Combination of BeGraft and Solaris Stent Grafts for the Covered Endovascular Reconstruction of Aortic Bifurcation-BS-CERAB Technique.

Background: This study examines the impact of the use of the combination of BeGraft and Solaris stent grafts on the outcomes during the covered endovascular reconstruction of aortic bifurcation (BS-CERAB) technique and extension to the iliac arteries. Methods: Consecutive patients with aortoiliac occlusive disease who underwent endovascular treatment using BS-CERAB between January 2020 and December 2023 were included. Patient demographics, symptoms, lesion characteristics, and procedural and follow-up details were collected and analyzed. Perioperative complications and reinterventions were also identified. Results: A total of 42 patients met the inclusion criteria (32 men, 76.2%, median age 72 years, range 59-85). Indications for treatment were intermittent claudication (42.9%) and critical limb ischemia (57.1%). Procedure success was achieved in all cases. The median patient follow-up time was 14 months (1-36). One patient died at a 10-month follow-up due to lung cancer. The mean pre-operative ABI increased from 0.37 ± 0.19 before intervention to 0.71 ± 1.23 post-operatively at 12 months (p = 0.037). The estimated primary patency rates at 3, 6, and 12 months were 90.5%, 85.7%, and 81.0% and primary assisted patency rates were 90.5%, 90.5%, and 85.7%, respectively. Secondary patency was 95.2% at 3 and 6 months and 90.5% at a 12-month follow-up. Active cancer (p = 0.023, OR 2.12 95%CI 1.14-3.25) was a risk factor for restenosis. Conclusions: This mid-term experience shows that the CERAB technique using the combination of BeGraft and Solaris stents grafts, for the endovascular treatment of severe aortoiliac atherosclerotic disease, may allow an effective reconstruction of the aortic bifurcation and iliac arteries related to high-patency and lower-reintervention rates.

Pulmonary vascular reactivity in growth restricted fetuses using computational modelling and machine learning analysis of fetal Doppler waveforms.

The aim of this study was to investigate the pulmonary vasculature in baseline conditions and after maternal hyperoxygenation in growth restricted fetuses (FGR). A prospective cohort study of singleton pregnancies including 97 FGR and 111 normally grown fetuses was carried out. Ultrasound Doppler of the pulmonary vessels was obtained at 24-37 weeks of gestation and data were acquired before and after oxygen administration. After, Machine Learning (ML) and a computational model were used on the Doppler waveforms to classify individuals and estimate pulmonary vascular resistance (PVR). Our results showed lower mean velocity time integral (VTI) in the main pulmonary and intrapulmonary arteries in baseline conditions in FGR individuals. Delta changes of the main pulmonary artery VTI and intrapulmonary artery pulsatility index before and after hyperoxygenation were significantly greater in FGR when compared with controls. Also, ML identified two clusters: A (including 66% controls and 34% FGR) with similar Doppler traces over time and B (including 33% controls and 67% FGR) with changes after hyperoxygenation. The computational model estimated the ratio of PVR before and after maternal hyperoxygenation which was closer to 1 in cluster A (cluster A 0.98 ± 0.33 vs cluster B 0.78 ± 0.28, p = 0.0156). Doppler ultrasound allows the detection of significant changes in pulmonary vasculature in most FGR at baseline, and distinct responses to hyperoxygenation. Future studies are warranted to assess its potential applicability in the clinical management of FGR.

Experiences in the use of multiple doses of convalescent plasma in critically ill patients with COVID-19: An early phase 1 descriptive study.

Background: At the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, transfusion of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) emerged as a potential therapeutic strategy to help patients severely afflicted by COVID-19. The efficacy of CCP has been controversial as it depends on many variables pertaining to the plasma donor and the patient with COVID-19, for example, time of convalescence or symptoms onset. This feasibility and descriptive study aimed to assess the safety of multiple doses of CCP in mechanically ventilated, intubated patients with respiratory failure due to COVID-19. Methods: A cohort of 30 patients all experiencing severe respiratory failure and undergoing invasive mechanical ventilation in an intensive care unit, received up to five doses of 300-600 mL of CCP on alternate days (0, 2, 4, 6, and 8) until extubation, futility, or death. Results: Nineteen patients received five doses, seven received four, and four received two or three doses. At 28-day follow-up mark, 57% of patients recovered and were sent home, and the long-term mortality rate was 27%. Ten severe adverse events reported in the study were unrelated to CCP transfusion. Independent of the number of transfused doses, most patients had detectable levels of total and neutralizing antibodies in plasma. Conclusion: This study suggests that transfusion of multiple doses of CCP is safe. This strategy may represent a viable option for future studies, given the potential benefit of CCP transfusions during the early stages of infection in unvaccinated populations and in settings where monoclonal antibodies or antivirals are contraindicated or unavailable.

Innovative Predictive Approach towards a Personalized Oxygen Dosing System.

Despite the large impact chronic obstructive pulmonary disease (COPD) that has on the population, the implementation of new technologies for diagnosis and treatment remains limited. Current practices in ambulatory oxygen therapy used in COPD rely on fixed doses overlooking the diverse activities which patients engage in. To address this challenge, we propose a software architecture aimed at delivering patient-personalized edge-based artificial intelligence (AI)-assisted models that are built upon data collected from patients' previous experiences along with an evaluation function. The main objectives reside in proactively administering precise oxygen dosages in real time to the patient (the edge), leveraging individual patient data, previous experiences, and actual activity levels, thereby representing a substantial advancement over conventional oxygen dosing. Through a pilot test using vital sign data from a cohort of five patients, the limitations of a one-size-fits-all approach are demonstrated, thus highlighting the need for personalized treatment strategies. This study underscores the importance of adopting advanced technological approaches for ambulatory oxygen therapy.

Imaging of chronic thromboembolic pulmonary hypertension before, during and after balloon pulmonary angioplasty.

Balloon pulmonary angioplasty (BPA) has recently been elevated as a class I recommendation for the treatment of inoperable or residual chronic thromboembolic pulmonary hypertension (CTEPH). Proper patient selection, procedural safety, and post-procedural evaluation are crucial in the management of these patients, with imaging work-up playing a pivotal role. Understanding the diagnostic and therapeutic imaging algorithms of CTEPH, the imaging features of patients amenable to BPA, all imaging findings observed during and immediately after the procedure and the changes observed during the follow-up is crucial for all interventional radiologists involved in the care of patients with CTEPH. This article illustrates the imaging work-up of patients with CTEPH amenable to BPA, the imaging findings observed before, during and after BPA, and provides a detailed description of all imaging modalities available for CTEPH evaluation.

Six-minute walking distance and desaturation-distance ratio in allogeneic stem cell transplantation.

BACKGROUND: Most patients with haematological malignancies who undergo allogeneic haematopoietic stem cell transplant (HSCT) receive chemotherapy before the transplant to control the disease. Certain chemotherapy drugs can cause lung toxicity. Conversely, in patients with chronic respiratory conditions, the 6-min walking test (6MWT) and the desaturation-distance ratio (DDR) have demonstrated prognostic significance. Our objective was to determine whether the 6MWD and DDR, assessed prior to HSCT, have a prognostic impact on survival at 24 months post-HSCT. METHODS: A prospective experimental study was conducted in consecutive patients referred for allogeneic HSCT at Hospital Clinic, Barcelona, Spain. A complete functional respiratory study, including the 6MWT and DDR, was conducted prior to admission. The area under the curve (AUC) and cut-off points were calculated. Data on patients' characteristics, HSCT details, main events, with a focus on lung complications, and survival at 24 months were analysed. RESULTS: One hundred and seventy-five patients (39% women) with mean age of 48 ± 13 years old were included. Before HSCT, forced vital capacity and forced expiratory volume in the first second were 96% ± 13% predicted and 92% ± 14% predicted, respectively; corrected diffusing capacity for carbon monoxide 79% ± 15% predicted; 6MWD was 568 ± 83 m and DDR of .27 (.20-.41). The cut-off points for 6MWD and DDR were 566 m, [.58 95% CI (.51-.64)], p = .024 and .306, [.63 95% CI (.55-.70)], p = .0005, respectively. The survival rate at 24 months was 55%. CONCLUSION: Our results showed that individuals who exhibit a 6MWD shorter than 566 ms or a decline in DDR beyond .306 experienced reduced survival rates at 24 months after HSCT.

Topical and Intralesional Immunotherapy for the Management of Skin Cancer in Special Locations: Lips and Eyelids.

The use of topical and intralesional immunotherapy in the treatment of cutaneous malignant neoplasia in sensitive areas such as the lips and eyelids is discussed. Surgery may not be feasible or may result in deformities in these areas, making alternative treatment options necessary. A narrative literature review was conducted using MEDLINE (PubMed) as the main literature database, collecting available evidence of experiences with various topical and intralesional therapies in the aforementioned anatomical locations, ranging from case reports to clinical trials. The clearance rates and potential adverse reactions of therapeutic options such as imiquimod 5%, 5-fluorouracil (5-FU), photodynamic therapy (PDT), ingenol mebutate (IM), diclofenac, intralesional methotrexate, and interferon are reviewed. Although limited by their heterogeneity and the scarcity of clinical trials, these studies point towards promising response rates and minimal adverse effects, making these treatments viable options in selected cases.

Pulmonary rehabilitation in sarcoidosis: A systematic review and meta-analysis.

BACKGROUND: Exercise intolerance, muscle weakness, dyspnoea, and fatigue are frequent complications in symptomatic sarcoidosis patients. Pulmonary rehabilitation improves exercise capacity, symptoms, and quality of life in patients with chronic respiratory diseases. Our objective was to systematically determine the effects of pulmonary rehabilitation in patients with sarcoidosis. METHODS: A systematic review was conducted in seven databases. Studies that applied pulmonary rehabilitation in patients with sarcoidosis were reviewed. Two independent reviewers analysed the studies, extracted the data and assessed the quality of evidence. RESULTS: Of the 406 reports returned by the initial search, five articles reporting on 184 patients were included in the data synthesis. Two studies included multi-component exercise, one inspiratory muscle training, one a physical activity incentivisation programme, and one a telerehabilitation program. In the intervention group (IG), we found significant improvement in exercise capacity (SMD 1.65, 95%CI 0.45, 2.86 points, p = 0.006). If we only analyse the studies that performed the 6-min walking test, the IG walked 40.3 (CI95% 20.3, 60.2) m higher than the control group (CG) (p < 0.001). Additionally, dyspnoea score was reduced (MD -0.42 95%CI -0.75, -0.10, p = 0.002). However, fatigue, quality of life and pulmonary function did not show any change. CONCLUSION: Pulmonary rehabilitation could improve exercise capacity and dyspnoea perception in patients with sarcoidosis.

Predictors of the response to phosphodiesterase-5 inhibitors in pulmonary arterial hypertension: an analysis of the Spanish registry.

BACKGROUND: Achieving and maintaining a low-risk profile is associated with favorable outcome in pulmonary arterial hypertension (PAH). The effects of treatment on risk profile are variable among patients. OBJECTIVE: To Identify variables that might predict the response to treatment with phosphodiesterase-5 inhibitors (PDE-5i) in PAH. METHODS: We carried out a cohort analysis of the Spanish PAH registry in 830 patients diagnosed with PAH that started PDE5i treatment and had > 1 year follow-up. 644 patients started PDE-5i either in mono- or add-on therapy and 186 started combined treatment with PDE-5i and endothelin receptor antagonist (ERA). Responders were considered when at 1 year they: (1) were alive; (2) did not present clinical worsening; and (3) improved European Society of Cardiology/European Respiratory Society (ESC/ERS) risk score or remained in low-risk. Univariate and multivariate logistic regression models were used to analyze variables associated with a favorable response. RESULTS: Two hundred and ten patients (33%) starting PDE-5i alone were classified as responders, irrespective of whether it was mono- or add-on therapy. In addition to known predictors of PAH outcome (low-risk at baseline, younger age), male sex and diagnosis of portopulmonary hypertension (PoPH) or HIV-PAH were independent predictors of favorable response to PDE-5i. Diffusing capacity for carbon monoxide (DLco) ≤ 40% of predicted was associated with an unfavorable response. When PDE-5i were used in upfront combination, 58% of patients were responders. In this group, diagnosis of idiopathic PAH (IPAH) was an independent predictor of favorable response, whereas connective tissue disease-PAH was associated with an unfavorable response. CONCLUSION: Male sex and diagnosis of PoPH or HIV-PAH are predictors of favorable effect of PDE-5i on risk profile when used as mono- or add-on therapy. Patients with IPAH respond more favorably to PDE-5i when used in upfront combination. These results identify patient profiles that may respond favorably to PDE-5i in monotherapy and those who might benefit from alternative treatment strategies.

Effects of Exercise Training on Circulating Biomarkers of Endothelial Function in Pulmonary Arterial Hypertension.

INTRODUCTION: In stable patients with pulmonary arterial hypertension (PAH), pulmonary rehabilitation (PR) is an effective, safe and cost-effective non-pharmacological treatment. However, the effects of PR on vascular function have been poorly explored. This study aimed to compare the amounts of circulating progenitor cells (PCs) and endothelial microvesicles (EMVs) in patients with PAH before and after 8 weeks of endurance exercise training as markers of vascular competence. METHODS: A prospective study of 10 consecutive patients with PAH that successfully finished a PR program (8 weeks) was carried out before and after this intervention. Levels of circulating PCs defined as CD34+CD45low progenitor cells and levels of EMVs (CD31+ CD42b-) were measured by flow cytometry. The ratio of PCs to EMVs was taken as a measure of the balance between endothelial damage and repair capacity. RESULTS: All patients showed training-induced increases in endurance time (mean change 287 s). After PR, the number of PCs (CD34+CD45low/total lymphocytes) was increased (p < 0.05). In contrast, after training, the level of EMVs (CD31+ CD42b-/total EMVs) was reduced. The ratio of PCs to EMVs was significantly higher after training (p < 0.05). CONCLUSION: Our study shows, for the first time, that endurance exercise training in patients with stable PAH has a positive effect, promoting potential mechanisms of damage/repair in favor of repair. This effect could contribute to a positive hemodynamic and clinical response.

Clinical Variables Related to Functional Capacity and Exertional Desaturation in Patients with COVID-19.

Impaired functional capacity is one of the most commonly reported consequences among post-COVID-19 patients. This study aimed to analyse the clinical variables related to functional capacity and exertional desaturation in post-COVID-19 patients at the time of hospital discharge. A cross-sectional study was conducted on patients recovering from COVID-19 pneumonia. The main outcomes measures were functional capacity, assessed using the 1 min sit-to-stand test (1 min STST), and exertional desaturation, defined as a drop of ≥4% in the arterial oxygen saturation. Factors used to characterise the participant outcomes included the use of a high-flow nasal cannula (HFNC), prolonged hospitalisation, occurrence of pulmonary embolism during hospitalisation, and underlying comorbidities. A total of 381 participants (mean age = 53.7 ± 13.2 years, 65.6% men) were included. Participants completed a mean of 16.9 ± 6.2 repetitions in the 1 min STST. Exertional desaturation was observed in 51% of the patients. Higher odds of exertional desaturation were found in the participants who used a HFNC (OR = 3.6; 95%CI: 1.6 to 7.8), were admitted in the hospital >10 days (OR = 4.2; 95%CI: 2.6 to 6.8), and had a pulmonary embolism (OR = 3.5; 95%CI: 2.2. to 5.3). Use of a HFNC (ß = -3.4; 95%CI: -5.3 to -1.44), a hospital stay >10 days (ß = -2.2; 95%CI: -3.4 to -0.9), and a history of pulmonary embolism (ß = -1.4; 95%CI: -2.6 to -0.2) were also negatively associated with the 1 min STST. Most post-COVID-19 patients exhibited reduced functional capacity at the time of hospital discharge, and approximately half had exertional desaturation after the 1 min STST. The use of a HFNC, prolonged hospitalisation and pulmonary embolism were the main clinical variables associated with worse a 1 min STST performance and a higher likelihood of exertional desaturation.

Management of Pulmonary Hypertension Associated with Chronic Lung Disease.

Pulmonary hypertension (PH) is a common complication of chronic lung diseases, particularly in chronic obstructive pulmonary disease (COPD) and interstitial lung diseases (ILD) and especially in advanced disease. It is associated with greater mortality and worse clinical course. Given the high prevalence of some respiratory disorders and because lung parenchymal abnormalities might be present in other PH groups, the appropriate diagnosis of PH associated with respiratory disease represents a clinical challenge. Patients with chronic lung disease presenting symptoms that exceed those expected by the pulmonary disease should be further evaluated by echocardiography. Confirmatory right heart catheterization is indicated in candidates to surgical treatments, suspected severe PH potentially amenable with targeted therapy, and, in general, in those conditions where the result of the hemodynamic assessment will determine treatment options. The treatment of choice for these patients who are hypoxemic is long-term oxygen therapy and pulmonary rehabilitation to improve symptoms. Lung transplant is the only curative therapy and can be considered in appropriate cases. Conventional vasodilators or drugs approved for pulmonary arterial hypertension (PAH) are not recommended in patients with mild-to-moderate PH because they may impair gas exchange and their lack of efficacy shown in randomized controlled trials. Patients with severe PH (as defined by pulmonary vascular resistance >5 Wood units) should be referred to a center with expertise in PH and lung diseases and ideally included in randomized controlled trials. Targeted PAH therapy might be considered in this subset of patients, with careful monitoring of gas exchange. In patients with ILD, inhaled treprostinil has been shown to improve functional ability and to delay clinical worsening.

Lobular Endocervical Glandular Hyperplasia, a mimicker and potential pitfall for HPV-independent well differentiated Gastric-type Endocervical Adenocarcinoma: Case report and literature review focusing on histology, immunophenotype, and molecular findings.

Lobular glandular endocervical hyperplasia is an uncommon benign entity within the spectrum of gastric-type endocervical lesions. We report a case of a 48-year-old woman who presented with a palpable mass and watery vaginal discharge. Ultrasound revealed an 8 cm × 4 cm × 3 cm multicystic mass affecting the cervix, and hysterectomy was performed. The well-delimited multicystic, mucinous mass distorted the entire cervix. Microscopically, endocervical glandular proliferation with a lobular architecture was observed. The glands were lined with a single layer of tall, mucin-rich, columnar cells with basal and bland nuclei. The lesion was positive for MUC6 marker and hormonal receptors were negative, while P53 expression was normal. Three years later, the patient remained disease free. Here, we discuss the differential diagnosis between lobular glandular endocervical hyperplasia and similar conditions, particularly gastric-type endocervical adenocarcinoma, and review the literature focusing on the molecular pathways underlying gastric-type endocervical lesions. This case highlights the importance of accurate diagnosis to ensure favorable outcomes.

Survivin inhibition with YM155 ameliorates experimental pulmonary arterial hypertension.

Background: Imbalance between cell proliferation and apoptosis underlies the development of pulmonary arterial hypertension (PAH). Current vasodilator treatment of PAH does not target the uncontrolled proliferative process in pulmonary arteries. Proteins involved in the apoptosis pathway may play a role in PAH and their inhibition might represent a potential therapeutic target. Survivin is a member of the apoptosis inhibitor protein family involved in cell proliferation. Objectives: This study aimed to explore the potential role of survivin in the pathogenesis of PAH and the effects of its inhibition. Methods: In SU5416/hypoxia-induced PAH mice we assessed the expression of survivin by immunohistochemistry, western-blot analysis, and RT-PCR; the expression of proliferation-related genes (Bcl2 and Mki67); and the effects of the survivin inhibitor YM155. In explanted lungs from patients with PAH we assessed the expression of survivin, BCL2 and MKI67. Results: SU5416/hypoxia mice showed increased expression of survivin in pulmonary arteries and lung tissue extract, and upregulation of survivin, Bcl2 and Mki67 genes. Treatment with YM155 reduced right ventricle (RV) systolic pressure, RV thickness, pulmonary vascular remodeling, and the expression of survivin, Bcl2, and Mki67 to values similar to those in control animals. Lungs of patients with PAH also showed increased expression of survivin in pulmonary arteries and lung extract, and also that of BCL2 and MKI67 genes, compared with control lungs. Conclusion: We conclude that survivin might be involved in the pathogenesis of PAH and that its inhibition with YM155 might represent a novel therapeutic approach that warrants further evaluation.

Atrophy signaling pathways in respiratory and limb muscles of guinea pigs exposed to chronic cigarette smoke: role of soluble guanylate cyclase stimulation.

Skeletal muscle dysfunction in chronic obstructive pulmonary disease (COPD) is characterized by a significant reduction in muscle strength and endurance. Preclinical studies show that stimulation of the soluble guanylate cyclase (sGC)-cGMP pathway attenuates muscle mass loss and prevents cigarette smoke-induced oxidative stress, indicating that pharmacological activation of the guanylyl cyclase pathway in COPD may provide a beneficial therapeutic strategy that reaches beyond the lung. In this study, conducted in an animal model of COPD, we first set out to assess the effect of cigarette smoke (CS) on biomarkers of muscle fatigue, such as protein degradation and its transcriptional regulation, in two types of muscles with different energy demands, i.e., the diaphragm and the gastrocnemius muscle of the limbs. Second, we evaluated the administration of an sGC stimulator on these markers to study the potential efficacy of such treatment in the recovery of skeletal muscle function. Exposure to CS led to weight loss, which was associated in the gastrocnemius with increased levels of proteolytic markers of muscle atrophy (MURF-1, Atrogin-1, proteasome C8 subunit 20 s, and total protein ubiquitination), whereas the size of fast-twitch muscle fibers decreased significantly. Long-term treatment with the sGC stimulator BAY 41-2272 resulted in a significant reduction in gastrocnemius levels of the aforementioned proteolytic markers, concomitant with a weight recovery and increased cGMP levels. Remarkably, levels of some of the analyzed biomarkers differed between respiratory and limb muscles. In conclusion, targeting sGC might exert beneficial effects on muscle alterations in patients with COPD.

Assessment of Exercise Capacity in Post-COVID-19 Patients: How Is the Appropriate Test Chosen?

There is a wide range of sequelae affecting COVID-19 survivors, including impaired physical capacity. These sequelae can affect the quality of life and return to work of the active population. Therefore, one of the pillars of following-up is the evaluation of physical capacity, which can be assessed with field tests (such as the six-minute walk test, the one-minute standing test, the Chester step test, and the shuttle walking test) or laboratory tests (such as the cardiopulmonary exercise test). These tests can be performed in different contexts and have amply demonstrated their usefulness in the assessment of physical capacity both in post-COVID-19 patients and in other chronic respiratory, metabolic, cardiologic, or neurologic diseases. However, when traditional tests cannot be performed, physical function can be a good substitute, especially for assessing the effects of an intervention. For example, the Short Physical Performance Battery assessment and the Timed Up and Go assessment are widely accepted in older adults. Thus, the test should be chosen according to the characteristics of each subject.