A Randomized Phase 2 Trial of Antibiotic Prophylaxis Versus No Intervention for Muscle Biopsy in A Neurology Department

Muscle biopsy can be used to confirm the diagnosis of neuromuscular diseases. However, it is unclear whether antibiotic prophylaxis prior to muscle biopsy is needed to prevent surgical site infection (SSI). We are conducting a phase 2, single-center, open-labeled, prospective randomized trial to clarify the need for antibiotic prophylaxis in patients at low risk for SSI undergoing muscle biopsy. Patients will be randomized to an antibiotic prophylaxis group or a control group, and the incidence of SSI will be compared between the groups. Our findings will clarify the need for antibiotic prophylaxis in this patient population

A reversible lesion of the corpus callosum splenium with adult influenza-associated encephalitis/encephalopathy: a case report

<p>ABstract</p> <p>Introduction</p> <p>Influenza virus-associated encephalitis/encephalopathy is a severe childhood illness with a poor prognosis. Adult case reports are rare and, to date, there have been no reports of adults with a mild subcortical encephalopathy with reversible lesions of the corpus callosum splenium.</p> <p>Case presentation</p> <p>A previously healthy 35-year-old man presented with acute progressive tetraplegia, transcortical motor aphasia and a mild decrease in his consciousness during his recovery after receiving oseltamivir phosphate treatment, and influenza type A antiviral medication. The initial magnetic resonance imaging study at day 1 showed symmetrical diffuse lesions in the white matter and a lesion on the central portion of the corpus callosum splenium. These findings had resolved on follow-up studies at day 8 and day 146. His neurological deficits mostly recovered within 12 hours following methylprednisolone pulse therapy. The levels of interleukin-6 and interleukin-10 in his blood and cerebrospinal fluid were initially elevated, but rapidly decreased to normal levels by day 8.</p> <p>Conclusion</p> <p>It is important for clinicians to recognize that even in adulthood, the subcortical encephalopathy observed during the therapeutic treatment for influenza type A infection can occur in conjunction with a reversible lesion of the corpus callosum, which may recover quickly. In addition, the cytokine storm in the blood system and the corticospinal cavity may play an important role in the etiology of the disease process.</p

メンエキ セイギョ ブンシ TRAIL ニ ヨル ジコ メンエキ シッカン ノ セイギョ キコウ ニ カンスル ケンキュウ

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is known to play a pivotal role in the inhibition of autoimmune disease. We previously reported a disease-preventive effect of embryonic stem cell-derived dendritic cells (ES-DC) genetically engineered to express TRAIL along with a myelin antigen, MOG, on experimental autoimmune encephalomyelitis (EAE), and also suggested that CD4+CD25+ regulatory T (Treg) cells were involved in mediating this preventive effect. In the current study, we investigated the effect of TRAIL on Treg cells as well as conventional T cells, using TRAIL-deficient mice. Upon induction of EAE, TRAIL-deficient mice showed more severe clinical symptoms, a higher frequency of IFN-γ-producing CD4+ T (Th1) cells, and a lower frequency of CD4+Foxp3+ Treg cells than wild type mice. In vitro, conventional T cells stimulated by bone marrow-derived DC (BM-DC) from TRAIL-deficient mice showed a higher magnitude of proliferation than those stimulated by BM-DC from wild type mice. In contrast, TRAIL expressed on the stimulator BM-DC enhanced the proliferative response of CD4+CD25+ Treg cells in the culture. The functional TRAIL-receptor, mDR5, was expressed in both conventional T cells and Treg cells upon stimulation. On the other hand, the decoy receptor, mDc-TRAIL-R1 was slightly expressed only on CD4+CD25+ Treg cells. Therefore, the distinct effects of TRAIL may be due to differences in the mDc-TRAIL-R1-expreesion or the signaling pathways down-stream of mDR5 between the two T cell subsets. Our data suggests that TRAIL suppresses autoimmunity by two mechanisms; one is the inhibition of Th1 cells and the other is the promotion of Treg cells

Change in Municipality-Level Health-Related Social Capital and Depressive Symptoms: Ecological and 5-Year Repeated Cross-Sectional Study from the JAGES

Prevalence of depressive symptoms is lower in communities with greater social capital (SC). However, it is unclear whether a prevalence of depressive symptoms will decrease in communities where SC has increased. We investigated the relationship between the changes in municipality-level SC and depressive symptoms by using 5-year repeated cross-sectional data from the Japan Gerontological Evaluation Study. In 2010 and 2016, self-reported questionnaires were mailed to functionally independent residents aged 65 years or older living in 44 municipalities; valid responses were received from 72,718 and 84,211 people in 2010 and 2016, respectively. All scores were aggregated at the municipality level. The dependent variable was the change in the prevalence of depressive symptoms that were diagnosed with a 15-item Geriatric Depression Scale. Independent variables were the score of change in health-related SC indicators, e.g., social participation, social cohesion, and reciprocity. A multiple regression analysis was employed. The average prevalence of depressive symptoms decreased from 28.6% in 2010 to 21.3% in 2016. The increases in the percentages of sports group participation (B, &minus;0.356), and reciprocity scores (B, &minus;0.597) were significantly associated with the decrease in the prevalence of depressive symptoms after adjusting for potential confounding variables. Our findings suggest that community SC might be an intervention for protecting depressive symptoms in municipalities

Aging-associated and CD4 T-cell–dependent ectopic CXCL13 activation predisposes to anti–PD-1 therapy-induced adverse events

がん免疫療法の副反応による臓器傷害の原因解明に新たな一歩 --がんに対する免疫応答と、有害事象に関わる免疫応答の違い--. 京都大学プレスリリース. 2022-07-13.Clinical success of immune-checkpoint blockade (ICB) cancer immunotherapy is compromised by increased risk of immune-related adverse events (irAEs). However, mechanistic action(s) of immune responses underlying development of irAE remain not fully explored. Here, we found that in tumor-bearing aged, but not young, mice, antiprogrammed death receptor (PD)-1 therapy elicited irAE-like multiorgan dysfunctions with ectopic accumulation of T and B cells in damaged organs. In this preclinical model, the organ toxicities were mediated by immunoglobulin G (IgG) deposition because administration of IG from ICB-treated aged mice induced the pathogenicity specifically in naïve aged hosts. Mechanistically, CD4 T-cell–derived interleukin (IL)-21 upregulated B-cell–homing chemokine, CXCL13, preferentially in irAE organs from aged mice treated with anti–PD-1 therapy. The ICB-induced pathogenicity was alleviated by B-cell depletion or by blockade of IL-21 or CXCL13 activity. These results suggest that age-associated immune regulatory milieu contributes to the formation of tertiary lymphoid structure-like lymphocytic aggregates in irAE organs and irAE-related toxicity employing IL-21-CXCL13-auto-antibody axis. Supporting this, a systemic increase in CXCL13 and Il21 expression in CD4 T cells correlated with irAE incidence in ICB-treated patients. These findings provide rationale for therapeutic usefulness of CXCL13 in irAE management

Degradation of amyloid beta by human induced pluripotent stem cell-derived macrophages expressing Neprilysin-2

The purpose of this study was to evaluate the therapeutic potential of human induced pluripotent stem (iPS) cell-derived macrophage-like cells for Alzheimer's disease (AD). In previous studies, we established the technology to generate macrophage-like myeloid lineage cells with proliferating capacity from human iPS cells, and we designated the cells iPS-ML. iPS-ML reduced the level of Aβ added into the culture medium, and the culture supernatant of iPS-ML alleviated the neurotoxicity of Aβ. We generated iPS-ML expressing the Fc-receptor-fused form of a single chain antibody specific to Aβ. In addition, we made iPS-ML expressing Neprilysin-2 (NEP2), which is a protease with Aβ-degrading activity. In vitro, expression of NEP2 but not anti-Aβ scFv enhanced the effect to reduce the level of soluble Aβ oligomer in the culture medium and to alleviate the neurotoxicity of Aβ. To analyze the effect of iPS-ML expressing NEP2 (iPS-ML/NEP2) in vivo, we intracerebrally administered the iPS-ML/NEP2 to 5XFAD mice, which is a mouse model of AD. We observed significant reduction in the level of Aβ in the brain interstitial fluid following administration of iPS-ML/NEP2. These results suggested that iPS-ML/NEP2 may be a potential therapeutic agent in the treatment of AD