-related) mortality in adult and paediatric cancer patients receiving chemotherapy that causes episodes of neutropenia. Secondary objectives were to assess time to first febrile episode, need for empirical antibiotic therapy, diet acceptability and quality of life. SEARCH METHODS: We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 4), the Database of Abstracts of Reviews of Effects (DARE) (2015, Issue 4), PubMed (from 1946 to 4 May 2015), EMBASE (from 1980 to 4 May 2015) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (from 1981 to 4 May 2015).In addition, we searched the reference lists of relevant articles and conference proceedings of American Society of Hematology (ASH; from 2000 to 2015), European Bone Marrow Transplantation (EBMT; from 2000 to 2015), Oncology Nurses Society (ONS; from 2000 to 2015), International Society for Paediatric Oncology (SIOP; from 2000 to 2014), Multinational Association of Supportive Care in Cancer (MASCC; from 2000 to 2015), American Society of Clinical Oncology (ASCO; from 2000 to 2015), Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC; from 2000 to 2015), European Society for Clinical Nutrition and Metabolism (ESPEN; from 2000 to 2015), American Society for Parenteral and Enteral Nutrition (ASPEN; from 2000 to 2015) and European Hematology Association (EHA; from 2000 to 2015). In May 2015, we scanned the National Institutes of Health Register via clinicaltrials.gov and the International Standard Randomised Controlled Trial Number (ISRCTN) Register (www.controlled-trials.com). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing use of an LBD versus a control diet with regard to infection rate, (infection-related) mortality, time to first febrile episode, need for empirical antibiotic therapy, diet acceptability and quality of life in adult and paediatric cancer patients receiving chemotherapy causing episodes of neutropenia. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, 'Risk of bias' assessment and data extraction. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: In the original version of this review, we identified three RCTs that assessed different intervention and control diets in 192 participants (97 randomised to intervention diet; 95 to control diet) with different types of malignancies. For the update, we identified no eligible new studies. Co-interventions (e.g. protective environment, antimicrobial prophylaxis, central venous catheter care, oral care, hygiene practices, colony-stimulating factors) and outcome definitions also differed between studies. In all included studies, it was standard policy to give empirical antibiotics (and sometimes also antimycotics) to (some of) the participants diagnosed with an infection. Two studies included adults and one study included children. In all studies, only a scant description of treatment regimens was provided. All studies had methodological limitations. Pooling of results of included studies was not possible. In two individual studies, no statistically significant differences in infection rate were identified between intervention and control diets; another study showed no significant differences between treatment groups in the number of chemotherapy cycles with an infection. None of the studies mentioned infection-related mortality, but in one study, no significant difference in overall survival was observed between treatment groups. Time from onset of neutropenia to fever, duration of empirical antibiotics and antimycotics, diet acceptability (i.e. following the diet easily and following the diet throughout all chemotherapy cycles) and quality of life were all evaluated by only one study; for all outcomes, no statistically significant differences between treatment arms were identified. AUTHORS' CONCLUSIONS: At the moment, no evidence from individual RCTs in children and adults with different malignancies underscores use of an LBD for prevention of infection and related outcomes. All studies differed with regard to co-interventions, outcome definitions and intervention and control diets. As pooling of results was not possible, and as all studies had serious methodological limitations, we could reach no definitive conclusions. It should be noted that 'no evidence of effect', as identified in this review, is not the same as 'evidence of no effect'. On the basis of currently available evidence, we are not able to provide recommendations for clinical practice. Additional high-quality research is needed.

Effect of zinc added to a daily small-quantity lipid-based nutrient supplement on diarrhoea, malaria, fever and respiratory infections in young children in rural Burkina Faso: a cluster-randomised trial.

OBJECTIVE: Preventive zinc supplementation in the form of tablets or syrup reduces the incidence of diarrhoea and acute lower respiratory tract infections (RTI), but its effect on malaria is inconsistent. When zinc is administered with other micronutrients or foods, its effect is also uncertain. We assessed the effects of different amounts and sources of zinc on the frequency of diarrhoea, malaria, fever and RTI in young children. DESIGN, SETTING AND POPULATIONS: This community-based, double-blind, placebo-controlled, cluster-randomised trial of 2435 children 9 months of age was carried out between April 2010 and July 2012 in rural southwestern Burkina Faso. INTERVENTIONS: Participants were randomly assigned at the concession level to receive daily 1 of 4 interventions for 9 months: (1) 20 g small-quantity lipid-based nutrient supplement (SQ-LNS) without zinc and placebo tablet, (2) 20 g SQ-LNS with 5 mg zinc and placebo tablet, (3) 20 g SQ-LNS with 10 mg zinc and placebo tablet or (4) 20 g SQ-LNS without zinc and 5 mg zinc tablet. Participants were visited weekly in their homes for morbidity surveillance for 9 months, and those with uncomplicated diarrhoea and malaria received treatment from the study field workers in the community. MAIN OUTCOMES: Incidence and longitudinal prevalence of diarrhoea, malaria, fever, and lower and upper RTI by intervention group. RESULTS: The incidence of diarrhoea, malaria and fever was 1.10 (±1.03 SD), 0.61 (±0.66 SD) and 1.49 (±1.12 SD) episodes per 100 child-days at risk, respectively, and did not differ by intervention group (p=0.589, p=0.856 and p=0.830, respectively). The longitudinal prevalence of acute lower RTI (0.1%; 95% IC 0.1-0.2%) and of upper RTI (7.8%; 95% IC 7.1-8.4%) did not differ among groups (p=0.234 and p=0.501, respectively). CONCLUSIONS: Inclusion of 5 or 10 mg zinc in SQ-LNS and provision of 5 mg zinc dispersible tablet along with SQ-LNS had no impact on the incidence of diarrhoea, malaria and fever or the longitudinal prevalence of RTI compared with SQ-LNS without zinc in this population. TRIAL REGISTRATION NUMBER: NCT00944281.

Ketogenic diet exhibits anti-inflammatory properties.

The ketogenic diet (KD) is an established treatment for refractory epilepsy, including some inflammation-induced epileptic encephalopathies. In a lipopolysaccharide (LPS)-induced fever model in rats, we found that animals given the KD for 14 days showed less fever and lower proinflammatory cytokine levels than control animals. However, KD rats exhibited a decrease in circulating levels of arachidonic acid and long-chain n-3 polyunsaturated fatty acids (PUFAs), suggesting that the anti-inflammatory effect of KD was probably not due to an increase in anti-inflammatory n-3 PUFA derivatives. These properties might be of interest in some conditions such as fever-induced refractory epileptic encephalopathy in school-aged children.

A is for aphorisms - feed a fever, starve a cold? Or could it be starve a fever, feed a cold?

The recommendations for management of fever have changed throughout the course of history, as has the very concept of fever. It has changed from something viewed as a diagnosis in its own right to a sign of something to be measured and as a trigger for a diagnostic trail to be made.

Calorie restriction dose-dependently abates lipopolysaccharide-induced fever, sickness behavior, and circulating interleukin-6 while increasing corticosterone.

In mice a 50% calorie restriction (CR) for 28days attenuates sickness behavior after lipopolysaccharide (LPS) and these mice demonstrate a central anti-inflammatory bias. This study examined the dose-dependent effect of CR on sickness behavior (fever, anorexia, cachexia) and peripheral immune markers post-LPS. Male Sprague-Dawley rats fed ad libitum or CR by 50% for 14, 21, or 28days were injected on day 15, 22, or 29 with 50µg/kg of LPS or saline (1mL/500g). Changes in body temperature (Tb), locomotor activity, body weight, and food intake were determined. A separate cohort of rats was fed ad libitum or CR by 50% for 28days and serum levels of corticosterone (CORT), interleukin 6 (IL-6), and IL-10 were determined at 0, 2, and 4h post-LPS. The rats CR for 28days demonstrated the largest attenuation of sickness behavior: no fever, limited reduction in locomotor activity, no anorexia, and reduced cachexia following LPS. Rats CR for 14 and 21days demonstrated a partial attenuation of sickness behavior. Rats CR for 14days demonstrated a larger increase in Tb, larger reduction in locomotor activity, and larger weight loss compared to rats CR for 21days. Serum CORT was increased at 2h post-LPS in ad libitum and CR groups; however it was two times larger in the CR animals. Levels of IL-6 were significantly attenuated at 2h post-LPS in the CR animals. IL-10 levels were similar post-LPS. CR results in an enhanced anti-inflammatory response in the form of increased CORT and diminished pro-inflammatory signals.

Low bacterial diet versus control diet to prevent infection in cancer patients treated with chemotherapy causing episodes of neutropenia.

BACKGROUND: Neutropenia is a potentially serious side effect of chemotherapy and a major risk factor for infections, which can be life-threatening. It has been hypothesised that a low bacterial diet (LBD) can prevent the occurrence of infections and (infection-related) mortality in cancer patients receiving chemotherapy causing episodes of neutropenia, but much remains unclear. OBJECTIVES: The primary objective was to determine the efficacy of an LBD versus a control diet in preventing the occurrence of infection and to decrease (infection-related) mortality in adult and paediatric cancer patients receiving chemotherapy causing episodes of neutropenia. Secondary objectives were to assess the time to first febrile episode, the need for empirical antibiotic therapy, diet acceptability and quality of life. SEARCH METHODS: We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, issue 3 2011), Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library, issue 3 2011), PubMed (from 1946 to 20 October 2011), EMBASE (from 1980 to 20 October 2011) and CINAHL (from 1981 to 20 October 2011). In addition, we searched several conference proceedings (from 2000 to either 2010 or 2011) and reference lists of relevant articles. To identify ongoing trials we contacted researchers working on this topic and we scanned the National Institute of Health Register and the ISRCTN Register (www.controlled-trials.com; searched May 2012). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the use of an LBD with a control diet with regard to infection rate, (infection-related) mortality, time to first febrile episode, need for empirical antibiotic therapy, diet acceptability, and quality of life in adult and paediatric cancer patients receiving chemotherapy causing episodes of neutropenia. DATA COLLECTION AND ANALYSIS: Two review authors independently performed the study selection, 'Risk of bias' assessment and data extraction. Analyses were performed according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: We identified three RCTs assessing different intervention and control diets in 192 patients (97 randomised to intervention diet; 95 to control diet) with different types of malignancies. Co-interventions (e.g. protective environment, antimicrobial prophylaxis, central venous catheter care, oral care, hygiene practices and colony-stimulating factors) and outcome definitions also differed between studies. In all included studies it was standard policy to give empirical antibiotics (and sometimes also antimycotics) to (some of) the patients diagnosed with an infection. Two studies included adults and one study included children. In all studies only a scant description of treatment regimens was provided. All studies had methodological limitations. Pooling of results of included studies was not possible. In two individual studies no statistically significant difference in infection rate between the intervention and control diet was identified; another study showed no significant difference in the number of chemotherapy cycles with an infection between the treatment groups. None of the studies mentioned infection-related mortality, but in one study no significant difference in overall survival between the treatment groups was observed. Time from onset of neutropenia to fever, the duration of empirical antibiotics and antimycotics, diet acceptability (i.e. following the diet easily and following the diet throughout all chemotherapy cycles) and quality of life were all evaluated by only one study; for all outcomes no statistically significant differences between the treatment arms was observed. AUTHORS' CONCLUSIONS: At the moment there is no evidence from individual RCTs in children and adults with different malignancies that underscores the use of an LBD for the prevention of infection and related outcomes. All studies differed with regard to co-interventions, outcome definitions, and intervention and control diets. Since pooling of results was not possible and all studies had serious methodological limitations, no definitive conclusions can be made. It should be noted that 'no evidence of effect', as identified in this review, is not the same as 'evidence of no effect'. Based on the currently available evidence, we are not able to give recommendations for clinical practice. More high-quality research is needed.

The duration of diarrhea and fever is associated with growth faltering in rural Malawian children aged 6-18 months.

Nutrition support programs that only focus upon better complementary feeding remain an insufficient means of limiting growth faltering in vulnerable populations of children. To determine if symptoms of acute infections correlate with the incidence of growth faltering in rural Malawian children, the associations between fever, diarrhea, and cough with anthropometric measures of stunting, wasting, and underweight were investigated. Data were analyzed from a trial where 209 children were provided with adequate complementary food and followed fortnightly from 6-18 months of age. Linear mixed model analysis was used to test for associations. Diarrheal disease was inversely associated with changes in height-for-age Z-score (HAZ), mid-upper arm circumference Z-score (MUACZ), and weight-for-age Z-score (WAZ). Fever was also inversely associated with changes in MUACZ and WAZ. These results suggest that initiatives to reduce febrile and diarrheal diseases are needed in conjunction with improved complementary feeding to limit growth faltering in rural Malawi.

"Starve a fever and feed a cold": feeding and anorexia may be adaptive behavioral modulators of autonomic and T helper balance.

Anorexia is a common symptom accompanying infections, but the teleology of the phenomenon remains unexplained. We hypothesize that anorexia may represent a prehistoric behavioral adaptation to fight infection by maintaining T helper (Th)2 bias, which is particularly vital in fighting bacterial pathogens. Specifically, we propose that anorexia may avert the reduction of Th2/Th1 ratio by preventing feeding-induced neurohormonal and vagal output from the gut. Emerging evidence suggests that the vagal and neurohormonal output of the gut during feeding promotes Th1 function, which is desirable in fighting viral infections. Since fever may be an adaptation to fight bacteria and "colds" are generally viral in origin, the adage "starve a fever and feed a cold" may reflect a sensible behavioral strategy to tilt autonomic and Th balance in directions that are optimal for fighting the particular type of infection. The ability to modulate T helper balance through the neurohormonal and autonomic axis by adjusting food intake may be the mechanism behind other unexplained clinical observations such as the improved outcomes of ICU patients after enteric versus parenteric feedings. Compared to the prehistoric period when bacterial infection was commonplace, the anorexic response may be less adaptive today when viruses and cancers have become common triggers of anorexia. By promoting host anorexia, cachexia, and insomnia, cancers and viruses can deter behaviors such as digestion and sleep that would raise vagal and Th1 activity against tumors and viruses. Hydration and sleep, unexplained but widely accepted recommendations for flu patients, may also work by promoting vagal and Th1 functions. Modulating feeding, hydration, and sleep may prove beneficial in treating other conditions associated with abnormal autonomic and Th balance.

[Effect of a high-protein diet on clinical and some biochemical indices of patients with torpid and latent courses of recurrent rheumatic heart disease]. / Vliianie vysokobelkovoi diety na klinicheskie i nekotorye biokhimicheskie pokazateli u bol'nykh vialo i latentno tekushchim vozvratnym revmokarditom

The effect of a protein-rich diet containing 141 g of protein on the clinical and some biochemical findings in 145 patients with a torpidly, and latently running recurrent rheumatic heart disease was studied. Pertinent observations have shown the protein-rich diet to have a very beneficial effect on the clinico-biochemical and immunological indices that are pathognomic of rheumatism with low activity and torpid course.