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Keywords = extrapulmonary disease

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7 pages, 2239 KiB  
Case Report
Silently Wrapped: Embolization and Surgical Strategy for Giant Sciatic-Sparing Myxoid Liposarcoma—Case Report
by Radu Aurelian Vișan and Victor Baluța
Reports 2025, 8(3), 124; https://doi.org/10.3390/reports8030124 - 28 Jul 2025
Viewed by 309
Abstract
Background and Clinical Significance: Myxoid liposarcoma (MLS) is a malignant soft tissue tumor that often presents as a painless, slow-growing mass and is known for its atypical extrapulmonary metastatic pattern. Although sciatic nerve involvement is rare, when present, it usually causes neurologic symptoms. [...] Read more.
Background and Clinical Significance: Myxoid liposarcoma (MLS) is a malignant soft tissue tumor that often presents as a painless, slow-growing mass and is known for its atypical extrapulmonary metastatic pattern. Although sciatic nerve involvement is rare, when present, it usually causes neurologic symptoms. In this case, a large MLS silently expanded and completely encased the sciatic nerve without causing deficits, highlighting the importance of early imaging, multidisciplinary planning, and individualized surgical strategy in managing complex soft tissue sarcomas. Case Presentation: This case report describes a 67-year-old male with a 30 cm encapsulated myxoid liposarcoma of the posterior left thigh. The tumor had grown insidiously over one year and completely encased the sciatic nerve without causing pain, paresthesia, or motor impairment. Selective embolization was performed preoperatively to minimize blood loss. A posteromedial surgical approach allowed for en bloc resection with negative margins and preservation of sciatic nerve integrity. Histopathology confirmed a myxoid liposarcoma composed primarily of spindle-shaped tumor cells. The patient experienced no postoperative complications or neurologic deficits. At the two-year follow-up, he remains disease-free with full functional recovery. Conclusions: This case illustrates the potential for large, asymptomatic myxoid liposarcomas to encase critical neurovascular structures without infiltration. Preoperative embolization as part of a multidisciplinary plan was key to achieving safe resection and excellent functional outcomes. Full article
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24 pages, 3224 KiB  
Review
Quercetin in Idiopathic Pulmonary Fibrosis and Its Comorbidities: Gene Regulatory Mechanisms and Therapeutic Implications
by Verónica Rocío Vásquez-Garzón, Juan Manuel Velázquez-Enríquez, Jovito Cesar Santos-Álvarez, Alma Aurora Ramírez-Hernández, Jaime Arellanes-Robledo, Cristian Jiménez-Martínez and Rafael Baltiérrez-Hoyos
Genes 2025, 16(8), 856; https://doi.org/10.3390/genes16080856 - 23 Jul 2025
Viewed by 1008
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease associated with high morbidity and mortality. Both pulmonary and extrapulmonary comorbidities significantly influence disease progression and patient outcomes. Despite current therapeutic options, effective treatments remain limited. Quercetin, a naturally occurring flavonoid, [...] Read more.
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease associated with high morbidity and mortality. Both pulmonary and extrapulmonary comorbidities significantly influence disease progression and patient outcomes. Despite current therapeutic options, effective treatments remain limited. Quercetin, a naturally occurring flavonoid, has emerged as a promising compound due to its antioxidant, anti-inflammatory, and antifibrotic properties. Preclinical and clinical studies have demonstrated its ability to modulate key molecular pathways involved in IPF, including Nrf2, SIRT1/AMPK, and the regulation of fibrosis-associated microRNAs (miRNAs). Furthermore, quercetin shows therapeutic potential across a range of IPF-related comorbidities, including chronic obstructive pulmonary disease, pulmonary hypertension, lung cancer, cardiovascular disease, diabetes, and psychiatric disorders. Under these conditions, quercetin acts via epigenetic modulation of miRNAs and regulation of oxidative stress and inflammatory signaling pathways. This review highlights the multifunctional role of quercetin in IPF and its comorbidities, emphasizing its gene regulatory mechanisms and potential as an adjunctive or alternative therapeutic strategy. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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11 pages, 237 KiB  
Article
Mycobacterium bovis Infection Frequently Requires Surgical Intervention in Individuals with HIV
by Sergio Zuñiga-Quiñonez, Pedro Martinez-Ayala, Monserrat Alvarez-Zavala, Andrea Torres-Rojas, Isaac D. V. Garcia-Govea, Luz A. Gonzalez-Hernandez, Jaime F. Andrade-Villanueva and Fernando Amador-Lara
Infect. Dis. Rep. 2025, 17(4), 82; https://doi.org/10.3390/idr17040082 - 11 Jul 2025
Viewed by 471
Abstract
Background: Zoonotic infection with Mycobacterium bovis continues to occur, particularly in regions lacking bovine tuberculosis surveillance and where the consumption of unpasteurized dairy products, including artisanal cheeses, is common. We describe the clinical and microbiological characteristics, diagnostic procedures, and treatment outcomes of individuals [...] Read more.
Background: Zoonotic infection with Mycobacterium bovis continues to occur, particularly in regions lacking bovine tuberculosis surveillance and where the consumption of unpasteurized dairy products, including artisanal cheeses, is common. We describe the clinical and microbiological characteristics, diagnostic procedures, and treatment outcomes of individuals with HIV with M. bovis infection. Methods: We conducted a retrospective study analyzing sociodemographic, clinical, microbiological, and computed tomography (CT) data, as well as treatment outcomes, in 12 patients with HIV with confirmed M. bovis infection. These findings were compared with those of 14 individuals with HIV diagnosed with Mycobacterium tuberculosis infection during the same period. Results: Consumption of unpasteurized dairy products was significantly associated with M. bovis. Patients with M. bovis infection had higher CD4+ T-cell counts compared to those with M. tuberculosis infection (p = 0.01, r = 0.45). All M. bovis cases presented with extrapulmonary disease. CT imaging in M. bovis infection more frequently demonstrated retroperitoneal lymphadenopathy, hepatosplenomegaly, and splenic abscesses compared to M. tuberculosis infection. Microbiological identification was exclusively from extrapulmonary sites in all M. bovis cases. Surgical interventions, including abscess drainage or splenectomy, were significantly more common among M. bovis patients. Conclusions: M. bovis infection in individuals with HIV is characterized by consistent extrapulmonary, often abdominal, involvement. Surgical procedures are frequently required for both diagnosis and management. Targeted efforts to identify M. bovis are warranted, particularly in high-burden regions where unpasteurized dairy consumption remains prevalent. Full article
(This article belongs to the Section Tuberculosis and Mycobacteriosis)
29 pages, 14985 KiB  
Article
Spatiotemporal Characterization of Changes in the Respiratory Tract and the Nervous System, Including the Eyes in SARS-CoV-2-Infected K18-hACE2 Mice
by Malgorzata Rosiak, Tom Schreiner, Georg Beythien, Eva Leitzen, Anastasiya Ulianytska, Lisa Allnoch, Kathrin Becker, Lukas M. Michaely, Sandra Lockow, Sabrina Clever, Christian Meyer zu Natrup, Asisa Volz, Wolfgang Baumgärtner, Malgorzata Ciurkiewicz, Kirsten Hülskötter and Katharina M. Gregor
Viruses 2025, 17(7), 963; https://doi.org/10.3390/v17070963 - 9 Jul 2025
Viewed by 554
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is known to affect multiple organ systems, including the respiratory tract and nervous and ocular systems. This retrospective study aimed to characterize the spatiotemporal distribution of viral antigen [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is known to affect multiple organ systems, including the respiratory tract and nervous and ocular systems. This retrospective study aimed to characterize the spatiotemporal distribution of viral antigen and associated pathological changes in the nose, lungs, brain, and eyes of K18-hACE2 mice intranasally infected with SARS-CoV-2. Using histology and immunohistochemistry, tissues were examined at 3, 6, and 7/8 days post-infection (dpi). In addition, lung and brain tissues were analyzed by means of RT-qPCR to determine viral RNA titers. Viral antigen was most pronounced in the nose, brain, and lung at 3, 6, and 7/8 dpi, respectively, whereas viral antigen was detected at 6 and 7/8 dpi in the retina. Quantitative PCR confirmed increasing viral RNA levels in both lung and brain, peaking at 7/8 dpi. Nasal and lung inflammation mirrored viral antigen distribution and localization. In the brain, the predominantly basal viral spread correlated with lymphohistiocytic meningoencephalitis, neuronal vacuolation, and altered neurofilament immunoreactivity. Retinal ganglion cells showed viral antigen expression without associated lesions. Microglial activation was evident in both the optic chiasm and the brain. These findings highlight the K18-hACE2 model’s utility for studying extrapulmonary SARS-CoV-2 pathogenesis. Understanding the temporal and spatial dynamics of viral spread enhances insights into SARS-CoV-2 neurotropism and its clinical manifestations. Full article
(This article belongs to the Section Coronaviruses)
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12 pages, 4130 KiB  
Article
Gastrointestinal Tuberculosis: Clinical Presentations and Diagnostic Approaches
by Timur Gonchar, Mauro Sidney De Robertis, Carola Güther, Madlen Löbel and Tobias Kleemann
J. Clin. Med. 2025, 14(13), 4398; https://doi.org/10.3390/jcm14134398 - 20 Jun 2025
Viewed by 1024
Abstract
Background: Gastrointestinal tuberculosis (GI TB) is a rare form of extrapulmonary TB that often mimics other conditions, such as Crohn’s disease (CD) or GI malignancies. Conventional diagnostics, like direct microscopy and culture, are often inconclusive or slow, delaying treatment. In Germany, a [...] Read more.
Background: Gastrointestinal tuberculosis (GI TB) is a rare form of extrapulmonary TB that often mimics other conditions, such as Crohn’s disease (CD) or GI malignancies. Conventional diagnostics, like direct microscopy and culture, are often inconclusive or slow, delaying treatment. In Germany, a low-incidence country, GI TB is underrecognized. Rising migration has led to a resurgence of TB cases, increasing the likelihood of encountering extrapulmonary presentations. This study evaluates the performance and utility of various diagnostic tools and proposes a diagnostic approach to reduce delays and avoid unnecessary interventions. Methods: We retrospectively analyzed eight patients suspected of GI TB based on clinical presentation and testing. Two recent cases are described in detail to highlight diagnostic and therapeutic challenges. Results: GI TB was confirmed in five cases (62.5%), and all the patients presented with abdominal complaints, with the majority experiencing systemic symptoms such as weight loss or fever. Histopathology supported the diagnosis in all GI TB cases, while PCR testing was positive in four. Direct microscopy detected acid-fast bacilli in only one case. The remaining patients were diagnosed with latent genital TB, disseminated TB without GI involvement, or were ruled out clinically. Conclusions: GI TB remains a diagnostic challenge that often mimics other conditions, such as CD or malignancy. Early use of histopathology and PCR in patients with a high risk of GI TB is critical for timely diagnosis. In low-incidence settings like Germany, clinicians should maintain high suspicion in at-risk populations (e.g., migrants from areas or immunocompromised patients), especially when symptoms mimic CD or malignancy, to improve outcomes and avoid unnecessary procedures. Full article
(This article belongs to the Section Infectious Diseases)
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17 pages, 4719 KiB  
Article
Head and Neck Tuberculosis: A Rare Diagnosis and the Role of Surgical Biopsy and Histopathological Evaluation in Extrapulmonary Disease
by Carmen Aurelia Mogoantă, Andrei Osman, Alina-Maria Georgescu, Alexandra Maria Mitroi, Constantin Ioan Busuioc, Ionuţ Tănase, Ramona Cioboată, Ilona Mihaela Liliac, Ovidiu Lucian Cimpeanu and Mircea Sorin Ciolofan
Pathogens 2025, 14(5), 479; https://doi.org/10.3390/pathogens14050479 - 14 May 2025
Viewed by 755
Abstract
(1) Background: Extrapulmonary tuberculosis (EPTB) of the head and neck is a rare but difficult diagnosis due to mostly absent pulmonary involvement and high clinical resemblance to neoplastic or chronic inflammatory conditions. This diagnosis still poses a challenge for otorhinolaryngologists, due to non-specific [...] Read more.
(1) Background: Extrapulmonary tuberculosis (EPTB) of the head and neck is a rare but difficult diagnosis due to mostly absent pulmonary involvement and high clinical resemblance to neoplastic or chronic inflammatory conditions. This diagnosis still poses a challenge for otorhinolaryngologists, due to non-specific symptoms and the low index of suspicion in non-endemic regions. (2) Methods: This study presents a retrospective review of nine cases of head and neck EPTB diagnosed at two regional hospitals in southern Romania. Patients presented with pharyngeal, laryngeal, or cervical lymph node involvement. All cases underwent surgical biopsies for histopathological and microbiological confirmation, followed by standard anti-tubercular therapy. (3) Results: In all nine cases, surgical biopsies were essential for the accurate diagnosis and excluded malignancy or other granulomatous diseases. Diagnostic delays were observed due to atypical clinical presentations. Integration of biopsy findings with anti-tubercular treatment resulted in favorable disease control and clinical recovery. (4) Conclusions: Head and neck EPTB requires a high index of suspicion and clinical discernment. Surgical biopsy remains a critical diagnostic tool in practice and should be considered early in the diagnostic process when encountering atypical lesions. A timely use improves diagnostic accuracy, may eliminate delays, ensures patient safety, and improves therapeutic outcomes. Full article
(This article belongs to the Special Issue Feature Papers on the Epidemiology of Infectious Diseases)
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17 pages, 348 KiB  
Article
Association Between Nursing Diagnoses and Mortality in Hospitalized Patients with COVID-19: A Retrospective Cohort Study
by José Ángel Hernández-Mariano, Olivia Mendoza-Macario, María del Carmen Velázquez-Núñez, María del Carmen Cedillo-Ordaz, Blanca Estela Cervantes-Guzmán, Dulce Milagros Razo-Blanco-Hernández, Erick Alberto Landeros-Olvera, Fani Villa-Rivas, Rocío Castillo-Díaz and Guillermo Cano-Verdugo
Nurs. Rep. 2025, 15(5), 147; https://doi.org/10.3390/nursrep15050147 - 28 Apr 2025
Viewed by 1112
Abstract
Previous studies suggest that nursing diagnoses (NDs) could predict clinical outcomes, such as mortality, among patients with non-communicable diseases. However, evidence in patients with COVID-19 is still scarce. Objective: To evaluate the association between NDs and COVID-19 mortality among hospitalized patients. Methods: A [...] Read more.
Previous studies suggest that nursing diagnoses (NDs) could predict clinical outcomes, such as mortality, among patients with non-communicable diseases. However, evidence in patients with COVID-19 is still scarce. Objective: To evaluate the association between NDs and COVID-19 mortality among hospitalized patients. Methods: A retrospective cohort study was conducted on 498 paper clinical records of patients hospitalized for at least 72 h in the internal medicine unit for COVID-19 from June to December 2020. The interest association was assessed using logistic regression models. Results: NDs focused on COVID-19 pulmonary responses, such as impaired gas exchange (OR = 3.04; 95% CI = 1.87, 4.95), impaired spontaneous ventilation (OR = 3.67; 95% CI = 2.17, 6.21), or ineffective airway clearance (OR = 2.47; 95% CI = 1.48, 4.12), were significant predictors of mortality. NDs on COVID-19 extrapulmonary responses, such as risk for unstable blood glucose level (OR = 2.45; 95% CI = 1.45, 4,15), risk for impaired liver function (OR = 2.02; 95% CI = 1.11, 3.63), hyperthermia (OR = 2.08; 95% CI = 1.29, 3.35), decreased cardiac output (OR = 2.95; 95% CI = 1.42, 6.11), or risk for shock (OR = 3.03; 95% CI = 1.28, 7.13), were associated with a higher risk of in-hospital mortality. Conversely, patients with NDs of fear (OR = 0.56; 95% CI = 0.35, 0.89) and anxiety (OR = 0.44; 95% CI = 0.26, 0.77) had a lower risk of death. Conclusions: NDs on pulmonary and extrapulmonary responses to COVID-19 were associated with in-hospital mortality, suggesting that they are indicators of the severity of these patients. Therefore, NDs may help nursing staff identify individuals who require closer monitoring and guide early interventions for their recovery. Full article
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13 pages, 233 KiB  
Article
Diagnostic Challenges in Extrapulmonary Tuberculosis: A Single-Center Experience in a High-Resource Setting at a German Tertiary Care Center
by Jonas Wilmink, Richard Vollenberg, Ioana D. Olaru, Julia Fischer, Jonel Trebicka and Phil-Robin Tepasse
Infect. Dis. Rep. 2025, 17(3), 39; https://doi.org/10.3390/idr17030039 - 23 Apr 2025
Viewed by 697
Abstract
Background/Objectives: Extrapulmonary tuberculosis accounts for a significant portion of tuberculosis cases, presenting unique diagnostic challenges due to its heterogeneous manifestations and paucibacillary nature. This study aims to fill this gap by evaluating the diagnostic outcomes and correlations between different specimen types and [...] Read more.
Background/Objectives: Extrapulmonary tuberculosis accounts for a significant portion of tuberculosis cases, presenting unique diagnostic challenges due to its heterogeneous manifestations and paucibacillary nature. This study aims to fill this gap by evaluating the diagnostic outcomes and correlations between different specimen types and test results. Methods: A retrospective analysis of electronic medical records of patients diagnosed with TB between January 2013 and December 2023 was carried out. The data extracted included patient demographics, comorbidities, TB classification, specimen types, microbiological test results, and time intervals to diagnosis. Statistical analysis was applied to compare the variables between pulmonary and extrapulmonary/disseminated TB groups. Results: Most patients were male (62.4%) and born outside of Germany (74.2%). Comorbidities, such as diabetes, cardiac disease, immunosuppressed status, and HIV, were common. Among the 194 patients, 98 had pulmonary TB, and 96 had extrapulmonary/disseminated TB. A comparison of pulmonary vs. extrapulmonary TB showed that extrapulmonary TB patients had a longer diagnostic delay (p = 0.013), more symptoms (p = 0.001), and more complications (42.7% vs. 16.3%, p < 0.001). Diagnostic challenges were evident, with multiple invasive procedures required in 43.5% of the extrapulmonary TB cases. Conclusions: This study highlights the complex clinical presentation of tuberculosis, particularly in patients with extrapulmonary and disseminated forms, who experience delayed diagnosis and more complications. These challenges in diagnosing extrapulmonary TB emphasize the need for improved diagnostic strategies and early identification, especially in high-risk populations. Full article
(This article belongs to the Section Tuberculosis and Mycobacteriosis)
23 pages, 1515 KiB  
Article
Comparative Insights into COVID-19 and Tuberculosis: Clinical Manifestations, Inflammatory Markers, and Outcomes in Pulmonary Versus Extrapulmonary Tuberculosis and SARS-CoV-2 Co-Infection
by Camil Mihuta, Adriana Socaci, Patricia Hogea, Emanuela Tudorache, Monica Simina Mihuta and Cristian Oancea
J. Clin. Med. 2025, 14(8), 2782; https://doi.org/10.3390/jcm14082782 - 17 Apr 2025
Viewed by 606
Abstract
Background: Tuberculosis and COVID-19 co-infection poses significant clinical challenges, with pulmonary TB (PTB) and extrapulmonary TB (extraPTB) potentially influencing disease progression and outcomes differently. This study aims to compare the clinical manifestations, inflammatory markers, and outcomes between PTB and extraPTB patients with [...] Read more.
Background: Tuberculosis and COVID-19 co-infection poses significant clinical challenges, with pulmonary TB (PTB) and extrapulmonary TB (extraPTB) potentially influencing disease progression and outcomes differently. This study aims to compare the clinical manifestations, inflammatory markers, and outcomes between PTB and extraPTB patients with SARS-CoV-2 co-infection. Methods: A retrospective, cross-sectional study was conducted on 55 hospitalized adults with TB-COVID-19 co-infection from March 2020 to March 2022. Patients were divided into PTB (n = 32) and extraPTB (n = 23) groups. Demographic, clinical, laboratory, and imaging data were collected and analyzed using statistical models, including ANCOVA, LASSO regression, and Random Forest classification, to identify key predictors of hospitalization duration and mortality. Results: PTB patients had significantly lower BMI, worse oxygenation status, and greater lung involvement on CT compared to extraPTB patients. CRP was elevated in PTB, while IL-6 levels were higher in extraPTB. Hospitalization duration was primarily influenced by inflammatory and coagulation markers (IL-6, D-dimer, neutrophil count, systemic inflammatory index), while higher BMI was associated with shorter stays. Mortality risk was strongly correlated with oxygenation impairment (worst SpO2, SpO2 at diagnosis), inflammatory burden (CRP, LDH), and CT severity score, rather than TB localization. Conclusions: TB localization did not independently affect hospitalization duration or mortality risk. Instead, severe lung involvement, systemic inflammation, and hypoxemia were the strongest predictors of poor outcomes. These findings emphasize the importance of early risk stratification based on respiratory and inflammatory markers to optimize patient management. Further research is needed to clarify the long-term impact of TB-COVID-19 co-infection, particularly in extraPTB cases. Full article
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38 pages, 2337 KiB  
Review
Leptin and Insulin in COPD: Unveiling the Metabolic-Inflammatory Axis—A Narrative Review
by Oana Maria Catana, Alexandra Floriana Nemes, Ramona Cioboata, Claudia Lucia Toma, Denisa Maria Mitroi, Cristina Calarasu and Costin Teodor Streba
J. Clin. Med. 2025, 14(8), 2611; https://doi.org/10.3390/jcm14082611 - 10 Apr 2025
Cited by 1 | Viewed by 1391
Abstract
Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating condition characterized by airflow limitations and systemic inflammation. The interaction between the metabolic and inflammatory pathways plays a key role in disease progression, with leptin and insulin emerging as pivotal metabolic regulators. Leptin, [...] Read more.
Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating condition characterized by airflow limitations and systemic inflammation. The interaction between the metabolic and inflammatory pathways plays a key role in disease progression, with leptin and insulin emerging as pivotal metabolic regulators. Leptin, an adipokine that regulates energy homeostasis, and insulin, the primary regulator of glucose metabolism, are both altered in COPD patients. This narrative review provides an in-depth examination of the roles of leptin and insulin in COPD pathogenesis, focusing on the molecular mechanisms through which these metabolic regulators interact with inflammatory pathways and how their dysregulation contributes to a spectrum of extrapulmonary manifestations. These disturbances not only exacerbate COPD symptoms but also increase the risk of comorbidities such as metabolic syndrome, diabetes, cardiovascular disease, or muscle wasting. By exploring the underlying mechanisms of leptin and insulin dysregulation in COPD, this review underscores the significance of the metabolic–inflammatory axis, suggesting that restoring metabolic balance through leptin and insulin modulation could offer novel therapeutic strategies for improving clinical outcomes. Full article
(This article belongs to the Special Issue Moving Forward to New Trends in Pulmonary Diseases)
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43 pages, 3187 KiB  
Review
Marine-Derived Bioactive Compounds: A Promising Strategy for Ameliorating Skeletal Muscle Dysfunction in COPD
by Meiling Jiang, Peijun Li, Xiaoyu Han, Linhong Jiang, Lihua Han, Qinglan He, Chen Yang, Zhichao Sun, Yingqi Wang, Yuanyuan Cao, Xiaodan Liu and Weibing Wu
Mar. Drugs 2025, 23(4), 158; https://doi.org/10.3390/md23040158 - 4 Apr 2025
Cited by 1 | Viewed by 1117
Abstract
Chronic obstructive pulmonary disease (COPD) is frequently accompanied by skeletal muscle dysfunction, a critical and severe extrapulmonary complication. This dysfunction contributes to reduced exercise capacity, increased frequency of acute exacerbations, and elevated mortality, serving as an independent risk factor for poor prognosis in [...] Read more.
Chronic obstructive pulmonary disease (COPD) is frequently accompanied by skeletal muscle dysfunction, a critical and severe extrapulmonary complication. This dysfunction contributes to reduced exercise capacity, increased frequency of acute exacerbations, and elevated mortality, serving as an independent risk factor for poor prognosis in COPD patients. Owing to the unique physicochemical conditions of the marine environment, marine-derived bioactive compounds exhibit potent anti-inflammatory and antioxidant properties, demonstrating therapeutic potential for ameliorating COPD skeletal muscle dysfunction. This review summarizes marine-derived bioactive compounds with promising efficacy against skeletal muscle dysfunction in COPD, including polysaccharides, lipids, polyphenols, peptides, and carotenoids. The discussed compounds have shown bioactivities in promoting skeletal muscle health and suppressing muscle atrophy, thereby providing potential strategies for the prevention and treatment of COPD skeletal muscle dysfunction. These findings may expand the therapeutic strategies for managing COPD skeletal muscle dysfunction. Full article
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24 pages, 2801 KiB  
Article
Clinicopathological Characteristics of Extrapulmonary Neuroendocrine Carcinomas: Treatment Responses and Survival Outcomes: Single-Center Experience
by Harun Muğlu, Erdem Sünger, Maral Martin Mıldanoğlu, Ebru Engin Delipoyraz, Mehmet Haluk Yücel, Hakan Özçelik, Jamshid Hamdard, Özgür Açıkgöz, Ömer Fatih Ölmez, Özcan Yıldız and Ahmet Bilici
J. Clin. Med. 2025, 14(7), 2264; https://doi.org/10.3390/jcm14072264 - 26 Mar 2025
Viewed by 774
Abstract
 Background/Objectives: Extrapulmonary neuroendocrine carcinomas (EP-NECs) are rare, aggressive malignancies with no standardized treatment approach. Although platinum-based chemotherapy is considered the first-line therapy, overall survival (OS) and progression-free survival (PFS) remain limited. This study aims to evaluate the clinical and pathological characteristics of [...] Read more.
 Background/Objectives: Extrapulmonary neuroendocrine carcinomas (EP-NECs) are rare, aggressive malignancies with no standardized treatment approach. Although platinum-based chemotherapy is considered the first-line therapy, overall survival (OS) and progression-free survival (PFS) remain limited. This study aims to evaluate the clinical and pathological characteristics of EP-NEC patients, their treatment responses, and survival outcomes. Methods: This retrospective observational study included 29 EP-NEC patients diagnosed and followed between 2015 and 2024. Clinical and demographic data, tumor localization, disease stage, administered treatments, and survival outcomes were analyzed. Kaplan–Meier survival analysis was used to assess OS and PFS, with subgroup comparisons performed via the log-rank test. Results: The most common primary tumor sites were the pancreas (21%), prostate (17%), and cervix (14%). At diagnosis, 55.2% of patients had metastatic disease. First-line platinum-based chemotherapy achieved an objective response rate of 82.1%, with a median PFS of 8.16 months and a median OS of 14.16 months. Surgical intervention significantly improved survival (p = 0.020), while a high Ki-67 proliferation index (>80%) was associated with worse PFS (p = 0.032). Other factors, including smoking status and liver-directed therapies, had no significant impact on survival. Conclusions: EP-NECs present with a poor prognosis despite platinum-based chemotherapy achieving high response rates. Surgical resection improves survival outcomes, whereas high Ki-67 expression is associated with a worse prognosis. These findings highlight the need for further research into novel therapeutic strategies for EP-NECs. Full article
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15 pages, 1720 KiB  
Perspective
Intricacies of Global Tuberculosis Management—EndTB-2035 on the Fence?
by Radha Gopalaswamy and Selvakumar Subbian
J. Respir. 2025, 5(1), 4; https://doi.org/10.3390/jor5010004 - 17 Mar 2025
Viewed by 925
Abstract
Tuberculosis (TB) is a leading cause of death from a single infectious agent in humans. The morbidity and mortality due to TB are further worsened by co-existing health conditions and the emergence of drug-resistant (DR-TB) cases. The WHO has declared TB as a [...] Read more.
Tuberculosis (TB) is a leading cause of death from a single infectious agent in humans. The morbidity and mortality due to TB are further worsened by co-existing health conditions and the emergence of drug-resistant (DR-TB) cases. The WHO has declared TB as a global emergency and endorsed global efforts to improve diagnosis, and treatment while reducing the catastrophic cost in an EndTB strategy in 2013, with a vision to create a TB-free world. In the past decade, molecular diagnostic tools, such as nucleic acid amplification technologies (NAATs), have replaced the conventional smear microscopy of TB, thus offering better bacteriological confirmation and case detection along with drug resistance in pulmonary and extrapulmonary samples. Follow-on testing using a more advanced targeted next-generation sequencing (tNGS) system has improved the diagnosis of cases resistant to first- and second-line anti-TB drugs, including newer ones. TB treatment has been improved with the introduction of newer drugs including an all-oral regimen for DR-TB, thereby improving patient compliance. Improved TB prevention is achieved through the broadening of BCG vaccination as well as preventive therapy for asymptomatic, latent TB (LTBI) cases, which, otherwise, can reactivate to symptomatic disease. However, the recent goal of the WHO’s EndTB-2035 strategy has been met with significant challenges in the areas of implementing improved diagnosis and treatment modalities in resource-limited TB endemic countries. The complexity of global TB management is confounded by malnutrition, comorbidities with other infectious and non-infectious diseases, and the socio-economic landscape of vulnerable populations. Political commitment to universal health coverage (UHC), including service coverage and reduction in catastrophic cost, are some of the essential components that need to be addressed to achieve the EndTB strategy. In this perspective, we have highlighted the intricacies of global TB management and summarized some of the key challenges that may keep the WHO’s EndTB-2035 strategy on the fence. Full article
(This article belongs to the Collection Feature Papers in Journal of Respiration)
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15 pages, 549 KiB  
Review
Telomeropathies in Interstitial Lung Disease and Lung Transplant Recipients
by Brian D. Southern and Shruti K. Gadre
J. Clin. Med. 2025, 14(5), 1496; https://doi.org/10.3390/jcm14051496 - 24 Feb 2025
Cited by 1 | Viewed by 1547
Abstract
Telomeropathies, or telomere biology disorders (TBDs), are syndromes that can cause a number of medical conditions, including interstitial lung disease (ILD), bone marrow failure, liver fibrosis, and other diseases. They occur due to genetic mutations to the telomerase complex enzymes that result in [...] Read more.
Telomeropathies, or telomere biology disorders (TBDs), are syndromes that can cause a number of medical conditions, including interstitial lung disease (ILD), bone marrow failure, liver fibrosis, and other diseases. They occur due to genetic mutations to the telomerase complex enzymes that result in premature shortening of telomeres, the caps on the ends of cellular DNA that protect chromosome length during cell division, leading to early cell senescence and death. Idiopathic pulmonary fibrosis (IPF) is the most common manifestation of the telomere biology disorders, although it has been described in other interstitial lung diseases as well, such as rheumatoid arthritis-associated ILD and chronic hypersensitivity pneumonitis. Telomere-related mutations can be inherited or can occur sporadically. Identifying these patients and offering genetic counseling is important because telomerapathies have been associated with poorer outcomes including death, lung transplantation, hospitalization, and FVC decline. Additionally, treatment with immunosuppressants has been shown to be associated with worse outcomes. Currently, there is no specific treatment for TBD except to transplant the organ that is failing, although there are a number of promising treatment strategies currently under investigation. Shortened telomere length is routinely discovered in patients undergoing lung transplantation for IPF. Testing to detect early TBD in patients with suggestive signs or symptoms can allow for more comprehensive treatment and multidisciplinary care pre- and post-transplant. Patients with TBD undergoing lung transplantation have been reported to have both pulmonary and extrapulmonary complications at a higher frequency than other lung transplant recipients, such as graft-specific complications, increased infections, and complications related to immunosuppressive therapy. Full article
(This article belongs to the Special Issue Updates on Interstitial Lung Disease)
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14 pages, 275 KiB  
Article
Rheumatologic Perspectives on Sarcoidosis: Predicting Sarcoidosis-Associated Arthritis Through Comprehensive Clinical and Laboratory Assessment
by Ali Ekin, Salim Mısırcı, Oğuzhan Sertkaya, Belkıs Nihan Coşkun, Burcu Yağız, Ediz Dalkılıç and Yavuz Pehlivan
J. Clin. Med. 2024, 13(24), 7563; https://doi.org/10.3390/jcm13247563 - 12 Dec 2024
Viewed by 1112
Abstract
Background/Objectives: The primary aim of our study was to evaluate the demographic, clinical, and laboratory characteristics of sarcoidosis patients with musculoskeletal symptoms; investigate the relationship between arthritis development and various laboratory parameters (such as vitamin D, liver enzymes, and ACE levels); and compare [...] Read more.
Background/Objectives: The primary aim of our study was to evaluate the demographic, clinical, and laboratory characteristics of sarcoidosis patients with musculoskeletal symptoms; investigate the relationship between arthritis development and various laboratory parameters (such as vitamin D, liver enzymes, and ACE levels); and compare the sarcoidosis-associated arthritis cases with those without. We also explored the factors influencing arthritis development and the role of biopsy in diagnosing sarcoidosis within rheumatology practice. Methods: This retrospective study analyzed 147 sarcoidosis patients from 2000 to 2024, categorized by the presence (n = 45) or absence (n = 102) of arthritis. Demographic, clinical, and laboratory data, including biopsy results, were collected and compared. Results: The mean age was 56.02 ± 11.21 years, with a mean disease duration of 134.33 ± 56.98 months. Females constituted 86.4% of the cohort. All of the patients presented musculoskeletal involvement. Pulmonary involvement was present in 93.7% of cases, and extrapulmonary involvement included the skin (21.20%), the eyes (14.30%), and peripheral lymphadenopathy (10.6%). Methotrexate was the most common treatment after corticosteroids. In the arthritis group, diabetes mellitus was more frequent (p = 0.024), the GGT levels were higher (p = 0.044), and the 25-hydroxyvitamin D levels (p = 0.002) and the DLCO Adj (p = 0.039) were lower. Multivariable regression showed diabetes mellitus (p = 0.028, OR: 4.805, 95% CI: 1.025–22.518) and low 25-hydroxyvitamin D levels (p = 0.034, OR: 0.914, 95% CI: 0.841–0.993) as factors influencing arthritis development. The other parameters showed no significant differences. Conclusions: This study identified significant clinical, demographic, and laboratory differences between sarcoidosis patients with and without arthritis. The patients with sarcoidosis-associated arthritis exhibited a higher frequency of diabetes mellitus, lower levels of 25-hydroxyvitamin D, and elevated GGT levels. Additionally, the lower DLCO values in the patients with arthritis indicate a more severe impact on pulmonary function, underscoring the importance of comprehensive pulmonary evaluation in this subgroup. Full article
(This article belongs to the Section Immunology)
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