Search Results (5,375)

Background and Clinical Significance: Granulomatosis with polyangiitis (GPA), an immune-mediated systemic small-vessel vasculitis affecting the upper/lower respiratory tracts and kidneys, frequently presents with non-specific nasal symptoms that lead to misdiagnosis. Case Presentation: We report a case of a 55-year-old female with GPA complicated by Bartter syndrome. She presented with one month of left nasal congestion, rhinorrhea, epistaxis, and headache. Initial diagnosis was acute sinusitis. Computed tomography (CT) revealed left maxillary and ethmoid sinus inflammation with bone destruction, while metagenomic next-generation sequencing (mNGS) suggested conventional bacterial infection. Postoperative pathology demonstrated chronic mucosal inflammation with lymphoid tissue hyperplasia. GPA was ultimately diagnosed based on PR3-ANCA seropositivity and chest CT findings of cavitary pulmonary nodules. Postoperatively, severe hypokalemia and hypomagnesemia secondary to Bartter syndrome emerged. Following electrolyte correction, induction therapy with glucocorticoids and cyclophosphamide was initiated. Conclusions: This case underscores that GPA’s head and neck manifestations are frequently misdiagnosed as infections or malignancies. Early diagnosis requires vigilance for GPA ‘red flags’, such as refractory nasal symptoms to conventional therapy (e.g., bloody rhinorrhea), characteristic CT findings (e.g., sinus opacification without ostiomeatal complex obstruction), and nasal endoscopy findings (e.g., ulcers/crusting). Otolaryngologists play a pivotal role in recognizing early disease onset and initiating timely treatment. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus are major respiratory pathogens associated with substantial morbidity and a risk of severe disease. However, the effectiveness of current vaccines and antiviral drugs is limited by viral mutations. Umeboshi, a traditional Japanese food prepared from pickled Prunus mume, is known for its health benefits; certain components of P. mume have exhibited antimicrobial properties. However, the efficacy of P. mume against SARS-CoV-2 and influenza virus remains unknown. We aimed to examine the antiviral activity of P. mume extracts against SARS-CoV-2 and influenza virus. Cytopathic effect (CPE) assays and reverse transcription–quantitative polymerase chain reaction (RT-qPCR) analyses with full-time treatment demonstrated that four extracts (PM2, PM3, PM4, and PM6) among eight tested inhibited the replication of both viruses. Subsequent time-of-addition assays, plaque assays, and transmission electron microscopy (TEM) confirmed that PM2 directly inactivated viral particles of both viruses by disrupting their structural integrity. Additional evaluations of virion integrity and infectivity suggested that the antiviral activity of PM2 may also involve mechanisms other than direct virion disruption. These findings suggest that P. mume-derived components exhibit direct antiviral activities against SARS-CoV-2 and influenza virus, supporting their potential development as antiviral agents or infection-preventive dietary products. Full article

Background: Influenza A virus (IAV) is a major human pathogen, contributing to substantial morbidity and mortality during seasonal outbreaks and pandemics. Human infection with IAV can lead to pneumonia and acute respiratory distress syndrome (ARDS), and numerous clinical and basic research studies have established an association between IAV and pulmonary fibrosis (PF). However, the treatment of IAV-induced PF fibrosis has not been studied and discussed. Methods: An IAV-induced PF mouse model was established. Herbacetin (HBT) was identified as the most effective compound in the in vitro study of seven components of Rhodiola rosea L. (R. rosea L.). The effect of HBT on IAV-induced lung injury and PF was evaluated in vivo and in vitro. The binding between HBT and neuraminidase (NA) protein was investigated by biological layer interferometry (BLI) and cell thermal shift assay (CETSA). Results: Following IAV infection, the TGF-β/Smad3 pathway is activated, leading to the upregulation of fibrosis-related proteins that promote fibrosis. HBT exhibited a significant ability to reduce influenza virus-induced lung injury and fibrosis both in vitro and in vivo. Mechanistically, HBT binds to the NA protein of the influenza virus, reducing viral infection and the activation of the TGF-β/Smad3 pathway, thereby mitigating the formation of lung injury and PF. Conclusions: HBT represents a promising therapeutic agent for modulating influenza virus-induced lung injury and PF, marking a significant step toward the development of effective treatments for influenza-induced PF. Full article

Many patients experience unique or persistent symptoms several months following the onset of infection with severe acute respiratory syndrome coronavirus 2, the causative agent of COVID-19. While this condition is commonly referred to as long COVID, no universally accepted definition exists; therefore, many patients go underrecognized and underreported. Long COVID can involve almost any major organ system and is characterized by widely heterogeneous persistent or recurrent symptoms including fatigue, headache, cough, dyspnea, chest pain, cognitive dysfunction, anxiety, and depression. In line with the wide array of symptoms, numerous potential underlying pathophysiologic pathways, including viral persistence, prolonged inflammation, autoimmune reactions, endothelial dysfunction, and dysbiosis of the microbiome of the gut, may contribute to the symptomology of long COVID. Therapy is directed at symptomatic control; however, no pharmacologic treatments are specifically approved for the management of symptoms associated with long COVID. Several common symptoms of long COVID may be managed with nonprescription treatments (pharmacologic and nonpharmacologic). The goal of this review is to provide clinicians with a better understanding of long COVID and review the latest recommendations for managing common mild-to-moderate symptoms with nonprescription treatment options. Full article

Cathepsin L (CatL) is a critical protease involved in cleaving the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), facilitating viral entry into host cells. Inhibition of CatL is essential for preventing SARS-CoV-2 cell entry, making it a potential therapeutic target for drug development. Six QSAR models were established to predict the inhibitory activity (expressed as IC₅₀ values) of candidate compounds against CatL. These models were developed using statistical method heuristic methods (HMs), the evolutionary algorithm gene expression programming (GEP), and the ensemble method random forest (RF), along with the kernel-based machine learning algorithm support vector regression (SVR) configured with various kernels: radial basis function (RBF), linear-RBF hybrid (LMIX2-SVR), and linear-RBF-polynomial hybrid (LMIX3-SVR). The particle swarm optimization algorithm was applied to optimize multi-parameter SVM models, ensuring low complexity and fast convergence. The properties of novel CatL inhibitors were explored through molecular docking analysis. The LMIX3-SVR model exhibited the best performance, with an $R^2$ of 0.9676 and 0.9632 for the training set and test set and RMSE values of 0.0834 and 0.0322. Five-fold cross-validation $R_{5-fold}^2$ = 0.9043 and leave-one-out cross-validation $R_{loo}^2$ = 0.9525 demonstrated the strong prediction ability and robustness of the model, which fully proved the correctness of the five selected descriptors. Based on these results, the IC₅₀ values of 578 newly designed compounds were predicted using the HM model, and the top five candidate compounds with the best physicochemical properties were further verified by Property Explorer Applet (PEA). The LMIX3-SVR model significantly advances QSAR modeling for drug discovery, providing a robust tool for designing and screening new drug molecules. This study contributes to the identification of novel CatL inhibitors, which aids in the development of effective therapeutics for SARS-CoV-2. Full article

Interleukin-24 (IL-24) is a cytokine known for its role in immune regulation and apoptosis, with potential implications in viral infections like COVID-19. This study aimed to investigate the association between IL-24 serum levels and the severity of COVID-19 disease. In this prospective bi-center cross-sectional study, we enrolled 41 COVID-19 patients from two hospitals in Germany. Serial blood samples were collected from a subset of patients, resulting in 88 total blood samples. Patients were categorized into critical, severe, moderate, and mild disease groups based on WHO criteria. IL-24 serum levels were measured during the acute or convalescent phase using an ELISA assay. Inflammatory markers, and kidney and liver function parameters were also evaluated. Statistical analysis included non-parametric tests and correlation analysis. Elevated IL-24 serum levels were observed in ambulant patients (mild disease), compared to hospitalized patients (critical, severe, moderate disease, p < 0.05). IL-24 levels were also significantly higher in patients without oxygenation disorder compared to those with oxygenation therapy (p < 0.05). A negative correlation was found between IL-24 levels and markers of inflammation and liver/kidney function. Elevated IL-24 serum levels were associated with milder COVID-19 courses, suggesting a protective role in modulating immune responses and promoting antiviral apoptosis. Conversely, reduced IL-24 in severe cases may reflect impaired immune regulation, highlighting its potential as a biomarker and therapeutic target. Full article

Background: Hyperventilation Syndrome (HVS) is a well-recognized physiological consequence of acute anxiety, often resulting in respiratory alkalosis and subsequent electrolyte imbalances. Among these, a reduction in ionized calcium levels can lead to neuromuscular irritability and electrocardiographic abnormalities such as QTc prolongation. Although well-documented in specific settings, including autism spectrum disorders and drug-induced crises, such complications are rarely described in otherwise healthy pediatric patients presenting with isolated anxiety episodes. This report aims to raise awareness of anxiety-driven somatic manifestations, particularly in the context of the rising prevalence of mental health disorders among children and adolescents. Methods: We report the case of a previously healthy 10-year-old girl presenting to the emergency department with acute agitation and hyperventilation. Clinical examination revealed neuromuscular symptoms, including Trousseau’s sign and flexion posture. Initial laboratory testing and arterial blood gas analysis indicated respiratory alkalosis with decreased ionized calcium levels, and a resting ECG showed QTc prolongation (510 ms). Treatment included intravenous midazolam, a balanced electrolyte solution, and oral bromazepam during intensive observation with cardiac monitoring. Results: The patient’s symptoms progressively improved following anxiolytic and supportive therapy. Electrolyte abnormalities normalized within 48 h, with complete resolution of the prolonged QTc (430 ms). No arrhythmias or other complications occurred. Outpatient psychological follow-up was arranged upon discharge. Conclusions: This case underscores the importance of considering anxiety as a primary etiology in pediatric patients with apparent metabolic or cardiac abnormalities. Early psychiatric recognition and targeted supportive care can prevent overtreatment and reduce the burden on emergency and cardiologic resources. Full article

Acute respiratory distress syndrome (ARDS) is a common and highly heterogeneous condition in the critically ill. The association between hyper- and hypo-inflammatory subphenotypes and clinical outcomes has generated significant interest in precise ARDS management. The value of identifying biomarkers to guide treatment and enrollment in future ARDS trials is undisputable. We describe multiple factors complicating the search for subphenotypes and their treatable traits. The observed heterogeneity seen in the clinical course of ARDS is dynamic and influenced by factors beyond lung pathophysiology, including variations in the delivery of best critical care practices, patient comorbidities, and functional status, and patient or family preferences. Current subphenotype definitions lack strong biological plausibility and without clear evidence of benefit from targeted treatments, their use in clinical practice is currently unwarranted. Full article

Background and Aim: Mechanical ventilatory support is often required in patients with acute respiratory distress syndrome (ARDS). However, early differences in ventilatory mechanics and severity scores between COVID-19 and non-COVID-19 ARDS patients remain unclear. This study aimed to compare respiratory parameters and clinical severity scores in COVID-19 and non-COVID-19 ARDS patients managed in the emergency department (ED) and evaluate their association with in-hospital mortality. Methods: In this retrospective cohort study, adult patients with ARDS (PaO₂/FiO₂ < 300 mmHg) who received mechanical ventilation in the ED were included. Ventilator parameters and clinical severity scores (SOFA, APACHE II, PSI, and Charlson Comorbidity Index) were recorded at the 120th minute after intubation. Patients were categorized as COVID-19 or non-COVID-19 ARDS, and outcomes were compared between survivors and non-survivors. Logistic regression was used to identify independent predictors of in-hospital mortality. Results: A total of 70 patients were enrolled (32 COVID-19, 38 non-COVID). Plateau pressure, driving pressure, and PEEP were significantly higher in COVID-19 patients, while compliance was without statistical significance. Overall, in-hospital mortality did not differ significantly between the COVID-19 (53.1%) and non-COVID-19 groups (71.1%, p = 0.12). Mechanical power (21.6 vs. 16.8 J/min, p = 0.01) and Charlson Comorbidity Index (6 vs. 5.5, p = 0.02) were significantly higher in non-survivors across the full cohort. Among clinical scores, SOFA was significantly higher in the COVID-19 group (p = 0.02), and APACHE II was significantly higher in non-survivors within the COVID-19 subgroup (p = 0.02). In multivariate analysis, mechanical power and Charlson Comorbidity Index were associated with mortality. Conclusions: COVID-19 patients with ARDS exhibited higher early ventilatory pressures than non-COVID-19 patients, yet early respiratory mechanics were not independently associated with mortality. Mechanical power and Charlson Comorbidity Index were significantly associated with in-hospital mortality. These findings underscore the need to consider both ventilatory load and systemic health status in early outcome assessments of ARDS patients. Full article

Sickle cell disease (SCD) is a hereditary hemoglobin disorder characterized by chronic hemolysis and recurrent vaso-occlusive crises, leading to a wide spectrum of complications. While common SCD manifestations have well-established management protocols, rare and atypical complications pose significant diagnostic and therapeutic challenges. A critical barrier is diagnostic overshadowing, where common SCD symptoms (pain, fever, respiratory distress) mask infrequent but life-threatening conditions, resulting in delayed recognition and suboptimal outcomes. This narrative review synthesizes the literature from 2000–2025 on rare SCD complications, including atypical neurological events (e.g., spontaneous epidural or subdural hematoma, central retinal artery occlusion, cerebral arteriovenous malformations, posterior reversible encephalopathy syndrome), uncommon hematologic syndromes (acute leukemia, extramedullary hematopoiesis in unusual sites, hemophagocytic lymphohistiocytosis), severe cardiopulmonary emergencies (acute multiorgan failure and fat embolism syndromes), unusual hepatic crises (acute hepatic sequestration, intrahepatic cholestasis), and others (e.g., compartment syndrome). Key insights underscore the need for high clinical suspicion and prompt use of advanced diagnostics (e.g., MRI, specialized laboratory tests) when patients present with atypical or disproportionate symptoms. Clinical implications: Heightening clinician awareness of these rare complications and implementing structured diagnostic strategies can facilitate earlier intervention, improving outcomes and reducing the high morbidity and mortality associated with these infrequent but severe events. Full article

Background/Objectives: This study investigated the gene expression levels of High Mobility Group Box 1 (HMGB1), nuclear factor kappa B (NF-κB) and interleukin-17 (IL-17) in the serum of patients with acute pancreatitis (AP) and analyzed the correlation of these three with the severity of AP, local and systemic complications, transfer to intensive care unit (ICU) and death. Methods: AP was diagnosed and stratified according to the revised Atlanta classification. The diagnosis of AP requires two of the following three features: abdominal pain (acute onset of persistent severe, epigastric pain often radiating to the back); serum lipase/or amylase activity at least three times higher than normal; characteristic findings of AP on computed tomography or abdominal ultrasonography. Results: This study confirmed that NF-kB is a significant marker of AP severity, as well as for ICU transfer, and correlates with acute respiratory distress syndrome (ARDS), while IL-17 is shown as a significant marker of systemic complications (pleural effusions, ARDS, and renal failure). HMGB1 correlates with pancreatic necrosis, systemic inflammatory response syndrome, and ICU transfer. Conclusions: Over the past years, the role of HMGB1, NF-kB, and IL-17 in the pathogenesis of AP has been under intense scrutiny, and they have been proposed as prognostic biomarkers for AP severity, poor prognosis, and death outcome. The advantage of this research is that changes in gene expression can be detected before the increase in serum concentrations of these biomarkers, and it allows early prediction of a severe form of AP, as well as the development of complications. Full article

Background: Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), are critical conditions lacking effective pharmacologic therapies. Lipopolysaccharide (LPS), a bacterial endotoxin, is a well-established trigger of ALI. Emerging evidence suggests that heparin derivatives may attenuate lung injury, but their mechanisms remain unclear. Methods: This study evaluated the protective effects of 2-O, 3-O desulfated heparin (ODSH) in a murine model of LPS-induced ALI. Mice received LPS intratracheally with or without ODSH pre-treatment. Lung injury was assessed by bronchoalveolar lavage fluid (BALF) analysis, Evans blue dye albumin EBDA) extravasation, and histopathology. Results: ODSH treatment significantly reduced BALF protein concentration, inflammatory cell infiltration, and EBDA leakage. ODSH preserved endothelial barrier function in vitro, as evidenced by transendothelial electrical resistance (TER) measurements in human lung microvascular endothelial cell (HLMVEC) monolayers. Histological assessment (H&E staining) and myeloperoxidase (MPO) staining demonstrated reduced lung injury and neutrophil infiltration in the ODSH group. ODSH also downregulated pro-inflammatory mediators (NF-κB, IL-6, p38 MAPK) and upregulated the anti-inflammatory cytokine IL-10. Conclusions: ODSH mitigates LPS-induced ALI by reducing vascular permeability, neutrophilic inflammation, and pro-inflammatory signaling while enhancing IL-10 expression. These findings suggest ODSH may offer a novel therapeutic approach for treating ALI. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) raced around the world across different populations; there needs to be a consolidated effort to understand the divergence of the epidemiology of SARS-CoV-2. Population-based epidemiological characteristics studies measure the extent of SARS-CoV-2 infection in a country. The current research study was designed to report epidemiological data from Pakistan. For this purpose, 246 SARS-CoV-2-infected patients were included in the study. For SARS-CoV-2 confirmation, viral samples were collected from all the study participants; SARS-CoV-2 infection was confirmed by viral nucleic acid detection using a nucleic acid detection kit. After SARS-CoV-2 confirmation, all the study participants were interviewed for epidemiological data through a detailed questionnaire. The study results showed that the disease ratio was higher between 30 and 59 years (51.21%) of age. The male ratio (55.28%) was higher compared to the female ratio (44.71%). The patients’ illiteracy and low socioeconomic status were 32.52% and 59.75%, respectively. The majority of the patients (97.56%) had cough, smell or taste disturbance (79.67%), or fever (76.42%), and 70.73% had fatigue. For comorbidities, a higher ratio was observed for diabetes (38.61%), hypertension (36.17%), and respiratory disease (16.26%). The vaccination status analysis revealed that 51.21% of patients had not received routine immunizations, and 65.5% were un-vaccinated against SARS-CoV-2. Notably, not a single patient was vaccinated for influenza vaccine. The current research study concluded that SARS-CoV-2 was more prevalent in individuals who were middle aged, male, and had low socio-economic status. The most common symptoms were cough, smell or taste disturbance, and fever. The patients’ vaccination status highlights a critical gap in preventive healthcare and shows the need to strengthen vaccination awareness and accessibility in the population to reduce vulnerability to future outbreaks. Future research should focus on investigating the impact of COVID-19 outcomes on comorbidities such as diabetes and hypertension. Full article

Funded during the emergency phase of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, messenger RNA (mRNA) vaccines are single-stranded, 5′-capped mRNAs produced using a cell-free in vitro transcription from the corresponding plasmid DNA (pDNA) templates, encoding the viral spike (S) protein of SARS-CoV-2 [...] Full article

Obesity Hypoventilation Syndrome (OHS), also known as Pickwickian syndrome, is a complex disorder characterized by obesity (BMI > 30 kg/m²), daytime hypercapnia (PaCO₂ ≥ 45 mmHg), and sleep-disordered breathing, primarily affecting individuals with severe obesity. Its diagnosis requires the exclusion of other causes of alveolar hypoventilation and involves comprehensive assessments, including clinical history, physical examination, pulmonary function tests, arterial blood gases, and sleep studies. The pathophysiology of OHS involves mechanical constraints from excessive adipose tissue, diminished central respiratory drive often linked to leptin resistance, mitochondrial dysfunction, and oxidative stress, all contributing to impaired ventilation and systemic inflammation. The condition often coexists with obstructive sleep apnea (OSA), exacerbating nocturnal hypoxia and hypercapnia, which can lead to severe cardiopulmonary complications such as pulmonary hypertension and right-sided heart failure. Epidemiologically, the rising global prevalence of obesity correlates with an increased incidence of OHS, yet underdiagnosis remains a significant challenge, often resulting in critical presentations like acute hypercapnic respiratory failure. Management primarily centers on non-invasive ventilation modalities like CPAP and BiPAP, with an emphasis on individualized treatment plans, continuous monitoring, and addressing comorbidities such as hypertension and diabetes. Pharmacological interventions are still evolving, focusing on supportive care and metabolic regulation. Long-term adherence, psychological factors, and complications like ventilator failure or device intolerance highlight the need for ongoing multidisciplinary management. Overall, advancing our understanding of OHS’s multifactorial mechanisms and optimizing tailored therapeutic strategies are crucial for improving patient outcomes and reducing mortality associated with this increasingly prevalent syndrome. Full article