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22 pages, 1668 KB  
Article
Chromosomal Mechanisms of Colistin Resistance in Clinical Isolates of Carbapenem-Resistant Klebsiella pneumoniae from a Tunisian Tertiary-Care Hospital
by Zaineb Hamzaoui, Hajer Kilani, Alain Ocampo-Sosa, Sana Ferjani, Elaa Maamar, Lamia Kanzari, Ahmed Fakhfakh, Amel Rehaiem, Luis Martínez-Martínez and Ilhem Boutiba Ben Boubaker
Infect. Dis. Rep. 2026, 18(3), 42; https://doi.org/10.3390/idr18030042 - 1 May 2026
Abstract
Background/Objectives: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major nosocomial pathogen. Although newer agents have reduced colistin use in high-income countries, this polymyxin remains important in many low- and middle-income settings. Colistin resistance in K. pneumoniae is most commonly associated with chromosomal alterations affecting [...] Read more.
Background/Objectives: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major nosocomial pathogen. Although newer agents have reduced colistin use in high-income countries, this polymyxin remains important in many low- and middle-income settings. Colistin resistance in K. pneumoniae is most commonly associated with chromosomal alterations affecting the MgrB–PhoPQ pathway, or with plasmid-mediated mcr genes. This study aimed to investigate chromosomally mediated colistin resistance in CRKP clinical isolates from a Tunisian tertiary hospital. Methods: Between 2010 and 2015, 317 non-duplicate CRKP isolates were collected at Charles Nicolle Hospital, Tunis. Colistin MICs were determined by broth microdilution. Phenotypic tests and PCR characterized carbapenemases, extended-spectrum β-lactamases, AmpC, plasmid-mediated quinolone resistance, mcr and virulence genes. Porins (OmpK35/OmpK36) and the mgrB, phoP and phoQ loci were analyzed by SDS-PAGE and sequencing. Clonal relatedness was assessed by ERIC-PCR and multilocus sequence typing. We additionally compared colistin-resistant isolates with a panel of colistin-susceptible CRKP controls and assessed phenotypic stability after serial passages without colistin. Results: Five isolates (1.6%) were colistin-resistant. All were multidrug-resistant, produced OXA-48, and two also carried NDM-1. The isolates belonged to five distinct sequence types, including high-risk clones (ST11, ST101, ST147). No mcr genes were detected. Four isolates carried disruptive mutations in mgrB, and the remaining strain harbored inactivating mutations in both phoP and phoQ with an intact mgrB. Truncating alterations in PhoP/PhoQ and frequent loss or truncation of OmpK35/OmpK36 were observed. No mgrB/phoP/phoQ alterations were detected among colistin-susceptible controls, and colistin MICs remained stable after 7 days of drug-free passaging. Conclusions: In Tunisian CRKP, colistin resistance was associated with chromosomal alterations, predominantly involving disruption of the MgrB–PhoPQ pathway, in the absence of mcr genes. These mechanisms in both high-risk and emerging sequence types underscore the adaptability of CRKP and the need for surveillance where colistin remains an important therapeutic option. Full article
(This article belongs to the Section Antimicrobial Stewardship and Resistance)
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16 pages, 28163 KB  
Article
Extraction, Purification, and Characterization of a Bacteriocin from Marine Lactococcus lactis NAN6399: Evaluating Antioxidant and Antimicrobial Activities
by Fatma A. Ameen, Mahmoud E. Soliman, Amira M. Hamdan and Sherif F. Hammad
Microorganisms 2026, 14(5), 1030; https://doi.org/10.3390/microorganisms14051030 - 1 May 2026
Abstract
We evaluated the antimicrobial and antioxidant capabilities of a bacteriocin purified from a recently identified marine Lactococcus lactis (L. lactis) NAN6399 strain, a lactic acid bacterium recovered from Mediterranean coastal waters near Alexandria, Egypt, and identified by combined API 50 CHL [...] Read more.
We evaluated the antimicrobial and antioxidant capabilities of a bacteriocin purified from a recently identified marine Lactococcus lactis (L. lactis) NAN6399 strain, a lactic acid bacterium recovered from Mediterranean coastal waters near Alexandria, Egypt, and identified by combined API 50 CHL phenotypic profiling and 16S rRNA gene sequencing. Bacteriocin purification was achieved by sequential ammonium sulfate precipitation and reverse-phase high-performance liquid chromatography (RP-HPLC). The purified bioactive fraction had an approximate molecular weight of 20 kDa by SDS-PAGE and a 106-amino-acid N-terminal sequence that, upon BLAST alignment, returned 98.1% overall identity to the Lactococcin 972 family bacteriocin AAK06118.1 from L. lactis IL1403, with divergence confined exclusively to the terminal two C-terminal residues. This sequence is structurally and functionally distinct from canonical Lcn972 (L. lactis IPLA 972): the two peptides share an identical 25-residue signal peptide but diverge entirely in their mature bioactive domains, which exhibit only 9.1% sequence identity. Canonical Lcn972 operates through Lipid II-mediated septum disruption and inhibits only Lactococcus species; the NAN6399 peptide, correctly designated as a novel member of the Lcn972-like peptide family, demonstrated broad-spectrum antimicrobial efficacy against multiple indicator organisms (Staphylococcus aureus, Salmonella typhimurium, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecalis), producing inhibition zones of up to 30 mm and minimum inhibitory concentration (MIC) values as low as 1.25 μg/mL against S. aureus. Antioxidant capacity was assessed using the DPPH radical scavenging assay, with the purified preparation achieving 73.14 ± 0.34% inhibition. Collectively, these data establish L. lactis NAN6399 as the producer of a bifunctional Lcn972-family bacteriocin with both antimicrobial and antioxidant potential, provide the first experimental characterization of the antimicrobial activity of this Lcn972-family branch, and highlight marine LAB as a productive reservoir for novel bioactive peptide discovery. Full article
(This article belongs to the Section Microbial Biotechnology)
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7 pages, 275 KB  
Case Report
Early-Onset Group B Streptococcal Infection in Bichorionic/Biamniotic Twins Case Study: Is It Time for Changes in Laboratory Diagnosis and Prevention?
by Defkalion Karakalpakis, Sofia Kanatsou, Zoe Siateli, Kalliopi Pappa, Panagiotis Antsaklis, Anastasia Barbouni, Louis Gros and Ekaterina Charvalos
Acta Microbiol. Hell. 2026, 71(2), 10; https://doi.org/10.3390/amh71020010 - 30 Apr 2026
Abstract
Early-onset infection caused by Streptococcus agalactiae (Group B Streptococcus, GBS) may occur during gestation or delivery and can lead to severe neonatal sepsis, meningitis, or pneumonia. Discordant GBS infections in twin gestations are rare. We report a fatal case of early-onset GBS infection [...] Read more.
Early-onset infection caused by Streptococcus agalactiae (Group B Streptococcus, GBS) may occur during gestation or delivery and can lead to severe neonatal sepsis, meningitis, or pneumonia. Discordant GBS infections in twin gestations are rare. We report a fatal case of early-onset GBS infection in dichorionic–diamniotic twins conceived via IVF and delivered by caesarean section at 32 weeks’ gestation due to discordant fetal growth and abnormal Doppler indices in Twin A (Umbilical Artery PI = 1.4; Middle Cerebral Artery PI = 1.5). Twin A had Apgar scores of 3, 5, and 5 and rapidly developed tachycardia, respiratory distress, and systemic infection, while Twin B, with Apgar scores of 7, 8, and 9, remained clinically stable. Both infants were admitted to the NICU and underwent routine blood, urine, and cerebrospinal fluid testing. Despite the prompt initiation of parenteral ceftriaxone and respiratory support, Twin A deteriorated rapidly and died within 28 h. GBS was isolated from Twin A’s blood culture, and maternal placental tissue and high vaginal samples collected before antibiotic administration also grew GBS, with all isolates demonstrating identical antimicrobial resistance profiles. Molecular analysis revealed matching rib1 and alp2/3 gene patterns in isolates from the mother and Twin A. Maternal anovaginal immunochromatography at delivery was positive, whereas screening cultures obtained at 29 weeks’ gestation were negative. This case highlights the limitations of culture-based GBS screening in high-risk pregnancies and preterm deliveries and underscores the potential value of molecular assays and point-of-care testing to improve detection of S. agalactiae throughout pregnancy and the peripartum period. Emerging preventive strategies, including modulation of the genital microbiome and maternal vaccination aligned with WHO recommendations, may further reduce the burden of neonatal GBS disease. Full article
15 pages, 1450 KB  
Article
A New Endolysin Lys59: A Broad-Spectrum Phage Endolysin Targeting Both Gram-Negative and Gram-Positive Bacteria
by Yunhan Zhang, Chenwei Deng, Yanni Liu, Weiqing Lan, Yong Zhao and Xiaohong Sun
Microorganisms 2026, 14(5), 1027; https://doi.org/10.3390/microorganisms14051027 - 30 Apr 2026
Abstract
To address the emerging multidrug-resistance crisis caused by Klebsiella pneumoniae, we expressed the endolysin Lys59 derived from phage VB_KpP_HS106 and performed a comprehensive analysis of its antibacterial activity and structural features. Molecular modeling revealed that Lys59 carries a highly positively charged N-terminus [...] Read more.
To address the emerging multidrug-resistance crisis caused by Klebsiella pneumoniae, we expressed the endolysin Lys59 derived from phage VB_KpP_HS106 and performed a comprehensive analysis of its antibacterial activity and structural features. Molecular modeling revealed that Lys59 carries a highly positively charged N-terminus and an amphipathic helix at the C-terminus. In vitro antibacterial assays showed that Lys59 exhibited significant bactericidal activity against K. pneumoniae with an approximately 4 log reduction at 50 µg/mL in 2 h. Meanwhile, Lys59 exhibited potent, broad-spectrum activity against both Gram-negative and Gram-positive bacteria. Stability analysis indicated that Lys59 retained high activity over a pH range of 3–9 and a temperature range of 4–55 °C. Notably, the antibacterial activity of Lys59 was found to be regulated by metal ions. Molecular docking indicated that K+ can enhance binding stability by interacting with ASN35 and VAL57. In contrast, Mg2+ and Ca2+ suppressed catalytic function by binding to the essential GLU17 residue. Furthermore, treatment with 200 µg/mL of Lys59 resulted in a 44.6% reduction in K. pneumoniae biofilm biomass. Overall, this study identified a phage-derived endolysin with broad-spectrum antimicrobial activity and demonstrated its potential as an antibacterial agent against multidrug-resistant K. pneumoniae. Full article
(This article belongs to the Special Issue New Strategies for Antimicrobial Treatment)
22 pages, 3135 KB  
Article
A PTPRO-Related Five-Gene Blood Transcriptional Signature with Diagnostic Potential for Tuberculosis
by Fengjiao Wu, Ru Huang, Yuxuan Lin, Xixi Zhu, Yujie Li, Huiting Dai, Xiaoyu Zhou, Fang Fang, Ying Liang, Tao Xu, Chuanwang Song, Wei Li, Xiaojing Wang, Xianyou Chang, Hongtao Wang, Ting Wang, Jingzhu Lv and Zhongqing Qian
Biomedicines 2026, 14(5), 1021; https://doi.org/10.3390/biomedicines14051021 - 30 Apr 2026
Abstract
Background/Objectives: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains a major global health problem. Drug resistance and the limitations of sputum-based diagnostic methods highlight the need for additional host-response biomarkers. Protein tyrosine phosphatase receptor type O (PTPRO) has been implicated in inflammatory signaling [...] Read more.
Background/Objectives: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains a major global health problem. Drug resistance and the limitations of sputum-based diagnostic methods highlight the need for additional host-response biomarkers. Protein tyrosine phosphatase receptor type O (PTPRO) has been implicated in inflammatory signaling and macrophage immune regulation, but its relationship with TB-related host transcriptional responses remains unclear. This study aimed to identify and preliminarily evaluate a PTPRO-related blood transcriptional signature with potential relevance to TB discrimination and treatment-response assessment. Methods: Genes correlated with PTPRO expression were first screened using TCGA-LUSC as a large human transcriptomic discovery resource. The resulting candidate genes were then filtered in TB-related whole-blood datasets by intersecting genes upregulated in TB compared with healthy controls, pneumonia, and lung cancer. This strategy yielded a five-gene PTPRO-related signature, termed PO5. The signature was evaluated in independent GEO cohorts and further explored by RT-qPCR in H37Ra-infected THP-1-derived macrophages and in a small clinical blood cohort. A PO5-derived TB risk score was calculated for each sample, and receiver operating characteristic analysis was used to assess discriminatory performance. Changes in TB risk scores during anti-TB treatment were also examined. Results: PTPRO expression was increased in TB whole-blood transcriptomic data and in H37Ra-infected macrophages. In public datasets, PO5 showed potential for distinguishing TB from healthy controls, latent TB, pneumonia, and lung cancer. PO5-derived TB risk scores also decreased after anti-TB treatment. In the exploratory clinical cohort, several PO5 genes showed expression changes in the same general direction as those observed in the public datasets, although the small sample size limited the strength of this evidence. Conclusions: PO5 represents a preliminary PTPRO-related blood transcriptional signature with potential relevance to TB discrimination and treatment-response assessment. These findings remain exploratory and require validation in larger prospective multicenter cohorts, together with further mechanistic studies. Full article
18 pages, 392 KB  
Systematic Review
Complications and Revision Patterns After 3D-Printed Vertebral Body Replacement for Spinal Tumors: A Systematic Review and Critical Appraisal
by Viktor Aleinikov, Talgat Kerimbayev, Daryn Borangaliyev, Galymzhan Kadirbekov, Zhandos Tuigynov, Nurzhan Abishev, Daniyar K. Zhamoldin, Meirzhan Oshayev, Yergen Kenzhegulov, Yermek Urunbayev, Zhanibek Baiturlin, Makar Solodovnikov and Serik Akshulakov
J. Clin. Med. 2026, 15(9), 3447; https://doi.org/10.3390/jcm15093447 - 30 Apr 2026
Abstract
Background: Three-dimensional (3D)-printed vertebral body replacement (VBR) and artificial vertebral body (AVB) implants are increasingly used for anterior column reconstruction after spinal tumor resection. However, the available evidence on complications remains limited, heterogeneous, and methodologically inconsistent. This systematic review aimed to synthesize [...] Read more.
Background: Three-dimensional (3D)-printed vertebral body replacement (VBR) and artificial vertebral body (AVB) implants are increasingly used for anterior column reconstruction after spinal tumor resection. However, the available evidence on complications remains limited, heterogeneous, and methodologically inconsistent. This systematic review aimed to synthesize reported complications, revision patterns, and mechanical outcomes of 3D-printed VBR/AVB implants in spinal oncology and to critically appraise the quality of the available clinical literature. Methods: This systematic review was conducted in accordance with PRISMA 2020. PubMed/MEDLINE, Embase, and the Cochrane Library were searched from 1 January 1980 to 26 February 2026. Eligible studies included clinical series and cohort studies reporting extractable complication and/or revision data in patients who underwent spinal tumor resection followed by reconstruction with a 3D-printed VBR/AVB implant. Methodological quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Case Series. Due to substantial clinical and methodological heterogeneity, a structured narrative synthesis was performed. Results: Eleven studies comprising 217 analyzable 3D-printed reconstructions were included. Most were retrospective single-center series and showed marked heterogeneity in tumor histology, spinal level, implant strategy, follow-up duration, and complication definitions. Because adverse-event reporting was inconsistent across studies, no pooled overall complication rate was calculated. Reported perioperative non-mechanical complications included neurological deterioration, cerebrospinal fluid- or dural-related events, wound infection, pleural effusion, pneumonia, and vascular injury. Mechanical implant failure appeared relatively uncommon, although radiographic subsidence was variably defined and inconsistently reported. Implant mismatch and hardware-related problems were infrequent but clinically relevant, particularly with prefabricated or off-the-shelf devices. Revision procedures were most commonly associated with wound complications, clinically significant subsidence, hardware failure, or tumor recurrence. Overall study quality was limited by retrospective designs, small sample sizes, and non-standardized outcome reporting. Conclusions: Current evidence suggests that 3D-printed VBR/AVB implants are a feasible option with encouraging mechanical performance for spinal reconstruction after tumor resection. Most reported adverse events appear to reflect the complexity of oncologic spine surgery rather than device-specific failure alone. However, the available evidence remains low level and heterogeneous. Larger multicenter comparative studies with standardized outcome definitions and longer follow-up are needed to better define the clinical value and durability of 3D-printed vertebral reconstruction in spinal oncology. Full article
(This article belongs to the Section Oncology)
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17 pages, 3564 KB  
Review
Managing Respiratory Failure in Late Pregnancy
by Kate Williams, Alastair White, Melanie Nana, Catherine Nelson-Piercy and Luigi Camporota
J. Clin. Med. 2026, 15(9), 3449; https://doi.org/10.3390/jcm15093449 - 30 Apr 2026
Abstract
Background/Objectives: Respiratory failure in late pregnancy represents a complex and high-risk clinical scenario due to physiological adaptations during pregnancy that reduce maternal respiratory reserve, with tightly coupled maternal and foetal outcomes. This review aims to synthesise current evidence on epidemiology, maternal–foetal physiology, and [...] Read more.
Background/Objectives: Respiratory failure in late pregnancy represents a complex and high-risk clinical scenario due to physiological adaptations during pregnancy that reduce maternal respiratory reserve, with tightly coupled maternal and foetal outcomes. This review aims to synthesise current evidence on epidemiology, maternal–foetal physiology, and management strategies for respiratory failure in late gestation. Methods: This narrative review integrates contemporary literature, national surveillance data, physiological principles, and expert consensus to summarise the causes, clinical implications, and management of respiratory failure in pregnancy. Results: Respiratory failure in pregnancy arises from diverse obstetric and non-obstetric conditions, including pneumonia, asthma, pulmonary embolism, cardiogenic pulmonary oedema, and ARDS. Maternal hypoxaemia is strongly associated with foetal compromise. Management requires pregnancy-specific ventilatory targets, avoidance of permissive hypercapnia, cautious use of non-invasive and invasive ventilation, and safe implementation of prone or semi-prone positioning. ECMO use has expanded, with maternal survival improving to approximately 75%, although optimal anticoagulation and timing of delivery remain uncertain. Conclusions: Effective management of respiratory failure in late pregnancy requires early recognition, multidisciplinary coordination, and adaptation of respiratory support to maternal–foetal physiology. Despite improvements in critical care and ECMO outcomes, key evidence gaps persist, underscoring the need for integrated maternal critical care pathways and further research to optimise outcomes for both mother and baby. Full article
(This article belongs to the Special Issue Acute Hypoxemic Respiratory Failure: Progress, Challenges and Future)
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15 pages, 6998 KB  
Article
Characterizing the Profiles of Gram-Negative Bacterial Pathogens of Wound Infections and Their Drug-Resistance Disposition
by Lorina Badger-Emeka
Microorganisms 2026, 14(5), 1020; https://doi.org/10.3390/microorganisms14051020 - 30 Apr 2026
Abstract
Wound infections result from contamination of compromised skin following either intentional or accidental trauma. The failure of infected wounds to heal has a huge impact on global healthcare finances. For surveillance purposes, this investigation looks at wound infections and their susceptibility to antibiotics. [...] Read more.
Wound infections result from contamination of compromised skin following either intentional or accidental trauma. The failure of infected wounds to heal has a huge impact on global healthcare finances. For surveillance purposes, this investigation looks at wound infections and their susceptibility to antibiotics. Data obtained from the microbiology laboratory for the years 2014 and 2019 included wound characteristics, patient demographics, and causative bacteria pathogen. Also retrieved from an −80° C freezer were 270 Gram-negative bacteria isolates from wounds that formed part of patient care. Vitek Compact 2 was used for bacteria IDs and AST testing. Wound swabs were the majority (74.07%), followed by bedsore samples (12.22%). Others were tissue cultures (6.3%), skin swabs (3.7%), necrotizing fasciitis (1.48%), foot swabs (1.10%), and cervical wounds (1.11%). Isolated pathogens included Pseudomonas aeruginosa (33.6%), Escherichia coli (24.78%), Acinetobacter baumannii (21.85%), Klebsiella pneumoniae (17.65%), Proteus mirabilis (1.7%), and Morganelli morganii (0.41%). Most isolates had become MDR after 5 years, with extensive (100%) resistance to β-lactam and fluoroquinolone. Only tigecycline and amikacin maintained their antimicrobial activity for the period with some bacteria species. Suitable therapeutic options were few, irrespective of the year of isolation, particularly among the ESKAPE isolates. Overall results demonstrate that after a 5-year period, about 75% of the isolates of the bacteria pathogens had become resistant to most of the antibiotics used for their management. Full article
(This article belongs to the Special Issue Bacterial Infection in Soft Tissue and Diabetic Foot)
16 pages, 305 KB  
Review
Early Versus Late Tracheostomy in Traumatic Spinal Injury: A Narrative Review
by Saeed Mahmood, Mohammad Asim, Ayman El-Menyar, Sandro Rizoli and Hassan Al-Thani
Neurol. Int. 2026, 18(5), 85; https://doi.org/10.3390/neurolint18050085 - 30 Apr 2026
Abstract
Traumatic spinal cord injury (TSCI) frequently necessitates prolonged ventilatory support, raising the clinical dilemma of early versus late tracheostomy. Despite decades of debate, no randomized controlled trials (RCTs) have been conducted exclusively in TSCI populations, and evidence remains largely observational. This review synthesizes [...] Read more.
Traumatic spinal cord injury (TSCI) frequently necessitates prolonged ventilatory support, raising the clinical dilemma of early versus late tracheostomy. Despite decades of debate, no randomized controlled trials (RCTs) have been conducted exclusively in TSCI populations, and evidence remains largely observational. This review synthesizes contemporary evidence on the timing and outcomes of tracheostomy in acute TSCI. Across multiple cohort studies and meta-analyses, early tracheostomy (≤7 days) is consistently associated with shorter mechanical ventilation duration, shorter ICU length of stay, reduced sedation exposure, and fewer immobility-related complications. Data suggested a lower incidence of ventilator-associated pneumonia, though mortality outcomes remain unchanged. Importantly, cervical-level injuries appear to derive the most significant benefit, while variability in defining “early” versus “late” complicates direct comparisons. Despite methodological limitations, including reliance on retrospective data, inconsistent definitions, and lack of long-term follow-up, cumulative evidence indicates that early tracheostomy improves short-term outcomes. The optimal timing of tracheostomy in TSCI remains uncertain. Current observational evidence suggests that early tracheostomy in cervical SCI is associated with a reduction in the duration of mechanical ventilation, ICU stay, and respiratory complications. These benefits might come from better access to the airways, less anatomical dead space, better clearance of secretions, less need for sedation, together with earlier mobilization and rehabilitation. Mortality outcomes remain inconclusive. In the absence of randomized trials and long-term data, individualized decisions based on injury level, clinical course, and institutional expertise are essential. Full article
(This article belongs to the Topic Neurological Updates in Neurocritical Care)
16 pages, 746 KB  
Article
Lung Ultrasound Abnormalities and LUS Score After COVID-19 Pneumonia: Determinants and Associations with Dyspnoea in a Prospective Cohort
by Francisco Navarro-Romero, Cristina Asencio-Méndez, Francisco Rivas-Ruiz, Blanca Sánchez-Mesa, María Dolores Martín-Escalante and Julián Olalla-Sierra
J. Clin. Med. 2026, 15(9), 3438; https://doi.org/10.3390/jcm15093438 - 30 Apr 2026
Abstract
Background/Objectives: The clinical determinants and functional relevance of persistent lung ultrasound (LUS) abnormalities after COVID-19 pneumonia remain poorly characterized. We aimed to identify determinants of qualitative LUS abnormalities and global lung involvement assessed by the LUS score, and to evaluate their association [...] Read more.
Background/Objectives: The clinical determinants and functional relevance of persistent lung ultrasound (LUS) abnormalities after COVID-19 pneumonia remain poorly characterized. We aimed to identify determinants of qualitative LUS abnormalities and global lung involvement assessed by the LUS score, and to evaluate their association with persistent dyspnoea. Methods: We conducted a prospective observational study that included 261 patients who were hospitalized for COVID-19 pneumonia and were assessed 1–6 months after discharge. A standardized 14-zone LUS protocol was used to assess qualitative abnormalities (pleural line irregularity, ≥3 B-lines, and subpleural consolidations) and to calculate the LUS score. Associations with clinical variables, including dyspnoea assessed by the modified Medical Research Council (mMRC) scale, were analyzed using multivariable logistic regression. Results: The severity of the acute pneumonia episode emerged as the strongest determinant of qualitative LUS abnormalities and elevated LUS score (>6). Increasing age was independently associated with ultrasound findings. Persistent dyspnoea (mMRC ≥ 1) was associated with all qualitative abnormalities and with a higher prevalence of elevated LUS score (56.6% vs. 22.1%; p < 0.001). A graded association was observed between dyspnoea severity and both qualitative findings and LUS score. An increase in dyspnoea from baseline (ΔmMRC ≥ 1) remained independently associated with an elevated LUS score. Conclusions: Persistent LUS abnormalities are strongly associated with the severity of the acute episode. The LUS score provides a robust, clinically meaningful measure of residual lung involvement and shows a stronger association with persistent dyspnoea than qualitative findings, supporting its role in follow-up and risk stratification. Full article
(This article belongs to the Special Issue Update on Acute Severe Respiratory Infections: 2nd Edition)
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14 pages, 273 KB  
Article
Risk Factors for Barotrauma with Extra-Alveolar Air in a Selected COVID-19 Patient Population: Experience from a Tertiary University Hospital
by Jian Hai Chai, Azlina Masdar, Aliza Mohamad Yusof, Nadia Md Nor, Rufinah Teo, Iskandar Khalid and Wan Rahiza Wan Mat
J. Clin. Med. 2026, 15(9), 3422; https://doi.org/10.3390/jcm15093422 - 30 Apr 2026
Abstract
Background/Objectives: Mechanical ventilation (MV) is a crucial intervention in managing severe respiratory failure due to COVID-19. However, its use may be complicated by pulmonary barotrauma, a serious event associated with increased morbidity and mortality. Understanding its incidence and associated risk factors is [...] Read more.
Background/Objectives: Mechanical ventilation (MV) is a crucial intervention in managing severe respiratory failure due to COVID-19. However, its use may be complicated by pulmonary barotrauma, a serious event associated with increased morbidity and mortality. Understanding its incidence and associated risk factors is essential for optimising ventilatory strategies and improving patient outcomes. The aim of this study was to determine the incidence and risk factors associated with the development of pulmonary barotrauma in mechanically ventilated patients with COVID-19. Methods: All mechanically ventilated patients aged 18 years and above who were admitted to the COVID-19 Intensive Care Unit (ICU) from January 2021 to June 2022 were included. Patients who developed pulmonary barotrauma prior to or within 24 h of ICU admission, had iatrogenic pneumothorax, were readmitted to the ICU, or were ventilated for causes other than COVID-19-related respiratory failure were excluded. Data on patient demographics, vaccination status, ventilator parameters, laboratory findings, and the use of steroid or immunomodulatory therapies were collected and analysed. Univariate and multivariate logistic regression analyses were performed to identify the potential risk factors and clinical outcomes associated with pulmonary barotrauma. Results: The medical records of 204 patients were included. The incidence of pulmonary barotrauma was 22.5%. Lower C-reactive protein (CRP) levels at ICU admission, lower FiO2 requirements during the first week of MV, a higher positive end-expiratory pressure (PEEP) during the second week, and a prolonged mechanical ventilation duration were significantly associated with pulmonary barotrauma (p = 0.039, 0.049, 0.021, and 0.036, respectively). Patients who developed pulmonary barotrauma experienced longer ICU stays (p = 0.006) and higher all-cause ICU mortality (p = 0.009). Conclusions: Lower CRP levels and a lower FiO2 requirements, a higher PEEP use, and longer ventilator days were the independent risk factors for pulmonary barotrauma in our study population, leading to a longer ICU stay and higher all-cause ICU mortality. Full article
(This article belongs to the Section Anesthesiology)
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19 pages, 897 KB  
Review
Biliary Microbiota in Health and Disease: Clinical Implications in Lithiasis, Infection, and Antimicrobial Resistance
by Claudia Marinaccio, Marta Giovanetti, Benedetto Neri, Dario Biasutto, Andrea D’Amico, Annamaria Altomare, Francesco Branda, Laura Restaneo, Massimo Ciccozzi, Michele Cicala and Michele Pier Luca Guarino
Antibiotics 2026, 15(5), 445; https://doi.org/10.3390/antibiotics15050445 - 29 Apr 2026
Abstract
The biliary tract, long considered a sterile environment, is now recognized to harbor a resident microbiota with important implications for health and disease. This review aims to summarize current knowledge on the composition and function of the biliary microbiota in physiological conditions, and [...] Read more.
The biliary tract, long considered a sterile environment, is now recognized to harbor a resident microbiota with important implications for health and disease. This review aims to summarize current knowledge on the composition and function of the biliary microbiota in physiological conditions, and its alterations in pathological states such as infection and lithiasis, with a particular focus on antimicrobial resistance. In healthy individuals, the biliary microbiota appears to be shaped by bile acids and gut–bile axis interactions, playing a role in local immune modulation. In disease, microbial dysbiosis contributes to conditions such as acute cholecystitis, cholangitis, and gallstone formation, with distinct microbial signatures linked to specific stone types. Common biliary pathogens, including E. coli, Enterococcus spp., Pseudomonas spp., and K. pneumoniae, often exhibit concerning resistance patterns, impacting therapeutic strategies. Emerging evidence highlights the interplay between intestinal and biliary microbiota, suggesting potential diagnostic and prognostic applications. Understanding these dynamics opens new avenues for microbiota-informed antibiotic stewardship, targeted microbiota modulation, and precision medicine approaches. Further research, particularly culture-independent and longitudinal studies, is crucial to fully elucidate the clinical significance of the biliary microbiota and to integrate microbiota profiling into patient management strategies. Full article
(This article belongs to the Special Issue New Advances in Antibiotic Therapy in the Gastroenterology Field)
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15 pages, 608 KB  
Article
Comorbidity Burden in Lung Cancer and Malignant Pleural Mesothelioma: Nationwide Database Results of Turkey
by Çiğdem Özdilekcan, Tarkan Özdemir, Mustafa Hamidullah Türkkanı, Naim Ata, Mesut Akyol, Mevlüt Karataş, Aslıhan Gürün Kaya, Aydın Yılmaz, Akın Kaya and Şuayip Birinci
Medicina 2026, 62(5), 845; https://doi.org/10.3390/medicina62050845 - 29 Apr 2026
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Abstract
Background and Objectives: The presence of comorbidities in both the pre- and post-diagnostic periods is a critical consideration in the diagnosis and management of patients with cancer. This study aimed to investigate the prevalence and burden of pulmonary and extrapulmonary comorbidities in patients [...] Read more.
Background and Objectives: The presence of comorbidities in both the pre- and post-diagnostic periods is a critical consideration in the diagnosis and management of patients with cancer. This study aimed to investigate the prevalence and burden of pulmonary and extrapulmonary comorbidities in patients diagnosed with lung cancer (LC) and malignant pleural mesothelioma (MPM). Materials and Methods: The data were obtained from official patient records of the Turkish Ministry of Health. Patients diagnosed with either lung cancer (LC) or malignant pleural mesothelioma (MPM) between 2015 and 2018 were included in the study. Comorbidities were classified as pulmonary or extrapulmonary. Results: A total of 74,835 patients with LC and 1678 patients with MPM were included. The burden of comorbid conditions increased significantly in the post-diagnostic period in both males and females across both cancer types. When the two cancer groups were compared with respect to diagnostic periods, comorbidities such as hypertension (HT), phlebitis/venous thrombosis/thrombophlebitis, pulmonary embolism, pneumothorax, and pleural effusion were significantly more prevalent in the MPM group (p < 0.05). Compared with the pre-diagnostic period, the comorbidity risk in LC was highest for pulmonary embolism, ARF, and pneumonia in the post-diagnostic period, whereas renal failure was the most frequent comorbidity in the MPM group (p < 0.001 and p = 0.024). When comparing changes in comorbidity burden between sexes in the lung cancer group, male patients had higher frequencies of pulmonary embolism, pneumonia, pneumothorax, and coronary artery disease than females. In contrast, in the female lung cancer group, the prevalence of chronic renal failure was higher than in males (OR = 2.14 vs. 2.00), whereas acute renal failure was more prominent in the male patient group (OR = 2.64 vs. 1.94). In gender-based comparison of comorbid conditions among patients with MPM, the risk of renal failure was higher in females than in males (CRF and ARF respectively: OR = 2.63 vs. 2.16 and OR = 6.80 vs. 5.44). Additionally, increased rates of COPD were observed in male patients within this group (OR = 1.93 vs. 1.81). Conclusions: Patients with LC and MPM are burdened not only by their primary malignancies but also by a wide spectrum of comorbidities, particularly in the post-diagnostic period. Comprehensive knowledge of comorbid conditions is essential for clinicians to guide clinical decision-making, anticipate disease progression, and optimize treatment strategies, thereby informing national healthcare policies. Future studies incorporating matched control groups or longitudinal designs with standardized surveillance protocols may help conduct better research. Full article
(This article belongs to the Special Issue Advancements in Lung Cancer Diagnosis and Treatment)
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13 pages, 2446 KB  
Case Report
Delayed Diagnosis of Alpha-1 Antitrypsin Deficiency in an Elderly Patient
by Beatrice Ragnoli, Patrizia Pochetti, Xheni Veselagu and Mario Malerba
Diagnostics 2026, 16(9), 1329; https://doi.org/10.3390/diagnostics16091329 - 28 Apr 2026
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Abstract
Background and Clinical Significance: Alpha-1 antitrypsin deficiency (AATD) is an autosomal codominant disorder caused by pathogenic variants in the SERPINA1 gene, resulting in reduced circulating alpha-1 antitrypsin (AAT) or production of dysfunctional protein. AAT is the principal inhibitor of neutrophil elastase, and its [...] Read more.
Background and Clinical Significance: Alpha-1 antitrypsin deficiency (AATD) is an autosomal codominant disorder caused by pathogenic variants in the SERPINA1 gene, resulting in reduced circulating alpha-1 antitrypsin (AAT) or production of dysfunctional protein. AAT is the principal inhibitor of neutrophil elastase, and its deficiency leads to unchecked proteolytic activity, progressive destruction of lung parenchyma, and increased susceptibility to infections. Severe deficiency, particularly in individuals homozygous for the Z allele (PI*ZZ), predisposes to early-onset panacinar emphysema, chronic airflow obstruction, and liver disease. Despite its clinical relevance, AATD remains markedly underdiagnosed and is frequently misclassified as smoking-related chronic obstructive pulmonary disease (COPD), delaying access to disease-modifying therapy, genetic counselling, and preventive strategies. Early recognition is therefore essential to improve outcomes. Case Presentation: We report the case of a 68-year-old ex-smoker with a long-standing diagnosis of “COPD” who presented with acute-on-chronic type 2 respiratory failure and community-acquired pneumonia. Spirometry revealed severe airflow obstruction, and high-resolution computed tomography demonstrated extensive basilar panlobular emphysema, raising suspicion for AATD. Serum AAT concentration was critically low at 26.8 mg·dL−1, and isoelectric focusing confirmed a PI*ZZ phenotype. Next-generation sequencing identified homozygosity for the SERPINA1 c.1096G>A (Z) variant, with no additional pathogenic alleles. Cascade family screening revealed multiple heterozygous PI*MZ relatives. Before augmentation therapy could be initiated, the patient developed severe Legionella pneumophila pneumonia with secondary bacterial superinfection, progressing to refractory septic shock and death. Conclusions: This case illustrates how AATD can masquerade as smoking-related COPD for years, leading to missed opportunities for timely intervention. It underscores the importance of testing all adults with COPD or refractory asthma at least once, regardless of age or smoking history. Early diagnosis enables initiation of augmentation therapy, targeted vaccination, lifestyle modification, and genetic counselling, ultimately improving prognosis and reducing preventable morbidity and mortality. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
17 pages, 3150 KB  
Article
Short Synthetic Lipopeptides C16-KK-NH2 and (C10)2-KKKK-NH2 Enhance the Activities of Erythromycin and Tetracycline Against ESKAPE Pathogens
by Malgorzata Anna Paduszynska, Alena Shchuka and Katarzyna Ewa Greber
Antibiotics 2026, 15(5), 439; https://doi.org/10.3390/antibiotics15050439 - 28 Apr 2026
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Abstract
Background: ESKAPE constitutes a group of six nosocomial bacteria that can evade available antimicrobials due to their great potential to develop multi-drug resistance and biofilm-forming abilities. These pathogens often cause hospital-acquired infections and pose a serious threat to public health. The search for [...] Read more.
Background: ESKAPE constitutes a group of six nosocomial bacteria that can evade available antimicrobials due to their great potential to develop multi-drug resistance and biofilm-forming abilities. These pathogens often cause hospital-acquired infections and pose a serious threat to public health. The search for efficient innovative therapeutic strategies to fight ESKAPE bacteria have been intensively investigated topics. One promising approach to fight resistant pathogens and their biofilms is combination therapy, which allows the effectiveness against microorganisms to be increased while reducing the applied concentrations and risks of potential unwanted side effects. Objectives: The object of the study was to determine if there is an interaction of short lipopeptides ((C10)2-KKKK-NH2, C16-KK-NH2) together with erythromycin and tetracycline against pathogens of the ESKAPE group (Acinetobacter baumannii, Enterobacter aerogenes, Enterococcus faecium Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus). Methods: The checkerboard assay was used to examine the activity of compounds applied in combinations against ESKAPE strains in planktonic cells and toward biofilms formed by Staphylococcus aures and Pseudomonas aeruginosa. Results: The lipopeptides demonstrated a great potential of their application as additives to conventional antimicrobials against Gram-negative bacteria, including microorganisms within biofilms. Full article
(This article belongs to the Special Issue Peptide-Based Drugs in the Era of Antimicrobial Resistance)
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