Background: Features of post-traumatic stress disorder and anxiety may be present in Pulmonary Embolism (PE) patients along with impaired Quality of Life (QoL). We aim to evaluate health related QoL, anxiety and satisfaction with life, during the pandemic, in patients with a PE. Methods: Patients with PE were enrolled during their follow-up. All participants completed the Short Form 36 (SF-36) questionnaire, the State Trait Anxiety Inventory (STAI) X1 and X2 form, and the Satisfaction with Life Scale (SWLS). Results: 92 PE patients were included (mean age±SD=62.50±15.33 years, 56.5% males). Most of the mean values of the SF36 subscales were above the normative value except for “physical role functioning”) (45.92±42.41). “Emotional role functioning” (51.26±43.31) and “general health perceptions” (GH) (54.02±18.79) were slightly above the normative value of 50. Mean STAIX1 levels were 37.05±11.17 and mean STAIX2 levels were 39.80±10.47. Mean SWLS levels were 23.31±6.58. According to multiple linear regression analysis, mental healthscore (MH) and GH were predictive of SWLS(F (10,76) = 10.576, p

Extracorporeal membrane oxygenation (ECMO) can be a life-saving intervention in cases of potentially reversible refractory respiratory failure. One such indication can be bleomycin-induced lung injury. However, in some cases, the injury can be so severe that it becomes irreversible and creates complex medical decisions regarding life support and the continuation of care when no additional therapeutic options are feasible, particularly in cases of patients who were young and fully functional prior to an acute illness. In cases of full pulmonary replacement with mechanical support and the degree of functionality that can be attained utilizing modalities such as ECMO can obscure the true severity of illness and make end-of-life decisions significantly harder for families and caregivers.

The epithelial-mesenchymal transition (EMT) is a major event in idiopathic pulmonary fibrosis pathogenesis. Here, we investigated whether growth arrest-specific protein 6 (Gas6) plays a protective role in lung fibrosis via suppression of the EMT and fibroblast activation. rGas6 ad-ministration inhibited the EMT in isolated mouse ATII cells 14 days post-BLM treatment based on morphologic cellular alterations, changes in mRNA and protein expression profiles of EMT markers, and induction of EMT-activating transcription factors. BLM-induced increases in gene expression of fibroblast activation-related markers and the invasive capacity of primary lung fi-broblasts in primary lung fibroblasts were reversed by rGas6 administration. Furthermore, the hydroxyproline content and collagen accumulation in interstitial areas with damaged alveolar structures in lung tissue were reduced by rGas6 administration. Targeting Gas6/Axl signaling events with specific inhibitors of Axl (BGB324), COX-2 (NS-398), EP1/EP2 receptor (AH-6809), or PGD2 DP2 receptor (BAY-u3405) reversed the inhibitory effects of rGas6 on EMT and fibroblast activation. Finally, we confirmed the antifibrotic effects of Gas6 using Gas6−/− mice. Therefore, Gas6/Axl signaling events play a potential role in inhibition of EMT process and fibroblast acti-vation via COX-2-derived PGE2 and PGD2 production, ultimately preventing the development of pulmonary fibrosis.

Polyelectrolyte-drug complexes are interesting alternatives to improve unfavourable drugs properties. Vancomycin (VAN) is an antimicrobial used in the treatment of methicillin-resistant Staphylococcus aureus pulmonary infections in patients with cystic fibrosis. It is generally administered intravenously with high incidence of adverse side effects, which could be reduced by intrapulmonary administration. Currently, there are no commercially available inhalable formulations containing VAN. Thus, the present work focuses on the preparation and characterization of an ionic complex between hyaluronic acid (HA) and VAN with potential use as inhalable formulations. Particulate-solid HA-VAN25 complex by spray drying from an aqueous dispersion was obtained. FTIR spectroscopy and thermal analysis confirmed the ionic interaction between HA and VAN, while an amorphous diffraction pattern by X-ray was observed. The powder density, geometric size and morphology showed a suitable aerosolization and aerodynamic performance of the powder, indicating the capability of reaching the deep lung. An in vitro extended-release profile of VAN from the complex was obtained, exceeding 24 hours. Microbiological assays against methicillin-resistant and -sensitive reference strains of Staphylococcus aureus, showed that VAN preserves its antibacterial efficacy. In conclusion, HA-VAN25 exhibited interesting properties for the development of inhalable formulations with potential efficacy and safety advantages over conventional treatment.

: Cardiac surgery (CS) with extracorporeal circulation (ECC), induces oxidative stress and systemic inflammatory response, which may seriously affect postoperative lung function. We aimed to test if high parenteral (200mg/kg/24h) perioperative (48h) doses of Vitamin C (VitC) may reduce the incidence and severity of postoperative pulmonary complications (PPC) in selected CS patients. Single centered, prospective, randomized, single-blinded, interventional study included 150 patients, assigned to control group A (n=75) and interventional group B (n=75). Group B intraoperatively received 1/4 of the planned daily Vit C dose (200mg/kg/24h), diluted in 10 ml of normal saline, divided into three parts, while Group A received an equal volume of normal saline at the same time frames. After 6 h from the first intraoperative dose, the following regimen was applied: Group B: 200 mg/kg/24h - 30 min i.v. infusion of VitC in 50 ml of normal saline, every 6h, for the next 48h, and Group A: 30 min i.v. infusion of an equal volume of normal saline every 6 hours, for the next 48h. Modified Kroenke’s score was used to determine the incidence and severity of PPC. The overall incidence of PPC was 36.7% and was significantly lower in Group B (13.3% v.s. 60.0%, p<0.001). The severity of PPC was also significantly lower in Group B [1(1) v.s. 3(2), p<0.001]. Besides, patients from Group B had significantly less damaged lungs and better postoperative renal function, shorter ICU stay, fewer ICU re-admissions, and lower hospital mortality. High parenteral daily VitC doses (200mg/kg/24h) given to selected CS patients for 48h after CS are safe and effective in reducing the incidence and severity of PPC. Further multicenter RCT is needed to confirm these results.

Background: Pulmonary sequestration (PS), generally diagnosed using computed tomography pulmonary angiography (CTPA), is a rare congenital developmental malformation of the lung that is characterized by nonfunctional lung tissue independent of the normal lung tissue. This study summarizes the imaging features of the supplying arteries and draining vessels in patients with PS with an aim to assist with timely clinical diagnosis and operation guidance. Materials and Methods: A total of 55 patients with PS diagnosed on CTPA from multiple clinical centers were retrospectively analyzed. Data included demographic characteristics, imaging features, disease location, isolation type, and the features of supplying and draining vessels, as shown on CTPA images. Results: Of the 55 patients reviewed, 3 (5.45%) were children, 3 (5.45%) were adolescents, and 49 (89.09%) were adults, with a mean age of 44 years. Fifty-four (98.18%) patients had intralobar sequestration and one (1.82%) had extralobar sequestration. PS was noted 3.5 times more frequently in the left lower lobe than in the right lower lobe. For the supplying arteries, 47 (85.45%) were derived from the descending thoracic aorta, 1 (1.82%) from the abdominal aorta, 7 (12.73%) from the celiac axis, and 1 (1.82%) from the bronchial artery. The draining vessels were the pulmonary veins in 49 patients (89.09%), the umbilical vein in 1 (1.82%), the venae intercostal in 1 (1.82%), the pulmonary arteries in 11 (20.00%), and not shown on the images in 2 (3.64%). Conclusion: Clinical presentations of PS are non-specific and can be easily missed or misdiagnosed. However, CTPA can help improve the diagnostic accuracy and identify the supplying arteries and draining vessels, which significantly contribute to surgical planning.

Degenerative mitral valve disease (DMVD) consists of progressive degeneration of the mitral valve that can occur either in isolation or in association with the tricuspid valve, leading to incomplete coaptation of its leaflets and subsequent valve regurgitation. It's the most common cardiac condition in small animals, accounting for about 75% of cases of heart disease in dogs, mainly affecting elderly small-breed dogs. Breeds with a genetic predisposition such as Cavalier King Charles Spaniels and Bull Terriers tend to develop the disease early. It can be classified into 4 stages: A, B, C, and D, with B having subdivisions (B1 and B2). Animals in stages A, B1, and B2 are asymptomatic, showing clinical signs only from stage C onwards. The report details the case of a 13-year-old Fox Terrier diagnosed at stage B2 of the disease, progressing to stage C within two years. A cardiologist conducted annual monitoring.

The emergence of drug-resistant strains of M. tuberculosis (Mtb) and the phenomenon of phe-notypic tolerance to drugs challenge the goal of tuberculosis (TB) elimination worldwide. By using the ex vivo cultures of alveolar macrophages obtained from lung tissues of TB patients after intensive antimicrobial chemotherapy before surgery, different subpopulations of multi-drug-tolerant Mtb with a spectrum of phenotypic and growth features were identified in the same TB lesions. Our results indicative of not only passive mechanisms generating nonheritable resistance of Mtb to antibiotics, which are associated mainly with a lack of Mtb growth, but also some active mechanisms of Mtb persistence, such as cell wall and metabolic pathway remod-eling. In one of the subpopulations, non-acid-fast Mtb have undergone significant repro-gramming with the restoration of acid-fastness, lipoarabinomannan expression and replication in host cells of some patients after withdrawal of anti-TB drugs. Our data indicate the universal stress protein Rv2623 as a clinically relevant biomarker of Mtb that have lost acid-fastness in human lungs. The studies of Mtb persistence, dormancy, and resumption and the identification of biomarkers characterizing these phenomena are very important to develop vaccines and drug regimens with the individualized management of patients for overcoming the re-sistance/tolerance crisis in anti-TB therapy.

Pulmonary arterial hypertension (PAH) is a pathophysiological condition characterized by pulmonary vascular remodeling and elevated vascular resistance, which may ultimately result in cardiovascular failure and sudden cardiac death. In recent years, the occurrence of pregnancy complicated by pulmonary arterial hypertension has witnessed a notable increase, whereas the incidence of postpartum pulmonary arterial hypertension is comparatively rare. This study presents a case involving a 39-year-old female who exhibited severe pulmonary arterial hypertension, finally diagnosed as idiopathic pulmonary arterial hypertension, within 2 days postpartum. The diagnosis was made following a thorough clinical examination. This case report emphasizes the significance of promptly initiating targeted therapy as an initial step in effectively managing patients and the criticality of conducting a thorough assessment of multidisciplinary collaboration in postpartum management. Furthermore, the report has the potential to enhance awareness and education regarding the future management of similarly intricate conditions.

Haemolytic anaemia represents a risk factor for the development of pulmonary hypertension (PH), currently classified as World Health Organization group 5 PH and data regarding appropriate therapeutic strategy are limited. A total of 28 patients, 85.7% with thalassemia and 14,3% with sickle cell disease, with a diagnosis of PH confirmed by right heart catheterization, were included in the study. The patients were divided into three groups according to haemodynamics and overall diagnostic approach: 42,9% had precapillary PH (Pulmonary Arterial Hypertension -PAH group), 25% post-capillary PH and 32.1% Chronic Thromboembolic PH (CTEPH) (29% of b-thalassemia and 50% of SCD patients). The therapeutic approach in each group and its impact on the outcome and haemodynamics was recorded. PAH-specific drug therapy received 82.1% of patients and Balloon Pulmonary Angioplasty (BPA) was performed in 6 patients with CTEPH. There were statistically significant differences in baseline mPAP and PVR values between the CTEPH-haemolytic anaemia group and other groups. PAH-specific drug therapy resulted in haemodynamic improvement for PAH-group. Patients who underwent BPA improved Pulmonary Haemodynamics. Median survival time was 162 months and the survival rate was 1yr-100%, 2,3,4,5,6 years 96%, 9yrs 90% and 13yrs 78%. In patients with haemolytic anaemia, the wide spectrum of induced PH highlights the importance of a correct diagnosis. BPA in CTEPH patients and specific-PAH drug therapy for PAH patients represent potential therapeutic strategies, however the management should be offered in expert PH centers under patients’ individualized approach.

Abstract: Cancer patients are explored by CT-scans more than others. The study reports the local prevalence of these embolisms, the oncological profile of the cases as well as the therapeutic management. Patients and methods: The work was based on the Analysis of the CT-examinations performed on patients of the Radiology department, for reasons other than the search for pulmonary embolism. The examinations are interpreted by 2 radiologist doctors. Results: In 389 patients, 12 cases of asymptomatic pulmonary embolism were detected, representing a prevalence of the order of 3%. The mean age of onset is 67 years. 11 patients had metastatic cancer at the time of diagnosis of pulmonary embolism. 4 PE patients are proximal, while 8 others had segmental and / or sub-segmental PE. 10 patients are treated for carcinomas, the rest for melanoma and splenic lymphoma. After analysis of clinical records, 3 of the 4 proximal pulmonary embolisms were manifested by a discrete clinical symptom attributed to diagnoses other than pulmonary embolism. 10 patients are undergoing chemotherapy alone or combined with radiotherapy, surgery or hormone therapy. At the time of the diagnosis of pulmonary embolism, 3 patients were hospitalized, while 9 were followed up on an outpatient basis. Conclusion: Asymptomatic pulmonary embolism in cancer patients is becoming more frequent. Asymptomatic pulmonary embolisms are mainly peripheral, segmental or sub-segmental. As for symptomatic VTE, asymptomatic pulmonary embolism is diagnosed in patients with metastatic cancer, especially carcinoma type, and treated with chemotherapy.

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a common, preventable and treatable disease. The first PREM (Patient Reported Outcome Measure) type questionnaire that has been dedicated to asses experience of care in COPD is the PREM-C9. Aim: To create a Polish version of the PREM-C9 and determine its the psychometric characteristics. Methods: The validation procedure involved forward and back translation and included 42 COPD patients. The psychometric properties were assessed using Cronbach's alpha, Bartlett's test, Kaiser-Meyer-Olkin and Spearman correlation coefficient. The validity of the questionnaire was assessed using Principal Component Analysis for the extracted principal components. The validity of the factor analysis was demonstrated by the Bartlett's sphericity test and the Kaiser-Meyer-Olkin (KMO). Factor analysis was performed using the Oblimin and Varimax rotation. The reliability of the questionnaire was assessed using the Cronbach's alpha. Results: The Polish version of the PREM-C9 questionnaire met all validation criteria: face, translation, psychometric, functional and reconstruction equivalence. The Spearman correlation results between Polish PREM-C9&CAT: rho= 0,44, p=0,003539; HADS-Anxiety: rho= 0.370864, p=0,015612, HADS-Depression: rho= 0,387405, p=0,011253. Conclusion: The developed Polish PREM-C9 questionnaire is a reliable and valid tool that assesses Polish COPD patients' experiences of their disease and the care they receive.

Venous thromboembolism (VTE) is a prevalent medical condition with high morbidity, mortality, and associated cost. Anticoagulation remains the main treatment for VTE, though the decision on when, how, and for how long to administer anticoagulants is increasingly complex. This review highlights the different phases of VTE management, special circumstances for consideration such as antiphospholipid syndrome, coronary artery disease, cancer associated thrombus and COVID, and future anticoagulation options. Anticoagulation management will continue to be a complex decision, applying evidence-based medicine to individual patients with the hope to maximize effectiveness while minimizing risks.

COVID-19 generated a scenario for global health with multiple systemic impairments. This retrospective study evaluated the clinical, radiological, and pulmonary functional evolution in 302 post-COVID-19 patients. Regarding post-COVID-19 pulmonary symptoms, dry cough, dyspnea, and chest pain were the most frequent. Of the associated comorbidities, asthma was more frequent (23.5%). Chest Tomography (CT) initially showed a mean pulmonary involvement of 69.7%, and the evaluation in the subsequent months showed an improvement in the evolutionary image, and with less than six months post-pathology, there was a commitment of 37 .7%, from six to twelve months, 20% and after 12 months, 9.9%. And as for most of the sample, 50.3% of the patients presented CT normalization in less than six months after infection, 23% normalized between six and twelve months, and 5.2% normalized the images after twelve months, with one remaining. Percentage of 17.3% who maintained post-COVID-19 pulmonary residual sequelae. Regarding spirometry, in less than six months after the pathology, 59.3% of the patients already showed a regular exam; 12.3% normalized their function within six to twelve months, and 6.3% concluded a normal exam after twelve months of post-pathology evaluation. Only 3.6% of the patients still showed some alteration in this period.

Background: Congenital Pulmonary Malformations (CPMs) are rare benign lesions potentially causing infective complications and/or malignant transformation requiring surgery even when asymptomatic. CPMs are infrequent in adult but potentially detected at any age. There is not a consensus indicating the correct extent of resection in both adults and paediatrics. This retrospective multicentric study aims to identify the appropriate surgical resection to prevent the recurrence of related respiratory symptoms. Methods: Between 2010 and 2020, a total of 96 patients (adult and pediatric) underwent surgery for CPMs in 4 centers. A 2:1 propensity score matching (considering sex and lesion side) was performed, identifying 2 groups: 50 patients underwent lobectomy (group A) and 25 sub-lobar resections (group B). Clinical and histopathological characteristics, early and late complications and symptom’s recurrence were retrospectively analyzed and compared between the two groups by univariate and multivariate analyses. Results: Patients who underwent lobectomy had a statistically significant lower rate of recurrence (4% vs 24% of group B, p = 0.014) and a lower rate of intraoperative complications (p = 0.014). Logistic regression identified sub-lobar resection (p=0.040), intra- and post-operative complications (p=0.105 and 0.022) and associated developed neoplasm (p=0.062) as possible risk factors for symptoms recurrence after surgery. Conclusions: Pulmonary lobectomy seems to be the most effective surgical treatment for CPMs, guaranteeing stable remission of symptoms and a lower rate of intra- and postoperative complications. To our knowledge this is one of the largest studies comparing lobectomy and sub-lobar resections in patients affected by CPMs, considering the low incidence worldwide.

It has been reported that prostaglandin I2, such as epoprostenol, develops Grave's disease. A 34-year-old woman was diagnosed with idiopathic pulmonary arterial hypertension and started receiving continuous intravenous epoprostenol. Three years after starting epoprostenol, she started complaining of neck swelling and was diagnosed with Grave’s disease. Thyroid function was controlled by thiamazole and levothyroxine. Nevertheless, her thyroid gland enlargement worsened as epoprostenol dose was titrated. After 23 years of treatment with epoprostenol, she suddenly experienced respiratory failure with a giant goiter leading to airway stenosis and passed away. The autopsy confirmed a giant goiter associated with hyperthyroidism and airway stenosis. We experienced a case of idiopathic pulmonary hypertension with a giant goiter and airway stenosis after long-term intravenous epoprostenol therapy.

On the thirty-fifth anniversary of the first description of O2-sensitive K+ channels in the carotid body chemoreceptors [1], O2 sensing remains a salient issue in the literature. Whereas much has been learned about this subject, important questions such as the identity of the specific K+ channel subtype(s) responsible for O2 sensing by chemoreceptors and the mechanism(s) by which their activities are altered by hypoxia have not yet been definitively answered. O2 sensing is a fundamental biological process necessary for the acute and chronic responses to varying environmental O2 levels which allow organisms to adapt to hypoxia. Whereas chronic responses depend on the modulation of hypoxia-inducible transcription factors which determine the expression of numerous genes encoding enzymes, transporters and growth factors, acute responses rely mainly on the dynamic modulation of ion channels by hypoxia, causing adaptive changes in cell excitability, contractility, and secretory activity in specialized tissues. The most widely studied oxygen-sensitive ion channels are potassium channels but oxygen sensing by members of both the calcium and sodium channel families has also been demonstrated. Given the explosion of information on this topic, in this review we will focus on the mechanisms of physiological oxygen chemotransduction by PO2-dependent K+ channels, with particular emphasis on their function in carotid body chemoreceptor cells (CBCC) and pulmonary artery smooth muscle cells (PASMC), highlighting areas of consensus and controversy within the field. We will first describe the most well-established concepts, those reproduced in multiple laboratories, and then discuss selected observations or questions that remain unresolved, and that limit our progress in this field.

Background: Currently, many detection methods have high sensitivity to the diagnosis of lung cancer. However, some postoperative patients with pulmonary nodule were eventually diagnosed as benign nodules. The ideal evaluation of an individual with a pulmonary nodule would expedite therapy for a malignant nodule and minimize testing for those with a benign nodule.Methods: This case-control study is designed to explore the relationship between ACE1 rs4646994 polymorphism and the risk of lung cancer in patients with pulmonary nodules, 400 individuals with lung cancer and benign pulmonary nodules were included. A DNA extraction kit was used to extract plasm DNA from peripheral blood. The relationship between ACE1 rs4646994 and the risk of lung cancer in patients with pulmonary nodules was determined by chi-square test, logistic regression analysis and cross analysis. Results: The results showed that the DD genotype of ACE1 rs4646994 may increase the risk of lung cancer in patients with pulmonary nodules, and this correlation was more significant in the female subgroup. In the age stratification analysis, it was found that the risk of lung cancer was significantly increased in the DD genotype of ACE1 rs4646994 in the older subgroup (> 45 years). In addition, the possibility of EGFR mutation in lung adenocarcinoma patients with ACE1 rs4646994 DD genotype was lower than that of II or ID genotype carriers. Conclusions: Our study indicated that ACE1 rs4646994 polymorphism increases the risk of lung cancer in patients with pulmonary nodules from China.

Introduction and Aims: COVID-19-associated invasive pulmonary aspergillosis (CAPA) is common and is associated with poor outcomes in critically ill patients. This prospective observational study aimed to explore the association between CAPA development and the incidence and prognosis of cytomegalovirus (CMV) reactivation in critically ill COVID-19 patients. Materials and Methods: We included all consecutive critically ill adult patients with confirmed COVID-19 infection who were admitted to three COVID-19 intensive care units (ICUs) in an Italian hospital from February 25, 2020, to May 8, 2022. A standardized procedure was employed for early detection of CAPA. Risk factors associated with CAPA and CMV reactivation and the association between CMV recurrence and mortality were estimated using adjusted Cox proportional hazard regression models. Results: CAPA occurred in 96 patients (16,6%) of the 579 patients analyzed. Among the CAPA population 40 (41,7%) patients developed CMV blood reactivation with a median time of 18 days (IQR 7-27). The CAPA+CMV group did not exhibit a significantly higher 90-day mortality rate (62.5% vs. 48.2%) than the CAPA alone group (p=0.166). The CAPA+CMV group had a longer ICU stay, fewer ventilation-free days, and a higher rate of secondary bacterial infections than the control group of CAPA alone. In the CAPA population, prior immunosuppression was the only independent risk factor for CMV reactivation (HR 2.33, 95% C.I. 1.21-4.48, p=0.011). Conclusions: In critically ill COVID-19 patients, CMV reactivation is common in those with a previous CAPA diagnosis. Basal immunosuppression before COVID-19 appeared to be the primary independent variable affecting CMV reactivation in patients with CAPA. Furthermore, the association of CAPA+CMV versus CAPA alone appears to impact ICU length of stay and secondary bacterial infections but not mortality.

This study evaluated the effectiveness of an electronic system for managing drug-sensitive pulmonary tuberculosis patients in the Kyrgyz Republic. This was a cohort study using programmatic data. The study included patients registered on the paper-based system in 2019 and the electronic system between June 2021 and May 2022. Data was taken from 302 individuals from the electronic system for completeness and concordance in comparison with the paper-based system. The study showed that for most variables the completeness and concordance was 85.3%-93.0% and was lowest for non-mandatory fields such as medication side effects (26.8% vs 13.6%). No significant difference was observed in time taken from symptom onset to diagnosis and treatment initiation between the two systems. However, the electronic system had a significantly higher percentage of patients who initiated treatment on the same day of diagnosis (80.3% vs. 57.1%). The proportion with successful outcomes was similar in both groups, but the electronic system had a significantly lower proportion of patients with outcomes that were not evaluated or recorded (4.8% vs. 14.3%, p < 0.001). The study highlights the potential advantages of implementing an electronic TB register system for improving records. We advocate for similar studies in other regions in Kyrgyz Republic.

Several criteria exist to diagnose pulmonary aspergillosis with varying degrees of certainty in specific populations, including oncohaematological patients (EORTC/MSG), ICU patients (AspICU) and Covid-19 patients (ECMM). At the beginning of the pandemic, however, the diagnosis of Covid-19 Associated Pulmonary Aspergillosis (CAPA) could not be performed easily, and the decision to treat (DTT) was empirical. In this cross-sectional retrospective study including patients with SARS-CoV-2 infection and a suspicion of CAPA, we studied the concordance between the DTT and the three diagnostic criteria using Cohen’s coefficient, then we identified the factors associated with the DTT and we corrected by treatment to study the influence of the diagnostic criteria on survival. We showed good concordance of DTT and AspICU and ECMM criteria, with “compatible signs”, “positive culture” and “positive galattomannan” influencing the DTT. Treatment also showed a positive effect on survival once corrected for a putative, possible or probable diagnosis of CAPA using AspICU and ECMM criteria. We conclude that EORTC/MSGERC are not considered applicable in clinical practice due to lack of inclusion of signs and symptoms and do not lead to improved survival. AspICU and ECMM criteria showed a good degree of agreement with the DTT and a positive correlation with patient recovery.

Chest trauma is one of the most serious and difficult injuries, with various complications that can lead to ventilation - perfusion (V/Q) mismatch and systemic hypoxia. We are presenting a case of 53 – year - old male with no comorbidities or chronic therapy, who was admitted to the Intensive Care Unit due to severe respiratory failure after chest trauma. He developed right - sided pneumothorax and then thoracic drain was placed. On admission, the patient was hemodynamically unstable and tachypneic. The patient was intubated and mechanically ventilated, febrile (38.9°C) and unconscious. A lung CT showed massive non-ventilated areas predominantly in the right lung. He was ventilated with PEEP of 10 cmH2O with a FiO2 of 0.6 – 0.8. Empirical broad-spectrum antimicrobial therapy was immediately initiated. Both high FiO2 and moderate PEEP were maintained and adjusted according to the current blood gas values and oxygen saturation. After Stenotrophomonas maltophilia was identified and treated with sulfamethoxazole/trimethoprim his general condition gradually improved, and he was weaned from mechanical ventilation. In conclusion, both ventilatory and antibiotic therapy were needed to improve oxygenation and outcome of the patient with pneumonia due to the resistant S. maltophilia with V/Q mismatch.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with a poor prognosis. Pirfenidone is approved and widely used for the treatment of IPF and reduces lung function decline. The aim of this study was to evaluate the efficacy of different doses of pirfenidone for the prevention of disease progression in patients with IPF. Methods: This was a prospective, observational, single-center cohort study conducted in Haeundae Paik Hospital, Republic of Korea, from April 2021 to March 2023. IPF patients were assigned to three groups according to the dose of pirfenidone (600mg, 1,200mg, 1,800mg). The primary endpoint was the efficacy of pirfenidone according to dose for the prevention of disease progression over 12 months. The secondary endpoint was the role of Krebs von den Lungen-6 (KL-6) in predicting disease progression. Results: A total of 44 patients were enrolled, of whom 39 completed the study, with 13 patients assigned to each of the three groups. The median age was 71.7 years, and 79.5% of patients were men. The baseline characteristics were similar across groups, except the 600mg group was older (75.9 vs. 69.2 vs. 68.2 years, p = 0.016). Fourteen patients (35.9%) suffered disease progression. The rate of disease progression did not differ according to the dose of pirfenidone (38.5 vs. 38.5 vs. 30.8%, p = 1.000). In multivariable logistic regression analysis, KL-6 was not a statistically significant predictor of disease progression. Conclusions: In our study, regardless of dose, consistent pirfenidone use for 12 months resulted in similar efficacy for the prevention of disease progression in patients with IPF. Large-scale, randomized, double-blind, placebo-controlled clinical trials are needed.

Hemodynamics is the eternal theme of the circulatory system. Abnormal hemodynamics and cardiac and pulmonary development intertwine to form the most important features of children with congenital heart diseases (CHDs), thus determining these children’s long-term quality of life. However, due to the lack of neonatal rodent models of CHDs, it is unclear how CHD-associated hemodynamics shape postnatal cardiac and pulmonary development. Here, we review the varieties of hemodynamic abnormalities that exist in children with CHDs, the recently developed neonatal rodent models of CHDs, and the inspirations these models have brought us in the areas of cardiomyocyte proliferation and maturation, and in alveolar development. Furthermore, current limitations, future directions, and clinical decision-making based on these inspirations are highlighted. Understanding how CHD-associated hemodynamic scenarios shape postnatal heart and lung development may provide a novel path to improving the long-term quality of life of children with CHDs, transplantation of stem cell–derived cardiomyocytes, and cardiac regeneration.

Background: In chronic obstructive pulmonary disease (COPD), there are two known classifications for assessing what is called disease severity. One is the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, which is based on the post-bronchodilator value of FEV1 (% reference). The other is the STaging of Airflow obstruction by Ratio (STAR). Methods: We reanalyzed data from our outpatient cohort study, which included 141 participants with COPD from 2015 to 2023. We compared mortality and COPD-specific health status between the GOLD 1 to 4 groups and the STAR 1 to 4 groups. Results: By simple calculation, GOLD and STAR severity classes coincided in 75 participants (53.2%). The weighted Bangdiwala B value with linear weights was 0.775. The participants were observed for up to 95 months, with a median of 54 months. Death was confirmed in 29 participants (20.5%). In univariate Cox proportional hazards analyses, there was a significant difference in mortality between the GOLD 1 and GOLD 3+4 groups, with the GOLD 1 group used as the reference [Hazard Ratio 4.222 (95% CI 1.298 - 13.733), p=0.017]. However, there was no statistically significant predictive relationship between STAR 1 and STAR 2, or between STAR 1 and STAR 3+4. The St. George's Respiratory Questionnaire (SGRQ) Total and COPD Assessment Test (CAT) scores were significantly different between all GOLD groups, except for the CAT score between GOLD 1 and GOLD 2. The SGRQ Total and CAT scores were significantly different between STAR 1 and STAR 3+4, but not between STAR 1 and STAR 2. Conclusion: From the perspective of all-cause mortality and COPD-specific health status, the GOLD classification is more discriminative than STAR.

Background: Interstitial lung disease (ILD) is a frequent complication in systemic sclerosis (SSc). So, an increased awareness of this complication is a real need in the clinical setting, because it may affect the prognosis of patients. In particular, an accurate strategy is desirable in order to detect ILD in its stages. So, we investigate the validity of ultrasound (US) in detecting subclinical ILD in SSc, and to determine its potential in disease progression. Methods: 133 patients without respiratory symptoms and 133 healthy controls were included. Borg scale, Rodnan skin score (RSS), pulmonary auscultation, chest radiographs and respiratory function tests (RFT) were performed. An expert rheumatologist performed the lung US. High-resolution CT (HRCT) was also performed. After the baseline assessment, the patients were followed every 3 months for 12 months. Results: A total of 79 of 133 patients (59.4%) showed US signs of ILD in contrast to healthy controls (4.8%) (p=0.0001). The clinical and laboratory variables associated with ILD were anti-centromere antibodies (p=0.005) and RSS (p=0.004). A positive correlation was demonstrated between the US and HRCT findings (p=0.001). Sensitivity and specificity of US in detecting ILD was 91.2% and 88.6% respectively. A good inter-observer reliability was observed (k = 0.72). In the follow-up, a total of 30 patients out of 79 (37.9%) who demonstrated US signs of ILD at baseline, showed changes in the ILD score by US. Conclusions: US showed a high prevalence of subclinical ILD in SSc patients. It demonstrated to be a valid, reliable and feasible tool to detect ILD in SSc and to monitoring the disease progression.

(1) Background: This retrospective study aimed to compare the efficacy and safety of one-stage computed tomography (OSCT)- to that of two-stage computed tomography (TSCT)-guided localization for the surgical removal of small lung nodules. (2) Methods: We collected data from patients with ipsilateral pulmonary nodules who underwent localization before surgical removal at Veteran General Hospital Kaohsiung between October 2017 and January 2022. The patients were divided into the OSCT and TSCT groups. (3) Results: We found that OSCT significantly reduced the localization time and risky time compared to TSCT, and the success rate of localization and incidence of pneumothorax were similar in both groups. However, the time spent under general anesthesia was longer in the OSCT group than in the TSCT group. (4) Conclusions: The OSCT-guided approach to localize pulmonary nodules in hybrid operation room is a safe and effective technique for the surgical removal of small lung nodules.

Electrocardigraphy remains as a first-line evaluation method for cardiac function, recording the electrical activity of the heart from the body surface. Since atrial activation is seen on the ECG as P-wave, several factors are known to impact the appearance of the P-wave, such as direction of electric impulse, conduction abnormalities and anatomical characteristics of the atria. The aim of this retrospective study was to find statistically significant associations between anatomy of pulmonary veins (PVs) osberved in cardiac computed tomography (CT) and P-wave appearance during sinus rhythm on resting ECG. For each patient, a resting 12-lead ECG was recorded, the field of analysis was P wave – its’ duration, morphology and axis. The evaluation of the CT scan recordings was performed by creating 3D models of the left atrium and analyzing anatomy of the PVs and left atrial appendage (LAA). Noteworthy correlations were found: anatomy of the left PVs showed an association with LAA volume, LAA morphology and P-wave notching in lead II. The right PVs demonstrated relation with P wave axis and amplitude. Although these correlations cannot be classified as strong, they may play a role in significant scientific discoveries in future research projects.

Colorectal cancer is the third most diagnosed cancer in males and in females, representing 8% of estimated new cases and the third cause of cancer-related death in both sexes, accounting for 9% of cancer deaths in men and 8% in women. About 20% of patients diagnosed with CRC present metastatic disease. Although lung metachronous or synchronous metastatic spread without other involved sites has been reported in only a small proportion of patients, considering that this tumor is frequently diagnosed, the clinical approach to CRC pulmonary metastases represents a major issue for thoracic surgeons and CRC oncologists. Among patients diagnosed with pulmonary metastases from CRC, about 9 – 12% are eligible for local treatments with radical intent, including surgical resection, SBRT and ablation therapy. Due to the lack of randomized controlled trials among different local strategies, there is no definitive evidence about the optimal approach, although surgical resection is considered the most effective therapeutic option in this clinical scenario. Oncological achievement of primary radical resection, the biology of primary tumor and metastatic sites, disease free interval and or progression free survival are independent prognostic factors which make it possible to define a cohort of patients which might significantly benefit from pulmonary metastasectomy.

Background: Pulmonary emboli (PE) is a life threatening condition that is discovered in many patients only "post mortem". Adequate and timely detection of PE is crucial, because of the high mortality and morbidity and the sudden unexpected hemodynamic collapse that may occur in patients with PE. Objectives: To assess the ability to predict clinical outcome of patients with acute PE, using a non-gated computed tomography pulmonary angiography (CTPA), based on the dimensions of the right ventricle. Methods: A retrospective study that analyzed CTPA images of patients admitted with acute PE during the years 2012-2017 in Baruch Padeh Medical Center. The cohort study included 300 patients with documented acute PE, among them 255 were hospitalized in medical (non-intensive care unit) wards, and 45 were patients were hospitalized in an intensive care unit (ICU). Results: Among the 45 patients admitted to the ICU, 8% died. Larger RV diameters predicted mortality (OR=10.14, 95% CI [1.09-93.86]) as well as lower systolic and diastolic blood pressure measurements (p=0.001 and 0.01). Among the 255 patients that were admitted in the Internal Medicine Ward 7% died. Older age (p=0.028), sepsis and cancer (both p<0.001), high WBCs count (p<0.001), and renal failure (p<0.001) predicted death. Overall, of all 300 patients that were admitted, lower blood pressure (systolic and diastolic) (p<0.001, 0.008), older age (p<0.007), sepsis (p<0.001), cancer (p=0.006), higher WBCs count (p<0.001), and impaired renal function (p<0.001) predicted death among patients admitted with confirmed acute PE. Conclusions: Clinical parameters and hematological parameters could predict the outcome of patients admitted with acute PE. RV diameter, measured by the non-ECG gated CTPA had an additive predictive value for patients who were hemodynamically unstable on admission and were hospitalized in the ICU.

Background: Influenza vaccine is a tool for preventing infection and reducing exacerbations in patients with asthma and chronic obstructive pulmonary disease (COPD). Purpose of this study is to investigate dynamics of CRP and serum cytokines (IL-2, IL-6, IL-10, IL-17) in patients with asthma and COPD, as well as to perform a correlation analysis with the clinical parameters of the disease manifestation. Methods: The study included 34 patients with asthma, 20 patients with COPD vaccinated against influenza during a period of remission from 2 to 4 weeks, both groups being under a basic maintenance therapy, and 26 healthy individuals vaccinated with the trivalent polymer-subunit vaccine Grippol® Plus, containing 5 µg of influenza virus strains and 500 µg of azoximer bromide. Results: Observing patients with asthma and COPD, during a year after the vaccination, has revealed a significant reduction in exacerbations frequency (p < 0.05) and duration (p < 0.05) of the bronchial obstructive syndrome (BF). Before the vaccination the IL-6 level in patients with asthma had a direct moderate correlation with duration of exacerbations of the underlying disease (p < 0.05), along with the number of systemic corticosteroids courses during exacerbations (p < 0.05). In 12 months after the vaccination, while assessing cytokine profile of all study groups, a significant reduction in the level of IL-6 was observed, compared to the baseline values (p< 0.05). Conclusion: Conducted analysis of immunological, clinical, and functional parameters of patients with asthma and COPD has proven for influenza vaccine to be effective in BF patients.

The right heart catheterisation constitutes the gold standard for pulmonary hypertension (PH) diagnosis. However, echocardiography remains a reliable, non-invasive, inexpensive, convenient, and easily reproducible modality not only for the preliminary screening of PH but also for PH prognosis. The aim of this review is to describe a cluster of echocardiographic parameters for the detection and prognosis of PH and analyse the challenges of echocardiography implementation in patients with suspected or established PH. The most important echocardiographic index is the calculation of pulmonary arterial systolic pressure (PASP) through the tricuspid regurgitation (TR). It has shown high correlation with invasive measurement of pulmonary pressure, but several drawbacks have questioned its accuracy. Besides this, the right ventricular outflow track acceleration time (RVOT-AT) has been proposed for PH diagnosis. A plethora of echocardiographic indices: right atrial area, pericardial effusion, the tricuspid annular plane systolic excursion (TAPSE), the TAPSE/PASP ratio, tricuspid annular systolic velocity (s′) and recently, can reflect the severity and prognosis of PH. Recent advances in echocardiography with 3-dimensional right ventricular (RV) ejection fraction, RV free wall strain and right atrial strain may further assist the prognostication of PH.

Catheter-based revascularization procedures developed as an alternative of systemic thrombolysis for patients at intermediate-high and high-risk pulmonary embolism. USAT IH-PE is a retrospective and prospective multicenter registry of such patients treated with ultrasound-facilitated, catheter-directed thrombolysis, whose preliminary results are presented in this study. The primary endpoint was the incidence of pulmonary hypertension (PH) at follow up. Secondary endpoints were short- and mid-term changes in echocardiographic parameters of right ventricle (RV) function, in-hospital and all-cause mortality, and procedure-related bleeding events. Between March 2018 and July 2023, 102 patients were included. The majority were at intermediate-high risk PE (86%), mostly female (57%), median age 66.5 years (IQR 56-74), and 28.4% had active cancer. Echocardiographic follow-up was available for 70 patients, and in only one the diagnosis of PH was confirmed by right heart catheterization, resulting in an incidence of 1.43% (CI 95%, 0.036-7.7). RV echocardiographic parameters improved both at 24 hours and at follow up. In-hospital mortality was 3.9% (CI 95%, 1.08-9.74) while all-cause mortality was 11% (CI 95%, 5.4-19.2). Only 12% had bleeding complications, oh whom 4.9% were BARC 3. Preliminary results from USAT IH-PE registry showed low incidence of PH, improvement in RV function and a safe profile.

Pulmonary Hypertension (PH) is a terminal disease characterized by severe pulmonary vascular remodeling. Unfortunately, targeted therapy to prevent disease progression is limited. Here, the vascular cell populations that contribute to the molecular and morphological changes of PH in conjunction with current animal models for studying vascular remodeling in PH will be examined. The status quo of epigenetic targeting for treating vascular remodeling in different PH subtypes will be dissected, while parallel epigenetic threads between pulmonary hypertension and pathogenic cancer provide insight into future therapeutic PH opportunities.

This study aimed to elucidate the similarities and differences between amyloid-forming corpora amylacea (CA) in the prostate and lung, examine the nature of CAs in cystic tumors of the atrioventricular node (CTAVN), and clarify the distinctions between amyloid-forming CA and spheroid-type amyloid deposition. We conducted proteomics analyses using liquid chromatography–tandem mass spectrometry with laser microdissection and immunohistochemistry to validate the characteristics of CAs in the lung and prostate. Our findings revealed that CAs in these organs primarily consist of common proteins (β2-microglobulin and lysozyme) and locally produced proteins. Moreover, we observed a discrepancy between the histopathological and proteomic analysis results in CTAVN-associated CAs. In addition, while the histopathological appearance of amyloid-forming CAs and spheroid-type amyloid deposits were nearly identical, the latter deposition lacked β2-microglobulin and lysozyme, and exhibited evident destruction of surrounding tissue. A literature review further supported these findings. These results suggest that amyloid-forming CAs in the lung and prostate are formed through a shared mechanism, serving as waste containers (wasteosomes) and/or storage for excess proteins (functional amyloids). In contrast, we hypothesize that while amyloid-forming CA and spheroid-type amyloid deposits are formed, in part, through common mechanisms, the latter are pathological.

This study aimed to assess the prognostic significance of total leukocyte count (TLC) and hemoglobin (Hb) levels upon admission for patients with acute pulmonary embolism (PE), considering the European Society of Cardiology (ESC) model for mortality risk. 1622 patients from a regional PE registry were included. Decision tree statistics were employed to evaluate TLC and Hb's prognostic value, both independently and in conjunction with the ESC model. Results indicated all-cause and PE-related in-hospital mortality rates of 10.7% and 6.5% respectively. Subgrouping patients based on TLC cutoff values (≤11.2, 11.2-16.84, &gt;16.84 x10^9/L) revealed increasing all-cause mortality risks (7.0%, 11.8%, 30.2%). Incorporating Hb levels (≤126 g/L or above) further stratified the lowest risk group into two strata with all-cause mortality rates of 10.1% and 4.7%. Similar trends were observed for PE-related mortality. Notably, TLC improved risk assessment for intermediate-high risk patients within the ESC model, while Hb levels enhanced mortality risk stratification for lower risk PE patients in the ESC model for all-cause mortality. In conclusion, TLC and Hb levels upon admission can refine the ESC model's mortality risk classification for patients with acute PE, providing valuable insights for improved patient management.

Neutrophil elastase (NE) is taken up by macrophages, retains intracellular protease activity and induces a pro-inflammatory phenotype. However, the mechanism of NE-induced pro-inflammatory polarization of macrophages is not well understood. We hypothesized that intracellular NE degrades histone deacetylases (HDAC) and Sirtuins, disrupting the balance of lysine acetylation and deacetylation, and resulting in nuclear to cytoplasmic translocation of a major alarmin, High Mobility Group Box 1 (HMGB1), a pro-inflammatory response in macrophages. Human blood monocytes were obtained from healthy donors, or from subjects with cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD). Monocytes were differentiated into blood monocyte derived macrophages (BMDM) in vitro. Human BMDM were exposed to NE or control vehicle and the abundance of HDACs and Sirtuins was determined by western blotting of total cell lysates or nuclear extracts, or determined by ELISA. HDAC, Sirtuin, and Histone acetyltransferase (HAT) activities were measured. NE degraded most HDACs and Sirtuin (Sirt)1, resulting in decreased HDAC and sirtuin activities, with minimal change in HAT activity. We then evaluated whether the NE-induced loss of Sirt activity or loss of HDAC activities would alter the cellular localization of HMGB1. NE-treatment or treatment with Trichostatin A (TSA), a global HDAC inhibitor, both increased HMGB1 translocation from the nucleus to the cytoplasm, consistent with HMGB1 activation. NE significantly degraded Class I and II HDAC family members and Sirt 1 which shifted BMDM to a pro-inflammatory phenotype.

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown origin, with a median survival time of ~3 years after diagnosis without anti-fibrotic therapy. It is characterized by progressive fibrosis indicated by increased collagen deposition and high numbers of fibroblasts in the lung. It was demonstrated that CCL18 induces collagen and αSMA synthesis in fibroblasts. We aimed to identify the CCL18 receptor responsible for its pro-fibrotic activities. Methods: We used a random phage display library to screen for potential CCL18-binding peptides, demonstrated its expression in human lungs and fibroblast lines by PCR and immunostaining and verified its function in cell lines. Results: We identified CCR6 (CD196) as a CCL18 receptor and found its expression in fibrotic lung tissue and on lung fibroblast lines derived from fibrotic lungs but it is almost absent in control lines and tissue. CCL18 induces receptor-internalization in a CCR6-overexpressing cell line. CCR6 blockade in primary human lung fibroblasts reduces CCL18-induced FGF2 release as well as collagen-1 and αSMA expression. Knock-down of CCR6 in a mouse fibroblast cell line abolishes the induction of collagen and -smooth muscle actin expression. Conclusion: Our data indicate that CCL18 triggers pro-fibrotic processes via CCR6, highlighting its role in fibrogenesis.

Background. Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous systemic syn-drome that often coexists with multiple comorbidities. In high-complex COPD patients the role of the Cumulative Illness Rating Scale (CIRS) as a risk predictor of COPD exacerbation is not known. Objective. To determine the effectiveness of the CIRS score in detecting the association of comorbidities and disease severity with the risk of acute exacerbations in COPD patients. Methods. 105 adults with COPD were included in this prospective study. All participants at baseline had at least 2 moderate exacerbations or 1 leading to hospitalization. The primary outcome was a composite of moderate or severe COPD exacerbation during 12-months follow-up. Results. CIRS indices (CIRS total score, Severity Index and Comorbidity Index) showed a positive correlation with mMRC, CAT and a negative correlation with FEV1, FVC, FEV1/FVC. The three CIRS indices were able to predict the 12-month rate of moderate or severe exacerbation (CIRS-Total Score: Hazard Ratio (HR) = 1.12 (95% CI: 1.08-1.21); CIRS-Severity Index: HR = 1.21 (95% CI: 1.12-1-31); CIRS-Comorbidity Index = 1.58 (95% CI: 1.33-1.89)). Conclusions. Among patients with COPD, comorbidity number and severity, assessed by the CIRS score, influence the risk in moderate to severe exacerbations. The CIRS score also correlates with the severity of respiratory symptoms and lung function

Pulmonary tuberculosis (PTB) is one of the leading causes of death in developing countries. This global health burden is worsened by the emergence of multi-drug resistance, which calls for new interventions to address the pandemic and medicinal plants remain a source for the new interventions. This study aimed to investigate the in vitro immunomodulatory effects of three plants used traditionally for the treatment of PTB in the Eastern Cape Province of South Africa. Eradication of Mycobacterium. tuberculosis in the lung tissue, requires the pro-inflammatory M1 phenotype. Thus, a plant extract with a high potential for anti-tuberculosis effects is expected to produce a high concentration of nitric oxide (NO) as the indicator for the pro-inflammatory M1 phenotype. To test this effect, lipopolysaccharide-activated RAW 264.7 macrophages were cultured and treated with the ethanolic crude extracts of three plants: Anthrixia philycoides, Lippia javaniva, and Sanicula elata at concentrations of 50µg/ml, 100µg/ml, and 200 µg/ml. After 24h, 50µl Griess reagent was added to the plates and absorbance was measure at 540nm. A standard curve of sodium nitrite dissolved in culture media was used to determine the concentration of NO in each sample. The results showed Anthrixia philycoides, and Lippia javanica, as anti-inflammatory when compared with the positive control, while Sanicula elata pro-inflammatory, producing a high amount of NO, compared with the positive control. Our results revealed the polarizing activity of Sanicula elata on macrophages towards M1 phenotype, with evidence of the nitric oxide production, warranting further in-vivo investigations of medicinal plant for anti-TB activity.

While investigating the outcomes of balloon dilatation procedures in patients with congenital obstructive lesions of the heart, several parallel observations have been made. The purpose of this review is to present these observations/phenomena/innovations related to balloon dilatation of pulmonary stenosis (PS), aortic stenosis (AS), and aortic coarctation (AC). In subjects who had balloon pulmonary valvuloplasty (BPV), development of infundibular obstruction, electrocardiographic (ECG) changes, changes in right ventricular filling, role of balloon/annulus ratios on the results of BPV, and double balloon vs. single balloon BPV will be reviewed. In patients who had balloon aortic valvuloplasty (BAV), causes of aortic insufficiency and trans-umbilical venous approach for BAV will be tackled. In children who had balloon angioplasty (BA) of AC, aortic remodeling and biophysical response after BA of AC will be discussed.

Introduction: The predictive value of the risk stratification scales in elderly patients with IPAH might differ from that in younger. It is unknown whether young and older IPAH patients have the same survival dependence on PAH-specific therapy numbers. The aim of the study was to evaluate the prognostic relevance of risk stratification scales and PAH medication numbers in elderly in comparison with young IPAH patients. Material and methods: 119 patients from a prospective single-center PAH registry were divided on to group I <60 years old (n=89) and group II ≥60 years old (n=30). ESC/ERS, REVEAL, and REVEAL 2.0 risk stratification scores were assessed at baseline, as well as H2FpEF- score and survival at follow-up. Results: During a mean follow-up period of 2.9 years (1.63; 6.0) 42 (35.3%) patients died; at 1, 2, 3, 5, 7, and 10 years survival was 95%, 88.6%, 78.5%, 61.7%, 48.5% and 33.7%, respectively. No survival difference was observed between the two groups despite the use of monotherapy in elderly patients. The best predictive value exhibited the REVEAL in group II (IPAH patients ≥60 years) - AUC 0.73 (0.56-0.91), p = 0.03; and in patients with LHD comorbidities in the entire cohort - AUC 0.73 (0.59-0.87), p<0.009. Factors independently associated with death in the entire cohort were CKD (p=0.01, HR 0.2), the right-to-left ventricle dimension ratio (p=0.0047, HR 5.97), and NT-proBNP >1400 pg/ml (p=0.008, HR 3.18). Conclusion: Risk stratification in elderly IPAH patients requires a fundamentally different approach than that of younger patients, taking into account the initial limitations in physical performance and comorbidities that interfere with current assessment scores. The REVEAL score reliably stratifies patients at any age and LHD comorbidities. The initial monotherapy seems to be reasonable in patients over 60 years. Selection tools for initial combination PAH therapy in older IPAH patients with comorbidities need to be validated in prospective observational studies.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD) affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of the disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is focused nowadays on the potential role of the genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the TGF-β pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield safe results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. The following review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

We investigated whether cigarette smoking and dietary acid load (DAL) are associated with the risk of chronic obstructive pulmonary disease (COPD) in middle-aged healthy Korean men. Healthy men without diagnosed chronic disease (40-64 yrs) from the KNHANES-VI (2013–2015) included in the analysis (n=774) were subdivided by smoking status and DAL levels as estimated by the net endogenous acid production (NEAP) quartile. Current smokers tended to have a higher risk of COPD than non-smokers before and after the adjustment. When divided by the DAL quartile, the Q4 tended to have a higher risk of COPD than the Q1. Additionally, current smokers with lower (Q2), modest (Q3), and highest NEAP scores (Q4) showed more than 4-fold higher risks of COPD than the non-smokers with the lowest NEAP scores (Q1). Ex–smokers with higher NEAP scores (Q3 and Q4) showed more than 4-fold higher risks of COPD than the Q1. Interestingly, the risk of COPD was also more than 6-fold higher in non-smokers with the highest NEAP scores compared to the Q1. NEAP scores and smoking status synergistically increased the risk of COPD in middle-aged healthy Korean men. It suggests that DAL levels are an important factor for the prevention and management of COPD.

Background and Objectives: To evaluate the effectiveness and safety of balloon pulmonary angio-plasty in patients with inoperable chronic thromboembolic pulmonary hypertension in Vilnius Pulmonary Hypertension Referral centre and provide comparative analysis with other centres. Materials and Methods. This study included all balloon pulmonary angioplasty procedures per-formed between 2019 and 2024 in a single tertiary centre. Invasive haemodynamic parameters and clinical variables were assessed at baseline, at the end of invasive treatment, and at the con-clusion of follow-up (average 8.6 months) following the last balloon pulmonary angioplasty. Ad-ditionally, respective literature review was performed. Results. Twenty-six patients with inoper-able chronic thromboembolic pulmonary hypertension were enrolled. The mean age of the pa-tients was 61.6 (40-80) years. Each patient underwent an average of 4.2 (1-9) procedures. Fol-low-up data were available for 12 patients. Mean pulmonary arterial pressure decreased by 38.8% (p

Fatal hemoptysis secondary to severe pulmonary veins stenosis is an exceptional late complication of radiofrequency ablation for atrial fibrillation. We report the case of a 53-year-old male with a history of atrial fibrillation treated by radiofrequency ablation and admitted in our center 6 months after the initial procedure because of aggravating dyspnea and fatigability. Transthoracic echocardiography showed moderate dilation of right heart cavities, severe pulmonary hypertension, and a turbulent flow in superior pulmonary veins. The cardiologist suspected pulmonary vein(s) stenosis and cardiac computed tomography (CT) angiography was performed with findings of severe stenosis of the right superior, right inferior and left inferior pulmonary veins, near-occlusion of the left superior pulmonary vein and the vein draining the apical segment of the right lower lobe. The CT scan also revealed soft tissue attenuation of the mediastinum posterior to the left atrium suggesting fibrosing mediastinitis together with parenchymal findings consistent with pulmonary venooclusive disease and an area of hemorrhagic infarction. Fatal hemoptysis occurred 3 days after the evaluation before any treatment was attempted. In conclusion, severe pulmonary stenosis remains a rare but severe complication of radiofrequency ablation. Prevention is the key element together with an early diagnosis as the entity is potentially life-threatening.

Interstitial lung diseases (ILDs) constitute a group of more than 200 disorders, being idiopathic pulmonary fibrosis (IPF) one of the most frequent. Telomere length (TL) shortening causes loss of function of the lung parenchyma. However, little is known about its role as prognostic factor in ILD patients. With the aim of investigating the role of TL and telomerase activity in the prognosis of patients affected by ILDs, we analysed lung tissue samples from 61 patients. We measured relative TL and telomerase activity by conventional procedures. Both clinical and molecular parameters were associated with overall survival by the Kaplan-Meier method. Patients with IPF had poorer prognosis than patients with other ILDs (p = 0.034). When patients were classified according to TL, those with shortened telomeres reported lower overall survival (p = 0.085); differences reached statistical significance after excluding ILD patients who developed cancer (p = 0.021). In a Cox regression analysis, TL behaved as a risk-modifying variable for death associated with rheumatological disorders (RD) co-occurrence (p = 0.029). Also, in patients without cancer, ferritin was significantly increased in cases with RD and IPF co-occurrence (p = 0.032). In relation to telomerase activity, no significant differences were detected. In conclusion, TL in lung tissue emerges as a prognostic factor in ILD patients, Specifically, in cases with RD and IPF co-occurrence, TL can be considered as a risk-modifying variable for death.

Objective: to retrospectively evaluate the incidence rate (IR) of echocardiographic signs suspected for pulmonary hypertension (PH) in Systemic sclerosis (SSc) patients after the introduction of a combination therapy with bosentan and sildenafil for treatment or prevention of digital ulcers. Methods: patients attending the Scleroderma Unit of the Universital Hospital of Careggi from July 2010 to July 2023 were enrolled. Patients older than 18 years old, with an history of digital ulcers, treated with bosentan and sildenafil in combination for at least 12 months were included. Patients with a diagnosis of PH preceding the introduction of the therapy were excluded. Demographical data, disease duration, laboratoristic and instrumental data (pulmonary function tests, echocardiographic estimation of pulmonary artery pressure (PAPs) and ultrasonographic value of renal resistive index) were collected. The IR of echocardiographic signs suspected for pulmonary hypertension and their 95% confidence interval were calculated in events/1000 patients-years.Results: forty-seven patients were enrolled; mean disease duration was 12,14 years (SD 5,87). Mean duration of the combination treatment was 78.33 (SD 41.37) months and total at-risk time was 3525 months. Two patients (4,2%) presented echocardiographic signs of PH (sPAP 50 mmHg and 40 mmHg); the IR was calculated to be 6.8/1000 patients-years (95% CI 6,02-7,7). In one of the 2 patients RHC excluded PAH, while the other patient refused to undergo to RHC and PAH could not be confirmed/excluded. A stability of PFTs and echocardiografic PAPs was observed during the observation time. Conclusions: the results of this retrospective study suggest that combination therapy with endothelin receptor antagonist and Phosphodiesterase-5 (PDE5) inhibitors could help in preventing PAH in SSc; prospective case-control studies on larger population are needed to improve knowledge in this field.

Regulatory T cells are key immune cells to initiate tolerable immune responses. TGFβ is the key cytokine of regulatory T cells. TGFβ is also the master cytokine to stimulate tissue fibrosis. Systemic sclerosis is an autoimmune disease related to overt organ fibrosis. Thus, systemic sclerosis is a disease related to regulatory T cell over-representation. Besides, many end stage organ failures including heart failure, liver cirrhosis, uremia, and pulmonary fibrosis also related to tissue fibrosis. Thus, TGFβ producing regulatory T cells are also involved in the pathogenesis of these end stage organ failure. Once we know the significance of TGFβ and it induced tolerable immune reactions in the pathophysiology of end organ failure, we can develop better prevention or therapeutic strategies to combat these detrimental disorders.

Recurrent respiratory papillomatosis (RRP) is a non- malignant disease, characterized by the production of wart-like growths in respiratory tract, affecting both young and adults (Juvenile-Onset Recurrent Respiratory Papillomatosis, JORRP and Adult-Onset Recurrent Respiratory Papillomatosis, AORRP, respectively). Infection caused by Human Papillomavirus (HPV) is known as the main factors involved in RRP development. Complications of RRP may rarely occur, including lung involvement and malignant transformation. The present systematic review was aimed to evaluate the prevalence of severe complications, as lung involvement and lung tumor in JORRP and AORRP patients, following the guideline for reporting systematic reviews and meta-analysis (PRISMA Statement). Among the 378 studies were found on PubMed and Scopus using the following MESH terms “recurrent respiratory papillomatosis and lung tumor” and “pulmonary tumor and recurrent respiratory papillomatosis”. Basing on inclusion and exclusion criteria, a total of 11 studies were included in the systematic review. We found a pooled prevalence of 8% (95% CI:4%-14%; I2: 87.5%) for lung involvement in RRP patients. In addition, we found a pooled risk difference of 5% in lung involvement between JORRP and AORRP (95% CI: -7%-18%; I2 :85.6%, p-value: 0.41). Among patients with lung involvement, we observed a pooled prevalence of lung tumor of 4% (95% CI:1%- 7%; I2: 67.1%), and a pooled prevalence mortality for this group of 4% (95% CI:2%-6%; I2: 0%). Overall, the positivity rate for HPV-6 and -11 in patients with RRP was 91%. Considering only cases with pulmonary involvement, the pooled prevalence for HPV 11 was 21% (95% CI: 5%-45%; I2: 77.2%). Our results evidenced a low/middle risk of pulmonary involvement and lung tumor in JORRP and AORRP patients, with an increased risk for HPV-11 positive patients. Further studies should be performed to improve knowledge and adopt preventive measures to contrast the progression to severe diseases in RRP patients.

Introduction: Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common condition associated with high morbidity and mortality. Although patients with heart failure (HF) are known to have an increased risk of PE, there is limited evidence regarding its specific impact on patients with acute PE, both in presentation and outcomes, and its relationship with left ventricular ejection fraction (LVEF). Material and Methods: A prospective observational study was conducted at two tertiary hospitals, including patients with symptomatic acute PE between January 2012 and December 2022. The primary objective of the study was the development of a composite outcome (mortality, major bleeding, and recurrence) within the first 30 days. The secondary objective was the development of early complications in patients with HF and reduced LVEF. Results: Out of 1991 patients included with symptomatic acute PE, 7.13% had a history of HF. Patients with HF were older and had more comorbidities. The HF group showed higher mortality (11.27% vs. 4.33%, p<0.001) and major bleeding (9.86% vs. 4.54%, p=0.005). In multivariate analysis, HF was an independent risk factor for the development of the composite outcome (HR 1.93; 95% CI: 1.35-2.76). Reduced LVEF was independently associated with a higher risk of bleeding (HR 3.44; 95% CI: 1.34-8.81). Conclusion: In patients with symptomatic acute pulmonary embolism, heart failure is independently associated with a higher risk of early complications. Additionally, heart failure with reduced LVEF is an independent risk factor for major bleeding.

Hypoxia can induce pulmonary edema (PE) and inflammation. Furthermore, hypoxia depresses left ventricular (LV) inotropy despite sympathetic activation. Here, we investigated the role of nitrosative stress and cardiovascular dysfunction in hypoxic lung injury. Additionally, we studied effects of adrenergic blockade (AB) on hypoxia-induced pulmonary injury. Eighty-six female rats were exposed for 72 h to normoxia or normobaric hypoxia and received infusions with NaCl, prazosin, propranolol or prazosin-propranolol combination. We evaluated hemodynamic function and performed histological and immunohistochemical analyses of the lung. Hypoxia significantly depressed LV but not right ventricular (RV) inotropic and lusitropic functions. AB significantly decreased LV function both in normoxia and hypoxia. AB effects on RV were weaker. Hypoxic rats showed signs of moderate PE and inflammation. This was accompanied by elevated levels of tumor necrosis factor (TNF)  and nitrotyrosine, a marker of nitrosative stress in the lungs. In hypoxia, all types of AB significantly reduced both TNF and nitrotyrosine to normoxic levels. However, AB did not attenuate PE. Results suggest that hypoxia-induced sympathetic activation contributes to inflammation and nitrosative stress in the lungs but not to PE. We suggest that AB in hypoxia aggravates hypoxia-induced inotropic LV dysfunction and backlog into pulmonary circulation, thus promoting PE.

(1) Background: Bronchial artery embolization has been shown to be effective in the management of neoplastic hemoptysis. However, knowledge of pulmonary artery embolization is lacking. To evaluate safety and efficacy of pulmonary artery embolization in patients presenting with hemoptysis related to lung tumors. (2) Methods: This retrospective study reviewed all consecutive patients with cancer and at least one episode of hemoptysis that required pulmonary artery embolization from December 2008 to December 2020. The endpoints of the study were technical success, clinical success, recurrence of hemoptysis and complications. (3) Results: A total of 92 patients were treated with pulmonary artery embolization (63.1 years ± 9.9; 70 men). Most patients had stage III or IV advanced disease. Pulmonary artery embolization was technically successful in 82 (89%) patients and clinically successful in 77 (84%) patients. Recurrence occurred in 49% of patients. Infectious complications occurred in 15 patients (16%). The 30-days mortality rate was 31%. At 3 years, survival rate was 3.6%. Tumor size, tumor cavitation and necrosis and pulmonary artery pseudo-aneurysm were significantly associated with recurrence and higher mortality. (4) Conclusions: Pulmonary artery embolization is an effective treatment to initially control hemoptysis in patient with lung carcinoma but recurrence rate remains high and overall survival remains poor.

Previously, we described a 19-base pair double-stranded RNA with 3'-trinucleotide overhangs, acting as immunostimulatory RNA (isRNA). This molecule demonstrated notable antiproliferative effects on cancer cells, inhibited tumor growth, and elicited immunostimulatory and antiviral responses by inducing cytokine and interferon production. Within this study, we compared the efficiency of lung fibrosis development, initiated in mice by BLM or LPS using different schemes of induction. Then we compared the effect of isRNA used in a preventive or therapeutic regimen on the development of fibrosis in selected BLM- and LPS-induced mouse models and showed that isRNA can be used in pathological conditions accompanied by the development of inflammation and the risk of fibrosis formation, without adverse side effects. Prophylactic regimen of isRNA application is beneficial for prevention of the development of pulmonary fibrosis.

Experimental evidence suggests that chronic intermittent hypoxia (CIH), a major hallmark of obstructive sleep apnea (OSA), boosts carotid body (CB) responsiveness, thereby causing in-creased sympathetic activity, arterial and pulmonary hypertension, and cardiovascular disease. An enhanced circulatory chemoreflex, oxidative stress, and NO signaling appear to play im-portant roles in these responses to CIH in rodents. Since the guinea pig has a hypofunctional CB (i.e., it is a natural CB knockout), in this study we used it as a model to investigate the CB de-pendence of the effects of CIH on pulmonary vascular responses, including those mediated by NO, by comparing them with those previously described in the rat. We have analyzed pulmonary artery pressure (PAP), the hypoxic pulmonary vasoconstriction (HPV) response, endothelial function both in vivo and in vitro, and vascular remodeling (intima-media thickness, collagen fiber content, and vessel lumen area). We demonstrate that 30 days of exposure of guinea pigs to CIH (FiO2, 5% for 40 s, 30 cycles/h) induces pulmonary artery remodeling but does not alter en-dothelial function or the contractile response to phenylephrine in these arteries. In contrast, CIH exposure increased the systemic arterial pressure, and enhanced the contractile response to phenylephrine while decreasing endothelium-dependent vasorelaxation to carbachol in the aorta, without causing its remodeling. We conclude that since all of these effects are independent of CB sensitization, there must be other oxygen sensors, beyond the CB, with the capacity to alter the autonomic control of the heart and vascular function and structure in CIH.

Pulmonary arteriovenous malformations (PAVMs) are vascular anomalies resulting in abnormal connection between pulmonary arteries and veins. In 80% of cases, PAVMs are present from birth, but clinical manifestations are rarely seen in childhood. These congenital malformations are typically associated with Hereditary Hemorrhagic Telangiectasia (HHT), a rare disease that affects 1 in 5,000/8,000 individuals. HHT disease is frequently caused by mutations in genes involved in the TGF-β pathway. However, approximately 15% of patients do not have a genetic diagnosis and, among the genetically diagnosed, more than 33% do not meet the Curaçao Criteria. This makes clinical diagnosis even more challenging in the pediatric age group. Here, we introduce an 8 years old patient bearing a severe phenotype of multiple diffuse PAVMs caused by an unknown mutation which ended in lung transplantation. Phenotypically, the case of study follows a molecular pattern HHT-like. Therefore, molecular biology and cellular functional analysis has been performed in primary endothelial cells (ECs) isolated from the explanted lung. The findings revealed a loss of functionality in lung endothelial tissue and a stimulation of endothelial to mesenchymal transition. Understanding the molecular basis of this transition could potentially offer new therapeutic strategies to delay lung transplantation in severe cases.