暂无摘要。

BACKGROUND: The aim of this study was to evaluate the clinical significance of blood-cell associated inflammation markers in patients with sickle cell disease (SCD) and sickle cell retinopathy (SCR).
METHODS: Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), systemic immune inflammation index (SIII), systemic inflammation response index (SIRI), systemic inflammation modulation index (SIMI) and aggregate systemic inflammation index (AISI) were calculated. This study included 45 healthy controls (Group 1) and 100 SCD (Group 2). Patients in Group 2 were then divided into two groups: without SCR (Group 3) and with SCR (Group 4), and patients with SCR (Group 4) were further divided into two groups: non-proliferative sickle cell retinopathy (NPSCR) (Group 5) and proliferative sickle cell retinopathy (PSCR) (Group 6).
RESULTS: The mean values for NLR, PLR, SIII, SIRI, AISI, and SIMI were significantly higher in Group 2 compared to Group 1 (p = 0.011 for NLR, p = 0.004 for SIII, and p < 0.001 for others). Furthermore, AISI and SIMI parameters demonstrated statistically significant discriminatory power to distinguish Group 5 from Group 6 (p = 0.0016 and p = 0.0006, respectively).
CONCLUSIONS: Given the critical role of inflammatory mechanisms in the pathogenesis of SCD and its related complications, the assessment of blood-cell-associated inflammatory markers may present a pragmatic and advantageous approach to the clinical oversight and therapeutic intervention of SCD.

OBJECTIVE: Previous studies have provided evidence that the discontinuation of hydroxychloroquine (HCQ), and chloroquine (CQ), in patients with systemic lupus erythematosus (SLE) is associated with an increased risk of disease flares, with limited information on the level of disease activity at the time of HCQ/CQ discontinuation. Here we aimed to describe the risk of SLE flare after withdrawal of HCQ or CQ in patients with SLE in remission.
METHODS: Case-control study (1:2) comparing the evolution of patients with SLE after HCQ/CQ withdrawal for antimalarial retinopathy (cases) with patients with SLE matched for sex, antimalarial treatment duration and age at SLE diagnosis, whose antimalarial treatment was continued throughout the entire follow-up period (controls). To be included in the study, patients had to be in remission for at least one year according to DORIS classification. The primary endpoint was the proportion of patient experiencing a flare according to the SELENA-SLEDAI Flare Index after a 36-month follow-up.
RESULTS: We studied 48 cases and 96 controls. Proportion of patients experiencing a flare was significantly higher in the HCQ/CQ withdrawal group as compared to the maintenance group (15 (31.3%) patients versus 12(12.5%); OR 3.1 (95%CI 1.2-8.2), p=0.01). Withdrawal of HCQ/CQ was inferior with respect to occurrence of severe SLE flare (12 (25.0%) vs 11 (11.5%); OR 2.5 (95%CI 0.9-6.9), p=0.053) and time to first flare (HR 6.3 [2.0-19.9], p<0.005. Elevated serum levels of anti-dsDNA antibodies were identified as a risk factor for SLE flare following HCQ/CQ discontinuation (HR 5.4 [1.5-18.7], p<0.01).
CONCLUSIONS: Withdrawal of HCQ or CQ in patients with SLE in remission is associated with a 3-fold increased risk of relapse.

暂无摘要。

BackgroundRetinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare, autosomal dominant, universally fatal disease without effective treatment options. This study explores the safety and preliminary efficacy of crizanlizumab, a humanized monoclonal antibody against P-selectin approved for the prevention of sickle cell crises, in slowing retinal nonperfusion and preserving vision in patients with RVCL-S.METHODSEleven patients with RVCL-S with confirmed exonuclease 3 prime repair exonuclease 1 (TREX1) mutations received monthly crizanlizumab infusions over 2 years. The study measured the nonperfusion index within 3 retinal zones and the total retina with fluorescein angiography, visual acuity, intraocular pressure (IOP), and optical coherence tomography central subfield thickness (CST) at baseline, 1 year, and 2 years. A mixed repeated-measures analysis was performed to assess the progression rates and changes from baseline.RESULTSEleven participants received crizanlizumab infusions. All of the participants tolerated crizanlizumab well, with 8 of 11 (72.7%) reporting mild adverse effects such as nausea, fatigue, and gastrointestinal symptoms. The change in total retinal nonperfusion was 7.22% [4.47, 9.97] in year 1 and -0.69% [-4.06, 2.68] in year 2 (P < 0.001). In the mid periphery, the change in nonperfusion was 10.6% [5.1, 16.1] in year 1 and -0.68% [-3.98, 5.35] in year 2 (P < 0.01), demonstrating a reduction in progression of nonperfusion in the second year of treatment. Visual acuity, IOP, and CST remained stable.CONCLUSIONCrizanlizumab has an acceptable safety profile. These results show promising potential for examining crizanlizumab in larger studies of RVCL-S and similar small-vessel diseases and for using the retina as a biomarker for systemic disease.Trial registrationClinicalTrials.gov NCT04611880.FUNDINGThe Clayco Foundation; DeNardo Education and Research Foundation Grant; Jeffrey T. Fort Innovation Fund; Siteman Retina Research Fund; unrestricted grant from Research to Prevent Blindness Inc.; National Heart,Lung, and Blood Institute (NHLBI), NIH (R01HL129241); National Institute of Neurological Disorders and Stroke (NINDS), NIH (RF1NS116565).

Mitochondria-related neurodegenerative diseases have been implicated in the disruption of primary cilia function. Mutation in an intrinsic mitochondrial complex I component NDUFAF2 has been identified in Leigh syndrome, a severe inherited mitochondriopathy. Mutations in ARMC9, which encodes a basal body protein, cause Joubert syndrome, a ciliopathy with defects in the brain, kidney, and eye. Here, we report a mechanistic link between mitochondria metabolism and primary cilia signaling. We discovered that loss of NDUFAF2 caused both mitochondrial and ciliary defects in vitro and in vivo and identified NDUFAF2 as a binding partner for ARMC9. We also found that NDUFAF2 was both necessary and sufficient for cilia formation and that exogenous expression of NDUFAF2 rescued the ciliary and mitochondrial defects observed in cells from patients with known ARMC9 deficiency. NAD+ supplementation restored mitochondrial and ciliary dysfunction in ARMC9-deficient cells and zebrafish and ameliorated the ocular motility and motor deficits of a patient with ARMC9 deficiency. The present results provide a compelling mechanistic link, supported by evidence from human studies, between primary cilia and mitochondrial signaling. Importantly, our findings have significant implications for the development of therapeutic approaches targeting ciliopathies.

A study was conducted to investigate the associations of the diseases of the organ of vision and its accessory apparatus with anxiety and depression in the elderly people. The study included 678 participants of the ESSE-RF3 population study in the Arkhangelsk region in the age of 60-74 years. We used a questionnaire, including the hospital scale of anxiety and depression score (HADS), and the assessment of the ophthalmological status. It was found that all the study participants had diseases of the visual organ. Elevated depression scores were associated with sex, age, marital status (being single), and disability, elevated anxiety scores - with sex. The scores on the anxiety scale were on average 25% higher in participants whose visual acuity decreased to 0,5 units, and showed no independent associations with diagnosed ophthalmological diseases. The scores on the depression scale were on average 33% higher in participants with visual acuity 0,5 units, and 22% higher in the presence of retinopathy. In conclusion, anxiety and depression in the elderly people were more associated with visual deficits rather than with the presence of ophthalmological diseases underlying a decrease in functional status.
Проведено исследование связи заболеваний органа зрения и его придаточного аппарата и тревоги/депрессии у пожилых жителей. В данное исследование были включены 678 участников 60–74 лет популяционного исследования ЭССЕ-РФ3 в Архангельской обл. Использовали анкетирование, включающее Госпитальную шкалу тревоги и депрессии (HADS), и оценку офтальмологического статуса. Повышение шкальных оценок депрессии было связано с характеристиками по полу и возрасту, семейным положением и инвалидностью, повышение уровня тревоги — с женским полом. Уровень тревоги был в среднем на 25% выше у участников со снижением остроты зрения вдаль до ≤0,5 и не имел независимых связей с заболеваниями глаз. Уровень депрессии в среднем был не выше 33% при снижении остроты зрения до ≤0,5 у. е. и на 22% выше — при наличии ретинопатии. Следовательно, тревожность и депрессия у лиц пожилого возраста в большей степени ассоциированы со зрительным дефицитом, чем с наличием офтальмологических заболеваний, лежащих в основе снижения функционального статуса.

BACKGROUND: The purpose of this review was to examine if dipeptidyl peptidase-4 inhibitor (DPP4i) use affects the risk of diabetic retinopathy (DR).
METHODS: Cohort studies published up to 20th July 2023 in the databases of PubMed, CENTRAL, Embase, Scopus, and Web of Science were searched. The adjusted effect size was pooled to calculate the odds ratio (OR).
RESULTS: Seven studies were included. Meta-analysis showed that the use of DPP4i was not associated with any significant change in the risk of DR (OR: 0.86 95% CI: 0.70, 1.06 I2 = 78%). The pooled analysis also found that DPP4i use was not associated with any significant risk of progression of DR (OR: 0.87 95% CI: 0.47, 1.59 I2 = 86%). The results did not change during sensitivity analysis.
CONCLUSIONS: Present evidence from a limited number of real-world studies shows that DPP4i may not affect the incidence and progression of DR. There is a need for further studies from different countries using accurate definitions of DR and its progression to validate the current results.

UNASSIGNED: In this extensive review work, the important role of AMP-activated protein kinase (AMPK) in causing of diabetes mellitus has been highlighted. Structural feature of AMPK as well its regulations and roles are described nicely, and the association of AMPK with the diabetic complications like nephropathy, neuropathy and retinopathy are also explained along with the connection between AMPK and β-cell function, insulin resistivity, mTOR, protein metabolism, autophagy and mitophagy and effect on protein and lipid metabolism.
UNASSIGNED: Published journals were searched on the database like PubMed, Medline, Scopus and Web of Science by using keywords such as AMPK, diabetes mellitus, regulation of AMPK, complications of diabetes mellitus, autophagy, apoptosis etc.
UNASSIGNED: After extensive review, it has been found that, kinase enzyme like AMPK is having vital role in management of type II diabetes mellitus. AMPK involve in enhance the concentration of glucose transporter like GLUT 1 and GLUT 4 which result in lowering of blood glucose level in influx of blood glucose into the cells; AMPK increases the insulin sensitivity and decreases the insulin resistance and further AMPK decreases the apoptosis of β-cells which result into secretion of insulin and AMPK is also involve in declining of oxidative stress, lipotoxicity and inflammation, owing to which organ damage due to diabetes mellitus can be lowered by activation of AMPK.
UNASSIGNED: As AMPK activation leads to overall control of diabetes mellitus, designing and developing of small molecules or peptide that can act as AMPK agonist will be highly beneficial for control or manage diabetes mellitus.

UNASSIGNED: Type 2 diabetes mellitus (T2DM) is a chronic condition associated with various microvascular complications, including neuropathy, retinopathy, and nephropathy. Recent studies have suggested a potential association between serum omentin levels and the risk of developing microvascular complications in patients with T2DM. However, the existing evidence remains inconclusive. Therefore, we conducted a systematic review and meta-analysis to examine the association between serum omentin levels and microvascular complications in T2DM patients.
UNASSIGNED: A comprehensive search was conducted in PubMed, Scopus, and Google Scholar databases to retrieve relevant articles published up to May 2023. Observational studies investigating omentin levels association with microvascular complications in T2DM patients were included. Data was extracted and hence analyzed.
UNASSIGNED: A total of seven cross-sectional articles met the inclusion criteria, with a total population of 1587 participants. The meta-analysis revealed a significant association between serum omentin levels and microvascular complications in patients with T2DM. Serum omentin levels were lower in patients with microvascular complications than in those without complications (Mean difference, 95% confidence interval: -1.31 [-2.50, -0.13], I2 = 99.62%).
UNASSIGNED: This systematic review and meta-analysis provides evidence supporting an association between serum omentin levels and microvascular complications in patients with T2DM. The findings suggest that Omentin may be lower in T2DM patients with microvascular complications. Further research is warranted to elucidate the underlying mechanisms and explore the clinical implications of these findings.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s40200-023-01359-2.