Reliable quantification of pulmonary arterial pressure is essential in the diagnostic and prognostic assessment of a range of cardiovascular pathologies including rheumatic heart disease, yet an accurate and routinely available method for its quantification remains elusive. This work proposes an approach to infer pulmonary arterial pressure based on scientific machine learning techniques and non-invasive, clinically available measurements. A 0-D multicompartment model of the cardiovascular system was optimized using several optimization algorithms, subject to forward-mode automatic differentiation. Measurement data were synthesized from known parameters to represent the healthy, mitral regurgitant, aortic stenosed and combined valvular disease situations with and without pulmonary hypertension. Eleven model parameters were selected for optimization based on 95 % explained variation in mean pulmonary arterial pressure. A hybrid Adam and limited-memory Broyden-Fletcher-Goldfarb-Shanno optimizer yielded the best results with input data including valvular flow rates, heart chamber volume changes and systematic arterial pressure. Mean absolute percentage errors ranged from 1.8 % to 3.78 % over the simulated test cases. The model was able to capture pressure dynamics under hypertensive conditions with pulmonary arterial systole, diastole, and mean pressure average percentage errors of 1.12 %, 2.49 % and 2.14 %, respectively. The relatively low errors highlight the potential of the proposed model to recover pulmonary pressures for diseased heart valve and pulmonary hypertensive conditions.

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.

Pulmonary arterial hypertension is a rare disease with high mortality despite recent therapeutic advances. The disease is caused by both genetic and environmental factors, and likely gene x environment interactions. While PAH can manifest across the lifespan, pediatric-onset disease is particularly challenging because it is frequently associated with a more severe clinical course and comorbidities including lung/heart developmental anomalies. In light of these differences, it is perhaps not surprising that emerging data from genetic studies of pediatric-onset PAH indicate that the genetic basis is different than that of adults. There is a greater genetic burden in children, with rare genetic factors contributing to at least 36% of pediatric-onset idiopathic PAH (IPAH) compared to ~11% of adult-onset IPAH. De novo variants are frequently associated with PAH in children, and contribute to at least 15% of all pediatric cases. The standard of medical care for pediatric PAH patients is based on extrapolations from adult data. However, the increased etiologic heterogeneity, poorer prognosis and increased genetic burden for pediatric-onset PAH calls for a dedicated pediatric research agenda to improve molecular diagnosis and clinical management. A genomics-first approach will improve the understanding of pediatric PAH and how it is related to other rare pediatric genetic disorders.

Pulmonary hypertension (PH) is a progressive condition that affects pulmonary vessels, but its main prognostic factor is right ventricle (RV) function. Many mice/rat models are used for research in PAH, but results fail to translate in clinical trials. This study reviews studies that test interventions on pulmonary artery banding (PAB), a model of isolated RV disfunction, and PH models. Multiple tested drugs both improved pulmonary vascular hemodynamics in PH models and RV structure and function in PAB animals. PH models and PAB frequently exhibited similar results (73.1% concordance) with drugs other than endothelin receptor antagonists and phosphodiesterase inhibitors. RV systolic pressure accounted for most differences between PH models and PAB. On the other side, all results on RV fibrosis agreed (12 drugs). Macitentan, sildenafil and tadalafil improved most tested pathophysiological parameters in PH models, but almost none in PAB animals. Dapagliflozin was the only drug that improved no parameters. This review shows that many drugs currently under research for PAH have a cardioprotective effect on animals that may translate to humans. To improve the translational potential of drugs in this field, researchers should test them in multiple models, including PAB, while optimizing induction methods for human disease translation.

Endothelial autocrine signaling is essential to maintain vascular hemostasis. There is limited in-formation about the role of endothelial autocrine signaling in regulating severe pulmonary vas-cular remodeling during the onset of pulmonary arterial hypertension (PAH). In this study, we employed the first severe PAH mouse model, Egln1Tie2Cre (Tie2Cre-mediated disruption of Egln1) mice, to identify the novel autocrine signaling mediating the pulmonary vascular endothelial cells (PVECs) hyperproliferation and the pathogenesis of PAH. PVECs isolated from Egln1Tie2Cre lung expressed upregulation of many growth factors or angiocrine factors such as CXCL12, and exhib-ited hyperproliferative phenotype in coincident with upregulation of proliferation specific tran-scriptional factor FoxM1. Treatment of CXCL12 on PVECs increased FoxM1 expression, which was blocked by CXCL12 receptor CXCR4 antagonist AMD3100 in culture human PVECs. Endo-thelial specific deletion of Cxcl12 (Egln1/Cxcl12Tie2 Cre) or AMD3100 treatment in Egln1Tie2Cre mice downregulated FoxM1 expression in vivo. We then generated and characterized a novel mouse model with endothelial specific FoxM1 deletion in Egln1Tie2Cre mice (Egln1/Foxm1Tie2Cre), and found that endothelial FoxM1 deletion reduced pulmonary vascular remodeling and right ventricular systolic pressure. Together, our study identified a novel mechanism of endothelial autocrine sig-naling in regulating PVECs hyperproliferation and pulmonary vascular remodeling in PAH.

Nanoparticles have been used as a novel drug delivery system. Drug-incorporated nanoparticles for local delivery might optimize the efficacy and minimize the side effects of drugs. The efficacy and safety of intratracheal administration of prostacyclin analog (beraprost)-incorporated nanoparticles and imatinib, a PDGF-receptor tyrosine kinase inhibitor, -incorporated nanoparticles in Sugen-hypoxia-normoxia or monocrotaline rat models of PAH and in human PAH-pulmonary arterial smooth muscle cells have been reported. The use of inhaled drug-incorporated nanoparticles might be a novel approach for treatment of PAH.

Pulmonary arterial hypertension (PAH) is a complex and devastating disease that the underlying cellular and molecular mechanisms are largely remains unknown. This study aimed to elucidate the key hub genes and pathways in PAH by bioinformatics analysis. In the current study, we performed WGCNA analysis to systematically identify the hub genes for PAH using transcriptome microarray data. From the Gene Expression Omnibus (GEO) database, one microarray dataset (GSE113439) was downloaded for this study. There were 26 samples in this data set, including 15 PHA samples and 11 normal controls. Based on weighted correlation network analysis, 11 modules were identified and the MEgreenyellow module showed a significantly positive correlation with PAH (r = 0.93, P = 1e−06). The genes in greenyellow module were mainly significantly enriched in mitophagy related pathways by KEGG analyses. Combined with the protein–protein interaction (PPI) and co-expression networks, ten hub genes were identified as candidate biomarkers for PAH in the greenyellow module, including CTNNB1, NIPBL, ROCK2, ROCK1, SCAF11, JAK1, BIRC6, KIF5B, PPP1R12A and XRN1. These hub genes might be potential targets for clinical therapy against PAH. The molecular mechanisms involved in these genes that affected the prognosis of PAH should be further validated through biological and basic studies.

Pulmonary hypertension (PH) is a severe vascular complication of connective tissue diseases (CTD). Patients with CTD may develop PH belonging to different groups: 1) pulmonary arterial hypertension (PAH), 2) PH secondary to lung disease and/or hypoxia, 3) PH due to left heart disease, and 4) chronic thromboembolic pulmonary hypertension (CTEPH). PAH most often develops in systemic scleroderma (SSc), mostly in its limited variant. PAH-CTD is a progressive disease characterized by poor prognosis, therefore the early diagnosis should be established A specific treatment for PAH-CTD is currently available and recommended: prostacyclin derivative (treprostinil, epoprostenol, iloprost, selexipag), nitric oxide and natriuretic pathway: stimulators of soluble guanylate cyclase (sGC: riociguat) and phosphodiesterase 5 inhibitors (PDE5i: sildenafil, tadalafil), endothelin receptor antagonists (ERA: bosentan, macitentan, ambrisentan). Moreover, novel drugs e.g. sotatercept are intensively investigated in the clinical trials. The aim of this paper is to review the literature on the recent advances in treatment strategy and prognosis of patients with PAH-CTD.

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.

Background: At altitudes beyond 2500 m the risk of developing high altitude pulmonary edema (HAPE) grows with the increases in pulmonary arterial pressure. HAPE is characterized by severe pulmonary hypertension, though the incidence and relevance of individual risk factors are not yet predictable. However, the systolic pulmonary pressure (SPAP) and peak in tricuspid regurgitation velocity (TVR) are crucial factors when diagnosing pulmonary hypertension by echocardiography. Methods: The SPAP and TVR of 27 trekkers aged 20-65 years en route in the Solu Khumbu region of Nepal was assessed. Echocardiograph measurements were performed at Lukla (2,860 m), Gorak Shep (5170 m), and the summit of Kala Patthar (5,675 m). The altitude profile and the participant’s characteristics were also compiled for correlation with the measured data. Results: The results showed a highly significant increase of SPAP and TVR after ascending Kala Patthar. The study revealed a lower increase of SPAP and TVR in the group of older participants, although the initial respective measurements in Gorak Shep were significantly higher for this group. A similar finding occurred in those using Diamox® as prophylaxis. There was an inverse relationship between TVR and SPAP, the peripheral capillary oxygen saturation and heart rate. Conclusions: The echocardiograph results indicate that older people are a risk group for developing a HAPE. The prophylactic use of acetazolamid led to higher initial SPAP values in Gorak Shep, and a lower increase of SPAP as well as TRV after ascending Kala Patthar. Arterial oxygen saturation measurements can provide an indicator for the self-assessment for the risk of developing HAPE and provide a rule of thumb for the altitude profile but does not replace a HAPE diagnosis. The collected data variables concerning backpack weight, sex, workload (actual ascent speed), and pre-existing diseases were not statistically significant factors related to SPAP and TVR (p=<0.05).

A key feature of pulmonary arterial hypertension (PAH) is the hyperplastic proliferation exhibited by the vascular smooth muscle cells from patients (HPASMC). The growth inducers FOXM1 and PLK1 are highly upregulated in these cells. The mechanism by which these two proteins direct aberrant growth in these cells is not clear. Herein we identify cyclin dependent kinase 1 (CDK1) also termed cell division cycle protein 2 (CDC2), as having a primary role in promoting progress of the cell cycle leading to proliferation in HPASMC. HPASMC obtained from PAH patients and pulmonary arteries from Sugen/hypoxia rats were investigated for their expression of CDC2. Protein levels of CDC2 were much higher in PAH than in cells from normal donors. Knocking down FOXM1 or PLK1 protein expression with siRNA or pharmacological inhibitors lowered the cellular expression of CDC2 considerably. However, knockdown of CDC2 with siRNA or inhibiting its activity with RO-3306 did not reduce the protein expression of FOXM1 or PLK1. Expression of CDC2 and FOXM1 reached its maximum at G1/S, while PLK1 reached its maximum at G2/M phase of the cell cycle. The expression of other CDKs such as CDK2, CDK4, CDK6, CDK7 and CDK9 did not change in PAH HPASMC. Moreover, inhibition via Wee1 inhibitor adavosertib or siRNAs targeting Wee1, Myt1, CDC25A, CDC25B, or CDC25C led to dramatic decreases in CDC2 protein expression. Lastly, we found CDC2 expression at the RNA and protein level to be upregulated in pulmonary arteries during disease progression Sugen/hypoxia rats. In sum, our present results illustrate that the increased expression of FOXM1 and PLK1 in PAH leads directly to increased expression of CDC2 resulting in a potentiated growth hyperactivity of PASMC from patients with pulmonary hypertension. Our results further suggest that the regulation of CDC2, or associated regulatory proteins, will prove beneficial in the treatment of this disease.

Objectives: Chronic pulmonary aspergillosis (CPA) is a fungal lung infection characterized by slowly progressive destruction of the lung parenchyma and has four main subtypes. The objective of this work was to evaluate the epidemiology of CPA in our area and evaluate the involvement of the different subtypes in mortality. Methods: This was a descriptive longitudinal retrospective study developed in three tertiary hospitals in Spain. Among all patients admitted with a pulmonary aspergillosis diagnosis, we selected those who fulfilled the criteria for chronic aspergillosis according to the criteria of Denning, excluding those with a haematological disorder. Results: Among 409 inpatients recorded as having pulmonary aspergillosis infection, only 76 (18.5%) fulfilled the criteria for CPA, with an estimated incidence of 0.67 cases/100,000 inhabitants/year. The subtypes detected were subacute invasive aspergillosis (SAIA) in 33 (43.4%) patients, simple aspergilloma (SA) in 25 (32.9%) patients, cavitary chronic aspergillosis (CCPA) in 13 (17.1%) patients and chronic fibrosant (CFAP) in 5 (6.5%) patients. The overall three-month mortality was 23%, which was higher in SAIA patients. The predictors of early mortality were age >65 years (OR 3.0 CI 95 1.0–9.5 0.043) and SAIA subtype vs. other subtypes (OR 3.1 CI 95 1.0–9.5 p 0.042). Conclusions: The incidence rate estimated was inferior to that previously reported. Three-month mortality in patients with CPA was high, with older age and SAIA subtype being the variable independent predictors of a worse prognosis.

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.

Background: The annual mortality of patients with untreated chronic thromboembolism pulmonary hypertension (CTEPH) is approximately 50% unless a timely diagnosis is followed by adequate treatment. In pulmonary embolism (PE) survivors with functional limitation the diagnostic work-up starts with echocardiography. It is followed by lung scintigraphy and right heart catheterization. However, noninvasive test providing diagnostic clues to CTEPH, or ascertain this diagnosis as very unlikely, would be extremely useful since the majority of post PE functional limitations is caused by deconditioning. Methods: Patients after acute PE underwent a structured clinical evaluation with electrocardiogram, routine laboratory tests including NT-proBNP and echocardiography. The aim of study was to verify whether the parameters from echocardiographic or perhaps electrocardiographic examination and NT-proBNP concentration best determine the risk of CTEPH. Results: A total (n = 261, male n = 123) patients after PE were included into the study, in group of 155 patients (59.4%) with reported functional impairment 13 patients (8.4%) had CTEPH and 7 PE survivors had chronic thromboembolic pulmonary disease (CTEPD) (4,5%). Echo parameters differed significantly between CTEPH/CTEPD cases and other symptomatic PE survivors. Patients with CTEPH/CTEPD had also higher level of NT-proBNP (p = 0.022) but concentration of NT-proBNP above 125 pg/ml did not differentiate patients with CTEPH/CTEPD (p>0.05). Additionally, proportion of patients with right bundle brunch block registered in ECG was higher in group with CTEPH/CTED (23.5% vs. 5.8%, p = 0.034) but there were no differences between other ECG characteristics of right ventricle overload. Conclusion: Screening for CTEPH/CTEPD should be performed in patients with reduced exercise tolerance compared to pre PE period, It is not effective in asymptomatic PE survivors. Patients with CTEPH/CTED had predominantly abnormalities indicatingchronic thromboembolism in the echocardiographic assessment. NT-proBNP and electrocardiographic characteristics of right ventricle overload proved to be insufficient in predicting CTEPH/CTEPD development.

Background: Knowledge of the anatomy of pulmonary arteries is essential in many invasive procedures concerning pulmonary circulation. In the diagnosis and treatment of chronic thromboembolic pulmonary hypertension (CTEPH), two-dimensional (2D) pulmonary angiography is used. Recognizing the topographic course of the pulmonary arteries and understanding the status in three-dimensions (3D) is paramount. The study aimed to evaluate and describe the branching variant of pulmonary arteries in a single case, as well as morphological parameters of the segmental arteries, like length, diameter and branching angles. Methods: One pair of embalmed human cadaver lungs were dissected by scalpel, surgical forceps and measured until the subsegmental arteries. Results: The diameters (ranging from 3.04 to 9.29 mm) and lengths (ranging from 9.09 to 53.91 mm) of the pulmonary segmental arteries varied. The proximal branching angles were wide and close to perpendicular, while distally, the angles between the segmental and subsegmental arteries were narrower (30-45°). Upon evaluating the branching, rare variations were identified and delineated, notably in the lower lobes of both lungs. Conclusions: Utilizing knowledge and data in clinical settings is instrumental for effectively diagnosing and treating CTEPH. Further research is required to explore the complications in invasive procedures related to various anatomical variations.

: We report the case of a 2-year-old Norwegian Forest cat diagnosed with pulmonary edema and pulmonary hypertension (PH) secondary to cor triatriatum sinister, who showed improved breathing following furosemide treatment. Sildenafil was prescribed post-discharge without diuretic. Thirty-eight days later, no abnormalities were observed in the septum or accessory chamber of the left atrium; however, continuous mosaic blood flow (maximum velocity, 3.14 m/s) was observed in two enlarged pulmonary veins. Pulmonary artery enlargement (main pulmonary artery to thoracic aorta ratio: 1.90), pulmonary vein stenosis (PVS), and diffuse bilateral ground-glass lung opacities were observed using computed tomography. PH with partial PVS and pulmonary parenchymal disease was diagnosed. The cat was further treated with furosemide with no clinical symptoms, but succumbed to acute dyspnea 51 days after the first visit. PH, despite partial PVS, may also be associated with concurrent parenchymal lung disease. Sildenafil can worsen pulmonary edema in the affected lung but did not in this case.

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.

:. Background and Objectives: Pulmonary embolism, PE, incidence had been increasing in the last ten years. Computed thoracic pulmonary angiography, CTPA, had a major role in confirming PE di-agnosis.The main purpose of the study was to establish the prognostic value of a CTPA parameter: pulmonary artery obstruction index, PAOI, for PE risk assessment . A second objective of the re-search was to investigate the predictive accuracy of biomarkers (D-dimer, and cardiac Troponin T, c-TnT ), and PAOI, in 7-day mortality. The third objective of the study was the relationship between PAOI, and these biomarkers, in different etiologies of PE. Materials and Methods: The study com-prised 109 patients with PE, hospitalized, and treated between February 2021, and August 2022. They had different etiologies: deep vein thrombosis, DVT; persistent atrial fibrillation, AF; chronic obstructive pulmonary disease, COPD, exacerbation; Covid; and cancers. The investigations were the following: clinical examination; D-dimer testing, as a mandatory method for PE suspicion( values ≥ 500 µg/L were highly suggestive for PE); c-TnT , as a marker of myocardial injury(values ≥ 14 ng/L were abnormal); CTPA, with right ventricle dysfunction, RVD, signs, and PAOI. Treat-ments were according to PE risk: systemic thrombolysis (in high risk , and hemodynamic instability); low weight molecular heparins, LWMH, after systemic thrombolysis, or in high risk PE, with he-modynamic stability; direct oral anticoagulants, DOAC (in low, and intermediate risk). Results: The relationship PAOI- D-dimer, and PAOI- c-TnT, had very strong statistical correlation, for the entire sample, and for DVT, AF, COPD, Covid subgroups ( Rho = 0.815-0.982). PAOI had a high predic-tive accuracy for intermediate , and high risk together (area under curve, AUC=0.948), and high risk PE (AUC= 0.993). For 7-day mortality, D-dimer , and c-TnT had high predictive accura-cy(AUC=0.921, and 0.979). PAOI had statistical significance for 7-day mortality in Covid (p=0.045), and cancer (p=0.038) patients. Conclusions: PAOI was an important tool for PE risk as-sessment. D-dimer , and c-TnT were valuable predictors, for 7-day mortality in PE. PAOI, and D-dimer; PAOI, and c-TnT were strongly correlated, for the entire PE sample, and for DVT, AF, COPD, and Covid patients.

This review brings together the current knowledge regarding the risk factors, and the clinical, radiologic and histological features of both post-COVID-19 interstitial pul-monary fibrosis (PCPF) and Idiopathic Pulmonary Fibrosis (IPF) with a particular fo-cus on describing the similarities and the disparities between the fibrotic changes in these two diseases. It is important to highlight the common points of PCPF and IPF to observe if they are some targetable changes to improve patient outcomes. The litera-ture review was performed using numerous databases to identify relevant articles published in English through October 2022. This review would help clinicians, pathologists and researchers to make an accurate diagnosis, which can be useful in identifying the group of patients who can be selected for antifibrotic therapies, and future therapeutic perspectives.

Background/Objectives: Pulmonary diseases are common in patients with thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA). Although high prevalences of chronic obstructive pulmonary disease and lung cancer (LC) are known, the prevalence of these and other pulmonary diseases regarding their relation to outcome of TAA and/or AAA are not determined. Methods: Pulmonary diseases present at aortic aneurysm (AA) diagnosis and follow-up periods and cause of death of 952 patients with TAA, AAA, or TAA+AAA (including thoracoabdominal AA) treated at our institution in Japan, were retrospectively analyzed. Cox regression analysis was used to investigate potential risk factors of mortality. Results: Mean patient age was 72.4 years, and median follow-up was 4.92 years. At diagnosis, 528 (55.5%) patients had pulmonary diseases, including emphysema without interstitial lung disease (ILD) or LC, LC, idiopathic pulmonary fibrosis (IPF) without LC, non-IPF ILD without LC, and interstitial lung abnormalities (ILAs) without LC in 250, 85, 65, 15, and 58 patients, respectively. During follow-up, LC and acute exacerbation (AE) of IPF developed in 50 and 12 patients, respectively. In 213 patients who died, there were 45 (21.1%) aortic disease-related deaths. Other causes of death included LC (27.7%), cardiovascular event (9.4%), pneumonia (5.6%), and interstitial lung disease (4.7%). In a multivariate Cox regression hazard model, age, larger maximum aneurysm diameter, and coexisting LC, IPF, or concomitant cancer were associated with poor prognosis. Conclusions: In patients with AA, not only age and aneurysm diameter but also coexisting LC and IPF were prognostic factors for mortality.

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

Background: The diagnosis of Pulmonary Embolism (PE) is based on the application of a priori probability scales such as the Wells scale or PERC criteria. However, the clinical heterogeneity of this pathology results in the absence of a target population to apply these algorithms. Moreover, these scales do not consider the possible influence of the presence of an objective alternative diagnosis to PE, complicating its clinical assessment and possibly leading to an increase in unnecessary testing or missed diagnoses. Objective: The aim of this study is to evaluate the discrimination capacity of clinical objective factors with a high negative predictive value for PE, compared to PERC in terms of reducing unnecessary testing across different risk strata of the Wells scale. Materials and Methods: This was a single-center retrospective cohort study, including patients who underwent chest CT angiography to rule out PE at a University Hospital between 2008 and 2017, considering the presence of PE as the study outcome. The study collected demographic data, comorbidities, and clinical presentation data. The presence of objective criteria for pneumonia, heart failure, exacerbation of COPD, or the use of anticoagulation in non-oncological patients was considered a priori criteria with a high negative predictive value. Results: The analyses were performed on a cohort of 399 patients with an average age of 65 years and 53% females. A total of 139 patients were diagnosed with PE by CT angiography. The presence of factors with a high NPV showed a sensitivity and NPV of 100% in low-risk patients according to Wells, with sensitivity dropping below 50% in other populations. The association of these factors in the PERC plus criteria would allow a reduction of up to 34% in CT angiographies in patients with low risk according to the Wells scale. Conclusions: The combination of risk stratification of the Wells scale and PERC plus criteria allows an absolute reduction of 34.3% in the performance of CT angiographies in patients classified as low risk with a sensitivity and a negative predictive value of 100%. The preexistence of an alternative diagnosis does not allow ruling out PE in patients with intermediate or high risk according to the Wells scale.

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.

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.

Studies have shown increased nontuberculous mycobacterial pulmonary disease (NTM) incidence with inhaled corticosteroid (ICS) use in patients with chronic respiratory diseases; however, this association in chronic obstructive pulmonary disease (COPD) remains insufficiently studied. Using a nationwide population-based database of the Korean National Health Insurance Service, newly diagnosed COPD patients (20052018) treated with inhaled bronchodilators were selected. An NTM case was defined by the presence of the first diagnostic code following inhaled bronchodilator use. Results indicated that ICS users did not have an increased risk of NTM disease compared to non-ICS users (hazard ratio [HR], 1.121; 95% confidence interval [CI], 0.9501.323; p = 0.1755). The highest quartile of the cumulative ICS dose was associated with the development of NTM (1.200, 0.9501.323, p = 0.0497). Medium (1.229, 1.0081.499, p = 0.0410) and high daily doses of ICS (1.637, 1.2412.160, p = 0.0005) were associated with an increased risk of NTM disease. There was no difference in the risk of NTM according to ICS type. ICS use may not increase the risk of developing NTM disease in patients with COPD. However, physicians should weigh the potential benefits and risks of ICS, especially when using high doses and prolonged durations.

Hantavirus cardiopulmonary syndrome (HCPS) is characterized by capillary leak, pulmonary edema (PE) and shock that leads to death in up to 40% of patients. Treatment is supportive, including mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO). Hemodynamic monitoring is critical to titrate therapy and to decide ECMO support. Transpulmonary thermodilution (TPTD) provides hemodynamic and PE data that has not been systematically used to understand HCPS pathophysiology. We identified 11 HCPS patients monitored with TPTD; 5 on MV, 3 on ECMO. We analyzed 133 measurements to describe the hemodynamic pattern and its association to PE. The main findings were reduced stroke volume, global ejection fraction (GEF) and preload parameters associated to increased extravascular lung water and pulmonary vascular permeability compatible with hypovolemia, myocardial dysfunction and increased permeability PE. Lung water correlated positively with heart rate (HR, r=0.20) and negatively with mean arterial pressure (r=-0.27) and GEF (r=-0.36), suggesting that PE is linked to hemodynamic impairment. Pulmonary vascular permeability correlated positively with HR (r=0.31) and negatively with cardiac index (r=-0.49), end-diastolic volume (r=-0.48) and GEF (r=-0.40), suggesting that capillary leak contributes to hypovolemia and systolic dysfunction. In conclusion, TPTD data suggests that in HCPS patients, increased permeability leads to PE, hypovolemia and circulatory impairment.

Pulmonary hypertension (PH) is a severe and chronic disease characterized by increased pulmonary vascular resistance and remodeling often precipitating right-sided heart dysfunction and death. Although the condition is progressive and incurable, current therapies for the disease focus on multiple different drugs and general supportive therapies to manage symptoms and prolong survival, ranging from medications more specific to pulmonary arterial hypertension (PAH) to exercise training. Moreover, there are multiple studies exploring novel experimental drugs and therapies including unique neurostimulation, to help better manage the disease. Here we provide a narrative review focusing on current PH treatments that target multiple underlying biochemical mechanisms, including but not limited to imbalances in vasoconstrictor-vasodilator and autonomic nervous system function, inflammation, and bone morphogenic protein (BMP) signaling. We also focus on the potential of novel therapies for managing PH, focusing on multiple types of neu-rostimulation including acupuncture. Lastly, we also touch upon the disease’s different subgroups, clinical presentations and prognosis, diagnostics, demographics, and cost.

Pulmonary artery stenosis represents a group of disorders involving main, branch or peripheral pulmonary arteries resulting either in pain, dyspnea, hemoptysis or even no symptoms. Early diagnosis and timely intervention are crucial for reducing mortality, while timely diagnosis is challenging due to the nonspecific symptoms. Computed tomography pulmonary angiography (CTPA) is useful in the diagnosis because it can provide more details about the abnormal changes in the lumen, vessel wall and adjacent mediastinal structures. Congenital and acquired pulmonary artery anomalies have some characteristics on CTPA, which can be useful for differential diagnosis. Awareness of these conditions and is important for the radiologists. This pictorial review provides an overview of CTPA imaging features of pulmonary artery stenosis.

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.

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.

This case report demonstrates the rare but potentially serious complication of pulmonary vein stenosis (PVS) diagnosed several years after radiofrequency ablation for atrial fibrillation. Pulmonary vein stenosis can remain asymptomatic until significant occlusion occurs, after which it can present with a variety of symptoms, mimicking numerous cardiovascular and pulmonary pathologies. Early diagnosis and treatment rely on consistent follow-up using appropriate diagnostic imaging modalities, which are paramount in preventing severe complications.

Despite offering several potential benefits over standard prosthetic aortic valve replacement, the use of the pulmonary autograft has been limited to date, due to concerns over the risk of pulmonary autograft expansion and the need for reintervention. Several techniques using materials with biomimetic potential have been developed to reduce this complication. The incidence, risk factors and pathophysiology of pulmonary autograft dilatation are discussed in this article. This seminar will provide an overview of the techniques of external pulmonary autograft support and their advantages and limitations. It also considers future directions for further investigation and future clinical applications of external pulmonary autograft support. Dilatation of the autograft is more likely to occur in patients with aortic regurgitation and a dilated aortic annulus. External scaffolding may prevent autograft stretching and expansion in these specific cases. However, from a biomimetic point of view, any permanent scaffold potentially restricts the movement of the autograft root. This reduces some of the benefits associated with the use of autologous tissue, which is the priority of the Ross procedure. To address this issue, several bioresorbable matrix could be used to support the root during its initial adaptive phase. Control of blood pressure with aggressive therapy is the first line to avoid this problem in the first year after pulmonary autograft implantation, together with support of the annular and sino-tubular junction in some selected cases. This is the best way to maintain stable autograft root dimensions while preserving root dynamics. However, to determine the efficacy of this combined external support and best medical management, it is important to perform regular imaging and clinical follow-up.

Idiopathic pulmonary fibrosis, a chronic and fatal condition with no effective cure, is a challenging disease within the group of interstitial lung diseases. The pathogenic mechanisms of this disease are still not fully understood. In this context, the research on miRNAs, which are small non-coding RNAs that regulate messenger RNAs, is of utmost importance. These miRNAs, released into the circulation outside the cell through exosomes, play a crucial role in the pathogenic pathways and mechanisms involved in IPF development. The analysis of miRNAs in the serum/plasma of IPF patients has opened up new possibilities in the search for biomarkers. This review focuses on circulating miRNAs validated by real-time PCR in IPF and the evidence reported about the pulmonary fibrotic process.

Lymphangioleiomyomatosis (LAM) is a cystic pulmonary disorder that has been known to primarily affect women of childbearing age. The disorder can develop with mutations in the tuberous sclerosis (TSC) genes TSC1 & TSC2 but may arise by other irregular cases in the lack of these mutations. LAM can manifest in a wide variety of ways and generally compounded in symptoms of other lung disorders such as bronchitis, emphysema, & asthma. However, due to lack of effective diagnostic methods, biomarkers of LAM leading to a treatment for the disorder are currently unmet. Using integrative dating analytics and bioinformatics approaches; this study used publicly available microarray data to identify biomarkers in LAM. The results showed important differential expressed genes (DEGs) including: CDH2, CXCL6, ANXA10, MFAP5, RPS4Y1, DCBLD2, PAPPA, TFPI2, SERPINE1, LOX, MYH11, RGS1, SEPP1, TMOD1, ID1, SFTPB, CDH1, HTR2B, OGN, and IGLC1. Furthermore, gene – network and gene ontology (GO) analysis were conducted to show the importance of these genes from a molecular understanding. Taken together, the results revealed could serve as diagnostic and prognostic biomarkers with LAM patients.

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.

Multi-walled carbon nanotubes are engineered nanomaterials (ENMs) that have a fiber-like structure which may be a concern for the development of cellular senescence. Premature senes-cence, a state of irreversible cell cycle arrest, is implicated in the pathogenesis of chronic lung dis-eases such as pulmonary fibrosis (PF). However, the crosstalk between downstream pathways mediating fibrotic and senescent responses of MWCNTs is not well defined. Here, we exposed human bronchial epithelial cells (BEAS2B) to MWCNTs for up to 72 hours and demonstrate that MWCNTs increase reactive oxygen species production (ROS) accompanied by inhibition of cell growth and proliferation. In addition, exposure resulted in the increase of p21 protein and senes-cence associated β-galactosidase (SA β-gal) activity. We also determined that co-exposure with the cytokine, transforming growth factor-β (TGF-β) exacerbated cellular senescence indicated by increased protein levels of p21, p16, and γH2A.X Furthermore, the production of fibronectin and plasminogen activator inhibitor (PAI-1) was significantly elevated with the co-exposure compared to MWCNTs or TGF-β alone. Together, this suggests that the senescence potential of MWCNTs may be enhanced by pro-fibrotic mediators in the surrounding microenvironment.

Background and Objectives: Pulmonary Hypertension (PH) is a clinical condition with high mortality rates, particularly in patients over 65. Current guidelines recommend assessing the Probability of Pulmonary Hypertension (PHP) using advanced echocardiography, before pro-ceeding to right heart catheterization. This study proposes using the common femoral vein (CFV), an accessible vein that reflects right atrial pressure, as an alternative method to assess the like-lihood of severe PHP. Materials and Methods: This prospective observational study included 175 emergency patients from three hospitals. Ultrasound assessed the Pulsed Wave Doppler (PW-Doppler) morphology of the CFV. This diagnostic yield for high PHP was evaluated along-side traditional ultrasound parameters (right-to-left ventricular basal diameter ratio greater than 1 (RV>LV), septal flattening, right ventricular outflow acceleration time of less than 105 ms and/or mesosystolic notching, pulmonary artery diameter greater than the aortic root diameter or over 25 mm, early pulmonary regurgitation maximum velocity >2.2 m/s, TAPSE/PASP less than 0.55, in-ferior vena cava (IVC) diameter over 21 mm with decreased inspiratory collapse, and right atrial (RA) area over 18 cm²). Results: The CFV's PW-Doppler cardiac pattern correlated strongly with high PHP, showing a sensitivity (Sn) of 72% and a specificity (Sp) of 96%. RA dilation and TAPSE/PASP < 0.55 also played significant diagnostic roles. Conclusions: The CFV's PW-Doppler cardiac pattern is an effective indicator of high PHP, allowing reliable exclusion of this condition when absent. This approach could simplify initial PHP evaluation in emergency settings or where echocardiographic resources are limited.

The standard treatment for early-stage lung cancer is complete tumor excision by limited resection of the lung. Pre-operative localization is used before video-assisted thoracoscopic surgery (VATS) to improve the accuracy of pulmonary nodule excision. However, lung atelectasis and hypoxia resulting from controlling apnea during the localization procedure may affect the localization accuracy. Pre-procedural pulmonary recruitment may improve respiratory mechanics and oxygenation during localization. In this study, we investigated the potential benefits of pre-localization pulmonary recruitment prior to pulmonary ground-glass nodule localization in a hybrid operating room. We hypothesized that pre-localization pulmonary recruitment would increase localization accuracy, improve oxygenation, and prevent the need for re-inflation during the localization procedure. We retrospectively enrolled patients with multiple pulmonary nodule localizations before surgical intervention in our hybrid operating room. We compared localization accuracies between patients who had undergone pre-procedure pulmonary recruitment and patients who had not. Saturation, re-inflation rate, apnea time, procedure-related pneumothorax, and procedure time were also recorded as secondary outcomes. Patients who had undergone pre-procedure recruitment had better saturation, shorter procedure time, and higher localization accuracy. The pre-procedure pulmonary recruitment maneuver was effective in increasing regional lung ventilation, leading to improved oxygenation and localization accuracy.

In the last decade, the role of Computed Tomography Pulmonary Angiography (CTPA) in diagnosing and managing pulmonary embolism (PE) has significantly evolved. Once a purely diagnostic tool, CTPA now plays a crucial role in initial emergency department assessments and treatment planning tailored to the patient’s condition. Advances in CTPA technology, including image quality enhancements and artificial intelligence (AI) applications, necessitate a reassessment of its current utility. This narrative review updates on new CTPA tools and techniques and focuses on data extraction challenges in emergency settings. CTPA studies, often conducted with multidetector scanners, provide essential information for risk stratification and treatment planning. The quantification of thrombotic burden using CTPA is vital for predicting mortality and determining appropriate treatments. Classical scoring systems, such as those developed by Qanadli, Mastora, and Ghanima, convert CTPA findings into quantifiable data to assist clinical decision-making. Despite CTPA not being a standard mortality predictor, significant research suggests including CTPA data, especially RV dysfunction indicators, for prognostic purposes. Recent studies highlight automated techniques for quantifying pulmonary perfusion and thrombus composition, enhancing the accuracy of PE severity assessment. The integration of AI in CTPA, particularly through deep learning algorithms, shows promise in automating thrombus load assessment and improving risk stratification. The continuous development of imaging techniques positions CTPA as a potential tool for comprehensive PE management, aiding in diagnosis, prognosis, and treatment decisions.

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.

Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with airways inflammation and lung parenchyma fibrosis. The primary goals of COPD treatment are to re-duce symptoms and risk of exacerbations, therefore pulmonary rehabilitation is considered the key component of managing COPD patients. Oxidative airway damage, inflammation and re-duction of endogenous antioxidant enzymes are known to play a crucial role in the pathogenesis of COPD. Natural antioxidants have also recently been considered as they play an important role in metabolism, DNA repair and fighting the effects of oxidative stress. In this paper we evaluated the response of 105 elderly COPD patients to pulmonary rehabilitation (PR), based on high or low vegetable consumption, by analyzing clinical parameters and biological measure-ments at baseline and after completion of the three weeks PR. We found that high vegetable in-take in normal diet, without any specific intervention, can increase the probability to success-fully respond to rehabilitation (65.4% of responders ate vegetables daily vs. 40.0% of Non-Responders, p=0.033). Three weeks of pulmonary rehabilitation are probably too short to reveal a reduction of the oxidative stress and DNA damage, but are enough to show an im-provement in the patient's inflammatory state.

Patients with chronic obstructive pulmonary disease (COPD) often require frequent hospitalization due to worsening symptoms. Preventing prolonged hospital stay and readmission becomes a challenge for healthcare professionals treating patients with COPD. Although the integration of health and social care supports greater collaboration and enhanced patient care, organizational structure and poor leadership may hinder the implementation of patient-oriented goals. This paper presents a case of a 64-year-old chronic smoker with severe COPD who was to be discharged on long-term oxygen therapy (LTOT). It further highlights the healthcare decisions made to ensure the patient’s safety at home and further provides a long-lasting solution to the existing medical and social needs. The goal was accomplished through a discharge plan that reflects multidisciplinary working, efficient leadership, and change management using Havelock’s theory. While COPD is characterized by frequent exacerbation and hospital readmission, it was emphasized that most failed discharges could be attributed to bureaucratic organizational workflow which might not be in the patient’s best interest. It was further demonstrated that healthcare professionals are likely to miss the window of opportunity to apply innovative and long-lasting solutions to the patient’s health condition in an attempt to remedy the immediate symptoms of COPD

Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with airways inflammation and lung parenchyma fibrosis. The primary goals of COPD treatment are to re-duce symptoms and risk of exacerbations, therefore pulmonary rehabilitation is considered the key component of managing COPD patients. Oxidative airway damage, inflammation and re-duction of endogenous antioxidant enzymes are known to play a crucial role in the pathogenesis of COPD. Natural antioxidants have also recently been considered as they play an important role in metabolism, DNA repair and fighting the effects of oxidative stress. In this paper we evaluated the response of 105 elderly COPD patients to pulmonary rehabilitation (PR), based on high or low vegetable consumption, by analyzing clinical parameters and biological measure-ments at baseline and after completion of the three weeks PR. We found that high vegetable in-take in normal diet, without any specific intervention, can increase the probability to success-fully respond to rehabilitation (65.4% of responders ate vegetables daily vs. 40.0% of Non-Responders, p=0.033). Three weeks of pulmonary rehabilitation are probably too short to reveal a reduction of the oxidative stress and DNA damage, but are enough to show an im-provement in the patient's inflammatory state.

Background: Pulmonary embolism (PE) is a common multifactorial disease, but high-risk PE s a life-threatening condition associated with high mortality and morbidity and a heavy prognostic burden. Systemic thrombolysis is the first-line treatment approach for severe high-risk PE, but only few agents are indicated for use by international guidelines. Tenecteplase, a thrombolytic agent, is proven to reduce mortality and right ventricle dysfunction in high-risk PE, but is not approved yet by major recommendations. Aim: We present a series of cases of high-risk PE treated with Tenecteplase, with satisfying hemodynamic and clinical outcomes. Our goal is to encourage the usage of Tenecteplase with secure safety and efficacy in situations of unavailability of guidelines-approved fibrinolytic agents. Cases : Patients were included from January 2022 to January 2024. We report 3 cases of patients with high-risk PE treated with Tenecteplase where rtPA and other second-generations agents were not available. Clinical, biological and imaging data were detailed for each case. Conclusion: Tenecteplase was effective in our patients, without bleeding complications, and should be suggested in settings of unavailability of first-line recommended agents.

D-dimer testing in combination with clinical assessment is commonly used to diagnose suspected DVT and pulmonary embolism. However, as D-dimer levels are physiologically higher in elderly patients, this test loses clinical specificity in the setting of geriatric patients. The aim of our study was to investigate the changes in D-dimer levels with age and the specificity of the D-dimer test in the diagnosis of pulmonary embolism. 1617 elderly patients consecutively admitted to the Geriatric Emergency Care Department of the INRCA-IRCCS hospital between January 2013 and February 2014 and for whom D-dimer results were available were included. The D-dimer immunoturbidimetric assay was performed on a cs-2100i Sysmex Siemens using a conventional cut-off level of 500 µg/L. The median D-dimer level was 1200 [550-2990] µg/L FEU, and the percentage of patients with D-dimer levels below the conventional cut-off was only 22.1%. As expected, there was a significant age-related increase in D-dimer, even when sex was considered, and a significant decrease in the specificity of D-dimer assay with age. The most established use of D-dimer testing is in the diagnosis of deep vein thrombosis or pulmonary embolism. Our study confirms the need for an age-adjusted cut-off for D-dimer testing in geriatric patients.

(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.

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.

Pulmonary fibrosis is a chronic, progressive and fatal disease of the interstitial lung， there still lack of efficient therapy to reverse the prognosis of patients currently. In this study, a fucoidan from Costaria costata was isolated and its anti-idiopathic fibrosis activity was investigated both in vitro and in vivo. The chemical composition analysis results show that Costaria costata polysaccharide (CCP) is consisting of galactose and fucose as the main monosaccharides with a sulfate group content of 18.54%. The results found that CCP could resist TGF-β1-induced epithelial-mesenchymal transition (EMT) in A549 cells by inhibiting the TGF-β/Smad and PI3K/AKT/mTOR signaling pathways. In vivo data found that CCP treatment alleviated bleomycin (BLM)-stimulated fibrosis and inflammation in mice lung tissue. This study suggests that CCP could protect the lung from fibrosis by relieving the EMT process and inflammation in lung cells.

Pulmonary vein stenosis (PVS) causes a rare type of Pulmonary Hypertension (PH), by impacting the flow and pressure within the pulmonary vasculature resulting in endothelial dysfunction and metabolic changes. A prudent line of treatment in this type of PH would be targeted therapy in order to relieve the pressure and reverse the flow related changes. We used a swine model in order to mimic PH post PVS using pulmonary vein banding (PVB) of the lower lobes for 12 weeks to mimic the hemodynamic profile associated with PH and investigate the molecular alterations that provide an impetus for development of PH. Our current study aimed to employ unbiased proteomic and metabolomic analyses on both the upper and lower lobes of the swine lung to identify the regions with metabolic alterations. We detected changes in the upper lobes for the PVB animals mainly pertaining to fatty acid metabolism, ROS signaling and extracellular matrix remodeling, and small albeit significant changes in the lower lobes for purine metabolism.

The quarantine imposed as the response to the COVID 19 pandemic has been related to an increase in cases of thromboembolism in Non-COVID19 patients .We report the case of a patient with pulmonary thromboembolism without usual triggering causes during the quarantine period, related to a previously undiagnosed hypercoagulable condition.

Background and Objective: Type 2 diabetes mellitus (DM2) and breast cancer (BC) are diseases of high prevalence worldwide. Both alter lung function separately. So suffering both tables would increase this decrease in lung function. The objetive was to determine the effects of DM2 and BC on ventilation volumes and pressures in adult women. Material and Methods: Forty-two women patients were recruited, of whom 40 were accepted under the exclusion criteria. They were divided into four groups: control group (CG), DM2, BC and DM2+BC. Body plethysmography was used to measure forced vital capacity, lung volumes, airway resistance and muscle pressures. Finally the normality of the data was determined using Student's t test or the Mann-Whitney U test; the threshold of significance was p<0.05. Results: No significant differences were observed in the anthropometric variables between the control group and the other groups. The ventilation flows showed no significant differences, while the lung volumes presented significant differences in the inspiratory capacity (IC) variables (p<0,002). Maximum inspiratory and expiratory pressures (MIP-MEP) also presented significant diminution (p<0,001; p<0,041, respectively). Conclusions: From the results obtained we can conclude that the combination of type 2 diabetes mellitus with breast cancer caused a diminution in ventilation volumes and pressures, specifically in IC, MIP and MEP.

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.

Background: Exercise rehabilitation programs are important for long-term health and wellbeing among people with cardiac and pulmonary disease. De-spite this, many people struggle to maintain their physical activity once reha-bilitation ends. This repeated measures study tracked changes in physical ac-tivity behaviour and motivation during and after completing a communi-ty-based exercise rehabilitation program. Methods: Cardiac and pulmonary exercise rehabilitation patients (N=31), com-pleted six once-monthly measures of physical activity (MET·min), self-determined motivation, intention, and habit strength for rehabilitation ex-ercise (within rehabilitation sessions) and lifestyle physical activity (outside of rehabilitation sessions). Linear regression and random effects models with es-timated marginal means were used to test for associations between physical activity motivation and behaviour and change during and post-rehabilitation. Results: Overall physical activity decreased after rehabilitation (823 MET·min) despite patients becoming more self-determined for lifestyle physical activity during rehabilitation. More self-determined motivation, stronger intentions, and stronger habits were associated with more lifestyle physical activity be-haviour. However, none of these motivation variables were significantly asso-ciated with rehabilitation exercise behaviour. Conclusions: Among community-based cardiac and pulmonary rehabilitation patients, physical activity levels decreased following exercise rehabilitation programs. The findings revealed clear distinctions in the motivation of reha-bilitation exercise compared to lifestyle physical activity. Exercise rehabilitation programs might improve the longevity of outcomes by integrating approaches to enhance lifestyle physical activity beyond the clinic.

Introduction: Pulmonary hypertension (PH) in systemic sclerosis (SSc) can be caused by different pathophysiological mechanisms, including precapillary PH (pulmonary arterial hypertension), post-capillary PH (secondary to left heart diastolic dysfunction), or combined pre- and post-capillary PH. To unmask occult post-capillary PH, fluid loading with saline during right heart catheterization (RHC) is recommended. In the present study, we investigated the response to fluid challenge test (FCT) in patients with SSc who were referred for RHC due to their high likelihood of PH on screening echocardiography. Methods: Demographic data, clinical characteristics, echocardiographic and RHC data, and cardiac magnetic resonance imaging (CMR) results were obtained from the patients' hospital records or by contacting their rheumatologist. A positive FCT was defined as an increase in pulmonary capillary wedge pressure (PCWP) to more than18 mmHg with rapid saline infusion. Patients were followed for a median (IQR) of 15 (7-20) months. Results: Of the total 98 scleroderma patients 34 patients (29 female) were included. The mean age (SD) was 50.6(8.2) years. Baseline RHC data showed that 20 patients had no PH and 14 patients had mild precapillary PH (mPAH). Ten patients (50%) of the patients with no PH and 10 patients (71.4%) with mPAH had a significant increase in PCWP after a fluid loading. There was no statistically significant difference between the patients with positive and negative FCT in terms of the presence of LGE/inflammation on CMR examination. During follow-up, 3 patients died. Mortality was due to SSc-related complications in two patients. Conclusion: This study provides preliminary evidence that FCT may be a useful adjunct to baseline RHC testing to identify SSc patients with latent postcapillary PH. Further studies are needed to confirm these results and determine the optimal role of the fluid challenge test in the clinical management of SSc patients with suspected PH.

(1) Background: LUS has emerged as a simple, rapid and non-invasive method for the dynamic assessment of pulmonary congestion, a major prognostic factor and a therapeutic target in AHF. (2) Methods: In the single-center prospective observational study, 42 patients hospitalized for AHF in the post-emergency polyvalent medicine department of CHU Grenoble were successively included between May 2021 and July 2022. Clinical examination, LUS and electrolyte panel results were collected daily. Vital status was assessed 30 days after the last LUS. The primary endpoint was the evolution of the number of B-lines according to the dose of diuretic administered ; (3) Results: We performed 188 LUS. Our patients were elderly (85.8 [SD 8.1]) and comorbid. The median number of B-lines decreased from 17 at admission to 7 in the middle of the hospital stay, then stagnated until discharge. Simultaneously, the median dose of diuretics, initially stable at a maximum of 40 mg/d IV, decreased to 20mg/d IV by the end of hospital stay. Patients with CKD had a higher mean number of B-lines at entry (24.2 [SD 11.6]) compared to those without CKD (8.2 [SD 8.8]). However, the evolution of B-lines number was independent of creatinine levels. 30-day all-causes mortality was significantly related to the number of B-lines at discharge (15.2 [SD 10.1] in deceased patients versus 3.9 [SD 5.4] in living patients, p

This is a single center retrospective study to assess safety and tolerability of continuous inhaled iloprost use as rescue therapy for refractory pulmonary hypertension (PH) in critically ill neonates and infants. Retrospective chart review was performed on 58 infants and data was collected at baseline, 1, 6, 12, 24, 48, and 72 hours of iloprost initiation. Primary outcomes were change in heart rate (HR), fraction of inspired oxygen (FiO2), mean airway pressures (MAP), blood pressure (BP) and oxygenation index (OI). Secondary outcomes were need for extracorporeal membrane oxygenation (ECMO) and death. 51 patients treated for > 6 hours were analyzed in 2 age groups, neonate (≤28 days: n=32) and infant (29-365 days: n=19). FiO2 (p

Pulmonary Embolism (PE) is the obstruction of blood arteries in the lungs by a blood clot. The mortality risk for PE is approximately 30%. Detecting pulmonary embolism in the segmental arteries of the lung is more challenging than in the main arteries and is very prone to being missed. A computer-based approach was created in this work to automatically identify pulmonary embolism in the segmental arteries using computed tomography images. The system's infrastructure includes an enhanced Mask R-CNN deep neural network that has been trained with images containing PE. The network accurately identifies the location of the pulmonary embolism on the computed tomography picture and successfully extracts its borders. The investigation was conducted by generating a local dataset. The study's performance was evaluated using pulmonary embolisms identified manually by the expert radiologist. The sensitivity, specificity, accuracy, dice coefficient, and Jaccard index values for 2130 pictures were 96.4%, 93.5%, 96.1%, 0.96, and 0.90, respectively. The improved Mask R-CNN model has demonstrated superior performance when compared to the traditional Mask R-CNN and U-Net models. This high-performance technology is designed to identify pulmonary embolism and will aid professionals in assessing the size of the embolism.

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.

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.

Despite the advancements in evidence-based medicine, many hospitals still maintain high rates of patients undergoing prolonged preoperative fasting. The goal of this study is to determine the prevalence of prolonged fasting time among patients undergoing elective surgeries at a Brazilian university hospital and its associations with clinical and sociodemographic variables. This cross-sectional study was conducted between May and November 2019 and included patients of all ages undergoing elective surgeries. Out of the 293 patients analyzed, 64.2% were male, with ages ranging from 1 to 85 years, and 93.9% were classified as ASA I or II. The prevalence of preoperative fasting exceeding 8 hours was 89.4%. An average fasting time exceeding 11 hours was observed across all age groups. Patients who underwent procedures in the afternoon had an average fasting time that was 16% longer than those in the morning period (13.84 vs. 11.92, p<0.001). Surgery time (r=0.134, p<0.03) and anesthesia times (r=0.121, p<0.04) demonstrated a weak correlation with fasting time. Despite the international consensus on preoperative fasting time, our study demonstrated low adherence to current recommendations. Therefore, healthcare professionals should ensure the comprehension of fasting guidelines, and further studies should aim to identify effective solutions to mitigate prolonged fasting.

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.

The objective of this study was to analyze the effects of a pulmonary telerehabilitation (TR) program in young adults with post-COVID-19 syndrome. The information of sixteen students' medical files were analyzed and allocated to one of two groups (control=CG/experimental=EG). Twelve TR sessions were performed distantly and asynchronously at the EG patients' homes during 4-weeks. The program included diaphragmatic pattern breathing and aerobic exercises. The parameters: i) vital signs (oxygen saturation "SpO2", heart rate "HR", respiratory rate "RR" and blood pressure "BP"; ii) physical capacity “Sit-to-stand test”; iii) cardiorespiratory capacity “6-Minute Walk Test”; and iv) perceived effort "Borg scale" were assessed in both groups. The statistical analyses showed a significant decrease of RR and HR (p < 0.012) accompanied by a significant increase in SpO2 (p < 0.042), physical (p < 0.012) and respiratory (p < 0.028) capacity. The perceived effort decreased significantly in both groups (CG: p < 0.006; EG p < 0.001) only for physical but not for cardiorespiratory capacity (p < 0.106). There were no statistical changes registered in BP (p > 0.05). The current study suggests that a TR program that involves breathing and aerobics exercises is feasible and effective in treating post-COVID-19 syndrome in young patients.

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.

Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of granulomas in various organs, especially lung and mediastinal hilar lymph nodes. The clinical course and manifestations are unpredictable: spontaneous remission can occur in approximately two thirds of patients; up to 20% of patients have chronic course of the lung disease (called Ad-vanced Pulmonary Sarcoidosis) resulting in progressive loss of lung function, sometimes life-threatening that can lead to respiratory failure and death. The immunopathology mechanism leading from granuloma formation to the fibrosis in APS still remains elusive. Recent studies have provided new insights into the genetics factors and immune components involved in the clinical manifestation of the disease. In this review we aim to summarize the clinical-prognostic charac-teristics and molecular pathways which are believed to be associated with the development of APS

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.

Aim: In individuals with COVID-19, the study assessed the relationship between cytokine expression and pulmonary dysfunction. These correlations may help to suggest strategies for prevention and therapies of coronavirus disease outbreak. Patients and methods: 50 healthy participants and 100 COVID-19 patients participated in this study. COVID-19 participants were subdivided into moderate and severe groups based on the severity of their symptoms. In both patients and controls, measurements of white blood cells (WBCs), lymphocytes, C-reactive protein (CRP), interleukin (IL)-1, IL-4, IL-6, IL-18, and IL-35 were estimated. All the patients performed chest CT and CO-RADS score was assessed. Results: All patients had increased WBCs count and CRP, IL-1, IL-4, IL-6, IL-18, and IL-35 levels than healthy controls. While WBCs, CRP, and cytokines like IL-1β and IL-6 showed significantly higher levels in the severe group as compared to moderate patients, IL-4, IL-35, and IL-18 showed comparable levels in both disease groups. Furthermore, CO-RADS score was positively connected with WBCs, CRP, and cytokine levels (IL-35, IL-18, IL-6, IL-4 and IL-1β) in both groups, and lymphocyte levels in all patient groups considerably decreased as compared to the controls. CO-RADS score, also demonstrated a positive correlation with lymphocytes in the moderate COVID-19 patients, whereas in the severe patients, it demonstrated a negative correlation with lymphocytes. Conclusion: Severe COVID-19 patients, compared to individuals with moderate illness and healthy controls, patients had lower lymphocyte counts and increased CRP with greater WBCs counts. In contrast to moderate COVID-19 patients, severe COVID-19 patients had higher levels of IL-1β and IL-6, but IL-4, IL-18, and IL-35 between both illness categories at close levels. CO-RADS 5 was the most frequent category in both moderate and severe cases. Patients with a typical CO-RADS involvement had a higher CRP and white blood cell count with a lower lymphocyte count than the others. Cytokine levels were considered a surrogate markers of severe lung affection in COVID 19 patients.

Pulmonary arteriovenous malformation (PAVMs) in children are rare lesions characterized by abnormal low resistance vascular structures connecting a pulmonary artery to a pulmonary vein, resulting in an intrapulmonary right-to-left shunt. The insidious onset and variable signs&nbsp;and symptoms make diagnosis difficult, especially in children. PAVMs&nbsp; can be single or multiple, congenital or acquired, and up to 47-80% of cases are associated with hereditary hemorrhagic telangiectasia (HHT).We present the&nbsp; case of a 12-year-old female teenager referred to our center for epistaxis, headache, fatigue and weakness, with evidence of mild oxygen desaturation.&nbsp; Bubble test showed a right-to-left shunt and pulmonary angio-CT confirmed the diagnosis. Percutaneous selective embolization was performed with full recovery of normal arterial oxygen saturation. When differentiating between mild oxygen desaturation and exercise intolerance in children and adolescents, physicians should be aware of the possibility of PAVMs as a cause.&nbsp;

Background and objective: Addressing the global morbidity associated with pulmonary disease is an important need for the respiratory community. However, there is also a growing momentum to show the efficacy of new tools of diagnosis. Despite this, there are few physiotherapeutic tools that help identify and categorize these conditions. The aim was to analyze the variables of physiotherapy index of the ventilatory workload (PIVW) in people with chronic obstructive pulmonary disease (COPD) during stability and exacerbation in an outpatient setting. Material and Methods: Analyzed retrospectively of 198 clinical records were reviewed. The PIVW was extracted in stability and exacerbation of these patients with COPD. After applying the exclusion and inclusion criteria; 54 patients were classified. Through the statistical analysis of chi-square, a significant association was reported for each of the variables and the total PIVW score. Results: when analyzing the baseline with the peak of PIVW, there was a significant increase in patients COPD exacerbation. Similarly, the variables that constitute the loads, translations and supports underwent a significant increase from baseline to exacerbation (p<0.0001), except for the additional oxygen contribution, where the frequency of patients was the same in basal and exacerbation as well. Conclusions: the PIVW, serves to determine ventilatory problemas in outpatients, characterizing the specific changes of loads, translators or assistance.

Background: Systemic-to pulmonary collaterals (SPC) are common in congenital heart disease (CHD). Particularly in single ventricle anatomy and Fontan circulation, SPC can both complicate the postoperative course and lead to clinical deterioration in the long term. Treatment of SPC is controversial. The aim of our study was (1) to analyze retrospectively patients who underwent SPC embolization using Concerto™ Helix nylon-fibred microcoils (CHM) and (2) to describe the interventional technique. Methods: In this a single-center retrospective observational cohort study, we analyzed clinical and imaging data of all patients who underwent transcatheter embolization of SPC using CHM from January 2016 to December 2023. Results: In 38 consecutive patients (65.8 % male, median age 41 months, range 2 – 490), a total number of 141 CHM had been implanted into 64 SPC in 49 procedures. The majority were arterial SPC (n = 59/64) originating from the thoracic aorta or its branches; 5/64 were veno-venous SPC. Primary closure succeeded in all procedures. The CHM diameters ranged from 3 to 8 mm, with 5 mm being the most commonly used diameter. The mean coil / SPC ratio was 2.6 (range 1.3 – 5.3). CHM implantation was performed via 4 French sheaths. Both detachment and stable positioning was simple and safe. Neither non-target embolization nor coil migration occurred. One complication occurred with a minor vascular injury without clinical relevance. Conclusion: CHM are easy to use and appropriate for SPC embolization in all age groups, including infants, with a low complication rate. The coils are particularly suitable for closure of collaterals with small diameter or tortuous course.

Background: Tuberculosis (TB) manifests itself primarily in the lungs as pulmonary disease (PTB) and sometimes disseminates to other organs to cause extra-pulmonary TB, such as lymph node TB (LNTB). This study aimed to investigate the role of host genetic polymorphism in immunity related genes to find a genetic basis for such differences. Methods: Sixty-three, Single nucleotide polymorphisms (SNPs) in twenty-three, TB-immunity related genes including eleven innate immunity (SLCA11, VDR, TLR2, TLR4, TLR8, IRGM, P2RX7, LTA4H, SP110, DCSIGN and NOS2A) and twelve cytokine (TNFA, IFNG, IL2, Il12, IL18, IL1B, IL10, IL6, IL4, IL1RA, IL8 and TNFB) genes were investigated to find genetic associations in both PTB and LNTB as compared to healthy community controls. The serum cytokine levels were correlated for association with the genotypes. Results: PTB and LNTB showed differential genetic associations. The genetic variants in the cytokine genes (IFNG, IL12, IL4, TNFB and IL1RA and TLR2,4 associated with PTB susceptibility and cytokine levels but not LNTB (p &lt; 0.05). Similarly, genetic variants in LTA4H, P2RX7, DCSIGN and SP110 showed susceptibility to LNTB and not PTB. Pathway analysis showed abundance of cytokine related variants for PTB and apoptosis related variants for LNTB. Conclusions: PTB and LNTB outcomes of TB infection have a genetic component and should be considered for any future susceptibility and functional studies.

Pulmonary hypertension (PH) has a high mortality, and few treatment options. Adaptive immune mediators of PH in mice challenged with antigen/particulate matter (antigen/PM) has been the focus of our prior work. We identified key roles of type 2 and type 17 responses in C57BL/6 mice. Here, we focused on type 2 response related cytokines, specifically Resistin-like-molecule (RELM)α, a critical mediator of hypoxia-induced PH. Because of strain differences in the immune responses to type 2 stimuli, we compared C57BL/6J and BALB/c mice. A model of intraperitoneal antigen sensitization with subsequent, intranasal challenges with antigen/PM (ovalbumin and urban ambient PM2.5) or saline was used in C57BL/6 and BALB/c wild type or RELMα-/- mice. Vascular remodeling was assessed by histology, right ventricular (RV) pressure, RV weights and cytokines were quantified. Upon challenge with antigen/PM2.5, both C57BL/6 and BALB/c mice developed pulmonary vascular remodeling; these changes were more prominent in the C57BL/6 strain. Compared to wild type mice, RELMα-/- had significantly reduced pulmonary vascular remodeling in BALB/c, but not in C57BL/6 mice. RV weights, RV IL-33 and RV ST2-IL-33-receptor were significantly increased in BALB/c wild type mice, but not in BALB/c-RELMα-/- or in C57BL/6-wild type or C57BL/6-RELMα-/- mice. RV systolic pressures (RVSP) were higher in BALB/c compared to C57BL/6J mice, and RELMα-/- were not different from their respective wild type controls. In BALB/c mice, RELMα was a key contributor to antigen/PM2.5 induced pulmonary vascular remodeling, RV thickening and RV cytokine responses, highlighting the significance of the genetic background. The RELMα-/- animals demonstrated significantly decreased expression of RELMβ and RELM which makes these mice comparable to a situation where human RELMα levels would be significantly modified, as humans only have one RELM molecule.

Background: Hairy cell leukemia (HCL) is a rare indolent B-cell lymphoid malignancy. The majority of patients are asymptomatic and HCL is usually diagnosed incidentally during a routine blood cell counts. In symptomatic patients, typical symptoms are related to pancytope-nia and splenomegaly. In this review we present, rare clinical symptoms in patients with HCL. Methods: A literature search was conducted of PubMed, Web of Science, and Google Scholar for articles concerning hairy cell leukemia, leukemia cutis, bone lesions, neurological manifesta-tions, pulmonary symptoms, ocular manifestations, cardiac manifestation, rare symptoms. Publications from January 1980 to August 2024 were scrutinized. Additional relevant publica-ions were obtained by reviewing the references from the chosen articles. Results: Extra medul-lary and extra nodal manifestations of classic HCL are rare. However, leukemic involvement in the skin, bone, central nervous system, gastrointestinal tract, heart, kidney, liver, lung, ocular and other organs have been reported.

The incidence of venous thromboembolism is estimated at around 3% of cancer patients. However, a majority of incidental pulmonary embolism (iPE) can be overlooked by radiologists in asymptomatic patients, performing CT scans for disease surveillance, which may significantly impact the patient's health and management. Routine imaging in oncology is usually reviewed with delayed hours after the acquisition of images. Nevertheless, the advent of AI in radiology could reduce the risk of diagnostic delay of iPE by an optimal triage immediately at the acquisition console. This study aimed to determine the accuracy rate of an AI algorithm (CIN A-iPE) in detecting iPE and the duration until the management of cancer patients in our center in addition to describing the characteristics of patients with a confirmed pulmonary embolism (PE). MATERIALS AND METHODS This is a retrospective analysis of the role of Avicenna's CE-certified and FDA-cleared CINA-iPE algorithm in oncology patients treated at Gustave Roussy Cancer Campus. The results obtained from the AI algorithm were compared with the attending radiologist's report and analyzed by both a radiology resident and a senior radiologist. In case of any discordant results, the reason for this discrepancy was further investigated. The duration between the exact time of the CT scan and analysis was assessed as well as the duration from the result’s reporting and the start of active management. RESULTS Out of 3047 patients, 104 alerts were detected for iPE (prevalence of 1.3%) while 2942 had negative findings. 36 of the 104 patients had confirmed PE while 68 alerts were false positives. Only one patient reported as negative by the AI tool was deemed to have a PE by the radiologist. The sensitivity and specificity of the AI model were 97.3% and 97.74% while the PPV and NPV were 34.62% and 99.97% respectively. Most causes of FP were artifacts (22 cases, 32.3%) and lymph nodes (11 cases, 16.2%). Seven patients experienced delayed diagnosis, requiring them to return to the ER for treatment after being sent home following their scan. The remaining patients received prompt care immediately after their testing with a mean delay time of 8.13 hours. CONCLUSION The addition of an AI system for the detection of unsuspected PEs on chest CT scans in routine oncology care demonstrated a promising efficacy in comparison to human performance. Despite a low prevalence, the sensitivity and specificity of the AI tool reached 97.3% and 97.7% respectively with detection of all the reported clinical PEs except one single case. This study describes the potential synergy between AI and radiologists for an optimal diagnosis of iPE in routine clinical cancer care.

Midkine (MDK) is a multifunctional heparin-binding growth factor, and has been shown to regulate cell growth, survival and migration. It also plays important roles in several inflammatory diseases such as sepsis. However, the role of MDK in the lungs has not yet been elucidated. In the present study, we investigated the role of MDK in pulmonary inflammation experiments using a mouse lipopolysaccharide (LPS)-induced pneumonia model and human bronchial cells. Wild-type and MDK-deficient mice were injected intratracheally with LPS, and several inflammatory parameters were analyzed. In the wild-type mice, mRNA expression of MDK in lung tissues was significantly increased after intratracheal LPS injection. The MDK-deficient mice showed significantly lower counts of total cells and neutrophils, as well as lower concentrations of neutrophil chemokines, KC and MIP-2 in bronchoalveolar lavage fluid, compared to wild-type mice. Moreover, mRNA expressions of TNF-α, KC and MIP-2 in lung tissues, as well as histopathological lung inflammation score, were significantly lower in the MDK-deficient mice. Furthermore, in in vitro experiments using bronchial epithelial cells, LPS stimulation increased mRNA expression of MDK, and MDK knockdown by siRNA decreased LPS-induced TNF-α and CXCL8 upregulation. These findings suggest that deficiency of MDK attenuates LPS-induced pulmonary inflammation.

Idiopathic pulmonary fibrosis [IPF] is a chronic progressive disease characterised by the accumulation of scar tissue in the lung parenchyma. It primarily occurs in middle-aged and elderly adults and results in significant morbidity and mortality worldwide. The disease occurs due to repetitive lung epithelial injury, subsequent fibroblast activation and myofibroblast differentiation, resulting in excessive extracellular matrix deposition. This leads to scar formation and subsequent loss of lung function. Current treatment options for patients with IPF include the two anti-fibrotic drugs, pirfenidone and nintedanib, which can slow disease progression; however, there are currently no known cures for the disease. As such, novel methods and drug targets are warranted. In this review, we provide an up-to-date account of the importance of specific cytokines and the potential role of regulatory immune cells. We discuss their role in the pathogenesis of IPF and address some of the key gaps in knowledge.

Fatigue and dyspnea are the most commonly presented long-term complaints in individuals previously infected with SARS-CoV-2. The purpose of the study was to comprehensively evaluate diaphragm muscle function in COVID-19 survivors, as well as investigate whether potential diaphragm dysfunction will contribute to physical functioning impairment. 46 patients qualified to pulmonary rehabilitation were examined. Diaphragm muscle function parameters were evaluated using ultrasonography, while severity of dyspnea, aerobic capacity and amount of energy used by the body during physical activity were assessed by 6-minute walk test, mMRC scale and Metabolic Equivalent Task (MET), respectively. We identified 69.5% patients with diaphragm atrophy and 6.5% with diaphragm paralysis. Percentage of atrophy was not related to age, gender, BMI index, oxygen therapy use during COVID-19 infection course and severity of disease. Patients with presence of cough, fever and without loss of smell during COVID-19 course had a significantly greater values of diaphragm inspiratory thickness, while patients with cough and no smell disorders had a significantly lower percentage of diaphragm atrophy. Diaphragm functional parameters were strongly associated with selected variables of person's exercise tolerance, such as distance in 6-minute walk test, saturation level, fatigue and exertion in Borg scale. In conclusion, diaphragm muscle dysfunction is a serious long-term post-COVID aftermath and can be viewed as a major contributing factor of prolonged functional impairments.

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.

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.

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.

Fungal-bacterial co-colonization and co-infections are emerging among TB-suspected patients, yet the underlying mechanisms that enable and arise from their interactions are poorly understood. Understanding how environmental microbes such as fungi and bacteria co-evolve and develop traits to evade host immune responses and resist treatment is critical to controlling opportunistic co-infections. Our previous work has demonstrated that fungal-bacterial interactions can have dramatic impacts on fungal pathogenesis and drug resistance. Here, we, therefore, hypothesize that cross-kingdom synergistic interactions between environmental fungi and bacteria may influence both fungal and bacterial virulence, antimicrobial resistance patterns and aetiology. Through this, we aimed to establish the prevalence of fungal–bacterial microbial communities associated with chronic primary or opportunistic pulmonary infections. Concordantly, through surveilling 302 clinical samples from 151 patients, we established the prevalence of TB (0.7%) to be lower than that of fungi (1.3%) and non-TB bacterial (4.6%) mono-aetiologies Figure 2. However, our main observation was the unexpected taxonomic diversity with a striking twist of fungal-bacterial di-kingdom aetiological conformities. Interestingly, the majority of the patients presented with at least a di or mono-kingdom aetiological pairings. Importantly, fungi and non-TB bacteria formerly regarded as atypical opportunists are now frequently isolated as possible aetiology for chronic pulmonary infection. Hence, we revealed many di-kingdom aetiological pairings here but their significance remains a question of further examination. Among which Acremonium spp + K. pneumoniae (n=5), Acremonium spp +Streptococcus pneumoniae (n=4), Acremonium spp + C. albicans + K. pneumoniae (n=3) were among the most dominant aetiological pairings observed. Interestingly, Acremonium spp + K. pneumoniae pairings were also seen to be the most commonly associated with pulmonary TB both during and after treatment. Isolation from the same infection niche as seen here calls for further investigations into any interaction signatures that may exist between these organisms. Taken together, our data suggest that fungal-bacterial co-existence may influence their virulence attributes and antimicrobial resistance patterns, with relevance to patient outcomes. Therefore, our data reveals an array of fungal-bacterial pairings that may influence the prognosis of chronic pulmonary disease. Importantly, suggesting that the diversity of pulmonary infective fungi and bacteria, and their complex population structures may pose challenges to the analysis and interpretation of conventional data. Thus, there is a need to redirect our diagnostic approaches to encompass polymicrobial aetiology in order to enhance our suspicion index for better management of opportunistic fungal-bacterial co-infections.

Background: To our knowledge, the sudden onset of symptomatic pulmonary hypertension after COVID-19 vaccination has not been described. Both cases presented here resulted in functional limitations and likely permanent organ damage. Case Summary: We report two cases of acute onset pulmonary hypertension in previously healthy adult males within three weeks of receiving the second dose of the Pfizer (BNT162b2) mRNA COVID-19 vaccine from different lots. Both patients experienced the sudden onset of severe fatigue and dyspnea on exertion with negative COVID-19 PCR testing. The diagnosis was made by serial transthoracic echocardiography in the first case and by both transthoracic echocardiography and right heart catheterization in the second. Discussion: Pulmonary hypertension is a serious disease characterized by damage to lung vasculature and restricted blood flow through narrowed arteries from the right to left heart. The onset of symptoms is typically insidious, progressive and incurable, leading to right heart failure and premature death. The World Health Organization (WHO) classifies pulmonary hypertension into 5 categories and recently re-defined as a resting mean pulmonary artery pressure greater than 20 mmHg. Sudden onset pulmonary hypertension would only be expected in the settings of surgical pneumonectomy or massive pulmonary emboli with compromise of at least 50% of the lung vasculature.

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 (&gt; 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.

Transmembrane protein 100 (TMEM100) plays an important role in angiogenesis, vascular morphogenesis, integrity and cardiovascular development. TMEM100 is a downstream target of the BMP9/10 and BMPR2/ALK1 signaling pathways. Our recent study demonstrates TMEM100 is a lung endothelium enriched gene. Endothelial-specific deletion of Tmem100 impairs lung endothelial cells regeneration. Activation of Tmem100 signaling represents a novel strategy for lung vascular repair and regeneration. It is interesting and important to understand the roles of TMEM100 in the physiological and pathological conditions. In this review, we summarized the current knowledge of TMEM100.

Patients under immunosuppressive therapy for kidney diseases or on maintenance hemodialysis are more susceptible to infection than the general population since loss of renal function per se was an immunocompromised condition. Of relevance, CT imaging plays a crucial role in the detection and management of pulmonary infectious diseases. We hence presented diverse CT findings of pulmonary infections in the above said patients collected during our arduous work against a wide range of pathogens including klebsiella pneumoniae, staphylococcus aureus, candida parapsilosis, aspergillus, cryptococcus, mucor, pneumocystis carinii, cytomegalovirus, mycobacterium and nocardia. Notably, the pulmonary pathological changes were either primary pneumonia or secondary to the catheter-associated bloodstream infection. For a descriptive purpose, pulmonary manifestations of Wegener’s granuloma, lung cancer and diffuse alveolar hemorrhage/infection in vasculitis were also examined. As such, we retrospectively elaborated most likely CT features of each individual pathogen and briefly covered the differential diagnosis as well. Arguably, combination of pattern recognition with knowledge of the clinical setting could make a presumptive diagnosis and early treatment even more convenient. From the experience of first-line nephrologists, our work could make a substantial contribution to the expeditious and efficacious management of pulmonary infections in the pertinent patient population.

Most striking observations in COVID-19 patients are the hints on pulmonary edema (also seen on CT scans as ground glass opacities), dry cough, fluid restrictions to prevent more severe hypoxia, the huge PEEP that is needed while lungs are compliant, and the fact that anti-inflammatory therapies are not powerful enough to counter the severity of the disease. We propose that the severity of the disease and many deaths are due to a local vascular problem due to activation of B1 receptors on endothelial cells in the lungs. SARS-CoV-2 enters the cell via ACE2, a cell membrane bound molecule with enzymatic activity that next to its role in RAS is needed to inactivate des-Arg⁹ bradykinin, the potent ligand of the bradykinin receptor type 1 (B1). In contrast to bradykinin receptor 2 (B2), the B1 receptor on endothelial cells is upregulated by proinflammatory cytokines. Without ACE2 acting as a guardian to inactivate the ligands of B1, the lung environment is prone for local vascular leakage leading to angioedema. Angioedema is likely a feature already early in disease, and might explain the typical CT scans and the feeling of people that they drown. In some patients, this is followed by a clinical worsening of disease around day 9 due to the formation antibodies directed against the spike (S)-antigen of the corona-virus that binds to ACE2 that could contribute to disease by enhancement of local immune cell influx and proinflammatory cytokines leading to damage. In parallel, inflammation induces more B1 expression, and possibly via antibody-dependent enhancement of viral infection leading to continued ACE2 dysfunction in the lung because of persistence of the virus. In this viewpoint we propose that a bradykinin-dependent local lung angioedema via B1 and B2 receptors is an important feature of COVID-19, resulting in a very high number of ICU admissions. We propose that blocking the B1 and B2 receptors might have an ameliorating effect on disease caused by COVID-19. This kinin-dependent pulmonary edema is resistant to corticosteroids or adrenaline and should be targeted as long as the virus is present. In addition, this pathway might indirectly be responsive to anti-inflammatory agents or neutralizing strategies for the anti-S-antibody induced effects, but by itself is likely to be insufficient to reverse all the pulmonary edema. Moreover, we provide a suggestion of how to ventilate in the ICU in the context of this hypothesis.

Objective: To estimate for the first time the burden of serious fungal infections in Romania; Methods: Data derived from the World Health Organization (WHO), National Institute of Statistics, Romanian public health agencies and non-profit health organizations and published annual reports on local epidemiology were used in the present study. When no data was available, specific at-risk populations were used to calculate frequencies of serious fungal diseases, using previously published epidemiological parameters. All data refer to the year 2016; 3) Results: The estimated number of serious fungal infections in Romanian population was 435,930 in 2016. Recurrent vulvovaginal candidiasis accounts for up to 80% of total cases (more than 350,000 women annually). Concerning the HIV related infections, among 14349 infected persons, Pneumocystis pneumonia occurred in about 10% of late presenters (30 cases in 2016), while cryptococcal meningitis is rarely diagnosed (less than 20 cases). Annually, the total number of oesophageal candidiasis and oral thrush cases in HIV-positive patients may be as high as 1229 and 3066, respectively. In immunocompromised and cancer patient population, the annual incidence of candidaemia is 295, and at least 158 invasive aspergillosis cases and 4 mucormycosis cases occur yearly. With 4,966 critical care beds and approximately 200,000 abdominal surgeries performed, the estimated annual incidence of candidaemia and Candida peritonitis is 689 and 344, respectively. The annual incidence of pulmonary tuberculosis is still high in Romania (12,747 cases). Thus, the prevalence of post-TB chronic pulmonary aspergillosis is estimated to be 8.98/100,000 (1768 cases). The prevalence of chronic obstructive pulmonary disease (COPD) and asthma in adults is 6% and 6.5%, respectively. Therefore, allergic bronchopulmonary aspergillosis prevalence is estimated at 29,387 and severe asthma with fungal sensitisation at 38,731 cases annually. 4) Conclusions: Not being on the list of reportable diseases, the number of patients presenting with severe mycoses in Romania can only be roughly estimated. Based on local reports and prevalence estimation, we consider that at least 2.2% of Romanians suffer a serious form of fungal disease.

Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in the regulation of idiopathic pulmonary fibrosis (IPF) is ambiguous. Our previous study demonstrated that miR-30a may function as a novel therapeutic target for lung fibrosis by blocking mitochondrial fission, which is dependent on dynamin-related protein-1 (Drp-1). However, the regulatory mechanism between miR-30a and Drp-1 has yet to be investigated. In addition, whether miR-30a can act as a potential therapeutic has not been verified in vivo. In this study, the miR-30a expression in IPF patients was evaluated. Computational analysis and a dual luciferase reporter system assay were used to identify the target gene of miR-30a, and cell transfection was used to confirm this relationship. Ten-eleven translocation 1 (TET1) was validated as a direct target of miR-30a, and the transfection of miR-30a mimic/inhibitor significantly reduced/increased the expression of TET1 protein. Further experiment verified that the interference on TET1(siRNA) could inhibit the hydroxymethlation of the Drp-1 promoter. Finally, miR-30a agomir was designed and applied to identify and validate the therapeutic effect of miR-30a in vivo. Our study demonstrated that miR-30a could inhibit the TET1 expression by base pairing with complementary sites in the 3′ untranslated region to regulate the hydroxymethlation of the Drp-1 promoter. Furthermore, miR-30a could act as a potential therapeutic target for IPF.

Background/Objectives: This study aimed to compare the diagnostic accuracy of the Wells and Geneva scores, used with a 500 ng/mL D-dimer cutoff, along with the age-adjusted D-dimer (AADD), YEARS, and PEGeD algorithms in patients with and without COVID-19. The performance of various D-dimer thresholds was also evaluated. Methods: This retrospective study included patients who presented to the emergency department and underwent computed tomography pulmonary angiography (CTPA) for suspected pulmonary embolism (PE). The diagnostic performance of clinical prediction algorithms was compared between two groups. Results: We analyzed data from 1423 patients; PE diagnosis and COVID-19 positivity rates were 7.3% and 69.9%, respectively. In patients with COVID-19, the Wells score with a 500 ng/mL D-dimer threshold exhibited 97.22% sensitivity (95% CI: 80.53–100.00) and 4.99% specificity (95% CI: 3.58–6.39). Using AADD increased the specificity to 7.81% (95% CI: 6.08–9.54) while maintaining sensitivity at 97.22% (95% CI: 93.43–100.00); similar results were observed for the Geneva score. The YEARS algorithm exhibited 86.11% sensitivity (95% CI: 78.12–94.10) and 32.75% specificity (95% CI: 29.73–35.78), whereas the PEGeD algorithm exhibited 86.11% sensitivity (95% CI: 78.12–94.10) and 34.06% specificity (95% CI: 31.00–37.12). The YEARS and PEGeD algorithms demonstrated better performance in patients with COVID-19 in terms of specificity and accuracy. Conclusion: COVID-19 infection did not significantly affect the diagnostic performances of the clinical algorithms for PE. YEARS and PEGeD performed better in patients with COVID-19, making them preferable. Higher D-dimer thresholds improved specificity but increased the risk of missed PE diagnoses.

This case represents the association between the presence of large fibroid tumor and pulmonary embolism in 47-year-old women. We highlight the diagnostic investigations and treatment methods for PE, followed by further evaluation of the underlying explanation of this pathology and eliminating other related risk factors.

Background. Myocardial involvement mediated by chronic obstructive pulmonary disease (COPD) is a common cause of morbidity and mortality. Conventional transthoracic echocardiography (TTE) parameters are poor in the detection of subclinical myocardial dysfunction. Aim.To investigate the contribution of strain in the early detection of cardiac damage in stable COPD patients Methods. Group A and B patients with COPD were enrolled in this study. The COPD assessment test, spirometry, 6-minute walk test, and both conventional TTE and strain were performed in these patients. Results. 80 COPD patients, with a mean age 65.6 ± 8.9 years, were included. The. Left ventricular ejection fraction (LVEF) was 60.7 ± 5.1%. Right atrium and right ventricle (RV) strain were 24.5 ± 6.6% and -19.9 ± 3.7%, respectively. Additionally, left ventricle global longitudinal strain (LV GLS) was -21.1 ± 2. Forty-eight patients had impaired RV strain. Compared to COPD patient with normal RV strain, those with RV reduced starin had a lower 6meter walk distance (6MWD) (p=0.001) and forced expiratory volume in the first second (FEV1) (p=0.012), and a higher CAT score (p=0.012). A reduced RV strain was correlated with a higher risk of hospitalizations for acute exacerbation in the post inclusion year (55% versus 25%; p=0.024). No deaths were recorded during the follow-up period. No significant factors causing neither RA starin alteration nor LV GLS reduction were revealed. Conclusion. Group A and B COPD patients having normal conventional TTE parameters, speckle tracking is a key parameter in the detection of subclinical myocardial dysfunction.

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.

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.

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.

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.

Idiopathic pulmonary fibrosis (IPF) is one of the most common forms of interstitial lung disease characterized by progressive parenchymal fibrosis and respiratory failure. In a model of bleomycin-induced pulmonary fibrosis, the antifibrotic and anti-inflammatory activity of Longidaza (bovhyaluronidase azoxymer), which contains a conjugate of the hyaluronidase enzyme with a high molecular weight synthetic carrier azoxymer bromide, was investigated. Experiments were conducted in male C57BL/6 mice. Longidaza was administered at different doses by intranasal and intramuscular routes. Histology, hematology and enzyme-linked immunosorbent assay were used in the study. The use of Longidaza reduced pulmonary fibrosis as evidenced by an improvement in histopathologic damage to the lungs, a decrease in the area of connective tissue and the levels of profibrotic factors (TGF-β1, hydroxyproline, collagen I) in lung tissue. In addition, Longidaza inhibited the inflammatory response in pulmonary fibrosis, decreased the levels of IL-6, TNF-α, hyaluronic acid in lung tissue and the recruitment of inflammatory cells into lung tissue. The highest therapeutic efficacy was observed with the use of Longidaza at doses of 120 and 1200 U/kg intramuscularly, which was superior to that of the reference drug pirfenidone axunio. The data presented in this study suggest that Longidaza is a new and promising drug for the treatment of IPF that warrants further investigation in patients with fibrotic interstitial lung disease.

Pulmonary aspiration is a serious anaesthetic complication with morbidity and up to 9% of all anaesthesia-related mortality. Aspiration risk is especially focused on fastening time. We aimed to evaluate the prevalence of 'risky stomach' defined by ultrasound imagine of solid contents and/or calculated gastric fluid volume >1.25 mL/kg in elective surgery also comparing this definition with the 0-2 qualitative rating scale used for "empty/risky stomach". This prospective study has 97 patients aged 2-18. Ultrasonographic evaluations of the gastric antrum content is scaled with qualitative assessment in supine and right lateral decubitus (RLD) position. Gastric volume was calculated. In our study, stomach content and volume were evaluated by ultrasound in 97% of children and 5.2% had Grade 2 antrum. In RLD position, antral CSA was 2.36 cm², and the median gastric volume was 0.46 mL/kg. In patients with grade 0 antrum has moderate and positive correlation between antral CSA and BMI, and strong and positive correlation between antral CSA and age like grade 1 antrum. We showed that 0.1%-4.7% of elective children had gastric fluid volumes of >1.25 mL/kg as "risky stomach". Ultrasound for gastric contents could be used routine practice to determine pulmonary aspiration risk in emergency and elective procedures.

(1) Infective endocarditis is a severe inflammatory disease associated with substantial mortality and morbidity. Alkaline phosphatase (AP) levels have been shown to change significantly during sepsis additionally we previously found higher initial AP drop after cardiac surgery is associat-ed with unfavorable outcomes. Therefore, the course of AP after surgery for endocarditis is of special interest. (2) 314 patients with active isolated left-sided infective endocarditis at the De-partment of Cardiac Surgery (Medical University of Vienna, Austria) between 2009 and 2018 were enrolled in this retrospective analysis. Blood samples were analyzed at different time points (baseline, postoperative day 1-7, postoperative days 14, and 30). Patients were categorized ac-cording to relative alkaline phosphatase drop (≥30% vs. <30%). (3) The rate of postoperative renal replacement therapy with or without prior renal replacement therapy (7.4 vs. 21.8%; p=0.001 and 6.7 vs. 15.6%; p=0.015, respectively) and extracorporeal membrane oxygenation (2.2 vs. 19.0%; p=0.000) was observed after a higher initial alkaline phosphatase drop. Short-term (30-day mor-tality 3.0 vs. 10.6%; p=0.010) and long-term mortality (p=0.008) were significantly impaired after a higher initial alkaline phosphatase drop. (4) The higher initial alkaline phosphatase drop was accompanied by impaired short and long-term outcomes after cardiac surgery for endocarditis. Future risk assessment scores for cardiac surgery should consider alkaline phosphatase.

A 57-year-old male with a history of hyperlipidemia and mild pulmonary hypertension presented for a left inguinal hernia repair. Preoperative electrocardiogram showed severe right axis deviation at 177 degrees and abnormal repolarization. Right ventricular hypertrophy secondary to pulmonary hypertension was the primary differential but was quickly ruled out due to the patient being asymptomatic and having great exercise tolerance. Dextrocardia was also ruled out due to normal progression on the precordial leads. The simultaneous severe right axis deviations of P, R, and T waves raised suspicion for erroneous lead placement. The repeat electrocardiogram confirmed the diagnosis.

Pulmonary thromboembolism is a very common cardiovascular disease, with a still high mortality rate. Despite the clear guidelines, this disease still represents a great challenge both in diagnosis and treatment. Heterogeneous clinical picture, often without pathognomonic signs and symptoms, represents a huge differential diagnostic problem even for experienced doctors. The decision on the therapeutic regimen also represents a major dilemma in the group of patients who are hemodynamically stable at initial presentation and have signs of right ventricular (RV) dysfunction proven by echocardiography and positive biomarker values (pulmonary embolism of intermediate-high risk). Studies have shown conflicting results about the benefit of using fibrinolytic therapy in this group of patients until hemodynamic decompensation, due to the risk of major bleeding. The latest recommendations give preference to new oral anticoagulants (NOACs) compared to vitamin K antagonists (VKA), except for certain categories of patients (patients with antiphospholipid syndrome, mechanical valves, pregnancy). When using oral anticoagulant therapy, special attention should be paid to drug-drug interactions, which can lead to many complications, even to the death of the patient. Special population groups such as pregnant women, obese patients, patients with antiphospholipid syndrome and cancer represent a great therapeutic challenge in the application of anticoagulant therapy. In these patients, not only the effectiveness of the drugs must be taken into account, but great attention must be paid to their safety and possible side effects, which is why a multidisciplinary approach is emphasized in order to provide the best therapeutic option.

Cultural recovery of Mucorales from hyphae-laden tissue is poor, and the clinical implications of culture positivity are scarcely studied. Therefore, we compared clinical and histological characteristics of culture-positive and culture-negative histology-proven pulmonary mucormycosis cases among cancer patients. Histology specimens were blindly reviewed by a Thoracic Pathologist and graded on four histopathologic features: hyphal quantity, tissue necrosis, tissue invasion, and vascular invasion. Twenty cases with a corresponding fungal culture were identified; five were culture-positive, and 15 culture-negative. Although no statistically significant differences were found, culture-positive patients were more likely to exhibit a high burden of necrosis and have a high burden of hyphae but tended to have less vascular invasion than culture-negative patients. In terms of clinical characteristics, culture-positive patients were more likely to have acute myeloid leukemia (60% vs. 27%, p=0.19), a history of hematopoietic cell transplant (80% vs. 53%, p=0.31), severe lymphopenia (absolute lymphocyte count ≤500/µL, 100% vs. 73%, p=0.36), and monocytopenia (absolute monocyte count ≤100/µL, 60% vs. 20%, p=0.11). Forty-two-day all-cause mortality was comparable between culture-positive and culture-negative patients (60% and 53%, p=0.80). This pilot study represents the first comprehensive histopathological scoring method to examine the relationship between histopathologic features, culture positivity, and clinical features of pulmonary mucormycosis.