Association between atherosclerosis-related cardiovascular disease and uveitis: A systematic review and meta-analysis

Background: Uveitis is not only an intraocular inflammatory disease, but also an indicator of systemic inflammation. It is unclear whether uveitis can increase the risk of cardiovascular disease (CVD) through the atherosclerotic pathway. Methods: PubMed and Embase databases were searched until 5 September, 2022. Original studies investigating uveitis and cardiovascular events were selected. The random-effects model was used to calculate the difference of groups in pooled estimates. Results: A total of six observational studies that included mainly ankylosing spondylitis (AS) patients were included. Of these, three studies reported data on carotid plaques and carotid intima-media thickness (cIMT) and the other three studies provided data on atherosclerosis-related CVD. No significant difference was found in cIMT between uveitis and controls (MD = 0.01, 95% CI = -0.03-0.04, p = 0.66), consistent with the findings of carotid plaque incidence (OR = 1.30, 95% CI = 0.71-2.41, p = 0.39). However, uveitis was associated with a 1.49-fold increase in atherosclerosis-related CVD (HR = 1.49, 95% CI = 1.20-1.84, p = 0.0002). Conclusions: Uveitis is a predictor of atherosclerosis-related CVD in AS patients. For autoimmune disease patients with uveitis, earlier screening of cardiovascular risk factors and the implementation of corresponding prevention strategies may be associated with a better prognosis. Keywords: ankylosing spondylitis; atherosclerosis; cardiovascular risk; carotid plaques; intima-media thickness; uveiti

Superconductive "sodalite"-like clathrate calcium hydride at high pressures

Hydrogen-rich compounds hold promise as high-temperature superconductors under high pressures. Recent theoretical hydride structures on achieving high-pressure superconductivity are composed mainly of H2 fragments. Through a systematic investigation of Ca hydrides with different hydrogen contents using particle-swam optimization structural search, we show that in the stoichiometry CaH6 a body-centred cubic structure with hydrogen that forms unusual "sodalite" cages containing enclathrated Ca stabilizes above pressure 150 GPa. The stability of this structure is derived from the acceptance by two H2 of electrons donated by Ca forming a "H4" unit as the building block in the construction of the 3-dimensional sodalite cage. This unique structure has a partial occupation of the degenerated orbitals at the zone centre. The resultant dynamic Jahn-Teller effect helps to enhance electron-phonon coupling and leads to superconductivity of CaH6. A superconducting critical temperature (Tc) of 220-235 K at 150 GPa obtained from the solution of the Eliashberg equations is the highest among all hydrides studied thus far.Comment: 19 pages, 4 figure

Association Between Atherosclerosis-Related Cardiovascular Disease and Uveitis: A Systematic Review and Meta-Analysis

Background: Uveitis is not only an intraocular inflammatory disease, but also an indicator of systemic inflammation. It is unclear whether uveitis can increase the risk of cardiovascular disease (CVD) through the atherosclerotic pathway. Methods: PubMed and Embase databases were searched until 5 September, 2022. Original studies investigating uveitis and cardiovascular events were selected. The random-effects model was used to calculate the difference of groups in pooled estimates. Results: A total of six observational studies that included mainly ankylosing spondylitis (AS) patients were included. Of these, three studies reported data on carotid plaques and carotid intima-media thickness (cIMT) and the other three studies provided data on atherosclerosis-related CVD. No significant difference was found in cIMT between uveitis and controls (MD = 0.01, 95% CI = -0.03-0.04, p = 0.66), consistent with the findings of carotid plaque incidence (OR = 1.30, 95% CI = 0.71-2.41, p = 0.39). However, uveitis was associated with a 1.49-fold increase in atherosclerosis-related CVD (HR = 1.49, 95% CI = 1.20-1.84, p = 0.0002). Conclusions: Uveitis is a predictor of atherosclerosis-related CVD in AS patients. For autoimmune disease patients with uveitis, earlier screening of cardiovascular risk factors and the implementation of corresponding prevention strategies may be associated with a better prognosis

Efficacy of guideline-directed medical treatment in heart failure with mildly reduced ejection fraction.

Heart failure with mildly reduced ejection fraction (HFmrEF) has received increasing attention following the publication of the latest ESC guidelines in 2021. However, it remains unclear whether patients with HFmrEF could benefit from guideline-directed medical treatment (GDMT), referring the combination of ACEI/ARB/ARNI, β-blockers, and MRAs, which are recommended for those with reduced ejection fraction. This study explored the efficacy of GDMT in HFmrEF patients. This was a retrospective cohort study of HFmrEF patients admitted to The First Affiliated Hospital of Dalian Medical University between 1 September 2015 and 30 November 2019. Propensity score matching (1:2) between patients receiving triple-drug therapy (TT) and non-triple therapy (NTT) based on age and sex was performed. The primary outcome was all cause death, cardiac death, rehospitalization from any cause, and rehospitalization due to worsening heart failure. Of the 906 patients enrolled in the matched cohort (TT group, n = 302; NTT group, N = 604), 653 (72.08%) were male, and mean age was 61.1 ± 11.92. Survival analysis suggested that TT group experienced a significantly lower incidence of prespecified primary endpoints than NTT group. Multivariable Cox regression showed that TT group had a lower risk of all-cause mortality (HR 0.656, 95% CI 0.447-0.961, P = 0.030), cardiac death (HR 0.599, 95% CI 0.380-0.946, P = 0.028), any-cause rehospitalization (HR 0.687, 95% CI 0.541-0.872, P = 0.002), and heart failure rehospitalization (HR 0.732, 95% CI 0.565-0.948, P = 0.018). In patients with HFmrEF, combined use of neurohormonal antagonists produces remarkable effects in reducing the occurrence of the primary outcome of rehospitalization and death. Thus, the treatment of HFmrEF should be categorized as HFrEF due to the similar benefit of neurohormonal blocking therapy in HFrEF and HFmrEF. [Abstract copyright: © 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Prognostic value of cardiovascular magnetic resonance in immune checkpoint inhibitor‐associated myocarditis: A systematic review and meta‐analysis

Background: Immune checkpoint inhibitors (ICI) are increasingly used in the first‐line treatment of malignant tumors. There is increasing recognition of their cardiotoxicity and, in particular, their potential to lead to myocarditis. Cardiovascular magnetic resonance (CMR) can quantify pathological changes, such as myocardial edema and fibrosis. The purpose of this systematic review and meta‐analysis was to examine the evidence for the roles of CMR in predicting prognosis in ICI‐associated myocarditis. Methods: PubMed, Cochrane Library, and Web of Science databases were searched until October 2023 for published works investigating the relationship between CMR parameters and adverse events in patients with ICI‐associated myocarditis. The analysis included studies reporting the incidence of late gadolinium enhancement (LGE), T1 values, T2 values, and CMR‐derived left ventricular ejection fraction (LVEF). Odds ratios (OR) and weighted mean differences (WMD) were combined for binary and continuous data, respectively. Newcastle‐Ottawa Scale was used to assess the methodological quality of the included studies. Results: Five cohort studies were included (average age 65–68 years; 25.4% female). Of these, four studies were included in the meta‐analysis of LGE‐related findings. Patients with major adverse cardiovascular events (MACE) had a higher incidence of LGE compared with patients without MACE (OR = 4.18, 95% CI: 1.72–10.19, p = 0.002). A meta‐analysis, incorporating data from two studies, showed that patients who developed MACE exhibited significantly higher T1 value (WMD = 36.16 ms, 95% CI: 21.43–50.89, p < 0.001) and lower LVEF (WMD = − 8.00%, 95% CI: −13.60 to −2.40, p = 0.005). Notably, T2 value (WMD = −0.23 ms, 95% CI: −1.86 to −1.39, p = 0.779) was not associated with MACE in patients with ICI‐related myocarditis. Conclusions: LGE, T1 value, and LVEF measured by CMR imaging have potential prognostic value for long‐term adverse events in patients with ICI‐related myocarditis

Efficacy of guideline‐directed medical treatment in heart failure with mildly reduced ejection fraction

Aims: Heart failure with mildly reduced ejection fraction (HFmrEF) has received increasing attention following the publication of the latest ESC guidelines in 2021. However, it remains unclear whether patients with HFmrEF could benefit from guideline‐directed medical treatment (GDMT), referring the combination of ACEI/ARB/ARNI, β‐blockers, and MRAs, which are recommended for those with reduced ejection fraction. This study explored the efficacy of GDMT in HFmrEF patients. Methods: This was a retrospective cohort study of HFmrEF patients admitted to The First Affiliated Hospital of Dalian Medical University between 1 September 2015 and 30 November 2019. Propensity score matching (1:2) between patients receiving triple‐drug therapy (TT) and non‐triple therapy (NTT) based on age and sex was performed. The primary outcome was all cause death, cardiac death, rehospitalization from any cause, and rehospitalization due to worsening heart failure. Results: Of the 906 patients enrolled in the matched cohort (TT group, n = 302; NTT group, N = 604), 653 (72.08%) were male, and mean age was 61.1 ± 11.92. Survival analysis suggested that TT group experienced a significantly lower incidence of prespecified primary endpoints than NTT group. Multivariable Cox regression showed that TT group had a lower risk of all‐cause mortality (HR 0.656, 95% CI 0.447–0.961, P = 0.030), cardiac death (HR 0.599, 95% CI 0.380–0.946, P = 0.028), any‐cause rehospitalization (HR 0.687, 95% CI 0.541–0.872, P = 0.002), and heart failure rehospitalization (HR 0.732, 95% CI 0.565–0.948, P = 0.018). Conclusions: In patients with HFmrEF, combined use of neurohormonal antagonists produces remarkable effects in reducing the occurrence of the primary outcome of rehospitalization and death. Thus, the treatment of HFmrEF should be categorized as HFrEF due to the similar benefit of neurohormonal blocking therapy in HFrEF and HFmrEF

Visual Morbidity Due to Inaccurate Spectacles among School Children in Rural China: The See Well to Learn Well Project, Report 1

PURPOSE. Inadequately corrected refractive error is the leading cause of visual disability among children in China; inaccurate spectacles are a potential cause. The prevalence and visual impact of spectacle inaccuracy were studied among rural, secondary-school children, to determine the optimal timing for updating of refraction. METHODS. A random sample of children from years 1 and 2 in all junior and senior high schools in Fuyang Township, Guangdong Province, underwent ocular examination. All children who reported wearing glasses received cycloplegic refraction, vision assessment, and measurement of current spectacles. RESULTS. Among 3226 examined children, 733 (22.7%) reported owning spectacles. Refractive error and spectacle power were assessed for 588 (80.2%) children. They had a mean age of 15.0 Ϯ 1.6 years; 70.2% were girls, 83.3% had more than Ϫ1.5 D of myopia, and 17.9% had presenting vision Յ 6/12 in the better eye. The glasses of 48.8% of children were inaccurate by Ն1 D; inaccuracy was Ն2 D in 17.7%. Children with inaccurate glasses (Ն1 D) had presenting vision in the better eye significantly (P Ͻ 0.001) worse than that of children with accurate glasses, and 30.3% had presenting acuity Յ 6/12. In multivariate models, younger age (P ϭ 0.004), more myopic refractive error (P Ͻ 0.001), and having glasses Ն 1 year old (P ϭ 0.04) were associated with inaccurate spectacles. DISCUSSION. Inaccurate spectacles are common and are associated with significant visual impairment among children in rural China. Reducing outdated glasses could lessen the visual burden, although refractive services may have to be offered on an annual basis for optimal benefit. (Invest Ophthalmol Vis Sci

Deep diversification of an AAV capsid protein by machine learning.

Modern experimental technologies can assay large numbers of biological sequences, but engineered protein libraries rarely exceed the sequence diversity of natural protein families. Machine learning (ML) models trained directly on experimental data without biophysical modeling provide one route to accessing the full potential diversity of engineered proteins. Here we apply deep learning to design highly diverse adeno-associated virus 2 (AAV2) capsid protein variants that remain viable for packaging of a DNA payload. Focusing on a 28-amino acid segment, we generated 201,426 variants of the AAV2 wild-type (WT) sequence yielding 110,689 viable engineered capsids, 57,348 of which surpass the average diversity of natural AAV serotype sequences, with 12-29 mutations across this region. Even when trained on limited data, deep neural network models accurately predict capsid viability across diverse variants. This approach unlocks vast areas of functional but previously unreachable sequence space, with many potential applications for the generation of improved viral vectors and protein therapeutics