Association of Retinal Nerve Fiber Layer Thickness with Brain Microstructural Changes in Participants with White Matter Hyperintensities.

PURPOSE: White matter hyperintensity (WMH) is suggested to cause stroke and dementia in older adults. Retinal structural thicknesses revealed by optical coherence tomography (OCT) are associated with structural changes in the brain. We aimed to explore the association between the peripapillary retinal nerve fiber layer (RNFL) and cerebral microstructural changes in participants with white matter hyperintensities (WMH). METHODS: Seventy-four participants (37 controls, healthy control (HC), and 37 older adults with WMH) underwent retinal and brain imaging using OCT and magnetic resonance imaging (MRI) respectively. Peripapillary RNFL thickness was assessed by the OCT. Gray matter volume (GMV) was assessed from a T1-weighted MRI. White matter integrity was assessed with diffusion tensor imaging (DTI) while WMH severity was assessed with the Fazekas scale. All participants underwent a neuropsychological examination (Mini-Mental State Examination, MMSE). RESULTS: Older adults with WMH showed thinner peripapillary RNFL (p = 0.004) thickness when compared with the control group after adjusting for age, hypertension and gender. In our older adults with WMH, RNFL thickness correlated with fractional anisotropy (FA) in the superior longitudinal fasciculus (SLF) (Rho = -0.331, p < 0.001). In older adults with WMH, RNFL was significantly associated with MMSE scores (Rho = 0.422, p < 0.001) and Fazekas scores (Rho = -0.381, p = 0.022) respectively. CONCLUSIONS: We suggest neurodegeneration of peripapillary RNFL in older adults with WMH was associated with cerebral microstructural volume, impaired cerebral axonal damage, and cognitive performances. OCT metrics may provide evidence of neurodegeneration that may underpin WMH and cerebral microstructural changes in the brain. CLINICAL TRIAL REGISTRATION: This study was registered online at the China Clinical Trial Registration Center (registration number: ChiCTR-ROC-17011819).

Long-Term Outcomes in Older Patients with Sepsis in the ICU: A Retrospective Study.

Objective: The primary objectives of this study were to compare the characteristics of older and younger patients with sepsis and to analyze risk factors associated with 28-day and 90-day mortality in critically ill patients. Our study aimed to explore whether there are significant differences between sepsis patients in different age groups and whether these differences are related to the association between disease severity and mortality. Methods: We conducted a single-center, retrospective study of 5783 critically ill patients over 18 years of age from the Medical Information Mart for Intensive Care III database diagnosed with sepsis and admitted to the intensive care unit between 2008 and 2012. We performed a retrospective analysis, selected the Critical Care Medicine Information Mart III database, and collected data on patients with sepsis. We then collated and analyzed these data to compare differences in characteristics between older and younger patients and identify associated risk factors, which can help understand patient mortality. This approach leverages existing clinical data and avoids new experiments or data collection. Kaplan-Meier survival curve was used to assess 28-day and 90-day mortality, and a Cox proportional hazards regression model was used to evaluate the associated risk factors with 28-day and 90-day mortality. Results: Our study identified significant differences in mortality between older and younger patients with sepsis, finding that older patients had significantly higher mortality than younger patients. Furthermore, we successfully identified risk factors associated with mortality, results that have important implications for optimizing patient care and making clinical decisions. Of 5783 patients with sepsis, 2044 (35.3%) were younger than 60 years, and 3739 (64.7%) were aged 60 years or older. The 28-day mortality rate was 11.8% and 21.2% in the younger and older cohorts, respectively (P < .01). In the age-stratified analysis, the 28-day mortality was the highest in patients aged over 80 years (14.6% vs. 21.2% vs. 26.8%, P < .001). Factors associated with 28-day and 90-day mortality in patients with sepsis included age, weight, the need for mechanical ventilation, congestive heart failure, chronic pulmonary disease, malignancy, and Sequential Organ Failure Assessment score. Higher mortality in older patients with sepsis suggests the need for more aggressive treatment and monitoring. We also identified risk factors associated with mortality, helping to develop individualized treatment strategies. In addition, the different clinical characteristics of patients in different age groups emphasize the need for refined care pathways to meet their special needs. These results will help improve the treatment effect and quality of life of patients with sepsis. Conclusions: Our study fills the knowledge gap on the manifestations of sepsis patients in different age groups and helps medical staff better predict and manage disease progression in these two groups and provide personalized treatment. This lays the foundation for future in-depth research on age-related sepsis factors and is expected to improve patient survival and recovery rates. Older patients with sepsis had higher mortality rates and adverse outcomes. The mortality rate in patients with sepsis gradually increased with age. The importance of these findings is that they can help guide patient care and clinical decision-making, particularly when dealing with older and younger patients with sepsis, to improve treatment outcomes and reduce mortality. We would like to acknowledge that there are several limitations to the study, including the selectivity of the database and the retrospective nature, which preclude inference of causal relationships. In addition, some unconsidered variables may affect the results, and missing information in the data may also have an impact on the study. Future research could further explore these issues.This study highlights the critical role of age in sepsis patient outcomes and provides a strong basis for more sophisticated care and treatment. Our findings will help save more lives and improve patients' chances of recovery, which has profound implications for future research and clinical practice in the field of sepsis.

PSD-95 inhibitor Tat-NR2B9c (NA-1) protects the integrity of the blood-brain barrier after transient middle artery occlusion in rats by downregulating matrix metalloprotease-9 and upregulating endothelial nitric oxide synthase.

BACKGROUND: Protection against ischemic stroke may be most effective when multiple components of the neurovascular unit are protected, yet current treatments target mainly neurons. Here we explored whether the PSD-95 inhibitor Tat-NR2B9c (NA-1) can protect not only neurons but also the blood-brain barrier. METHODS: Adult male Sprague-Dawley rats were randomly divided into three groups, which were subjected to either sham surgery or transient cerebral ischemia-reperfusion, after which some animals were treated with Tat-NR2B9c. The therapeutic efficacy of Tat-NR2B9c was assessed in terms of the degree of neurological deficit and cerebral infarction, integrity of the blood-brain barrier, cerebral water content, as well as expression of PSD-95, nitric oxide synthase, and matrix metalloprotease-9. RESULTS: Tat-NR2B9c (NA-1) ameliorated neurofunctional deficit, reduced cerebral infarction, mitigated blood-brain barrier injury and improved its integrity following ischemia-reperfusion, leading to less cerebral edema. These improvements were associated with upregulation of tight junction proteins in the blood-brain barrier. At the same time, Tat-NR2B9c (NA-1) downregulated neuronal nitric oxide synthase and matrix metalloprotease-9, while reversing the ischemia-induced downregulation of endothelial nitric oxide synthase in brain. We report here the first evidence that PSD-95 is expressed in vascular endothelial cells in the brain. CONCLUSION: Our experiments in a rat model of transient occlusion of the middle cerebral artery suggest that Tat-NR2B9c (NA-1) can mitigate ischemic injury to the blood-brain barrier, and that it may do so by downregulating matrix metalloprotease-9 and upregulating endothelial nitric oxide synthase.