An aging-related immune landscape in the hematopoietic immune system.

BACKGROUND: Aging is a holistic change that has a major impact on the immune system, and immunosenescence contributes to the overall progression of aging. The bone marrow is the most important hematopoietic immune organ, while the spleen, as the most important extramedullary hematopoietic immune organ, maintains homeostasis of the human hematopoietic immune system (HIS) in cooperation with the bone marrow. However, the overall changes in the HIS during aging have not been described. Here, we describe a hematopoietic immune map of the spleen and bone marrow of young and old mice using single-cell sequencing and flow cytometry techniques. RESULTS: We observed extensive, complex changes in the HIS during aging. Compared with young mice, the immune cells of aged mice showed a marked tendency toward myeloid differentiation, with the neutrophil population accounting for a significant proportion of this response. In this change, hypoxia-inducible factor 1-alpha (Hif1α) was significantly overexpressed, and this enhanced the immune efficacy and inflammatory response of neutrophils. Our research revealed that during the aging process, hematopoietic stem cells undergo significant changes in function and composition, and their polymorphism and differentiation abilities are downregulated. Moreover, we found that the highly responsive CD62L + HSCs were obviously downregulated in aging, suggesting that they may play an important role in the aging process. CONCLUSIONS: Overall, aging extensively alters the cellular composition and function of the HIS. These findings could potentially give high-dimensional insights and enable more accurate functional and developmental analyses as well as immune monitoring in HIS aging.

Intravitreal dexamethasone implants facilitate the management of refractory Behçet's uveitis with vasculitis.

To investigate the efficacy and safety of dexamethasone (DEX) implant, Ozurdex ®, as an adjunctive treatment for refractory Behçet's uveitis (BU), a total of 61 patients (80 eyes) were included in this cross-sectional study and divided into the non-DEX and DEX groups. After >12 months of treatment, the improvement in the fluorescein angiography score and vitritis score was significantly higher in the DEX group than in the non-DEX group. Although the posterior capsule opacification score was exacerbated, the rate of low-dose systemic glucocorticoid was higher and the relapse times were fewer in the DEX group. Therefore, Ozurdex® is an effective and safe option for patients with BU that are refractory to systemic immunosuppressant treatments by controlling vasculitis, stabilizing vitreous inflammation, preventing recurrence, and reducing daily glucocorticoid doses.

The Efficacy of Adalimumab in Children with Chronic Non-infectious Posterior Uveitis and Panuveitis: A Retrospective Cohort Study.

INTRODUCTION: This study aimed to assess the efficacy and safety of adalimumab in pediatric patients with chronic non-infectious posterior uveitis and panuveitis (not associated with juvenile idiopathic arthritis). METHODS: The medical records of children (< 18 years old) with chronic non-infectious posterior uveitis and panuveitis were collected and analyzed in this retrospective cohort study. Children were allocated to a conventional adalimumab-free treatment (CT) or adalimumab (ADA) group based on whether they additionally received adalimumab. RESULTS: In total, 69 children (138 eyes) were included, with 21 (42 eyes) and 48 (96 eyes) in the CT and ADA groups, respectively. During the average follow-up period of 24 months, the improvement in all ocular parameters (best-corrected visual acuity, intraocular inflammation, fluorescein angiography score) was better in the ADA group than in the CT group, except for changes in central macular thickness, which did not significantly differ between the groups. The mean time of first alleviation, which was after 1.03 ± 0.12 months of therapy, was earlier in the ADA group than in the CT group (2.30 ± 0.46 months). In the ADA group, 90.6% of children had remission within 3 months, and 47.9% had no relapse during follow-up. Cough and cold were the most common adverse events in the ADA group; however, the number of adverse events was similar between both the groups. CONCLUSIONS: Adalimumab was effective in the treatment of chronic noninfectious posterior uveitis and panuveitis in pediatric patients, and disease inactivity was accomplished in the majority of the patients, thereby improving visual outcomes and maintaining disease stability. Adverse events were limited and tolerable.

Successful Remission with Upadacitinib in Two Patients with Anti-TNF-Refractory Macular Edema Associated with Behçet's Uveitis.

PURPOSE: Behçet's syndrome (BS) is a chronic inflammatory disease affecting the small and large vessels of the venous and arterial systems and is characterized by recurrent oral and genital ulcers. Uveitis represents the most typical ocular manifestation and completes the triple symptom complex originally described. Recognized treatments for Behçet's uveitis (BU) include systemic glucocorticoids and immunosuppressive agents. No study has reported on the use of upadacitinib for BS with panuveitis. Herein, we report the use of upadacitinib in two patients with BU suffering from macular edema and persistent inflammation, which was refractory to systemic glucocorticoids and immunosuppressive agents. METHODS: We retrospectively followed-up two cases, including an adolescent girl and a man in his thirties, with a 2- and 10-year history of BS, respectively. RESULTS: Upadacitinib successfully treated BU, leading to improved visual acuity, controlled intraocular inflammation, and the disappearance of macular edema in both patients. The patients in this study were either recalcitrant to or intolerant to conventional therapy and adalimumab. Only the female patient revealed a mildly abnormal blood picture and slight transaminitis after 6 months of upadacitinib administration. However, no serious adverse events were reported in either of the two patients during follow-up. CONCLUSION: Upadacitinib can be considered an important future option for managing recurrent and recalcitrant cases of BU, especially in those with chronic ocular inflammation and macular edema, which are refractory to conventional therapies.

Cerebellar infarction caused by vertebral artery dissection: A case report.

RATIONALE: Vertebral artery dissection is an important cause of posterior circulation ischemic stroke in young and middle-aged people. We reported a young man with cerebellar infarction caused by dissection of the right vertebral artery. PATIENT CONCERNS: A 34-year-old man presented with intermittent dizziness, blurred vision, nausea, and transient tinnitus 10 days before admission. All these symptoms were gradually aggravated and followed by vomiting and unfavorable movement of the right limbs. All these symptoms gradually aggravated. DIAGNOSIS: Neurological examination on admission showed ataxia of the right limbs. Magnetic resonance imaging of the head revealed a right cerebellar infarction. High-resolution vessel wall magnetic resonance imaging showed dissection of the right vertebral artery. Whole-brain CT digital subtraction angiography revealed occlusion of the third segment (V3) of the right vertebral artery. This supports the diagnosis of vertebral artery dissection. INTERVENTIONS: The patient received anticoagulant treatment with warfarin. OUTCOMES: After 2 weeks of treatment, the patient showed remarkably alleviated dizziness and unfavorable movement of the right limbs. After 3 months of treatment, the modified Rankin Scale score was 0. MRI of the head revealed that the original right cerebellar focus was softened, and there were no newly formed infarct foci. LESSONS: When young and middle-aged patients without atherosclerotic risk factors encounter sudden dizziness, tinnitus, and unfavorable limb movement, vertebral artery dissection may be considered. Careful inquiry into the medical history may help make a final diagnosis. Further high-resolution vessel wall magnetic resonance imaging is an effective means to find arterial dissection. Early diagnosis and treatment for vertebral artery dissection has a favorable prognosis.

Adalimumab plus Conventional Therapy versus Conventional Therapy in Refractory Non-Infectious Scleritis.

Long-term systemic glucocorticoids and non-specific immunosuppressants remain the mainstay of treatment for refractory scleritis, and result in serious side-effects and repeated inflammation flares. To assess the efficacy and safety of additional adalimumab, patients diagnosed with refractory non-infectious scleritis were enrolled. They were assigned to the conventional-therapy (CT, using systemic glucocorticoids and other immunosuppressants) group or the adalimumab-plus-conventional-therapy (ACT) group according to the treatments they received. The primary outcome was time to achieve sustained remission, assessed by a reduction in modified McCluskey's scleritis scores. Other outcomes included changes in McCluskey's scores, scleritis flares, best-corrected visual acuity, and spared glucocorticoid dosage. Patients in the ACT group achieved faster remission than those in the CT group, as the median periods before remission were 4 months vs. 2.5 months (p = 0.016). Scleritis flares occurred in 11/11 eyes in the CT group and 5/12 eyes in the ACT group (p = 0.005). Successful glucocorticoid sparing was realized in both groups, but the ACT group made it faster. No severe adverse events were observed. Data suggest that adalimumab plus conventional therapy could shorten the time to remission, reduce disease flares, and accelerate glucocorticoid withdrawal compared with conventional therapy alone.