Emergency critical care: closing the gap between onset of critical illness and intensive care unit admission.

Critical illness is an exquisitely time-sensitive condition and follows a disease continuum, which always starts before admission to the intensive care unit (ICU), in the majority of cases even before hospital admission. Reflecting the common practice in many healthcare systems that critical care is mainly provided in the confined areas of an ICU, any delay in ICU admission of critically ill patients is associated with increased morbidity and mortality. However, if appropriate critical care interventions are provided before ICU admission, this association is not observed. Emergency critical care refers to critical care provided outside of the ICU. It encompasses the delivery of critical care interventions to and monitoring of patients at the place and time closest to the onset of critical illness as well as during transfer to the ICU. Thus, emergency critical care covers the most time-sensitive phase of critical illness and constitutes one missing link in the chain of survival of the critically ill patient. Emergency critical care is delivered whenever and wherever critical illness occurs such as in the pre-hospital setting, before and during inter-hospital transfers of critically ill patients, in the emergency department, in the operating theatres, and on hospital wards. By closing the management gap between onset of critical illness and ICU admission, emergency critical care improves patient safety and can avoid early deaths, reverse mild-to-moderate critical illness, avoid ICU admission, attenuate the severity of organ dysfunction, shorten ICU length of stay, and reduce short- and long-term mortality of critically ill patients. Future research is needed to identify effective models to implement emergency critical care systems in different healthcare systems.

Daily compliance of the ABCDEF liberation bundle for patients in the intensive care unit: A retrospective descriptive study / Cumplimiento diario del bundle ABCDEF de liberación de los pacientes de cuidados intensivos: estudio descriptivo retrospectivo.

Introduction: Implementing the ABCDEF bundle has demonstrated improved outcomes in patients with critical illness. This study aims to describe the daily compliance of the ABCDEF bundle in a Chilean intensive care unit. Methods: Retrospective observational study of electronic clinical records of nursing, physiotherapy, and medical professionals who cared for patients over 18 years of age, admitted to an intensive care unit for at least 24 hours, with or without mechanical ventilation. Daily bundle compliance was determined by considering the daily records for each element: Assess pain (element A), both spontaneous awakening trials (element B1) and spontaneous breathing trials (element B2), choice of sedation (element C), delirium assessment (element D), early mobilization (element E), and family engagement (element F). Results: 4165 registered bundle elements were obtained from nursing (47%), physiotherapy (44%), and physicians (7%), including 1134 patient/days (from 133 patients). Elements E and C showed 67 and 40% compliance, while D, A, and B2 showed 24, 14 and 11%, respectively. For B1 and F, 0% compliance was achieved. Compliance was higher in patients without mechanical ventilation for A and E, while it was similar for D. Conclusions: Early mobilization had the highest compliance, while spontaneous awakening trials and family engagement had absolute non-compliance. Future studies should explore the reasons for the different degrees of compliance per bundle element in clinical practice.

Introducción: La implementación del ABCDEF ha demostrado mejores resultados en los pacientes críticos. El objetivo de este trabajo es identificar el cumplimiento del registro diario del ABCDEF en una unidad de cuidados intensivos chilena. Métodos: Estudio observacional retrospectivo de los registros clínicos electrónicos de profesionales de enfermería, kinesiología y medicina que trataron a pacientes mayores de 18 años, hospitalizados en una unidad de cuidados intensivos durante al menos 24 horas, con o sin requerimiento de ventilación mecánica. Se determinó el cumplimiento diario del considerando la presencia del registro en la ficha clínica de cada elemento: evaluación del dolor (elemento A), prueba de interrupción de la sedación (elemento B1) y ventilación espontánea (elemento B2), elección de la sedación (elemento C), evaluación del (elemento D), movilización temprana (elemento E) y empoderamiento de la familia (elemento F). Resultados: Se obtuvieron 4165 elementos del registrados provenientes de enfermería (47%), kinesiología (44%) y medicina (7%), incluyendo 1134 días/paciente (133 pacientes). Los elementos E y C mostraron un cumplimiento del 67 y 40%, mientras que D, A, y B2 mostraron 24, 14 y 11%, respectivamente. Para B1 y F se obtuvo 0% de cumplimiento. El cumplimiento fue mayor en los pacientes sin ventilación mecánica para A y E, mientras que para D fue similar. Conclusiones: La movilización temprana fue el elemento con mayor cumplimiento, mientras que las pruebas de interrupción de sedación y el empoderamiento de la familia tuvieron incumplimiento absoluto. Futuros estudios deberían explorar las razones que expliquen los diferentes grados de cumplimiento por elemento del en la práctica clínica.

Psychotropic prescribing after hospital discharge in survivors of critical illness, a retrospective cohort study (2012-2019).

Background: Many people survive critical illness with the burden of new or worsened mental health issues and sleep disturbances. We examined the frequency of psychotropic prescribing after critical illness, comparing critical care to non-critical care hospitalised survivors, and whether this varied in important subgroups. Methods: This retrospective cohort study included 23,340 critical care and 367,185 non-critical care hospitalised adults from 2012 through 2019 in Lothian, Scotland, who survived to discharge. Results: One-third of critical care survivors (32%; 7527/23,340) received a psychotropic prescription within 90 days after hospital discharge (25% antidepressants; 14% anxiolytics/hypnotics; 4% antipsychotics/mania medicines). In contrast, 15% (54,589/367,185) of non-critical care survivors received a psychotropic prescription (12% antidepressants; 5% anxiolytics/hypnotics; 2% antipsychotics/mania medicines). Among patients without psychotropic prescriptions within 180 days prior to hospitalisation, after hospital discharge, the critical care group had a higher incidence of psychotropic prescription (10.3%; 1610/15,609) compared with the non-critical care group (3.2%; 9743/307,429); unadjusted hazard ratio (HR) 3.39, 95% CI: 3.22-3.57. After adjustment for potential confounders, the risk remained elevated (adjusted HR 2.03, 95% CI: 1.91-2.16), persisted later in follow-up (90-365 days; adjusted HR 1.38, 95% CI: 1.30-1.46), and was more pronounced in those without recorded comorbidities (adjusted HR 3.49, 95% CI: 3.22-3.78). Conclusions: Critical care survivors have a higher risk of receiving psychotropic prescriptions than hospitalised patients, with a significant proportion receiving benzodiazepines and other hypnotics. Future research should focus on the requirement for and safety of psychotropic medicines in survivors of critical illness, to help guide policy for clinical practice.

The post-septic peripheral myeloid compartment reveals unexpected diversity in myeloid-derived suppressor cells.

Introduction: Sepsis engenders distinct host immunologic changes that include the expansion of myeloid-derived suppressor cells (MDSCs). These cells play a physiologic role in tempering acute inflammatory responses but can persist in patients who develop chronic critical illness. Methods: Cellular Indexing of Transcriptomes and Epitopes by Sequencing and transcriptomic analysis are used to describe MDSC subpopulations based on differential gene expression, RNA velocities, and biologic process clustering. Results: We identify a unique lineage and differentiation pathway for MDSCs after sepsis and describe a novel MDSC subpopulation. Additionally, we report that the heterogeneous response of the myeloid compartment of blood to sepsis is dependent on clinical outcome. Discussion: The origins and lineage of these MDSC subpopulations were previously assumed to be discrete and unidirectional; however, these cells exhibit a dynamic phenotype with considerable plasticity.

Navigating Nutritional Strategies: Permissive Underfeeding in Critically Ill Patients.

Nutritional support is a critical component of care for critically ill patients, impacting their recovery and overall prognosis. Traditional approaches to feeding in the intensive care unit (ICU) have focused on meeting estimated energy requirements, often resulting in unintended consequences such as overfeeding and associated complications. Permissive underfeeding, a concept gaining attention recently, offers a more controlled approach by intentionally providing fewer calories than traditionally recommended. This comprehensive review explores the rationale, evidence, and practical considerations surrounding permissive underfeeding in critically ill patients. We discuss the physiological basis of permissive underfeeding, its potential benefits in mitigating the risks of overfeeding, and the challenges associated with implementation in clinical practice. Through an analysis of critical studies and clinical trials, we evaluate the comparative effectiveness of permissive underfeeding versus traditional feeding methods and examine its impact on patient outcomes. Recommendations for patient selection, monitoring, and future research directions are provided to guide clinicians in optimizing nutritional support strategies for critically ill individuals. By considering the role of permissive underfeeding alongside traditional feeding approaches, healthcare professionals can tailor nutritional interventions to individual patient needs, ultimately improving outcomes in the ICU.

Comparison of percutaneous single-stage dilatational tracheostomy and surgical tracheostomy in critically ill patients: A randomized controlled trial.

Background: This study was done to compare single stage percutaneous dilation tracheostomy (PDT) and open surgical tracheostomy (ST) in critically ill patients. Methods: A randomized controlled study was conducted on 60 critically ill patients admitted in the intensive care unit (ICU). The patients were randomized into ST or PDT group with 30 in each group. The duration of procedure and associated perioperative/postoperative complications were noted and compared. Results: A total of 60 critically ill patients were included with 30 each in both groups. Compared to ST, PDT had significantly lesser mean duration of procedure (5 ± 1.64 vs. 21.33 ± 4.77 min, P < 0.0001) and comparable incidence of complications (3.33% vs. 20%, P = 0.103), which included 5-10 ml of bleeding (0% vs. 13.33%), cardiac arrest (0% vs. 3.33%), atrial fibrillation (3.33% vs. 0%), and tracheoesophageal fistula (0% vs. 3.33%). Conclusion: PDT performed in the ICU is a quick, safe, and reliable procedure with comparable complications to ST.

COVID-19 with high-sensitivity CRP associated with worse dynamic clinical parameters and outcomes.

Objective: This study aimed to evaluate the relationship between high-sensitivity C-reactive protein (hsCRP) in hospitalized COVID-19 patients and their clinical outcomes, including trajectory of hsCRP changes during hospitalization. Method and results: Patients with positive COVID-19 tests between 2021 and 2023 were admitted to two hospitals. Among 184 adult patients, approximately half (47.3%) had elevated hsCRP levels upon admission, which defined as exceeding the laboratory-specific upper limit of test (> 5.0 mg/L). Clinical outcomes included critical illness, acute kidney injury, thrombotic events, intensive care unit (ICU) requirement, and death during hospitalization. Elevated hsCRP levels had a higher risk of ICU requirement than those with normal, 39.1% versus 16.5%; adjusted odds ratio (aOR), 2.3 [95% CI, 1.05-5.01]; p = 0.036. Patients with extremely high (≥2 times) hsCRP levels had aOR, 2.65 [95% CI, 1.09-6.45]; p < 0.001. On the fifth day hospitalization, patients with high hsCRP levels associated with acute kidney injury (aOR, 4.13 [95% CI, 1.30-13.08]; p = 0.016), ICU requirement (aOR, 2.67 [95%CI, 1.02-6.99]; p = 0.044), or death (aOR, 4.24 [95% CI, 1.38-12.99]; p = 0.011). The likelihood of worse clinical outcomes increased as hsCRP levels rose; patients with elevated hsCRP had lower overall survival rate than those with normal (p = 0.02). The subset of high hsCRP patients with high viral load also had a shorter half-life compared to those with normal hsCRP level (p = 0.003). Conclusion: Elevated hsCRP levels were found to be a significant predictor of ICU requirement, acute kidney injury, or death within 5 days after hospitalization in COVID-19 patients. This emphasized the importance of providing more intensive care management to patients with elevated hsCRP.

Association between the stress hyperglycemia ratio and 28-day all-cause mortality in critically ill patients with sepsis: a retrospective cohort study and predictive model establishment based on machine learning.

BACKGROUND: Sepsis is a severe form of systemic inflammatory response syndrome that is caused by infection. Sepsis is characterized by a marked state of stress, which manifests as nonspecific physiological and metabolic changes in response to the disease. Previous studies have indicated that the stress hyperglycemia ratio (SHR) can serve as a reliable predictor of adverse outcomes in various cardiovascular and cerebrovascular diseases. However, there is limited research on the relationship between the SHR and adverse outcomes in patients with infectious diseases, particularly in critically ill patients with sepsis. Therefore, this study aimed to explore the association between the SHR and adverse outcomes in critically ill patients with sepsis. METHODS: Clinical data from 2312 critically ill patients with sepsis were extracted from the MIMIC-IV (2.2) database. Based on the quartiles of the SHR, the study population was divided into four groups. The primary outcome was 28-day all-cause mortality, and the secondary outcome was in-hospital mortality. The relationship between the SHR and adverse outcomes was explored using restricted cubic splines, Cox proportional hazard regression, and Kaplan‒Meier curves. The predictive ability of the SHR was assessed using the Boruta algorithm, and a prediction model was established using machine learning algorithms. RESULTS: Data from 2312 patients who were diagnosed with sepsis were analyzed. Restricted cubic splines demonstrated a "U-shaped" association between the SHR and survival rate, indicating that an increase in the SHR is related to an increased risk of adverse events. A higher SHR was significantly associated with an increased risk of 28-day mortality and in-hospital mortality in patients with sepsis (HR > 1, P < 0.05) compared to a lower SHR. Boruta feature selection showed that SHR had a higher Z score, and the model built using the rsf algorithm showed the best performance (AUC = 0.8322). CONCLUSION: The SHR exhibited a U-shaped relationship with 28-day all-cause mortality and in-hospital mortality in critically ill patients with sepsis. A high SHR is significantly correlated with an increased risk of adverse events, thus indicating that is a potential predictor of adverse outcomes in patients with sepsis.

Efficacy and safety of enteral supplementation with high-dose vitamin D in critically ill patients with vitamin D deficiency.

BACKGROUND: Vitamin D deficiency is associated with mortality and morbidity in critically ill patients. This study investigated the safety and effectiveness of enteral high-dose vitamin D supplementation in intensive care unit (ICU) patients in Asia. METHODS: This was a multicenter, prospective, randomized-controlled study. Eligible participants with vitamin D deficiency were randomly assigned to the control or vitamin D supplementation group. In the vitamin D supplementation group, the patients received 569,600 IU vitamin D. The primary outcome was the serum 25(OH)D level on day 7. RESULTS: 41 and 20 patients were included in the vitamin D supplementation and control groups, respectively. On day 7, the serum 25(OH)D level was significantly higher in the vitamin D supplementation group compared to the control group (28.5 [IQR: 20.2-52.6] ng/mL and 13.9 [IQR: 11.6-18.8] ng/mL, p < 0.001). Only 41.5% of the patients achieved serum 25(OH)D levels higher than 30 ng/mL in the supplementation group. This increased level was sustained in the supplementation group on both day 14 and day 28. There were no significant adverse effects noted in the supplementation group. Patients who reached a serum 25(OH)D level of >30 ng/mL on day 7 had a significantly lower 30-day mortality rate than did those who did not (5.9% vs 37.5%, p < 0.05). CONCLUSIONS: In our study, less than half of the patients reached adequate vitamin D levels after the enteral administration of high-dose vitamin D. A reduction in 30-day mortality was noted in the patients who achieved adequate vitamin D levels. TRIAL REGISTRATION CLINICALTRIALS. GOV ID: NCT04292873, Registered, March 1, 2020.

Statistical analysis plan for the replacing protein via enteral nutrition in a stepwise approach in critically ill patients (REPLENISH) randomized clinical trial.

BACKGROUND: The optimal amount and timing of protein intake in critically ill patients are unknown. REPLENISH (Replacing Protein via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial evaluates whether supplemental enteral protein added to standard enteral nutrition to achieve a high amount of enteral protein given from ICU day five until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve a moderate amount of enteral protein would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients. METHODS: In this multicenter randomized trial, critically ill patients will be randomized to receive supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition to achieve a high amount of enteral protein (range of 2-2.4 g/kg/day) or no supplemental enteral protein to achieve a moderate amount of enteral protein (0.8-1.2 g/kg/day). The primary outcome is 90-day all-cause mortality; other outcomes include functional and health-related quality-of-life assessments at 90 days. The study sample size of 2502 patients will have 80% power to detect a 5% absolute risk reduction in 90-day mortality from 30 to 25%. Consistent with international guidelines, this statistical analysis plan specifies the methods for evaluating primary and secondary outcomes and subgroups. Applying this statistical analysis plan to the REPLENISH trial will facilitate unbiased analyses of clinical data. CONCLUSION: Ethics approval was obtained from the institutional review board, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia (RC19/414/R). Approvals were also obtained from the institutional review boards of each participating institution. Our findings will be disseminated in an international peer-reviewed journal and presented at relevant conferences and meetings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04475666 . Registered on July 17, 2020.

Urea to creatinine ratio as a predictor of persistent critical illness.

INTRODUCTION: Persistent critical illness (PCI) is a syndrome in which the acute presenting problem has been stabilized, but the patient's clinical state does not allow ICU discharge. The burden associated with PCI is substantial. The most obvious marker of PCI is prolonged ICU length of stay (LOS), usually greater than 10 days. Urea to Creatinine ratio (UCr) has been suggested as an early marker of PCI development. METHODS: A single-center retrospective study. Data of patients admitted to a general mixed medical-surgical ICU during Jan 1st 2018 till Dec 31st 2022 was extracted, including demographic data, baseline characteristics, daily urea and creatinine results, renal replacement therapy (RRT) provided, and outcome measures - length of stay, and mortality (ICU, and 90 days). Patients were defined as PCI patients if their LOS was >10 days. We used Fisher exact test or Chi-square to compare PCI and non-PCI patients. The association between UCr with PCI development was assessed by repeated measures linear model. Multivariate Cox regression was used for 1 year mortality assessment. RESULTS: 2098 patients were included in the analysis. Patients who suffered from PCI were older, with higher admission prognostic scores. Their 90-day mortality was significantly higher than non-PCI patients (34.58% vs 12.18%, p < 0.0001). A significant difference in UCr was found only on the first admission day among all patients. This was not found when examining separately surgical, trauma, or transplantation patients. We did not find a difference in UCr in different KDIGO (Kidney Disease Improving Global Outcomes) stages. Elevated UCr and PCI were found to be significantly associated with 1 year mortality. CONCLUSION: In this single center retrospective cohort study, UCr was not found to be associated with PCI development.

Invasive Pulmonary Aspergillosis in Critically Ill Patients with Hantavirus Infection, Austria.

We investigated a cohort of 370 patients in Austria with hantavirus infections (7.8% ICU admission rate) and detected 2 cases (cumulative incidence 7%) of invasive pulmonary aspergillosis; 1 patient died. Hantavirus-associated pulmonary aspergillosis may complicate the course of critically ill patients who have hemorrhagic fever with renal syndrome.

Renin in critically ill patients.

The renin-angiotensin system (RAS) constitutes one of the principal mechanisms to maintain hemodynamic and fluid homeostasis. However, most research until now on RAS primarily focuses on its relationship with hypertension and its role in critically ill hypotensive populations is not well understood. With the approval of angiotensin II (Ang II) in the United States and Europe, following a phase 3 randomized controlled trial showing efficacy in catecholamine-resistant vasodilatory shock, there is growing interest in RAS in critically ill patients. Among the fundamental components of RAS, renin acts as the initial stimulus for the entire system. In the context of hypotension, its release increases in response to low blood pressure sensed by renal baroreceptors and attenuated negative Ang II feedback loop. Thus, elevated renin could reflect disease severity and predict poor outcomes. Studies investigating this hypothesis have validated the prognostic accuracy of renin in various critically ill populations, with several reports indicating its superiority to lactate for mortality prediction. Accordingly, renin reduction has been used to assess the effectiveness of Ang II administration. Furthermore, renin holds potential to identify patients who might benefit from Ang II treatment, potentially paving the way for personalized vasopressor management. Despite these promising data, most available evidence is derived from retrospective analysis and necessitates prospective confirmation. The absence of a rapid, point-of-care and reliable renin assay presents another hurdle to its integration into routine clinical practice. This narrative review aims to describe the current understanding and future directions of renin as a biomarker during resuscitation of critically ill patients.

Evaluation of a Novel Enteral Phosphorus Therapy with Enteral Nutrition during a National Intravenous Sodium Phosphate Shortage.

The purpose of this study was to evaluate the efficacy and safety of intragastric administration of small volumes of sodium enema solution containing phosphorus as phosphorus replacement therapy in critically ill patients with traumatic injuries who required continuous enteral nutrition. Adult patients (>17 years of age) who had a serum phosphorus concentration <3 mg/dL (0.97 mmol/L) were evaluated. Patients with a serum creatinine concentration >1.4 mg/dL (124 µmol/L) were excluded. Patients were given 20 mL of saline enema solution intragastrically, containing 34 mmol of phosphorus and mixed in 240 mL water. A total of 55% and 73% of patients who received one (n = 22) or two doses (n = 11) had an improvement in the serum phosphorus concentration, respectively. The serum phosphorus concentration increased from 2.5 [2.1, 2.8] mg/dL (0.81 [0.69, 0.90] mmol/L) to 2.9 [2.2, 3.0] mg/dL (0.94 [0.71, 0.97 mmol/L) for those who received two doses (p = 0.222). Excluding two patients with a marked decline in serum phosphorus by 1.3 mg/dL (0.32 mmol/L) resulted in an increase in the serum phosphorus concentration from 2.3 [2.0, 2.8] mg/dL (0.74 [0.65, 0.90] mmol/L) to 2.9 [2.5, 3.2] mg/dL (0.94 [0.81, 1.03] mmol/L; n = 9; p = 0.012). No significant adverse effects were noted. Our data indicated that intragastric phosphate administration using a small volume of saline enema solution improved the serum phosphorus concentrations in most patients.

Metabolomics Characterization of Disease Markers in Diabetes and Its Associated Pathologies.

With the change in lifestyle of people, there has been a considerable increase in diabetes, which brings with it certain follow-up pathological conditions, which lead to a substantial medical burden. Identifying biomarkers that aid in screening, diagnosis, and prognosis of diabetes and its associated pathologies would help better patient management and facilitate a personalized treatment approach for prevention and treatment. With the advancement in techniques and technologies, metabolomics has emerged as an omics approach capable of large-scale high throughput data analysis and identifying and quantifying metabolites that provide an insight into the underlying mechanism of the disease and its progression. Diabetes and metabolomics keywords were searched in correspondence with the assigned keywords, including kidney, cardiovascular diseases and critical illness from PubMed and Scopus, from its inception to Dec 2023. The relevant studies from this search were extracted and included in the study. This review is focused on the biomarkers identified in diabetes, diabetic kidney disease, diabetes-related development of CVD, and its role in critical illness.

Pathogenesis and therapeutic opportunities of gut microbiome dysbiosis in critical illness.

For many years, it has been hypothesized that pathological changes to the gut microbiome in critical illness is a driver of infections, organ dysfunction, and other adverse outcomes in the intensive care unit (ICU). The advent of contemporary microbiome methodologies and multi-omics tools have allowed researchers to test this hypothesis by dissecting host-microbe interactions in the gut to better define its contribution to critical illness pathogenesis. Observational studies of patients in ICUs have revealed that gut microbial communities are profoundly altered in critical illness, characterized by markedly reduced alpha diversity, loss of commensal taxa, and expansion of potential pathogens. These key features of ICU gut dysbiosis have been associated with adverse outcomes including life-threatening hospital-acquired (nosocomial) infections. Current research strives to define cellular and molecular mechanisms connecting gut dysbiosis with infections and other outcomes, and to identify opportunities for therapeutic modulation of host-microbe interactions. This review synthesizes evidence from studies of critically ill patients that have informed our understanding of intestinal dysbiosis in the ICU, mechanisms linking dysbiosis to infections and other adverse outcomes, as well as clinical trials of microbiota-modifying therapies. Additionally, we discuss novel avenues for precision microbial therapeutics to combat nosocomial infections and other life-threatening complications of critical illness.

Nutrition in the intensive care unit: from the acute phase to beyond.

Recent randomized controlled trials (RCTs) have shown no benefit but  dose-dependent harm by early full nutritional support in critically ill patients. Lack of benefit may be explained by anabolic resistance, suppression of cellular repair processes, and aggravation of hyperglycemia and insulin needs. Also early high amino acid doses did not provide benefit, but instead associated with harm in patients with organ dysfunctions. However, most studies focused on nutritional interventions initiated during the first days after intensive care unit admission. Although the intervention window of some RCTs extended into the post-acute phase of critical illness, no large RCTs studied nutritional interventions initiated beyond the first week. Hence, clear evidence-based guidance on when and how to initiate and advance nutrition is lacking. Prolonged underfeeding will come at a price as there is no validated metabolic monitor that indicates readiness for medical nutrition therapy, and an adequate response to nutrition, which likely varies between patients. Also micronutrient status cannot be assessed reliably, as inflammation can cause redistribution, so that plasma micronutrient concentrations are not necessarily reflective of total body stores. Moreover, high doses of individual micronutrients have not proven beneficial. Accordingly, current evidence provides clear guidance on which nutritional strategies to avoid, but the ideal nutritional regimen for individual patients remains unclear. In this narrative review, we summarize the findings of recent studies, discuss possible mechanisms explaining the results, point out pitfalls in interpretation of RCTs and their effect on clinical practice, and formulate suggestions for future research.

Persistent Inflammation, Immunosuppression, and Catabolism Syndrome in Pediatric Populations: A Brief Perspective.

Surviving near-lethal insults, such as sepsis, trauma, and major surgery is more common due to advances in medical care. The decline in mortality has unmasked a population of chronic critically ill patients, many with the pathological immunophenotype known as Persistent inflammation, Immunosuppression, and Catabolism Syndrome (PICS). Though initially described in adults, many critically ill children exhibit the hallmarks of PICS, including lymphopenia, hyperinflammation, and evidence of ongoing somatic protein catabolism. These patients are plagued with recurrent infections and suffer worse outcomes. There remains a need to understand the pathophysiology underlying this condition to elucidate potential therapies and develop interventions. This perspective provides the most current update of PICS within the pediatric population.

Severe mold fungal infections in critically ill patients with COVID-19.

The SARS-CoV-2 pandemic put an unprecedented strain on modern societies and healthcare systems. A significantly higher incidence of invasive fungal co-infections was noted compared with the pre-COVID-19 era, adding new diagnostic and therapeutic challenges in the critical care setting. In the current narrative review, we focus on invasive mold infections caused by Aspergillus and Mucor species in critically ill COVID-19 patients. We discuss up-to-date information on the incidence, pathogenesis, diagnosis and treatment of these mold-COVID-19 co-infections, as well as recommendations on preventive and prophylactic interventions. Traditional risk factors were often not recognized in COVID-19-associated aspergillosis and mucormycosis, highlighting the role of other determinant risk factors. The associated patient outcomes were worse compared with COVID-19 patients without mold co-infection.