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Search Results (162)

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13 pages, 4344 KiB  
Article
Heterogeneity of the Immunological and Pathogenic Profiles in Patients Hospitalize Early Versus Late During an Acute Vital Illness as Shown in Native SARS-CoV-2 Infection
by Krzysztof Laudanski, Ahmed Sayed Ahmed, Mohamed A. Mahmoud, Mohamed Antar and Hossam Gad
Int. J. Mol. Sci. 2025, 26(5), 2349; https://doi.org/10.3390/ijms26052349 - 6 Mar 2025
Viewed by 159
Abstract
The immune system’s response to an invading pathogen is the critical determinant in recovery from illness. Here, we hypothesize that the immune response will swiftly follow classical activation and a resolution trajectory in patients with the rapid evolution of symptoms if challenged by [...] Read more.
The immune system’s response to an invading pathogen is the critical determinant in recovery from illness. Here, we hypothesize that the immune response will swiftly follow classical activation and a resolution trajectory in patients with the rapid evolution of symptoms if challenged by a viral pathogen for the first time. Alternatively, a dysregulated response will be signified by a protracted clinical trajectory. Consequently, we enrolled 106 patients during the first wave of COVID-19 and collected their blood within 24 h, 48 h, 7 days, and over 28 days from symptoms onset. The pathogenic burden was measured via serum levels of the S-spike protein and specific immunoglobulin titers against the S and N proteins of SARS-CoV-2. The nonspecific immunological response was gauged using interleukin 6, leukocytosis, and C-reactive protein. Coagulation status was assessed. Several serum biomarkers were used as surrogates of clinical outcomes. We identified four clusters depending on the onset of symptoms (immediate [A], 6 days [B], 12 days [C], and over 21 days [D]). High variability in the S-spike protein in cluster A was present. The corresponding immunoglobulin titer was random. Only procalcitonin differentiated clusters in terms of markers of nonspecific inflammation. Coagulation markers were not significantly different between clusters. Serum surrogates on cardiomyopathy and neuronal pathology exhibited significant variability. Implementation of ECMO or noninvasive ventilation was more prominent in cluster C and D. Interestingly, SOFA or APACHE II scores were not different between nominal (A and B) versus dysregulated clusters (C and D). Full article
(This article belongs to the Section Molecular Immunology)
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<p>Patients clustered in four groups depending on the onset of the symptoms to hospitalization. Cluster A included patients (n = 41) when the onset of the symptoms and admission had almost no time separation (tint = 0) (<a href="#ijms-26-02349-f001" class="html-fig">Figure 1</a>). Cluster B was characterized by patients (n = 41) with an average delay of six days between the onset of the symptoms and admission to the hospital. Cluster C (n = 13) aggregated patients with the average onset of symptoms being 12 days. Cluster D showed patients with an average onset of symptoms over 21 days or more (n = 11).</p>
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<p>(<b>A</b>,<b>B</b>). There were differences in serum S-spike protein between clusters at baseline, with a significant increase in cluster B compared to other clusters. * Statistically significant differences between baseline and subsequent time points within the cluster at a given sampling time point.</p>
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<p>(<b>A</b>–<b>C</b>). There were no differences in serum IgA, IgM, and IgG between clusters at baseline. Analysis of the IgA and IgG revealed some variability, but it was minimal. * Statistically significant differences between baseline and subsequent time points within the cluster at a given sampling time point. &amp; Statistically significant differences between clusters at a given sampling time point.</p>
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<p>There were no differences in serum WBC, IL-6, and CRP between clusters at baseline (<b>A</b>–<b>D</b>). Analysis of the PCT demonstrated significant variability in cluster B. * Statistically significant differences between baseline and subsequent time points within the cluster at a given sampling time point.</p>
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<p>Symptomology presentation of patients in different clusters at admission. We grouped patients with none symptoms (NONE) as well as exhibiting predominantly respiratory problems (RESP; cough, runny nose, and breathing difficulty), cardiac system-related symptoms (CARD; chest pain), gastrointestinal symptomatology problems (GI; diarrhea, nausea, and vomiting), abnormalities in temperature management (TEMP; fever and chills), predominant musculoskeletal issues (MSK; fatigue and muscle pain), or neurological issues (NEURO; headache, loss of smell, and confusion). n represents the number of patients in each of the clusters.</p>
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<p>There were no differences in serum NT-BNP or TnI between clusters at baseline (<b>A</b>). Time-wise analysis within markers revealed several differences across all studied clusters except (<b>B</b>). * Statistically significant differences between baseline and subsequent time points within the cluster at a given sampling time point.</p>
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<p>There were no differences in serum surrogates of peripheral nerve injury (NCAM-1) (<b>A</b>), and neurodegeneration (NRNG, BCL-2) (<b>B</b>,<b>C</b>). Time-wise analysis within markers revealed several differences across all studied clusters except B. &amp;—statistical difference when comparing clusters at the same time point; #—statistical difference when comparing to cluster A.</p>
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16 pages, 1327 KiB  
Article
The Importance of Frailty in Determining Survival After Intensive Care
by Orsolya Szűcs, László G. Élő, Gábor Élő, Réka Varga, Réka Jung, Edit Benkovics, László Szabó and László Zubek
J. Clin. Med. 2025, 14(5), 1760; https://doi.org/10.3390/jcm14051760 - 5 Mar 2025
Viewed by 194
Abstract
Background: Estimating survival and long-term quality of life after intensive care has been a crucial bioethical endeavour in recent decades to improve end-of-life decision-making. Scientific studies have also shown that patient frailty influences survival, but only a few long-term data are available. Methods: [...] Read more.
Background: Estimating survival and long-term quality of life after intensive care has been a crucial bioethical endeavour in recent decades to improve end-of-life decision-making. Scientific studies have also shown that patient frailty influences survival, but only a few long-term data are available. Methods: We conducted a prospective observational study at the Department of Anaesthesiology and Intensive Care of Semmelweis University, Hungary, to investigate the association between physical status on admission, the chance of survival, and the long-term quality of life of the patient. We recorded the pre-admission frailty score (Clinical Frailty Scale), APACHE II, and SAPS II scores on admission. The first follow-up was 3 months after discharge when the quality of life of the patient was assessed using the EQ5-D questionnaire. During the second follow-up one year later, we recorded the EQ5-D, Mini-Mental Test, and the Beck Depression Inventory scales. Results: Our study demonstrated that the ROC analysis of predicted overall mortality based on CFS score is similar in accuracy to that of predicted mortality by APACHE II and SAPS II point systems. The multivariate logistic regression calculations show that the best performing of the three independent variables is the SAPS II estimator (78.5%), but the estimators of both acute condition scoring systems (APACHE and SAPS) can be improved (79.5% vs. 84%) when taking into account the CFS value. The prevalence of mood and mental disorders among patients who survived one year was not different from that of the general population. Conclusions: The physiological scoring systems examined are all suitable for estimating the risk of overall mortality. The CFS shows similar efficacy and appears to be additive in value, with scales describing the severity of acute illness, which are indicative of the chronic condition of the patient. Full article
(This article belongs to the Special Issue Key Advances in the Treatment of the Critically Ill: 2nd Edition)
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<p>Flow chart of patient follow-up.</p>
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<p>Distribution of CFS scores among patients admitted to the ICU.</p>
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<p>Kaplan–Meier survival curves for patients admitted, divided into groups of two and three based on CFS. The test comparing groups was based on log-rank test. The figure shows that the survival probability in groups CFS 1–5 (blue curve—(<b>A</b>)), CFS 1–3 (blue curve—(<b>B</b>)) was higher, compared to the other groups (orange line—(<b>A</b>), orange and green line—(<b>B</b>)).</p>
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<p>Kaplan–Meier survival curves for patients admitted, divided into groups of two and three based on CFS. The test comparing groups was based on log-rank test. The figure shows that the survival probability in groups CFS 1–5 (blue curve—(<b>A</b>)), CFS 1–3 (blue curve—(<b>B</b>)) was higher, compared to the other groups (orange line—(<b>A</b>), orange and green line—(<b>B</b>)).</p>
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<p>(<b>A</b>) Distributions of APACHE II by CFS. (<b>B</b>) Distributions of SAPS II by CFS.</p>
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<p>(<b>A</b>) Distributions of APACHE II by CFS. (<b>B</b>) Distributions of SAPS II by CFS.</p>
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<p>The mortality rate of all patients (<span class="html-italic">n</span> = 212) based on CFS points.</p>
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<p>Prediction of mortality by CFS, APACHE II, SAPS II scores and age.</p>
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15 pages, 706 KiB  
Article
Prolonged T-Piece Spontaneous Breathing Trial and Extubation Outcomes in Patients Received Prolonged Mechanical Ventilation
by Tsung-Ming Yang, Yu-Hung Fang, Chia-Hao Chang, Shih-Jiun Lin, Cheng-Chi Liu, David Ming Then Tsai, Chun-Liang Lin, Chieh-Mo Lin and Yung-Chien Hsu
Medicina 2025, 61(3), 412; https://doi.org/10.3390/medicina61030412 - 26 Feb 2025
Viewed by 214
Abstract
Background and Objectives: Unassisted breathing through a T-piece was the most used spontaneous breathing trial (SBT) in endotracheal intubated prolonged mechanical ventilation (PMV) patients. However, the optimal duration of an SBT in PMV patients remains uncertain. In this study, we compared the extubation [...] Read more.
Background and Objectives: Unassisted breathing through a T-piece was the most used spontaneous breathing trial (SBT) in endotracheal intubated prolonged mechanical ventilation (PMV) patients. However, the optimal duration of an SBT in PMV patients remains uncertain. In this study, we compared the extubation outcome between a 12 h T-piece SBT and a 24 h T-piece SBT in PMV patients. Materials and Methods: We reviewed the medical records of PMV patients who were extubated after passing a 12 h or 24 h T-piece SBT. The extubation, weaning, and hospital outcomes between the 12 h T-piece SBT group and the 24 h T-piece SBT group were compared. Kaplan–Meier survival plots and Cox proportional hazard models were used to evaluate the risk of extubation failure between groups. Results: In this study, 120 patients were extubated after passing the 12 h T-piece SBT and 234 patients were extubated after passing 24 h T-piece SBT. Patients in the 24 h T-piece SBT group had higher APACHE II score and lower Glasgow coma scale upon RCC arrival than patients in the 12 h T-piece SBT group. There was no difference in gender, age, or ventilator days before extubation between these two groups of patients. After extubation, patients in the 12 h T-piece SBT group and 24 h T-piece SBT group had similar extubation failure rates within 5 days (26.7% vs. 26.1%, p = 0.904). There was no difference in the RCC weaning rate (85% vs. 85.5%, p = 0.929) and hospital mortality rate (19.8% vs. 21.8%, p = 0.821) between the 12 h T-piece SBT group and the 24 h T-piece SBT group. Subgroup analysis showed that 24 h T-piece SBT was associated with a lower extubation failure rate in PMV patients with myocardial infarction or heart failure, but not in older PMV patients or those with cerebrovascular disease. Conclusions: The extubation and weaning outcomes were similar in PMV patients extubated after passing 12 h T-piece SBT or 24 h T-piece SBT. Full article
(This article belongs to the Section Pulmonology)
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<p>Process of patient selection. RCC—respiratory care center; PSV—pressure support ventilation; CPAP—continuous positive airway pressure; SBT—spontaneous breathing trial.</p>
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<p>Kaplan–Meier survival curves for extubation failure in patients who were extubated after they passed 12 h T-piece spontaneous breathing trial (SBT, black) or 24 h T-piece SBT (red). SBT—Spontaneous breathing trial.</p>
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13 pages, 1840 KiB  
Article
Association Between Plasma Granzyme B Levels, Organ Failure, and 28-Day Mortality Prediction in Patients with Sepsis
by Min Seo Ki, Ju Hye Shin, Min Dong Sung, Shihwan Chang, Ah Young Leem, Su Hwan Lee, Moo Suk Park, Young Sam Kim and Kyung Soo Chung
J. Clin. Med. 2025, 14(5), 1461; https://doi.org/10.3390/jcm14051461 - 21 Feb 2025
Viewed by 132
Abstract
Background/Objectives: Sepsis is basically an inflammatory disease that involves the host’s immune response. Granzyme B, a cytotoxic protease, has garnered attention for its involvement in modulating immune responses. This study aimed to elucidate the clinical implications of granzyme B in critically ill [...] Read more.
Background/Objectives: Sepsis is basically an inflammatory disease that involves the host’s immune response. Granzyme B, a cytotoxic protease, has garnered attention for its involvement in modulating immune responses. This study aimed to elucidate the clinical implications of granzyme B in critically ill patients with sepsis, focusing on plasma granzyme B levels as a potential prognostic marker. Methods: We conducted a retrospective analysis of sequentially collected blood samples from 57 sepsis patients admitted to the medical intensive care unit at Severance Hospital, a tertiary hospital in Seoul, South Korea. Clinical and laboratory data were comparatively analyzed between 28-day survivors and nonsurvivors. Results: The number of patients in the survivor and nonsurvivor groups was 32 (56.1%) and 25 (43.9%), respectively. Compared to survivors, nonsurvivors had higher APACHE II (23.5 vs. 34, p = 0.007) and SOFA (10 vs. 15, p = 0.001) scores, as well as increased levels of serum lactate (1.8 vs. 9.2 mmol/L, p < 0.001) and plasma granzyme B (28.2 vs. 71 pg/mL, p < 0.001). Granzyme B exhibited a robust area under the receiving operating characteristic (AUROC) for predicting 28-day mortality (AUROC = 0.794), comparable to lactate (0.804), SOFA (0.764), and APACHE II (0.709). The combined index of lactate and granzyme B demonstrated the highest AUROC (0.838) among all investigated predictors. Significant positive correlations were observed between log granzyme B and various inflammatory cytokines, including log IFN-γ (r = 0.780), IL-4 (r = 0.540), IL-10 (r = 0.534), and IL-6 (r = 0.520). Conclusions: Plasma granzyme B demonstrated fair short-term mortality prediction among patients admitted to the ICU, suggesting its potential utility for risk stratification and managing patients with sepsis. Full article
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<p>Flowchart of the study patient selection process.</p>
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<p>Area under the receiver operating characteristics curve for 28-day mortality of the study participants.</p>
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<p>Kaplan–Meier curves for 28-day survival rate in patients with sepsis: High-Gzm B group vs. Low-Gzm B group.</p>
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<p>Serial trend of plasma granzyme B (<b>A</b>) and SOFA score (<b>B</b>). (<b>A</b>) * <span class="html-italic">p</span> &lt; 0.05 for the difference in log<sub>10</sub>(Granzyme B) in 28-day survivors vs. 28-day nonsurvivors at a specified time point. † <span class="html-italic">p</span> &lt; 0.05, as analyzed by generalized estimating equations, for the change in log<sub>10</sub>(Granzyme B) from time point 0 to a specified time point in 28-day survivors vs. 28-day nonsurvivors. <sup>#</sup> There were 3 cases of missing blood samples. (<b>B</b>) * <span class="html-italic">p</span> &lt; 0.05 for the difference in SOFA score in 28-day survivors vs. 28-day nonsurvivors at a specified time point. † <span class="html-italic">p</span> &lt; 0.05, as analyzed by generalized estimating equations, for the change in SOFA score from time point 0 to a specified time point in 28-day survivors vs. 28-day nonsurvivors.</p>
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<p>Correlation analysis between plasma granzyme B and inflammatory cytokines, lactate, and SOFA score. Scatter plots illustrate the Pearson correlations between log-transformed granzyme B and various inflammatory cytokines (IFN-γ, IL-4, IL-10, and IL-6), as well as lactate and the SOFA score. Each dot represents an individual data point. The solid regression line depicts the fitted linear relationship between the variables, while the shaded area represents the 95% confidence interval. The Pearson correlation coefficient (r) and its corresponding <span class="html-italic">p</span>-value are displayed in each plot.</p>
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15 pages, 2181 KiB  
Article
The Role of I-FABP, REG3α, sCD14-ST, and LBP as Indicators of GI Tract Injury in MODS Patients
by Yermek Turgunov, Alina Ogizbayeva, Sofiko Assamidanova, Dmitriy Matyushko, Miras Mugazov, Dana Amanova, Shynggys Nuraly and Yerzhan Sharapatov
Diagnostics 2025, 15(5), 515; https://doi.org/10.3390/diagnostics15050515 - 20 Feb 2025
Viewed by 186
Abstract
Background/Objectives: The aim of this study was to evaluate potential biomarkers of bacterial translocation (lipopolysaccharide-binding protein (LBP) and soluble CD14 subtype (sCD14-ST)) and intestinal wall damage (intestinal fatty acid binding protein (I-FABP), Zonulin, and regenerating islet-derived protein-3α (REG3α)) in patients with multiple [...] Read more.
Background/Objectives: The aim of this study was to evaluate potential biomarkers of bacterial translocation (lipopolysaccharide-binding protein (LBP) and soluble CD14 subtype (sCD14-ST)) and intestinal wall damage (intestinal fatty acid binding protein (I-FABP), Zonulin, and regenerating islet-derived protein-3α (REG3α)) in patients with multiple organ dysfunction syndrome (MODS). Methods: The study involved 327 patients divided into two groups: Group 1 comprised 227 patients with MODS (main group), while Group 2 comprised 100 patients with identical pathologies but without MODS (control group). To examine these biomarkers in the blood, venous blood was taken in the control group on the day of admission to the hospital, in patients with MODS on the first day of MODS staging, and later on Days 3 and 7 of its development. Levels of these markers in blood serum were determined by enzyme-linked immunosorbent assays according to the manufacturers’ instructions. Results: In the control group, values of all the investigated markers were lower than in the group of MODS patients (p < 0.0001). In the main group, the mortality rate was 44.9% (n = 102). The values of sCD14-ST on Day 1 and of I-FABP and REG3α on Days 1 and 3 were higher in deceased MODS patients (p < 0.05), while LBP levels on Day 7 were conversely lower in the deceased patients (p = 0.006). SOFA and APACHE II scores were higher in the deceased patients (p < 0.0001). Conclusions: In MODS patients, the increased I-FABP, REG3α, and sCD14-ST but decreased LBP levels may indicate increased intestinal wall permeability and bacterial translocation, which may exacerbate the course of multiple organ dysfunction and increase the risk of mortality. Despite the limitations of this study, the studied potential biomarkers can be considered noteworthy candidates for identifying MODS patients at high risk of mortality. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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<p>Schematic representation of the inclusion and exclusion criteria for the study patients.</p>
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<p>The levels of (<b>a</b>) lipopolysaccharide-binding protein (LBP), (<b>b</b>) soluble CD14 subtype (sCD14-ST), (<b>c</b>) intestinal fatty acid binding protein (I-FABP), (<b>d</b>) regenerating islet-derived protein-3α (REG3α), and (<b>e</b>) Zonulin on Day 1 in the study groups. The Mann–Whitney statistical test was used to identify significant differences for all markers between the study groups.</p>
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<p>The levels of (<b>a</b>) lipopolysaccharide-binding protein (LBP), (<b>b</b>) soluble CD14 subtype (sCD14-ST), (<b>c</b>,<b>d</b>) intestinal fatty acid binding protein (I-FABP), and (<b>e</b>,<b>f</b>) regenerating islet-derived protein-3α (REG3α) in deceased and surviving patients with multiple organ dysfunction syndrome (MODS). The Mann–Whitney statistical test was used to identify significant differences for all markers between the study groups.</p>
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<p>ROC analysis of the (<b>a</b>) soluble CD14 subtype (sCD14-ST), (<b>b</b>) lipopolysaccharide-binding protein (LBP), (<b>c</b>) intestinal fatty acid binding protein (I-FABP), and (<b>d</b>) regenerating islet-derived protein-3α (REG3α) in multiple organ dysfunction syndrome patients for the prediction of mortality.</p>
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9 pages, 730 KiB  
Article
Relationship Between Inflammatory Markers (IL-6, Neutrophil–Lymphocyte Ratio, and C-Reactive Protein-Albumin Ratio) and Diabetic Ketoacidosis Severity: Correlation with Clinical Outcomes
by Hatice Aslan Sirakaya, Hilal Sipahioglu, Ali Cetinkaya and Kaniye Aydin
Medicina 2025, 61(2), 321; https://doi.org/10.3390/medicina61020321 - 12 Feb 2025
Viewed by 441
Abstract
Background and Objectives: The use of additional biomarkers to predict clinical course in diabetic ketoacidosis (DKA) is becoming increasingly important. The aim of this study was to investigate the relationship between interleukin-6 (IL-6) levels and the length of stay in the intensive [...] Read more.
Background and Objectives: The use of additional biomarkers to predict clinical course in diabetic ketoacidosis (DKA) is becoming increasingly important. The aim of this study was to investigate the relationship between interleukin-6 (IL-6) levels and the length of stay in the intensive care unit (ICU) in patients with DKA without signs of infection and to investigate the relationship between the neutrophil–lymphocyte ratio (NLR) and C-reactive protein (CRP) albumin ratio (CAR). Materials and Methods: This retrospective, single-center study included 78 patients with DKA without infection who were treated in the Medical ICU between July 2022 and June 2024. The patients were divided into two groups: moderate DKA (Group 1) and severe DKA (Group 2). The patients’ IL-6 levels, peripheral blood inflammatory markers (CAR, NLR), Acute Physiology and Chronic Health Evaluation (APACHE) II scores, and the duration of ICU stay were recorded. Results: The median duration of stay in the ICU was 2.00 (1–6) days in group 1 and 3.00 (1–26) days in group 2 (p = 0.001). The mean pH, HCO3, and CO2 values in Group 1 were 7.20 ± 0.07, 13.58 ± 2.11 mEq/L, and 29.45 ± 6.27 mmHg, while the mean pH, HCO3, and PCO2 values in Group 2 were 7.01 ± 0.11, 7.11 ± 1.91 mEq/L, and 20.35 ± 4.91 mmHg (p < 0.001, p < 0.001, p < 0.001, respectively). There was a strong positive correlation between IL-6 levels and the length of stay in the ICU (r = 0.813, p < 0.001). Additionally, there was a moderate positive correlation between the length of stay in the ICU with the severity of DKA (r = 0.475, p < 0.001), CAR (r = 0.336, p < 0.001), and NLR (r = 0.562, p < 0.001). Conclusions: Inflammatory markers such as NLR and CAR, and more specifically IL-6, were found to be associated with the clinical course and duration of stay in the ICU in patients with DKA. Full article
(This article belongs to the Section Intensive Care/ Anesthesiology)
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<p>The flowchart of the patient selection process.</p>
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<p>Correlation graph between length of stay in ICU with CAR and NLR.</p>
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16 pages, 643 KiB  
Article
Clinical Significance of Sarcopenia Defined by the Cross-Sectional Area of the Masseter Muscle in Cerebrovascular Events: A Retrospective Cohort Study
by Fatih Seğmen, Semih Aydemir, Temel Kayan, Firdevs Tuğba Bozkurt Biçer, Cihangir Doğu, Esra Yakışık Aktekin, Deniz Erdem and Elif Uzun Ata
Medicina 2025, 61(2), 268; https://doi.org/10.3390/medicina61020268 - 4 Feb 2025
Viewed by 535
Abstract
Background and Objectives: This study aimed to investigate the clinical significance of sarcopenia, defined by the cross-sectional area of the masseter muscle (CSA-M), as an early marker for sarcopenia diagnosis and its association with mortality in patients with cerebrovascular events (CVE). Materials [...] Read more.
Background and Objectives: This study aimed to investigate the clinical significance of sarcopenia, defined by the cross-sectional area of the masseter muscle (CSA-M), as an early marker for sarcopenia diagnosis and its association with mortality in patients with cerebrovascular events (CVE). Materials and Methods: In this retrospective cohort study, 120 patients aged 65 years or older with CVE admitted to Bilkent City Hospital between September 2020 and September 2023 were included. Patients with malignancy, prior CVE, or incomplete data were excluded. Parameters such as CSA-M measured via brain CT, Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores, Nutritional Risk Score (NRS), duration of ICU and hospital stays, and 28-day mortality were evaluated. The CSA-M thresholds for sarcopenia were defined as <400 mm2 for men and <300 mm2 for women. Results: Sarcopenia prevalence was significantly associated with prolonged ICU (27.0 ± 33.1 days vs. 16.5 ± 22.4 days, p = 0.042) and hospital stays (34.8 ± 38.4 days vs. 21.3 ± 22.3 days, p = 0.017). Right and left CSA-M values were significantly lower in sarcopenic patients (p < 0.001). ROC analysis revealed CSA-M cut-off values of <300 mm2 (AUC = 0.82) for men and <295 mm2 (AUC = 0.83) for women as strong predictors of sarcopenia. Multivariate regression analysis showed a significant association between CSA-M and 28-day mortality (p < 0.05). Sarcopenia also correlated with lower albumin levels, a higher prevalence of ischemic stroke, and increased mechanical ventilation needs. Conclusions: CSA-M measured via brain CT is a reliable marker for sarcopenia and a predictor of clinical outcomes in CVE patients. Early identification and management of sarcopenia could improve patient prognosis. Further research is warranted to explore its potential in broader clinical contexts. Full article
(This article belongs to the Section Neurology)
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<p>ROC analysis results in patients with sarcopenia.</p>
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12 pages, 1034 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 - 25 Jan 2025
Viewed by 712
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)
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<p>Comparison of outcomes: colistin in monotherapy or combination therapy and empirical or targeted therapy. The analysis was performed with the chi-square test or Fisher’s exact test.</p>
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<p>Comparison of outcomes: use or non-use of the colistin loading dose and route of administration—intravenously or nebulization with intravenous infusion. The analysis was performed with the chi-square test or Fisher’s exact test.</p>
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16 pages, 1381 KiB  
Article
Differences in Characteristics of Peripartum Patients Who Did and Did Not Require an Upgrade to the Intensive Care Unit: A Propensity Score Matching Study
by Jennifer A. Walker, Jerry M. Yang, Saad Pirzada, Manahel Zahid, Samantha Asuncion, Amanda Tuchler, Gillian Cooper, Allison Lankford, Emad Elsamadicy and Quincy K. Tran
Medicina 2025, 61(1), 163; https://doi.org/10.3390/medicina61010163 - 20 Jan 2025
Viewed by 892
Abstract
Background and Objectives: This study sought to identify predictors for peripartum patients admitted to non-intensive care wards who later upgraded to the Intensive Care Unit (ICU). Materials and Methods: This was a retrospective observational study of patients admitted to the Maternal Fetal Ward [...] Read more.
Background and Objectives: This study sought to identify predictors for peripartum patients admitted to non-intensive care wards who later upgraded to the Intensive Care Unit (ICU). Materials and Methods: This was a retrospective observational study of patients admitted to the Maternal Fetal Ward between 01/2017 and 12/2022, who later upgraded to the ICU. Upgraded patients were 1:1 propensity score matched with those who remained on the Maternal Fetal Ward (control). The Classification And Regression Tree, a machine learning algorithm, was used to identify significant predictors of ICU upgrade. Multivariable ordinal regression analysis was used to assess the time interval to upgrade. Results: From 1855 peripartum patients, we analyzed 37 control and 34 upgrade patients. Mean maternal age (±Standard Deviation) and gestational age for the group was 29.5 (±5.8) years and 31.5 (±7.5) weeks, respectively. The Median Sequential Organ Failure Assessment Score [Interquartile] at ward admission for the controls was 0 [0–1] versus 2 [0–3.3, p = 0.001] for upgrade patients. The Sequential Organ Failure Assessment score at Maternal Fetal Ward admission was most predictive, followed by the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and lactate dehydrogenase levels. The APACHE II score was also associated with ICU upgrade within 12 h of hospital admission (OR 1.4, 95% CI 1.08–1.91, p = 0.01). Conclusions: Compared to control patients, peripartum patients upgraded to the ICU are associated with higher physiologic scores at Maternal Fetal Ward admission. Until further studies are performed to confirm our observation, clinicians should pay attention to these physiologic scores, since they may be associated with higher-risk patients. Full article
(This article belongs to the Section Intensive Care/ Anesthesiology)
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<p>Flow diagram of patient selection illustrating source of study population. ICU = Intensive Care Unit; ED = Emergency Department; MFW = Maternal Fetal Ward.</p>
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<p>The tree diagram from the Classification And Regression Tree analysis. In this model, missing laboratory values were imputed as normal values. The Area Under Receiver Operating Curve was 0.67 (95% CI 0.54–0.80) with a misclassification cost = 0.57. The CART algorithm examined the interactions between the variables to provide the split (node) with the highest sensitivity and specificity. When the interaction cannot produce any further split, i.e., the variable may achieve the highest possible association with the outcome of interest, the series ends at a “terminal node”. ICU = Intensive Care Unit; LDH = Lactate dehydrogenase; SOFA = Sequential Organ Failure Assessment.</p>
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<p>Relative variable importance of clinical variables predicting the need for Intensive Care Unit upgrade after admission to the Maternal Fetal Ward. Variable importance measures model improvement when splits are made on a predictor. Relative importance is defined as a % improvement with respect to the top predictor. AST = Aspartate aminotransferase; ALT = Alanine aminotransferase; APACHE II = Acute Physiology and Chronic Health Evaluation II; BMI = Body mass index; GA = Gestational age; LDH = Lactate dehydrogenase; Rox = Respiratory Rate-Oxygenation index; SOFA = Sequential Organ Failure Assessment; WBC = White blood cell.</p>
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<p>Tree diagram of the Classification and Regression Tree (CART).</p>
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<p>Relative variable importance of the Classification and Regression Tree (CART).</p>
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13 pages, 791 KiB  
Article
Inflammatory Markers and Severity in COVID-19 Patients with Clostridioides Difficile Co-Infection: A Retrospective Analysis Including Subgroups with Diabetes, Cancer, and Elderly
by Teodor Cerbulescu, Flavia Ignuta, Uma Shailendri Rayudu, Maliha Afra, Ovidiu Rosca, Adrian Vlad and Stana Loredana
Biomedicines 2025, 13(1), 227; https://doi.org/10.3390/biomedicines13010227 - 17 Jan 2025
Viewed by 955
Abstract
Background and Objectives: The interplay of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and Clostridioides difficile infection (CDI) poses a critical clinical challenge. The resultant inflammatory milieu and its impact on outcomes remain incompletely understood, especially among vulnerable subgroups such as elderly [...] Read more.
Background and Objectives: The interplay of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and Clostridioides difficile infection (CDI) poses a critical clinical challenge. The resultant inflammatory milieu and its impact on outcomes remain incompletely understood, especially among vulnerable subgroups such as elderly patients, those with diabetes, and individuals with cancer. This study aimed to characterize inflammatory markers and composite inflammatory severity scores—such as Acute Physiology and Chronic Health Evaluation II (APACHE II), Confusion, Urea, Respiratory rate, Blood pressure, and age ≥ 65 years (CURB-65), National Early Warning Score (NEWS), and the Systemic Immune-Inflammation Index (SII)—in hospitalized Coronavirus Disease 2019 (COVID-19) patients with and without CDI, and to evaluate their prognostic implications across key clinical subgroups. Methods: We conducted a retrospective, single-center study of 240 hospitalized adults with Reverse Transcription Polymerase Chain Reaction (RT-PCR)-confirmed COVID-19 between February 2021 and March 2023. Of these, 98 had concurrent CDI. We collected baseline demographics, comorbidities, and laboratory parameters including C-reactive protein (CRP), Interleukin-6 (IL-6), ferritin, neutrophil and lymphocyte counts, albumin, platelet counts, and calculated indices (C-reactive protein to Albumin Ratio (CAR), Neutrophil-to-Lymphocyte Ratio (NLR), Prognostic Nutritional Index (PNI), SII). Patients were stratified by CDI status and analyzed for inflammatory marker distributions, severity scores (APACHE II, CURB-65, NEWS), and outcomes (Intensive Care Unit (ICU) admission, mechanical ventilation, mortality). Subgroup analyses included diabetes, elderly (≥65 years), and cancer patients. Statistical comparisons employed t-tests, chi-square tests, and logistic regression models. Results: Patients with CDI demonstrated significantly higher CRP, IL-6, SII, and CAR, coupled with lower albumin and PNI (p < 0.05). They also had elevated APACHE II, CURB-65, and NEWS scores. CDI-positive patients experienced increased ICU admission (38.8% vs. 20.5%), mechanical ventilation (24.5% vs. 12.9%), and mortality (22.4% vs. 10.6%, all p < 0.05). Subgroup analyses revealed more pronounced inflammatory derangements and worse outcomes in elderly, diabetic, and cancer patients with CDI. Conclusions: Concurrent CDI intensifies systemic inflammation and adverse clinical trajectories in hospitalized COVID-19 patients. Elevations in inflammatory markers and severity scores predict worse outcomes, especially in high-risk subgroups. Early recognition and targeted interventions, including infection control and supportive measures, may attenuate disease severity and improve patient survival. Full article
(This article belongs to the Section Microbiology in Human Health and Disease)
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<p>Correlations of inflammatory markers and severity scores with outcomes.</p>
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<p>Logistic regression for independent predictors of severe outcomes.</p>
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16 pages, 1769 KiB  
Review
Perioperative Risk: Short Review of Current Approach in Non Cardiac Surgery
by Andreea Boghean, Cristian Guțu and Dorel Firescu
J. Cardiovasc. Dev. Dis. 2025, 12(1), 24; https://doi.org/10.3390/jcdd12010024 - 13 Jan 2025
Viewed by 941
Abstract
The rate of major surgery is constantly increasing worldwide, and approximately 85% are non-cardiac surgery. More than half of patients over 45 years presenting for non-cardiac surgical interventions have cardiovascular risk factors, and the most common: chronic coronary syndrome and history of stroke. [...] Read more.
The rate of major surgery is constantly increasing worldwide, and approximately 85% are non-cardiac surgery. More than half of patients over 45 years presenting for non-cardiac surgical interventions have cardiovascular risk factors, and the most common: chronic coronary syndrome and history of stroke. The preoperative cardiovascular risk is determined by the comorbidities, the clinical condition before the intervention, the urgency, duration or type. Cardiovascular risk scores are necessary tools to prevent perioperative cardiovascular morbidity and mortality and the most frequently used are Lee/RCRI (Revised Cardiac Risk Index), APACHE II (Acute Physiology and Chronic Health Evaluation), POSSUM (Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity), The American University of Beirut (AUB)-HAS2. To reduce the perioperative risk, there is a need for an appropriate preoperative risk assessment, as well as the choice of the type and timing of surgical intervention. Quantification of surgical risk as low, intermediate, and high is useful in identifying the group of patients who are at risk of complications such as myocardial infarction, thrombosis, arrhythmias, heart failure, stroke or even death. Currently there are not enough studies that can differentiate the risk according to gender, race, elective versus emergency procedure, the value of cardiac biomarkers. Full article
(This article belongs to the Section Cardiovascular Clinical Research)
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<p>Total risk estimated by the interaction between the surgical risk and the patient’s cardiovascular risk. The red arrows signify the probability of perioperative cardiovascular complications (adapted according to the ESC 2022 guidelines).</p>
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<p>Pre-operative assessment before non-cardiac surgery.</p>
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<p>Level of evidence AHA/ACC and ESC.</p>
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8 pages, 709 KiB  
Article
A Possible Protective Effect of IgA Against Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) in Bronchoalveolar Lavage in COVID-19 Patients Admitted to Intensive Care Unit
by Mariantonietta Di Stefano, Lucia Mirabella, Antonella Cotoia, Giuseppina Faleo, Michela Rauseo, Anna Chiara Rizzo, Josè Ramon Fiore, Gilda Cinnella and Gaetano Serviddio
Viruses 2024, 16(12), 1851; https://doi.org/10.3390/v16121851 - 28 Nov 2024
Viewed by 722
Abstract
SARS-CoV-2 infection induces a humoral immune response, producing virus-specific antibodies such as IgM, IgG, and IgA. IgA antibodies are present at mucosal sites, protecting against respiratory and other mucosal infections, including SARS-CoV-2, by neutralizing viruses or impeding attachment to epithelial cells. Since SARS-CoV-2 [...] Read more.
SARS-CoV-2 infection induces a humoral immune response, producing virus-specific antibodies such as IgM, IgG, and IgA. IgA antibodies are present at mucosal sites, protecting against respiratory and other mucosal infections, including SARS-CoV-2, by neutralizing viruses or impeding attachment to epithelial cells. Since SARS-CoV-2 spreads through the nasopharynx, the specific IgAs of SARS-CoV-2 are produced quickly after infection, effectively contributing to virus neutralization. Dimeric IgA has been reported to be 10 to 15 times more potent than its equivalent IgG, suggesting that this isotype may be particularly interesting in developing new monoclonal antibodies and/or new vaccines efficiently neutralizing the virus at the mucosal sites. It is still unclear whether IgA antibodies in BAL might play a role in the disease course and if their presence may have a prognostic significance. However, a harmful effect on diseases with high IgA titers has been reported. This study evaluated mucosal-specific IgA and IgG profiles in BAL of patients with COVID-19 acute respiratory failure admitted to the ICU. We included 57 patients (41 males and 16 females), admitted to the ICU of the University of Foggia. We used a commercially available ELISA assay to evaluate the presence of SARS-CoV-2 IgG and IgA antibodies in plasma and BAL of the 57 hospitalized patients with severe COVID-19 respiratory failure. However, 40/57 BAL and plasma from infected patients were available for the ELISA test; the remaining specimens were unsuitable. IgG and IgA antibodies against SARS-CoV-2 were detectable in 37 (92.5%) and 40 (100%) plasma specimens, respectively. IgG antibodies were found in a single sample, while IgAs were detected in 19 of 40 BAL samples analyzed. Correlations between these parameters and patient outcomes reveal a signature associated with survival. Interestingly, a statistically significant inverse correlation was found between the mortality rate and the presence of IgA to SARS-CoV-2 in BAL specimens. None of the 19 patients with a positive IgA died, compared to 7 out of 12 patients with a negative IgA-BAL (p: <0.0004). Despite being limited in size, this study suggests a significant protective effect of mucosal immunity in COVID-19 patients, even in advanced disease stages, and a role of IgA in the defense against the virus, as well as the possible use of effective vaccines and therapeutic strategies based on IgA antibodies. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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<p>SARS-CoV-2 IgA in BAL according to SOFA score in infected patients enrolled in ICU.</p>
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<p>SARS-CoV-2 IgA in BAL according to APACHE II score in infected patients enrolled in ICU.</p>
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10 pages, 258 KiB  
Article
Assessment of Inflammatory Scores in Severity Prediction for Elderly Patients with Odontogenic Infections
by Gianina Tapalaga, Luminita Maria Nica, Laura-Elena Cirligeriu, Bogdan Andrei Bumbu and Marius Pricop
Dent. J. 2024, 12(11), 371; https://doi.org/10.3390/dj12110371 - 20 Nov 2024
Viewed by 716
Abstract
Background and Objectives: Odontogenic infections (OIs) can lead to severe complications, especially in elderly patients due to age-related physiological changes and comorbidities. This study aims to evaluate the predictive accuracy of inflammatory scores—APACHE II, CURB-65, SOFA, and NEWS2—in determining the severity of odontogenic [...] Read more.
Background and Objectives: Odontogenic infections (OIs) can lead to severe complications, especially in elderly patients due to age-related physiological changes and comorbidities. This study aims to evaluate the predictive accuracy of inflammatory scores—APACHE II, CURB-65, SOFA, and NEWS2—in determining the severity of odontogenic infections among elderly patients (>70 years) compared to younger patients (<70 years). Materials and Methods: A retrospective cohort study was conducted on patients diagnosed with an OI at the Maxillofacial Surgery Department between January 2018 and January 2024. Patients were divided into two groups: elderly patients (>70 years, n = 49) and younger patients (<70 years, n = 64). The Symptom Severity score (SS) of odontogenic infections was calculated for all patients. Inflammatory scores—APACHE II, CURB-65, SOFA, and NEWS2—were assessed at admission and correlated with infection severity. Additional subgroup analyses were performed based on comorbidities and infection sites. Results: Elderly patients exhibited significantly higher SS scores (mean 12.47 ± 2.93) compared to younger patients (mean 7.82 ± 2.17, p < 0.001). APACHE II, CURB-65, SOFA and NEWS2 scores were significantly elevated in the elderly group (all p < 0.001). The SOFA score demonstrated the highest predictive accuracy for severe OIs in elderly patients, with an area under the curve (AUC) of 0.89 (95% CI: 0.82–0.95). Subgroup analyses revealed that comorbidities such as diabetes mellitus and cardiovascular disease significantly influenced infection severity (p < 0.05). Conclusions: Inflammatory scores, particularly SOFA, are effective in predicting the severity of odontogenic infections in elderly patients. The integration of these scores into clinical practice may enhance early identification of high-risk patients and improve management strategies. Full article
13 pages, 596 KiB  
Article
Prognostic Implications of Initial Radiological Findings of Pulmonary Fibrosis in Patients with Acute SARS-CoV-2 Infection: A Prospective Multicentric Study
by Roxana-Elena Cîrjaliu, Sri Vidhya Gurrala, Balaji Nallapati, Vamsi Krishna, Cristian Oancea, Emanuela Tudorache, Monica Marc, Felix Bratosin, Iulia Bogdan, Ovidiu Rosca, Paula Irina Barata, Laurentiu Tony Hangan, Sergiu Ioachim Chirilă and Ariadna-Petronela Fildan
Diseases 2024, 12(11), 285; https://doi.org/10.3390/diseases12110285 - 8 Nov 2024
Viewed by 1002
Abstract
Pulmonary fibrosis detected during the acute phase of SARS-CoV-2 infection may significantly influence patient prognosis. This study aimed to evaluate the prognostic value of initial high-resolution computed tomography (HRCT) findings of pulmonary fibrosis in hospitalized COVID-19 patients and to examine how these findings [...] Read more.
Pulmonary fibrosis detected during the acute phase of SARS-CoV-2 infection may significantly influence patient prognosis. This study aimed to evaluate the prognostic value of initial high-resolution computed tomography (HRCT) findings of pulmonary fibrosis in hospitalized COVID-19 patients and to examine how these findings relate to disease severity and clinical outcomes, with a particular focus on the development and validation of predictive scoring systems. In this multicentric prospective cohort study from January 2023 to January 2024, 120 adult patients with confirmed SARS-CoV-2 infection requiring hospitalization were enrolled from two Romanian university hospitals. Patients were categorized based on the presence (n = 60) or absence (n = 60) of pulmonary fibrosis signs on admission HRCT scans, identified by reticular opacities, traction bronchiectasis, honeycombing, and architectural distortion. Biochemical analyses, severity scores (SOFA, APACHE II, NEWS 2), and novel compound scores combining clinical and radiological data were assessed. Patients with HRCT evidence of pulmonary fibrosis had significantly higher severity scores and worse clinical outcomes. The HRCT score alone was a strong predictor of severe COVID-19 (area under the ROC curve [AUC] = 0.885), with a best cutoff value of 9.72, yielding 85.7% sensitivity and 79.8% specificity. Compound Score 1, integrating SOFA, APACHE II, and HRCT scores, demonstrated excellent predictive performance with an AUC of 0.947, sensitivity of 92.5%, and specificity of 88.9%. Compound Score 2, combining systemic inflammation markers (SIRI, SII) and NEWS 2, also showed a strong predictive capability (AUC = 0.913), with 89.2% sensitivity and 85.7% specificity at the optimal cutoff. Regression analysis revealed that Compound Score 1 had the highest hazard ratio for severe COVID-19 outcomes (HR = 4.89; 95% CI: 3.40–7.05), indicating its superior prognostic value over individual markers and traditional severity scores. Initial HRCT findings of pulmonary fibrosis are significantly associated with increased disease severity in hospitalized COVID-19 patients. The HRCT score is a valuable prognostic tool, and, when combined with clinical severity scores into Compound Score 1, it enhances the prediction of severe COVID-19 outcomes with high sensitivity and specificity. These compound scores facilitate the early identification of high-risk patients, guiding clinical decision-making and optimizing patient management to improve outcomes. Full article
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<p>Forest plot analysis of risk for severe COVID-19 development in patients with evidence of pulmonary fibrosis at admission.</p>
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7 pages, 1328 KiB  
Communication
Impact of Extracorporeal Membrane Oxygenation (ECMO) on Serum Concentrations of Cefepime
by Christopher J. Destache, Raul Isern, Dorothy Kenny, Rima El-Herte, Robert Plambeck, Catherine Palmer, Brent S. Inouye, Maura Wong, E. Jeffrey North, Mariaelena Roman Sotelo and Manasa Velagapudi
Antibiotics 2024, 13(11), 1024; https://doi.org/10.3390/antibiotics13111024 - 30 Oct 2024
Viewed by 816
Abstract
ECMO is becoming widely used as a life-saving measure for critically ill patients. However, there is limited data on pharmacokinetics and the dosing of beta-lactam antibiotics in ECMO. In this study, we evaluated the serum concentrations of cefepime in patients on ECMO to [...] Read more.
ECMO is becoming widely used as a life-saving measure for critically ill patients. However, there is limited data on pharmacokinetics and the dosing of beta-lactam antibiotics in ECMO. In this study, we evaluated the serum concentrations of cefepime in patients on ECMO to determine the impact of ECMO circuitry and to guide therapeutic dosing. Methods: Patients 19 years or older admitted to the ICU, treated with ECMO and beta-lactam antibiotics for presumed or documented infection, were enrolled. Three blood samples (peak, midpoint, trough) were obtained before ECMO (pre-ECMO) and during ECMO (intra-ECMO) at a steady state. Results: Eight patients met inclusion criteria; six received cefepime. All patients were male. Average ± SD age was 45.8 ± 14.7. Four patients received ECMO for severe SARS-CoV-2 infection, and one each for Pneumocystis pneumonia and influenza A infection. Mean ± SD APACHE II and SOFA scores prior to ECMO were 24.6 ± 7.1 and 11.0 ± 3.9, respectively. All but one of the patients received venovenous (VV) ECMO. Cefepime 1 g every 6 h intravenously over 2 min was administered to all patients before and during ECMO. Cefepime concentrations were fit to non-compartment analysis (NCA) and area under the serum concentration–time curve averaged ± SE 211.9 ± 29.6 pre-ECMO and 329.6 ± 32.3 mg*h/L intra-ECMO, p = 0.023. No patients displayed signs of cefepime neurotoxicity. Patients received ECMO for 43.1± 30 days. All patients expired. Cefepime dosed at 1 g every 6 h intravenously appears to achieve therapeutic levels for critically ill patients on ECMO. Full article
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<p>Cefepime structure [<a href="#B9-antibiotics-13-01024" class="html-bibr">9</a>].</p>
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<p>Cefepime biodistribution pre-ECMO (dashed lines) and intra-ECMO (solid lines). Each color represents results from each patient.</p>
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