Chronic inflammation and infection of the nasal sinuses, also referred to as Chronic Rhinosinusitis (CRS), severely affects patients’ quality of life. Adhesions, ostial stenosis, infection and inflammation relapses complicate chronic sinusitis treatment strategies. Drug-eluting stents, packings or implants have been suggested as reasonable alternatives for addressing these concerns. This article reviewed potential drug candidates for nasal implants, formulation methods/optimization and characterization methods. Clinical applications and important considerations were also addressed. Clinically-approved implants (Propel™ implant, the Relieva stratus™ MicroFlow spacer, and the Sinu-Foam™ spacer) for CRS treatment was an important focus. The advantages and limitations, as well as future considerations, challenges and the need for additional research in the field of nasal drug implant development, were discussed.

The CHKB gene encodes choline kinase β, which catalyzes the first step in the biosynthetic pathway for the major phospholipid phosphatidylcholine. Homozygous loss-of-function variants in human CHKB are associated with a congenital muscular dystrophy. Dilated cardiomyopathy is present in some CHKB patients and can cause heart failure and death. Mechanisms underlying a cardiac phenotype due to decreased CHKB levels are not well characterized. We determined that there is cardiac hypertrophy in Chkb^−/− mice along with a decrease in left ventricle size, internal diameter, and stroke volume compared with wildtype and Chkb^+/− mice. Unlike wildtype mice, 60% of the Chkb^+/− and all Chkb^−/− mice tested displayed arrhythmic events when challenged with isoproterenol. Lipidomic analysis revealed that the major change in lipid level in Chkb^+/− and Chkb^−/− hearts was an increase in the arrhythmogenic lipid acylcarnitine. An increase in acylcarnitine level is also associated with a defect in the ability of mitochondria to use fatty acids for energy and we observed that mitochondria from Chkb^−/− hearts had abnormal cristae and inefficient electron transport chain activity. Atrial natriuretic peptide (ANP) is a hormone produced by the heart that protects against the development of heart failure including ventricular conduction defects. We determined that there was a decrease in expression of ANP, its receptor NPRA, as well as ventricular conduction system markers in Chkb^+/− and Chkb^−/− mice.

To examine the perioperative, postoperative, and long-term outcomes of fenestrated/branched endovascular aneurysm repair (F/BEVAR) in octogenarians compared with nonoctogenarians. A multicenter, retrospective cohort study was conducted using the Vascular Quality Improvement database, which prospectively captures information on patients who undergo vascular surgery across 1021 academic and community hospitals in North America. All patients who underwent F/BEVAR endovascular aortic repair from 2012 to 2022 were included. Patients were stratified into two groups: those aged <80 years and those aged ≥80 years at the time of the procedure. The preoperative, intraoperative, and postoperative factors were compared between the two groups. The primary outcome was long-term all-cause mortality; secondary outcomes included aortic-specific mortality and aortic-specific reintervention. A total of 6007 patients (aged <80 years, n = 4860; aged ≥80 years, n = 1147) who had undergone F/BEVAR procedures were included. No significant difference was found in technical success, postoperative length of stay, length of intensive care unit stay, postoperative bowel ischemia, and spinal cord ischemia. After adjustment for baseline covariates, octogenarians were more likely to suffer from a postoperative complication (odds ratio [OR]: 1.16; [95% confidence interval (CI): 0.98-1.37], P < .001) and be discharged to a rehabilitation center (OR: 1.60; [95% CI: 1.27-2.00], P < .001) or nursing home (OR: 2.23; [95% CI: 1.64-3.01], P < .001). Five-year survival was lower in octogenarians (83% vs 71%, hazard ratio [HR]: 1.70; [95% CI: 1.46-2.0], P < .0001). Multivariate Cox proportional hazard analysis demonstrated that age was associated with increased all-cause mortality (HR: 1.72, [95% CI: 1.39-2.12], P < .001) and aortic-specific mortality (HR: 1.92, [95% CI: 1.04-3.68], P = .038). Crawford extent II aortic disease was associated with an increase in all-cause mortality (HR 1.49; [95% CI: 1.01-2.19], P < .001), aortic-specific mortality (HR: 5.05; [95% CI: 1.35-18.9], P = .016), and aortic-specific reintervention (HR: 1.91; [95% CI: 1.24-2.93], P = .003). Functional dependence was associated with increased all-cause mortality (HR: 2.90; [95% CI: 1.87-4.51], P < .001) and aortic-specific mortality (HR: 4.93; [95% CI: 1.69-14.4], P = .004). Our findings suggest that octogenarians do have a mildly increased mortality rate and rate of adverse events after F/BEVAR procedures. Despite this, when adjusted for other risk factors, age is on par with other medical comorbidities and therefore should not be a strict exclusion criterion for F/BEVAR procedures, rather considered in the global context of patient's aortic anatomy, health, and functional status.

To investigate potential prevention or attenuation of anti- cancer drug induced cardiotoxicity using anti-ischemic drugs, a rat myoblast (H9c2) cell line was used as our in vitro cardiac model. Irinotecan and doxorubicin were found to be cytotoxic for the H9c2 cell line with IC₅₀ of 30.69 ± 6.20 and 20.94 ± 6.05 mmol L^-1, respectively. 5-Flurouracil and cladribine were not cytotoxic and thus IC₅₀ could not be calculated. When 100 mmol L^-1 doxorubicin was incubated for 72 hours with 50 mmol L^-1 diltiazem, 100 mmol L^-1 dexrazoxane and 100 mmol L^-1 losartan, respectively, there was a 58.7 ± 10.2, 52.2 ± 11.7 and 44.7 ± 5.4 % reduction in cell death. When 200 mmol L^-1 irinotecan was incubated for 72 hours with 100 mmol L^-1 dexrazoxane, losartan and diltiazem, respectively, a 27.7 ± 6.9, 25.6 ± 5.1, and 19.1 ± 2.3 % reduction in cell death was observed. Our data suggests that losartan and diltiazem were as effective as dexrazoxane in protecting the cells against irinotecan- and doxorubicin-induced cell toxicity. These findings offer potential uses of anti- -ischemic drugs for ablation of cytotoxicity in response to mitochondrial injury, thereby improving patient outcomes and reducing health-care costs.

There is no effective treatment for the total recovery of myocardial injury caused by an anticancer drug, doxorubicin (Dox). In this study, using a Dox-induced cardiac injury model, we compared the cardioprotective effects of ventricular cells harvested from 11.5-day old embryonic mice (E11.5) with those from E14.5 embryos. Our results indicate that tail-vein-infused E11.5 ventricular cells are more efficient at homing into the injured adult myocardium, and are more angiogenic, than E14.5 ventricular cells. In addition, E11.5 cells were shown to mitigate the cardiomyopathic effects of Dox. In vitro, E11.5 ventricular cells were more migratory than E14.5 cells, and RT-qPCR analysis revealed that they express significantly higher levels of cytokine receptors Fgfr1, Fgfr2, Pdgfra, Pdgfrb and Kit. Remarkably, mRNA levels for Fgf1, Fgf2, Pdgfa and Pdgfb were also found to be elevated in the Dox-injured adult heart, as were the FGF1 and PDGFB protein levels. Addition of exogenous FGF1 or PDGFB was able to enhance E11.5 ventricular cell migration in vitro, and, whereas their neutralizing antibodies decreased cell migration. These results indicate that therapies raising the levels of FGF1 and PDGFB receptors in donor cells and or corresponding ligands in an injured heart could improve the efficacy of cell-based interventions for myocardial repair.