The immune-stromal cell interactions play a key role in health and diseases.In periodontitis,the most prevalent infectious disease in humans,immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand(RANKL)expression in osteogenic cells such as osteoblasts and periodontal ligament cells.However,the detailed mechanism underlying immune-bone cell interactions in periodontitis is not fully understood.Here,we performed single-cell RNA-sequencing analysis on mouse periodontal lesions and showed that neutrophil-osteogenic cell crosstalk is involved in periodontitis-induced bone loss.The periodontal lesions displayed marked infiltration of neutrophils,and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production.Among the cytokines expressed in the periodontal neutrophils,oncostatin M(OSM)potently induced RANKL expression in the primary osteoblasts,and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss.Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells,and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism.These findings shed light on the role of neutrophils in bone regulation during bacterial infection,highlighting the novel mechanism underlying osteoimmune crosstalk.

Background/Aims: Hybrid endoscopic submucosal dissection (ESD), in which an incision is made around a lesion and snaring is performed after submucosal dissection, has some advantages in colorectal surgery, including shorter procedure time and preventing perforation. However, its value for rescue resection in difficult colorectal ESD cases remains unclear. This study evaluated the utility of rescue hybrid ESD (RH-ESD). Methods: We divided 364 colorectal ESD procedures into the conventional ESD group (C-ESD, n=260), scheduled hybrid ESD group (SH-ESD, n=69), and RH-ESD group (n=35) and compared their clinical outcomes. Results: Resection time was significantly shorter in the following order: RH-ESD (149 [90–197] minutes) >C-ESD (90 [60–140] minutes) >SH-ESD (52 [29–80] minutes). The en bloc resection rate increased significantly in the following order: RH-ESD (48.6%), SH-ESD (78.3%), and C-ESD (97.7%). An analysis of factors related to piecemeal resection of RH-ESD revealed that the submucosal dissection rate was significantly lower in the piecemeal resection group (25% [20%–30%]) than in the en bloc resection group (40% [20%–60%]). Conclusions RH-ESD was ineffective in terms of curative resection because of the low en bloc resection rate, but was useful for avoiding surgery.

Purpose: Determination of optimal treatment strategies for HER2-positive advanced gastric cancer (AGC) in randomized trials is necessary despite difficulties in direct comparison between trastuzumab deruxtecan (T-DXd) and nivolumab as third or later-line treatments. Materials and Methods: This single-institution, retrospective study aimed to describe the real-world efficacy and safety of T-DXd and nivolumab as ≥ third line treatments for HER2-positive AGC between March 2016 and May 2022. Overall, 58 patients (median age, 64 years;69% male) were eligible for the study (T-DXd group, n=20; nivolumab group, n=38). Results: Most patients exhibited a HER2 3+ status (72%) and presented metastatic disease at diagnosis (66%). The response rates of 41 patients with measurable lesions in the T-DXd and nivolumab groups were 50% and 15%, respectively. The T-DXd and nivolumab groups had a median progression-free survival of 4.8 months (95% confidence interval [CI], 3.3, 7.0) and 2.3 months (95% CI, 1.5, 3.5), median overall survival (OS) of 10.8 months (95% CI, 6.9, 23.8) and 11.7 months (95% CI, 7.6, 17.1), and grade 3 or greater adverse event rates of 50% and 2%, respectively. Overall, 64% patients received subsequent treatment. Among 23 patients who received both regimens, the T-DXd–nivolumab and nivolumab–T-DXd groups had a median OS of 14.0 months (95% CI, 5.0, not reached) and 19.3 months (95% CI, 9.5, 25.1), respectively. Conclusions T-DXd and nivolumab showed distinct efficacy and toxicity profiles as ≥ third line treatments for HER2-positive AGC. Considering the distinct features of each regimen, they may help clinicians personalize optimal treatment approaches for these patients.

Locally advanced breast cancer (tumor > 5 cm, widespread infiltration of the skin and muscle, or metastases to lymph nodes) is difficult to resect by surgery, and even when it is resectable, there is a high probability of local recurrence and distant metastasis. Therefore, systemic therapy should be administered first. However, as cutaneous infiltration progresses, the patient's quality of life is impaired by pain, bleeding, presence of exudates, and a foulsmelling odor. Treatment with Mohs paste with systemic therapy can control symptoms associated with skin infiltration and can also be expected to decrease tumor volume.Herein, we report a case in which a tumor was resected following Mohs paste and systemic chemotherapy administration, and the skin defect was reconstructed with a latissimus dorsi myocutaneous flap. We also review the literature for previously reported cases of breast cancer involving Mohs paste.

The purpose of the present study was to indicate the relationship between health-related quality of life (HRQOL) measures, the daily rhythm of oral temperature (OT), and lifestyle. Five-hundred young men volunteered to participate in this study. Their OT, measured using a digital thermometer, was recorded every 2h from the time they woke up to the time they went to sleep for 1 week. The daily rhythm of OT was calculated as a quadratic function using the 1-week data. The HRQOL was measured using the Short-Form 36-Item Health Survey version 2 (SF-36v2). The participants were divided into 3 groups: a high-value group (HG) with ≥ 55 points of each summary score and each subscale score, a middle-value group (MG) with score > 45 and < 55 points, and a low-value group (LG) with score ≤ 45 points. Lifestyle was assessed in terms of eating habits, sleeping and exercise, and the presence of unidentified complaints. At the mental component summary, the OT at the time of waking up and the peak OT in the HG were significantly higher than those in the LG. At the physical and mental component summary, lifestyle in the HG was more favorable. These data suggest that the daily rhythms of OT may reflect the mental health status of an individual. The entraining factors in circadian variation might play a role in improving mental health and reducing unidentified complaints. In conclusion, there appears to be an association between mental health status, lifestyle, and daily rhythms of OT.

BACKGROUND/AIMS: Peyer's patches (PPs) are aggregates of lymphoid follicles that are mainly located in the distal ileum; they play a major role in mucosal immunity. We recently reported that patients with ulcerative colitis (UC) have alterations in PPs that can be detected using narrow-band imaging with magnifying endoscopy (NBI-ME). However, the usefulness of NBI-ME in UC treatment as a whole is still unknown. METHODS: We collected NBI-ME images of PPs from 67 UC patients who had undergone ileocolonoscopy. We evaluated changes in the villi using the "villi index," which is based on three categories: irregular formation, hyperemia, and altered vascular network pattern. The patients were divided into two groups on the basis of villi index: low (L)- and high (H)-types. We then determined the correlation between morphological alteration of the PPs and various clinical characteristics. In 52 patients who were in clinical remission, we also analyzed the correlation between NBI-ME findings of PPs and clinical recurrence. RESULTS: The time to clinical recurrence was significantly shorter in remissive UC patients with H-type PPs than in those with L-type PPs (P<0.01). Moreover, PP alterations were not correlated with age, sex, disease duration, clinical activity, endoscopic score, or extent of disease involvement. Multivariate analysis revealed that the existence of H-type PPs was an independent risk factor for clinical recurrence (hazard ratio, 3.3; P<0.01). CONCLUSIONS: UC patients with morphological alterations in PPs were at high risk of clinical relapse. Therefore, to predict the clinical course of UC, it may be useful to evaluate NBI-ME images of PPs.
Colitis, Ulcerative* ; Endoscopy* ; Humans ; Hyperemia ; Ileum ; Immunity, Mucosal ; Multivariate Analysis ; Peyer's Patches* ; Recurrence* ; Risk Factors ; Ulcer*

BACKGROUND/AIMS: Peyer's patches (PPs) are aggregates of lymphoid follicles that are mainly located in the distal ileum; they play a major role in mucosal immunity. We recently reported that patients with ulcerative colitis (UC) have alterations in PPs that can be detected using narrow-band imaging with magnifying endoscopy (NBI-ME). However, the usefulness of NBI-ME in UC treatment as a whole is still unknown. METHODS: We collected NBI-ME images of PPs from 67 UC patients who had undergone ileocolonoscopy. We evaluated changes in the villi using the "villi index," which is based on three categories: irregular formation, hyperemia, and altered vascular network pattern. The patients were divided into two groups on the basis of villi index: low (L)- and high (H)-types. We then determined the correlation between morphological alteration of the PPs and various clinical characteristics. In 52 patients who were in clinical remission, we also analyzed the correlation between NBI-ME findings of PPs and clinical recurrence. RESULTS: The time to clinical recurrence was significantly shorter in remissive UC patients with H-type PPs than in those with L-type PPs (P<0.01). Moreover, PP alterations were not correlated with age, sex, disease duration, clinical activity, endoscopic score, or extent of disease involvement. Multivariate analysis revealed that the existence of H-type PPs was an independent risk factor for clinical recurrence (hazard ratio, 3.3; P<0.01). CONCLUSIONS: UC patients with morphological alterations in PPs were at high risk of clinical relapse. Therefore, to predict the clinical course of UC, it may be useful to evaluate NBI-ME images of PPs.
Colitis, Ulcerative* ; Endoscopy* ; Humans ; Hyperemia ; Ileum ; Immunity, Mucosal ; Multivariate Analysis ; Peyer's Patches* ; Recurrence* ; Risk Factors ; Ulcer*

OBJECTIVE: A recent study suggested that rs6504340, a polymorphism within the homeobox B (HOXB) gene cluster, is associated with the susceptibility for malocclusions in Europeans. The resulting malocclusions require orthodontic treatment. The aim of this study was to investigate the association of rs6504340 and other dentition-implicated polymorphisms with dental and occlusal traits in Korean and Japanese populations. METHODS: The study participants included 223 unrelated Koreans from the Busan area and 256 unrelated Japanese individuals from the Tokyo metropolitan area. DNA samples were extracted from saliva specimens. Genotyping for rs6504340 and four single nucleotide polymorphisms (SNPs) that have been shown to be associated with the timing of first tooth eruption and the number of teeth at 1 year of age (rs10506525, rs1956529, rs9674544, and rs8079702) was performed using TaqMan assays. The Index of Orthodontic Treatment Need (IOTN), overjet, overbite, arch length discrepancy, crown sizes, and length and width of the dental arches were measured. Spearman's correlation coefficients were calculated to evaluate relationships between rs6504340 and these dental/occlusal traits. RESULTS: We evaluated the aesthetic components and dental health components of the IOTN in the Korean and Japanese populations and found that neither rs6504340 nor the other four SNPs showed any association with dental and occlusal traits in these East Asian populations. CONCLUSIONS: These negative results suggest that further research is needed to identify the genetic determinants of malocclusions in order to reach a consensus.
Asian Continental Ancestry Group* ; Busan ; Consensus ; Crowns ; Dental Arch ; DNA ; Genes, Homeobox ; Genetics ; Humans ; Index of Orthodontic Treatment Need ; Malocclusion ; Multigene Family ; Overbite ; Polymorphism, Single Nucleotide ; Saliva ; Tooth Eruption* ; Tooth*

This is a case report evaluating the improvement of activities of daily living (ADL) after TKA in stroke patient with hemiplegia and knee osteoarthritis. The case was a 73-year-old female with left hemiplegia caused by cerebral infarction. She also suffered from severe bilateral knee osteoarthritis and obesity. The hemiplegia and knee dysfunction disturbed her ADL. When she was admitted to our hospital, her FIM motor subscore was 23 and body mass index (BMI) was 36.0. She went on a diet and continued rehabilitation. Her knees were treated conservatively. Six months after the stroke, her FIM motor subscore was 35 and BMI was 29.8. For the purpose of pain relief and improvement of range of motion, right TKA was performed seven months after stroke. And left TKA and lengthening of the gastrocnemius were performed eleven months after her stroke. Rehabilitation was continued carefully in order to avoid deep venous thrombosis. In addition, a left obturator nerve block was performed as treatment for spasticity of her hip adductor muscle. Fifteen months after the stroke, her FIM motor subscore was 77 and BMI was 25.7. TKA is a common treatment for osteoarthritis but when a patient has a stroke, it is difficult to determine whether to perform surgery or not. In this case, bilateral TKA achieved improvement of ADL. We suggest that even if a patient has stroke hemiplegia, TKA should be considered for knee osteoarthritis based on the appropriate assessment and careful risk management.