Association between traditional cardiovascular risk factors and mortality in the oldest old: untangling the role of frailty.

BACKGROUND: To date, there is no consensus regarding cardiovascular risk management in the very old. Studies have shown that the relationship between traditional cardiovascular risk factors and mortality is null or even inverted within this age group. This relationship could be modified by the presence of frailty. This study was performed to examine the effect of frailty on the association between cardiovascular risk factors and mortality in the oldest old. METHODS: The BELFRAIL study is a prospective, observational, population-based cohort study of 567 subjects aged 80 years and older. Data on cardiovascular risk factors were recorded. Frailty was assessed using three different models: the Groningen Frailty Indicator, Fried and Puts models. Participants were considered robust if they were 'not frail' according to all three models, and frail if they met the frailty criteria for one of the three models. The follow-up data on mortality and cause of death were registered. RESULTS: No cardiovascular risk factor was associated with mortality in subjects with and without cardiovascular disease. The presence of frailty was a strong risk factor for mortality [HR: 2.5, 95%CI: (1.9-3.2) for all-cause mortality; HR: 2.2, 95%CI: (1.4-3.4) for cardiovascular mortality]. In robust patients, a history of cardiovascular disease increased the risk for mortality [HR: 1.7, 95%CI: (1.1-2.5) for all-cause mortality; HR: 2.2, 95%CI: (1.2-3.9) for cardiovascular mortality]. In frail patients, there was no association between any of the traditional risk factors and mortality. CONCLUSIONS: Traditional cardiovascular risk factors were not associated with mortality in very old subjects. Frailty was shown to be a strong risk factor for mortality in this age group. However, frailty could not be used to identify additional subjects who might benefit more from cardiovascular risk management.

Polyhydrated ionogen with MgBr2 accelerates in vitro respiratory epithelial healing.

BACKGROUND: Remucoslization of the sinonasal cavity after sinus surgery is critical for successful outcomes. Recently, a novel antiprotease and antifibroblast compound, polyhydrated ionogen (PHI) with MgBr2, showed improved wound healing in a rabbit maxillary sinus mucosal wound model. We set out to determine if this effect was reproducible in an in vitro respiratory epithelial culture system. METHODS: Fully differentiated mature murine nasal septal air-liquid interface cultures were injured by creating a full-thickness 400-mM-wide scratch through the monolayer. Cultures were then treated with nothing, saline, or PHI with MgBr2 for 1 hour on the apical surface. Twenty-four hours after the injury cultures were fixed and processed for immunofluorescence with type IV beta-tubulin and Hoechst stain. RESULTS: Initial injury resulted in a wound of 394 micromolar (377-411 micromoler; 95% CI; n = 8). After 24 hours with no intervention the wound closed to 161 micromolar (138-184 micromolar; 95% CI; n = 9) and treatment with saline resulted in a residual gap of 88 micromolar (60-116 micromolar; 95% CI; n = 9; p < 0.05) and treatment with PHI with MgBr2 resulted in a gap of only 30 micromolar (14-46 micromolar; 95% CI; n = 9; p < 0.05). CONCLUSION: Poor healing of the sinonasal mucosa after surgery with loss of ciliary function results in adverse clinical outcomes. In an in vitro sinonasal respiratory epithelial injury model, a one-time treatment with PHI with MgBr2 showed significantly improved wound healing compared with saline or nothing. This is a viable model to further investigate the mechanism by which PHI with MgBr2 improves sinonasal remucosolization.

Murine ciliotoxicity and rabbit sinus mucosal healing by polyhydrated ionogen.

OBJECTIVES: Determine the toxicity and efficacy of a novel antiprotease topical irrigation, polyhydrated ionogen (PHI) ± MgBr2, in improving sinonasal remucosalization following surgery. STUDY DESIGN: Blinded, randomized controlled study. Setting. Academic. SUBJECTS AND METHODS: Ciliary beat frequency (CBF) of murine nasal septal explants was continuously recorded before and after addition of PHI solution to asses for ciliotoxicity. To evaluate for efficacy in remucosalization, 9 New Zealand white rabbits underwent bilateral medial-wall maxillary mucosal stripping followed by placement of an indwelling irrigation catheter. In a randomized fashion one side received 3 mL of normal saline (NS) daily, whereas the contralateral side received PHI ± MgBr2. Following a 14-day therapeutic trial, remucosalization was assessed by hematoxylin and eosin staining and immunohistochemistry for ß-tubulin, a marker of cilia. A semiquantitative grading of ciliated remucosalization was applied with a chi-square test to compare the saline with the PHI ± MgBr2 treatment. RESULTS: Safety evaluation of the PHI solutions demonstrated no evidence of ciliotoxicity. Histologic semiquantitative analysis of maxillary sinus remucosalization demonstrated significantly more ciliated epithelium (>60%) in the majority of PHI (n = 4) and PHI with MgBr2 (n = 5) treatment compared with the saline treatment (<30%) (n = 9). This was confirmed with immunohistochemical staining for type IV ß-tubulin a marker of respiratory cilia. CONCLUSIONS: Success of functional endoscopic sinus surgery depends on restoration of normal mucociliary clearance. Topical PHI application has previously been demonstrated to significantly increase dermal wound healing. PHI solution is not ciliotoxic, and daily topical PHI or PHI MgBr2 irrigation enhances ciliated remucosalization compared with saline.

Polyhydrated ionogen enhances postoperative sinonasal ciliated remucosalization.

BACKGROUND: Mucosalization of the sinonasal cavity following surgery is critical for successful outcomes. Recently a novel anti-protease compound, polyhydrated-ionogen (PHI) with Mg(2+)/Br(-), demonstrated improved dermal wound healing. We set out to investigate the effect of PHI Mg(2+)/Br(-) on sinus remucosalization following surgery. METHODS: A total of 24 rabbits underwent bilateral medial-wall maxillary mucosal stripping followed by placement of an indwelling irrigation catheter. In a randomized fashion 1 side received 3 cc normal saline (NS) daily, while the contralateral side received PHI Mg(2+)/Br(-). Following a 14-day therapeutic trial, remucosalization was assessed by hematoxylin and eosin (H&E) staining and immunohistochemistry for ß-tubulin, a marker of cilia. A semiquantitative grading of ciliated remucosalization was applied with a chi-square test used to compare distributions for each treatment. RESULTS: H&E staining comparison demonstrated NS treated sinuses (n = 24) had substantial bare areas with predominant ciliation scores under 30%. The PHI Mg(2+)/Br(-)-treated group (n = 24) achieved a statistically significant improvement in reciliation (>60%) when compared with NS (p < 0.01). These results were confirmed with Type IV ß-tubulin staining (p < 0.01). CONCLUSION: Poor postsurgical sinonasal mucosa healing results in adverse clinical outcomes. In a rabbit model of sinonasal mucosal healing, daily irrigation for 14 days with PHI Mg(2+)/Br(-)-enhanced ciliated remucosalization compared to saline.