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The pathomechanisms of autonomic disorders in systemic lupus erythematosus (SLE) remain unclear. We herein report a patient with SLE who developed autonomic disorders presumably caused by autoimmune autonomic ganglionopathy (AAG). A 42-year-old woman with SLE under treatment with corticosteroids and hydroxychloroquine was admitted for recurrence of SLE with thrombocytopenia and nephritis. On admission, she presented with weight loss, orthostatic dizziness, abdominal distension, and difficulty urinating. Marked intestinal dilatation, kidney swelling, bilateral hydronephrosis, and ureteral dilatation were noted on ultrasonography and computed tomography. No evidence of obstruction was observed in the intestines, urinary tracts, or bladder. Transverse myelitis was also ruled out by magnetic resonance imaging. After starting the treatment for the recurrent SLE (intravenous immunoglobulin and methylprednisolone pulse therapy, followed by high-dose oral corticosteroid, mycophenolate mofetil, and tacrolimus), orthostatic dizziness, abdominal distension, and difficulty urinating subsided along with increases in platelet count and decreases in urinary protein. The intestinal dilatation, hydronephrosis, and ureteral dilatation improved. We inferred that her SLE was complicated by AAG based on a positive anti-ganglionic acetylcholine receptor antibody. This case suggested that AAG should be considered as a type of autonomic disorder in SLE.

AbstractYKL-40 is implicated in inflammation and tissue repair, but no reports have investigated its involvement in myositis in polymyositis (PM) and dermatomyositis (DM). Therefore, we aimed to investigate the relationship between YKL-40 and PM/DM. We retrospectively enrolled 35 patients diagnosed with PM/DM along with 26 healthy controls (HCs). Both PM and DM were diagnosed according to Bohan and Peter’s criteria. Serum YKL-40 levels were measured, age-corrected to YKL-40 percentile values, and compared to HCs. Patients with myositis without interstitial lung disease were also enrolled and compared to HCs. Immunofluorescence staining was performed to identify YKL-40-positive inflammatory cells in muscle biopsy samples from two patients each with PM and DM. Age-corrected serum YKL-40 levels were significantly higher in patients with PM/DM compared to HCs with and without lung disease; however, these levels decreased significantly after treatment. Immunohistochemical analysis showed infiltration of YKL-40-positive inflammatory cells into the intramuscular sheath and perimuscular membrane. Immunofluorescence staining showed CD68 expression in YKL-40-positive inflammatory cells, suggesting that these cells were macrophages. To the best of our knowledge, this is the first study to demonstrate that YKL-40-positive macrophages are present in PM and DM, indicating that YKL-40 may be involved in PM/DM.

Abstract The standard treatment for platinum-sensitive relapsed ovarian cancer (PSROC) is platinum-based chemotherapy followed by olaparib monotherapy. A retrospective study was conducted to identify factors affecting the survival of patients with PSROC undergoing olaparib monotherapy in real-world clinical settings. The study enrolled 122 patients who received olaparib monotherapy between April 2018 and December 2020 at three national centers in Japan. The study used the Kaplan–Meier method and univariable and multivariable Cox proportional hazards models to evaluate the associations between factors and progression-free survival (PFS). Patients with BRCA1/2 mutations had a significantly longer median PFS than those without these mutations. Both the BRCA1/2 mutation-positive and mutation-negative groups exhibited a prolonged PFS when the platinum-free interval (PFI) was ≥ 12 months. Cancer antigen 125 (CA-125) level within reference values was significantly linked to prolonged PFS, while a high platelet-to-lymphocyte ratio (≥ 210) was significantly associated with poor PFS in the BRCA1/2 mutation-negative group. The study suggests that a PFI of ≥ 12 months may predict survival after olaparib monotherapy in patients with PSROC, regardless of their BRCA1/2 mutation status. Additionally, a CA-125 level within reference values may be associated with extended survival in patients without BRCA1/2 mutations. A larger prospective study should confirm these findings.

Aim. The aim of this study was to investigate whether cytokines associated with tumour necrosis factor- (TNF-) α and interleukin- (IL-) 6 signalling could predict rheumatoid arthritis (RA) clinical remission (CR) with Janus kinase inhibitor (JAKinib) treatment using the Simplified Disease Activity Index (SDAI). Methods. Eighty-nine patients with RA treated with JAKinibs were enrolled, and their clinical data were collected retrospectively. CR was defined as an SDAI≤3.3 after 6 months of treatment with JAKinib. The serum samples of 89 patients were analysed for IL-6, soluble IL-6 receptor (sIL-6R), soluble gp130 (spg130), and soluble TNF receptor- (sTNFR-) I and sTNFR-II titres. Results. There were no significant differences in the baseline clinical parameters between the CR and non-CR groups. Serum levels of IL-6, sIL-6R, and sgp130 were not significantly different; whereas, the serum sTNFR-I and sTNFR-II levels were significantly lower in the CR group. Univariate and multivariate logistic regression analysis showed that the baseline log sTNFR II values (OR: 0.002; p=0.034) were predictors of CR. Conclusions. Patients with RA can be stratified prior to JAKinib administration using serum sTNFR-I and sTNFR-II levels but not serum IL-6 axis cytokine levels (IL-6, sIL-6R, and sgp130).

AbstractWe examined whether serum B cell activating factor (BAFF) is useful for predicting the remission of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) following rituximab treatment. We used the Birmingham Vasculitis Activity Score (BVAS) 2008 version 3 for the evaluation of 27 patients with AAV 6 months after rituximab treatment. Those with BVAS = 0 achieved remission, whereas those with BVAS score > 0 did not achieve remission. We considered changes in serum BAFF before rituximab treatment, 1 month after treatment, and 6 months after treatment. In the remission group, the serum BAFF increased consistently. In the non-achieved group, serum BAFF was within the normal range. In addition, there was no statistically significant difference between the two groups in terms of serum BAFF before and 1 month after rituximab treatment. However, the serum BAFF level at 6 months after rituximab treatment was significantly higher in the remission group than in the non-achieved group. If serum BAFF does not increase after 6 months of rituximab in AAV, it may be assumed that there are residual B cells and plasma cells in the tissues. Enhanced treatment targeting B cells, including re-administration of rituximab or the addition of other immunosuppressive drugs, should be considered.

Abstract Background TAFRO syndrome is an acute or subacute systemic inflammatory disease with no apparent cause, presenting with fever, generalized edema, thrombocytopenia, renal damage, anemia, and organ enlargement. Interleukin-6, vascular endothelial growth factor, and other cytokines are thought to be the etiologic agents that increase vascular permeability and cause the resulting organ damage. Only few reports of renal biopsy performed in patients with TAFRO syndrome exist. Case presentation A 61-year-old woman, with a history of Sjogren’s syndrome, was admitted to our hospital with anasarca and abdominal distension. Based on the clinical course and various laboratory findings, we diagnosed TAFRO syndrome. Renal biopsy revealed thrombotic microangiopathy, including endothelial cell swelling, subendothelial space expansion, and mesangiolysis. She was treated with oral prednisolone and cyclosporine, with consequent resolution of anasarca, pleural effusion, and ascites, and improvement in renal function and urinary findings. The patient’s platelet count also normalized after 2 months of treatment. Conclusions Given that only few reports of improvement in the systemic symptoms of TAFRO syndrome using steroids and cyclosporine exist, our study investigating the relationship between the pathogenesis of TAFRO syndrome and renal disorders, as well as treatment methods, provides valuable insights.

BackgroundOlaparib-induced anemia is a frequently occurring complication in patients with advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer and is associated with a marked deterioration in patients’ health-related quality of life. This study aimed to clarify patient-specific risk factors for severe anemia in patients with advanced ovarian or breast cancer receiving olaparib monotherapy in a real-world setting.MethodsThis multicenter, retrospective, observational study enrolled consecutively presenting patients with advanced ovarian or breast cancer who received olaparib monotherapy as maintenance or palliative treatment between April 2018 and December 2020 at three participating medical institutions in Japan. The primary endpoint was patient-associated risk factors underlying the onset of grade ≥3 anemia from olaparib treatment initiation to 90 days after treatment. Receiver operating characteristic curves were constructed and univariable and multivariable logistic regression analyses were performed to evaluate the association between patient-associated risk factors and grade ≥3 anemia.ResultsOf 113 patients evaluated in this study, 32.7% (n = 37) had grade ≥3 anemia. Multivariable logistic regression analysis revealed that low baseline red blood cell (RBC) count (

A weird electronic state accompanied with an anomalous superconducting precursor and/or exotic orders, called the pseudogap state, arises prior to a superconducting condensate in underdoped cuprates that are situated near Mott transition. Another way to make the system approach the Mott transition is the variation of bandwidth or correlation strength, which gives a new dimension to exploring this exotic state. Here we report nuclear magnetic resonance (NMR) studies on layered organic superconductors with half-filled bands whose widths are pressure tuned near the Mott transition. The system situated on the verge of the Mott transition shows a pseudogap-like anomalous suppression of spin excitations on cooling from well above the superconducting critical temperature T_{c}. The pressure variation of the NMR relaxation rate shows that the pseudogap-like behavior is rapidly suppressed by applying pressure. The NMR experiments under various magnetic fields varied up to 18 T proves the absence of symmetry breaking orders that compete with superconductivity, such as charge orders, in the metallic phase. Remarkably, the pseudogap-like behavior above T_{c} and the superconducting condensate fade out in parallel under ascending magnetic fields with similar field-orientation dependence, indicating a superconducting precursor is the predominant origin of the pseudogap. Our further investigation of different materials, which take different “distances” from the Mott transition by chemical pressure, confirms that the superconducting precursor is not the conventional amplitude fluctuations arising from low dimensionality but unconventional preformation of Cooper pairs enhanced near the Mott transition. These findings conclude that preformed Cooper pairs persist up to twice as high as T_{c} on the verge of the bandwidth-controlled Mott transition.

BackgroundEndogenous DNA derived from nuclei or mitochondria is released into the blood circulation as cell-free DNA (cfDNA) following cell damage or death. cfDNA is associated with various pathological conditions; however, its clinical significance in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) remains unclear. This study aimed to evaluate the clinical significance of cfDNA in AAV.MethodsWe enrolled 35 patients with AAV, including 10 with eosinophilic granulomatosis with polyangiitis (EGPA), 13 with microscopic polyangiitis, and 12 with granulomatosis with polyangiitis. Serum cf-nuclear DNA (cf-nDNA) and cf-mitochondrial DNA (cf-mtDNA) levels were measured by quantitative polymerase chain reaction before and after the initiation of immunosuppressive therapy. Tissue samples from EGPA patients were examined by immunofluorescence and transmission electron microscopy. The structure of eosinophil extracellular traps (EETs) and neutrophil extracellular traps (NETs) and stability against DNase were assessed in vitro. Platelet adhesion of EETs were also assessed.ResultsSerum cf-nDNA and cf-mtDNA levels were significantly higher in AAV than in healthy controls, with the highest levels in EGPA; however, serum DNase activities were comparable among all groups. cf-nDNA and cf-mtDNA decreased after treatment and were associated with disease activity only in EGPA. Blood eosinophil count and plasma D-dimer levels were significantly correlated with cf-nDNA in EGPA and cf-mtDNA. EGPA tissue samples showed lytic eosinophils and EETs in small-vessel thrombi. The structure of EETs showed bolder net-like chromatin threads in vitro and EETs showed greater stability against DNase than NETs. EETs provided a scaffold for platelet adhesion.ConclusioncfDNA was increased in EGPA, associated with disease activity. The presence of DNase-resistant EETs in small-vessel thrombi might contribute to higher concentration of cfDNA and the occurrence of immunothrombosis in EGPA.

BackgroundNivolumab and pembrolizumab are the standard treatments for patients with advanced non-small-cell lung cancer (NSCLC). While there are reports on several inflammatory indices and the prognosis of patients with cancer, no study has combined baseline medication with the neutrophil-to-lymphocyte ratio (NLR) to predict clinical outcomes. This study investigated the efficacy of baseline medications plus NLR to predict the effectiveness of nivolumab and pembrolizumab in a real-world clinical setting.MethodsWe conducted a single-center retrospective observational study of consecutive patients with advanced NSCLC who received nivolumab or pembrolizumab as first-line, second-line, or beyond treatment between December 2015 and November 2018 at the National Cancer Center Hospital in Japan. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. The drug-based prognostic score for baseline medications plus NLR was weighed based on the regression β coefficients. The multivariable Cox proportional hazard model was used to assess the association between the prognostic score-stratified groups and survival outcomes.ResultsIn total, 259 patients were evaluated in this study. A prognostic score calculated from the baseline medications plus NLR was used to categorize the patients into good (score 0), intermediate (scores 1–2), and poor (scores 3–6) -prognosis groups. The multivariable Cox proportional hazard model revealed a significant association between the poor-prognosis group and reduced OS. The hazard ratio of OS was 1.75 (95% confidence interval: 1.07–2.99; P = 0.031). In contrast, no association between these prognosis groups and PFS was observed.ConclusionsThe findings suggest that the baseline medications with nivolumab or pembrolizumab plus NLR could lead to progressively shorter survival outcomes in patients with advanced NSCLC and could be used as a prognostic index for poor outcomes. However, to ascertain the clinical application of these findings, these concomitant medications need further validation in a large-scale multicenter study.

Several organic materials exhibit spin liquid phases, which are predicted to host exotic spinon excitations that emerge from non-local quantum effects. Here, the authors identify a quasi-continuous phase transition in κ-(ET)2Cu2(CN)3 that may be associated with the presence of spinons.

Electrical control of magnetic response in bulk material without electric or magnetic order is rare and potentially attractive for high efficient spintronics. Here, the authors report magnetization in elemental tellurium driven purely by current without any (anti-)ferroic order.

Chiral matter has a structure that lacks inversion, mirror, and rotoreflection symmetry; thus, a given chiral material has either a right- or left-handed structure. In chiral matter, electricity and magnetism can be coupled in an exotic manner beyond the classical electromagnetism (e.g., magneto chiral effect in chiral magnets). In this paper, we give a firm experimental proof of the linear electric-current-induced magnetization effect in bulk nonmagnetic chiral matter elemental trigonal tellurium. We measured a ^{125}Te nuclear magnetic resonance (NMR) spectral shift under a pulsed electric current for trigonal tellurium single crystals. We provide general symmetry considerations to discuss the electrically (electric-field- and electric-current-) induced magnetization and clarify that the NMR shift observed in trigonal tellurium is caused by the linear current-induced magnetization effect, not by a higher-order magnetoelectric effect. We also show that the current-induced NMR shift is reversed by a chirality reversal of the tellurium crystal structure. This result is direct evidence of crystal-chirality-induced spin polarization, which is an inorganic-bulk-crystal analog of the chirality-induced spin selectivity in chiral organic molecules. The present findings also show that nonmagnetic chiral crystals may be applied to spintronics and coil-free devices to generate magnetization beyond the classical electromagnetism.