Effect of Vericiguat on Left Ventricular Reverse Remodeling in Patients Who Have Heart Failure With Reduced Ejection Fraction - Special Focus on Patients Without Quadruple Medical Therapy.

Background: A novel cardioprotective drug, vericiguat, reduces the risk of cardiovascular mortality for patients already on guideline-directed medical therapy. However, the effect of vericiguat on left ventricular (LV) reverse remodeling in patients with reduced LV ejection fraction (LVEF) with or without guideline-directed medical therapy, known as quadruple medical therapy, remains undetermined.

Methods And Results: This study comprised 73 heart failure (HF) patients with reduced LVEF (<45%) from 5 institutions in Japan.

Clinical practice guidelines for multiple sclerosis, neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-associated disease 2023 in Japan.

Background: The previous Japanese clinical practice guidelines for multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) were published in 2017. Recently, for the first time in 6 years, the MS and NMOSD guideline development committee revised the Japanese guidelines for MS, NMOSD, and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).

Methods: The committee utilized the Grading of Recommendations Assessment, Development, and Evaluation system based on the "Minds Handbook for Clinical Practice Guideline Development 2020 Ver.

Stage-dependent immunity orchestrates AQP4 antibody-guided NMOSD pathology: a role for netting neutrophils with resident memory T cells in situ.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the CNS characterized by the production of disease-specific autoantibodies against aquaporin-4 (AQP4) water channels. Animal model studies suggest that anti-AQP4 antibodies cause a loss of AQP4-expressing astrocytes, primarily via complement-dependent cytotoxicity. Nonetheless, several aspects of the disease remain unclear, including: how anti-AQP4 antibodies cross the blood-brain barrier from the periphery to the CNS; how NMOSD expands into longitudinally extensive transverse myelitis or optic neuritis; how multiphasic courses occur; and how to prevent attacks without depleting circulating anti-AQP4 antibodies, especially when employing B-cell-depleting therapies.

Fifteen-Year Clinical Outcomes After Sirolimus-Eluting Stent Implantation.

Background: Clinical outcomes after percutaneous coronary intervention have improved with the use of drug-eluting stents, but data beyond 10 years are limited. The purpose of this study was to evaluate the clinical outcomes of patients undergoing sirolimus-eluting stent implantation with follow-up beyond 10 years and to determine the impact of clinical and angiographic characteristics on long-term prognosis.

Methods and results: The clinical outcomes of 885 patients who had undergone sirolimus-eluting stent implantation at a single institution were retrospectively reviewed.

Resident Memory-like CD8 T Cells Are Involved in Chronic Inflammatory and Neurodegenerative Diseases in the CNS.

Background And Objectives: Resident memory T (Trm) cells are a unique population that can survive and function in a compartmentalized tissue with inflammatory potential. We aim to investigate the alteration of Trm population in acute/chronic inflammatory and neurodegenerative diseases in the CNS.

Methods: The frequencies of CD4 and CD8 T cells expressing both CD69 and CD103, the markers for Trm cells, were quantified in the peripheral blood and CSF (n = 80 and 44, respectively) in a cross-sectional manner.

Urosepsis Risk in Neuromyelitis Optica Spectrum Disorder Patients Administered Satralizumab.

Objective The interleukin-6 (IL-6) inhibitor satralizumab is an established treatment for neuromyelitis optica spectrum disorder (NMOSD). Although IL-6 inhibitors are generally well-tolerated, serious infections, including sepsis, can occur. In this study, we compared the sepsis characteristics in NMOSD patients administered satralizumab (NMOSD-satralizumab) to those in rheumatoid arthritis patients administered tocilizumab (RA-tocilizumab), another IL-6 inhibitor.

Association of cerebrospinal inflammatory profile with radiological features in newly diagnosed treatment-naïve patients with multiple sclerosis.

Objective: Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. Without reliable diagnostic biomarkers, the clinical and radiological heterogeneity of MS makes diagnosis difficult. Although magnetic resonance imaging (MRI) is a major diagnostic tool for MS, the association of MRI findings with the inflammatory profile in cerebrospinal fluid (CSF) has been insufficiently investigated.

T cells from MS Patients with High Disease Severity Are Insensitive to an Immune-Suppressive Effect of Sulfatide.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Its early phase is characterized by a relapse-remitting disease course, followed by disability progression in the later stage. While chronic inflammation accompanied with degeneration is well-established as the key pathological feature, the pathogenesis of MS, particularly progressive MS, remains elusive.

A tumefactive anti-MOG antibody associated disorder heralding central nervous system B-cell lymphoma: Case report on diagnostic challenge.

We present the case of a 52-year-old woman with right hemiparesis due to a mass lesion in the left parietal white matter and corpus callosum. The lesion was hyperintense on diffusion weighted image and homogenously enhanced with gadolinium on magnetic resonance imaging, and was radiologically indistinguishable with lymphoma. Following progressive aggravation of symptoms, craniotomy for biopsy of the lesion was performed, and it was revealed that the patient had anti-myelin oligodendrocyte glycoprotein-associated disease by histopathological and serological diagnosis.

Radiological and Laboratory Features of Multiple Sclerosis Patients With Immunosuppressive Therapy: A Multicenter Retrospective Study in Japan.

Multiple sclerosis (MS) is a relapsing, inflammatory, and demyelinating disease of central nervous system showing marked clinical heterogeneity. Many factors might influence the choice of relapse prevention drug, and treatment response varies among patients. Despite the enlargement of disease-modifying drugs for MS (MS-DMDs), some patients have been treated with corticosteroid and/or immunosuppressant (CS/IS).

Immune Skew of Circulating Follicular Helper T Cells Associates With Myasthenia Gravis Severity.

Objective: To clarify functional alterations of follicular helper T cells (Tfh) in myasthenia gravis (MG) because Tfh play important roles in helping B cells generate antibody-producing cells.

Methods: A total of 24 immunotherapy-naive patients with anti-acetylcholine receptor (AchR) antibody-positive MG and 18 age-matched healthy subjects (HS) were enrolled. Samples from 6 patients were available for posttreatment analysis.

Altered features of monocytes in adult onset leukoencephalopathy with axonal spheroids and pigmented glia: A clue to the pathomechanism of microglial dyshomeostasis.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is an autosomal-dominant type of leukoencephalopathy caused by gene mutation of colony stimulating factor 1 receptor, which is expressed mainly on monocyte lineage cells such as monocytes in the peripheral blood and microglia in the brain. Hence, microglial dysfunction is regarded as critical in the pathogenesis of ALSP. However, functional changes in these cells have not been elucidated.

Clinical characteristics of autoimmune disorders in the central nervous system associated with myasthenia gravis.

Myasthenia gravis (MG) is occasionally associated with autoimmune diseases in the central nervous system (CNS), such as neuromyelitis optica spectrum disorder (NMOSD), multiple sclerosis (MS), Morvan syndrome, and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Here, we report five original cases associated with autoimmune disorders in the CNS among 42 patients with MG in a single tertiary hospital in Japan (11.9%).

Persistent microscopic active inflammatory lesions in the central nervous system of a patient with neuromyelitis optica treated with oral prednisolone for more than 40 years.

We have reported an autopsy case of neuromyelitis optica (NMO) that exhibited persisting active inflammatory lesions in the central nervous system (CNS) despite a 45-year-long treatment with oral corticosteroids. To our knowledge, our case had received the longest course of maintenance treatment. This case study suggests that the current treatment of NMO with immunosuppressive agents may offer a good prospect for improving life expectancy.

Signaling via toll-like receptor 4 and CD40 in B cells plays a regulatory role in the pathogenesis of multiple sclerosis through interleukin-10 production.

Background: B cells play an important role in the development of multiple sclerosis (MS), but can also exhibit regulatory functions through IL-10 production. Toll-like receptors (TLR) and CD40 signaling are likely to be involved in this process.

Objective: To investigate the ability of MS B cells to produce IL-10 in response to TLR stimulation in the presence or absence of CD40 co-stimulation.

Altered T cell phenotypes associated with clinical relapse of multiple sclerosis patients receiving fingolimod therapy.

Multiple sclerosis (MS) is a T cell-mediated autoimmune disease. Fingolimod, a highly effective disease-modifying drug for MS, retains CCR7 central memory T cells in which autoaggressive T cells putatively exist, in secondary lymphoid organs, although relapse may still occur in some patients. Here, we analyzed the T cell phenotypes of fingolimod-treated, fingolimod-untreated patients, and healthy subjects.

Utility of SPM8 plus DARTEL (VSRAD) combined with magnetic resonance spectroscopy as adjunct techniques for screening and predicting dementia due to Alzheimer's disease in clinical practice.

We validated the utility of SPM8 plus DARTEL (VSRAD) combined with magnetic resonance spectroscopy (1H MRS) as an adjunct screening technique for dementia due to Alzheimer's disease (AD). We examined the posterior cingulate gyri of 228 subjects using VSRAD and 1H MRS in addition to conventional cerebrospinal fluid biomarkers at baseline. At the 3-year follow-up, the 228 subject were classified as follows: 93 healthy subjects, 42 MCI-non-converters (MCI-NC), 25 MCI-converters to AD (MCI-C), 44 AD, 8 dementia with Lewy bodies (DLB), 5 normal pressure hydrocephalus, and 11 patients with other neurological diseases.

Sjögren syndrome presenting with encephalopathy mimicking Creutzfeldt-Jakob disease.

A 61-year-old man developed subacute progressive dementia, general fatigue, a tonic-clonic seizure, and a decreased level of consciousness. He had a past history of chronic hepatitis type C and was diagnosed as having hepatic encephalopathy due to hyperammonemia. His level of consciousness did not improve even though the serum ammonia level improved.

Demyelinating features in sensory nerve conduction in Fisher syndrome.

Objective: A significant number of patients with Fisher syndrome (FS) exhibit sensory symptoms in addition to the classical triad of opthalmoplegia, ataxia and areflexia. Previous studies have shown the amplitudes of sensory nerve action potentials (SNAPs) to decrease in patients with FS, thus implying the presence of an axonal pathology in the sensory nerves.

Methods: We included ten consecutive patients with FS who were divided into the following two groups: those with hypesthesia (group H) and those without hypesthesia (group NS).

Top of the basilar syndrome in a young adult initially presenting with a convulsive seizure.

A 23-year-old man was admitted to our hospital due to loss of consciousness and a generalized convulsive seizure. He was diagnosed as having primary epilepsy and treated with antiepileptic drugs. Emergency CT scan of the head showed no abnormality.

Usefulness of serum S100B as a marker for the acute phase of aquaporin-4 autoimmune syndrome.

The aquaporin-4 (AQP4) water channel antibody is used in the diagnosis of neuromyelitis optica (NMO) due to its high sensitivity and high specificity. However, some patients are reported to have neither optic neuritis nor myelitis despite being positive for the AQP4-autoantibody (AQP4-Ab). Therefore, recent reports suggest that such patients should be diagnosed as having 'AQP4-autoimmune syndrome'.