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13 pages, 1542 KiB  
Case Report
Reclassification of Seronegative Rheumatoid Arthritis as Anti-PL-12 Antisynthetase Syndrome with Interstitial Lung Disease and Joint Involvement–Case Report
by Diana Elena Cosău, Alexandru Dan Costache, Irina Iuliana Costache Enache, Ionela Lăcrămioara Șerban, Luiza Andreea Petrariu, Cristina Pomîrleanu, Mara Russu, Vladia Lăpuște and Codrina Ancuța
Reports 2025, 8(3), 123; https://doi.org/10.3390/reports8030123 - 26 Jul 2025
Viewed by 372
Abstract
Background and Clinical Significance: Antisynthetase syndrome (ASyS) is a rare autoimmune entity defined by the presence of anti-aminoacyl-t ribonucleic acid (RNA) synthetase autoantibodies and classically associated with a triad of interstitial lung disease (ILD), inflammatory myopathy, and arthritis. Additional clinical features may include [...] Read more.
Background and Clinical Significance: Antisynthetase syndrome (ASyS) is a rare autoimmune entity defined by the presence of anti-aminoacyl-t ribonucleic acid (RNA) synthetase autoantibodies and classically associated with a triad of interstitial lung disease (ILD), inflammatory myopathy, and arthritis. Additional clinical features may include Raynaud’s phenomenon and “mechanic’s hands”. Among antisynthetase antibodies, anti-PL-12 is notably associated with predominant or isolated ILD and may occur in the absence of clinically evident myositis, thereby complicating timely diagnosis. Case Presentation: We are presenting a 45-year-old non-smoking female patient with a prior diagnosis of seronegative rheumatoid arthritis (RA) who developed progressive dyspnea, dry cough, and sicca symptoms. High-resolution computed tomography revealed a nonspecific interstitial pneumonia (NSIP) pattern. Despite normal creatine kinase and lactate dehydrogenase levels, serological work-up revealed positive anti-PL-12 and anti-Ro52 antibodies, supporting a diagnosis of antisynthetase syndrome without myositis, fulfilling the diagnostic criteria for ASyS per Connors and Solomon. Treatment with corticosteroids and cyclophosphamide induced clinical and functional respiratory improvement, while azathioprine was initiated for maintenance. Conclusions: This case underscores the clinical heterogeneity of antisynthetase syndrome and highlights the diagnostic challenge posed by anti-PL-12–associated ILD in the absence of myositis. Importantly, it demonstrates that in patients with pre-existing rheumatologic diagnoses, the emergence of atypical pulmonary manifestations warrants repeat serologic evaluation to assess ASyS and other autoimmune conditions. Early diagnosis and immunosuppressive treatment are essential to optimize outcomes. Full article
(This article belongs to the Section Critical Care/Emergency Medicine/Pulmonary)
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14 pages, 1519 KiB  
Article
Harnessing Radiomics and Explainable AI for the Classification of Usual and Nonspecific Interstitial Pneumonia
by Turkey Refaee, Ouf Aloofy, Khalid Alduraibi, Wael Ageeli, Ali Alyami, Rafat Mohtasib, Naif Majrashi and Philippe Lambin
J. Clin. Med. 2025, 14(14), 4934; https://doi.org/10.3390/jcm14144934 - 11 Jul 2025
Viewed by 463
Abstract
Objectives: Accurate differentiation between usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP) is crucial for guiding treatment in interstitial lung diseases (ILDs). This study evaluates the efficacy of clinical, radiomic, and combined models in classifying UIP and NSIP using high-resolution computed [...] Read more.
Objectives: Accurate differentiation between usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP) is crucial for guiding treatment in interstitial lung diseases (ILDs). This study evaluates the efficacy of clinical, radiomic, and combined models in classifying UIP and NSIP using high-resolution computed tomography (HRCT) scans. Materials and Methods: A retrospective analysis was performed on 105 HRCT scans (UIP = 60, NSIP = 45) from Faisal Hospital and Research Center. Demographic and pulmonary function data formed the clinical model. Radiomic features, extracted using the pyRadiomics package, were refined using recursive feature elimination. A combined model was developed by integrating clinical and radiomic features to assess their complementary diagnostic value. Model performance was assessed via the area under the receiver operating characteristic curve (AUC). SHapley Additive exPlanations (SHAP) analysis, including both global feature importance and individual-level explanations, was used to interpret the model predictions. Results: The clinical model achieved an AUC of 0.62 with a sensitivity of 54% and a specificity of 78%. The radiomic model outperformed it with an AUC of 0.90 with a sensitivity and specificity above 85%. The combined model showed an AUC of 0.86 with a sensitivity of 88% and a specificity of 78%. SHAP analysis identified texture-based features, such as GLCM_Idmn and NGTDM_Contrast, as influential for classification. Conclusions: Radiomic features enhance classification accuracy for UIP and NSIP compared to clinical models. Integrating HCR into clinical workflows may reduce variability and improve diagnostic accuracy in ILD. Future studies should validate findings using larger, multicenter datasets. Full article
(This article belongs to the Section Nuclear Medicine & Radiology)
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21 pages, 795 KiB  
Review
The Role of Monocytes in the Natural History of Idiopathic Pulmonary Fibrosis: A Systematic Literature Review
by Diego Lema, Esteban Kosak Lopez, Justin Lam, Irakli Tskhakaia, Yurilu Gonzalez Moret and Shahrzad Abdollahi
Int. J. Mol. Sci. 2025, 26(13), 6538; https://doi.org/10.3390/ijms26136538 - 7 Jul 2025
Viewed by 671
Abstract
Emerging evidence suggests a significant association between monocytes and the pathophysiology and prognosis of idiopathic pulmonary fibrosis (IPF). This review aims to systematically evaluate current knowledge regarding blood monocyte counts and their relationship with the etiology, progression, and prognosis of IPF. We conducted [...] Read more.
Emerging evidence suggests a significant association between monocytes and the pathophysiology and prognosis of idiopathic pulmonary fibrosis (IPF). This review aims to systematically evaluate current knowledge regarding blood monocyte counts and their relationship with the etiology, progression, and prognosis of IPF. We conducted a systematic search in the PubMed database for articles published through 17 February 2025, using the MeSH terms “lung diseases, interstitial” and “monocytes,” which yielded 314 results. After filtering for full-text articles in English (n = 242), we included only studies focusing on blood monocyte counts with clinical implications in IPF. Articles relating to other cell types or non-IPF lung diseases were excluded. Our systematic search identified 12 relevant articles. Monocytes play an essential role in regulating inflammatory responses and resolution across multiple diseases, with established but incompletely understood contributions to lung fibrosis development in IPF. Correlations have been demonstrated between elevated blood monocyte counts and the following: (1) the presence and progression of interstitial lung abnormalities, (2) the progression from an indeterminate usual interstitial pneumonia (UIP) pattern on CT scans to definitive IPF, and (3) worse lung function parameters, an increased risk of acute exacerbations, and reduced overall survival in IPF patients. Monocytes serve as critical orchestrators throughout IPF’s natural history—from early interstitial changes to disease progression and acute exacerbations. Targeting monocyte recruitment pathways and reprogramming their differentiation represents a promising therapeutic approach, while circulating monocyte counts offer potential as accessible biomarkers for disease progression and treatment response. Future research should characterize stage-specific monocyte phenotypes to enable precision-targeted interventions. Full article
(This article belongs to the Special Issue New Advances in Autoimmune Diseases)
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12 pages, 1120 KiB  
Case Report
First Case of Infective Endocarditis Caused by Vibrio metschnikovii: Clinico-Diagnostic Complexities and a Systematic Literature Review
by Alessandro Carrozzo, Vittorio Bolcato, Luigi Martinelli, Ferdinando Dodi, Antonella Vulcano, Giuseppe Basile and Livio P. Tronconi
Clin. Pract. 2025, 15(7), 118; https://doi.org/10.3390/clinpract15070118 - 25 Jun 2025
Viewed by 418
Abstract
Background: Non-cholera Vibrio species are rare waterborne pathogens that can cause severe infections. Among these, few cases of Vibrio metschnikovii infections have been reported, especially in the gastrointestinal tract, with no cardiac tissue involvement as a result. Following the PRISMA checklist, we conducted [...] Read more.
Background: Non-cholera Vibrio species are rare waterborne pathogens that can cause severe infections. Among these, few cases of Vibrio metschnikovii infections have been reported, especially in the gastrointestinal tract, with no cardiac tissue involvement as a result. Following the PRISMA checklist, we conducted a literature review, and thirteen articles for twenty-two cases overall were included: seven cases of sepsis (in three cases, the echocardiographic results were negative), seven cases of pneumonia, two skin infections, eleven cases of diarrhoea, and a gastroenteritis outbreak. This report documents the expanding clinical spectrum and the role played by V. metschnikovii in infective endocarditis. Case report: A 28-year-old male patient was referred to the cardiac surgery unit for urgent mitral valve replacement due to suspicion of infective endocarditis. Microbiological tests yielded negative results. Following recovery and discharge with antimicrobial therapy for 6 weeks, the patient experienced prosthesis detachment, necessitating re-hospitalisation for an emergency valve replacement. Vibrio metschnikovii was identified on the prosthesis valve through PCR and successfully treated with ciprofloxacin. However, a spontaneous rupture of the ascending thoracic aorta led to a neurological injury. Discussion: This case represents the first case of valve infection caused by Vibrio metschnikovii, characterised by diagnostic and therapeutic challenges and the involvement of the great vessels. Also considered in this case, for a disease with a median age of 58 years (11–83) and a male-to-female ratio of 2.2, were one male neonate and six cases for whom neither sex nor age was indicated. Excluding gastrointestinal cases, the septic forms are associated with high morbidity, although the single case described involved a young and healthy subject. Risk factors for the pathogen or predisposing/pathological conditions for endocarditis did not emerge. The routes and the time of infection could not be determined, deepening the possibility of occupational exposure via the patient’s position as a boat worker. Poor sensitivity to third-generation cephalosporins has been reported in the literature: the absence of an antibiogram does not allow for a comparison, although resolution was achieved with ciprofloxacin. Conclusion: The rising global incidence of non-cholera Vibrio infections, driven by environmental changes, calls for urgent research into the factors behind their pathogenicity and infection routes. Diagnostic complexities have emerged together with clinical severity. Full article
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14 pages, 840 KiB  
Article
Efficacy and Safety of Fosfomycin Disodium in Patients with Bacterial Infections: A Single-Center, Real-Life Clinical Study
by Fabio Luciano, Lorenzo Bertolino, Fabian Patauner, Filomena Boccia, Raffaella Gallo, Pino Sommese, Anna Maria Carolina Peluso, Oriana Infante, Silvia Mercadante, Augusto Delle Femine, Arta Karruli, Roberto Andini, Rosa Zampino and Emanuele Durante-Mangoni
J. Clin. Med. 2025, 14(12), 4386; https://doi.org/10.3390/jcm14124386 - 19 Jun 2025
Viewed by 738
Abstract
Objectives: Fosfomycin is an old antibiotic that has recently gained attention owing to its preserved activity against multidrug-resistant (MDR) bacteria. Data on its use in real life are limited. Thus, we evaluated the efficacy and safety of fosfomycin disodium in the context of [...] Read more.
Objectives: Fosfomycin is an old antibiotic that has recently gained attention owing to its preserved activity against multidrug-resistant (MDR) bacteria. Data on its use in real life are limited. Thus, we evaluated the efficacy and safety of fosfomycin disodium in the context of our hospital clinical practice. Methods: Single-center, retrospective, observational study on 56 patients who received fosfomycin disodium from September 2016 to July 2023, focusing on clinical and microbiological outcomes and adverse events. Results: Included in this study were 56 patients. Fosfomycin disodium was administered for a median duration of 10 days [5–13.5] and was always used in combination with other antibiotics, more frequently with meropenem (16 cases, 28.6%) and colistin (11 cases, 19.6%). It was mostly used for treating pneumonia (41%), followed by bloodstream infections (19.6%), urinary tract infections (16.1%), bone infections (16.1%), and surgical site infections (7.1%). The most common isolated pathogen was Pseudomonas aeruginosa (17%), and polymicrobial infections were detected in 18 patients (32%). Among the isolated bacteria, 36 (44.4%) were MDR. The complete resolution, defined as the disappearance of symptoms, eradication of the causative microorganism, and decrease in CRP levels, was achieved in 39% of cases. During treatment, we observed electrolyte imbalances, in particular a decrease in serum potassium (0.6 mEq/L [0.3–1.1]), calcium (0.7 mEq/L [0.3–1.1]) and magnesium levels (0.3 mg/dL [0.20–0.48]), and an increase in serum sodium levels (4 mEq/dL [2–7]). Changes in potassium and sodium levels were more pronounced in patients with prior kidney dysfunction and heart failure, respectively, and in patients receiving fosfomycin diluted with saline compared with 5% glucose solution (p = 0.04). Conclusions: Fosfomycin is effective in treating complicated infections in comorbid patients when combined with other antimicrobials. During treatment, major electrolyte imbalances occur that require careful monitoring and correction, especially in patients with prior kidney disease. Full article
(This article belongs to the Section Infectious Diseases)
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24 pages, 2795 KiB  
Article
Discovery of Novel Phenolic Compounds from Eutypa lata Through OSMAC Approach: Structural Elucidation and Antibiotic Potential
by Ana Cotán, Inmaculada Izquierdo-Bueno, Abdellah Ezzanad, Laura Martín, Manuel Delgado, Isidro G. Collado and Cristina Pinedo-Rivilla
Int. J. Mol. Sci. 2025, 26(12), 5774; https://doi.org/10.3390/ijms26125774 - 16 Jun 2025
Viewed by 451
Abstract
Among grapevine trunk diseases, Eutypa dieback, caused by the fungus Eutypa lata, is one of the most critical ones, due to its widespread infection in vineyards and the lack of effective treatments. This fungus is a vascular pathogen that enters grapevines through [...] Read more.
Among grapevine trunk diseases, Eutypa dieback, caused by the fungus Eutypa lata, is one of the most critical ones, due to its widespread infection in vineyards and the lack of effective treatments. This fungus is a vascular pathogen that enters grapevines through pruning wounds. The infection process is associated with phytotoxic metabolites produced by the fungus, and as such, the identification of new metabolites from different culture conditions and broths could provide valuable insights into the fungus’s enzymatic system and help its control. For the purposes of this study, the OSMAC (one strain, many compounds) approach was applied to investigate the secondary metabolism of E. lata strain 311 isolated from Vitis vinifera plants in Spain. A total of twenty metabolites were isolated, including five reported for the first time from E. lata and four that are newly identified compounds in the literature: eulatagalactoside A, (R)-2-(4′-hydroxy-3′-methylbut-1′-yn-1′-yl)-4-(hydroxymethyl)phenol, (S)-7-hydroxymethyl-3-methyl-2,3-dihydro-1-benzoxepin-3-ol, and (3aR,4S,5R,7aS)-4,5-dihydroxy-6-((R)-3′-methylbuta-1′,3′-dien-1′-ylidene)hexahydrobenzo[d][1,3]dioxol-2-one. These compounds were extracted from fermentation broths using silica gel column chromatography and high-performance liquid chromatography (HPLC). Their structures were elucidated through extensive 1D and 2D NMR spectroscopy, along with high-resolution electrospray ionization mass spectrometry (HRESIMS). Compounds were evaluated for phytotoxicity against Phaseolus vulgaris, with only eulatagalactoside A producing white spots after 48 h. Additionally, the antibacterial activity against Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae of selected compounds was tested. The compounds (R)-2-(4′-hydroxy-3′-methylbut-1′-yn-1′-yl)-4-(hydroxymethyl)phenol and (S)-7-(hydroxymethyl)-3-methyl-2,3-dihydrobenzo[b]oxepin-3-ol showed the most significant antimicrobial activity against Gram-positive bacteria, inhibiting S. aureus by over 75%, with IC50 values of 511.4 µg/mL and 617.9 µg/mL, respectively. Full article
(This article belongs to the Special Issue Molecular Characterization of Plant–Microbe Interactions)
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13 pages, 526 KiB  
Review
The Role of Bronchoscopy in the Diagnosis of Interstitial Lung Disease: A State-of-the-Art Review
by A. Rolando Peralta and Al Muthanna Shadid
J. Clin. Med. 2025, 14(9), 3255; https://doi.org/10.3390/jcm14093255 - 7 May 2025
Viewed by 1591
Abstract
The diagnostic evaluation of interstitial lung diseases (ILDs) remains challenging due to their heterogeneous etiologies and overlapping clinical and radiographic patterns. A confident diagnosis often necessitates histopathological sampling, particularly when high-resolution computed tomography and serologic assessments are inconclusive. While surgical lung biopsy (SLB) [...] Read more.
The diagnostic evaluation of interstitial lung diseases (ILDs) remains challenging due to their heterogeneous etiologies and overlapping clinical and radiographic patterns. A confident diagnosis often necessitates histopathological sampling, particularly when high-resolution computed tomography and serologic assessments are inconclusive. While surgical lung biopsy (SLB) has long been considered the diagnostic gold standard, its invasiveness, associated morbidity, and limited feasibility in high-risk patients have driven the pursuit of less invasive alternatives. Here, we review the current applications, diagnostic yield, procedural techniques, and complications of several bronchoscopic modalities. Bronchoalveolar lavage (BAL) aids in characterizing inflammatory profiles and differentiating among conditions such as hypersensitivity pneumonitis, sarcoidosis, and eosinophilic pneumonia. Endobronchial biopsies (EBBs) and endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) are valuable in diagnosing granulomatous diseases with lymphadenopathy. Transbronchial lung biopsy (TBLB) is effective for peribronchial and centrilobular diseases but is limited by small sample size and tissue distortion. Transbronchial lung cryobiopsy (TBC) enables acquisition of larger, well-preserved parenchymal tissue samples from the peripheral lung. Over recent years, studies have demonstrated that TBC, when interpreted within a multidisciplinary discussion (MDD), achieves diagnostic concordance rates with SLB exceeding 75%, and up to 95% in cases where high diagnostic confidence is reached. When performed in experienced centers using standardized protocols, TBC is considered a viable first-line histopathologic tool in the diagnostic evaluation of ILD. Adequate training and standardization of the TBC procedure are needed to ensure low complication rates and a high yield. Full article
(This article belongs to the Section Respiratory Medicine)
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9 pages, 1143 KiB  
Article
Effectiveness and Tolerability of Dual Antiviral Therapy in Immunosuppressed Patients with Protracted SARS-CoV-2 Infection
by Giovanna Travi, Francesco Peracchi, Marco Merli, Emanuele Ravano, Anna Frustaci, Marina Deodato, Diana Fanti, Alice Nava, Valeriana Colombo, Nicholas Brian Bana, Carlotta Rogati, Alessandro Raimondi, Cristina Moioli, Anna Maria Pazzi, Marta Vecchi, Davide Motta, Roberto Rossotti, Chiara Oltolini, Fulvio Crippa, Enrico Minetti, Chiara Vismara, Roberto Cairoli and Massimo Puotiadd Show full author list remove Hide full author list
Infect. Dis. Rep. 2025, 17(2), 17; https://doi.org/10.3390/idr17020017 - 26 Feb 2025
Viewed by 908
Abstract
Background: Immunosuppressed patients still exhibit a high mortality rate due to SARS-CoV-2 infection, up to 21%. Persistent viral load replication and protracted viral symptoms result in a high risk of developing pneumonia, a potential risk of antiviral resistance, and a subsequent delay of [...] Read more.
Background: Immunosuppressed patients still exhibit a high mortality rate due to SARS-CoV-2 infection, up to 21%. Persistent viral load replication and protracted viral symptoms result in a high risk of developing pneumonia, a potential risk of antiviral resistance, and a subsequent delay of onco-hematological treatments. Methods: Hematological patients and kidney transplant patients with SARS-CoV-2 infection, treated at GOM Niguarda Hospital (Milan) with combined antiviral therapy (remdesivir plus nirmatrelvir/ritonavir at standard doses) between November 2022 and March 2024, were retrospectively reviewed. Results: Thirty-four patients were analyzed. Twenty-four (71%) patients had pneumonia. The median duration of SARS-CoV-2 positivity before antiviral treatment was 40 (10–34) days. The median treatment duration was 11 (10–10) days. All patients went through clinical resolution. Thirteen patients were exposed to a new immune-chemotherapy cycle early after antiviral treatment (median 13, IQR 6–12 days), while five resumed a standard immunosuppressive regimen immediately after viral clearance. No relapse or recurrence of symptoms was reported for up to 226 (106–318) days of follow-up. Antiviral therapy was well tolerated, and no adverse events were observed. The 30-day overall survival was 94%, while the 90-day survival was 88%. No patient died of SARS-CoV-2 infection. Conclusions: The administration of nirmatrelvir/ritonavir and remdesivir lead to the complete resolution of SARS-CoV-2 pneumonia with no side effects in this cohort. The combination of these two antivirals may be a safe option in immunosuppressed population at risk of severe complications and prolonged SARS-CoV-2 infection in order to treat severe clinical presentation and to avoid viral recurrence after chemotherapy. Full article
(This article belongs to the Section Viral Infections)
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15 pages, 5420 KiB  
Article
Presence and Evolution of Radiological Changes at 6 and 12 Months After COVID-19 Pneumonia and Their Risk Factors
by Celia Roig-Martí, Antonio Navarro-Ballester, María-Pilar Fernández-García, Ignacio Pérez-Catalán, Ana Segura-Fábrega, María Varea-Villanueva, Sofía Folgado-Escudero, Germán Herrero-Rodríguez, Elena Domínguez-Bajo, Sergio Fabra-Juana, María-José Esteve-Gimeno, María-Lidón Mateu-Campos, Jorge Usó-Blasco and José-Manuel Ramos-Rincón
Medicina 2025, 61(3), 382; https://doi.org/10.3390/medicina61030382 - 22 Feb 2025
Viewed by 1478
Abstract
Background and Objectives: The pulmonary sequelae of COVID-19 and their evolution are of interest to the scientific community. We aimed to determine the radiological changes at 6 and 12 months after COVID-19 pneumonia, its evolution and its risk factors. Materials and Methods [...] Read more.
Background and Objectives: The pulmonary sequelae of COVID-19 and their evolution are of interest to the scientific community. We aimed to determine the radiological changes at 6 and 12 months after COVID-19 pneumonia, its evolution and its risk factors. Materials and Methods: This retrospective longitudinal study included adults admitted for COVID-19 pneumonia from 1 March 2020 to 30 April 2021 who had a high-resolution computed tomography (HRCT) scan at 6 months and 12 months after hospital discharge. The primary outcome was the appearance of radiological abnormalities on HRCT and the number of lung segments affected by them at 6 and 12 months, while the main explanatory variables were about the disease course, analytical parameters and treatment. Results: This study included n = 108 patients, with a mean age of 64 years. There was a decrease in the percentage of patients presenting parenchymal (93.5% to 88.9%, p < 0.001) and reticular (63% to 62%, p < 0.001) patterns on HRCT at 12 months compared to 6, and an increase in those presenting a fibrotic pattern (62% to 63.9%, p < 0.001). Ground-glass opacities were the most frequent radiological change at 6 and 12 months (91.7% and 87%, respectively). There was a significant reduction in the total number of lung segments with ground-glass opacities (445 to 382, p < 0.001) and consolidation (158 to 136, p = 0.019) and an increase in those with bronchiectasis (66 to 80, p = 0.033) between the two moments. After multivariate analysis, high-flow oxygen therapy (HFOT), highest ferritin levels, hypertension and ≥71 years showed an association with the development of subpleural parenchymal bands, consolidation, bronchiectasis and septal thickening at 6 and 12 months. Conclusions: Parenchymal patterns seem to be more frequent than reticular and fibrotic patterns after COVID-19 pneumonia. The fibrotic pattern was the only one that worsened significantly over time, with bronchiectasis being the only change that increased at 12 months. Older age, hypertension, the need for HFOT, and high levels of ferritin may be directly associated with worse radiological outcomes after COVID-19 pneumonia. Full article
(This article belongs to the Section Infectious Disease)
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18 pages, 274 KiB  
Article
Mortality and Predictive Factors for Death Following the Diagnosis of Interstitial Lung Disease in Patients with Rheumatoid Arthritis: A Retrospective, Long-Term Follow-Up Study
by Shunsuke Mori, Fumikazu Sakai, Mizue Hasegawa, Kazuyoshi Nakamura and Kazuaki Sugahara
J. Clin. Med. 2025, 14(4), 1380; https://doi.org/10.3390/jcm14041380 - 19 Feb 2025
Viewed by 1571
Abstract
Objective: The aim of this study was to determine mortality and predictive factors for death in patients with rheumatoid arthritis (RA) diagnosed with and without interstitial lung disease (ILD). Methods: We retrospectively performed a long-term follow-up study of patients diagnosed with RA at [...] Read more.
Objective: The aim of this study was to determine mortality and predictive factors for death in patients with rheumatoid arthritis (RA) diagnosed with and without interstitial lung disease (ILD). Methods: We retrospectively performed a long-term follow-up study of patients diagnosed with RA at our medical center between April 2001 and June 2023. The diagnosis and classification of ILD were made based on pulmonary high-resolution computed tomography (HRCT), taken at RA diagnosis and during follow-up. Results: Among 781 patients with RA, 78 were diagnosed with ILD; all cases except one were subclinical. The most common HRCT pattern was definite usual interstitial pneumonia (UIP) followed by nonspecific interstitial pneumonia (NSIP)/UIP, probable UIP, NSIP, and early UIP. During follow-up (mean of 10.0 years), the crude incidence rate of death (95% confidence interval [CI]) was 7.1 (5.2–10.0) and 1.5 (1.0–1.9) per 100 person-years in RA patients with and without ILD. Poor control of RA activity was associated with increased incidence rates of death. The standardized mortality ratio (95% CI) compared with the general population was 1.32 (1.11–1.53) for all RA patients, 2.09 (1.45–2.73) for RA-ILD patients, and 1.16 (0.95–1.38) for non-ILD RA patients. Lung cancer and respiratory failure were the most common causes of death in RA-ILD patients. The Multivariable Fine-Gray regression analysis revealed that ILD (adjusted hazard ratio [HR] 2.97 [95% CI 1.95–4.53]), advanced age (1.08 per additional year [1.05–1.10]), and low body mass index (3.07 [2.10–4.49]) were strong predictive factors for mortality in RA patients. HRCT patterns did not affect the risk of death in RA-ILD patients. Conclusions: Regardless of HRCT pattern, RA-ILD contributes to the increased mortality risk in patients with RA. Full article
(This article belongs to the Special Issue Rheumatoid Arthritis: Clinical Updates on Diagnosis and Treatment)
17 pages, 1114 KiB  
Article
Transthoracic Lung Ultrasound in Systemic Sclerosis-Associated Interstitial Lung Disease: Capacity to Differentiate Chest Computed-Tomographic Characteristic Patterns
by Cinzia Rotondo, Giuseppe Busto, Valeria Rella, Raffaele Barile, Fabio Cacciapaglia, Marco Fornaro, Florenzo Iannone, Donato Lacedonia, Carla Maria Irene Quarato, Antonello Trotta, Francesco Paolo Cantatore and Addolorata Corrado
Diagnostics 2025, 15(4), 488; https://doi.org/10.3390/diagnostics15040488 - 17 Feb 2025
Cited by 1 | Viewed by 1041
Abstract
Background/Objectives: Even today, interstitial lung disease (ILD) is diagnosed by chest high-resolution computed tomography (lung HR-CT). Large amounts of data are available about the usefulness of transthoracic lung ultrasound (LUS) in ILD. This study aimed to evaluate the transthoracic LUS capacity to [...] Read more.
Background/Objectives: Even today, interstitial lung disease (ILD) is diagnosed by chest high-resolution computed tomography (lung HR-CT). Large amounts of data are available about the usefulness of transthoracic lung ultrasound (LUS) in ILD. This study aimed to evaluate the transthoracic LUS capacity to discriminate different ILD patterns in systemic sclerosis (SSc) patients, such as usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP) with ground glass opacification/opacity (GGO), and NSIP with GGO and reticulations, as well as the possibility of identifying progressive fibrosing ILD. Methods: We enrolled SSc-patients attending the outpatient Clinic of the Rheumatology Unit of Policlinico of Foggia and the Rheumatology Unit of Policlinico of Bari who satisfied these inclusion criteria: age older than 18 years; the satisfaction of ACR/EULAR 2013 classification criteria for SSc; chest HR-CT scan within three months before or three months after transthoracic LUS evaluation; and availability of recent and complete pulmonary function test. The exclusion criteria were as follows: history or recent reactivation of chronic obstructive pulmonary disease, lung cancer, lung infection, heart failure, pulmonary oedema, pulmonary arterial hypertension, acute respiratory distress syndrome and diffuse alveolar haemorrhage and thoracic surgery. All enrolled SSc-patients underwent transthoracic LUS, performed by an experienced sonographer. The ILD diagnosis and the respective patterns were assessed by chest HR-CT, which still represents the best diagnostic tool. Results: ILD was observed in 99 (63.5%) patients. Of these, 25% had the UIP pattern and 75% the NSIP pattern (46 with GGO, 28 with GGO and reticulations). By receiver operating characteristic (ROC) curve analysis, higher values of accuracy, sensitivity, specificity, and negative clinical utility index (CUI) were found for pleural line irregularity (0.84 (95% CI: 0.75–0.91), 96%, and 73.6%, p = 0.0001; 0.72), and pleural line thickness (0.84 (95% CI: 0.74–0.91), 72%, and 96.4%, p = 0.0001; 0.85) for detecting the UIP pattern. The best performance among transthoracic LUS signs for NSIP with the GGO pattern was observed for B-lines (accuracy: 0.88 (95% CI: 0.80–0.93), sensitivity: 93.4% and specificity: 82.4, p = 0.0001; CUI+: 0.75, CUI−: 0.77). LUS signs with higher accuracy, sensitivity, and specificity for NSIP with GGO and reticulations were pleural line irregularity (0.89 (95% CI: 0.80–0.95), 96.4%, and 82.4%, p = 0.0001) with CUI−: 0.72, and B-lines (0.89 (95% CI: 0.80–0.95), 96.4%, 82.4%, p = 0.0001), with CUI+: 0.80 and CUI−: 0.70. Furthermore, a total number of B-lines > 10 maximises LUS performance with 92.3% sensitivity, and an accuracy of 0.83 (p = 0.0001) for detecting the NSIP pattern, particularly GGO. A sample-restricted analysis (66 SSc patients) evidenced the presence of progressive fibrosing ILD in 77% of these patients. By binary regression analysis, the unique LUS sign associated with progressive fibrosing ILD was the presence of pleural line irregularity (OR: 3.6; 95% CI 1.08–11.9; p = 0.036). Conclusions: Our study demonstrated that transthoracic LUS presented a high capacity to discriminate the different patterns of SSc-ILD. Therefore, the hypothesis that transthoracic LUS is an effective screening method for the evaluation of the presence of SSc-ILD and establishing the correct timing of chest HR-CT, in order to avoid patients receiving excessive exposure to ionising radiation, is supported. Full article
(This article belongs to the Special Issue Diagnosis, Classification, and Monitoring of Pulmonary Diseases)
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13 pages, 2606 KiB  
Review
The Role of Nailfold Videocapillaroscopy in the Diagnosis and Monitoring of Interstitial Lung Disease Associated with Rheumatic Autoimmune Diseases
by Daniela Anghel, Oana-Georgiana Prioteasă, Iulia-Nadine Nicolau, Săndica Bucurică, Daniela-Opriș Belinski, Gilda-Georgeta Popescu, Minerva Claudia Ghinescu, Anca Bobircă, Maria-Laura Groșeanu and Violeta-Claudia Bojincă
Diagnostics 2025, 15(3), 362; https://doi.org/10.3390/diagnostics15030362 - 4 Feb 2025
Cited by 2 | Viewed by 1462
Abstract
Interstitial lung disease (ILD) is a severe complication of certain connective tissue diseases (CTDs) such as systemic sclerosis (SSc), mixed connective tissue disease (MCTD), idiopathic inflammatory myopathies (IIM), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and it is associated with nailfold videocapillaroscopy [...] Read more.
Interstitial lung disease (ILD) is a severe complication of certain connective tissue diseases (CTDs) such as systemic sclerosis (SSc), mixed connective tissue disease (MCTD), idiopathic inflammatory myopathies (IIM), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and it is associated with nailfold videocapillaroscopy (NVC) changes and increased morbidity and mortality rates. Early diagnosis is crucial in order to prevent the progression of ILD, prevent respiratory failure and enhance the patient’s overall quality of life. The most common paraclinical investigations are high-resolution computed tomography (HRCT) and functional respiratory tests such as forced vital capacity (FVC) and the diffusing capacity of the lungs for carbon monoxide (DLCO). The most frequent CTD associated with both ILD and NVC changes is systemic sclerosis. The “late” scleroderma pattern was the most common abnormality identified in NVC results in SSc patients. Other autoimmune diseases were also correlated with ILD and NVC changes, especially when the Raynaud phenomenon was present. Low capillary density was associated with the presence and severity of ILD and a reduction in FVC and DLCO. NVC can also differentiate the capillaroscopic changes in some particular types of ILD, such as the usual interstitial pneumonia (UIP) pattern from the non-specific interstitial pneumonia (NSIP) pattern. Nevertheless, further extensive research is necessary in order to establish the diagnostic value of NVC in CTD-ILD in clinical practice. Full article
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16 pages, 3689 KiB  
Article
Single Disulfide Bond in Host Defense Thanatin Analog Peptides: Antimicrobial Activity, Atomic-Resolution Structures and Target Interactions
by Swaleeha Jaan Abdullah, Jia Sheng Guan, Yuguang Mu and Surajit Bhattacharjya
Int. J. Mol. Sci. 2025, 26(1), 51; https://doi.org/10.3390/ijms26010051 - 24 Dec 2024
Cited by 1 | Viewed by 1250
Abstract
Host defense antimicrobial peptides (AMPs) are promising lead molecules with which to develop antibiotics against drug-resistant bacterial pathogens. Thanatin, an inducible antimicrobial peptide involved in the host defense of Podisus maculiventris insects, is gaining considerable attention in the generation of novel classes of [...] Read more.
Host defense antimicrobial peptides (AMPs) are promising lead molecules with which to develop antibiotics against drug-resistant bacterial pathogens. Thanatin, an inducible antimicrobial peptide involved in the host defense of Podisus maculiventris insects, is gaining considerable attention in the generation of novel classes of antibiotics. Thanatin or thanatin-based analog peptides are extremely potent in killing bacterial pathogens in the Enterobacteriaceae family, including drug-resistant strains of Escherichia coli and Klebsiella pneumoniae. A single disulfide bond that covalently links two anti-parallel β-strands in thanatin could be pivotal to its selective antibacterial activity and mode of action. However, potential correlations of the disulfide covalent bond with structure, activity and target binding in thanatin peptides are currently unclear to. Here, we examined a 16-residue designed thanatin peptide, namely disulfide-bonded VF16QK, and its Cys to Ser substituted variant, VF16QKSer, to delineate their structure–activity relationships. Bacterial growth inhibitory activity was only detected for the disulfide-bonded VF16QK peptide. Mechanistically, both peptides vastly differ in their bacterial cell permeabilizations, atomic-resolution structures, interactions with the LPS-outer membrane and target periplasmic protein LptAm binding. In particular, analysis of the 3-D structures of the two peptides revealed an altered folded conformation for the VF16QKSer peptide that was correlated with diminished LPS-outer membrane permeabilization and target interactions. Analysis of docked complexes of LPS–thanatin peptides indicated potential structural requirements and conformational adaptation for antimicrobial activity. Collectively, these observations contrast with those for the disulfide-bonded β-hairpin antimicrobial protegrin and tachyplesin peptides, where disulfide bonds are dispensable for activity. We surmise that the atomistic structures and associated molecular interactions presented in this work can be utilized to design novel thanatin-based antibiotics. Full article
(This article belongs to the Section Molecular Biophysics)
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9 pages, 2901 KiB  
Article
Chest X-Ray Features in 130 Patients with Bronchiectasis
by Hikaru Sawada, Ryohei Kudoh, Atsushi Yokoyama, Akihiko Hagiwara, Kazufumi Hiramatsu, Jun-ichi Kadota and Kosaku Komiya
Diseases 2024, 12(12), 323; https://doi.org/10.3390/diseases12120323 - 10 Dec 2024
Viewed by 3538
Abstract
Background/Objectives: The prevalence of bronchiectasis is increasing globally, and early detection using chest imaging has been encouraged to improve its prognosis. However, the sensitivity of a chest X-ray as a screening tool remains unclear. This study examined the chest X-ray features predictive of [...] Read more.
Background/Objectives: The prevalence of bronchiectasis is increasing globally, and early detection using chest imaging has been encouraged to improve its prognosis. However, the sensitivity of a chest X-ray as a screening tool remains unclear. This study examined the chest X-ray features predictive of bronchiectasis. Methods: We retrospectively reviewed the chest X-rays of patients with bronchiectasis diagnosed using high-resolution computed tomography who visited our institute from January 2013 to March 2020. Patients with cardiac pacemakers, lung cancer, and interstitial pneumonia, which might bias the detection of bronchiectasis, were excluded. Two respiratory physicians independently determined the presence or absence of potential features reflecting bronchiectasis, including a vague cardiac silhouette on chest X-rays. Results: The study enrolled 130 patients, including 72 women (55.4%), with a mean age of 72 years. The features observed on chest X-rays included granular shadows (88.5%, n = 115), vague cardiac silhouettes (48.5%, n = 64), nodular shadows (45.4%, n = 59), a tram-track appearance (35.4%, n = 46), pleural thickening (26.9%, n = 35), vague diaphragm silhouettes (25.4%, n = 33), and a ring sign (24.6%, n = 32). The kappa values for these features were 0.271, 0.344, 0.646, 0.256, 0.312, 0.514, and 0.376, respectively. Conclusions: Although traditional chest X-ray features believed to reflect bronchiectasis, such as the tram-track appearance or ring sign, were not frequently seen, vague cardiac silhouettes and granular shadows had high positivity rates, indicating their potential utility for bronchiectasis screening. However, the interobserver concordance rates were unsatisfactory. Full article
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14 pages, 1218 KiB  
Article
Long-Term Pulmonary Sequelae and Immunological Markers in Patients Recovering from Severe and Critical COVID-19 Pneumonia: A Comprehensive Follow-Up Study
by Edita Strumiliene, Jurgita Urbonienė, Laimute Jurgauskiene, Ingrida Zeleckiene, Rytis Bliudzius, Laura Malinauskiene, Birutė Zablockiene, Arturas Samuilis and Ligita Jancoriene
Medicina 2024, 60(12), 1954; https://doi.org/10.3390/medicina60121954 - 27 Nov 2024
Viewed by 1325
Abstract
Background and Objectives: Severe and critical COVID-19 pneumonia can lead to long-term complications, especially affecting pulmonary function and immune health. However, the extent and progression of these complications over time are not well understood. This study aimed to assess lung function, radiological [...] Read more.
Background and Objectives: Severe and critical COVID-19 pneumonia can lead to long-term complications, especially affecting pulmonary function and immune health. However, the extent and progression of these complications over time are not well understood. This study aimed to assess lung function, radiological changes, and some immune parameters in survivors of severe and critical COVID-19 up to 12 months after hospital discharge. Materials and Methods: This prospective observational cohort study followed 85 adult patients who were hospitalized with severe or critical COVID-19 pneumonia at a tertiary care hospital in Vilnius, Lithuania, for 12 months post-discharge. Pulmonary function tests (PFTs), including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and diffusion capacity for carbon monoxide (DLCO), were conducted at 3, 6, and 12 months. High-resolution chest computed tomography (CT) scans assessed residual inflammatory and profibrotic/fibrotic abnormalities. Lymphocyte subpopulations were evaluated via flow cytometry during follow-up visits to monitor immune status. Results: The median age of the cohort was 59 years (IQR: 51–64). Fifty-three (62.4%) patients had critical COVID-19 disease. Pulmonary function improved significantly over time, with increases in FVC, FEV1, VC, TLC, and DLCO. Residual volume (RV) did not change significantly over time, suggesting that some aspects of lung function, such as air trapping, remained stable and may require attention in follow-up care. The percentage of patients with restrictive spirometry patterns decreased from 24.71% at 3 months to 14.8% at 12 months (p < 0.05). Residual inflammatory changes on CT were present in 77.63% at 6 months, decreasing to 69.62% at 12 months (p < 0.001). Profibrotic changes remained prevalent, affecting 82.89% of patients at 6 months and 73.08% at 12 months. Lymphocyte counts declined significantly from 3 to 12 months (2077 cells/µL vs. 1845 cells/µL, p = 0.034), with notable reductions in CD3+ (p = 0.040), CD8+ (p = 0.007), and activated CD3HLA-DR+ cells (p < 0.001). This study found that higher CD4+ T cell counts were associated with worse lung function, particularly reduced total lung capacity (TLC), while higher CD8+ T cell levels were linked to improved pulmonary outcomes, such as increased forced vital capacity (FVC) and vital capacity (VC). Multivariable regression analyses revealed that increased levels of CD4+/CD28+/CD192+ T cells were associated with worsening lung function, while higher CD8+/CD28+/CD192+ T cell counts were linked to better pulmonary outcomes, indicating that immune dysregulation plays a critical role in long-term respiratory recovery. Conclusions: Survivors of severe and critical COVID-19 pneumonia continue to experience significant long-term impairments in lung function and immune system health. Regular monitoring of pulmonary function, radiological changes, and immune parameters is essential for guiding personalized post-COVID-19 care and improving long-term outcomes. Further research is needed to explore the mechanisms behind these complications and to develop targeted interventions for long COVID-19. Full article
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