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12 pages, 388 KiB  
Article
Evolution of Respiratory Pathogens and Antimicrobial Resistance over the COVID-19 Timeline: A Study of Hospitalized and Ambulatory Patient Populations
by Luigi Regenburgh De La Motte, Loredana Deflorio, Erika Stefano, Matteo Covi, Angela Uslenghi, Carmen Sommese and Lorenzo Drago
Antibiotics 2025, 14(8), 796; https://doi.org/10.3390/antibiotics14080796 - 5 Aug 2025
Viewed by 38
Abstract
Background: The COVID-19 pandemic has profoundly altered the clinical and microbiological landscape of respiratory tract infections (RTIs), potentially reshaping pathogen distribution and antimicrobial resistance (AMR) profiles across care settings. Objectives: The objective of this study was to assess temporal trends in respiratory bacterial [...] Read more.
Background: The COVID-19 pandemic has profoundly altered the clinical and microbiological landscape of respiratory tract infections (RTIs), potentially reshaping pathogen distribution and antimicrobial resistance (AMR) profiles across care settings. Objectives: The objective of this study was to assess temporal trends in respiratory bacterial pathogens, antimicrobial resistance, and polymicrobial infections across three pandemic phases—pre-COVID (2018–2019), COVID (2020–2022), and post-COVID (2022–2024)—in hospitalized and ambulatory patients. Methods: We retrospectively analyzed 1827 respiratory bacterial isolates (hospitalized patients, n = 1032; ambulatory patients, n = 795) collected at a tertiary care center in Northern Italy. Data were stratified by care setting, anatomical site, and pandemic phase. Species identification and susceptibility testing followed EUCAST guidelines. Statistical analysis included chi-square and Fisher’s exact tests. Results: In hospitalized patients, a significant increase in Pseudomonas aeruginosa (from 45.5% pre-COVID to 58.6% post-COVID, p < 0.0001) and Acinetobacter baumannii (from 1.2% to 11.1% during COVID, p < 0.0001) was observed, with 100% extensively drug-resistant (XDR) rates for A. baumannii during the pandemic. Conversely, Staphylococcus aureus significantly declined from 23.6% pre-COVID to 13.7% post-COVID (p = 0.0012). In ambulatory patients, polymicrobial infections peaked at 41.2% during COVID, frequently involving co-isolation of Candida spp. Notably, resistance to benzylpenicillin in Streptococcus pneumoniae reached 80% (4/5 isolates) in hospitalized patients during COVID, and carbapenem-resistant P. aeruginosa (CRPA) significantly increased post-pandemic in ambulatory patients (0% pre-COVID vs. 23.5% post-COVID, p = 0.0014). Conclusions: The pandemic markedly shifted respiratory pathogen dynamics and resistance profiles, with distinct trends observed in hospital and community settings. Persistent resistance phenotypes and frequent polymicrobial infections, particularly involving Candida spp. in outpatients, underscore the need for targeted surveillance and antimicrobial stewardship strategies. Full article
(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)
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25 pages, 906 KiB  
Review
Evolution and Prognostic Variables of Cystic Fibrosis in Children and Young Adults: A Narrative Review
by Mădălina Andreea Donos, Elena Țarcă, Elena Cojocaru, Viorel Țarcă, Lăcrămioara Ionela Butnariu, Valentin Bernic, Paula Popovici, Solange Tamara Roșu, Mihaela Camelia Tîrnovanu, Nicolae Sebastian Ionescu and Laura Mihaela Trandafir
Diagnostics 2025, 15(15), 1940; https://doi.org/10.3390/diagnostics15151940 - 2 Aug 2025
Viewed by 265
Abstract
Introduction: Cystic fibrosis (CF) is a genetic condition affecting several organs and systems, including the pancreas, colon, respiratory system, and reproductive system. The detection of a growing number of CFTR variants and genotypes has contributed to an increase in the CF population which, [...] Read more.
Introduction: Cystic fibrosis (CF) is a genetic condition affecting several organs and systems, including the pancreas, colon, respiratory system, and reproductive system. The detection of a growing number of CFTR variants and genotypes has contributed to an increase in the CF population which, in turn, has had an impact on the overall statistics regarding the prognosis and outcome of the condition. Given the increase in life expectancy, it is critical to better predict outcomes and prognosticate in CF. Thus, each person’s choice to aggressively treat specific disease components can be more appropriate and tailored, further increasing survival. The objective of our narrative review is to summarize the most recent information concerning the value and significance of clinical parameters in predicting outcomes, such as gender, diabetes, liver and pancreatic status, lung function, radiography, bacteriology, and blood and sputum biomarkers of inflammation and disease, and how variations in these parameters affect prognosis from the prenatal stage to maturity. Materials and methods: A methodological search of the available data was performed with regard to prognostic factors in the evolution of CF in children and young adults. We evaluated articles from the PubMed academic search engine using the following search terms: prognostic factors AND children AND cystic fibrosis OR mucoviscidosis. Results: We found that it is crucial to customize CF patients’ care based on their unique clinical and biological parameters, genetics, and related comorbidities. Conclusions: The predictive significance of more dynamic clinical condition markers provides more realistic future objectives to center treatment and targets for each patient. Over the past ten years, improvements in care, diagnostics, and treatment have impacted the prognosis for CF. Although genotyping offers a way to categorize CF to direct research and treatment, it is crucial to understand that a variety of other factors, such as epigenetics, genetic modifiers, environmental factors, and socioeconomic status, can affect CF outcomes. The long-term management of this complicated multisystem condition has been made easier for patients, their families, and physicians by earlier and more accurate identification techniques, evidence-based research, and centralized expert multidisciplinary care. Full article
(This article belongs to the Special Issue Advances in the Diagnosis of Inherited/Genetic Diseases)
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18 pages, 1404 KiB  
Article
Comparative Analysis of the Long-Term Real-World Efficacy of Interleukin-17 Inhibitors in a Cohort of Patients with Moderate-to-Severe Psoriasis Treated in Poland
by Wiktor Kruczek, Aleksandra Frątczak, Iga Litwińska-Inglot, Karina Polak, Zuzanna Pawlus, Paulina Rutecka, Beata Bergler-Czop and Bartosz Miziołek
J. Clin. Med. 2025, 14(15), 5421; https://doi.org/10.3390/jcm14155421 - 1 Aug 2025
Viewed by 165
Abstract
Background: Bimekizumab, secukinumab, and ixekizumab are IL-17-targeting biologics approved for the treatment of moderate-to-severe plaque psoriasis. While secukinumab and ixekizumab selectively inhibit IL-17A, bimekizumab targets both IL-17A and IL-17F, potentially providing greater anti-inflammatory efficacy. This study aimed to compare the real-world effectiveness, [...] Read more.
Background: Bimekizumab, secukinumab, and ixekizumab are IL-17-targeting biologics approved for the treatment of moderate-to-severe plaque psoriasis. While secukinumab and ixekizumab selectively inhibit IL-17A, bimekizumab targets both IL-17A and IL-17F, potentially providing greater anti-inflammatory efficacy. This study aimed to compare the real-world effectiveness, safety, and tolerability of these agents in a Polish dermatology center between 2019 and 2024. Methods: We conducted a retrospective analysis of 98 patients meeting at least one of the following criteria: PASI ≥ 10, BSA ≥ 10, DLQI ≥ 10, or involvement of special areas with inadequate response or contraindications to ≥2 systemic therapies. Patients with prior exposure only to IL-17 inhibitors were excluded. PASI, BSA, and DLQI scores were recorded at baseline, week 4, and week 12. Due to differences in dosing schedules, outcomes were aligned using standardized timepoints and exponential modeling of continuous response trajectories. Mixed-effects ANOVA was used to assess the influence of baseline factors (age, BMI, PsA status) on treatment outcomes. Adverse events were documented at each monthly follow-up visit. Results: Bimekizumab showed the greatest effect size for PASI reduction (Hedges’ g = 3.662), followed by secukinumab (2.813) and ixekizumab (1.986). Exponential modeling revealed a steeper response trajectory with bimekizumab (intercept = 0.289), suggesting a more rapid PASI improvement. The efficacy of bimekizumab was particularly notable in patients who were previously treated with IL-23 inhibitors. All three agents demonstrated favorable safety profiles, with no serious adverse events or discontinuations. The most frequent adverse events were mild and included upper respiratory tract infections and oral candidiasis. Conclusions: This real-world analysis confirmed that IL-17 inhibitors effectively improved PASI, BSA, and DLQI scores in moderate-to-severe psoriasis. Bimekizumab demonstrated the most rapid early improvements and a higher modeled likelihood of complete clearance, without significant differences at week 12. All agents were well tolerated, underscoring the need for further individualized, large-scale studies. Full article
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11 pages, 720 KiB  
Study Protocol
A Study Protocol to Assess the Association Between Ambient Air Pollution and Asthma and Other Respiratory Health Outcomes Amongst Children Below 5 Years of Age in Alexandra Township’s Early Childhood Development Centers, Johannesburg
by Velisha Thompson, Joyce Shirinde, Masilu D. Masekameni and Thokozani P. Mbonane
Methods Protoc. 2025, 8(4), 84; https://doi.org/10.3390/mps8040084 - 1 Aug 2025
Viewed by 197
Abstract
Air pollution is linked to childhood mortality and morbidity in low- and middle-income countries globally. There is growing evidence linking air pollution to asthma and other respiratory diseases in children. Studies have shown that children are likely to experience asthma due to their [...] Read more.
Air pollution is linked to childhood mortality and morbidity in low- and middle-income countries globally. There is growing evidence linking air pollution to asthma and other respiratory diseases in children. Studies have shown that children are likely to experience asthma due to their narrow airways and their heightened sensitivity to environmental irritants. This study aims to investigate the relationship between ambient air pollution and respiratory diseases in children under the age of 5. The study will be conducted in the informal township of Alexandra, north of Johannesburg, South Africa. A quantitative approach will be used in this cross-sectional analytical study. Data will be collected using different tools that include a questionnaire to determine the prevalence of asthma and respiratory disease and potential risk factors. While environmental air pollution will be measured using Radiello passive samplers and Gillian pumps. Data will be analyzed using the latest version of the STATANow/MP 19.5 software. Furthermore, health risk assessment will be conducted for lifetime non-carcinogenic and carcinogenic risk estimation following the USEPA framework. The study will identify environmental triggers that exacerbate asthma and other respiratory conditions in other similar community settings and will contribute to the body of knowledge in public health. Ethical approval was obtained from the Research Ethics Committee, Faculty of Health Sciences at the University of Johannesburg. Full article
(This article belongs to the Section Public Health Research)
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15 pages, 664 KiB  
Article
Real-World Safety of Vedolizumab in Inflammatory Bowel Disease: A Retrospective Cohort Study Supported by FAERS Signal Analysis
by Bojana Milašinović, Sandra Vezmar Kovačević, Srđan Marković, Marija Jovanović, Tamara Knežević Ivanovski, Đorđe Kralj, Petar Svorcan, Branislava Miljković and Katarina Vučićević
Pharmaceuticals 2025, 18(8), 1127; https://doi.org/10.3390/ph18081127 - 28 Jul 2025
Viewed by 410
Abstract
Background/Objectives: Vedolizumab is a gut-selective anti-integrin monoclonal antibody approved for the treatment of inflammatory bowel disease (IBD). While clinical trials have demonstrated a favorable safety profile, real-world studies are essential for identifying rare adverse events (AEs) and evaluating post-marketing safety. This study [...] Read more.
Background/Objectives: Vedolizumab is a gut-selective anti-integrin monoclonal antibody approved for the treatment of inflammatory bowel disease (IBD). While clinical trials have demonstrated a favorable safety profile, real-world studies are essential for identifying rare adverse events (AEs) and evaluating post-marketing safety. This study assessed vedolizumab’s safety in a real-world cohort and supported the detection of potential safety signals. Methods: A retrospective chart review was conducted on adult IBD patients treated with vedolizumab at a tertiary center in the Republic of Serbia between October 2021 and August 2022. Data included demographics, AEs, and newly reported extraintestinal manifestations (EIMs). Exposure-adjusted incidence rates were calculated per 100 patient-years (PYs). Disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) was performed to identify safety signals, employing reporting odds ratios (RORs) and proportional reporting ratios (PRRs) for AEs also observed in the cohort. Prior IBD therapies and reasons for discontinuation were evaluated. Results: A total of 107 patients (42.1% Crohn’s disease, 57.9% ulcerative colitis) were included, with a median vedolizumab exposure of 605 days. There were 92 AEs (56.51/100 PYs), most frequently infections (23.95/100 PYs), gastrointestinal disorders (4.30/100 PYs), and skin disorders (4.30/100 PYs). The most frequently reported preferred terms (PTs) included COVID-19, COVID-19 pneumonia, nephrolithiasis, and nasopharyngitis. Arthralgia (12.90/100 PYs) was the most frequent newly reported EIM. No discontinuations due to vedolizumab AEs occurred. FAERS analysis revealed potential signals for events not listed in prescribing information but observed in the cohort: nephrolithiasis, abdominal pain, diarrhea, malaise, cholangitis, gastrointestinal infection, blood pressure decreased, weight decreased, female genital tract fistula, respiratory symptom, and appendicectomy. Most patients had received three prior therapies, often stopping one due to AEs. Conclusions: Vedolizumab demonstrated a favorable safety profile in the IBD cohort. However, FAERS-identified signals, such as nephrolithiasis, gastrointestinal infections, and decreased blood pressure, warrant further investigation in larger, more diverse populations. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring and Adverse Drug Reactions: 2nd Edition)
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11 pages, 495 KiB  
Article
Multiple Organ Failure as a Strong Predictor of Mortality in Patients with Hypoxic Hepatitis
by Ji Yoon Kwak, Hankyu Jeon, Hyeon Uk Kwon, Jae Eun Kim, Seong Je Kim, Ji Hee Han, Ra Ri Cha, Jae Min Lee and Sang Soo Lee
J. Clin. Med. 2025, 14(15), 5286; https://doi.org/10.3390/jcm14155286 - 26 Jul 2025
Viewed by 311
Abstract
Background: Hypoxic hepatitis contributes to the development and progression of multiple organ failure (MOF). We evaluated whether MOF is associated with 30-day mortality in patients with hypoxic hepatitis. Methods: This retrospective study included 1011 patients diagnosed with hypoxic hepatitis at two [...] Read more.
Background: Hypoxic hepatitis contributes to the development and progression of multiple organ failure (MOF). We evaluated whether MOF is associated with 30-day mortality in patients with hypoxic hepatitis. Methods: This retrospective study included 1011 patients diagnosed with hypoxic hepatitis at two centers in South Korea between 2010 and 2021. Organ failure was defined as a sequential organ failure assessment score ≥ 3 for each individual organ system. Results: Circulatory failure was the most common organ failure (n = 521), followed by respiratory (n = 380), cerebral (n = 307), renal (n = 236), coagulation (n = 182), and hepatic failure (n = 73). The proportions of patients without organ failure, with single organ failure, and with MOF were 28.7%, 22.3%, and 49.1%, respectively, with corresponding 30-day mortality rates of 17.9%, 29.3%, and 70.0%. In the multivariate Cox regression model, the presence of MOF grade 1 (two organ failures), grade 2 (three organ failures), and grade 3 (≥four organ failures) increased the risk of 30-day mortality by approximately threefold, fourfold, and fivefold, respectively, compared to patients without MOF. Conclusions: MOF is frequently observed in patients with hypoxic hepatitis and is a strong independent predictor of short-term mortality. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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11 pages, 1250 KiB  
Article
Height Velocity in Pediatric Cystic Fibrosis Under Triple CFTR Modulator Therapy: A Real-Life Monocentric Experience
by Alessandra Boni, Francesco d’Aniello, Grazia Ubertini, Marco Cappa, Fabiana Ciciriello, Fabio Majo, Luca Cristiani, Federico Alghisi, Enza Montemitro, Sergio Bella, Matteo De Marchis, Renato Cutrera and Alessandro G. Fiocchi
J. Clin. Med. 2025, 14(15), 5259; https://doi.org/10.3390/jcm14155259 - 25 Jul 2025
Viewed by 268
Abstract
Background/Objectives: Cystic fibrosis (CF) is a multi-system disorder characterized by chronic respiratory failure, malnutrition, and impaired growth. Achieving linear growth above the 50th percentile is associated with better pulmonary outcomes. Since October 2022, Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been approved in Italy for children aged [...] Read more.
Background/Objectives: Cystic fibrosis (CF) is a multi-system disorder characterized by chronic respiratory failure, malnutrition, and impaired growth. Achieving linear growth above the 50th percentile is associated with better pulmonary outcomes. Since October 2022, Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been approved in Italy for children aged ≥6 years. However, data on its impact on height velocity (HV) remain lacking. This study aims to evaluate growth patterns by HV and explore differences according to the CFTR variant genotype. Methods: We conducted a prospective single-center study at the CF Unit of Bambino Gesù Children’s Hospital involving 24 children aged 6–11 years eligible for ETI treatment. Baseline assessments included height, weight, body mass index (BMI), bone mineral density (BMD), body composition (via bioelectrical impedance analysis, BIA), and muscle strength (one-minute sit-to-stand test (1STST)). Height, weight, HV, and BMI standard deviation scores (SDS) were calculated for the 6 months before and after ETI initiation. Results: The mean age of the cohort was 8.7 ± 1.9 years (F/M: 12/12), with most patients naïve to CFTR modulators. A significant increase in HV was observed post-ETI: from 4.2 ± 2.0 cm/year (−1.96 ± 2.4 SDS) in the 6 months before treatment to 7.1 ± 3.0 cm/year (+1.5 ± 3.7 SDS) after treatment initiation (p < 0.0001). Patients with F508del/minimal function (F/MF) genotypes (n = 11) showed significantly greater HV compared to those with F508del/F508del (F/F, n = 5) and F508del/residual function (F/RF, n = 8) genotypes (p < 0.0001). No significant differences were observed among genetic groups in baseline BMD or lean mass. Conclusions: ETI treatment significantly and rapidly improves HV in children with CF, particularly in those with F/MF genotypes. These findings underscore the role of CFTR modulator therapy in promoting linear growth, a key indicator of health in pediatric CF populations. Full article
(This article belongs to the Special Issue Cystic Fibrosis: Diagnosis and Treatment)
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13 pages, 1952 KiB  
Article
Real-Time Dose Measurement in Brachytherapy Using Scintillation Detectors Based on Ce3+-Doped Garnet Crystals
by Sandra Witkiewicz-Łukaszek, Bogna Sobiech, Janusz Winiecki and Yuriy Zorenko
Crystals 2025, 15(8), 669; https://doi.org/10.3390/cryst15080669 - 23 Jul 2025
Viewed by 222
Abstract
Conventional detectors based on ionization chambers, semiconductors, or thermoluminescent materials generally cannot be used to verify the in vivo dose delivered during brachytherapy treatments with γ-ray sources. However, certain adaptations and alternative methods, such as the use of miniaturized detectors or other specialized [...] Read more.
Conventional detectors based on ionization chambers, semiconductors, or thermoluminescent materials generally cannot be used to verify the in vivo dose delivered during brachytherapy treatments with γ-ray sources. However, certain adaptations and alternative methods, such as the use of miniaturized detectors or other specialized techniques, have been explored to address this limitation. One approach to solving this problem involves the use of dosimetric materials based on efficient scintillation crystals, which can be placed in the patient’s body using a long optical fiber inserted intra-cavernously, either in front of or next to the tumor. Scintillation crystals with a density close to that of tissue can be used in any location, including the respiratory tract, as they do not interfere with dose distribution. However, in many cases of radiation therapy, the detector may need to be positioned behind the target. In such cases, the use of heavy, high-density, and high-Zeff scintillators is strongly preferred. The delivered radiation dose was registered using the radioluminescence response of the crystal scintillator and recorded with a compact luminescence spectrometer connected to the scintillator via a long optical fiber (so-called fiber-optic dosimeter). This proposed measurement method is completely non-invasive, safe, and can be performed in real time. To complete the abovementioned task, scintillation detectors based on YAG:Ce (ρ = 4.5 g/cm3; Zeff = 35), LuAG:Ce (ρ = 6.75 g/cm3; Zeff = 63), and GAGG:Ce (ρ = 6.63 g/cm3; Zeff = 54.4) garnet crystals, with different densities ρ and effective atomic numbers Zeff, were used in this work. The results obtained are very promising. We observed a strong linear correlation between the dose and the scintillation signal recorded by the detector system based on these garnet crystals. The measurements were performed on a specially prepared phantom in the brachytherapy treatment room at the Oncology Center in Bydgoszcz, where in situ measurements of the applied dose in the 0.5–8 Gy range were performed, generated by the 192Ir (394 keV) γ-ray source from the standard Fexitron Elektra treatment system. Finally, we found that GAGG:Ce crystal detectors demonstrated the best figure-of-merit performance among all the garnet scintillators studied. Full article
(This article belongs to the Special Issue Recent Advances in Scintillator Materials)
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12 pages, 439 KiB  
Article
Non-Invasive Capnography Versus Pulse Oximetry for Early Detection of Respiratory Depression During Pediatric Procedural Sedation: A Prospective Observational Study
by Laura Català Altarriba, Sean Yeh Hsi, Aude Marie Ravit, Sònia Brió Sanagustín and Xoan González-Rioja
Children 2025, 12(7), 938; https://doi.org/10.3390/children12070938 - 16 Jul 2025
Viewed by 310
Abstract
Background/Objectives: Continuous ventilation monitoring during pediatric sedation is essential, as respiratory depression may occur silently and may not be detected promptly by conventional methods such as pulse oximetry. Non-invasive capnography has been proposed to improve early detection of respiratory compromise. This prospective observational [...] Read more.
Background/Objectives: Continuous ventilation monitoring during pediatric sedation is essential, as respiratory depression may occur silently and may not be detected promptly by conventional methods such as pulse oximetry. Non-invasive capnography has been proposed to improve early detection of respiratory compromise. This prospective observational study evaluated the diagnostic accuracy of non-invasive capnography, compared to pulse oximetry, for detecting respiratory depression in pediatric patients undergoing sedation. Methods: We conducted a single-center, prospective observational study at a tertiary pediatric hospital, enrolling 101 patients (ages 1–17 years) undergoing sedation for diagnostic or therapeutic procedures. Patients were monitored using both pulse oximetry and non-invasive capnography. Episodes of respiratory depression—defined as apnea, hypopneic hypoventilation, bradypneic hypoventilation, and desaturation—were recorded. We compared the diagnostic performance and time to detection between capnography and pulse oximetry. Results: We identified 93 episodes of respiratory depression in 52 patients (51.1%). Capnography detected all apnea episodes and 76.9% of hypopneic hypoventilation episodes that were not identified by pulse oximetry. The median time advantage of capnography over pulse oximetry was 35 s (p = 0.0055). Combining capnography and pulse oximetry identified more events than pulse oximetry alone (93 vs. 53 episodes). Conclusions: Non-invasive capnography improves the early detection of respiratory depression compared to conventional monitoring with pulse oximetry in pediatric procedural sedation. While these findings support its routine use to enhance patient safety, larger multicenter studies are needed to demonstrate its diagnostic accuracy and impact on clinical outcomes. Full article
(This article belongs to the Section Pediatric Anesthesiology, Pain Medicine and Palliative Care)
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12 pages, 1016 KiB  
Article
Clinical Characteristics and Outcomes for Neonates with Respiratory Failure Referred for Extracorporeal Membrane Oxygenator (ECMO) Support
by Pooja Musuku, Keith Meyer, Felipe E. Pedroso, Fuad Alkhoury and Balagangadhar R. Totapally
Children 2025, 12(7), 925; https://doi.org/10.3390/children12070925 - 13 Jul 2025
Viewed by 253
Abstract
Objective: The aim of this study was to describe the presenting characteristics and outcomes of neonates with respiratory failure referred for extracorporeal membrane oxygenation (ECMO) support, compare those who received ECMO support (ECMO group) to those who did not (non-ECMO group), and [...] Read more.
Objective: The aim of this study was to describe the presenting characteristics and outcomes of neonates with respiratory failure referred for extracorporeal membrane oxygenation (ECMO) support, compare those who received ECMO support (ECMO group) to those who did not (non-ECMO group), and evaluate the predictive variables requiring ECMO support. Methods: All neonates (<15 days) with respiratory failure (without congenital diaphragmatic hernia or congenital heart disease) referred to our regional ECMO center from 2014 to 2023 were included in this retrospective study. Patient demographics, birth history, and clinical and outcome variables were analyzed. Oxygenation indices and vasoactive–inotropic scores obtained at PICU arrival and four hours after arrival were compared between the two groups using ROC analysis, with ECMO initiation as an outcome variable. Youden’s index was used for optimal threshold values. Chi-square, Mann–Whitney U, and binary logistic regression were used for comparative analyses. Results: Out of the 147 neonates, 96 (65%) required ECMO support. The two groups significantly differed in the prevalence of pulmonary hypertension (pHTN; systemic or suprasystemic pulmonary pressures), lactate level, and oxygenation indices. Mortality was not different between the two groups. Presence of oxygen saturation index (OSI) ≥ 10 had a sensitivity 96.8% in predicting the need for ECMO support. On regression analysis, OSI and pHTN were independent predictors of ECMO support. Conclusions: Oxygenation indices and echo findings predict the need for ECMO support in neonatal hypoxemic respiratory failure. These findings help non-ECMO centers make appropriate and timely transfers of neonates with respiratory failure to ECMO centers. Full article
(This article belongs to the Special Issue Diagnosis and Management of Newborn Respiratory Distress Syndrome)
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36 pages, 4581 KiB  
Article
Temporal Trends and Patient Stratification in Lung Cancer: A Comprehensive Clustering Analysis from Timis County, Romania
by Versavia Maria Ancusa, Ana Adriana Trusculescu, Amalia Constantinescu, Alexandra Burducescu, Ovidiu Fira-Mladinescu, Diana Lumita Manolescu, Daniel Traila, Norbert Wellmann and Cristian Iulian Oancea
Cancers 2025, 17(14), 2305; https://doi.org/10.3390/cancers17142305 - 10 Jul 2025
Viewed by 621
Abstract
Background/Objectives: Lung cancer remains a major cause of cancer-related mortality, with regional differences in incidence and patient characteristics. This study aimed to verify and quantify a perceived dramatic increase in lung cancer cases at a Romanian center, identify distinct patient phenotypes using unsupervised [...] Read more.
Background/Objectives: Lung cancer remains a major cause of cancer-related mortality, with regional differences in incidence and patient characteristics. This study aimed to verify and quantify a perceived dramatic increase in lung cancer cases at a Romanian center, identify distinct patient phenotypes using unsupervised machine learning, and characterize contributing factors, including demographic shifts, changes in the healthcare system, and geographic patterns. Methods: A comprehensive retrospective analysis of 4206 lung cancer patients admitted between 2013 and 2024 was conducted, with detailed molecular characterization of 398 patients from 2023 to 2024. Temporal trends were analyzed using statistical methods, while k-means clustering on 761 clinical features identified patient phenotypes. The geographic distribution, smoking patterns, respiratory comorbidities, and demographic factors were systematically characterized across the identified clusters. Results: We confirmed an 80.5% increase in lung cancer admissions between pre-pandemic (2013–2020) and post-pandemic (2022–2024) periods, exceeding the 51.1% increase in total hospital admissions and aligning with national Romanian trends. Five distinct patient clusters emerged: elderly never-smokers (28.9%) with the highest metastatic rates (44.3%), heavy-smoking males (27.4%), active smokers with comprehensive molecular testing (31.7%), young mixed-gender cohort (7.3%) with balanced demographics, and extreme heavy smokers (4.8%) concentrated in rural areas (52.6%) with severe comorbidity burden. Clusters demonstrated significant differences in age (p < 0.001), smoking intensity (p < 0.001), geographic distribution (p < 0.001), as well as molecular characteristics. COPD prevalence was exceptionally high (44.8–78.9%) across clusters, while COVID-19 history remained low (3.4–8.3%), suggesting a limited direct association between the pandemic and cancer. Conclusions: This study presents the first comprehensive machine learning-based stratification of lung cancer patients in Romania, confirming genuine epidemiological increases beyond healthcare system artifacts. The identification of five clinically meaningful phenotypes—particularly rural extreme smokers and age-stratified never-smokers—demonstrates the value of unsupervised clustering for regional healthcare planning. These findings establish frameworks for targeted screening programs, personalized treatment approaches, and resource allocation strategies tailored to specific high-risk populations while highlighting the potential of artificial intelligence in identifying actionable clinical patterns for the implementation of precision medicine. Full article
(This article belongs to the Section Cancer Epidemiology and Prevention)
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15 pages, 1110 KiB  
Review
Sleep-Disordered Breathing and Interactions with Opioids: A Narrative Review
by Peyton J. Murin, Jora Wang and Yuri Chaves Martins
J. Clin. Med. 2025, 14(13), 4758; https://doi.org/10.3390/jcm14134758 - 4 Jul 2025
Viewed by 674
Abstract
Opioid use in patients with sleep disordered breathing (SDB) presents therapeutic challenges within chronic pain and sleep medicine. Opioids impair respiratory drive through μ-opioid receptor activation in brainstem respiratory centers, exacerbating both obstructive and central apneas. Chronic opioid use is also linked to [...] Read more.
Opioid use in patients with sleep disordered breathing (SDB) presents therapeutic challenges within chronic pain and sleep medicine. Opioids impair respiratory drive through μ-opioid receptor activation in brainstem respiratory centers, exacerbating both obstructive and central apneas. Chronic opioid use is also linked to a high prevalence of central sleep apnea and increased nocturnal hypoventilation. Simultaneously, SDB contributes to heightened pain sensitivity via intermittent hypoxia, systemic inflammation, and alterations in neural plasticity. These mechanisms may influence opioid efficacy and dosing requirements. This review summarizes current evidence on how SDB and opioid use interact, emphasizing chronic opioid use in the setting of chronic pain management. We discuss the underlying mechanisms, clinical impacts, and potential avenues for enhanced diagnosis and therapy in this population. We conclude that the intersection of SDB and opioid use presents a complex clinical challenge that demands a multidisciplinary approach. Enhanced screening, personalized pharmacologic strategies, and integration of advanced diagnostics are essential for mitigating risks and optimizing care. Future research should focus on mechanistic studies and interventional trials to guide evidence-based management of this high-risk population. Full article
(This article belongs to the Section Anesthesiology)
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9 pages, 206 KiB  
Article
Predictors of Impaired Treatment Outcomes in COVID-19: A Single-Center Observational Study from Serbia
by Tatjana Adzic-Vukicevic, Milan Racic, Nikolina Tovarisic-Racic, Marija Laban-Lazovic, Sead Dalifi and Jovana Radmilovic
Diagnostics 2025, 15(13), 1685; https://doi.org/10.3390/diagnostics15131685 - 2 Jul 2025
Viewed by 393
Abstract
Background: COVID-19 disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); it is characterized by a hypercoagulable state that results in an increased risk for embolic and thrombotic vascular complications. The incidence of pulmonary embolism (PE) in COVID-19 varies between 20 and 30%. [...] Read more.
Background: COVID-19 disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); it is characterized by a hypercoagulable state that results in an increased risk for embolic and thrombotic vascular complications. The incidence of pulmonary embolism (PE) in COVID-19 varies between 20 and 30%. In addition to PE, older age, male sex, the presence of comorbidities, invasive mechanical ventilation, and prolonged hospitalization in intensive care units (ICUs) seem to be the main predictors for impaired treatment outcomes in COVID-19. Materials and methods: A retrospective observational single-center study was conducted between 1 September 2021 and 24 December 2021 involving 2111 patients admitted to the COVID Hospital “Batajnica”, University Clinical Center of Serbia, Belgrade. A total of 200 consecutive patients were enrolled in study. Patients were divided into two groups—the study group (100 patients), with COVID-19 and PE, and the control group (100 patients), with COVID-19 but without PE. Results: According to the multivariate regression analysis, the predictors of impaired outcomes in COVID-19 patients are age (p < 0.001; OR 1.134; 95% HR 1.062–1.211), C reactive protein level (CRP) (p = 0.043; OR 1.006; 95% 1.000–1.013), invasive mechanical ventilation (IMV) (p < 0.001; OR 58.72; 95% HR 13.784–254.189), pulmonary embolism (PE) (p = 0.025; OR 3.718; 95% HR 1.183–11.681), and hospitalization in ICU (p = 0.012; OR 9.673; 95% 1.660–56.363). Conclusions: We report increased mortality and mechanical ventilation rates in COVID-19 patients with acute PE. Older age, elevated levels of CRP, hospitalization in ICU, and PE present independent predictors for impaired outcomes in COVID-19 patients. To determine predictors for treatment outcomes in patients with COVID-19 and their associations with clinical and laboratory parameters Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Management of Respiratory Illnesses)
20 pages, 2564 KiB  
Article
Investigating the Mechanisms Underlying Citral-Induced Oxidative Stress and Its Contribution to Antifungal Efficacy on Magnaporthe oryzae Through a Multi-Omics Approach
by Yonghui Huang, Ruoruo Wang, Yumei Tan, Yongxiang Liu, Xiyi Ren, Congtao Guo, Rongyu Li and Ming Li
Plants 2025, 14(13), 2001; https://doi.org/10.3390/plants14132001 - 30 Jun 2025
Viewed by 347
Abstract
Citral, an organic compound found in lemongrass (Cymbopogon citratus) oil and Litsea cubeba essential oil, has been reported to exhibit notable antifungal activity against Magnaporthe oryzae (M. oryzae), the pathogen of rice blast, which causes significant economic losses in [...] Read more.
Citral, an organic compound found in lemongrass (Cymbopogon citratus) oil and Litsea cubeba essential oil, has been reported to exhibit notable antifungal activity against Magnaporthe oryzae (M. oryzae), the pathogen of rice blast, which causes significant economic losses in rice production. However, the role of citral in inducing oxidative stress related to antifungal ability and its underlying regulatory networks in M. oryzae remain unclear. In this study, we investigated the oxidative effects of citral on M. oryzae and conducted transcriptomic and widely targeted metabolomic (WTM) analyses on the mycelia. The results showed that citral induced superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) activities but reduced glutathione S-transferase (GST) activity with 25% maximal effective concentration (EC25) and 75% maximal effective concentration (EC75). Importantly, citral at EC75 reduced the activities of mitochondrial respiratory chain complex I, complex III and ATP content, while increasing the activity of mitochondrial respiratory chain complex II. In addition, citral triggered a burst of reactive oxygen species (ROS) and a loss of mitochondrial membrane potential (MMP) through the observation of fluorescence. Furthermore, RNA-seq analysis and metabolomics analysis identified a total of 466 differentially expression genes (DEGs) and 32 differential metabolites (DAMs) after the mycelia were treated with citral. The following multi-omics analysis revealed that the metabolic pathways centered on AsA, GSH and melatonin were obviously suppressed by citral, indicating a disrupted redox equilibrium in the cell. These findings provide further evidences supporting the antifungal activity of citral and offer new insights into the response of M. oryzae under oxidative stress induced by citral. Full article
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18 pages, 652 KiB  
Article
Nasopharyngeal Carriage, Serotype Distribution, and Antimicrobial Susceptibility of Streptococcus pneumoniae Among PCV13-Vaccinated and -Unvaccinated Children in Iran
by Fatemeh Ashrafian, Mona Sadat Larijani, Saiedeh Haji Maghsoudi, Delaram Doroud, Alireza Fahimzad, Zahra Pournasiri, Elham Jafari, Masoumeh Parzadeh, Sara Abdollahi, Elham Haj Agha Gholizadeh Khiavi, Anahita Bavand, Morvarid Shafiei, Mahdi Rohani and Amitis Ramezani
Vaccines 2025, 13(7), 707; https://doi.org/10.3390/vaccines13070707 - 29 Jun 2025
Viewed by 505
Abstract
Background and Aim: Pneumococcal pneumonia is a major cause of death globally, emphasizing the importance of vaccination, especially in low- and middle-income countries. In Iran, the 13-valent pneumococcal conjugate vaccine (PCV13) is available exclusively through private healthcare systems, resulting in a lack [...] Read more.
Background and Aim: Pneumococcal pneumonia is a major cause of death globally, emphasizing the importance of vaccination, especially in low- and middle-income countries. In Iran, the 13-valent pneumococcal conjugate vaccine (PCV13) is available exclusively through private healthcare systems, resulting in a lack of studies on the prevalence of Streptococcus pneumoniae (S. pneumoniae) serotypes among vaccinated children. This research aimed to explore and compare the prevalence of nasopharyngeal pneumococcal carriage, serotype distribution, and antibiotic resistance patterns in healthy PCV13-vaccinated and -unvaccinated children. Methods: From August 2023 to November 2024, a multi-center, cross-sectional observational study was conducted in Tehran, Iran. This study included 204 nasopharyngeal samples collected from children aged from 18 to 59 months, involving both cases of children vaccinated with PCV13 and unvaccinated populations. S. pneumoniae was identified through a combination of culture methods and biochemical tests, confirmed by real-time PCR. Serotyping was achieved using cpsB sequencing, and the minimum inhibitory concentration method was employed to assess antibiotic resistance. Results: This study revealed similar S. pneumoniae carriage rates between PCV13-vaccinated and -unvaccinated Iranian children (20.6% vs. 21.6%). Serotypes 23F and 19F were prevalent in unvaccinated children, while 15B/15C was more prevalent in PCV13-vaccinated children. The included S. pneumoniae serotypes in PCV13 were detected more in the unvaccinated group. PCV13-vaccinated children exhibited no penicillin-resistant pneumococcal isolates, although four isolates were non-susceptible in unvaccinated children. Both groups showed substantial resistance to erythromycin and SXT. Previous respiratory infections, daycare attendance, residence in Tehran, and a history of antibiotic consumption increased the risk of pneumococcal carriage. Conclusions: PCV13 vaccination influences pneumococcal serotype distribution and antimicrobial susceptibility, although there was no significant difference regarding carriage rates between vaccinated and unvaccinated groups. These findings highlight the critical importance of vaccination in reducing invasive serotypes and antimicrobial resistance in children under five years old, emphasizing the importance of national PCV vaccination programs alongside continuous serotype surveillance. Full article
(This article belongs to the Section Epidemiology and Vaccination)
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