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Search Results (3,022)

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22 pages, 772 KB  
Review
Phase-Specific Nutritional Therapy in Critical Illness: When Protein May Help and When It May Harm, from Acute Metabolic Adaptation to Post-ICU Recovery
by Mircea Stoian, Adina Stoian, Claudia Bănescu, Sergio Rares Bandilă, Alina Danilesco, Hajnal Finta and Leonard Azamfirei
Nutrients 2026, 18(17), 2840; https://doi.org/10.3390/nu18172840 (registering DOI) - 29 Aug 2026
Abstract
Background: Nutritional support in critically ill patients remains one of the most debated aspects of intensive care medicine. Although international guidelines have long recomm.ended early nutritional support with progressive protein delivery, recent clinical evidence has questioned the benefit of aggressive early calorie and [...] Read more.
Background: Nutritional support in critically ill patients remains one of the most debated aspects of intensive care medicine. Although international guidelines have long recomm.ended early nutritional support with progressive protein delivery, recent clinical evidence has questioned the benefit of aggressive early calorie and protein provision during the acute phase of critical illness, highlighting the need for phase-adapted nutritional strategies. Methods: This narrative review summarizes current evidence on individualized, phase-adapted nutritional therapy in critically ill adults and post-ICU survivors, focusing on protein dose and timing, anabolic resistance, muscle wasting, and nutritional management during recovery. Relevant studies published between January 2011 and June 2026 were identified through structured searches of PubMed/MEDLINE, supplemented by reference screening and forward citation tracking. A total of 59 publications were included in the final narrative synthesis. Results: Recent clinical trials indicate that early high-dose protein administration does not consistently improve survival or functional outcomes and may be associated with harm in selected patient subgroups, particularly those with acute kidney injury, severe organ dysfunction, or shock. More conservative early calorie and protein delivery during the early acute phase has been associated with improved gastrointestinal tolerance and faster clinical stabilization without increasing mortality. Complementary mechanistic evidence supports these findings, highlighting persistent endogenous energy production, anabolic resistance, impaired protein utilization, and reduced autophagy during early critical illness. In contrast, the post-ICU recovery phase is characterized by ongoing muscle wasting, weakness, reduced oral intake, and persistent nutritional deficits, while structured nutritional support after ICU discharge remains inconsistently implemented. Conclusions: Current evidence increasingly supports an individualized, phase-adapted approach to nutritional therapy rather than uniform early aggressive calorie and protein targets. Nutritional strategies should consider illness severity, metabolic phase, organ dysfunction, gastrointestinal tolerance, and recovery trajectory. Further studies are needed to define optimal nutritional targets during post-ICU recovery. An evidence-informed practical framework for phase-adapted nutritional therapy is proposed. Full article
(This article belongs to the Section Clinical Nutrition)
32 pages, 2226 KB  
Review
Personalizing Peri-Intubation Oxygenation in Patients at Risk of Acute Hypoxemic Respiratory Failure: A Phenotype-Driven Narrative Review of High-Flow Nasal Oxygen and Non-Invasive Ventilation
by Daniele Salvatore Paternò, Luigi La Via, Rossella Moltisanti, Antonio Putaggio, Angela Maria Piccolo, Giorgia Maria Noce, Roberta Scuto, Gilberto Duarte-Medrano, Natalia Nuño-Lámbarri, Emilia Concetta Lo Giudice and Massimiliano Sorbello
J. Pers. Med. 2026, 16(9), 455; https://doi.org/10.3390/jpm16090455 (registering DOI) - 29 Aug 2026
Abstract
Tracheal intubation in patients at risk of acute hypoxemic respiratory failure (AHRF) carries a high risk of life-threatening desaturation, and the choice of peri-intubation oxygenation strategy critically influences patient safety. This narrative review synthesizes current evidence on non-invasive oxygenation techniques—high-flow nasal oxygen (HFNO), [...] Read more.
Tracheal intubation in patients at risk of acute hypoxemic respiratory failure (AHRF) carries a high risk of life-threatening desaturation, and the choice of peri-intubation oxygenation strategy critically influences patient safety. This narrative review synthesizes current evidence on non-invasive oxygenation techniques—high-flow nasal oxygen (HFNO), non-invasive ventilation (NIV), and their combination—across the pre-oxygenation, apneic, and awake-intubation phases of airway management. We examine the physiological mechanisms underlying each modality, appraise landmark randomized trials and meta-analyses (including PREOXI, OPTINIV, and OPTIMASK), and address disease-specific considerations in chronic obstructive pulmonary disease, heart failure, interstitial lung disease, severe obesity, obstructive sleep apnea, and obstetric, pediatric, and trauma populations. The evidence supports a phenotype-driven hierarchy rather than a single dominant technique: NIV—optionally combined with HFNO for apneic oxygenation—is preferred in severely hypoxemic critically ill patients, whereas HFNO alone is adequate for many moderately hypoxemic or non-hypoxemic patients. Progressive hypercapnia limits apneic oxygenation, particularly in chronic CO2 retainers, underscoring the value of continuous CO2 monitoring. Persistent under-implementation of NIV-based pre-oxygenation reveals a gap between evidence and practice. Individualized, physiology-guided oxygenation—aligned with the goals of personalized peri-procedural medicine—offers the greatest potential to reduce peri-intubation morbidity. Full article
(This article belongs to the Section Personalized Medical Care)
13 pages, 1002 KB  
Article
ICU-Acquired Weakness: Diagnostic Yield of a Clinical Diagnosis with Additional Quantification of Myosin Loss in Adult Critically Ill Patients
by Wouter Adema, Matthias Thomas Exl, Yvette Hedström, Lars Larsson, Joerg C. Schefold and Werner J. Z’Graggen
J. Clin. Med. 2026, 15(17), 6698; https://doi.org/10.3390/jcm15176698 (registering DOI) - 29 Aug 2026
Abstract
Background/Objectives: Intensive care unit acquired weakness (ICUAW) is common in critically ill patients. However, ICUAW is an umbrella term for multiple neuromuscular pathologies, including critical illness myopathy (CIM). This study aimed to evaluate the diagnostic yield of the clinical diagnosis of ICUAW compared [...] Read more.
Background/Objectives: Intensive care unit acquired weakness (ICUAW) is common in critically ill patients. However, ICUAW is an umbrella term for multiple neuromuscular pathologies, including critical illness myopathy (CIM). This study aimed to evaluate the diagnostic yield of the clinical diagnosis of ICUAW compared with that of preferential myosin loss, i.e., the hallmark of CIM. Methods: Critically ill patients were enrolled within 24 h of intubation. Primary outcome was the frequency of ICUAW on day 10 after ICU admission, defined by a Medical Research Council (MRC) sum score of <48. Secondary outcomes were the myosin-to-actin (M:A) ratio, strength progression and six month mortality. Results: A total of 46 out of 63 patients (73%) were diagnosed with ICUAW. Myosin loss correlated with muscle weakness and longer duration of mechanical ventilation. Overall, 29% had an M:A ratio ≤ 1.5 and 51% ≤ 1.7. In total, 58% of patients with an M:A ratio > 1.5 at day 10 reached the MRC sum score threshold at day 17 compared to 21% with an M:A ratio ≤ 1.5. Patients with ICUAW had a higher six-month mortality rate (24%) than patients without (0%). Conclusions: Absence of ICUAW at day 10 after ICU admission was related with a favourable outcome. Myosin loss with an M:A ratio ≤ 1.5 was associated with a slower recovery of muscle function. Full article
(This article belongs to the Section Intensive Care)
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15 pages, 508 KB  
Article
Chronic Venous Disease and In-Hospital Venous Thromboembolism in Critically Ill Patients: A Retrospective Cohort Study of the MIMIC-IV Database
by Alperen Kutay Yıldırım and Mesher Ensarioğlu
J. Clin. Med. 2026, 15(17), 6695; https://doi.org/10.3390/jcm15176695 (registering DOI) - 28 Aug 2026
Abstract
Background: Chronic venous disease (CVD), and varicose veins in particular, has been reported as a risk factor for venous thromboembolism (VTE) in ambulatory and surgical populations, but its independent contribution to VTE risk in critically ill patients has not been studied. Methods: A [...] Read more.
Background: Chronic venous disease (CVD), and varicose veins in particular, has been reported as a risk factor for venous thromboembolism (VTE) in ambulatory and surgical populations, but its independent contribution to VTE risk in critically ill patients has not been studied. Methods: A retrospective cohort study was performed using the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database, version 3.1. Adult patients with an intensive care unit (ICU) admission and length of stay ≥48 h were eligible. CVD, spanning Clinical-Etiological-Anatomical-Pathophysiological (CEAP) classes C2–C6, was ascertained from ICD-9 and ICD-10 codes using a cross-admission look-back. The primary outcome was in-hospital VTE. Multivariable logistic regression was performed with adjustment for age, sex, severity scores, comorbidities, and ICU treatments; additional analysis was performed with propensity score matching (1:3 nearest-neighbor) and multiple imputation for missing body mass index (BMI). Results: Of 28,741 eligible patients, 544 (1.9%) had documented CVD. Crude VTE incidence was 7.0% in CVD patients vs. 6.2% in those without CVD (unadjusted OR 1.14, 95% CI 0.82–1.59; adjusted OR 1.10, 95% CI 0.77–1.52, p = 0.571). After multiple imputation for BMI, the adjusted association attenuated to 1.03 (0.74–1.45, p = 0.849). Propensity score matching produced consistent results (OR 1.24, 0.84–1.84). In an exploratory severity analysis, crude VTE rates were 6.2% without CVD, 6.4% with uncomplicated CVD, and 16.7% with complicated CVD; the complicated stratum comprised only 30 patients with 5 events (aOR 2.90, 95% CI 1.09–7.08, p = 0.032), and the test for trend was not significant (p = 0.31). CVD patients received less pharmacological prophylaxis than non-CVD patients (61.2% vs. 66.0%, p = 0.023). Conclusions: Chronic venous disease was not independently associated with in-hospital VTE in this critically ill cohort, and the modest crude association attenuated further after accounting for BMI. An exploratory analysis suggested a higher risk in complicated CVD, but the stratum was too small and the trend test too weak to support a severity gradient; this requires confirmation in cohorts with prospective CEAP classification. CVD patients received less thromboprophylaxis than patients without CVD (61.2% vs. 66.0%, p = 0.023), although this difference did not persist after adjustment (aOR 0.88, 95% CI 0.74–1.06, p = 0.172). Full article
(This article belongs to the Section Intensive Care)
15 pages, 481 KB  
Systematic Review
Early Versus Late Tracheostomy: An Umbrella Review and Meta-Analysis
by Sven Mostberger, Marija Glisic, Magda R. Gamba, Claudio Perret and Gabi Mueller
J. Clin. Med. 2026, 15(17), 6685; https://doi.org/10.3390/jcm15176685 (registering DOI) - 28 Aug 2026
Abstract
Background: Optimal tracheostomy timing remains controversial due to conflicting evidence across published systematic reviews. To clarify this ambiguity within specific patient populations (critically ill, traumatic brain injury, stroke, trauma, COVID-19, and spinal cord injury), an umbrella review of systematic reviews was conducted comparing [...] Read more.
Background: Optimal tracheostomy timing remains controversial due to conflicting evidence across published systematic reviews. To clarify this ambiguity within specific patient populations (critically ill, traumatic brain injury, stroke, trauma, COVID-19, and spinal cord injury), an umbrella review of systematic reviews was conducted comparing early versus late tracheostomy or prolonged intubation. Additionally, potential benefits in clinical outcomes were evaluated across a mixed-etiology cohort of mechanically ventilated patients. Methods: MEDLINE, Embase, Cochrane Library, and Web of Science were searched from inception through July 2024. Systematic reviews evaluating the impact of tracheostomy timing on mechanical ventilation duration, ventilator-associated pneumonia risk, ICU/hospital length of stay, and mortality were included. Two authors independently extracted data using a standardized form. Methodological quality was assessed via AMSTAR 2 and certainty of evidence via GRADE. Random-effects meta-analyses were conducted for each outcome, stratified by study design (RCTs vs. non-RCTs), with subgroup analyses exploring patient subpopulations. Results: Evidence was synthesized from 9 systematic reviews (24 unique RCTs, 54 non-RCTs). In RCTs, moderate certainty evidence suggests that early tracheostomy reduces ventilator-associated pneumonia (OR 0.66, 95% CI 0.46 to 0.94, p = 0.02) and mechanical ventilation duration (MD −3.76 days, 95% CI −6.01 to −1.52, p < 0.001) compared to late tracheostomy or prolonged intubation. Early tracheostomy may reduce ICU length of stay (MD −6.64 days, 95% CI −9.92 to −3.35, p < 0.001, low certainty). The effect of early tracheostomy on hospital length of stay and mortality remains uncertain. Conclusions: Early tracheostomy shows potential to reduce ventilator-associated pneumonia and mechanical ventilation duration in mixed-etiology cohorts. It may also be associated with shorter ICU length of stay, while its effect on mortality and hospital stay remains uncertain. Future research should establish standardized definitions of tracheostomy timing and prioritize high-quality, etiology-specific RCTs in underrepresented cohorts (e.g., traumatic brain injury, stroke, spinal cord injury). Full article
(This article belongs to the Section Respiratory Medicine)
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24 pages, 4583 KB  
Article
Microwave Radar Sensing for Non-Invasive Intra-Abdominal Pressure Monitoring: A Simulation-Based Analysis with Phantom Testing
by Salar Tayebi, Ashkan Zarghami, Cheng Chen, Wojciech Dabrowski, Manu L. N. G. Malbrain and Johan Stiens
Sensors 2026, 26(17), 5452; https://doi.org/10.3390/s26175452 (registering DOI) - 28 Aug 2026
Abstract
Background: Intra-abdominal pressure (IAP) has recently been recognized as a new vital sign in critically ill patients. Microwave reflectometry has been proposed as a potential approach for non-invasive IAP measurement. However, systematic investigation on how individual anatomical and geometric factors influence changes in [...] Read more.
Background: Intra-abdominal pressure (IAP) has recently been recognized as a new vital sign in critically ill patients. Microwave reflectometry has been proposed as a potential approach for non-invasive IAP measurement. However, systematic investigation on how individual anatomical and geometric factors influence changes in the microwave reflection response of the abdominal compartment is limited. Complementary information regarding illumination frequency and specific absorption rate (SAR) also warrants consideration. Objective: This study aimed to advance the current knowledge on using microwave radar-based sensors in IAP monitoring by studying the most influencing factors. The penetration depth and spot size versus radiation frequency is studied as well. Information on energy deposition due to radio-frequency exposure is investigated too. Methods: Numerical simulations were performed using abdominal models adjusted to represent different IAP levels. Reflection signal features were analyzed in relation to IAP-induced changes, and SAR was calculated using human models. Subsequently, a radar sensor prototype was tested on a benchtop abdominal phantom. Lin’s concordance correlation analysis was used to evaluate absolute agreement between radar-estimated IAP and reference IAP. Additional statistical analyses assessed bias, precision, concordance, and risk levels. Results: Sagittal abdominal diameter was the dominant factor affecting the microwave reflection response. Reflection amplitude showed a periodic trend consistent with abdominal displacement corresponding to multiples of half-wavelength values of the applied electromagnetic waves. Numerical SAR simulations showed increasing SAR with frequency while remaining below the applicable exposure limits under the investigated conditions. The radar sensor showed a bias of 0.43 mmHg and a precision of 2.55 mmHg. Concordance analysis among the paired changes remaining after application of the predefined exclusion criteria showed agreement in the direction of IAP change. Conclusion: The present study should be considered a preliminary proof of concept. Clinically, the technology is currently more suitable for early warning and trend monitoring than for precise absolute IAP measurement, and it does not yet replace standard intravesical measurements. Its ability to support clinical decision-making, including guiding fluid therapy, requires prospective validation in patients. Full article
(This article belongs to the Section Biomedical Sensors)
17 pages, 470 KB  
Article
Predictive Value of Naples Prognostic Score in Determining the Prognosis of Acute Pancreatitis—A Single-Center Experience
by Fatih Sargin, Zeynep Gok Sargin, Ahmet Caliskan, Ayse Karaduru Avci, Celal Dogan and Ali Avci
J. Clin. Med. 2026, 15(17), 6659; https://doi.org/10.3390/jcm15176659 (registering DOI) - 28 Aug 2026
Abstract
Background/Objectives: The Naples Prognostic Score (NPS) is a composite index of nutritional and inflammatory status that has demonstrated prognostic value across various critical illnesses. This study aimed to evaluate the prognostic significance of NPS in patients with acute pancreatitis (AP). Methods: In this [...] Read more.
Background/Objectives: The Naples Prognostic Score (NPS) is a composite index of nutritional and inflammatory status that has demonstrated prognostic value across various critical illnesses. This study aimed to evaluate the prognostic significance of NPS in patients with acute pancreatitis (AP). Methods: In this retrospective cohort study, 452 patients diagnosed with AP between January 2024 and March 2026 were classified as mild (MAP), moderately severe (MSAP), or severe (SAP) according to the revised Atlanta classification. NPS was calculated from admission serum albumin, total cholesterol, neutrophil-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio. Results: Of the 452 patients, 276 (61.1%) had MAP, 124 (27.4%) had MSAP, and 52 (11.5%) had SAP. NPS was significantly higher in SAP patients than in MAP and MSAP patients (for both comparisons; p < 0.001). ROC analysis showed an AUC of 0.758 (95% CI: 0.693–0.824) for predicting SAP, with an optimal cut-off of NPS ≥ 3 yielding a sensitivity of 80.8% and a specificity of 61.3%. Patients were stratified into low (0–2) and high (3–4) NPS groups. High NPS was significantly associated with SAP (χ2 = 33.044, p < 0.001), with a negative predictive value of 96.1%. In multivariable analysis, high NPS was an independent predictor of SAP (OR: 4.346, 95% CI: 2.018–9.362; p < 0.001). Conclusions: NPS, calculated from four routine laboratory parameters available at admission, is a simple, rapid, and independent predictor of disease severity in AP and may support early risk stratification in the emergency setting. Full article
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26 pages, 2890 KB  
Systematic Review
Colistin Resistance in Critically Ill Adults: A Systematic Review of Epidemiological, Clinical, Laboratory, and Molecular Evidence
by Eugen Mihail Arnautu, Elena Leocadia Plesea, Ovidiu Mircea Zlatian, Georgiana Cristiana Camen, Radu Razvan Mititelu, Andrei Osman, Maria-Loredana Tieranu, Andreea Loredana Golli and Alice Elena Ghenea
Microorganisms 2026, 14(9), 1908; https://doi.org/10.3390/microorganisms14091908 - 28 Aug 2026
Abstract
Colistin resistance is an increasing concern in critically ill adults, but reported rates, clinical consequences, laboratory detection, and resistance mechanisms vary widely between studies. This systematic review evaluated epidemiological, clinical, laboratory, and molecular evidence on colistin resistance in adult intensive care populations. MEDLINE/PubMed, [...] Read more.
Colistin resistance is an increasing concern in critically ill adults, but reported rates, clinical consequences, laboratory detection, and resistance mechanisms vary widely between studies. This systematic review evaluated epidemiological, clinical, laboratory, and molecular evidence on colistin resistance in adult intensive care populations. MEDLINE/PubMed, the Cochrane Library, Scopus, and Web of Science Core Collection were searched, and the findings were synthesised descriptively because of substantial differences between studies. A total of 120 studies were included. In studies using BMD in broader ICU populations, colistin non-susceptibility ranged from approximately 0.3–57.4% at the isolate level, while patient-level carriage/acquisition estimates ranged from approximately 1.2% to 9.4%. Clinical studies often reported poorer outcomes in patients with colistin-resistant infections. However, the strength and direction of these associations were inconsistent, and most comparative analyses had substantial risk of bias. Laboratory methods influenced resistance detection, while heteroresistance required specific testing approaches. Molecular studies identified several resistance pathways, including mcr genes, mgrB disruption, regulatory alterations, clonal spread, and within-host evolution. Overall, colistin resistance in critical care is highly heterogeneous and should be interpreted according to the clinical, microbiological, and epidemiological context. Full article
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10 pages, 225 KB  
Article
Prognostic Value of APACHE II and RTS in Predicting ICU Mortality Among Multitrauma Patients: A Single-Center Study from Turkey
by Ahmet Düzgün, Maşallah Çakırer and Seher Yanatma
J. Clin. Med. 2026, 15(17), 6650; https://doi.org/10.3390/jcm15176650 - 28 Aug 2026
Abstract
Background/Objectives: Trauma remains a leading global cause of mortality and morbidity, particularly in low- and middle-income countries. Multitrauma patients often require intensive care and exhibit high mortality rates. Prognostic scoring systems such as the Acute Physiology and Chronic Health Evaluation II (APACHE [...] Read more.
Background/Objectives: Trauma remains a leading global cause of mortality and morbidity, particularly in low- and middle-income countries. Multitrauma patients often require intensive care and exhibit high mortality rates. Prognostic scoring systems such as the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Revised Trauma Score (RTS) are widely used to predict outcomes; however, their performance in middle-income settings like Turkey has not been well established. This study aimed to evaluate the prognostic accuracy of APACHE II and RTS in predicting intensive care unit (ICU) mortality among multitrauma patients. Methods: This retrospective observational study was conducted in the General ICU of Diyarbakır Gazi Yaşargil Training and Research Hospital between January 2022 and December 2024. Adult patients (≥18 years) with multitrauma involving at least two anatomical regions were included. Demographic data, clinical scores (APACHE II, RTS, Sequential Organ Failure Assessment [SOFA], Injury Severity Score [ISS], Trauma and Injury Severity Score [TRISS]), laboratory parameters, complications, and outcomes were recorded. Univariate and multivariate logistic regression analyses identified independent predictors of ICU mortality. Receiver operating characteristic (ROC) analysis assessed the discriminatory ability of prognostic scores. Results: A total of 145 patients were analyzed, with an ICU mortality rate of 13.1%. Non-survivors had significantly higher APACHE II (27 ± 4 vs. 13 ± 6, p < 0.001) and SOFA scores (7 [4–13] vs. 2 [1–6], p < 0.001) and lower RTS (4.2 ± 1.7 vs. 7.2 ± 1.1, p < 0.001). Acute kidney injury, sepsis, septic shock, and mechanical ventilation were more frequent among non-survivors (p < 0.01 for all). In multivariate analysis, APACHE II (odds ratio [OR]= 1.54, 95% confidence interval [CI] 1.16–2.04, p = 0.003) and RTS (OR = 0.36, 95% CI 0.16–0.81, p = 0.013) were independent predictors of ICU mortality. ROC analysis showed excellent prognostic performance for APACHE II (area under the curve [AUC] = 0.959) and RTS (AUC = 0.888). Conclusions: In this retrospective single-center cohort, APACHE II and RTS were independently associated with ICU mortality and demonstrated good discriminatory performance for early risk stratification in critically ill multitrauma patients. The lower mortality observed in our cohort should be interpreted cautiously, as it may also reflect differences in case-mix, injury severity, ICU admission practices, and referral patterns. These findings require external validation in larger multicenter cohorts before broader generalization. Future studies should also validate the identified cut-off values and further investigate the prognostic role of biomarkers such as procalcitonin. Full article
(This article belongs to the Section Intensive Care)
22 pages, 1262 KB  
Article
High Frequencies of Senescent and Exhausted Natural Killer Cells and SARS-CoV-2-Specific Memory CD8+ T Cells Distinguish Critically Ill from Asymptomatic Unvaccinated COVID-19 Patients
by Ruchi Srivastava, Swayam Prakash, Sweta Karan and Lbachir BenMohamed
Viruses 2026, 18(9), 940; https://doi.org/10.3390/v18090940 (registering DOI) - 28 Aug 2026
Abstract
COVID-19 disease severity in unvaccinated individuals spans a striking continuum from complete absence of symptoms to life-threatening critical illness, yet the immunological determinants driving this divergence remain poorly understood. While Natural Killer (NK) cells and CD4+/CD8+ T cells mount distinct [...] Read more.
COVID-19 disease severity in unvaccinated individuals spans a striking continuum from complete absence of symptoms to life-threatening critical illness, yet the immunological determinants driving this divergence remain poorly understood. While Natural Killer (NK) cells and CD4+/CD8+ T cells mount distinct responses against SARS-CoV-2, the phenotypic and functional signatures distinguishing protective immunity from pathogenic immune dysfunction have yet to be defined. In the present study, we present a comparative analysis of NK cell and SARS-CoV-2-specific T cell immunity in unvaccinated symptomatic (SYMP) versus asymptomatic (ASYMP) COVID-19 patients. Using multicolor flow cytometry, we interrogated key immune checkpoints, the senescence marker CD57, differentiation status (CD45RA/CCR7), exhaustion marker PD-1, and activation markers HLA-DR and CD38, across NK and T cell subsets from SYMP patients, ASYMP patients, and Healthy Donors (HD). SYMP COVID-19 patients harbor significantly elevated co-expression of exhaustion and senescence markers on both NK and T cells relative to ASYMP patients and HD controls. Within the T cell compartment, SYMP patients exhibit broad dysregulation across naïve, central memory, effector memory, and terminally differentiated effector memory subsets, with CD57 enriched most prominently on CD8+ TEM and CD8+ TEMRA populations. While cytokine profiles did not significantly differ between ASYMP and SYMP patients, both groups showed markedly elevated pro-inflammatory TNF-α, IFN-γ, IL-6, IL-8, and IL-17 compared to HD controls, underscoring systemic immune activation as a hallmark of SARS-CoV-2 infection regardless of clinical severity. Taken together, these findings suggest that NK and T cell exhaustion and senescence are correlates of severe COVID-19, highlighting potential targets for future mechanistic and therapeutic investigation. Full article
(This article belongs to the Special Issue Coronaviruses Pathogenesis, Immunity, and Antivirals (2nd Edition))
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13 pages, 500 KB  
Article
Late-Course Lactate/Albumin Ratio and In-Hospital Mortality in CRRT-Treated Critically Ill Patients: A Retrospective Severity-Adjusted Analysis
by Hasan Şenay, Mehmet Kürşad Orhan, Mahmut Sami Tutar, Munise Yıldız, Ece Ünüvar Şenay, Muhammed Halit Satıcı, Ahmet Erarkadaş and Betul Kozanhan
J. Clin. Med. 2026, 15(17), 6625; https://doi.org/10.3390/jcm15176625 - 27 Aug 2026
Abstract
Background/Objectives: The lactate/albumin ratio (LAR) integrates tissue hypoperfusion and nutritional reserve into a single dimensionless index. As a late-course measurement (last available value before the primary outcome), it may reflect terminal metabolic deterioration rather than early prognostic signal. We examined the association of [...] Read more.
Background/Objectives: The lactate/albumin ratio (LAR) integrates tissue hypoperfusion and nutritional reserve into a single dimensionless index. As a late-course measurement (last available value before the primary outcome), it may reflect terminal metabolic deterioration rather than early prognostic signal. We examined the association of the final LAR with in-hospital mortality after adjustment for validated severity scores (APACHE II, SOFA) in critically ill patients receiving CRRT, and evaluated its incremental value beyond lactate alone. Methods: A single-centre retrospective observational study was conducted, including 110 adult patients treated with CRRT/CVVHDF at Konya City Hospital (January 2024–January 2026). Multivariable logistic regression was performed across four hierarchically adjusted models. APACHE II was designated the primary adjustment covariate. ROC analyses compared the final LAR with final lactate and albumin alone. Results: In-hospital mortality was 70.9% (78/110); complete paired final lactate and albumin values were available for 109/110 patients (78 non-survivors, 31 survivors). After APACHE II adjustment, each 0.1-unit increase in the late-course LAR remained significantly associated with in-hospital mortality (OR 1.70; 95% CI 1.16–2.49; p = 0.007), a finding replicated in the ICU-stay sensitivity cohort (n = 100, 73 events; OR 1.63; 95% CI 1.09–2.42; p = 0.016). The LAR trajectory (ΔLAR; AUC 0.725) was significantly greater in non-survivors (+0.104 vs. −0.060; p < 0.001); however, ΔLAR did not significantly outperform the lactate trajectory alone (Δlactate; AUC 0.706; p = 0.212), and lost statistical significance after severity-score adjustment. Furthermore, the association was attenuated and non-significant after SOFA adjustment (OR 1.35; p = 0.077), and the final LAR did not provide statistically significant discriminative advantage over lactate alone (AUC 0.768 vs. 0.761; LRT p = 0.435). Conclusions: The late-course LAR remained significantly associated with mortality after APACHE II adjustment. Three qualifications temper this finding: the association was attenuated after SOFA adjustment, the final LAR did not outperform lactate alone, and the measurement design is susceptible to reverse causality. The LAR trajectory (ΔLAR; AUC 0.725) showed comparable discrimination to the final LAR but did not significantly outperform the lactate trajectory alone (Δlactate; AUC 0.706; p = 0.212) and lost statistical significance after severity-score adjustment, so it should likewise be regarded as hypothesis-generating rather than confirmatory; prospective evaluation with time-stamped serial measurements and landmark analyses in multi-centre CRRT cohorts is warranted. Full article
(This article belongs to the Special Issue Anesthesia and Intensive Care: Clinical Practices and Prospects)
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31 pages, 15610 KB  
Article
Single-Cell RNA Sequencing Combined with MEBOCOST Reveals Alveolar Macrophage-Mediated Immunometabolic Communication Mechanisms in Sepsis-Induced Acute Lung Injury
by Lixia Zhao, Xin Liu, Yubang Hu, Yuming Yang, Yue Peng and Youtan Liu
Genes 2026, 17(9), 1019; https://doi.org/10.3390/genes17091019 - 27 Aug 2026
Abstract
Background: Sepsis-induced acute lung injury (SI-ALI) leads to high mortality in critically ill patients, and no specific targeted treatments are available. Current studies mainly characterize intercellular crosstalk via protein–ligand–receptor frameworks, while metabolite-derived immune signal transmission is largely unclarified. Alveolar macrophages are located at [...] Read more.
Background: Sepsis-induced acute lung injury (SI-ALI) leads to high mortality in critically ill patients, and no specific targeted treatments are available. Current studies mainly characterize intercellular crosstalk via protein–ligand–receptor frameworks, while metabolite-derived immune signal transmission is largely unclarified. Alveolar macrophages are located at the alveolar barrier and may act as central metabolic coordinators to trigger neutrophil-mediated lung inflammation, yet the complete metabolite signaling network has not been systematically mapped. Methods: We integrated single-cell and bulk transcriptomic datasets from CLP-induced septic mouse lungs. CellChat and MEBOCOST were jointly used to reconstruct protein–metabolite dual communication networks. LASSO regression and random forest were combined to screen core metabolic hub genes, followed by single-cell expression mapping and in vivo histology & qPCR validation. Results: We identified a pivotal alveolar macrophage–neutrophil immunometabolic axis dominated by iron-Slc40a1 and LTB4-Ltb4r1 signaling. Three hub genes (Pmvk, Slc2a1, Slc7a11) coordinately regulate inflammatory pathways, among which myeloid-enriched Slc7a11 balances cellular redox and paracrine inflammatory responses. Conclusions: This study establishes the first dual-layer cell communication atlas for SI-ALI, proposes a macrophage-centered metabolic inflammatory regulatory model, and highlights Slc7a11 as a potential therapeutic target for septic lung injury. Full article
(This article belongs to the Section Bioinformatics)
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13 pages, 862 KB  
Article
From Triage to Outcome: How ED Parameters and Comorbidities Shape Pediatric Critical Illness Prognosis
by Ian Valencic, Fiorentina Guida, Laura Andreozzi, Ilaria Corsini, Eleonora Battelli, Marcello Lanari and Daniele Zama
Children 2026, 13(9), 1151; https://doi.org/10.3390/children13091151 - 27 Aug 2026
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Abstract
Objective: To describe the characteristics of children presenting with red-code triage to a tertiary Pediatric Emergency Department (PED) and to evaluate the association between variables at PED presentation and hospitalization outcomes. Methods: This retrospective study included patients aged 0–16 years presenting to [...] Read more.
Objective: To describe the characteristics of children presenting with red-code triage to a tertiary Pediatric Emergency Department (PED) and to evaluate the association between variables at PED presentation and hospitalization outcomes. Methods: This retrospective study included patients aged 0–16 years presenting to the PED with highest level of urgency at triage between 2021 and 2025. Demographic, clinical, laboratory, and outcome data were extracted from electronic medical records. Vital signs at presentation were categorized by severity using age-adjusted percentiles and established thresholds. Outcomes included hospital admission, PICU admission, need for advanced vital support (ALS) within 7 days, and hospitalization at 7 days. Univariable and multivariable logistic regression analyses were performed to identify predictors of outcomes. Results: Critically ill pediatric presentations accounted for 0.23% of PED attendances. Chronic comorbidities were present in 56.21%, mainly neuropsychiatric conditions. Seizures (33.99%) and respiratory conditions (25.49%) were the leading causes. Most patients were hospitalized (56.86% in ward, 20.26% in PICU). Invasive ventilation was required in 7.18% of patients and inotropic support in 3.92%. Increasing age was associated with significantly lower odds of both hospital admission (OR: 0.876, 95% CI: 0.783–0.976; p = 0.017) and PICU admission (OR: 0.890, 95% CI: 0.793–0.983; p = 0.031). Conversely, the need for advanced life support in the ED was independently associated with PICU admission (OR: 3.247, 95% CI: 1.345–7.997; p = 0.009). None of the evaluated ED clinical parameters were independently associated with 7-day outcomes. Conclusions: Our cohort demonstrates a high prevalence of chronic comorbidities, confirming their growing relevance in hospital resource allocation. Life-saving interventions were rarely required, underscoring the need for strategies to maintain medical competencies. Younger age was associated with an increased risk of hospitalization. Monitoring of clinical parameters in the ED, although a useful complementary measure, cannot replace a comprehensive medical assessment of the underlying condition. Full article
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19 pages, 1645 KB  
Article
A Pilot Study on the Evaluation of an Inpatient Glycaemic Management Protocol for Enteral Feeding in People with Diabetes
by Shayna Xueli Lin, Di Zhang, Khee Ling Choo, Qinghua Tan, Puja Sharda, Nur Kalimallah Khairul Anwar, Xin Yi Hannah Luah, Zongwen Wee, Priscilla Chiam Pei Sze, Angela Koh Fang Yung, Sueziani Bte Zainudin and Ling-Jun Chen
Diseases 2026, 14(9), 312; https://doi.org/10.3390/diseases14090312 - 26 Aug 2026
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Abstract
Aims: International diabetes guidelines recommend inpatient glycaemic management protocols for bolus enteral feeding in people with diabetes to improve clinical outcomes. This study aims to evaluate before and after hospital-wide implementation of an inpatient bolus enteral feeding protocol: (1) the incidence of hyperglycaemia [...] Read more.
Aims: International diabetes guidelines recommend inpatient glycaemic management protocols for bolus enteral feeding in people with diabetes to improve clinical outcomes. This study aims to evaluate before and after hospital-wide implementation of an inpatient bolus enteral feeding protocol: (1) the incidence of hyperglycaemia (>13.9 mmol/L) and hypoglycaemia (<4.0 mmol/L), (2) medication prescribing practices and capillary blood glucose monitoring and (3) health care professionals’ knowledge and confidence levels. Methods: We implemented an inpatient glycaemic management protocol for bolus enteral feeding developed by a multidisciplinary team of diabetes nurse educators and endocrinologists and approved by the institutional medical board in July 2024. This before-and-after quality improvement study was conducted over 3 months across eight inpatient wards. Adult inpatients were consecutively enrolled if they met the inclusion criteria: (1) a documented diagnosis of diabetes mellitus, (2) receiving bolus enteral feeding and (3) treatment with glucose-lowering medication. Patients listed as critically ill were excluded. Nurses working in the pilot wards were also recruited. Before implementing the protocol, diabetes nurse educators trained inpatient nurses on understanding and executing the protocol for administering capillary blood glucose monitoring and medications for patients with diabetes on enteral feeding. Nurses’ pre- and post-knowledge levels and perceived confidence were assessed using a structured questionnaire. Electronic medical records were reviewed to evaluate the incidence rates of hypoglycaemia and hyperglycaemia before and during the 3 months following protocol implementation. We also assessed adherence to protocol-recommended capillary blood glucose monitoring frequencies based on the diabetes medication regimen. Results: A total of 31 patients were observed during the 6-week baseline period and 28 patients following protocol implementation. A total of 192 clinical care episodes were audited, comprising 78 in the pre-intervention phase and 114 in the post-intervention phase. The incidence of hyperglycaemia decreased from 43.6% to 10.5%, while hypoglycaemia decreased from 3.8% to 2.6%. After adjusting for protocol adoption rates, protocol implementation was associated with significantly lower odds of hyperglycaemia (odds ratio [OR] 0.22, 95% CI [0.07, 0.65], p = 0.006). A significant increase in appropriate nursing practices was observed post-intervention (p < 0.001). Adoption of the protocol by nurses decreased the odds of hyperglycaemia by 70% (p = 0.014). Nurses’ knowledge scores improved significantly from baseline to 3 months post-implementation (p < 0.001). Conclusions: Implementation of a standardised inpatient glycaemic management protocol for PWD receiving bolus enteral feeding was associated with reduced rates of hyperglycaemia and hypoglycaemia. Larger-scale studies are warranted to evaluate the effectiveness and sustainability of wider implementation in improving clinical outcomes. Full article
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24 pages, 1673 KB  
Review
Oxford Nanopore Sequencing, a Promising Technology for Precision Diagnostics in Intensive Care Units: A Narrative Review
by Leonard Azamfirei, Dorin Bica, Maier Alexandru Mihai, Balla Beata and Claudia Banescu
Biomedicines 2026, 14(9), 1910; https://doi.org/10.3390/biomedicines14091910 - 26 Aug 2026
Viewed by 189
Abstract
Background: Precision diagnostics are more and more important in intensive care units (ICUs), where rapid identification of infectious agents and antimicrobial resistance determinants is crucial for timely and appropriate treatment. Conventional microbiological methods are frequently limited by long turnaround times and reduced [...] Read more.
Background: Precision diagnostics are more and more important in intensive care units (ICUs), where rapid identification of infectious agents and antimicrobial resistance determinants is crucial for timely and appropriate treatment. Conventional microbiological methods are frequently limited by long turnaround times and reduced sensitivity, which may delay appropriate treatment. Nanopore sequencing allows rapid, direct, and long-read sequencing of DNA/RNA molecules without the need for amplification, avoiding biases introduced by NGS during amplification and library preparation and generating data in real time. Objectives: This narrative review aims to summarize current knowledge of nanopore technology in the ICU, discuss nanopore principles and current clinical applications in intensive care medicine, highlight its advantages and limitations, and explore future perspectives for integrating nanopore-based diagnostics into precision critical care. Methods: A literature search was performed using PubMed and Web of Science. The literature search was conducted with no lower restriction, covering English-language publications. Results: Nanopore sequencing enables real-time, long-read, single-molecule analysis of native nucleic acid molecules, rapid pathogen identification, antimicrobial resistance profiling, metagenomic analysis, and direct sequencing without amplification. Recent studies have proved the clinical utility of nanopore sequencing in critically ill patients with sepsis, bloodstream infections, hospital-acquired pneumonia, ventilator-associated pneumonia, and fungal and viral infections. Its portability, rapid turnaround time, and potential for point-of-care implementation make it particularly attractive for ICU settings. Conclusions: Nanopore sequencing technology represents a promising molecular diagnostic tool, but wider clinical implementation warrants further larger studies with clinical outcome endpoints, standardized bioinformatic pipelines, and clearer validation pathways. Full article
(This article belongs to the Section Nanomedicine and Nanobiology)
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