Disparities in brain health comorbidity management in intracerebral hemorrhage

BackgroundIntracerebral hemorrhage (ICH) disproportionally affects underserved populations, and coincides with risk factors for cardiovascular events and cognitive decline after ICH. We investigated associations between social determinants of health and management of blood pressure (BP), hyperlipidemia, diabetes, obstructive sleep apnea (OSA), and hearing impairment before and after ICH hospitalization.MethodsSurvivors of the Massachusetts General Hospital longitudinal ICH study between 2016 and 2019 who received healthcare at least 6 months after ICH were analyzed. Measurements of BP, LDL and HbA1c and their management in the year surrounding ICH and referrals for sleep studies and audiology up to 6 months after ICH were gathered from electronic health records. The US-wide area deprivation index (ADI) was used as proxy for social determinants of health.ResultsThe study included 234 patients (mean 71 years, 42% female). BP measurements were performed in 109 (47%) before ICH, LDL measurements were performed in 165 (71%), and HbA1c measurements in 154 (66%) patients before or after ICH. 27/59 (46%) with off-target LDL and 3/12 (25%) with off-target HbA1c were managed appropriately. Of those without history of OSA or hearing impairment before ICH, 47/207 (23%) were referred for sleep studies and 16/212 (8%) to audiology. Higher ADI was associated with lower odds of BP, LDL, and HbA1c measurement prior to ICH [OR 0.94 (0.90–0.99), 0.96 (0.93–0.99), and 0.96 (0.93–0.99), respectively, per decile] but not with management during or after hospitalization.ConclusionSocial determinants of health are associated with pre-ICH management of cerebrovascular risk factors. More than 25% of patients were not assessed for hyperlipidemia and diabetes in the year surrounding ICH hospitalization, and less than half of those with off-target values received treatment intensification. Few patients were evaluated for OSA and hearing impairment, both common among ICH survivors. Future trials should evaluate whether using the ICH hospitalization to systematically address co-morbidities can improve long-term outcomes

The predictive validity of a Brain Care Score for dementia and stroke: data from the UK Biobank cohort

IntroductionThe 21-point Brain Care Score (BCS) was developed through a modified Delphi process in partnership with practitioners and patients to promote behavior changes and lifestyle choices in order to sustainably reduce the risk of dementia and stroke. We aimed to assess the associations of the BCS with risk of incident dementia and stroke.MethodsThe BCS was derived from the United Kingdom Biobank (UKB) baseline evaluation for participants aged 40–69 years, recruited between 2006–2010. Associations of BCS and risk of subsequent incident dementia and stroke were estimated using Cox proportional hazard regressions, adjusted for sex assigned at birth and stratified by age groups at baseline.ResultsThe BCS (median: 12; IQR:11–14) was derived for 398,990 UKB participants (mean age: 57; females: 54%). There were 5,354 incident cases of dementia and 7,259 incident cases of stroke recorded during a median follow-up of 12.5 years. A five-point higher BCS at baseline was associated with a 59% (95%CI: 40-72%) lower risk of dementia among participants aged <50. Among those aged 50–59, the figure was 32% (95%CI: 20-42%) and 8% (95%CI: 2-14%) for those aged >59 years. A five-point higher BCS was associated with a 48% (95%CI: 39-56%) lower risk of stroke among participants aged <50, 52% (95%CI, 47-56%) among those aged 50–59, and 33% (95%CI, 29-37%) among those aged >59.DiscussionThe BCS has clinically relevant and statistically significant associations with risk of dementia and stroke in approximately 0.4 million UK people. Future research includes investigating the feasibility, adaptability and implementation of the BCS for patients and providers worldwide

Accelerated stem cell labeling with ferucarbotran and protamine

To develop and characterize a clinically applicable, fast and efficient method for stem cell labeling with ferucarbotran and protamine for depiction with clinical MRI. The hydrodynamic diameter, zeta potential and relaxivities of ferucarbotran and varying concentrations of protamine were measured. Once the optimized ratio was found, human mesenchymal stem cells (MSCs) were labeled at varying incubation times (1–24 h). Viability was assessed via Trypan blue exclusion testing. 150,000 labeled cells in Ficoll solution were imaged with T1-, T2- and T2*-weighted sequences at 3 T, and relaxation rates were calculated. Varying the concentrations of protamine allows for easy modification of the physicochemical properties. Simple incubation with ferucarbotran alone resulted in efficient labeling after 24 h of incubation while assisted labeling with protamine resulted in similar results after only 1 h. Cell viability remained unaffected. R2 and R2* relaxation rates were drastically increased. Electron microscopy confirmed intracellular iron oxide uptake in lysosomes. Relaxation times correlated with results from ICP-AES. Our results show internalization of ferucarbotran can be accelerated in MSCs with protamine, an approved heparin antagonist and potentially clinically applicable uptake-enhancing agent

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.</p

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Species differences in choroidal vasodilative innervation: evidence for specific intrinsic nitrergic and VIP-positive neurons in the human eye

The presence of an intrinsic nerve cell plexus that is specifically localized in human eyes in the temporal-central portion of the choroid indicates a functional significance of the nitrergic choroidal innervation for the fovea