Airway collapse hinders recovery in bronchoscopy therapy for postintubation tracheal stenosis patients.

BACKGROUND: Expiratory central airway collapse (ECAC) following postintubation airway stenosis (PITS) is a rare phenomenon. The impact of airway malacia and collapse on the prognosis and the success rate of bronchoscopic interventional therapy in patients with PITS had been inadequately investigated. OBJECTIVE: The aim of this research was to assess the influence of airway malacia and collapse on the efficacy of bronchoscopic interventional therapy in patients with PITS. DESIGN: This retrospective analysis examined the medical documentation of individuals diagnosed with PITS who underwent bronchoscopic intervention at the tertiary interventional pulmonology center of Emergency General Hospital from 2014 to 2021. MAIN OUTCOME MEASURES: Data pertaining to preoperative, perioperative, and postoperative stages were documented and subjected to analysis. RESULTS: The patients in malacia and collapse group (MC group) exhibited a higher frequency of perioperative complications, including intraoperative hypoxemia, need for reoperation within 24 h, and postoperative intensive care unit admission rate (P < 0.05, respectively). Meanwhile, patients in group MC demonstrated significantly worse postoperative scores (higher mMRC score and lower KPS score) compared to those in pure stenosis group (P < 0.05, respectively), along with higher degrees of stenosis after treatment and a lower success rate of bronchoscopic intervention therapy cured (P < 0.05, respectively). Pearson analysis results showed that these terms were all significantly correlated with the occurrence of airway malacia and collapse in the airway (P < 0.05, respectively). CONCLUSION: The presence of malacia or collapse in patients with PITS was associated with increased perioperative complications following bronchoscopic interventional therapy, and significantly reduced the long-term cure rate compared to patients with pure tracheal stenosis. Trial registration Chinese Clinical Trial Registry on 06/12/2021. REGISTRATION NUMBER: ChiCTR2100053991.

Early and Mid-Term Outcomes of Using the Chimney Technique in Redo Mitral Valve Replacement in Patients with a Small Mitral Annulus.

The outcomes of redo mitral valve replacement (Re-MVR) in a small mitral annulus with the use of the chimney technique are not well documented. The purpose of this study is to present our early experience with this group of patients, illustrating the periop-erative complications and mortality outcomes. From 2019 to 2020, 77 consecutive patients underwent Re-MVR with the use of the chimney technique because of a small mitral annulus. To evaluate heart structural integrity and clinical outcomes, postoperative clinical data and echocardiograms were examined. The mean age was 56.7 ± 15.98 years. All patients underwent mitral valve surgery, of which 62 were mitral valve replacements, 7 mitral valve repairs, and 8 double valve replacements. The preoperative mitral valve mean gradient was 18.07 ± 9.40 mmHg, and the postoperative mitral prosthesis size was 28.51 ± 1.22 mm. The median increment of mitral size enlargement was 4 (0, 6) valve sizes. The mean mitral gradient coming out of the operating room was 10.34 ± 2.12 mmHg, and at the follow-up echocardiogram performed at 3 years after the procedure, it was 10.36 ± 1.70 mmHg. One-year survival was 93.3%, while the 4-year survival rate was 89.3%, with no reoperation. The use of the chimney technique in small mitral valve re-mitral valve replacement results in larger valve sizes. Moreover, the mean gradients over the mitral valve are acceptable both intraoperatively and over time.

Type and morphology affect the success rate of bronchoscopy for postintubation tracheal stenosis.

Objective: With advancements in respiratory interventional techniques, bronchoscopic intervention technology has emerged as a viable approach for managing postintubation tracheal stenosis (PITS). However, there was a paucity of research investigating the potential impact of stenosis characteristics and morphology (such as stenosis degree, length, type, and morphology) on bronchoscopic intervention treatment prognosis for PITS patients. This study was to assess the impact of various preoperative stenosis characteristic factors on the bronchoscopic cure rate among patients. Methods: This is a retrospective study analyzing the medical records of patients with PITS who received bronchoscopic intervention at the tertiary interventional pulmonology center. Results: Among the cases, 115 individuals achieved a in a success rate of 79.86% for bronchoscopic intervention therapy and were assigned to Group S. On the other hand, 29 cases required surgical intervention, accounting for a surgical treatment rate of 20.14% and were assigned to Group F. The stenosis in the Group F predominantly exhibited irregular shapes with scar granulation accompanied by tracheal chondromalacia collapse. Patients in group S experienced fewer total procedures, rigid bronchoscopy treatment, intraoperative hypoxemia, needed emergency re-bronchoscopy in 24 h and transferred to ICU postoperatively. Patients with pure scar and granuloma, the rate of bronchoscopic success cure was higher than patients with scar granulation accompanied by tracheal chondromalacia (odds ratio: 8.208; 95% confidence interval: 2.755-24.459), and regular stenosis morphology was associated with a higher bronchoscopic success cure rate (odds ratio: 9.463; 95% confidence interval: 3.128-28.623). Conclusion: Irregular airway stenosis, chondromalacia or airway collapse are key factors affecting the success rate of bronchoscopic treatment for post-intubation tracheal stenosis. Level of evidence: 4 (historically controlled studies).

The effect of phosphorylation on the conformational dynamics and allostery of the association of death-associated protein kinase with calmodulin.

Protein phosphorylation plays an important role in the signal transduction and is capable of regulation of cell activity. The death-associated protein kinase 1 (DAPK1), as a Ser/Thr kinase, interacts with calmodulin (CaM) to regulate apoptotic and autophagic signaling. Autophosphorylation of DAPK1 at Ser308 located at the autoregulatory domain (ARD) blocks CaM binding and inhibits kinase catalytic activity. However, the mechanism underlying the influence of Ser308 phosphorylation (pS308) on the DAPK1 activity remains unclear. Here, we performed multiple, microsecond length molecular dynamics (MD) simulations, the molecular mechanics generalized Born/surface area (MM-GBSA) binding free energy calculations, principal component analysis, and dynamic cross-correlation analysis to unravel the conformational dynamics and allostery of the DAPK1 - CaM interaction triggered by the pS308 at the ARD. MD simulations showed that pS308 affected the conformational stability of the DAPK1 - CaM complex. Further energetic and structural exploration revealed that pS308 weakened the association of the phosphorylated DAPK1 to CaM, which lowered the susceptibility of DAPK1 to be activated by CaM. This result can provide mechanistic insights into the molecular underpinning through which the DAPK1 kinase activity is modulated by the auto-phosphorylation.Communicated by Ramaswamy H. Sarma.

Nanoparticles targeting mutant p53 overcome chemoresistance and tumor recurrence in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) shows high drug resistance and leads to low survival due to the high level of mutated Tumor Protein p53 (TP53). Cisplatin is a first-line treatment option for NSCLC, and the p53 mutation is a major factor in chemoresistance. We demonstrate that cisplatin chemotherapy increases the risk of TP53 mutations, further contributing to cisplatin resistance. Encouragingly, we find that the combination of cisplatin and fluvastatin can alleviate this problem. Therefore, we synthesize Fluplatin, a prodrug consisting of cisplatin and fluvastatin. Then, Fluplatin self-assembles and is further encapsulated with poly-(ethylene glycol)-phosphoethanolamine (PEG-PE), we obtain Fluplatin@PEG-PE nanoparticles (FP NPs). FP NPs can degrade mutant p53 (mutp53) and efficiently trigger endoplasmic reticulum stress (ERS). In this study, we show that FP NPs relieve the inhibition of cisplatin chemotherapy caused by mutp53, exhibiting highly effective tumor suppression and improving the poor NSCLC prognosis.

Effect of Inorganic Fillers on Electrical and Mechanical Properties of Ceramizable Silicone Rubber.

Ceramizable silicone rubber (CSR) composed of silicone rubber matrix and inorganic fillers can be transformed into a dense flame-retardant ceramic upon encountering high temperatures or flames. Conventionally, CSR can be sintered into a dense ceramic at temperatures above 1000 °C, which is higher than the melting point of a copper conductor used in a power cable. In this study, the vulcanization process and mass ratio of inorganic fillers of CSR were studied to lower its ceramization temperature to 950 °C. The electrical and mechanical properties of CSRs and their ceramic bulks were studied with various ratios of wollastonite and muscovite. It was found that the CSR samples could be successfully fabricated using a two-step vulcanization technique (at 120 °C and 150 °C, respectively). As a high ratio of muscovite filler was introduced into the CSR, the sample presented a high dc electrical resistivity of 6.713 × 1014 Ω·cm, and a low dielectric constant of 4.3 and dielectric loss of 0.025 at 50 Hz. After the thermal sintering (at 950 °C for 1 h) of the CSR sample with a high ratio of muscovite, the ceramic sample exhibits a dense microstructure without any pores. The ceramic also demonstrates excellent insulating properties, with a volume resistivity of 8.69 × 1011 Ω·cm, and a low dielectric loss of 0.01 at 50 Hz. Meanwhile, the three-point bending strength of the ceramic sample reaches a value of 110.03 MPa. This study provides a potential route to fabricate CSR used for fire-resistant cables.