Oral Inflammation and Microbiome Dysbiosis Exacerbate Chronic Graft-versus-host Disease.

The oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in GVHD pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients post-hematopoietic cell transplantation associated with increased chronic GVHD (cGVHD) even in patients receiving post-transplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut with Enterococcaceae significantly increasing in both organs.

[DEVELOPMENT AND VALIDATION OF QUALITY OF LIFE QUESTIONNAIRE FOR CHILDREN WITH FOOD ALLERGY REPORTED BY PARENTS].

Objective: No questionnaire aimed at evaluating the quality of life (QOL) of children with food allergies has been developed in Japan. Therefore, this study was aimed at developing a Japanese version of a QOL questionnaire for children with food allergies to be responded to by their parents.

Methods: A 59-question primary questionnaire was developed for parents of children aged 0 to 15 years who had food allergies.

[DEVELOPMENT AND VALIDATION OF QUALITY OF LIFE QUESTIONNAIRE FOR PARENT BURDEN OF CHILDREN WITH FOOD ALLERGY].

Objective: Quality of life (QOL) questionnaires for parents of children with food allergies have been developed in the United States and Europe. However, no original Japanese QOL questionnaire has been developed till date. We aimed to develop an original questionnaire to evaluate the QOL in parents of children with food allergies in Japan.

Benralizumab in children with severe eosinophilic asthma: Pharmacokinetics and long-term safety (TATE study).

Background: Benralizumab is an anti-interleukin-5 receptor α monoclonal antibody approved as an add-on maintenance treatment for patients with uncontrolled severe asthma. Prior Phase 3 studies have evaluated benralizumab in patients aged ≥12 years with severe uncontrolled asthma. The TATE study evaluated the pharmacokinetics (PK), pharmacodynamics (PD), and safety of benralizumab treatment in children.

GSK343 modulates macrophage M2 polarization through the EZH2/MST1/YAP1 signaling axis to mitigate neurological damage induced by hypercalcemia in CKD mice.

Chronic kidney disease (CKD) often culminates in hypercalcemia, instigating severe neurological injuries that are not yet fully understood. This study unveils a mechanism, where GSK343 ameliorates CKD-induced neural damage in mice by modulating macrophage polarization through the EZH2/MST1/YAP1 signaling axis. Specifically, GSK343 downregulated the expression of histone methyltransferase EZH2 and upregulated MST1, which suppressed YAP1, promoting M2 macrophage polarization and thereby, alleviating neural injury in hypercalcemia arising from renal failure.

Safety and Efficacy of Upadacitinib for Atopic Dermatitis in Japan: Analysis of the 3-Year Phase 3 Rising Up Study.

Introduction: Upadacitinib is an oral Janus kinase inhibitor approved in multiple countries for moderate-to-severe atopic dermatitis (AD). Here we present long-term data for up to 3 years of continuous upadacitinib treatment in Japanese patients with AD.

Methods: Rising Up was a phase 3, randomized, multicenter study in Japan investigating the safety and efficacy of upadacitinib in patients with moderate-to-severe AD.

Acne Among Japanese Patients with Atopic Dermatitis Receiving Upadacitinib in the Phase 3 Rising Up Study.

Introduction: Upadacitinib, an oral selective Janus kinase (JAK) inhibitor, is used to treat moderate-to-severe atopic dermatitis (AD). Acne is the most common treatment-emergent adverse event in patients with AD treated with upadacitinib. In this post hoc analysis, we describe the acne events in Japanese patients with AD who received upadacitinib during the Rising Up study.

A case of coexistent poorly differentiated adenosquamous carcinoma (glassy cell carcinoma), usual-type adenocarcinoma, and squamous cell carcinoma in situ of the cervix.

Poorly differentiated adenosquamous carcinoma (glassy cell carcinoma) of the cervix is extremely rare, accounting for 1-2% of all cervical cancers. Herein, we report a case with coexistent poorly differentiated adenosquamous carcinoma (glassy cell carcinoma), "usual-type" adenocarcinoma, and squamous cell carcinoma in situ of the cervix. A female patient in her 60 s was referred to our hospital and diagnosed with poorly differentiated adenosquamous carcinoma based on cervical cytology and biopsy.

Safety and Efficacy of Upadacitinib for Atopic Dermatitis in Japan: 2-Year Interim Results from the Phase 3 Rising Up Study.

Introduction: Upadacitinib, an oral, selective Janus kinase inhibitor, is approved in Japan for the treatment of moderate-to-severe atopic dermatitis (AD), a chronic inflammatory skin disease characterized by eczematous morphology and intense itch.

Methods: Rising Up is an ongoing phase 3, randomized, multicenter study evaluating the long-term safety and efficacy of upadacitinib in Japan. Patients with moderate-to-severe AD were randomized 1:1:1 to topical corticosteroids plus upadacitinib 15 mg (UPA15), upadacitinib 30 mg (UPA30), or placebo at baseline; at week 16, placebo patients were rerandomized 1:1 to UPA15 or UPA30 (plus topical corticosteroids per investigator discretion).

Rituximab therapy for intractable pemphigus: A multicenter, open-label, single-arm, prospective study of 20 Japanese patients.

This was a multicenter clinical trial of rituximab, a chimeric monoclonal IgG antibody directed against CD20, for the treatment of refractory pemphigus vulgaris and pemphigus foliaceus. In total, 20 patients were treated with two doses of rituximab (1000 mg; 2 weeks apart) on days 0 and 14. The primary end point was the proportion of patients who achieved complete or partial remission on day 168 following the first rituximab dose.

Drp1 activates ROS/HIF-1α/EZH2 and triggers mitochondrial fragmentation to deteriorate hypercalcemia-associated neuronal injury in mouse model of chronic kidney disease.

Background: Chronic kidney disease (CKD), characterized as renal dysfunction, is regarded as a major public health problem which carries a high risk of cardiovascular diseases. The purpose of this study is to evaluate the functional significance of Drp1 in hypercalcemia-associated neuronal damage following CKD and the associated mechanism.

Methods: Initially, the CKD mouse models were established.

Novel Lung Growth Strategy with Biological Therapy Targeting Airway Remodeling in Childhood Bronchial Asthma.

Anti-inflammatory therapy, centered on inhaled steroids, suppresses airway inflammation in asthma, reduces asthma mortality and hospitalization rates, and achieves clinical remission in many pediatric patients. However, the spontaneous remission rate of childhood asthma in adulthood is not high, and airway inflammation and airway remodeling persist after remission of asthma symptoms. Childhood asthma impairs normal lung maturation, interferes with peak lung function in adolescence, reduces lung function in adulthood, and increases the risk of developing chronic obstructive pulmonary disease (COPD).

Inducible Depletion of Calpain-2 Mitigates Abdominal Aortic Aneurysm in Mice.

[Figure: see text].

Cobalt-chromium versus titanium alloy rods for correction of adolescent idiopathic scoliosis based on 1-year follow-up: a multicenter randomized controlled clinical trial.

Objective: For instrumented correction surgery for adolescent idiopathic scoliosis (AIS), surgeons are increasingly switching from titanium (Ti) alloy rods to stiffer cobalt-chromium (CoCr) rods. The authors conducted the first multicenter randomized controlled clinical trial to investigate whether these materials affect the outcomes in terms of spine correction and quality of life (QOL). This trial was registered at UMIN Clinical Trials Registry on September 3, 2012, under the identifier UMIN000008838 (level of evidence 1).

Oncologic outcomes and safety of percutaneous cryoablation for biopsy-proven renal cell carcinoma up to 4 cm in diameter: a prospective observational study.

Background: Percutaneous cryoablation is widely used for the treatment of renal cell carcinoma. We prospectively evaluated the oncologic outcomes and safety of percutaneous cryoablation for the treatment of tumors ≤ 4 cm in diameter.

Methods: We included patients aged ≥ 20 years, who had histologically proven renal cell carcinoma, tumor diameter ≤ 4 cm, a performance status of ≤ 1, acceptable laboratory parameters, were inoperable or refused to undergo surgery, and had signed a written informed consent.

Rituximab therapy for refractory autoimmune bullous diseases: A multicenter, open-label, single-arm, phase 1/2 study on 10 Japanese patients.

This was a multicenter study of rituximab, a chimeric monoclonal immunoglobulin G antibody directed against CD20, for the treatment of refractory autoimmune bullous diseases (pemphigus and pemphigoid). Ten patients (three with pemphigus vulgaris, six with pemphigus foliaceus and one with bullous pemphigoid) were treated with a single cycle of rituximab (four weekly infusions at a dose of 375 mg/m of body surface area). The primary end-points were the number of serious adverse events and rate of complete remission at 40 weeks.

A case of conservative management for left ventricular giant pseudoaneurysm without ST segment changes.

Left ventricular (LV) rupture after myocardial infarction (MI) occasionally results in formation of LV pseudoaneurysm (LVPA) which is prone to rupture because of its thin wall. However, cases of LVPA without ST changes including segment elevation in electrocardiogram (ECG) are rare. In this case, we describe a patient who had relatively mild symptoms and giant LVPA with no specific ECG changes following MI with a confirmed diagnosis via transthoracic echocardiography.

Intravenous immunoglobulin for maintenance treatment of chronic inflammatory demyelinating polyneuropathy: a multicentre, open-label, 52-week phase III trial.

Objective: Short-term efficacy of induction therapy with intravenous immunoglobulin (Ig) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) is well established. However, data of previous studies on maintenance therapy were limited up to 24-week treatment period. We aimed to investigate the efficacy and safety of longer-term intravenous Ig therapy for 52 weeks.

Variability of treatment planning of seed implantation: A Japanese multicenter simulation study.

Purpose: This multicenter study was conducted to evaluate the current variability of treatment planning of seed implantation in Japanese centers and the feasibility of two virtual trials.

Methods And Materials: Two types of contour data were sent to 12 radiation oncologists with a request letter that asked them to make treatment plans on the data in the same manner as in their own practice. Five of the 12 radiation oncologists were asked to participate in the two virtual trials in which the D90 (dose to the hottest 90% of prostate volume) was 1) required to be set at just 180 Gy and 2) increased as much as possible without violating other limitations.