Incident Dementia After Spontaneous Intracerebral Hemorrhage.

 Post-stroke cognitive impairment and dementia (PSCID) is a complication that affects long-term functional outcomes after stroke. Studies on dementia after long-term follow-up in stroke have focused predominantly on ischemic stroke, which may be different from the development of dementia after spontaneous intracerebral hemorrhage (ICH). In this review, we summarize the existing data and hypotheses on the development of dementia after spontaneous ICH, review the management of post-ICH dementia, and suggest areas for future research. Dementia after spontaneous ICH has a cumulative incidence of up to 32.0-37.4% at 5 years post-ICH. Although the pathophysiology of post-ICH dementia has not been fully understood, two main theoretical frameworks can be considered: 1) the triggering role of ICH (both primary and secondary brain injury) in precipitating cognitive decline and dementia; and 2) the contributory role of pre-existing brain pathology (including small vessel disease and neurodegenerative pathology), reduced cognitive reserve, and genetic factors predisposing to cognitive dysfunction. These pathophysiological pathways may have synergistic effects that converge on dysfunction of the neurovascular unit and disruptions in functional connectivity leading to dementia post-ICH. Management of post-ICH dementia may include screening and monitoring, cognitive therapy, and pharmacotherapy. Non-invasive brain stimulation is an emerging therapeutic modality under investigation for safety and efficacy. Our review highlights that there remains a paucity of data and standardized reporting on incident dementia after spontaneous ICH. Further research is imperative for determining the incidence, risk factors, and pathophysiology of post-ICH dementia, in order to identify new therapies for the treatment of this debilitating condition.

Effect of sarcopenia and frailty on outcomes among patients with brain metastases.

PURPOSE: Sarcopenia and frailty have been associated with increased mortality and duration of hospitalization in cancer. However, data investigating these effects in patients with brain metastases remain limited. This study aimed to investigate the effects of sarcopenia and frailty on clinical outcomes in patients with surgically treated brain metastases. METHODS: Patients who underwent surgical resection of brain metastases from 2011 to 2019 were included. Psoas cross-sectional area and temporalis thickness were measured by two independent radiologists (Cronbach's alpha > 0.98). Frailty was assessed using the Clinical Frailty Scale (CFS) pre-operatively and post-operatively. Overall mortality, recurrence, and duration of hospitalization were collected. Cox regression was performed for mortality and recurrence, and multiple linear regression for duration of hospitalization. RESULTS: 145 patients were included, with median age 60.0 years and 52.4% female. Psoas cross-sectional area was an independent risk factor for overall mortality (HR = 2.68, 95% CI 1.64-4.38, p < 0.001) and recurrence (HR = 2.31, 95% CI 1.14-4.65, p = 0.020), while post-operative CFS was an independent risk factor for overall mortality (HR = 1.88, 95% CI 1.14-3.09, p = 0.013). Post-operative CFS (ß = 15.69, 95% CI 7.67-23.72, p < 0.001) and increase in CFS (ß = 11.71, 95% CI 3.91-19.51, p = 0.004) were independently associated with increased duration of hospitalization. CONCLUSION: In patients with surgically treated brain metastases, psoas cross-sectional area was an independent risk factor for mortality and recurrence, while post-operative CFS was an independent risk factor for mortality. Post-operative frailty and increase in CFS significantly increased duration of hospitalization. Measurement of psoas cross-sectional area and CFS may aid in risk stratification of surgical candidates for brain metastases.

Trends in hemorrhagic stroke incidence and mortality in a National Stroke Registry of a multi-ethnic Asian population.

INTRODUCTION: High-quality epidemiological data on hemorrhagic stroke (HS) and its subtypes, intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH), remains limited in Asian ethnicities. We investigated the trends in HS incidence and 30-day mortality from 2005 to 2019 in a multi-ethnic Asian population from a national registry. PATIENTS AND METHODS: Data on all stroke cases from the Singapore Stroke Registry from 2005 to 2019 were collected. Cases were defined using centrally adjudicated review of diagnosis codes. Death outcomes were obtained by linkage with the national death registry. Incidence (per 100,000 people) and 30-day mortality (per 100 people) were measured as crude and age-standardized rates. Trends were analyzed using linear regression. RESULTS: We analyzed 19,017 cases of HS (83.9% ICH; 16.1% SAH). From 2005 to 2019, age-standardized incidence rates (ASIR) for HS remained stable from 34.4 to 34.5. However, age-standardized mortality rates (ASMR) decreased significantly from 29.5 to 21.4 (p < 0.001). For ICH, ASIR remained stable while ASMR decreased from 30.4 to 21.3 (p < 0.001); for SAH, ASIR increased from 2.7 to 6.0 (p = 0.006) while ASMR remained stable. In subgroup analyses, HS incidence increased significantly in persons <65 years (from 18.1 to 19.6) and Malays (from 39.5 to 49.7). DISCUSSION: From 2005 to 2019, ASIR of HS remained stable while ASMR decreased. Decreasing ASMR reflects improvements in the overall management of HS, consistent with global trends. CONCLUSION: Population health efforts to address modifiable risk factors for HS in specific demographic subgroups may be warranted to reduce incidence and mortality of HS.

Psychosocial Well-Being and Quality of Life in Uveitis: A Review.

PURPOSE: As a potentially sight-threatening disease with ocular, systemic, and treatment-related complications, uveitis diminishes quality of life (QOL) and affects psychosocial well-being. This review summarizes the existing tools for evaluating psychosocial well-being and/or QOL in patients with uveitis, explores the biological and non-biological factors affecting psychosocial well-being and/or QOL, and proposes future directions for incorporating these tools into clinical practice. METHODS: A systematic search of the MEDLINE, Embase, and Cochrane databases from inception to June 8, 2022 was conducted, screening for articles focused on psychosocial well-being and/or QOL in patients with uveitis. Both quantitative and qualitative analyses were performed. RESULTS: In uveitis research, the most frequently studied patient-reported outcome measures were vision-related QOL (e.g. Visual Function Questionnaire [VFQ-25]) and health-related QOL (e.g. Short Form Survey [SF-36]), followed by mental health indicators including depression and anxiety. Instruments have also been developed specific to the pediatric population (e.g. Effects of Youngsters' Eyesight on Quality of Life [EYE-Q]). Generally, studies report worse psychosocial outcomes and QOL in patients with uveitis compared to the general population. Contributory factors include both clinical (e.g. visual impairment, ocular comorbidities) and patient-related (e.g. older age, female sex) factors. CONCLUSION: Given the heterogeneity of instruments used, it is worth considering standardization across large uveitis studies and trials. Beyond research, given the biopsychosocial effects on patients with uveitis, there are benefits to incorporating QOL and psychosocial assessments into clinical practice. Simplification of questionnaires into abridged forms, focusing on the most clinically relevant aspects of patient care, may be considered.

Effect of blood type on mortality among patients with brain metastases.

OBJECTIVE: ABO blood type has been associated with mortality among patients with cancer, but this association has thus far not been investigated among patients with brain metastases. Hence, we aimed to investigate the association between ABO blood type and mortality among patients who underwent surgical resection of brain metastases. METHODS: A single-center retrospective study of patients who underwent surgical resection of brain metastases between 2011 and 2019 was conducted. Cox proportional hazards models were constructed, adjusting for potential confounders, to evaluate whether blood type was independently associated with overall mortality. RESULTS: A total of 158 patients were included in the analysis. The mean (SD) age of the cohort was 59.3 (12.0) years, and 67.7% of patients were female. The median overall survival of patients with blood type AB was 11.2 months, while the median overall survival of patients with blood types O, B, and A were 11.7, 13.5, and 14.4 months respectively. On univariate analysis, patients with blood type AB had a higher risk of overall mortality (p = 0.017). On multivariate analysis adjusting for potential confounders, blood type AB was again associated with a higher risk of overall mortality (HR: 2.29, 95% CI: 1.11-4.72, p = 0.025). CONCLUSION: Blood type AB was independently associated with a higher risk of overall mortality among patients who underwent surgical resection of brain metastases, indicating the potential prognostic value of ABO blood type in brain metastases.

Dysfunctional Autophagy, Proteostasis, and Mitochondria as a Prelude to Age-Related Macular Degeneration.

Retinal pigment epithelial (RPE) cell dysfunction is a key driving force of AMD. RPE cells form a metabolic interface between photoreceptors and choriocapillaris, performing essential functions for retinal homeostasis. Through their multiple functions, RPE cells are constantly exposed to oxidative stress, which leads to the accumulation of damaged proteins, lipids, nucleic acids, and cellular organelles, including mitochondria. As miniature chemical engines of the cell, self-replicating mitochondria are heavily implicated in the aging process through a variety of mechanisms. In the eye, mitochondrial dysfunction is strongly associated with several diseases, including age-related macular degeneration (AMD), which is a leading cause of irreversible vision loss in millions of people globally. Aged mitochondria exhibit decreased rates of oxidative phosphorylation, increased reactive oxygen species (ROS) generation, and increased numbers of mitochondrial DNA mutations. Mitochondrial bioenergetics and autophagy decline during aging because of insufficient free radical scavenger systems, the impairment of DNA repair mechanisms, and reductions in mitochondrial turnover. Recent research has uncovered a much more complex role of mitochondrial function and cytosolic protein translation and proteostasis in AMD pathogenesis. The coupling of autophagy and mitochondrial apoptosis modulates the proteostasis and aging processes. This review aims to summarise and provide a perspective on (i) the current evidence of autophagy, proteostasis, and mitochondrial dysfunction in dry AMD; (ii) current in vitro and in vivo disease models relevant to assessing mitochondrial dysfunction in AMD, and their utility in drug screening; and (iii) ongoing clinical trials targeting mitochondrial dysfunction for AMD therapeutics.

Uveitis Registries - A Digital Tool for Patient Care, Education, Research, and Collaboration.

PURPOSE: Clinical registries are increasingly important in research and clinical advancement. This review explores and compares current uveitis registries and recommends future directions on how uveitis registries can complement one another for synergistic effect and benefit. METHODS: From a systematic search, 861 citations were screened for longitudinal, non-interventional, and multicenter uveitis-specific registries. Additional registries were identified via consultations with uveitis experts. Characteristics of all registries were analyzed and compared. RESULTS: Four registries were identified: Treatment Exit Options for Non-infectious Uveitis, AutoInflammatory Disease Alliance International Registry, Ocular Autoimmune Systemic Inflammatory Infectious Study, and Fight Uveitis Blindness!. Despite certain differences, these registries have the overarching goal of collecting large quantities of real-world, high-quality patient data to improve the understanding of uveitis. CONCLUSION: The four uveitis registries share similar goals and collect clinical data from overlapping geographical regions. There is vast potential for collaboration, including data sharing to further augment datasets for analysis.

Vaccine equity in COVID-19: a meta-narrative review.

The topic of inequitable vaccine distribution has been widely discussed by academics, journalists and policy-makers in the context of the COVID-19 pandemic. However, research into perceptions of vaccine equity has been particularly neglected, resulting in a lack of universal understanding of vaccine equity. To address this, we conducted a meta-narrative review on COVID-19 vaccine equity according to the Realist And MEta-narrative Evidence Syntheses: Evolving Standards (RAMESES) publication standard. The review included articles published between January 2020 and September 2021. It aims to (1) identify research traditions that have considered this topic and investigate how it has been conceptualised; (2) explore any potential differences in understandings of the concept of vaccine equity adopted by distinct research groups; and (3) investigate the angles from which authors based their recommendations on how vaccine equity can be achieved. Five meta-narratives from the literature across various research traditions are identified, contextualised and discussed: frameworks and mechanisms for vaccine allocation, global health law, vaccine nationalism, ethics and morality, and reparative justice. Our findings indicate the need for a comparative review of existing global COVID-19 allocation frameworks, with a focus on explicating understandings of vaccine equity. COVID-19 will not be the last health crisis the world confronts. Heterogeneity in the academic literature is part of the way concepts are debated and legitimised, but in the interests of global public health policy-making, it is desirable to reach a consensus on what constitutes progress on equitable development, production, distribution and research.

Age-Related Eye Diseases in Individuals With Mild Cognitive Impairment and Alzheimer's Disease.

Introduction: Alzheimer's disease (AD) and age-related eye diseases pose an increasing burden as the world's population ages. However, there is limited understanding on the association of AD/cognitive impairment, no dementia (CIND) with age-related eye diseases. Methods: In this cross-sectional, memory clinic-based study of multiethnic Asians aged 50 and above, participants were diagnosed as AD (n = 216), cognitive impairment, no dementia (CIND) (n = 252), and no cognitive impairment (NCI) (n = 124) according to internationally accepted criteria. Retinal photographs were graded for the presence of age-related macular degeneration (AMD) and diabetic retinopathy (DR) using standard grading systems. Multivariable-adjusted logistic regression models were used to determine the associations between neurological diagnosis and odds of having eye diseases. Results: Over half of the adults had at least one eye disease, with AMD being the most common (60.1%; n = 356), followed by DR (8.4%; n = 50). After controlling for age, sex, race, educational level, and marital status, persons with AD were more likely to have moderate DR or worse (OR = 2.95, 95% CI = 1.15-7.60) compared with NCI. In the fully adjusted model, the neurological diagnosis was not associated with AMD (OR = 0.75, 95% CI = 0.45-1.24). Conclusion: Patients with AD have an increased odds of having moderate DR or worse, which suggests that these vulnerable individuals may benefit from specific social support and screening for eye diseases.

Novel technical and privacy-preserving technology for artificial intelligence in ophthalmology.

PURPOSE OF REVIEW: The application of artificial intelligence (AI) in medicine and ophthalmology has experienced exponential breakthroughs in recent years in diagnosis, prognosis, and aiding clinical decision-making. The use of digital data has also heralded the need for privacy-preserving technology to protect patient confidentiality and to guard against threats such as adversarial attacks. Hence, this review aims to outline novel AI-based systems for ophthalmology use, privacy-preserving measures, potential challenges, and future directions of each. RECENT FINDINGS: Several key AI algorithms used to improve disease detection and outcomes include: Data-driven, imagedriven, natural language processing (NLP)-driven, genomics-driven, and multimodality algorithms. However, deep learning systems are susceptible to adversarial attacks, and use of data for training models is associated with privacy concerns. Several data protection methods address these concerns in the form of blockchain technology, federated learning, and generative adversarial networks. SUMMARY: AI-applications have vast potential to meet many eyecare needs, consequently reducing burden on scarce healthcare resources. A pertinent challenge would be to maintain data privacy and confidentiality while supporting AI endeavors, where data protection methods would need to rapidly evolve with AI technology needs. Ultimately, for AI to succeed in medicine and ophthalmology, a balance would need to be found between innovation and privacy.

Liquid-liquid phase separation of RBGD2/4 is required for heat stress resistance in Arabidopsis.

As sessile organisms, plants are highly sensitive to environmental stresses. In response to stresses, globally repressed translation initiation leads to stress granule (SG) formation. Protein liquid-liquid phase separation (LLPS) contributes to SG formation, but a direct link between protein LLPS and stress resistance has not yet been found in plants. Here, we report that two RNA-binding proteins, RBGD2 and RBGD4, function redundantly to improve heat resistance in Arabidopsis. RBGD2 and RBGD4 undergo LLPS in vitro and condense into heat-induced SGs in vivo via tyrosine residue array (TRA). Importantly, disrupting LLPS by mutating TRA abolishes RBGD2/4 condensation in SGs and impairs their protective function against heat stress (HS). Further study found that upon HS, the RBGD2/4 interaction network expands with additional SG proteins and heat-responsive mRNA. Our work shows a mechanistic basis that underlies protein LLPS in HS response in plants and suggests manipulation of protein LLPS as a general strategy to improve plant stress resistance.