Comparison between hangeshashinto and dexamethasone for IL-1α and ß-defensin 1 production by human oral keratinocytes.

OBJECTIVE: Human ß-defensin 1 (hBD-1) is a antimicrobial peptide that is constantly secreted by oral tissues. Hangeshashinto (HST), a traditional Japanese medicine, has been reported to be effective against stomatitis. This study aimed to clarify the profile of HST by comparing the system of production of interleukin-1α (IL-1α) and hBD-1 in human oral mucosal epithelial cells with dexamethasone (DEX), a steroid used for the treatment of stomatitis. METHODS: Human oral keratinocytes (HOK) were treated with HST, DEX, or HST components (baicalein, baicalin, berberine, and glycyrrhizin) for 24 h, and subsequently cultured for 24 h with or without Pam3CSK4 or lipopolysaccharide (LPS). The cell supernatants, total RNA, and intracellular proteins were collected, and changes in IL-1α and hBD-1 protein production and gene expression were evaluated using ELISA and RT-PCR. The phosphorylation of NF-kB and the cell proliferative ability of HOK were evaluated by western blotting and XTT assay, respectively. RESULTS: DEX (0.01-10 µM) significantly suppressed IL-1α and hBD-1 production induced by either Pam3CSK4 or LPS, and also decreased cell growth. In contrast, HST inhibited Pam3CSK4- and LPS-induced IL-1α production at a concentration range of 12.5-100 µg/mL without affecting the cell proliferative capacity and hBD-1 production of HOK. Baicalein and baicalin, which are flavonoid ingredients of HST, showed anti-IL-1α production. CONCLUSION: HST may be useful as a therapeutic agent for stomatitis and other inflammatory diseases of the oral cavity.

Successful delivery of viviparous lantern shark from an artificial uterus and the self-production of lantern shark luciferin.

Our recent success in the long-term maintenance of lantern shark embryos in artificial uterine systems has provided a novel option for the medical treatment of premature embryos for captive viviparous elasmobranchs. The remaining issue with this system is that the embryos cannot survive the abrupt change in the chemical environment from artificial uterine fluid (AUF) to seawater during delivery. To overcome this issue, the present study developed a new protocol for seawater adaptation, which is characterized by a long-term and stepwise shift from AUF to seawater prior to delivery. This protocol was employed successfully, and the specimen survived for more than seven months after delivery, the longest captive record of the species. During the experiment, we unexpectedly detected bioluminescence of the embryonic lantern shark in the artificial uterus. This observation indicates that lantern sharks can produce luciferin, a substance for bioluminescence. This contradicts the recent hypothesis that lantern sharks lack the ability to produce luciferin and use luciferin obtained from food sources.

Development of Mn2+-Specific Biosensor Using G-Quadruplex-Based DNA.

Metal ions are used in various situations in living organisms and as a part of functional materials. Since the excessive intake of metal ions can cause health hazards and environmental pollution, the development of new molecules that can monitor metal ion concentrations with high sensitivity and selectivity is strongly desired. DNA can form various structures, and these structures and their properties have been used in a wide range of fields, including materials, sensors, and drugs. Guanine-rich sequences respond to metal ions and form G-quadruplex structures and G-wires, which are the self-assembling macromolecules of G-quadruplex structures. Therefore, guanine-rich DNA can be applied to a metal ion-detection sensor and functional materials. In this study, the IRDAptamer library originally designed based on G-quadruplex structures was used to screen for Mn2+, which is known to induce neurodegenerative diseases. Circular dichroism and fluorescence analysis using Thioflavin T showed that the identified IRDAptamer sequence designated MnG4C1 forms a non-canonical G-quadruplex structure in response to low concentrations of Mn2+. A serum resistance and thermostability analysis revealed that MnG4C1 acquired stability in a Mn2+-dependent manner. A Förster resonance energy transfer (FRET) system using fluorescent molecules attached to the termini of MnG4C1 showed that FRET was effectively induced based on Mn2+-dependent conformational changes, and the limit of detection (LOD) was 0.76 µM for Mn2+. These results suggested that MnG4C1 can be used as a novel DNA-based Mn2+-detecting molecule.

Choice of and response to treatment in patients with early-diagnosed rheumatoid arthritis: Real-world data from an inception cohort in Japan (NICER-J).

OBJECTIVE: Various guidelines recommend that patients with early rheumatoid arthritis (RA) try to achieve clinical remission within 6 months, and early therapeutic intervention is important to this end. This study aimed to investigate short-term treatment outcomes of patients with early-diagnosed RA in clinical practice and to examine predictive factors for achieving remission. METHODS: Of the 210 patients enrolled in the multicenter RA inception cohort, 172 patients who were followed up to 6 months after treatment initiation (baseline) were included. Logistic regression analysis was used to examine the impact of baseline characteristics on achievement of Boolean remission at 6 months. RESULTS: Participants (mean age, 62 years) initiated treatment after a mean of 19 days from RA diagnosis. At baseline and 3 and 6 months after treatment initiation, proportions of patients using methotrexate (MTX) were 87.8%, 89.0%, and 88.3%, respectively, and rates of Boolean remission were 1.8%, 27.8%, and 34.5%, respectively. Multivariate analysis revealed that physician global assessment (PhGA) (Odds ratio (OR): 0.84, 95% confidence interval (CI): 0.71-0.99) and glucocorticoid use (OR: 0.26, 95% CI: 0.10-0.65) at baseline were independent factors that predicted Boolean remission at 6 months. CONCLUSION: After a diagnosis of RA, satisfactory therapeutic effects were achieved at 6 months after the initiation of treatment centered on MTX according to the treat to target strategy. PhGA and glucocorticoid use at treatment initiation are useful for predicting the achievement of treatment goals.

Femoral Valgus Correction Angle for the Intramedullary Alignment Rod Is Strongly Associated with Femoral Lateral Bowing in Japanese Patients with Varus Knee Osteoarthritis Undergoing Total Knee Arthroplasty.

Background: This study aimed to investigate factors, such as differences in femoral shape, that could affect the femoral valgus correction angle (VCA) for the intramedullary alignment rod (IM rod) by using a three-dimensional (3D) measurement system in patients with varus knee osteoarthritis undergoing total knee arthroplasty (TKA). Methods: A total of 305 knees in 233 Japanese patients with varus knee osteoarthritis who underwent primary TKA by using Jig Engaged 3D Pre-Operative Planning Software for the TKA operation support system was examined. We retrospectively analysed factors, such as the shape of the proximal, middle, and distal femur in the coronal plane, all of which could affect the VCA for the IM rod, by multiple linear regression analyses. Results: The VCA for the IM rod was 5.9° ± 1.6° (range: 1.7° to 10.7°), and the femoral lateral bowing angle (FBA) was 3.5° ± 3.2°. Major factors independently associated with the VCA for the IM rod were the FBA (ß: 0.75), femoral offset (ß: 0.38), and the medial angle between the mechanical femoral axis and the line that connects the distal margins of the medial and lateral femoral condyles (ß: -0.16). The model was created by stepwise multiple linear regression (F = 266.6, p < 0.001, and estimated effect size = 4.4) explained 85% of the variance in the VCA for the IM rod (R 2 = 0.85). Conclusions: The VCA for the IM rod was most strongly associated with femoral lateral bowing in patients with varus knee osteoarthritis undergoing TKA. Our findings suggest that preoperatively measuring the VCA for the IM rod in patients with femoral lateral bowing by using a 3D measurement system could be useful for accurate coronal alignment of the femoral component in TKA.

Data of RNA-seq transcriptomes of liver, bone, heart, kidney and blood in klotho mice at a pre-symptomatic state and the effect of a traditional Japanese multi-herbal medicine, juzentaihoto.

We performed RNA-seq analyses of mRNA isolated from five organs, liver, bone, heart, kidney and blood at the pre-symptomatic state of klotho mice with/without administration of a Japanese traditional herbal medicine, juzentaihoto (JTT). Data of differentially expressed genes (DEG) with/without JTT was included. Intron retention (IR) is an important regulatory mechanism that affects gene expression and protein functions. We collected data in which retained-introns were accumulated in a particular set of genes of these organs, and showed that among these retained introns in the liver and bone a subset was recovered to the normal state by the medicine. All of the data present changes of molecular events on the levels of metabolites, proteins and gene expressions observed at the pre- symptomatic state of aging in klotho mice with/without JTT. The research article related to this Data in Brief is published in GENE entitled as "Intron retention as a new pre-symptomatic marker of aging and its recovery to the normal state by a traditional Japanese herbal medicine".

Clinical usefulness of a novel high-sensitivity hepatitis B core-related antigen assay to determine the initiation of treatment for HBV reactivation.

BACKGROUNDS: A fully automated, novel, high-sensitivity hepatitis B core-related antigen assay (iTACT-HBcrAg) has been developing. The purpose of this study is to evaluate the efficacy of measuring HBcrAg, using that assay, to diagnose HBV reactivation in a multi-center setting, compared with ultra-high-sensitivity HBsAg (iTACT-HBsAg) and HBV DNA assays. METHODS: Forty-four patients with HBV reactivation from 2008 to 2020 were enrolled in four hospitals. Serial serum specimens from the patients were assessed retrospectively for their HBcrAg levels by iTACT-HBcrAg (lower limit of detection; 2.0 log U/mL) and HBsAg levels by iTACT-HBsAg (lower limit of detection; 0.0005 IU/mL); these were compared to the HBV DNA levels. HBV reactivation was defined as detection of serum HBV DNA, including unquantifiable detection. RESULTS: At HBV reactivation and/or thereafter, HBV DNA levels were quantified (≥ 1.3 log IU/mL) in the sera of 27 patients, and were below the level of quantification (< 1.3 log IU/mL) in the sera of 17 patients. Of the 27 patients with HBV reactivation and whose serum HBV DNA was quantified, the sera of 26 and 24 patients (96.3% and 88.9%) were positive by iTACT-HBcrAg and iTACT-HBsAg, respectively. HBcrAg was detectable by iTACT-HBcrAg before HBV DNA was quantifiable in 15 of the 27 patients. Of the 11 patients with HBV reactivation and undetectable HBcrAg by iTACT-HBcrAg at HBV reactivation and/or thereafter, 10 had unquantifiable HBV DNA and none developed HBV reactivation-related hepatitis. CONCLUSIONS: The iTACT-HBcrAg assay is useful for monitoring HBV reactivation to determine the initiation of treatment with nucleos(t)ide analogues.

Management of hepatitis B virus (HBV) reactivation in patients with resolved HBV infection based on a highly sensitive HB core-related antigen assay.

AIMS: To prevent hepatitis B virus (HBV) reactivation-related hepatitis, we examined the clinical usefulness of a highly sensitive HB core-related antigen (iTACT-HBcrAg) assay in patients with resolved HBV infection after nucleos(t)ide analog (NA) treatment for HBV reactivation. METHODS: We retrospectively analyzed 27 patients with resolved HBV infection who experienced HBV reactivation (defined as HBV DNA levels of 1.3 log IU/ml or more), and who received systemic chemotherapies for hematological malignancies between 2008 and 2020. iTACT-HBcrAg, HBsAg-HQ, and antibodies against hepatitis B surface antigen (anti-HBs) were measured using samples stored after HBV reactivation. The lower limit of quantification for iTACT-HBcrAg was 2.0 log U/ml. RESULTS: HBV reactivation was diagnosed at a median HBV DNA level of 1.8 log IU/ml, and then all patients received NA treatment. No patient had HBV-related hepatitis with a median maximum HBV DNA level of 2.0 log IU/ml. The positivities of iTACT-HBcrAg and HBsAg-HQ were 96% and 52% after HBV reactivation, respectively. Of 25 patients with detectable iTACT-HBcrAg at the initiation of NA treatment, 17 (68%) achieved iTACT-HBcrAg loss. Median durations from NA treatment to HBV DNA loss and iTACT-HBcrAg loss or the last follow-up were 35 and 175 days, respectively. Recurrence of HBV reactivation after NA cessation was not observed in seven of eight patients who achieved iTACT-HBcrAg loss or seropositive for anti-HBs during follow-up, except for one without anti-HBs after allogeneic transplantation. CONCLUSIONS: iTACT-HBcrAg could be a potential surrogate marker for diagnosing early-stage HBV reactivation as well as safe cessation of NA treatment in patients with resolved HBV infection after HBV reactivation.

Evaluation of an operation support system using the femoral anterior tangent line to determine intraoperative femoral component rotation in total knee arthroplasty.

BACKGROUND: The femoral anterior tangent (FAT) line refers to a line parallel to the anterior surface of the distal femur in the axial plane. This study aimed to evaluate the effectiveness of a new operation support system which uses the FAT line to set the femoral component rotational alignment in total knee arthroplasty (TKA). METHODS: A total of 170 consecutive knees in 139 patients undergoing primary TKA with the JIGEN (Jig Engaged Three-dimensional (3D) Pre-Operative Planning Software for TKA) operation support system was examined. The JIGEN system creates 3D models of bones using computed tomography data, allowing for surgical simulations such as positioning of implants while calculating positions of the intramedullary alignment rod (IM rod) and surgical jig. We retrospectively analyzed the FAT line angle relative to the surgical epicondylar axis (SEA) on the axis plane perpendicular to the IM rod and evaluated the accuracy of the femoral component alignment after TKA with the 3D measurement system. RESULTS: The FAT line was 9.6° ± 3.7° (range, 1.4°-20.4°) internally rotated relative to the SEA. The average absolute error was 1.4° ± 1.1° in the coronal plane, 2.0° ± 1.5° in the sagittal plane, and 1.6° ± 1.3° in the axial plane. The femoral component outliers (i.e., >3° away from the goal alignment) were 7.7% in the coronal plane, 20.6% in the sagittal plane, and 10.3% in the axial plane. CONCLUSIONS: Our findings suggest that the FAT line is a reliable and reproducibly identifiable axis for the accurate determination of proper rotational alignment in TKA. An operation support system which uses the FAT line for determining intraoperative femoral component rotation can effectively achieve highly accurate positioning of the femoral component in TKA.

Intron retention as a new pre-symptomatic marker of aging and its recovery to the normal state by a traditional Japanese multi-herbal medicine.

Intron retention (IR) is an important regulatory mechanism that affects gene expression and protein functions. Using klotho mice at the pre-symptomatic state, we discovered that retained-introns accumulated in several organs including the liver and that among these retained introns in the liver a subset was recovered to the normal state by a Japanese traditional herbal medicine. This is the first report of IR recovery by a medicine. IR-recovered genes fell into two categories: those involved in liver-specific metabolism and in splicing. Metabolome analysis of the liver showed that the klotho mice were under starvation stress. In addition, our differentially expressed gene analysis showed that liver metabolism was actually recovered by the herbal medicine at the transcriptional level. By analogy with the widespread accumulation of intron-retained pre-mRNAs induced by heat shock stress, we propose a model in which retained-introns in klotho mice were induced by an aging stress and in which this medicine-related IR recovery is indicative of the actual recovery of liver-specific metabolic function to the healthy state. Accumulation of retained-introns was also observed at the pre-symptomatic state of aging in wild-type mice and may be an excellent marker for this state in general.

Comparison of the effects of baricitinib and tocilizumab on disease activity in patients with rheumatoid arthritis: a propensity score matching analysis.

OBJECTIVE: This study aimed to compare the effects of baricitinib, a Janus kinase inhibitor, and tocilizumab, a monoclonal anti-interleukin-6 receptor antibody, on disease activity in patients with rheumatoid arthritis (RA), and to investigate the influence of inflammation on improvement in patient global assessment (PGA) of disease activity. METHODS: This study was performed based on data from a multicenter registry, and included 284 and 113 patients treated with tocilizumab and baricitinib, respectively, who were observed for longer than 24 weeks. Propensity score matching was performed to address potential treatment-selection bias. To assess the influence of inflammation on PGA, patients were divided into two groups based on whether or not they achieved improvement in C-reactive protein (CRP, an objective marker of inflammation) at 24 weeks. RESULTS: A total of 48 matched pairs of patients were identified. Compared to treatment with tocilizumab, baricitinib showed a similar improvement in tender and swollen joint count and serum CRP levels, and a significantly greater improvement in PGA at 24 weeks. As a result, the baricitinib group had a significantly higher proportion of patients who achieved Boolean remission at 24 weeks. In subgroups of patients who did not achieve 50% or 70% CRP improvement, significant decreases from baseline to 24 weeks were observed in PGA in patients treated with baricitinib, but not in those treated with tocilizumab. CONCLUSION: Compared to tocilizumab, baricitinib significantly improved PGA despite similar effects on inflammation in patients with RA. Moreover, the influence of inflammation on PGA improvement differed between baricitinib and tocilizumab. Key-points • Baricitinib and tocilizumab had similar effects on inflammation in RA patients. • Baricitinib improved patient global assessment (PGA) more than tocilizumab. • Baricitinib had a higher Boolean remission rate than tocilizumab at 24 weeks. • Influence of inflammation on PGA improvement differed between the two drugs.

Clinical efficacy of a novel, high-sensitivity HBcrAg assay in the management of chronic hepatitis B and HBV reactivation.

BACKGROUND & AIMS: A fully automated, novel high-sensitivity hepatitis B core-related antigen assay (iTACT-HBcrAg) has been developed. We demonstrate the clinical utility of iTACT-HBcrAg for monitoring chronic hepatitis B (CHB) and for the early detection of HBV reactivation. METHODS: After fundamental assessments, the clinical performance of iTACT-HBcrAg was compared with other HBV markers. i) Serial sera, available from 161 HBeAg-negative patients with CHB and persistently undetectable HBV DNA, were measured by iTACT-HBcrAg and a conventional HBcrAg assay (G-HBcrAg). ii) Serial sera from 13 HBV-reactivated patients were measured by iTACT-HBcrAg and an ultra-high-sensitivity HBsAg immune complex transfer-chemiluminescent enzyme immunoassay (lower limit of detection; 0.0005 IU/ml, ICT-CLEIA) to compare HBV DNA detection. iii) To elucidate the various HBcrAg components detected by iTACT-HBcrAg, OptiPrep density gradient centrifugation analysis was performed on sera obtained before and after HBV reactivation. RESULTS: The analytical performance of iTACT-HBcrAg was satisfactory. The sensitivity of iTACT-HBcrAg (2.1 Log U/ml) was approximately 10-fold greater than that of G-HBcrAg (2.8 Log U/ml). i) HBcrAg was detectable in the sera of 97.5% (157/161) of patients with CHB by iTACT-HBcrAg, of whom 75.2% (121/161) had ≥2.8 Log U/ml HBcrAg and 22.4% (36/161) had 2.1-2.8 Log U/ml HBcrAg, which was undetectable by G-HBcrAg. ii) 9 and 2 of 13 HBV-reactivated patients were HBcrAg-positive by iTACT-HBcrAg before and at HBV DNA positivity, respectively; 7 and 4 were HBcrAg-positive by iTACT-HBcrAg before and at HBsAg-positivity by ICT-CLEIA, respectively. iii) The HBcrAg detected by iTACT-HBcrAg before HBV reactivation was contained in empty particles (22 KDa precore protein). CONCLUSIONS: iTACT-HBcrAg could be used to better monitor responses to anti-HBV treatments in HBeAg-negative patients and for the early detection of HBV reactivation. LAY SUMMARY: A fully automated, novel high-sensitivity hepatitis B core-related antigen assay (iTACT-HBcrAg) has been developed. iTACT-HBcrAg can be used to monitor HBeAg-negative patients with chronic hepatitis B, as well as for the early detection of HBV reactivation. iTACT-HBcrAg could be used as a general marker of disease progression and treatment response.

Higher doses of methotrexate associated with discontinuation of oral glucocorticoids after initiation of biological DMARDs: A retrospective observational study based on data from a Japanese multicenter registry study.

OBJECTIVE: Glucocorticoids are important drugs used to treat rheumatoid arthritis. We recommend glucocorticoid discontinuation as soon as possible given the associated side-effects, but many patients continue to take oral glucocorticoids long-term. The present study aimed to explore factors associated with glucocorticoid discontinuation at 52 weeks after initiating biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: Subjects were 564 patients from a Japanese multicenter registry who were administered glucocorticoids and methotrexate (MTX) followed by initiation of the first bDMARD. We examined the status of oral glucocorticoid use at 52 weeks after initiating the first bDMARD. RESULTS: By 52 weeks after bDMARD initiation, 164 patients (29.1%) discontinued glucocorticoids. Multivariable analysis identified age, MTX dose, and glucocorticoid dose as factors independently associated with glucocorticoid discontinuation. After adjusting for baseline characteristics using propensity score matching, among patient groups administered MTX ≤ 8 mg/week and MTX > 8 mg/week, 105 pairs remained. A significantly higher rate of glucocorticoid discontinuation (41.0%) was noted for patients administered MTX > 8 mg/week. CONCLUSION: Our findings suggest that glucocorticoids may be discontinued after initiating bDMARDs. Moreover, higher MTX doses (>8 mg/week) at the time of bDMARD initiation were associated with glucocorticoid discontinuation among patients treated with bDMARDs.

Baicalin suppresses type 2 immunity through breaking off the interplay between mast cell and airway epithelial cell.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Japanese herbal medicine Shin'iseihaito was reported to ameliorate the airway type 2 inflammatory response in clinical and experimental studies. Airway type 2 inflammatory diseases, including bronchial asthma and eosinophilic chronic rhinosinusitis (ECRS), often coexist and interact with each other. However, it is still unclear how Shin'iseihaito exerts its pharmacological effects on cells involved in airway mucosa. AIM OF THE STUDY: This study aims to examine the direct effect of baicalin, a representative bioactive compound of Shin'iseihaito, on type 2 immune responses in human airway epithelial cells and mast cells. MATERIAL AND METHODS: We measured the plasma pharmacokinetics of flavonoids derived from Shin'iseihaito and investigated the effects of baicalin on type 2 immune responses in human airway epithelial cells and human mast cells. RESULTS: Baicalin, wogonin, and wogonoside were detected in the plasma. The maximum plasma concentration of baicalin was highest at 1610 ng/ml (3.6 µM). In the normal human bronchial epithelial cells treated with baicalin, with or without stimulation by IFN-γ, the IL-33 expression was significantly downregulated. However, baicalin treatment did not affect the levels of thymic stromal lymphopoietin and IL-25. We noted that IL-33-dependent expression of tryptase mRNA in mast cells was significantly inhibited by baicalin. Also, the expression of IL-5 in mast cells enhanced by stimulation with TSLP plus IL-1ß was significantly downregulated by baicalin treatment. Moreover, the enhancement of IL-13 expression in mast cells by IL-33 simulation was also significantly inhibited by baicalin. CONCLUSIONS: Our results prove that by breaking off the vicious circle of mast cells and airway epithelial cells, baicalin may be an effective alternative therapeutic option for the treatment of type 2 inflammatory diseases, such as ECRS and comorbid asthma.

Parascolopsis akatamae, a new species of dwarf monocle bream (Perciformes: Nemipteridae) from the Indo-West Pacific, with redescription of closely related species P. eriomma.

A new species of dwarf monocle bream, Parascolopsis akatamae n. sp., is described from the Indo-West Pacific. The new species is distinguished from all other species of Parascolopsis in having 16-19 gill rakers on the first arch, length of forked part of caudal fin 5.8-6.5 times in standard length, eye diameter 1.3-1.8 times in length of the longest dorsal-fin spine, and a pale yellow stripe present from lower edge of the eye to posterior edge of the preopercle. Parascolopsis eriomma (Jordan Richardson, 1909) is morphologically very similar to the new species and the two have been confused with each other for a long time. Therefore, we redescribe P. eriomma based on the holotype and newly collected specimens. In addition, we found that patterns of biofluorescence emission for both species are clearly different. This suggests that their biofluorescence patterns may function in distinguishing each other.

Predictors for clinical effectiveness of baricitinib in rheumatoid arthritis patients in routine clinical practice: data from a Japanese multicenter registry.

This study aimed to evaluate the short-term effectiveness and safety profiles of baricitinib and explore factors associated with improved short-term effectiveness in patients with rheumatoid arthritis (RA) in clinical settings. A total of 113 consecutive RA patients who had been treated with baricitinib were registered in a Japanese multicenter registry and followed for at least 24 weeks. Mean age was 66.1 years, mean RA disease duration was 14.0 years, 71.1% had a history of use of biologics or JAK inhibitors (targeted DMARDs), and 48.3% and 40.0% were receiving concomitant methotrexate and oral prednisone, respectively. Mean DAS28-CRP significantly decreased from 3.55 at baseline to 2.32 at 24 weeks. At 24 weeks, 68.2% and 64.1% of patients achieved low disease activity (LDA) and moderate or good response, respectively. Multivariate logistic regression analysis revealed that no previous targeted DMARD use and lower DAS28-CRP score at baseline were independently associated with achievement of LDA at 24 weeks. While the effectiveness of baricitinib was similar regardless of whether patients had a history of only one or multiple targeted DMARDs use, patients with previous use of non-TNF inhibitors or JAK inhibitors showed lower rates of improvement in DAS28-CRP. The overall retention rate for baricitinib was 86.5% at 24 weeks, as estimated by Kaplan-Meier analysis. The discontinuation rate due to adverse events was 6.5% at 24 weeks. Baricitinib significantly improved RA disease activity in clinical practice. Baricitinib was significantly more effective when used as a first-line targeted DMARDs.

Author Correction: The Japanese herbal medicine Hangeshashinto enhances oral keratinocyte migration to facilitate healing of chemotherapy-induced oral ulcerative mucositis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A retrospective analysis of the relationship between anti-cyclic citrullinated peptide antibody and the effectiveness of abatacept in rheumatoid arthritis patients.

This study aimed to evaluate the effectiveness of abatacept (ABA) by anti-cyclic citrullinated peptide (ACPA) status on disease activity as well as radiographic progression in patients with rheumatoid arthritis (RA) in clinical settings. A retrospective cohort study was conducted using data from a multicenter registry. Data from a total of 553 consecutive RA patients treated with intravenous ABA were included. We primarily compared the status of disease activity (SDAI) and radiographic progression (van der Heijde modified total Sharp score: mTSS) between the ACPA-negative (N = 107) and ACPA-positive (N = 446) groups. 'ACPA positive' was defined as ≥ 13.5 U/mL of anti-CCP antibody. Baseline characteristics between groups were similar. The proportion of patients who achieved low disease activity (LDA; SDAI ≤ 11) at 52 weeks was significantly higher in the ACPA-positive group. Multivariate logistic regression analysis identified ACPA positivity as an independent predictor for achievement of LDA at 52 weeks. Drug retention rate at 52 weeks estimated by the Kaplan-Meier curve was significantly higher in the ACPA-positive group. Achievement rate of structural remission (ΔmTSS ≤ 0.5) at 52 weeks was similar between groups. ABA treatment demonstrated a significantly higher clinical response and higher drug retention rate in ACPA-positive patients. Progression of joint destruction was similar between the ACPA-negative and ACPA-positive groups. Close attention should be paid to joint destruction even in patients showing a favorable response to ABA, especially when the ACPA status is positive.

Clinically based score predicting cryptogenic NORSE at the early stage of status epilepticus.

OBJECTIVE: To determine whether a clinically based score predicts cryptogenic new-onset refractory status epilepticus (C-NORSE) at the early stage of status epilepticus (SE) with prominent motor symptoms (SE-M) of unclear etiology. METHODS: The score (range 0-6) included 6 clinical features: highly refractoriness to antiseizure drugs, previously healthy individual, presence of prodromal fever, absence of prodromal psychobehavioral or memory alterations, absence of dyskinesias, and symmetric brain MRI abnormalities (the first 2 mandatory). We retrospectively assessed the usefulness of a high scale score (≥5) in predicting C-NORSE in 83 patients with SE-M of unclear etiology, who underwent testing for neuronal surface antibodies (NS-Abs) between January 2007, and December 2019. RESULTS: Thirty-one (37.3%) patients had a high score. Patients with a high score had more frequent prodromal fever (28/31 vs 24/52), mechanical ventilatory support (31/31 vs 36/52), and symmetric MRI abnormalities (26/31 vs 12/52), had less frequent involuntary movements (2/31 vs 30/52), and had absent prodromal psychobehavioral alterations (0/31 vs 27/52), CSF oligoclonal band detection (0/27 vs 11/38), tumor association (0/31 vs 13/52), or NS-Abs (0/31 vs 29/52) than those with a low score (<5). Thirty-three patients (median age, 27 years; 18 [54.5%] female) were finally regarded as C-NORSE. The sensitivity and specificity of a high score for predicting C-NORSE were 93.9% (95% CI 0.87-0.94) and 100% (95% CI 0.95-1.00), respectively. CONCLUSIONS: Patients with a high score in the indicated scale are more likely to have C-NORSE, making it a useful diagnostic tool at the early stage of SE-M before antibody test results become available.