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Background: The treatment of pemphigus is based on systemic corticosteroid use and adjuvant therapies, but some patients are resistant to conventional therapy. Tirabrutinib is a highly selective oral Bruton's tyrosine kinase inhibitor that may be clinically effective in treating pemphigus by suppressing B-cell signaling., Objective: We investigated the efficacy and safety of tirabrutinib in patients with refractory pemphigus., Methods: This was a multicenter, open-label, single-arm phase 2 study of Japanese patients with refractory pemphigus receiving appropriate treatment with an oral corticosteroid and adjuvant therapies. Patients received postprandial oral tirabrutinib 80 mg once daily for 52 weeks. After 16 weeks of tirabrutinib treatment, the corticosteroid dose was tapered to ≤10 mg/day of prednisolone equivalent., Results: In total, 16 patients were evaluated (mean age, 52.5 years; 50 % male). The complete remission rate after 24 weeks of treatment (primary endpoint) was 18.8 % (3/16; 95 % confidence interval, 6.6 %-43.0 %). By Week 52, eight patients (50.0 %) achieved complete remission and 10 patients (62.5 %) achieved remission. Over 52 weeks of treatment, the mean prednisolone dose decreased from 17.03 to 7.65 mg/day. Incidences of adverse events (AEs) and adverse drug reactions were 87.5 % and 43.8 %, respectively. A relationship with tirabrutinib was ruled out for all serious AEs and Grade ≥3 AEs., Conclusion: Treatment with tirabrutinib enabled remission and reduced oral corticosteroid exposure over time and did not result in any major safety concerns in patients with refractory pemphigus. Thus, oral tirabrutinib may be a new treatment option for patients with refractory pemphigus., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Pharmaceutical care of capecitabine-related hand-foot syndrome (HFS) is extremely important to avoid the progression of the syndrome. Protocol-based pharmacotherapy management (PBPM) of HFS by community pharmacists has been introduced in our community, whereby the community pharmacist instructs patients to use steroid creams if they develop HFS of grade 2 or higher. This study aimed to evaluate the effectiveness of PBPM in cancer patients with HFS by comparing it to conventional pharmaceutical care using monitoring reports for pharmacotherapy management by community pharmacists., Methods: From September 2017 to August 2019, we retrospectively investigated the medical records of 396 cancer patients who received capecitabine adjuvant chemotherapy. Before PBPM implementation, conventional pharmaceutical care was administered from September 2017 to August 2018; these patients served as the control group. Care was switched to PBPM in September 2018, and PBPM was applied from September 2018 to August 2019; these patients served as the PBPM group. We excluded patients who received both conventional pharmaceutical care and PBPM. We categorized all cases into two groups: age ≤ 69 years and age ≥ 70 years., Results: In all, 396 cases were included, of which 227 were ineligible, such as those of cancer patients who received both conventional pharmaceutical care and PBPM. Among patients aged higher than 70 years, the incidence and severity of HFS associated with PBPM were significantly lower than those associated with conventional care (grade 0: 59.5% [44/74] vs. 30.6% [11/36], grade 1: 33.8% [25/74] vs. 63.9% [23/36]). All patients continued to receive the capecitabine, HFS severity improved to grade 1 during the study period, and treatment of HFS was not stopped., Conclusion: Our findings suggest that PBPM is effective for addressing capecitabine-related HFS among cancer patients aged higher than 70 years, in that it helps prevent an increase in HFS severity.

Purpose: Sjögren syndrome (SS) is a chronic inflammatory autoimmune disease of the lacrimal and salivary glands. This study compared the concentrations of epidermal fatty-acid binding protein (E-FABP) in the saliva, serum, and tears of SS patients with dry eye and dry mouth, with those of healthy adults to investigate the usefulness of E-FABP as a diagnostic marker for SS., Design: Prospective, observational case series., Participants: The subjects were 11 new patients with untreated Sjogren syndrome and 12 healthy control individuals., Methods: The diagnosis of SS was in accordance with the Ministry of Health, Labour and Welfare (Japan) Diagnostic Criteria (1999). Saliva, serum, and tear specimens were collected during internal medicine, dental, and ophthalmological examinations. The ophthalmological tests included the Dry Eye-related Quality of life Score (DEQS), tear break-up time (BUT), vital staining with fluorescein (FS) and lissamine green (LG), and the Schirmer test-1. The E-FABP concentration in the tears, saliva, and serum was measured by enzyme-linked immunosorbent assay (ELISA)., Main Outcome Measure: The E-FABP concentrations were compared between patients and controls., Results: There were significant differences between the patient and healthy control groups in all ophthalmological test results. There were no significant differences between the groups in the E-FABP concentrations in the saliva ( p = 0.1513) or the serum ( p = 0.4799), but the E-FABP concentration in the tears significantly differed between groups. The E-FABP concentration in tears tended to be significantly lower in patients with SS (mean, 323.5 ± 325.6 pg/mL) than healthy control subjects (mean, 4076 pg/mL; p = 0.0136). The E-FABP concentration in tears significantly correlated with the results of dry eye parameters., Conclusion: The E-FABP concentration in tears appears to be related to ocular surface epithelial damage and tear stability and may be a promising novel biomarker in the diagnosis of SS., Competing Interests: The authors declare no conflicts of interest.

The aim of the present study was to investigate the osteogenic capability of rat calvarial periosteal cells in hypoxic conditions in vitro. Periosteum was obtained from the calvarial bone of Sprague-Dawley rats. Following primary tissue culture, subcultured cells were used in hypoxic or normal conditions. On days 1, 2, 3 and 4 following the cell culture, cell proliferation and mRNA and protein expression levels were evaluated. No significant difference in the cell proliferation rate was found between the normal and hypoxic condition groups. The hypoxic condition group exhibited a stronger expression of hypoxia-inducible factor (HIF)1α, vascular endothelial growth factor (VEGF), Runx2, alkaline phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OCN) and periostin at the mRNA level compared to that of the normal condition group. The hypoxic condition group also exhibited a stronger expression of HIF1α, VEGF, bone morphogenetic protein (BMP)2, Runx2, ALP and BSP at the protein level compared to that of the normal condition group. In conclusion, periosteal cells cultured in hypoxic conditions demonstrated activated osteogenic capability in vitro.

Glucocorticoids such as prednisolone are used for their anti-inflammatory properties. But there is evidence to suggest that under certain conditions, glucocorticoids have pro-inflammatory effects, for example, enhancement of IL-1beta production. To date, it has been reported that IL-1beta production intensity was associated with single nucleotide polymorphisms at positions -1470, -511, and -31 in the promoter region and at position 3954 in exon 5 of the IL-1beta gene. In the present study, it was examined whether these IL-1beta genotypes were associated with the suppressive effect of prednisolone on IL-1beta production in human peripheral blood mononuclear cells (PBMC) stimulated by lipopolysaccharide (LPS). A midrange concentration (10(-6) M) of prednisolone suppressed the LPS-induced increase in IL-1beta mRNA expression and protein release, while higher concentrations (10(-5) M, 10(-4) M) exhibited less suppression or had a synergistic stimulative effect on IL-1beta production in certain subjects. Under treatment with 10(-4) M prednisolone, the levels of IL-1beta protein production stimulated by LPS in PBMC extracted from the subjects with the IL-1beta TT(-31), TC(-31), and CC(-31) genotypes were suppressed to 6.0+/-3.4%, 31.4+/-57.0%, and 87.7+/-84.8%, respectively, of the level in prednisolone-untreated control cells (TT(-31) vs. CC(-31), p<0.05). Glucocorticoid-based anti-inflammatory therapy might be less effective in patients with the IL-1beta TC(-31) and CC(-31) genotypes than those with the TT(-31) genotype.