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8 pages, 465 KiB  
Article
Cytomegalovirus Blood DNAemia in Patients with Severe SARS-CoV-2 Pneumonia
by Jean-Baptiste Mesland, Christine Collienne, Virginie Montiel, Alexis Werion, Philippe Hantson, Xavier Wittebole, Pierre-François Laterre and Ludovic Gerard
Infect. Dis. Rep. 2025, 17(1), 8; https://doi.org/10.3390/idr17010008 (registering DOI) - 26 Jan 2025
Abstract
Introduction: Cytomegalovirus (CMV) DNAemia has been described in critically ill patients, including patients with severe acute respiratory syndrome-coronavirus2 (SARS-CoV-2) infection. Our objective is to evaluate the prevalence and clinical impact of CMV DNAemia among patients undergoing invasive mechanical ventilation (IMV) for severe SARS-CoV-2 [...] Read more.
Introduction: Cytomegalovirus (CMV) DNAemia has been described in critically ill patients, including patients with severe acute respiratory syndrome-coronavirus2 (SARS-CoV-2) infection. Our objective is to evaluate the prevalence and clinical impact of CMV DNAemia among patients undergoing invasive mechanical ventilation (IMV) for severe SARS-CoV-2 infection and to explore the association between CMV DNAemia levels and clinical outcomes. Methods: In this retrospective monocentric study, we included patients admitted in a tertiary ICU for severe COVID-19 and who required IMV. We aimed to compare clinical and demographic variables between patients with and without CMV DNAemia. Univariate and Cox regression analyses were performed to identify factors associated with CMV DNAemia. Results: During the study period, CMV blood DNAemia occurred in 30/135 patients (22%). Patients with CMV blood DNAemia had longer ICU and hospital length of stay, as well as longer duration of IMV, and were more likely to have received dexamethasone. However, there was no significant difference in ICU mortality between patients with and without CMV DNAemia (64.8% vs. 56.7%, p = 0.42). The Cox regression analysis showed that dexamethasone was the only factor independently associated with CMV blood DNAemia (HR 4.23 [1.006–17.792], p = 0.049). Conclusions: In patients with severe SARS-CoV-2 pneumonia requiring IMV, CMV DNAemia is common and associated with prolonged ventilation and increased LOS but not with increased mortality. Full article
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<p>Study cohort flow chart.</p>
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12 pages, 836 KiB  
Article
Colistin Use for the Treatment of Multi-Drug-Resistant Gram-Negative Severe Infections in ICU Patients: A Single-Center Study
by Stanislaw Wojciech Rojek, Iga Wojtowicz, Fabio Silvio Taccone and Wieslawa Duszynska
J. Clin. Med. 2025, 14(3), 797; https://doi.org/10.3390/jcm14030797 (registering DOI) - 25 Jan 2025
Viewed by 361
Abstract
Background: Colistin is increasingly used to treat severe infections caused by multi-drug-resistant (MDR) bacteria, particularly in critically ill patients. Its effectiveness, especially in monotherapy, remains controversial. This study aimed to evaluate the effectiveness and toxicity of colistin therapy in severe MDR infections. Methods: [...] Read more.
Background: Colistin is increasingly used to treat severe infections caused by multi-drug-resistant (MDR) bacteria, particularly in critically ill patients. Its effectiveness, especially in monotherapy, remains controversial. This study aimed to evaluate the effectiveness and toxicity of colistin therapy in severe MDR infections. Methods: This retrospective study included patients treated with colistin (CMS) at the ICU. Patients’ treatments were divided into four subgroups: monotherapy vs. combination therapy, empirical vs. targeted therapy, intravenous vs. intravenous plus inhaled therapy, and standard doses with and without a loading dose. The primary outcome was clinical cure. Secondary outcomes included microbiological eradication, survival rate, and drug-related toxicity, particularly acute kidney injury (AKI). Exclusion criteria included Gram-positive infection, inhaled therapy alone, use of colistin <5 days. Results: A total of 150 patients (mean age 60 ± 18 years, APACHE II score 17 ± 10) were included. The most frequent condition was hospital-acquired pneumonia (n = 140, 93.3%). The most common pathogen was MDR Acinetobacter baumannii (n = 146, 97.3%). In most patients, colistin therapy was targeted (n = 113, 75.3%) and combined with other antibiotics (n = 124, 82.7%). Inhaled CMS was added in 47 (31.3%) patients. Mean duration of therapy was 10 ± 4 days. Clinical cure occurred in 64 (42.7%) patients, microbiological eradication in 20 (13.3%). AKI developed in 65 (53.7%) patients. Inhaled CMS improved the clinical cure rates (57.4% vs. 37.0%, p = 0.003). Conclusions: Intravenous CMS was mainly used for MDR Acinetobacter baumannii-related pneumonia. Clinical cure was observed in 42.7% of patients, but renal toxicity was high. Combining intravenous and inhaled CMS may improve outcomes. Full article
(This article belongs to the Special Issue Severe Infection and Antimicrobial Management in ICU)
11 pages, 635 KiB  
Viewpoint
Reevaluating the Value of (1,3)-β-D-Glucan for the Diagnosis of Intra-Abdominal Candidiasis in Critically Ill Patients: Current Evidence and Future Directions
by Emmanuel Novy, Mathieu Esposito, Anne Debourgogne and Claire Roger
J. Fungi 2025, 11(2), 91; https://doi.org/10.3390/jof11020091 - 24 Jan 2025
Viewed by 288
Abstract
Intra-abdominal candidiasis (IAC) is associated with significant diagnostic and therapeutic challenges in critically ill patients. Traditional fungal cultures are slow, delaying appropriate antifungal treatment. (1,3)-β-D-glucan (BDG), a component of the fungal cell wall, has emerged as a potential biomarker for IAC, but its [...] Read more.
Intra-abdominal candidiasis (IAC) is associated with significant diagnostic and therapeutic challenges in critically ill patients. Traditional fungal cultures are slow, delaying appropriate antifungal treatment. (1,3)-β-D-glucan (BDG), a component of the fungal cell wall, has emerged as a potential biomarker for IAC, but its use in ICU settings is complicated by frequent false-positives results from invasive procedures and underlying conditions. This review examines the diagnostic value of BDG when present in serum and peritoneal fluid. While serum BDG is effective for excluding invasive fungal infections like candidemia, its specificity for IAC remains low in critically ill patients. Recent studies suggest that BDG levels in peritoneal fluid may provide better diagnostic accuracy, distinguishing IAC from bacterial peritonitis with higher specificity. We discuss the advantages, limitations, and practical aspects of BDG testing, emphasizing the potential of peritoneal BDG as a complementary tool. Further research is needed to refine diagnostic thresholds, validate its clinical utility, and establish the role of peritoneal BDG in improving timely, targeted antifungal treatment for IAC. Full article
(This article belongs to the Special Issue Fungal Infections in Non-neutropenic Patients)
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<p>Proposed diagnostic algorithm for intra-abdominal candidiasis based on serum and peritoneal (1,3)-β-D-glucan: A literature-guided approach. Owing to the limited current literature, this algorithm should be interpreted in conjunction with clinical findings and other biomarker results. The serum and peritoneal BDG thresholds are derived from observational studies and have not yet been validated. Serum BDG must be measured postoperatively. Legend: ATF: antifungal; D: day; FA: Fungitell<sup>®</sup> assay, Associates of Cape Cod, Inc. (Falmouth, MA, USA); IAC: intra-abdominal candidiasis; sBDG: serum (1,3)-β-D-glucan; BT: β-glucan test<sup>®</sup>, Fujifilm Wako Chemicals Europe (Neuss, Germany).</p>
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15 pages, 1253 KiB  
Case Report
A One Health Zoonotic Vector Borne Infectious Disease Family Outbreak Investigation
by Edward B. Breitschwerdt, Ricardo G. Maggi, Charlotte O. Moore, Cynthia Robveille, Rosalie Greenberg and Emily Kingston
Pathogens 2025, 14(2), 110; https://doi.org/10.3390/pathogens14020110 - 23 Jan 2025
Viewed by 486
Abstract
This study reinforces the value of a One Health approach to infectious disease outbreak investigations. After the onset of neuropsychiatric symptoms in their son, our investigation focused on a family composed of a mother, father, two daughters, the son, two dogs, and a [...] Read more.
This study reinforces the value of a One Health approach to infectious disease outbreak investigations. After the onset of neuropsychiatric symptoms in their son, our investigation focused on a family composed of a mother, father, two daughters, the son, two dogs, and a rabbit, all with exposures to vectors (fleas and ticks), rescued dogs, and other animals. Between 2020 and 2022, all family members experienced illnesses that included neurological symptoms. Prolonged menorrhagia (130d) in the youngest daughter ultimately resolved following antibiotic administration. One dog was diagnosed with a splenic hematoma and months later spinal histiocytic sarcoma. The father, both daughters, and one dog were seroreactive to multiple Bartonella spp. antigens, whereas the mother and son were not seroreactive. Bartonella quintana DNA was amplified from specimens obtained from all family members. Based upon DNA sequencing, infection with B. quintana was confirmed for the mother and both pet dogs. Bartonella henselae DNA was amplified and sequenced from the youngest daughter, the son, and one dog (co-infected with B. quintana), and from Ctenocephalides felis collected from their pet rabbit. All five family members and one dog were infected with Babesia divergens-like MO-1. Both parents were co-infected with Babesia microti. Droplet digital PCR supported potential infection with a Borrelia species in three family members. This study provided additional case-based evidence supporting the role of stealth Babesia, Bartonella, and Borrelia pathogens as a cause or cofactor in neurological and neuropsychiatric symptoms. We conclude that a One Health investigation approach, particularly for stealth vector borne pathogens such as Babesia, Bartonella, and Borrelia spp., will enhance clinical and epidemiological understanding of these organisms for animal and human health. During outbreak investigations it is critical to document travel and vector exposure histories, symptoms, and pathology in pets and human patients, contact with rescued, wild, or feral animals and perform diagnostic testing that includes family members, pets, and vectors. Full article
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<p>Microbiological testing approach used in this study. <span class="html-italic">Bh</span>: <span class="html-italic">Bartonella henselae</span>; <span class="html-italic">Bvb</span> I or II: <span class="html-italic">Bartonella vinsonii</span> subsp. <span class="html-italic">berkhoffii</span> genotype I or II; <span class="html-italic">Bk</span>: <span class="html-italic">Bartonella koehlerae</span>; <span class="html-italic">Bq</span>: <span class="html-italic">Bartonella quintana</span>.</p>
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<p>Historical timeline for the youngest son who was 10 years old at the time of this investigation in August 2022. His illness and neurological symptoms reportedly predated the onset of neurological symptoms in other family members.</p>
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18 pages, 1212 KiB  
Review
Advancing Nutritional Care Through Bioelectrical Impedance Analysis in Critical Patients
by Ana Maria Dumitriu, Cristian Cobilinschi, Bogdan Dumitriu, Sebastian Vâlcea, Raluca Ungureanu, Angela Popa, Rǎzvan Ene, Radu Țincu, Ioana Marina Grințescu and Liliana Mirea
Nutrients 2025, 17(3), 380; https://doi.org/10.3390/nu17030380 - 21 Jan 2025
Viewed by 621
Abstract
Nutritional support in critically ill patients has been acknowledged as a pillar of ICU care, playing a pivotal role in preserving muscle mass, supporting immune function, and promoting recovery during and after critical illness. Providing effective nutritional support requires adapting it to the [...] Read more.
Nutritional support in critically ill patients has been acknowledged as a pillar of ICU care, playing a pivotal role in preserving muscle mass, supporting immune function, and promoting recovery during and after critical illness. Providing effective nutritional support requires adapting it to the patient’s diagnosis, unique characteristics, and metabolic state to minimize the risks of overfeeding or underfeeding while mitigating muscle loss. This level of care requires a comprehensive nutritional assessment and the establishment of a nutrition-focused protocol. Regular, consistent and detailed nutritional evaluation can influence both therapeutic decisions and clinical interventions, thus ensuring that the specific needs of critically ill patients are met from the acute phase through their entire recovery process. Bioelectrical impedance analysis (BIA) is increasingly recognized as a valuable tool for enhancing nutritional care in critically ill patients. By delivering precise, real-time insights into key aspects of body composition, BIA is thought to provide clinicians with a more comprehensive understanding of the complex physiological changes that occur during critical illness. This narrative review highlights the potential of BIA in offering these precise assessments, facilitating the development of more accurate and personalized nutritional strategies for critically ill patients. If BIA can reliably assess dynamic shifts in hydration and tissue integrity, it holds the promise of further advancing individualized care and optimizing clinical outcomes in this vulnerable population. Full article
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<p>Multicompartment body composition model. FFM: fat-free mass, SLM: soft lean mass, BCM: body cell mass, ICW: intracellular water, ECW: extracellular water, TBW: total body water.</p>
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<p>Low-frequency currents do not penetrate cell membranes and measure extracellular water impedance. High-frequency currents also penetrate wall cells and measured impedance reflects total body water (TBW).</p>
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<p>Impedance components in bioelectrical impedance analysis (BIA): resistance, reactance, and phase angle.</p>
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12 pages, 742 KiB  
Review
Rising Above the Limits of Critical Care ECMO: A Narrative Review
by Pietro Bertini, Alberto Marabotti, Paolo Meani, Fabio Sangalli and Gianluca Paternoster
Medicina 2025, 61(2), 174; https://doi.org/10.3390/medicina61020174 - 21 Jan 2025
Viewed by 880
Abstract
Extracorporeal membrane oxygenation (ECMO), an advanced life support method, was developed to treat severe cardiac and pulmonary failure in critically ill patients. ECMO was previously used to treat ARDS, cardiogenic shock, and after heart or lung transplant. It has since become a versatile [...] Read more.
Extracorporeal membrane oxygenation (ECMO), an advanced life support method, was developed to treat severe cardiac and pulmonary failure in critically ill patients. ECMO was previously used to treat ARDS, cardiogenic shock, and after heart or lung transplant. It has since become a versatile therapeutic and surgical tool. When conventional methods fail, this technique works well for high-risk procedures such as tracheal resections, ventricular tachycardia ablations, and complicated percutaneous coronary interventions. These uses demonstrate ECMO’s ability to oxygenate and stabilize the hemodynamics in challenging clinical circumstances. Clinical studies report survival rates exceeding 60% in ECMO-assisted thoracic surgeries, underscoring its efficacy in these settings. Recent advancements, such as portable ECMO systems and artificial intelligence-driven management tools, have further enhanced the safety and effectiveness of ECMO, enabling its use in diverse clinical environments. However, challenges remain, particularly in patient selection, resource allocation, and addressing ethical dilemmas. The integration of standardized protocols and technological innovations has mitigated complications such as vascular injury and infection, contributing to improved patient outcomes. This review examines ECMO applications and integration into multidisciplinary care, its configurations, and its growing role outside the intensive care unit in elective thoracic and cardiac surgery, trauma, and non-cardiac high-risk procedures. Full article
(This article belongs to the Topic Extracorporeal Membrane Oxygenation (ECMO))
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<p>Typical ECMO cannulation sequence and scenario during ECPR.</p>
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<p>VV ECMO circuit schematics: deoxygenated blood is withdrawn from the venous circulation, oxygenated (Oxy) and pushed via the pump into the right atrium (RA). RV: right ventricle, LA: left atrium, LV: left ventricle.</p>
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<p>VA ECMO circuit schematics: deoxygenated blood is withdrawn from the venous circulation, oxygenated (Oxy) and pushed via the pump into the systemic circulation bypassing the native lungs and heart. RA: right atrium, RV: right ventricle, LA: left atrium, LV: left ventricle.</p>
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12 pages, 866 KiB  
Article
Safety and Outcomes of Percutaneous Dilatational Tracheostomy in Patients with Hematologic Malignancies: A Retrospective Cohort Study
by Asaf Miller, Roee Noy, Omri Simchon, Natalia Gvozdev, Yotam Shkedy and Danny Epstein
J. Clin. Med. 2025, 14(2), 657; https://doi.org/10.3390/jcm14020657 - 20 Jan 2025
Viewed by 481
Abstract
Background/Objectives: Patients with hematologic malignancy (HM) often experience high rates of thrombocytopenia, thrombocytopathy, anemia, leukopenia, and coagulopathy, which can significantly increase the risk of procedural and postoperative complications. This study aimed to evaluate the safety and outcomes of percutaneous dilatational tracheostomy (PDT) [...] Read more.
Background/Objectives: Patients with hematologic malignancy (HM) often experience high rates of thrombocytopenia, thrombocytopathy, anemia, leukopenia, and coagulopathy, which can significantly increase the risk of procedural and postoperative complications. This study aimed to evaluate the safety and outcomes of percutaneous dilatational tracheostomy (PDT) in critically ill patients with HM. Methods: This retrospective cohort study included patients with HM who underwent PDT between 2012 and 2023 at a tertiary academic center. The primary outcome was early (7-day) bleeding complications rate. Secondary outcomes included PDT-related mortality, and mortality at 1 week, 30 days, and 1 year. Analyses were performed using a propensity-matched cohort to ensure balanced comparisons between groups. Results: Of the 1627 patients included in the analysis, 65 (4%) had HM. Patients with HM had a significantly higher Charlson comorbidity index and exhibited significantly higher rates of thrombocytopenia (platelet count < 100,000/mcL) compared to those without HM (8.0 [IQR 5.0–11.3] vs. 5.0 [IQR 2.0–7.0], p < 0.001; and 49.2% vs. 5.0%, p < 0.001, respectively). After propensity score matching, the one-week mortality rate was significantly higher in the HM group (23.4% vs. 4.3%, p = 0.007). However, the rates of intraoperative and bleeding complications as well as one-year mortality rates were similar between the groups. Conclusions: PDT can be safely performed in critically ill patients with HM. However, these patients exhibit high early mortality rates following the procedure. Full article
(This article belongs to the Section Hematology)
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<p>Study flow chart.</p>
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17 pages, 914 KiB  
Review
Unlocking the Potential of RNA Sequencing in COVID-19: Toward Accurate Diagnosis and Personalized Medicine
by Heba M. Saad Eldien, Abdulrahman H. Almaeen, Ahmed Abo El Fath, Ahmed E. Taha, Rehab Ahmed, Hassabelrasoul Elfadil and Helal F. Hetta
Diagnostics 2025, 15(2), 229; https://doi.org/10.3390/diagnostics15020229 - 20 Jan 2025
Viewed by 495
Abstract
COVID-19 has caused widespread morbidity and mortality, with its effects extending to multiple organ systems. Despite known risk factors for severe disease, including advanced age and underlying comorbidities, patient outcomes can vary significantly. This variability complicates efforts to predict disease progression and tailor [...] Read more.
COVID-19 has caused widespread morbidity and mortality, with its effects extending to multiple organ systems. Despite known risk factors for severe disease, including advanced age and underlying comorbidities, patient outcomes can vary significantly. This variability complicates efforts to predict disease progression and tailor treatment strategies. While diagnostic and therapeutic approaches are still under debate, RNA sequencing (RNAseq) has emerged as a promising tool to provide deeper insights into the pathophysiology of COVID-19 and guide personalized treatment. A comprehensive literature review was conducted using PubMed, Scopus, Web of Science, and Google Scholar. We employed Medical Subject Headings (MeSH) terms and relevant keywords to identify studies that explored the role of RNAseq in COVID-19 diagnostics, prognostics, and therapeutics. RNAseq has proven instrumental in identifying molecular biomarkers associated with disease severity in patients with COVID-19. It allows for the differentiation between asymptomatic and symptomatic individuals and sheds light on the immune response mechanisms that contribute to disease progression. In critically ill patients, RNAseq has been crucial for identifying key genes that may predict patient outcomes, guiding therapeutic decisions, and assessing the long-term effects of the virus. Additionally, RNAseq has helped in understanding the persistence of viral RNA after recovery, offering new insights into the management of post-acute sequelae, including long COVID. RNA sequencing significantly improves COVID-19 management, particularly for critically ill patients, by enhancing diagnostic accuracy, personalizing treatment, and predicting therapeutic responses. It refines patient stratification, improving outcomes, and holds promise for targeted interventions in both acute and long COVID. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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<p>Structure of human coronavirus.</p>
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14 pages, 593 KiB  
Article
Assessing the Impact of the Prone Position on Acute Kidney Injury
by Eden Ezra, Itai Hazan, Dana Braiman, Rachel Gaufberg, Jonathan Taylor, Adva Alyagon, Amit Shira Babievb and Lior Fuchs
J. Clin. Med. 2025, 14(2), 631; https://doi.org/10.3390/jcm14020631 - 19 Jan 2025
Viewed by 302
Abstract
Background: Prone positioning is a standard intervention in managing patients with severe acute respiratory distress syndrome (ARDS) and is known to improve oxygenation. However, its effects on other organs, particularly the kidneys, are less well understood. This study aimed to assess the [...] Read more.
Background: Prone positioning is a standard intervention in managing patients with severe acute respiratory distress syndrome (ARDS) and is known to improve oxygenation. However, its effects on other organs, particularly the kidneys, are less well understood. This study aimed to assess the association between prone positioning and the development of acute kidney injury (AKI), specifically in overweight and obese patients. Methods: A retrospective pre–post study was conducted on a cohort of 60 critically ill ARDS patients who were placed in the prone position during hospitalization. The development of AKI was assessed using the Acute Kidney Injury Network (AKIN) criteria, with AKI measured by both creatinine levels (AKINCr) and urine output (AKINUO). Patients were divided into two groups based on body mass index (BMI): overweight/obese (BMI ≥ 25) and non-obese (BMI < 25). Data were collected before and after prone positioning. Results: In overweight/obese patients (n = 39, 57 cases), both the median AKINCr and AKINUO scores increased significantly following prone positioning (from 0 to 1, median p < 0.01, and from 0 to 2, median p < 0.01, respectively). No statistically significant changes in AKIN scores were observed in non-obese patients nor were significant differences found in either group after repositioning to supine. Conclusions: Prone positioning is associated with an increased risk of acute kidney injury in overweight and obese ARDS patients. This may be due to the kidneys’ susceptibility to intra-abdominal hypertension in these patients. Further research is needed to explore optimal proning strategies for overweight and obese populations. Full article
(This article belongs to the Section Intensive Care)
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<p>Flow chart for outcome analysis. A total of 56 patients with acute respiratory distress syndrome (ARDS) who were placed in prone position were included in the first analysis, then grouped by body mass index (BMI) level. ESRD = end-stage renal disease; RRT = renal replacement therapy.</p>
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<p>Average urine output in patients with overweight or obesity before and after prone position. Mean urine output per hour measured 24 h before and after prone position. The lowest urine output among overweight or obese patients was measured six hours post prone position (<span class="html-italic">p</span> &lt; 0.01), then improved gradually. No significant change was observed among non-obese patients; thus, the chart only includes overweight or obese patients.</p>
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13 pages, 3979 KiB  
Article
Vitamin K1 Administration Increases the Level of Circulating Carboxylated Osteocalcin in Critically Ill Patients
by Nadide Aydin, Thomas Kander, Ulf Schött and Sassan Hafizi
Nutrients 2025, 17(2), 348; https://doi.org/10.3390/nu17020348 - 19 Jan 2025
Viewed by 524
Abstract
Background/Objectives: Vitamin K-dependent proteins (VKDPs) all commonly possess specially modified γ-carboxyglutamic acid residues created in a vitamin K-dependent manner. Several liver-derived coagulation factors are well characterised VKDPs. However, much less is known about extrahepatic VKDPs, which are more diverse in their molecular structures [...] Read more.
Background/Objectives: Vitamin K-dependent proteins (VKDPs) all commonly possess specially modified γ-carboxyglutamic acid residues created in a vitamin K-dependent manner. Several liver-derived coagulation factors are well characterised VKDPs. However, much less is known about extrahepatic VKDPs, which are more diverse in their molecular structures and functions, and some of which have been implicated in inflammatory disorders. Vitamin K metabolism was shown to be impaired in critically ill patients, in whom systemic inflammation and sepsis are common features. Therefore, the aim of this study was to investigate the effect of vitamin K administration to these patients on their circulating levels of selected VKDPs. A particular novelty of this study was the measurement of specifically carboxylated forms of these proteins in addition to their overall levels. Methods: Blood samples were taken from 47 patients in the intensive care unit before and approximately 24 h after intravenous vitamin K1 (10 mg) administration, and proteins were analysed by specific immunoassay. Results: Vitamin K1 induced increases in plasma levels of carboxylated osteocalcin and total Gas6 (p = 0.0002 and p = 0.0032, respectively). No changes were detected in levels of carboxylated Gas6 or PIVKA-II (undercarboxylated prothrombin), although the latter positively correlated with undercarboxylated osteocalcin (r = 0.38). Conclusion: Injected vitamin K1 increases the blood levels of two distinct VKDPs in critically ill patients, both of which have been implicated in inflammation regulation, including the increased carboxylation of one of them. Full article
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<p>Detection of total Gas6 (<b>A</b>) and γ-carboxylated Gas6 (Gla-Gas6; (<b>B</b>)) in blood plasma of ICU patients before and after vitamin K injection. Gla-Gas6 was quantified in samples all as appropriately diluted to contain equal concentrations of total Gas6. Total Gas6 is significantly increased by vitamin K. Statistical significance was determined using paired <span class="html-italic">t</span>-test; <span class="html-italic">* p =</span> 0.0318, ns = not significant, for comparisons indicated by lines (n = 43).</p>
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<p>Detection of undercarboxylated osteocalcin (ucOC; (<b>A</b>)) and carboxylated osteocalcin (Gla-OC; (<b>B</b>)) in blood plasma of ICU patients before and after vitamin K injection. Gla-OC is significantly increased after vitamin K injection. Also, the proportion of ucOC within total OC in samples is significantly decreased after vitamin K injection (<b>C</b>). Statistical analysis was determined using paired <span class="html-italic">t</span>-test for ucOC parametric data (n = 43 pairs) and Wilcoxon match-pair test for Gla-OC non-parametric data (n = 47 pairs) for comparisons indicated by lines; * <span class="html-italic">p</span> &lt; 0.05, *** <span class="html-italic">p</span> &lt; 0.001, ns = not significant.</p>
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<p>Detection of PIVKA-II in blood plasma of ICU patients before and after vitamin K injection. Statistical analysis was determined using paired <span class="html-italic">t</span>-test) for comparisons indicated by lines; ns = not significant (n = 47 pairs).</p>
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<p>Correlation analyses were performed between total Gas6, undercarboxylated osteocalcin (ucOC), carboxylated osteocalcin (Gla-OC) and PIVKA-II. The coefficient of determination (r) and statistical significance (<span class="html-italic">p</span>-value) were determined by Pearson correlation analysis, except for Gla-OC data, which were not normally distributed and hence Spearman correlation was applied. N = number of XY pairs representing both ‘before’ and ‘after’ samples from patients. Total Gas6 vs. ucOC (n = 86); total Gas6 vs. Gla-OC (n = 94); total Gas6 vs. PIVKA-II (n = 94); PIVKA-II vs. ucOC (n = 86); PIVKA-II vs. Gla-OC (n = 94). *** <span class="html-italic">p</span> &lt; 0.001, ns = not significant.</p>
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16 pages, 1269 KiB  
Article
Molecular Epidemiology Revealed Distinct Patterns Among Multidrug Resistant Clinical Acinetobacter baumannii Strains in Different Periods in the Main Hospital in Molise Region, Central Italy
by Manuela Tamburro, Adele Lombardi, Michela Lucia Sammarco and Giancarlo Ripabelli
Appl. Microbiol. 2025, 5(1), 9; https://doi.org/10.3390/applmicrobiol5010009 - 18 Jan 2025
Viewed by 431
Abstract
Background: Acinetobacter baumannii is a major cause of nosocomial infections in critically ill patients, and strains are frequently multidrug resistant (MDR). This study aimed to characterize 45 clinical A. baumannii isolates collected in different periods in the main hospital in the Molise Region, [...] Read more.
Background: Acinetobacter baumannii is a major cause of nosocomial infections in critically ill patients, and strains are frequently multidrug resistant (MDR). This study aimed to characterize 45 clinical A. baumannii isolates collected in different periods in the main hospital in the Molise Region, central Italy. Methods: Antimicrobial susceptibility was evaluated using an automated system, and PCRs were performed to detect resistance-associated genes. Pulsed-field gel electrophoresis (PFGE) was carried out with AscI and ApaI, and Multi-locus sequence typing (MLST) was performed according to the Oxford scheme. Results: All isolates exhibited MDR profiles, showing total susceptibility towards colistin. All strains harbored the blaOXA-23, blaOXA-51, and blaAmpC genes, as well as adeB, adeJ, adeG, abeS, and soxR. Dendrogram with AscI and ApaI revealed eleven and three clusters, respectively, and twenty-three and eighteen pulsotypes (Simpson’s index 0.96 and 0.93), and isolates from different periods were clearly distinguished. MLST revealed five sequence types, which varied depending on the isolation period, and ST1720 and ST369 were prevalent, followed by ST281, ST218, and ST513. Conclusions: Molecular characterization enables the identification of distinct patterns of MDR A. baumannii over time, underscoring its usefulness for improving epidemiological surveillance and combating antimicrobial resistance. This study provides previously unavailable information regarding A. baumannii circulating in the examined setting. Full article
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<p><span class="html-italic">AscI</span>-based dendrogram for 45 <span class="html-italic">A. baumannii</span> isolates including PTs, clusters, and STs.</p>
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<p><span class="html-italic">ApaI</span>-based dendrogram for 45 <span class="html-italic">A. baumannii</span> isolates including PTs, clusters, and STs.</p>
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16 pages, 1063 KiB  
Article
Potentials of Presepsin as a Novel Sepsis Biomarker in Critically Ill Adults: Correlation Analysis with the Current Diagnostic Markers
by Mai S. Sater, Nourah Almansour, Zainab Hasan Abdulla Malalla, Salim Fredericks, Muhalab E. Ali and Hayder A. Giha
Diagnostics 2025, 15(2), 217; https://doi.org/10.3390/diagnostics15020217 - 18 Jan 2025
Viewed by 368
Abstract
Background: Sepsis is a major cause of patient death in intensive care units (ICUs). Rapid diagnosis of sepsis assists in optimizing treatments and improves outcomes. Several biomarkers are employed to aid in the diagnosis, prognostication, severity grading, and sub-type discrimination of severe septic [...] Read more.
Background: Sepsis is a major cause of patient death in intensive care units (ICUs). Rapid diagnosis of sepsis assists in optimizing treatments and improves outcomes. Several biomarkers are employed to aid in the diagnosis, prognostication, severity grading, and sub-type discrimination of severe septic infections (SSIs), including current diagnostic parameters, hemostatic measures, and specific organ dysfunction markers. Methods: This study involved 129 critically ill adults categorized into three groups: sepsis (Se = 48), pneumonia (Pn = 48), and Se/Pn (33). Concentrations of five plasma markers (IL-6, IL-8, TREM1, uPAR, and presepsin) were compared with 13 well-established measures of SSI in critically ill patients. These measures were heart rate (HR), white blood count (WBC), C-reactive protein (CRP), procalcitonin (PCT), lactate plasma concentrations, and measures of hemostasis status (platelets count (PLT), fibrinogen, prothrombin time (PT), activated partial thromboplastin time (APTT), international normalization ratio (INR) and D-dimer). Plasma bilirubin and creatinine served as indicators of liver and kidney dysfunction, respectively. Results: Promising roles for these biomarkers were found. The best results were for presepsin, which scored 10/13, followed by IL-6 and IL-8 (each scored 7/13), and the worst were for TREM-1 and uPAR (scored 3/13). Presepsin, IL-6, and IL-8 discriminated between the SSI sub-types, whilst only presepsin correlated with bilirubin and creatinine. uPAR was positive for kidney dysfunction, and TREM-1 was the only indicator of artificial ventilation (AV). Conclusions: Presepsin is an important potential biomarker in SSIs. However, further work is needed to define this marker’s diagnostic and prognostic cutoff values. Full article
(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)
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<p>The effect of age and sex on the plasma levels of the tested biomarkers: IL-6, IL-8, TREM-1, uPAR, and presepsin. Upper figure [I]: scatter plot shows the correlations of the plasma levels of the biomarkers versus age. <span class="html-italic">p</span>-values are shown in the figure. The only borderline correlation was of the uPAR levels (<span class="html-italic">p</span> 0.051, CC (correlation coefficient) 0.181). Note: the open circles stand for each study subject separately. Lower figure [II]: plasma levels of biomarkers, comparisons between males and females. <span class="html-italic">p</span> values are placed in the figure. The plasma levels of the tested biomarkers; IL-6 (<b>A</b>), IL-8 (<b>B</b>), TREM-1 (<b>C</b>), uPAR (<b>D</b>), and presepsin (<b>E</b>), for each individual (black dots) are shown in the figure separately. However, for all study subjects, taken together the plasma median (75th and 25th percentile) concentrations (arbitrary units) of the above test biomarkers, as compared between females and males were 23.534, 3.865–59.393 vs. 24.825, 2.534–118.155 (<span class="html-italic">p</span> 0.479); −94.659, −104.036–−64.762 vs. −79.663, −104.929–−42.497 (<span class="html-italic">p</span> 0.312); −271.631, −455.717–209.744 vs. −364.803, −463.566–−23.093 (<span class="html-italic">p</span> 0.503); 2135.601, 1218.612–2953.504 vs. 1838.068, 1213.172–2821.403 (<span class="html-italic">p</span> 0.603); and 3.865, 1.156–10.704 vs. 4.459, 1.595–11.567 (<span class="html-italic">p</span> 0.752), respectively (MW). No significant differences were found in the levels of the biomarkers between both sexes.</p>
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<p>Scatter plot showing the correlations of plasma levels of each of the tested biomarkers, IL-6 (<b>A</b>), IL-8 (<b>B</b>), TREM-1 (<b>C</b>), uPAR (<b>D</b>), and presepsin (<b>E</b>), versus the five diagnostic parameters, heart rate (HR), white blood count (WBC), c-reactive protein (CRP), procalcitonin (PCT), and lactate. The Il-6 and IL-8 levels were significantly positively correlated with the HR and lactate levels, the TREM-1 levels were not correlated with any diagnostic parameter, and uPAR levels were positively correlated with PCT, while presepsin levels were significantly positively correlated with WBC, PCT, and lactate. The <span class="html-italic">p</span>-values and CC (correlation coefficient) are shown in the figure. Notably, the CRP levels were not correlated with any of the tested biomarkers.</p>
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<p>The median plasma concentrations (arbitrary units) of (<b>A</b>) IL-6 in sepsis (Se) (32.26, 1.66–114.79), pneumonia (Pn) (22.56, 3.81–53.97), and Se/Pn (24.49, 2.31–116.24) groups were comparable, <span class="html-italic">p</span> 0.581 (KW). (<b>B</b>) The plasma concentrations of IL-8 in the Se (−60.397, −73.872–3.775), Pn (−102.684, −108.145–−94.659), and Se/Pn (−101.943, −106.794–−78.764) groups were different, <span class="html-italic">p</span> &lt; 0.001 (KW). (<b>C</b>) The plasma concentrations of TREM1 in the Se (−349.10, −419.13–−236.89), Pn (−257.80, −654.24–563.93), and Se/Pn groups (−33.75, −618.46-739.41) were comparable, <span class="html-italic">p</span> 0.374 (KW). (<b>D</b>) The plasma levels of uPAR in the Se (1507.221, 976.191–2200.685), Pn (2259.057, 1293.304–3220.516) and Se/Pn (2242.496, 1964.184–3619.263) groups were different, <span class="html-italic">p</span> 0.000. (<b>E</b>) The plasma levels of presepsin in the Se (13.464, 5.393–20.599), Pn (3.548, 1.213–5.674), and Se/Pn (1.545, 0.214–3.475) groups were different, <span class="html-italic">p</span> &lt; 0.001. The horizontal line within each bar is the median value; the bottom and top lines of the bar are 25% and 75%, respectively; caps of the lower and upper vertical lines are the 5% and 95% percentiles; and the open circles are outliers.</p>
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14 pages, 620 KiB  
Article
Relationship Between Perilesional Skin Condition and Survival in Terminally Ill Patients with Pressure Ulcers
by María Isabel Pastor-Orduña, Federico Palomar-Llatas, David Palomar-Albert, María Teresa Murillo-Llorente, Ignacio Ventura, Francisco Tomás-Aguirre and Marcelino Pérez-Bermejo
Medicina 2025, 61(1), 147; https://doi.org/10.3390/medicina61010147 - 17 Jan 2025
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Abstract
Background and Objectives: In the context of palliative care, the aim is to alleviate suffering and improve quality of life, with particular attention to PUs, which have a significant impact on quality of life and survival. This study examines the relationship between perilesional [...] Read more.
Background and Objectives: In the context of palliative care, the aim is to alleviate suffering and improve quality of life, with particular attention to PUs, which have a significant impact on quality of life and survival. This study examines the relationship between perilesional skin condition and survival in terminally ill patients with pressure ulcers (PUs). Materials and Methods: A descriptive and observational study was conducted in two hospitals in Valencia with a sample of 100 terminally ill patients. Sociodemographic, clinical and PPU-specific variables were assessed using validated scales such as FEDPALLA-II and the Barthel Index. Results: Although it is a study of an observational nature, which may preclude establishing causality, the results showed that functional capacity, perilesional tissue epithelialization, and albumin levels were significant predictors of survival, while the number and location of PUs had no direct impact. Perilesional tissue epithelialization was highlighted as a critical indicator reflecting the systemic stability of the patient. Conclusions: The study highlights the importance of a comprehensive approach to palliative care that addresses both the local aspects of the lesions and the patient’s systemic and functional status. These findings support the implementation of therapeutic interventions based on a structured perilesional tissue assessment to improve quality of life and prolong survival in terminally ill patients. In addition, a positive correlation was found between Barthel Score and survival, suggesting that patients with greater functional independence have a longer life expectancy. On the other hand, the negative correlation between total lymphocyte count and survival suggests that lymphocytopenia may be a marker of adaptive immunosuppression. Perilesional tissue epithelialization, overall functionality and serum albumin levels are key factors in predicting survival, highlighting the need for a comprehensive palliative care approach to optimize quality of life and prolong survival in terminally ill patients with PUs. Full article
(This article belongs to the Section Dermatology)
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<p>Sample distribution according to the FEDPALLA-II Grade.</p>
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<p>Survival of the sample according to FEDPALLA-II Grade.</p>
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29 pages, 1517 KiB  
Review
Targeting Cytokine-Mediated Inflammation in Brain Disorders: Developing New Treatment Strategies
by Rahul Mallick, Sanjay Basak, Premanjali Chowdhury, Prasenjit Bhowmik, Ranjit K. Das, Antara Banerjee, Sujay Paul, Surajit Pathak and Asim K. Duttaroy
Pharmaceuticals 2025, 18(1), 104; https://doi.org/10.3390/ph18010104 - 15 Jan 2025
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Abstract
Cytokine-mediated inflammation is increasingly recognized for playing a vital role in the pathophysiology of a wide range of brain disorders, including neurodegenerative, psychiatric, and neurodevelopmental problems. Pro-inflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) cause neuroinflammation, alter brain [...] Read more.
Cytokine-mediated inflammation is increasingly recognized for playing a vital role in the pathophysiology of a wide range of brain disorders, including neurodegenerative, psychiatric, and neurodevelopmental problems. Pro-inflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) cause neuroinflammation, alter brain function, and accelerate disease development. Despite progress in understanding these pathways, effective medicines targeting brain inflammation are still limited. Traditional anti-inflammatory and immunomodulatory drugs are effective in peripheral inflammatory illnesses. Still, they face substantial hurdles when applied to the central nervous system (CNS), such as the blood–brain barrier (BBB) and unwanted systemic effects. This review highlights the developing treatment techniques for modifying cytokine-driven neuroinflammation, focusing on advances that selectively target critical cytokines involved in brain pathology. Novel approaches, including cytokine-specific inhibitors, antibody-based therapeutics, gene- and RNA-based interventions, and sophisticated drug delivery systems like nanoparticles, show promise with respect to lowering neuroinflammation with greater specificity and safety. Furthermore, developments in biomarker discoveries and neuroimaging techniques are improving our ability to monitor inflammatory responses, allowing for more accurate and personalized treatment regimens. Preclinical and clinical trial data demonstrate the therapeutic potential of these tailored techniques. However, significant challenges remain, such as improving delivery across the BBB and reducing off-target effects. As research advances, the creation of personalized, cytokine-centered therapeutics has the potential to alter the therapy landscape for brain illnesses, giving patients hope for better results and a higher quality of life. Full article
(This article belongs to the Special Issue Pharmacotherapy of Neurodegeneration Disorders)
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<p>Cytokine pathways in neuroinflammation. In neurodegenerative conditions, stromal cells (e.g., astrocytes) and microglia release proinflammatory cytokines in response to homeostatic imbalances. Early cytokine release may aid repair, but chronic secretion leads to neuronal damage and loss of tissue function. In addition, leukocyte infiltration and BBB disruption contribute to neuroinflammatory conditions. Lymphocytes and myeloid cells drive inflammation through cytokines such as IL-1β and IL-6, affecting neurons. IL-23 amplifies T cell pathogenicity, while GM-CSF activates monocyte-derived cells, exacerbating tissue damage. Other key players include IFNγ and TNFα, which fuel the inflammatory cascade.</p>
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<p>Brain disorders and cytokine dysregulation. Cytokines are closely linked to cognitive impairments in neurological disorders. Notably, IL-6 and TNF-α are common cytokines contributing to cognitive dysfunction across all disorders. Both solid and dotted lines denote cytokine involvement in the neurological disorders.</p>
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16 pages, 899 KiB  
Article
An Assessment of Intermittent and Continuous Enteral Feeding in Critically Ill Children
by Merve Misirlioglu, Dincer Yildizdas, Faruk Ekinci, Nihal Akcay, Ilyas Bingol, Ebru Sahin, Fatih Varol, Muhterem Duyu, Ayse Asik, Fatih Durak, Leyla Atman, Suleyman Bayraktar, Mehmet Alakaya, Ali Ertug Arslankoylu, Gurkan Bozan, Eylem Kiral, Ozden Ozgur Horoz, Hasan Ali Telefon, Abdullah Akkus, Abdullah Yazar, Ozlem Sandal, Hasan Agin, Alper Koker, Nazan Ulgen Tekerek, Nurettin Onur Kutlu, Mehmet Arda Kilinc, Ali Korulmaz, Hatice Feray Ari, Mutlu Uysal Yazici, Esra Sevketoglu, Mehmet Emin Menentoglu, Ebru Kacmaz, Mehmet Nur Talay, Ozhan Orhan, Berna Egehan Oruncu, Selman Kesici, Caglar Odek, Didar Arslan, Pinar Hepduman, Gultac Evren, Hatice Elif Kinik Kaya, Nazik Yener, Emrah Gun, Ilkem Gardiyanoglu, Muhammed Udurgucu, Sinan Yavuz, Ali Avci, Murat Ozkale, Yasemin Ozkale, Damla Pinar Yavas Kocaoglu, Sahin Sincar and Yasemin Cobanadd Show full author list remove Hide full author list
Nutrients 2025, 17(2), 301; https://doi.org/10.3390/nu17020301 - 15 Jan 2025
Viewed by 556
Abstract
Background: The inability to ensure adequate nutrition for patients, and failure to provide adequate calorie and protein intake, result in malnutrition, leading to increased morbidity and mortality. The present study assesses the two approaches to enteral nutrition—intermittent and continuous enteral feeding—in critically ill [...] Read more.
Background: The inability to ensure adequate nutrition for patients, and failure to provide adequate calorie and protein intake, result in malnutrition, leading to increased morbidity and mortality. The present study assesses the two approaches to enteral nutrition—intermittent and continuous enteral feeding—in critically ill pediatric patients in Türkiye to determine the superiority of one method over the other. Methods: Included in this multicenter prospective study were patients receiving enteral nutrition via a tube who were followed up over a 3-month period. Anthropometric data, calorie and protein intake, and signs of feeding intolerance were evaluated in a comparison of the different feeding methods. Results: A total of 510 patients were examined. In the continuous enteral feeding (CEF) group, 20.2% of patients developed metabolic abnormalities, and 49.5% experienced enteral nutrition intolerance, both of which were higher than in the intermittent enteral feeding (IEF) group, and the differences were statistically significant. No significant differences were observed between the two feeding methods in terms of reaching the target calorie intake on days 2 and 7 (p > 0.05). On day 7, there were significant differences between the two feeding methods in terms of calorie and protein intake (p = 0.023 and 0.014, respectively). Conclusions: In the present study, assessing the IEF and CEF approaches to enteral nutrition, critically ill pediatric patients receiving intermittent feeding exhibited lower rates of enteral nutrition intolerance and metabolic abnormalities. Furthermore, the calorie and protein intake on day 7 were noted to be higher in the IEF group than in the CEF group. Further randomized controlled trials are needed to confirm the findings of the present study. Full article
(This article belongs to the Section Pediatric Nutrition)
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<p>Algorithm used for the determination of the enteral feeding method [<a href="#B4-nutrients-17-00301" class="html-bibr">4</a>]. GIT: gastrointestinal tract, N/G: nasogastric, O/G: orogastric.</p>
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<p>Feeding protocol [<a href="#B4-nutrients-17-00301" class="html-bibr">4</a>,<a href="#B13-nutrients-17-00301" class="html-bibr">13</a>,<a href="#B14-nutrients-17-00301" class="html-bibr">14</a>].</p>
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