Search Results (16,094)

Objectives: We sought to document interim methodologic improvements and preliminary results for pulmonary suffusion. Methods: A Phase I/II trial of thoracoscopic lung suffusion for resectable sarcoma and colorectal carcinoma metastases followed a pilot study on oligometastatic lung malignancy at a comprehensive cancer center. Primary-specific chemotherapy doses (cisplatin, oxaliplatin, doxorubicin, or gemcitabine) suffused unilaterally for 30 min were escalated to amplify regional deliveries three-fold. Drug delivery was measured with tissue, blood samples, and ⁹⁹Tc; pulmonary function tests and clinical adverse events (AEs) assessed safety and tolerance. Results: From 2008–2025, 31 ECOG 0–2 patients (10 male) aged 33–75 years had unilateral lung suffusion (16 right, 14 left, 1 aborted, and 8 sides selected randomly). Vascular occlusion intolerance was immediate or delayed (25 min) in two cases. Two catheter-positioning grade 3 AEs occurred: hypotension with troponin leak (1) and atrial fibrillation (1). Patients averaged 1.3 ± 1.2 metastasectomies (17 sub-lobar, 8 lobar resections, and 2 intentional open cytoreductive metastasectomies). Hospitalizations were brief (1–4 days) except for 6–7 day stays in the only two open cases and one doxorubicin (grade 4 hypoxic respiratory failure) case. Ninety-day survival was 100%, and the Phase I delivery goal of 12.75 mg/m² 65 (15% systemic) was achieved for oxaliplatin. Lung function was preserved according to ⁹⁹Tc differentials within 6.1 ± 7.1% of the predicted reductions at 30 days. Sampling delays, tracer discordances, and atypical pharmacokinetics reduced tissue drug detections. Recent pulmonary artery snaring cases (two) demonstrated in-flow control more stable than that of balloon occlusions. Conclusions: Suffusion for metastatic malignancies appears safe and warrants further investigation. Full article

Background: Tularemia is a rarely identified disease in Slovenia. In summer 2024, we detected a tularemia outbreak in the Kranjsko-Sorško polje, located in North-Western part of Slovenia. Aim: To describe the epidemiological investigations and preventive measures to contain the outbreak. Methods: The patients with confirmed tularemia were interviewed. Serology and PCR was used for microbiological confirmation of tularemia and in some patients by isolation from blood or by RT-PCR. Results: The majority of confirmed tularemia cases in 2024 were infected in the geographically limited area in North-Western part of Slovenia (38/46). Tularemia was confirmed in two patients by isolation Francisella tularensis subsp. holarctica from blood or wound, in one by blood PCR, and in the others by serology. Most cases were associated with mowing or harvesting hay with intensive dusting. Twenty-eight (75.7%) out of 37 cases developed pulmonary tularemia. Sixteen cases were hospitalized. After confirming the outbreak, we alerted medical professionals in the region and the general public using the regional and national media and website of National Institute of Public Health. Conclusions: Endemic tularemia in Slovenia is associated with handling wild life and presents in ulceroglandular form. In the localized outbreak in year 2024 there was an extraordinary upsurge of pulmonary tularemia, with many of the cases initially investigated for lung cancer based on the radiology reports. Due to dry weather condition in summer 2024, excessive dusting associated with mowing the grass and handling hay resulted in inhalation of infective aerosols leading to the infection with F. tularensis. Full article

Progressive pulmonary fibrosis (PPF) is a clinical syndrome associated with worsening quality of life and increased mortality among patients with various interstitial lung diseases. This review aims to update the concepts and criteria that adequately define PPF, aiming to facilitate earlier recognition and optimize clinical management. Fibrosing interstitial lung disease (ILD-f) can progress over time despite optimal management of the underlying conditions. Current criteria for defining PPF include worsening respiratory symptoms, decline in pulmonary function tests (particularly forced vital capacity and diffusing capacity), and radiographic progression over a 1-year follow-up period. However, implementation of these criteria in clinical practice poses challenges. This review discusses the limitations of current evaluation methods and proposes future directions, including the need for validated symptom assessment tools, standardization of pulmonary function testing, and improvements in quantitative radiological evaluation methods. Full article

Alpha-1 antitrypsin deficiency (AATD) represents a paradigmatic genetic disorder with well-characterized hepatic manifestations but relatively underexplored pulmonary implications. While liver involvement has been extensively reviewed, the underlying mechanisms of lung disease progression remain poorly understood, particularly regarding immunological pathways and inflammatory processes. The pathophysiology involves defective alpha-1 antitrypsin (AAT) production, including AAT variants that induce neutrophil elastase activity, causing progressive alveolar destruction and sustained inflammation, leading to emphysema, as one of the main components of chronic obstructive pulmonary disease (COPD). AATD and smoking represent major risk factors for COPD, the third leading cause of death worldwide at present. In AATD patients, neutrophils, which constitute the majority of circulating leukocytes, become dysregulated. Under normal conditions, cells perform essential functions, including phagocytosis and neutrophil extracellular trap formation (NETosis); in AATD, however, they accumulate excessively in alveolar spaces due to impaired elastase control. The accumulation of Z-AAT polymers within epithelial cells creates a pathological cycle, acting as chemoattractants that sustain pro-inflammatory responses and contribute to chronic obstructive pulmonary disease development. In addition, monocytes, representing a smaller fraction of leukocytes, migrate to inflammatory sites and differentiate into macrophages while secreting AAT with anti-inflammatory properties. However, in PiZZ patients, this protective mechanism fails, as polymer accumulation within cells reduces both AAT secretion and the number of protective human leukocyte antigen(HLA)-DR-monocyte subsets. In particular, macrophages demonstrate remarkable plasticity, switching between pro-inflammatory M1 (classically activated macrophages) and tissue-repairing M2 (alternatively activated macrophages) phenotypes based on environmental cues. In AATD, this adaptive capability becomes compromised due to intracellular polymer accumulation, leading to impaired phagocytic function and dysregulated cytokine production and ultimately perpetuating chronic inflammation and progressive tissue damage. Recent advances in induced pluripotent stem cell (iPSC) technology have facilitated alveolar epithelial cell (AEC) generation, in addition to the correction of AATD mutations through gene editing systems. Despite the limitations of AAT correction, iPSC-derived organoid models harboring AATD mutations can deliver important insights into disease pathophysiology, while gene editing approaches help demonstrate causality between specific mutations and observed phenotypes. Therefore, in this review, we investigated recent studies that can serve as tools for gene editing and drug development based on recently developed iPSC-related technologies to understand the pathogenesis of AATD. Full article

Heart failure (HF) remains a global health challenge with high rates of hospitalization and mortality, particularly among the elderly. Many episodes of worsening HF occur before symptoms arise, underscoring the need for sensitive monitoring tools. Respiratory Stability Time (RST) is a novel index that quantifies the duration of stable respiration during sleep, reflecting pulmonary congestion and circulatory status. RST can be measured continuously and non-invasively using a contactless under-mattress sensor. Observational cohort studies show that low RST predicts poor prognosis, while its improvement parallels recovery from decompensation. Importantly, recent prospective multicenter observations involving 100 patients demonstrated that sustained RST decline often precedes HF readmission, probably enabling early intervention. A multicenter trial (ITMETHOD-HF III), involving 80 patients, is currently testing whether RST-guided therapy can reduce HF readmissions. RST might substantially enhance current HF management by enabling us to provide proactive therapeutic intervention, though further validation is warranted. Full article

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

Background: Distinguishing chronic obstructive pulmonary disease (COPD) from asthma–COPD overlap (ACO) remains challenging due to shared clinical and inflammatory features. Interleukin-13 (IL-13) is implicated in airway inflammation and remodeling and may represent a potential treatable trait. This study aimed to evaluate whether serum IL-13 could differentiate between COPD and ACO or define ACO subtypes and to explore its relationship with clinical and phenotype parameters. Materials and Methods: We conducted a cross-sectional bicentric study in 215 COPD and ACO patients recruited from outpatient clinics. The study measured blood IL-13 levels in COPD vs. ACO patients, across five ACO subtypes, and evaluated IL-13’s ability to predict ACO. Additionally, correlations were explored among endotype (IL-13) and different phenotype traits (e.g., fractional exhaled nitric oxide (FeNO), sputum eosinophilia, serum total immunoglobulin E (tIgE) levels, blood eosinophilia, and neutrophilia) and clinical outcomes (annualized exacerbation rate, symptom scores, and pulmonary function parameters). Results: No significant differences in IL-13 levels were found between COPD and ACO patients or among ACO subtypes. IL-13 did not predict ACO occurrence. We observed a weak correlation between IL-13 and tIgE levels in the entire cohort. Additionally, there was a weak correlation between IL-13 and FeNO in patients with eosinophil counts exceeding 300 cells/μL, as well as between IL-13 and age in the COPD cohort. No correlation was found between IL-13 and other phenotypic features or clinical outcomes in the overall cohort, including within both COPD and ACO groups. Conclusions: IL-13 cannot differentiate between COPD and ACO or ACO’s subtypes. Full article

Aim: This study aimed to evaluate the nutritional status of children with cystic fibrosis (CF) and investigate the correlation between malnutrition and the decline of pulmonary function in this population. Methods: We retrospectively analyzed the clinical data of children with CF admitted to four large tertiary centers in Upper Egypt. We compared clinical characteristics among children with different nutritional statuses and evaluated the correlation between malnutrition and pulmonary functions. Results: A total of 104 children with CF, including 54 males (52%), aged 3 to 18 years, were analyzed. Respiratory symptoms were present in all cases (100%). Malnutrition was observed in 72% (75/104) of the participants, with affected children exhibiting significantly lower body weight and serum albumin levels. Pulmonary function tests showed that vital capacity (VC) and the predicted values for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV₁), FEV₁/FVC, and expiratory flow at 25%, 50%, and 75% of FVC were all lower in the malnourished group compared to children with normal nutrition. Correlation analysis demonstrated that the body mass index (BMI) Z-score was positively correlated with these pulmonary function indicators. Conclusions: Malnutrition is highly prevalent among Egyptian children with CF and is associated with decreased pulmonary function. Improving nutritional status may enhance lung function in this population. Full article

Background and Clinical Significance: Arterial and venous thromboses are typically distinct clinical entities, each governed by unique pathophysiological mechanisms. The concurrent manifestation of both, particularly in the setting of massive pulmonary embolism (PE), is exceptionally rare and poses significant diagnostic and therapeutic challenges. Case Presentation: This report describes a 61-year-old male with well-controlled hypertension and type 2 diabetes who developed extensive thromboses involving deep vein thrombosis (DVT) of the right popliteal vein, arterial thrombosis of the left iliac artery, and massive PE. The patient was initially managed conservatively, in accordance with the European Society of Cardiology (ESC) 2019 Guidelines for Acute PE, using unfractionated heparin (UFH), low-molecular-weight heparin, a direct oral anticoagulant (DOAC), and adjunctive therapy. This approach was chosen due to the absence of hemodynamic instability. However, given failed percutaneous revascularization and persistent arterial occlusion, surgical thromboendarterectomy (TEA) was ultimately required. Post hoc genetic testing was prompted by the complex presentation in the absence of classical provoking factors—such as trauma, surgery, malignancy, or antiphospholipid syndrome—consistent with recommendations for selective thrombophilia testing in atypical or severe cases. The analysis revealed four thrombophilia-associated polymorphisms: heterozygous Factor V Leiden (FVL; R506Q genotype), Plasminogen Activator Inhibitor-1 (PAI-1; 4G/5G genotype), Methylenetetrahydrofolate reductase (MTHFR; c.677C > T genotype), and homozygous Angiotensin-Converting Enzyme Insertion/Deletion (ACE I/D; DD genotype). Conclusions: While each variant has been individually associated with thrombotic risk, their co-occurrence in a single patient with simultaneous arterial and venous thromboses has not, to our knowledge, been previously documented. This case underscores the potential for gene–gene interactions to amplify thrombotic risk, even in the presence of variants traditionally considered to confer only modest to moderate risk. It highlights the need for a multidisciplinary approach and raises questions regarding pharmacogenetics, anticoagulation, and future research into cumulative genetic risk in complex thrombotic phenotypes. Full article

Background/Objectives: Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by lung scarring, impaired function, and high mortality. Effective therapies to reverse fibrosis are lacking. This study aims to uncover the molecular mechanisms of IPF, explore diagnostic biomarkers, and identify therapeutic targets. Methods: Multi-omics data were integrated to identify biomarkers with causal associations to IPF using Mendelian randomization and transcriptomic analysis. Machine learning was employed to construct a diagnostic model, and single-cell transcriptomic analysis determined gene expression patterns in fibrotic lung tissue. Results: Seven core genes (GREM1, UGT1A6, CDH2, TDO2, HS3ST1, ADGRF5, and MPO) were identified, showing strong diagnostic potential (AUC = 0.987, 95% CI: 0.972–0.987). These genes exhibited distinct distribution patterns in fibroblasts, endothelial cells, epithelial cells, macrophages, and dendritic cells. Conclusions: This study highlights key genes driving IPF, involved in pathways related to metabolism, immunity, and inflammation. However, their utility as fluid-based biomarkers remains unproven and requires protein-level validation in prospective cohorts. By integrating genomic, immunological, and cellular insights, it provides a framework for targeted therapies and advances mechanism-based precision medicine for IPF. Full article

Background: Duchenne Muscular Dystrophy (DMD) is an X-linked recessive neuromuscular disorder that is characterized by progressive muscle weakness, musculoskeletal limitations, and pulmonary involvement, with cardiomyopathy and cardiovascular complications being a primary cause of morbidity and mortality. With advances in respiratory care, cardiac involvement has become the leading cause of death. There is growing interest in systemic inflammatory indices as potential predictors of cardiovascular involvement. This study aimed to evaluate the prognostic value of inflammatory markers—neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), and pan-immune inflammation value (PIV)—in children with DMD and to explore their association with cardiac findings. Methods: In this retrospective study, 25 male patients diagnosed with DMD and 25 age-matched healthy male controls were evaluated between January 2021 and July 2024. Demographic and clinical data, hematologic and biochemical parameters, and inflammatory indices were recorded. Cardiovascular involvement was assessed using electrocardiography (ECG) and transthoracic echocardiography (TTE). Group comparisons were performed using independent t-tests, while ROC and Pearson correlation analyses were used for diagnostic performance and associations. Results: Pathological Q waves were the most frequent ECG abnormality (24%), and 16% of patients had echocardiographic abnormalities. While most systemic inflammatory indices (NLR, MLR, SIRI, SII, PIV) did not significantly distinguish cardiovascular involvement, PLR demonstrated a strong positive correlation with Pro-BNP levels (r = 0.86, p < 0.05), suggesting a potential link between systemic inflammation and subclinical cardiac stress. Conclusions: Although the overall diagnostic utility of inflammatory indices in predicting cardiovascular complications in DMD was limited, PLR showed a correlation with Pro-BNP in our cohort. However, given the small sample size and limited number of patients with ventricular dysfunction, this finding should be interpreted with caution. PLR may warrant further investigation as a potential marker of cardiovascular involvement in DMD, but larger prospective studies are needed to validate its clinical significance. Full article

Background and Clinical Significance: Rhabdomyosarcoma (RMS) is a rare and aggressive malignant soft-tissue sarcoma (STS) arising from skeletal connective tissues and is most commonly seen in the pediatric population. The pleomorphic subtype is mostly seen in adults in the sixth and seventh decades of life, representing 1% of all histological types of RMS and having a very poor prognosis. Case Presentation: This report presents the case of a 63-year-old male with a medical history of papillary thyroid cancer, who presented with an ulcer-hemorrhagic malignant tumor, namely, a poorly differentiated desmin-positive pleomorphic rhabdomyosarcoma (PRMS), with impressive dimensions located on the posterior thoracic wall. This tumor was surgically removed via a wide resection, followed by palliative chemotherapy and radiotherapy. However, the patient relapsed locally, with pulmonary, bone, and lymph node metastases. The peculiarity of this case is represented by the rapid growth, aggressive nature, and high metastatic potential of the adult RMS, as well as its poor response to treatment. Conclusions: The presented case underscores the need for early diagnosis, multidisciplinary management, and exploration of molecular profiling for therapeutic planning. Full article

Background and Clinical Significance: Acquired angioedema (AAE) is a rare and potentially life-threatening condition characterized by acquired deficiency of C1-inhibitor (C1-INH) resulting in hyperactivation of the classical complement pathway. AAE occurs in association with malignancies or autoimmune diseases. Infectious triggers are rarely encountered, and the underlying mechanisms have yet to be completely clarified. Case Presentation: This case involves a previously healthy 19-year-old male who was admitted with Mycoplasma pneumonia and oral ulcers, subsequently developing unilateral facial angioedema. Laboratory studies demonstrated reduced C4, decreased levels and activity of C1-INH, and reduced C1q, all consistent with acquired C1-INH deficiency. These findings were attributed to the presence of cold agglutinins, which are frequently observed in Mycoplasma pneumoniae infections. Following treatment with icatibant, a bradykinin B2 receptor antagonist, the patient’s angioedema resolved rapidly. An exhaustive workup found no evidence of underlying systemic disorders, and the patient did not experience any angioedema attacks following resolution of the infection. Conclusions: The presence of cold agglutinins, commonly associated with Mycoplasma infections, can precipitate a decline in C1-INH levels, resulting in complement pathway dysregulation. This disruption leads to an excess of bradykinin, followed by increased vascular permeability and localized edema. Full article

Radical prostatectomy is the standard of care for the treatment of early, clinically localized prostate cancer (PC). In addition to known clinical prognosticators, perioperative conditions and the type of anesthesia may affect clinical outcomes through several mechanisms that favor a tumor-propagating state, including activation of the sympathetic system, increased opioid requirements, and inflammation. In this review, we provide an overview of the impact of the perioperative period on PC prognosis and patient outcomes. A non-systematic literature review was conducted to investigate the possible association between neuraxial anesthesia and outcomes after radical prostatectomy (RP) for prostate cancer. The following keywords were used: “cancer recurrence” OR “cancer prognosis” OR “metastasis” AND “neuraxial anesthesia” AND “prostate cancer”. Eligible studies were summarized in the form of a narrative review. In the era of limited use of ERAS protocols, the implementation of neuraxial anesthesia was found to reduce mortality after RP for primary prostate cancer when compared to general anesthesia. Although there was no significant association between anesthetic technique and radiological or biochemical-free survival, regional anesthesia may have an impact on short-term survival in patients with severe comorbidities, involving pulmonary complications and thrombosis. The effect of anesthetic technique on PC patient outcomes remains elusive, although preliminary retrospective evidence suggests a possible positive effect of neuraxial anesthesia on patient outcomes. As the perioperative period is considered a vulnerable timeframe for these patients, the role of the leadership dyad of surgeon and onco-anesthesiologist is crucial. Full article