Proteomic profiling of bronchoalveolar lavage fluid uncovers protein clusters linked to survival in idiopathic forms of interstitial lung disease.

Background: Idiopathic interstitial pneumonias (IIPs) such as idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia with autoimmune features (IPAF), present diagnostic and therapeutic challenges due to their heterogeneous nature. This study aimed to identify intrinsic molecular signatures within the lung microenvironment of these IIPs through proteomic analysis of bronchoalveolar lavage fluid (BALF). Methods: Patients with IIP (n=23) underwent comprehensive clinical evaluation including pre-treatment bronchoscopy and were compared to controls without lung disease (n=5). Proteomic profiling of BALF was conducted using label-free quantitative methods. Unsupervised cluster analyses identified protein expression profiles which were then analyzed to predict survival outcomes and investigate associated pathways. Results: Proteomic profiling successfully differentiated IIP from controls. k-means clustering, based on protein expression revealed three distinct IIP clusters, which were not associated with age, smoking history, or baseline pulmonary function. These clusters had unique survival trajectories and provided more accurate survival predictions than the Gender Age Physiology (GAP) index (C-index 0.794 vs. 0.709). The cluster with the worst prognosis featured decreased inflammatory signaling and complement activation, with pathway analysis highlighting altered immune response pathways related to immunoglobulin production and B cell-mediated immunity. Conclusions: The unsupervised clustering of BALF proteomics provided a novel stratification of IIP patients, with potential implications for prognostic and therapeutic targeting. The identified molecular phenotypes underscore the diversity within the IIP classification and the potential importance of personalized treatments for these conditions. Future validation in larger, multi-ethnic cohorts is essential to confirm these findings and to explore their utility in clinical decision-making for patients with IIP.

Neutrophil extracellular traps linked to idiopathic pulmonary fibrosis severity and survival.

Background: Idiopathic pulmonary fibrosis (IPF) leads to progressive loss of lung function and mortality. Understanding mechanisms and markers of lung injury in IPF is paramount to improving outcomes for these patients. Despite the lack of systemic involvement in IPF, many analyses focus on identifying circulating prognostic markers. Using a proteomic discovery method followed by ELISA validation in multiple IPF lung compartments and cohorts we explored novel markers of IPF survival. Methods: In our discovery analysis, agnostic label-free quantitative proteomics differentiated lung tissue protein expression based on survival trajectory (n=10). Following selection of the candidate pathway (neutrophil extracellular trap (NET) formation), we subsequently validated the presence of NETs in the IPF lung microenvironment using fully quantitative assays of known NET remnants in separate IPF cohorts (n=156 and n=52) with bronchoalveolar lavage fluid. We then assessed the correlation of these markers with baseline pulmonary function and survival. Results: Discovery lung tissue proteomics identified NET formation as significantly associated with poor IPF survival. Using fully quantitative confirmatory tests for reproducibility we confirmed the presence of NET markers in IPF BALF and found significant correlations with worse pulmonary function in both cohorts (p<0.03 and p = 0.04 respectively). In the survival cohort, higher levels of NET markers predicted worse survival after adjusting for gender, age, and baseline physiologic severity (hazard ratio range: 1.79-2.19). Conclusions: NET markers were associated with disease severity and worse survival in IPF. These findings suggest NET formation contributes to lung injury and decreased survival in IPF and may represent a potential therapeutic target.

Aortic valve reconstruction surgery using autologous pericardium: The experience in Vietnam.

OBJECTIVE: The study aimed to evaluate the indications and describe the aortic valve reconstruction techniques by Ozaki's procedure in Vietnam and report mid-term outcomes of this technique in Vietnam. METHODS: Between June 2017 and December 2019, 72 patients diagnosed with isolated aortic valve disease, with a mean age of 52.9 (19-79 years old), and a male:female ratio of 3:1 underwent aortic valve reconstruction surgery by Ozaki's technique at Cardiovascular Center, E Hospital, Vietnam. RESULTS: The aortic valve diseases consisted of aortic stenosis (42%), aortic regurgitation (28%), and a combination of both (30%). In addition, the proportion of aortic valves with bicuspid morphology and small annulus (≤21 mm) was 28% and 38.9%, respectively. The mean aortic cross-clamp time was 106 ± 13.8 min, mean cardiopulmonary bypass time was 136.7 ± 18.5 min, and 2.8% of all patients required conversion to prosthetic valve replacement surgery. The mean follow-up time was 26.4 months (12-42 months), the survival rate was 95.8%, the reoperation rate was 2.8%, and rate of postoperative moderate or higher aortic valve regurgitation was 4.2%. Postoperative valvular hemodynamics was favorable, with a peak pressure gradient of 16.1 mmHg and an effective orifice area index of 2.3 cm2 . CONCLUSIONS: This procedure was safe and effective, with favorable valvular hemodynamics and a low rate of valvular degeneration. However, more long-term follow-up data are needed.

Totally Endoscopic Surgical Repair of Partial Atrioventricular Septal Defect in Children: Two Cases.

There have been few reports on the application of totally endoscopic surgery for repairing partial atrioventricular septal defect. In this report, we present two children who were successfully repaired partial atrioventricular septal defect by using totally endoscopic surgery without robotic assistance.

Totally endoscopic atrial septal defect repair using transthoracic aortic cannulation in a 10.5-kg-boy.

INTRODUCTION: Although totally endoscopic surgery (TES) has been widely applied for the treatment of atrial septal defect (ASD), small children receive few benefits from this technique due to risks of the femoral cannulation. CASE PRESENTATION: A 23-month-old boy, weighing 10.5 kg, with the diagnosis of sinus venosus ASD underwent successful repair by TES. We performed this surgery through 4 small trocars (one 12 mm trocar and three 5 mm trocars), without robotic assistance. In this case, we inserted the arterial cannula directly into the ascending aorta instead of the femoral artery (FA). The defects were repaired on the beating heart with CO2 insufflation. DISCUSSION: Femoral cannulation in small children pose some risks, such as increased arterial line pressure, critical lower limb ischaemia, and post-operative iliac or femoral arterial stenosis. Putting the arterial cannula directly into the ascending aorta is a good solution but is difficult to be performed through TES, especially in small children. The major concern of operating on the beating heart is the air embolism, which requires special preventative methods. CONCLUSION: Transthoracic aortic cannulation may facilitate TES in small children. However, the safety and efficacy of this approach needs to be validated by larger studies preferably randomised controlled trials.

21st century natural product research and drug development and traditional medicines.

Natural products and related structures are essential sources of new pharmaceuticals, because of the immense variety of functionally relevant secondary metabolites of microbial and plant species. Furthermore, the development of powerful analytical tools based upon genomics, proteomics, metabolomics, bioinformatics and other 21st century technologies are greatly expediting identification and characterization of these natural products. Here we discuss the synergistic and reciprocal benefits of linking these 'omics technologies with robust ethnobotanical and ethnomedical studies of traditional medicines, to provide critically needed improved medicines and treatments that are inexpensive, accessible, safe and reliable. However, careless application of modern technologies can challenge traditional knowledge and biodiversity that are the foundation of traditional medicines. To address such challenges while fulfilling the need for improved (and new) medicines, we encourage the development of Regional Centres of 'omics Technologies functionally linked with Regional Centres of Genetic Resources, especially in regions of the world where use of traditional medicines is prevalent and essential for health.

Dose separation does not overcome the pharmacokinetic interaction between fosamprenavir and lopinavir/ritonavir.

Previous investigations have shown a significant negative two-way drug interaction between fosamprenavir (FPV) and lopinavir/ritonavir (LPV/RTV) in both human immunodeficiency virus (HIV)-infected patients and seronegative volunteers. This randomized, nonblinded, three-way crossover study of HIV-seronegative adult volunteers investigated dose separation and increased doses of RTV as a means to overcome the interaction between FPV and LPV/RTV. Eleven HIV-seronegative volunteers were given FPV plus LPV/RTV at 700 mg plus 400/100 mg every 12 hours (q12h) simultaneously for 10 days and then randomized to receive each of three 7-day treatments in one of six possible sequences, as follows: FPV plus LPV/RTV at 700 mg plus 400 mg/100 mg q12h simultaneously, FPV/RTV at 700 mg/100 mg q12h plus LPV/RTV at 400 mg/100 mg q12h, with doses separated by 4 h, and FPV/RTV at 1,400 mg/200 mg in the morning plus LPV/RTV at 800 mg/200 mg in the evening. Pharmacokinetic sampling was performed on day 8 of each treatment, and samples were analyzed for FPV, amprenavir (APV), LPV, and RTV concentrations by high-performance liquid chromatography-tandem mass spectrometry. Geometric mean ratios (GMR [with 95% confidence intervals]) for the 4- and 12-h dose separation strategies compared to simultaneous administration were calculated for the areas under the concentration-time curves from 0 to 24 h. Compared to simultaneous administration, RTV exposures increased with both 4-h and 12-h dose separation strategies (GMR, 5.30 [3.66 to 7.67] and 4.45 [3.09 to 6.41], respectively). LPV exposures also significantly increased with both 4-h and 12-h dose separation strategies (GMR, 1.76 [1.34 to 2.32] and 1.43 [1.02 to 2.01], respectively). However, both the 4- and 12-h strategies resulted in greater reductions in APV exposure (0.67 [0.54 to 0.83] and 0.77 [0.59 to 0.99], respectively) compared to simultaneous administration. Additional investigations are warranted to determine the optimal dosing of FPV with LPV/RTV.