[Extracranial/intracranial vascular bypass to control carotid artery blowout in postirradiated nasopharyngeal carcinoma patients].

Objective:To summarize and analyze the effect of extracranial/intracranial vascular bypass in the treatment of internal carotid artery burst hemorrhage after radiotherapy for nasopharyngeal carcinoma（NPC）. Methods:A retrospective analysis of the data of 9 patients with nasopharyngeal carcinoma and carotid artery blowout syndrome（CBS） who underwent extracranial/intracranial vascular bypass. Collected patient demographics, treatment course and dose of radiotherapy, analyze the effect of extracranial/intracranial vascular bypass on the prognosis of patients with internal carotid artery burst hemorrhage, including perioperative stroke and death, overall survival rate, and rebleeding rate. Results:Nine patients were included in the study. The average age is 53.5 years. The pathological types were all non-keratinizing squamous cell carcinoma, undifferentiated, stage Ⅳ; 7 cases of local NPC recurrence, 2 cases of skull base osteonecrosis; all 9 cases had internal carotid artery hemorrhage, including 7 cases of petrous carotid artery and 2 cases of cervical carotid artery; 3 cases of typeⅠthreatened CBS（33.3%）, 2 cases of type Ⅱ impending CBS（22.2%）, and 4 cases of type Ⅲ acute CBS（44.45%）. All patients underwent extracranial/intracranial vascular bypass surgery, and there were no perioperative deaths and strokes. The mean follow-up was 16.7 months. The median overall survival time of the patients was 22.1 months and the 90-day, 1-year and 2-year survival rates were 100.0%, 75.0% and 30.0%, respectively. Conclusion:Patients with internal carotid artery burst hemorrhage after radiotherapy for nasopharyngeal carcinoma can be safely treated by extracranial/intracranial vascular bypass surgery and obtain a longer survival rate.

Extracranial/Intracranial Vascular Bypass in the Treatment of Head and Neck Cancer - Related Carotid Blowout Syndrome.

OBJECTIVE/HYPOTHESIS: To investigate the endovascular intervention or extracranial/intracranial (EC/IC) vascular bypass in the management of patients with head and neck cancer-related carotid blowout syndrome (CBS). STUDY DESIGN: Retrospective case series. METHODS: Retrospective analysis of clinical data of patients with head and neck cancer-related CBS treated by endovascular intervention and/or EC/IC vascular bypass, analysis of its bleeding control, neurological complications, and survival results. RESULTS: Thrity-seven patients were included. Twenty-five were associated with external carotid artery (ECA); twelve were associated with internal or common carotid artery (ICA/CCA). All patients with ECA hemorrhage were treated with endovascular embolization. Of the 12 patients with ICA/CCA hemorrhage, 9 underwent EC/IC bypass, 1 underwent endovascular embolization, and 3 underwent endovascular stenting. For patients with ECA-related CBS, the median survival was 6 months, and the 90-day, 1-year, and 2-year survival rates were 67.1%, 44.7%, and 33.6%, respectively; the estimated rebleeding risk at 1-month, 6-month, and 2-year was 7.1%, 20.0%, and 31.6%, respectively. For patients with ICA/CCA-related CBS, the median survival was 22.5 months, and the 90-day, 1-year, and 2-year survival rates were 92.3%, 71.8%, and 41.0%, respectively; the estimated rebleeding risk at 1 month, 6 months, and 2 years is 7.7%,15.4%, and 15.4%, respectively. ICA/CCA-related CBS patients have significantly longer survival time and lower risk of rebleeding, which may be related to the more use of EC/IC vascular bypass as a definite treatment. CONCLUSIONS: For patients with ICA/CCA-related CBS, if there is more stable hemodynamics, longer expected survival, EC/IC vascular bypass is preferred. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1548-1556, 2021.

Calcium and oxidative stress mediate perillaldehyde-induced apoptosis in Candida albicans.

New anti-Candida albicans drugs are needed due to the emergence of resistant cases in recent years. Perillaldehyde (PAE) is a natural monoterpenoid compound derived from Perilla frutescens. The minimum inhibitory concentration of PAE against C. albicans was 0.4 µL/mL. We aimed to elucidate the antifungal mode of action of PAE against C. albicans. The antifungal activity of PAE against C. albicans was found to correlate with an elevation in intracellular Ca2+ and accumulation of ROS. Several downstream apoptosis events such as the disruption of mitochondrial membrane potential, phosphatidylserine externalization, cytochrome c release, and metacaspase activation were observed in PAE-treated cells. DNA damage and nuclear fragmentation assays also revealed apoptosis of C. albicans cells. In summary, by means of fluorescent microscopy, flow cytometer analysis, and Western blot, our data uncovered that PAE exerts its antifungal activity through Ca2+ and oxidative stress-mediated apoptosis mechanisms. This study deciphered the mode of action of PAE, which will be useful in the design of improved antifungal therapies.

Nerol triggers mitochondrial dysfunction and disruption via elevation of Ca2+ and ROS in Candida albicans.

The antifungal activity of Nerol (NEL) against Candida albicans, a pathogenic fungus, has a minimum inhibitory concentration (MIC) of 4.4mM that causes noteworthy candidacidal activity through an apoptosis-like mechanism. Calcium (Ca2+) levels and reactive oxygen species (ROS) production, which are the major causes of apoptosis, were determined in C. albicans cells treated with NEL and were found to increase, which related to mitochondrial dysfunction and disruption. A series of characteristic changes of apoptosis caused by NEL, including mitochondrial membrane depolarization, cytochrome c (cyt c) release, and metacaspase activation were examined using a flow cytometer and Western blot. The results showed that an increase in intracellular Ca2+ and ROS led to dramatically decreased mitochondrial membrane potential (MMP); cyt c was also released from the mitochondria to the cytosol. Other early apoptotic features were also observed with the metacaspase activation. Finally, the morphological changes of the cells were observed, including phosphatidylserine (PS) externalization, nuclear condensation, and DNA fragmentation through Annexin V-FITC and PI double staining, TUNEL assay, and DAPI staining. The results supported the hypothesis that NEL was involved in the apoptosis of C. albicans cells not only at the early stages, but also at the late stages. In summary, NEL can trigger mitochondrial dysfunction and disruption via elevation of Ca2+ and ROS leading to apoptosis in C. albicans. This research on the mechanism of cell death triggered by NEL against C. albicans has important significance for providing a novel treatment of C. albicans infections.

Perillaldehyde, a Promising Antifungal Agent Used in Food Preservation, Triggers Apoptosis through a Metacaspase-Dependent Pathway in Aspergillus flavus.

In the present study, we provide detailed insights into perillaldehyde (PAE)'s mechanisms of action on Aspergillus flavus and offer evidence in favor of the induction of an apoptosis-like phenotype. Specifically, PAE's antifungal mode of action was investigated through the detection of mitochondrial membrane potential (MtΔψ) and phosphatidylserine (PS) exposure, as well as intracellular Ca2+ level, reactive oxygen species accumulation, and metacaspase activation. This was done by way of fluorometry, measuring DNA fragmentation, and condensation by fluorescent microscopy. Furthermore, we searched for phenotypic changes characteristic of apoptosis by transmission electron microscopy and flow cytometry, determining the amount of cytochrome c released using Western blotting. Results indicated that cultivation of A. flavus in the presence of PAE caused depolarization of MtΔψ, rapid DNA condensation, large-scale DNA fragmentation, and an elevation of intracellular Ca2+ level. The percentage of early apoptotic cells with exposure of PS were 27.4% and 48.7%, respectively, after 9 h incubations with 0.25 and 0.5 µL/mL of PAE. The percentage of stained cells with activated intracellular metacaspases exposed to PAE at concentrations of 0.25 and 0.5 µL/mL compared with control subjects were increased by 28.4 ± 3.25% and 37.9 ± 4.24%, respectively. The above results has revealed that PAE induces fungal apoptosis through a caspase-dependent mitochondrial pathway. In all, our findings provide a novel mechanism for exploring a possible antifungal agent used in food preservation.