Search Results (2,405)

Background and Objectives: Heart failure (HF) represents a clinical syndrome characterized by symptoms and signs such as fatigue, dyspnea, edema of the lower limb, or pulmonary rales. It usually occurs in elderly individuals due to decreased cardiac pumping function and/or increased diastolic ventricular filling pressures. The COVID-19 pandemic deeply altered many daily life habits, and one of the most affected groups of people were those with chronic diseases because of their need for regular medical follow-up. Furthermore, SARS-CoV-2 infection itself has been shown to exacerbate cardiovascular diseases (CVDs). Materials and Methods: This retrospective, observational, and comparative study aimed to characterize and compare patients with chronic heart failure hospitalized in the Cardiology Department of Medical Clinic II, Mureș County Emergency Clinical Hospital, in Târgu Mureș, Romania, between January and December 2019 (pre-pandemic), January and December 2021 (pandemic), and January and December 2023 (post-pandemic). Results: A total of 406 patients were analyzed: 202 patients hospitalized in 2019, 101 patients hospitalized in 2021, and 103 patients hospitalized in 2023. Women with HF were significantly older (median age 72 years) than men (median age 65 years; p < 0.001). During the pandemic, the median length of hospitalization increased (8 days vs. 7 days in the other periods). The pandemic period was also associated with a decrease in left ventricular ejection fraction (LVEF), as reflected by a higher incidence of patients with HF with reduced ejection fraction (42% during the pandemic; p < 0.01). Conclusions: During and after the pandemic, men exhibited significantly higher rates of right and left bundle branch blocks, as well as chronic obliterating artery disease of the lower limb. Left ventricular function declined during the pandemic in both men and women. Throughout the years, we observed distinct patterns between male and female patients regarding associated diseases or behaviours, suggesting lifestyle and psychological changes due to the COVID-19 pandemic. Full article

We report the case of a 42-year-old, non-smoking male admitted with right upper-lobe pneumonia. Chest computed tomography (CT) demonstrated findings consistent with an infectious process. For further evaluation, serial bronchoscopies with biopsy sampling were performed. Histopathological examination revealed moderate squamous dysplasia of the tracheal epithelium, and subsequent immunohistochemical testing detected human papillomavirus (HPV) genotype 45. This case underscores the value of integrating imaging, endoscopic assessment, and molecular diagnostic techniques in the evaluation of atypical pulmonary lesions and highlights the potential role of HPV infection in airway epithelial dysplastic changes. Full article

Background: Nocardia are a group of bacteria known to cause pulmonary, cutaneous, neurologic, or disseminated diseases, usually in immunocompromised hosts. Within the Nocardia family is Nocardia transvalensis, a rarely encountered and underreported organism in the clinical literature. Case: Here, we report the case of an immunocompetent patient presenting with lumbar pain diagnosed and treated for disseminated Nocardia transvalensis infection. Our patient underwent magnetic resonance imaging (MRI), demonstrating possible abscess and subtle osteomyelitis of the L3-L4 facet joint and transverse process; a subsequent biopsy and culture resulted in Nocardia transvalensis. Further imaging with a computed tomography (CT) scan of the head revealed a 9 mm enhancing supratentorial lesion. The patient was treated with empiric antibiotics, but this was narrowed to levofloxacin, linezolid, and trimethoprim-sulfamethoxazole after antibiotic sensitivities cropped up. Conclusions: Within this case, we extensively discuss the clinical pathogenesis of Nocardia transvalensis in an unusual host, the diagnostic approach to confirming active Nocardia infection, and the susceptibility patterns in a relatively unstudied organism. Full article

Tuberculosis (TB) remains a significant worldwide health challenge due to the limitations of conventional treatments and the rising incidence of drug-resistant Mycobacterium tuberculosis strains. This review consolidates the advancements in nanotechnology-based therapeutics, inhalable formulations, CRISPR–Cas tools, host-directed therapies (HDTs), and nanoparticle-based vaccine development aimed at enhancing TB management. Novel nanocarriers such as liposomes, solid-lipid nanoparticles (SLNs), dendrimers, and polymeric nanoparticles (NPs) offer enhanced bioavailability of drugs, sustained release, as well as targeted delivery to infected macrophages, thereby reducing systemic toxicity and dosing frequency. Inhalable nanomedicines provide localized delivery to the pulmonary site, enhancing the concentration of the drug at the primary site of infection. CRISPR–Cas technology is emerging as a transformative approach to disabling drug-resistant genes and enhancing diagnostic precision. HDTs, including agents like vitamin D and metformin, show potential in modulating host immune responses and enhancing pathogen clearance. Nanoparticle-based vaccines, including mRNA and antigen-conjugated platforms, aim to overcome the limitations of the BCG vaccine by enhancing antigen presentation and eliciting stronger, longer-lasting immunity. Collectively, these modalities mark a shift toward more personalized, effective, and less toxic TB therapies. However, challenges such as regulatory approval, safety, scalability, and accessibility remain. This review highlights the integrated potential of nanomedicine, gene editing, and immunomodulation to transform TB care and combat drug resistance, paving the way for more robust and durable treatment strategies. Full article

Background/Objective: The SARS-CoV-2 pandemic, emerging in late 2019, led to a global health crisis, with many patients developing prolonged symptoms after infection known as sequelae of COVID-19. This condition is theorized to be driven by systemic inflammation and immune dysregulation and presents with diverse symptoms from cardiovascular, pulmonary, and neurological systems. This study investigates the prevalence, risk factors, and long-term impacts of sequelae of COVID-19. Method: Using Denmark’s healthcare databases, this population-based cohort study included 1,034,093 individuals over 40 years who tested positive for COVID-19 between 1 March 2020 and 28 February 2022. Participants were divided into two age groups: 40–59 years and 60 years or older. Part A examined the risk of sequelae of COVID-19 diagnoses (ICD-10 code B94.8A) based on the Charlson Comorbidity Index (CCI). Part B assessed two-year outcomes for patients diagnosed with sequelae of COVID-19. Results: Results showed a 0.55% prevalence of sequelae of COVID-19 in both age groups. Higher CCI scores correlated with an increased risk of sequelae of COVID-19. During the two-year follow-up, patients with sequelae of COVID-19 faced significantly elevated risks of thromboembolic events, chronic lung diseases, and infections. Adjusted hazard ratios were notably high: 14.50 (7.54–27.86) and 12.50 (6.95–22.49) for thromboembolic events in adults and older adults, respectively; 33.81 (13.30–85.96) and 9.83 (6.09–15.87) for chronic lung disease; and 8.40 (4.49–15.70) and 15.44 (10.47–22.78) for infections. Conclusions: While the overall prevalence of sequelae of COVID-19 was low among individuals over 40, those with higher comorbidity burdens were at greater risk of severe sequelae and subsequent health complications. These findings underscore the need for clinical monitoring, especially for patients with pre-existing comorbidities, to mitigate long-term health risks associated with COVID-19 sequelae. Full article

Host innate immunity is crucial for orchestrating a protective response against dangerous pathogens. Herein, we demonstrate that interferon-inducible protein (IFI204), a DNA sensor, is implicated in protection against pulmonary pathogenic Mannheimia haemolytica (M. haemolytica) infection by driving inflammasome signaling activation. Ifi204^−/− mice are more susceptible to pathogenic M. haemolytica infection compared with their wild-type (WT) counterparts, with decreased survival rates, extensive lung architecture destruction, exacerbated inflammatory cells infiltration, and more bacterial colonization. In vivo and in vitro findings elucidate that Ifi204 deficiency leads to a defect in inflammasome signaling activation, and exogenous recombinant IL-18 is sufficient to rescue the susceptibility of Ifi204^−/− mice. Inflammasome signaling downstream of IFI204 facilitates early bacterial killing and clearance. Mechanistically, IFI204 promotes gasdermin D (GSDMD)-dependent inflammasome activation, and GSDMD is required for IFI204-mediated host defense. Notably, IFI204 detects pathogenic M. haemolytica-derived genomic DNA for the inflammasome signaling response. Thus, these data highlight the requirement of IFI204 in host defense response to M. haemolytica infection, and reveal that IFI204 may be a potential therapeutic target for pathogen control. Full article

This review focuses on the diverse etiologies of secondary spontaneous pneumothorax (SSP) and the crucial role of imaging in their diagnosis. Unlike primary spontaneous pneumothorax (PSP), which is typically due to ruptured blebs, SSP results from a wide array of underlying pulmonary conditions that can pose significant diagnostic challenges. These include infections like tuberculosis, airway diseases such as chronic obstructive pulmonary disease, malignancies (primary and metastatic), interstitial lung diseases like sarcoidosis, cystic lung diseases such as lymphangioleiomyomatosis, and connective tissue disorders. In women, catamenial pneumothorax secondary to endometriosis should be considered. The role of radiologists is crucial in uncovering these underlying conditions. While chest radiography is the initial imaging modality, computed tomography (CT) provides superior sensitivity for detecting subtle parenchymal abnormalities. Advanced techniques like photon-counting detector CT offer further benefits, including enhanced spatial resolution, reduced noise, and lower radiation dose, potentially revealing underlying causes that might be missed with conventional CT. This enhanced visualization of subtle parenchymal changes, small airways, and vascular structures can be the key to diagnosing the underlying cause of pneumothorax. Recognizing the diverse etiologies of SSP and utilizing advanced imaging techniques is paramount for accurate diagnosis, appropriate management, and improved patient outcomes. Full article

Artificial intelligence (AI) is increasingly transforming biomedical research and patient care by integrating complex biological, radiological, and healthcare information. In the field of viral respiratory infections, AI-driven approaches have shown great promise in elucidating the complexity of lung immune responses and the dynamic interplay between host and pathogen. Applications include predicting cytokine storm and acute respiratory distress syndrome (ARDS), integrating imaging findings with immunological and laboratory data, and identifying molecular and cellular signatures through single-cell and multi-omics analyses. Similar methodologies have been applied to influenza and respiratory syncytial virus (RSV), providing insights into the mechanisms distinguishing protective from maladaptive pulmonary immunity. This narrative review summarizes current evidence on how AI can evolve into a form of translational intelligence, capable of bridging mechanistic immunology with clinical application. The review explores AI-based models for disease severity prediction, patient stratification, and therapeutic response assessment, as well as emerging approaches in drug repurposing and vaccine response prediction. By integrating biological complexity with clinical context, AI offers new opportunities to uncover immune signatures predictive of antiviral or immunomodulatory efficacy and to guide personalized management strategies. Full article

Nontuberculous mycobacteria (NTM) represent a heterogeneous group of environmental opportunistic pathogens that have emerged particularly in immunocompromised individuals and patients with underlying pulmonary disorders. NTM infections primarily affect the lungs, but can also manifest as lymphadenitis, skin and soft tissue infections, and disseminated disease. This retrospective study took into consideration 425 NTM-positive samples collected between May 2011 and December 2023, analyzed by sample type, sex, and age group (0–17, 18–49, 50–65, >65 years). Antimicrobial susceptibility analysis was performed on the 223 NTM strains with greater pathogenic power and most frequently isolated, from 2016 to 2023. Pulmonary NTM disease (NTM-PD) infections were most prevalent in patients over 65 years (52.1%), while extrapulmonary NTM disease (NTM-EPD) occurred most frequently in the 0–17 age group (56.4%). Women were slightly more affected (54.4%) than men (45.6%), with the highest incidence in female individuals over 65 years old. The most frequently isolated NTM species was the Mycobacterium avium complex (MAC) (47% of isolates). Antimicrobial susceptibility testing of 223 isolates from 2016 to 2023 revealed species-specific resistance patterns, with high susceptibility to clarithromycin in MAC (94.7%) and Mycobacterium chelonae (100%), but notable resistance in Mycobacterium abscessus complex (MABC). The increasing incidence of NTM infections underscores the need for improved diagnostic techniques and targeted treatment strategies. Full article

This review reappraises the anti-inflammatory potential of the contact activation system (CAS) in intensive care through an evolutionary lens. The authors propose that coagulation factor XII (FXII) and related components evolved in terrestrial animals as a “foreign-surface sensing–immunothrombosis” module, helping to explain the minimal bleeding phenotype of FXII deficiency and the secondary loss of F12 in marine mammals. CAS shares components with the kallikrein–kinin system (KKS): alpha-coagulation factor XIIa (α-FXIIa) drives coagulation factor XI (FXI) activation to amplify coagulation, whereas betacoagulation factor XIIa (β-FXIIa) activates the KKS to generate bradykinin, promoting vasodilation and vascular leak. Beyond proteolysis, zymogen FXII signals via urokinase-type plasminogen activator receptor (uPAR) to induce neutrophil extracellular trap formation (NETosis), thereby amplifying immunothrombosis. Clinically, the relevance spans sepsis and extracorporeal organ support: pathogens can hijack CAS/KKS to facilitate invasion, and artificial surfaces such as extracorporeal membrane oxygenation (ECMO) circuits chronically trigger contact activation. In animal models, selective inhibition of FXII/FXI prolongs circuit life and attenuates pulmonary edema and inflammation without materially increasing bleeding. The review also catalogs “non-coagulation” roles of CAS members: Activated coagulation factor XI (FXIa) modulates endothelial permeability and smooth-muscle migration, and the FXII heavy chain exhibits direct antimicrobial activity—underscoring CAS as a nexus for coagulation, inflammation, and host defense. Overall, CAS inhibitors may couple “safe anticoagulation” with “cascade-level anti-inflammation,” offering a testable translational path for organ protection in the ICU alongside infection control and informing combined, precision strategies for anticoagulation and anti-inflammatory therapy. Full article

Immune checkpoint inhibitors (ICIs) and thoracic radiotherapy are standard treatments for advanced non-small-cell lung cancer (NSCLC), especially in patients with high PD-L1 expression or symptoms such as superior vena cava syndrome (SVCS). Both therapies carry a risk of pulmonary toxicity, which may be exacerbated by opportunistic infections due to corticosteroid use. We report a unique case of a 65-year-old man with squamous-cell NSCLC and high PD-L1 expression (80%), who developed a rare complication: radiation recall pneumonitis (RRP), with superimposed Pneumocystis jirovecii pneumonia and severe symptomatic hyponatremia induced by trimethoprim/sulfamethoxazole (TMP-SMX). The coexistence of these three complications—radiotherapy- and immunotherapy-associated lung injury, opportunistic infection, and electrolyte imbalance—represents an exceptional clinical scenario not previously described in the literature. This report highlights the importance of differential diagnosis, early recognition of complications, and close monitoring of electrolytes in NSCLC patients undergoing complex treatment regimens. Full article

Background/Objectives: Obesity and hyperglycemia predispose patients to respiratory infections. Although the lung is a major organ to utilize glucose, pulmonary glucose homeostasis in type 2 diabetic (T2Dx) subjects remains poorly characterized. We hypothesized that pulmonary glucose transport would be altered during T2Dx, which would be rescued with long-term metformin treatment. Methods: T2Dx was induced by feeding mice a high-fat diet for 16 weeks, with metformin treatment administered during the final 8 weeks. Results: Glucose transporter (GLUT) protein expression and trafficking was quantified by Western blotting and the biotinylated photolabeling assay, respectively. T2Dx mice exhibited obesity, and increased glucose levels in blood and bronchoalveolar lavage (BAL) fluid. T2Dx also significantly decreased protein expression of GLUTs from Class I (i.e., GLUT-2 and -4) and class III (i.e., GLUT-10 and -12) isoforms in lung. Metformin treatment restored the protein expression of GLUT-2, -4, and -10, but not GLUT-12. Pulmonary cell surface expression of GLUT-4 and -8 was also significantly reduced in T2Dx mice and rescued by metformin. Conclusions: These findings suggest that alterations in pulmonary GLUT expression and trafficking during diabetes could contribute to the elevated airway glucose levels and severity of respiratory infections. Metformin treatment restored pulmonary glucose transport during T2Dx. Full article

Background: Influenza can cause severe complications, especially in patients with specific risk factors or comorbidities associated with poor outcomes. Some patients are at increased risk of a complicated disease course, including secondary infections, ICU admission, and the need for mechanical ventilation. The first post–COVID-19 seasonal influenza season placed a substantial burden on Dutch ICUs. This study investigates the disease course and outcomes of ICU patients with influenza. Methods: A retrospective influenza registry study was conducted across 34 Dutch ICUs, including patients aged 18 and older admitted to the ICU with a positive influenza RT-PCR test, between 1 November 2023 and 17 March 2024. Data on demographic information, medical history, clinical symptoms, laboratory and imaging results, parameters of mechanical ventilation, additional treatments, length of hospital stay, and mortality was retrieved from the electronic patient record. Results: A total of 498 patients were included in the study. The median age was 64 (IQR: 55–72) years and 58.8% of the patients were men. The most common comorbidities were cardiovascular disease (34.1%), chronic obstructive pulmonary disease (COPD) (31.5%), and diabetes (22.3%). Bacterial co-infections were present in 37.6% of the patients. Invasive mechanical ventilation (IMV) was necessary in 46.0% of patients, 38.0% of those requiring IMV were treated in prone position. A substantial mortality rate was observed, with an ICU mortality rate of 21.9% and an additional hospital mortality rate of 5.2%. Conclusion: This study described the characteristics and course of disease of all patients with laboratory-confirmed influenza infection admitted to one of the 34 participating Dutch ICUs between November 2023 and March 2024. The major findings of this study are the substantial mortality rate, a high proportion of patients with bacterial co-infections, and a significant percentage of patients requiring IMV and prone position ventilation. Finally, patients without comorbidities that were admitted to the ICU with an influenza virus infection showed severe disease parameters but had a lower mortality than patients with comorbidities. Full article

This study aimed to characterize Mycoplasmosis bovis strain 16M—a highly virulent isolate from one Chinese outbreak—as a candidate for challenge models and inactivated vaccine development. We assessed strain 16M through morphological observation, PCR identification, drug susceptibility testing, growth titer and biofilm quantification, immunological profiling, and calf challenge experiments. We used genomic resequencing to evaluate the genetic stability across 150 passages. Classified as the prevalent ST52 lineage in China, strain 16M showed phylogenetic proximity to strain 08M and exhibited multidrug resistance (notably to macrolides). It achieved higher titers and stronger biofilm formation than other isolates and the reference strain PG45. In calves, intratracheal inoculation with 16M induced universal infection, severe pulmonary consolidation, and peribronchial cuffing, with significantly higher disease scores (p < 0.01). The inactivated 16M vaccine elicited elevated antigen-specific IgG titers, PBMC proliferation, and IFN-γ production versus PG45. Post challenge, immunized calves showed reduced pathological lesions, shorter bacterial shedding, and lower disease scores than the infected controls (p < 0.05). Genetic stability was confirmed for virulence-associated genes (e.g., adhesion proteins), with stable titers and biofilm production within 50 generations. Strain 16M combines high virulence for challenge modeling and industrial-scale vaccine suitability, owing to its robust growth, stable immunogenicity, and genetic consistency. Full article

Background/Objectives: Lithocarpus litseifolius (Hance) Chun, also known as sweet tea, is a traditional Chinese tea-making plant. Acute lung injury (ALI), a life-threatening syndrome with symptoms like hypoxemia and dyspnea, can be triggered by infection or trauma, with high morbidity and mortality. Whether the water extract of Lithocarpus litseifolius (WEL) has therapeutic effects on ALI remains unclear. This study aimed to analyze WEL’s components, establish in vitro cellular inflammation and mouse ALI models, and investigate WEL’s protective effects against LPS-induced ALI. Methods: LC-MS analysis identified 42 compounds in WEL and quantified three key ones. In an LPS-induced mouse ALI model, WEL significantly reduced lung injury severity, lung wet-to-dry ratio, pulmonary edema, and levels of NO, ROS, IL-1β, TNF-α, and MPO in lung tissues and bronchial alveolar lavage fluid. Immunohistochemical analysis showed WEL pretreatment inhibited the upregulation of NLRP3, Caspase-1, and GSDMD-NT expression, mitigated tissue oxidative stress and cell pyroptosis, and alleviated ALI severity in mice. Cellular experiments confirmed WEL’s protective effects via anti-inflammatory, antioxidant actions, and inhibiting cell pyroptosis, with phlorizin and trilobatin as potential key active ingredients. Conclusions: This research demonstrates sweet tea’s significant protective effects against ALI and its potential to alleviate inflammation by inhibiting pyroptosis, providing a theoretical basis for developing new health-promoting functions of sweet tea. Full article