Clinical characteristics and MRI features of autoimmune glial fibrillary acidic protein astrocytopathy: a case series of 34 patients.

Objectives: To analyze the clinical and imaging characteristics of autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). Methods: Forty-three patients diagnosed with GFAP-A between March 2017 and July 2023 were retrospectively recruited. The clinical characteristics and magnetic resonance imaging (MRI) features were collected. Results: Twenty-one patients (61.8%) had a fever and 16 (47.1%) had a headache. Five patients (14.7%) had coexisting neural autoantibodies and one patient (2.9%) had a coexisting neoplasm. The most common presentation was meningoencephalomyelitis (13/34, 38.3%), followed by meningoencephalitis (12/34, 35.3%). The other clinical manifestations included blurred visions (5/34, 14.7%) and peripheral nervous system involvement (4/34, 11.8%). Twenty-six patients (76.5%) had elevated nucleated cell count, predominantly lymphocytes (15/15, 100%), and 27 (79.4%) had elevated protein levels of cerebrospinal fluid. One-half (50%) of the patients presented with hyponatremia. A majority of the patients (30/33, 90.9%) exhibited abnormal hyperintense lesions on T2WI, which were often located in juxtacortical white matter (18/33, 54.5%), followed by periventricular white matter (16/33, 48.5%), basal ganglia (15/ 33, 45.5%), brainstem (11/33, 33.3%), and thalamic lesions (9/33, 27.3%). Twenty-four patients (72.7%) had abnormal brain enhancement, with supratentorial leptomeningeal enhancement being the most frequent enhancement pattern (15/33, 45.5%), followed by linear perivascular radial enhancement (14/33, 42.4%). Nineteen patients (70.4%) had hyperintense intramedullary spinal cord lesions, with long segments (15/27, 55.6%) and transverse lesions (14/27, 51.9%) being the most frequent lesions. Most cases were sensitive to immunotherapy, such as glucocorticoids, intravenous immunoglobulin, and tacrolimus, with three patients (8.8%) experiencing relapses. Patients with brainstem lesions had higher onset modified Rankin scale scores and were more prone to intensive care unit admissions. Linear perivascular radial enhancement was positively associated with poor prognosis (p < 0.05). Conclusion: GFAP-A presented with meningoencephalomyelitis and meningoencephalitis. The brain lesions were often located in juxtacortical white matter, periventricular white matter, basal ganglia, brainstem, and thalamus. Long segments and transverse were the most frequent spine lesions. Leptomeningeal enhancement was the most frequent enhancement pattern, followed by linear perivascular radial enhancement, which may provide new insight into the differential diagnosis of GFAP-A.

Immunity-and-matrix-regulatory cells enhance cartilage regeneration for meniscus injuries: a phase I dose-escalation trial.

Immunity-and-matrix-regulatory cells (IMRCs) derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix, which could be mass-produced with stable biological properties. Despite resemblance to mesenchymal stem cells (MSCs) in terms of self-renew and tri-lineage differentiation, the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined. Here, we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury. Following injection into the knees of rabbits with meniscal injury, IMRCs enhanced endogenous fibrocartilage regeneration. In the dose-escalating phase I clinical trial (NCT03839238) with eighteen patients recruited, we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting. Furthermore, the effective results of magnetic resonance imaging (MRI) of meniscus repair and knee functional scores suggested that 5 × 107 cells are optimal for meniscus injury treatment. In summary, we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury. Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration.

Clinical manifestations and magnetic resonance imaging features of spinal cord infarction.

BACKGROUND AND OBJECTIVE: Spinal cord infarction (SCI) is a rare type of stroke, with no proposed classification or diagnostic criterium widely accepted and used in daily clinical practice currently. We try to explore the clinical manifestations and MRI features of SCI for improving the accurate diagnosis of SCI. METHODS: Retrospectively analyzed the clinical data, MRI features, laboratory findings and outcomes of 40 patients who had been consecutively diagnosed with SCI in our hospital from June 2016 to January 2022. RESULTS: Most of the SCI (92.5%) occurred at the level of T8-L2 and C4-T4. Transverse infarction (52.5%) and ASA territory infarction (27.5%) were the most common patterns. Longitudinally extensive lesions were noticed in 67.5% of the SCI and it might be a risk factor of poor prognosis (OR=21.11, 95%CI 2.14-208.29). Restricted diffusion of the SCI lesion occurred in 8h and a few lasted up to 60 days. All SCI showed spinal cord edema, accompanied by enhancement of the ventral cauda equina (13.8%), weakened enhancement of the dorsal venous plexus (44.8%), and vertebral infarction (25%). Most patients developed a stroke-like onset (92.5%) after movement (57.5%), with definite pain in the trunk or limbs (67.5%) and dissociative sensory disturbance (60.0%). The main etiologies of them include vascular abnormalities (45%) and iatrogenic injuries (15%). CONCLUSION: An MRI classification of SCI based on the spinal cord blood supply was proposed. Restricted diffusion and co-existing abnormality of vertebral body and cauda equina may be the key neuroimaging feature for SCI diagnosis. Detailed history of vascular diseases or triggering factors are also helpful.

The role of nanoparticles and nanomaterials in cancer diagnosis and treatment: a comprehensive review.

Cancer's pathological processes are complex and present several challenges for current chemotherapy methods. These challenges include cytotoxicity, multidrug resistance, the proliferation of cancer stem cells, and a lack of specificity. To address these issues, researchers have turned to nanomaterials, which possess distinct optical, magnetic, and electrical properties due to their size range of 1-100 nm. Nanomaterials have been engineered to improve cancer treatment by mitigating cytotoxicity, enhancing specificity, increasing drug payload capacity, and improving drug bioavailability. Despite a growing corpus of research on this subject, there has been limited progress in permitting nanodrugs for medical use. The advent of nanotechnology, particularly advances in intelligent nanomaterials, has transformed the field of cancer diagnosis and therapy. Nanoparticles' large surface area allows them to successfully encapsulate a large number of molecules. Nanoparticles can be functionalized with various bio-based substrates like RNA, DNA, aptamers, and antibodies, enhancing their theranostic capabilities. Biologically derived nanomaterials offer economical, easily producible, and less toxic alternatives to conventionally manufactured ones. This review offers a comprehensive overview of cancer theranostics methodologies, focusing on intelligent nanomaterials such as metal, polymeric, and carbon-based nanoparticles. I have also critically discussed their benefits and challenges in cancer therapy and diagnostics. Utilizing intelligent nanomaterials holds promise for advancing cancer theranostics, and improving tumor detection and treatment. Further research should optimize nanocarriers for targeted drug delivery and explore enhanced permeability, cytotoxicity, and retention effects.

Efficacy and safety of tacrolimus treatment for neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is a severe inflammatory autoimmune disease that mainly involves the optic nerves and spinal cord, causing blindness and paralysis. Although some immunosuppressants such as rituximab and azathioprine have proven to be effective in relapse prevention, the high costs or intolerable adverse events preclude their wide application. Thus, we have conducted a retrospective study in 25 NMOSD patients who were treated with tacrolimus, an immunosuppressant with high efficacy and good tolerance in other autoimmune diseases, to assess its efficacy and safety in NMOSD treatment during the last five years (2011-2016). The results revealed that tacrolimus could reduce the relapse rate by 86.2% and improve the Expanded Disability Status Scale (EDSS) scores (4.5 vs 2.3; P < 0.001) significantly. Relapses in tacrolimus treatment were associated with serum titers of aquaporin 4 antibody (AQP4-IgG) (P = 0.028). Further Cox proportional analysis demonstrated that patients with high titers of AQP4-IgG (≥1:64) had a significantly higher risk of relapse than those with low titers after tacrolimus therapy (HR:5.665; CI95: 1.012-31.705; P = 0.048). Tacrolimus tended to be superior to azathioprine (29 patients) in terms of efficacy and safety during the same period. Our study suggests that tacrolimus may be another promising immunosuppressant for NMOSD.