Stress Hyperglycemia and Osteocalcin in COVID-19 Critically Ill Patients on Artificial Nutrition

We aimed to study the possible association of stress hyperglycemia in COVID-19 critically ill patients with prognosis, artificial nutrition, circulating osteocalcin, and other serum markers of inflammation and compare them with non-COVID-19 patients. Fifty-two critical patients at the intensive care unit (ICU), 26 with COVID-19 and 26 non-COVID-19, were included. Glycemic control, delivery of artificial nutrition, serum osteocalcin, total and ICU stays, and mortality were recorded. Patients with COVID-19 had higher ICU stays, were on artificial nutrition for longer (p = 0.004), and needed more frequently insulin infusion therapy (p = 0.022) to control stress hyperglycemia. The need for insulin infusion therapy was associated with higher energy (p = 0.001) and glucose delivered through artificial nutrition (p = 0.040). Those patients with stress hyperglycemia showed higher ICU stays (23 ± 17 vs. 11 ± 13 days, p = 0.007). Serum osteocalcin was a good marker for hyperglycemia, as it inversely correlated with glycemia at admission in the ICU (r = −0.476, p = 0.001) and at days 2 (r = −0.409, p = 0.007) and 3 (r = −0.351, p = 0.049). In conclusion, hyperglycemia in critically ill COVID-19 patients was associated with longer ICU stays. Low circulating osteocalcin was a good marker for stress hyperglycemia.     

Effect of Whey Supplementation on Circulating C-Reactive Protein: A Meta-Analysis of Randomized Controlled Trials

Whey supplementation is beneficial for human health, possibly by reducing the circulating C-reactive protein (CRP) level, a sensitive marker of inflammation. Thus, a meta-analysis of randomized controlled trials was conducted to evaluate their relationship. A systematic literature search was conducted in July, 2014, to identify eligible studies. Either a fixed-effects model or a random-effects model was used to calculate pooled effects. The meta-analysis results of nine trials showed a slight, but no significant, reduction of 0.42 mg/L (95% CI −0.96, 0.13) in CRP level with the supplementation of whey protein and its derivates. Relatively high heterogeneity across studies was observed. Subgroup analyses showed that whey significantly lowered CRP by 0.72 mg/L (95% CI −0.97, −0.47) among trials with a daily whey dose ≥20 g/day and by 0.67 mg/L (95% CI −1.21, −0.14) among trials with baseline CRP ≥3 mg/L. Meta-regression analysis revealed that the baseline CRP level was a potential effect modifier of whey supplementation in reducing CRP. In conclusion, our meta-analysis did not find sufficient evidence that whey and its derivates elicited a beneficial effect in reducing circulating CRP. However, they may significantly reduce CRP among participants with highly supplemental doses or increased baseline CRP levels.     

Why Critically Ill Patients Are Protein Deprived

Critical illness dramatically increases muscle proteolysis and more than doubles the dietary protein requirement. Yet surprisingly, most critically ill patients receive less than half the recommended amount of protein during their stay in a modern intensive care unit. What could explain the wide gap between the recommendations in clinical care guidelines and actual clinical practice? We suggest that an important aspect of the problem is the failure of guidelines to explain the pathophysiology of protein‐energy malnutrition and the ways critical illness modifies protein metabolism. The difficulty created by the lack of a framework for reasoning about appropriate protein provision in critical illness is compounded by the many ambiguous and often contradictory ways the word malnutrition is used in the critical care literature. Failing to elucidate these matters, the recommendations for protein provision in the guidelines are incoherent, unconvincing, and easy to ignore.     

新型冠状病毒肺炎重症患者定点医院医务管理实践探索

新型冠状病毒肺炎疫情目前处于攻坚阶段,提高患者治愈率、降低病死率是定点医疗机构的核心目标。以华中科技大学同济医学院附属同济医院光谷院区医务管理工作实践为基础,总结重症患者定点医院医务工作经验,供公立医院和卫生行政部门参考。     

Clinical Significance of Micronutrient Supplementation in Critically Ill COVID-19 Patients with Severe ARDS

The interplay between inflammation and oxidative stress is a vicious circle, potentially resulting in organ damage. Essential micronutrients such as selenium (Se) and zinc (Zn) support anti-oxidative defense systems and are commonly depleted in severe disease. This single-center retrospective study investigated micronutrient levels under Se and Zn supplementation in critically ill patients with COVID-19 induced acute respiratory distress syndrome (ARDS) and explored potential relationships with immunological and clinical parameters. According to intensive care unit (ICU) standard operating procedures, patients received 1.0 mg of intravenous Se daily on top of artificial nutrition, which contained various amounts of Se and Zn. Micronutrients, inflammatory cytokines, lymphocyte subsets and clinical data were extracted from the patient data management system on admission and after 10 to 14 days of treatment. Forty-six patients were screened for eligibility and 22 patients were included in the study. Twenty-one patients (95%) suffered from severe ARDS and 14 patients (64%) survived to ICU discharge. On admission, the majority of patients had low Se status biomarkers and Zn levels, along with elevated inflammatory parameters. Se supplementation significantly elevated Se (p = 0.027) and selenoprotein P levels (SELENOP; p = 0.016) to normal range. Accordingly, glutathione peroxidase 3 (GPx3) activity increased over time (p = 0.021). Se biomarkers, most notably SELENOP, were inversely correlated with CRP (r_s = −0.495), PCT (r_s = −0.413), IL-6 (r_s = −0.429), IL-1β (r_s = −0.440) and IL-10 (r_s = −0.461). Positive associations were found for CD8⁺ T cells (r_s = 0.636), NK cells (r_s = 0.772), total IgG (r_s = 0.493) and PaO₂/FiO₂ ratios (r_s = 0.504). In addition, survivors tended to have higher Se levels after 10 to 14 days compared to non-survivors (p = 0.075). Sufficient Se and Zn levels may potentially be of clinical significance for an adequate immune response in critically ill patients with severe COVID-19 ARDS.     

COVID-19–Associated Mold Infection in Critically Ill Patients,Chile

Patients with severe coronavirus disease (COVID-19) may have COVID-19–associated invasive mold infection (CAIMI) develop. We report 16 cases of CAIMI among 146 nonimmunocompromised patients with severe COVID-19 at an academic hospital in Santiago, Chile. These rates correspond to a CAIMI incidence of 11%; the mortality rate for these patients was 31.2%.     

Nutritional Risk Assessment Scores Effectively Predict Mortality in Critically Ill Patients with Severe COVID-19

Background: Malnutrition predicts a worse outcome for critically ill patients. However, quick, easy-to-use nutritional risk assessment tools have not been adequately validated. Aims and Methods: The study aimed to evaluate the role of four biological nutritional risk assessment instruments (the Prognostic Nutritional Index—PNI, the Controlling Nutritional Status Score—CONUT, the Nutrition Risk in Critically Ill—NUTRIC, and the modified NUTRIC—mNUTRIC), along with CT-derived fat tissue and muscle mass measurements in predicting in-hospital mortality in a consecutive series of 90 patients hospitalized in the intensive care unit for COVID-19-associated ARDS. Results: In-hospital mortality was 46.7% (n = 42/90). Non-survivors had a significantly higher nutritional risk, as expressed by all four scores. All scores were independent predictors of mortality on the multivariate regression models. PNI had the best discriminative capabilities for mortality, with an area under the curve (AUC) of 0.77 for a cut-off value of 28.05. All scores had an AUC above 0.72. The volume of fat tissue and muscle mass were not associated with increased mortality risk. Conclusions: PNI, CONUT, NUTRIC, and mNUTRIC are valuable nutritional risk assessment tools that can accurately predict mortality in critically ill patients with COVID-19-associated ARDS.     

Influence of Nutritional Parameters on the Evolution,Severity and Prognosis of Critically Ill Patients with COVID-19

This study evaluated the clinical and nutritional status, the evolution over three days, and the relationship between nutritional, inflammatory, and clinical parameters of critically ill patients with COVID-19. A longitudinal study was conducted in the Intensive Care Unit of the Virgen de las Nieves University Hospital in Granada (Spain). The study population comprised patients with a positive polymerase chain reaction test for COVID-19 presenting critical clinical involvement. Clinical outcomes were collected, and inflammatory and nutritional parameters (albumin, prealbumin, transferrin, transferrin saturation index, cholesterol, triglycerides and Controlling Nutritional Status (CONUT) score) were determined. A total of 202 critical patients with COVID-19 were selected, presenting highly altered clinical-nutritional parameters. The evolution experienced by the patients on the third day of admission was a decrease in albumin (p < 0.001) and an increase in prealbumin (p < 0.001), transferrin (p < 0.002), transferrin saturation index (p < 0.018), and cholesterol (p < 0.001). Low levels of albumin, prealbumin (on the third day) and high CONUT score (on the third day) showed an association with higher mortality. Nutritional variables were inversely correlated with clinical and inflammatory parameters. Critically ill patients with COVID-19 have poor nutritional status related to a poor prognosis of disease severity and mortality.     

The Effects of Enteral Nutrition in Critically Ill Patients with COVID-19: A Systematic Review and Meta-Analysis

Background: Patients who are critically ill with COVID-19 could have impaired nutrient absorption due to disruption of the normal intestinal mucosa. They are often in a state of high inflammation, increased stress and catabolism as well as a significant increase in energy and protein requirements. Therefore, timely enteral nutrition support and the provision of optimal nutrients are essential in preventing malnutrition in these patients. Aim: This review aims to evaluate the effects of enteral nutrition in critically ill patients with COVID-19. Method: This systematic review and meta-analysis was conducted based on the preferred reporting items for systematic review and meta-Analysis framework and PICO. Searches were conducted in databases, including EMBASE, Health Research databases and Google Scholar. Searches were conducted from database inception until 3 February 2022. The reference lists of articles were also searched for relevant articles. Results: Seven articles were included in the systematic review, and four articles were included in the meta-analysis. Two distinct areas were identified from the results of the systematic review and meta-analysis: the impact of enteral nutrition and gastrointestinal intolerance associated with enteral nutrition. The impact of enteral nutrition was further sub-divided into early enteral nutrition versus delayed enteral nutrition and enteral nutrition versus parenteral nutrition. The results of the meta-analysis of the effects of enteral nutrition in critically ill patients with COVID-19 showed that, overall, enteral nutrition was effective in significantly reducing the risk of mortality in these patients compared with the control with a risk ratio of 0.89 (95% CI, 0.79, 0.99, p = 0.04). Following sub-group analysis, the early enteral nutrition group also showed a significant reduction in the risk of mortality with a risk ratio of 0.89 (95% CI, 0.79, 1.00, p = 0.05). The Relative Risk Reduction (RRR) of mortality in patients with COVID-19 by early enteral nutrition was 11%. There was a significant reduction in the Sequential Organ Failure Assessment (SOFA) score in the early enteral nutrition group compared with the delayed enteral nutrition group. There was no significant difference between enteral nutrition and parenteral nutrition in relation to mortality (RR = 0.87; 95% CI, 0.59, 1.28, p = 0.48). Concerning the length of hospital stay, length of ICU stay and days on mechanical ventilation, while there were reductions in the number of days in the enteral nutrition group compared to the control (delayed enteral nutrition or parenteral nutrition), the differences were not significant (p > 0.05). Conclusion: The results showed that early enteral nutrition significantly (p < 0.05) reduced the risk of mortality among critically ill patients with COVID-19. However, early enteral nutrition or enteral nutrition did not significantly (p > 0.05) reduce the length of hospital stay, length of ICU stay and days on mechanical ventilation compared to delayed enteral nutrition or parenteral nutrition. More studies are needed to examine the effect of early enteral nutrition in patients with COVID-19.     

Emerging Health Properties of Whey Proteins and Their Clinical Implications

The nursery rhyme “Little Miss Muffet sat on a tuffet (small stool) eating her curds and whey. …” is recognition of the fact that over the centuries “curds and whey”, the two major components of cow's milk, have been widely accepted as part of a healthy diet. Milk provides complete nourishment for the neonate for six months from birth, containing factors that help develop various organ systems including the brain, immune system, and the intestine. Importantly it provides immune protection at a time when the neonates own immune system, though fully developed, is albeit immature. Many adult consumers include cow's milk as part of a healthy diet as it provides protein and essential nutrients, vitamins, and minerals, in particular calcium for strong bones. There is a growing appreciation that milk, and in particular whey, contains components that not only provide nutrition, but can also prevent and attenuate disease, or augment conventional therapies, when delivered in amounts that exceed normal dietary intakes. This paper reviews the emerging health properties of whey proteins and their clinical implications.     

Does Route of Full Feeding Affect Outcome among Ventilated Critically Ill COVID-19 Patients: A Prospective Observational Study

The outbreak of the new coronavirus strain SARS-CoV-2 (COVID-19) highlighted the need for appropriate feeding practices among critically ill patients admitted to the intensive care unit (ICU). This study aimed to describe feeding practices of intubated COVID-19 patients during their second week of hospitalization in the First Department of Critical Care Medicine, Evaggelismos General Hospital, and evaluate potential associations with all cause 30-day mortality, length of hospital stay, and duration of mechanical ventilation. We enrolled adult intubated COVID-19 patients admitted to the ICU between September 2020 and July 2021 and prospectively monitored until their hospital discharge. Of the 162 patients analyzed (52.8% men, 51.6% overweight/obese, mean age 63.2 ± 11.9 years), 27.2% of patients used parenteral nutrition, while the rest were fed enterally. By 30 days, 34.2% of the patients in the parenteral group had died compared to 32.7% of the patients in the enteral group (relative risk (RR) for the group receiving enteral nutrition = 0.97, 95% confidence interval = 0.88–1.06, p = 0.120). Those in the enteral group demonstrated a lower duration of hospital stay (RR = 0.91, 95% CI = 0.85-0.97, p = 0.036) as well as mechanical ventilation support (RR = 0.94, 95% CI = 0.89–0.99, p = 0.043). Enteral feeding during second week of ICU hospitalization may be associated with a shorter duration of hospitalization and stay in mechanical ventilation support among critically ill intubated patients with COVID-19.     

Gut Microbiota and Probiotics/Synbiotics for Modulation of Immunity in Critically Ill Patients

Patients suffering from critical illness have host inflammatory responses against injuries, such as infection and trauma, that can lead to tissue damage, organ failure, and death. Modulation of host immune response as well as infection and damage control are detrimental factors in the management of systemic inflammation. The gut is the motor of multiple organ failure following injury, and it is recognized that gut dysfunction is one of the causative factors of disease progression. The gut microbiota has a role in maintaining host immunity, and disruption of the gut microbiota might induce an immunosuppressive condition in critically ill patients. Treatment with probiotics and synbiotics has been reported to attenuate systemic inflammation by maintaining gut microbiota and to reduce postoperative infectious complications and ventilator-associated pneumonia. The administration of prophylactic probiotics/synbiotics could be an important treatment option for preventing infectious complications and modulating immunity. Further basic and clinical research is needed to promote intestinal therapies for critically ill patients.     

Malnutrition May Worsen the Prognosis of Critically Ill Children With Hyperglycemia and Hypoglycemia

Objectives: To determine whether hyperglycemia and hypoglycemia are associated with higher mortality, longer length of intensive care unit (ICU) stay, and fewer ventilator‐free days in critically ill children while taking into account the clinical severity and nutrition status. Patients and Methods: A prospective observational cohort study was conducted on 221 children admitted to the ICU. Blood glucose levels were analyzed in the first 72 hours. Potential exposure variables for adverse prognosis included hyperglycemia (blood glucose >150 mg/dL), hypoglycemia (blood glucose ≤60 mg/dL), age <1 year, sex, nutrition status, the revised Pediatric Index of Mortality (PIM 2), and the Pediatric Logistic Organ Dysfunction (PELOD). Results: Of the patients, 47.1% were malnourished. Controlling for nutrition status, both hyperglycemia and hypoglycemia increased the risk of mortality in the malnourished patients compared with the well‐nourished ones. Adjusting for clinical severity, the odds ratio of mortality was higher in malnourished patients with hyperglycemia (odds ratio [OR], 3.98; 95% confidence interval [CI], 1.14–13.94; P = .03), whereas no significant associations were detected in the well‐nourished patients. After controlling for nutrition status, hypoglycemia was associated with longer length of ICU stay (OR, 6.5; 95% CI, 1.30–32.57; P < .01) and fewer ventilator‐free days (OR, 4.11; 95% CI, 1.26–13.40; P < .01) only in the malnourished group of patients. Conclusions: Compared with the well nourished, malnourished patients with hyperglycemia are at a greater risk of mortality, independent of clinical severity. Hypoglycemia was shown to be associated with mortality, longer length of ICU stay, and fewer ventilator‐free days only in malnourished patients.     

Dietary Linolenic Acid Increases Sensitizing and Eliciting Capacities of Cow’s Milk Whey Proteins in BALB/c Mice

α-Lactalbumin (BLA) and β-lactoglobulin (BLG) are the major whey proteins causing allergic reactions. Polyunsaturated fatty acids (PUFAs) stand among the extrinsic factors of the food matrix that can bind BLA and BLG and change their bioactivities, but their contribution to change the allergenic properties of these proteins has not been investigated. Here, we aimed to determine how PUFAs influence BLA and BLG to sensitize and trigger allergic responses in BALB/c mice. First, tricine–SDS–PAGE and spectroscopic assays identified that α-linolenic acid (ALA, as a proof-of-concept model) can induce BLA and BLG to form cross-linked complexes and substantially modify their conformation. Then, BALB/c mice (n = 10/group) were orally sensitized and challenged with BLA and BLG or ALA-interacted BLA and BLG, respectively. Allergic reactions upon oral challenge were determined by measuring clinical allergic signs, specific antibodies, levels of type-1/2 cytokines, the status of mast cell activation, and percentage of cell populations (B and T cells) in different tissues (PP, MLN, and spleen). Overall, systemic allergic reaction was promoted in mice gavage with ALA-interacted BLA and BLG by disrupting the Th1/Th2 balance toward a Th2 immune response with the decreased number of Tregs. Enhanced induction of Th2-related cytokines, as well as serum-specific antibodies and mast cell activation, was also observed. In this study, we validated that ALA in the food matrix promoted both the sensitization and elicitation of allergic reactions in BALB/c mice.     

C-reactive protein levels in the early stage of COVID-19

BackgroundCOVID-19 is a new infectious disease, for which there is currently no treatment. It is therefore necessary to explore biomarkers to determine the extent of lung lesions and disease severity.ObjectiveWe aimed to assess the usefulness of CRP levels in the early stage of COVID-19 and to correlate them with lung lesions and severe presentation.MethodsConfirmed cases of COVID-19 were selected at the Fever Unit in two regions of Guizhou, China. On admission CRP levels were collected, and the diameter of the largest lung lesion was measured in the most severe lung lesion by lung CT scan. Differences in the diameter and CRP levels were compared in the following groups of patients: mild group, moderate group, severe group, and critical group.ResultCRP levels and the diameter of the largest lung lesion in the moderate group were higher than those in the mild group (Mann-Whitney test = −2.647, −2.171, P ˂ 0.05), those in the severe group were higher than those in the moderate group (Mann-Whitney test = 0.693, −2.177, P ˂ 0.05), and those in the critical group were higher than those in the severe group (Mann-Whitney test = −0.068, −1.549, P ˂ 0.05). The difference was statistically significant. CRP levels were positively correlated with the diameter of lung lesion and severe presentation (correlation coefficient = 0.873, 0.734, P ˂ 0.001).ConclusionIn the early stage of COVID-19 CRP levels were positively correlated with lung lesions and could reflect disease severity.