Background: There is a growing demand for extending dosing intervals of dupilumab injections in patients with atopic dermatitis (AD) due to treatment burden and side effects. However, studies on successful dose reduction in real-world settings are lacking. Objective: To assess the efficacy of a patient-centered dupilumab tapering regimen and to propose guidelines for target patients, appropriate intervals, and timing for tapering. Methods: This single-center retrospective study included moderate to severe adult AD patients who underwent at least 16 weeks of dupilumab treatment. Interval prolongation was considered in controlled patients assessed by Eczema Area and Severity Index (EASI) score and serum inflammatory markers after at least 40 weeks of treatment with a standard regimen. Logistic regression model with generalized estimating equations was used to compare repetitive measurements over time between the two groups. Results: A total of 52 patients were included with 11 patients extending intervals to 3–4 weeks without flare-ups. The mean duration of dupilumab treatment before tapering was 53.27 weeks. The tapering group exhibited significantly lower body mass index. All patients of the tapering group showed EASI scores under 4 and immunoglobulin E (IgE) levels under 1,000 IU/mL at week 40. EASI scores and IgE levels remained consistently low after dose reduction, with a mean follow-up time of 14.36 months. Conclusion Patients with extended dosing intervals demonstrated sustained effectiveness. Dose tapering might be a valuable option for non-obese patients with positive clinical response characterized by an EASI score under 4 and IgE levels under 1,000 at week 40.

Background: Contrast-enhanced ultrasonography (CEUS) of the bowel wall has been suggested as an alternative imaging modality for the follow-up of children with Crohn’s disease. To demonstrate the feasibility and clinical usefulness of CEUS in the estimation of Crohn’s disease activity in children with endoscopy as the reference standard.Method: In this prospective study, 30 pediatric patients with Crohn’s disease (24 males and 6 females; median age 14 years) underwent CEUS from December 2020 to August 2021.The simple endoscopic score for Crohn’s disease, pediatric Crohn’s disease activity index, serologic inflammatory markers, fecal calprotectin and CEUS perfusion parameters were assessed and compared between the inactive and active group based on endoscopic findings. Results: CEUS was performed successfully in all 30 patients. Two patients showed mild adverse side effects such as temporary dysosmia. The active Crohn’s disease group showed higher erythrocyte sedimentation rate (mm/hr) (13.0 vs. 2.0, P = 0.003), C-reactive protein (mg/dL) (4.7 vs. 0.55, P = 0.018) and fecal calprotectin (mcg/g) (1,503 vs. 237.5, P = 0.005). Among the quantitative parameters for CEUS, the mean gradient to the peak value was higher in the active group (1.18 vs. 0.93, P = 0.034). The sensitivity and specificity of the mean gradient to the peak value for predicting active Crohn’s disease was 55.6% and 83.3%, respectively, with a cut-off of 1.09 (P = 0.015). Conclusion CEUS can be a safe and specific diagnostic modality for Crohn’s disease activity in children. Among quantitative CEUS parameters, the mean gradient to the peak value could be used to differentiate active and inactive Crohn’s disease.

The treatment of pathological scars, such as keloids and hypertrophic scars, can be challenging for dermatologists. The first-line treatment is intralesional corticosteroid injection, especially when patients complain of pain or discomfort. Laser treatment can also be used in patients with keloids and hypertrophic scars. However, even after multiple sessions of intralesional corticosteroid injections and laser treatment, desirable outcomes may not be achieved, and recurrence is common. Recent studies on the efficacy of intralesional bleomycin injection (BLMILI) in treating keloids and hypertrophic scars have suggested that a significant improvement is observed after BLMILI. However, there is limited research on the effectiveness of BLMILI for patients who do not respond to other treatments, such as intralesional corticosteroid injection or laser treatment. Here, we report four cases of BLMILI in keloids and hypertrophic scars that were unresponsive to previous intralesional corticosteroid injection and/or laser treatment.

Background: Exclusive enteral nutrition (EEN) induces remission in pediatric Crohn's disease (CD). The exact mechanism of EEN therapy in CD is unknown, but alteration of the intestinal microflora after EEN is thought to affect mucosal healing. To determine the link between EEN therapy and therapeutic efficacy in CD, we established a murine model of dextran sulfate sodium (DSS)-induced colitis and applied EEN therapy. Methods: Eight-week-old C57BL/6 mice were administered DSS for 4 days to induce colitis, and either normal chow (NC) or EEN was administered for the following 4 days. The mice were grouped according to the feeding pattern after DSS administration: DSS/NC and DSS/ EEN groups. The clinical course was confirmed via daily observation of the weight and stool. Fecal samples were collected and 16sRNA sequencing was used. The mice were sacrificed to confirm colonic histopathology. Results: Weight reduction and increase in disease activity were observed as the day progressed for 4 days after DSS administration. There was significant weight recovery and improvement in disease activity in the EEN group compared to that in the NC group. Verrucomicrobia and Proteobacteria abundances tended to increase and Bacteroidetes abundance decreased in the EEN group. In the EEN group, significant changes in the β-diversity of the microbiota were observed. In the analysis of microbiome species, abundances of Akkermansia muciniphila, Clostridium cocleatum, mucin-degrading bacteria, Flintibacter butyricus, and Parabacteroides goldsteinii, which are beneficial microbiota, were significantly increased in the EEN group compared to those in the NC group. More abundant mucins were confirmed in the colonic histopathology of the EEN group. These microbial and histopathological differences suggested that EEN might improve colitis symptoms in a murine colitis model by promoting mucin recycling and subsequently inducing the healing effect of the gut barrier. Conclusion EEN showed clinical efficacy in a murine model of colitis. Based on the increase in mucin-degrading bacteria and the pathological increase in mucin production after EEN administration, it can be observed that mucin plays an important role in the therapeutic effect of EEN.

PURPOSE: Phosphorylated ribosomal S6 kinase 1 (pS6K1) is a major downstream regulator of the mammalian target of rapamycin (mTOR) pathway. Recent studies have addressed the role of S6K1 in adipogenesis. pS6K1 may affect the outcome of estrogen depletion therapy in patients with hormone-sensitive breast cancer due to its association with adipogenesis and increased local estrogen levels. This study aimed to investigate the potential of pS6K1 as a predictive marker of adjuvant aromatase inhibitor (AI) therapy outcome in postmenopausal or ovarian function-suppressed patients with hormone-sensitive breast cancer. METHODS: Medical records were retrospectively reviewed in postmenopausal or ovarian function-suppressed patients with estrogen receptor-positive and node-positive primary breast cancer. pS6K1 expression status was scored on a scale from 0 (negative) to 3+ (positive) based on immunohistochemical analysis. RESULTS: A total of 428 patients were eligible. The median follow-up duration was 44 months (range, 1–90). In patients with positive pS6K1 expression, AIs significantly improved disease-free survival (DFS) compared to selective estrogen receptor modulators (SERMs) (5 year-DFS: 83.5% vs. 50.7%, p = 0.016). However, there was no benefit of AIs on DFS in the pS6K1 negative group (5 year-DFS 87.6% vs. 91.4%, p = 0.630). On multivariate analysis, AI therapy remained a significant predictor for DFS in the pS6K1 positive group (hazard ratio, 0.39; 95% confidence interval, 0.16–0.96; p = 0.041). pS6K1 was more effective in predicting the benefit of AI therapy in patients with ages < 50 (p = 0.021) compared to those with ages ≥ 50 (p = 0.188). CONCLUSION pS6K1 expression may predict AI therapy outcomes and serve as a potential predictive marker for adjuvant endocrine therapy in postmenopausal and ovarian function-suppressed patients with hormone-sensitive breast cancer. AIs may be more effective in patients with pS6K1 positive tumors, while SERM could be considered an alternative option for patients with pS6K1 negative tumors.

Cavernous hemangiomas are benign neoplasms of endothelial cells. Although this neoplasm has the potential to develop in all parts of the body, it rarely develops in the axilla; in fact, there are only two case reports of axillary cavernous hemangiomas in the literature. Here, we describe a third case, which occurred in a 30-year-old Korean woman. The patient presented with a palpable mass in the left axilla that was initially thought to be either a phyllodes tumor or a lymphoma based on imaging studies. However, the results of an excisional biopsy led to a diagnosis of cavernous hemangioma. Although uncommon, a cavernous hemangioma can be encountered unexpectedly, presenting as a mass in axilla. Although usually curative, surgery may be challenging not only because of the rarity of the condition, but also because of inconsistent preoperative findings and the involvement of large vessels.
Adult ; Axilla ; Biopsy ; Diagnosis ; Endothelial Cells ; Female ; Hemangioma, Cavernous ; Humans ; Lymphoma ; Phyllodes Tumor ; Ultrasonography ; Vascular Neoplasms

BACKGROUND AND PURPOSE: Semantic memory remains more stable than episodic memory across the lifespan, which makes it potentially useful as a marker for distinguishing pathological aging from normal senescence. To obtain a better understanding of the transitional stage evolving into Alzheimer's dementia (AD), we focused on the amnestic mild cognitive impairment (aMCI) stage stratified based on β-amyloid (Aβ) pathology. METHODS: We analyzed the raw data from Korean version of the Boston Naming Test (K-BNT) and the Controlled Oral Word Association Test (COWAT). For K-BNT, the frequencies of six error types and accuracy rates were evaluated. For a qualitative assessment of the COWAT, we computed the number of switching, number of clusters, and mean cluster size. RESULTS: The data from 217 participants were analyzed (53 normal controls, 66 with Aβ− aMCI, 56 with Aβ+ aMCI, and 42 disease controls). There were fewer semantically related errors and more semantically unrelated errors on the K-BNT in Aβ+ aMCI than in Aβ− aMCI, without a gross difference in the z score. We also found that Aβ+ aMCI showed a more prominent deficit in the number of clusters in the semantic fluency task [especially for animal names (living items)] than Aβ− aMCI. CONCLUSIONS: In spite of similar clinical manifestations, Aβ+ aMCI was more similar to AD than Aβ− aMCI in terms of semantic memory disruption. Semantic memory may serve as an early indicator of brain Aβ pathology. Therefore, semantic memory dysfunction deserves more consideration in clinical practice. Longitudinal research with the follow-up data is needed.
Aging ; Alzheimer Disease ; Animals ; Brain ; Dementia ; Follow-Up Studies ; Humans ; Memory* ; Memory, Episodic ; Mild Cognitive Impairment* ; Pathology ; Semantics* ; Word Association Tests

PURPOSE: This study aimed to examine the association between the maximum standardized uptake value (SUVmax) of different molecular subtypes of primary breast cancer with axillary lymph node (ALN) metastasis. METHODS: The medical records of 633 patients, who underwent 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET/CT) for preoperative staging, were retrospectively reviewed. The cohort was stratified by the following molecular subtypes with immunohistochemical examination: luminal A, luminal B, human epidermal growth factor receptor 2 positive (HER2+), and triple negative. We evaluated the optimal cutoff SUVmax to predict ALN metastasis in each subtype using the receiver operating characteristic (ROC) analysis. Moreover, the risk factors for ALN metastasis were evaluated. RESULTS: Overall, the SUVmax was positively correlated with the number of metastatic ALN (p=0.001). The mean SUVmax was higher in aggressive subtypes (4.5±0.2, 6.1±0.4, 6.5±0.5, and 7.5±0.5 in luminal A, luminal B, HER2+, and triple negative, respectively, p<0.001). Upon ROC analysis, the SUVmax of the HER2+ subtype predicted ALN metastasis most accurately, with a cutoff value of 5.5, area under the curve (AUC) of 0.708, sensitivity of 74.2%, and specificity of 64.6% (p=0.002). The triple negative subtype did not show a significant difference in SUVmax between patients with and without metastasis (p=0.13). Subtype-adjusted SUVmax, HER2 positivity, lymphovascular invasion, and T stage were significant predictors for ALN metastasis. CONCLUSION The SUVmax of primary breast cancer may be an independent predictor of ALN metastasis, being the most accurate in the HER2+ subtype. As PET/CT could facilitate tailored axillary management, this approach could be considered for the initial staging and treatment planning in patients with breast cancer.

PURPOSE: Endocrine therapy is the preferred treatment for hormone receptor (HR)-positive metastatic breast cancer (MBC). We investigated the efficacy of combined aromatase inhibitor (AI) and luteinizing hormone-releasing hormone (LHRH) agonist in premenopausal patients with HR-positive MBC. METHODS: We retrospectively analyzed the medical records of 21 HR-positive premenopausal MBC patients treated with combined AI and LHRH agonist therapy. RESULTS: The median follow-up period was 32.9 months. The overall response rate was 47.6%, with three complete responses (14.3%) and seven partial responses (33.3%). Nine patients (42.9%) achieved stable disease lasting more than 6 months; thus, the clinical benefit rate was 90.4%. The median time to progression was 45.4 months. No patients experienced grade 3 or 4 toxicity. CONCLUSION: Combined AI and LHRH agonist treatment safely and effectively induced remission or prolonged disease stabilization, suggesting that this could be a promising treatment option for HR-positive premenopausal patients with MBC.
Aromatase Inhibitors ; Aromatase* ; Breast Neoplasms* ; Breast* ; Follow-Up Studies ; Gonadotropin-Releasing Hormone* ; Goserelin ; Humans ; Lutein* ; Medical Records ; Premenopause ; Retrospective Studies

The evaluation of menopausal status is an important subject in the field of treatment of hormone receptor positive breast cancer. According to the menopausal status, endocrine therapy should be categorized by individual patient. However, the gonadal injury caused by various therapeutic drugs and its recovery would confuse the interpretation of clinical and biological markers for ovarian reserve. There are some methods to examine the functional ovarian reserve indirectly. Ultrasonography for counting follicles is a relatively reliable procedure, although it is not feasible because of time-labor consumption and high cost. Biological marker from blood samples such as serum follicle stimulating hormone (FSH), serum estradiol (E2), serum inhibin, or anti-Müllerian hormone (AMH) would be a better choice. The examination of serum FSH and E2 is already recommended as biomarkers for measuring functional ovarian reserve in many guidelines. However, there are limitation of serum FSH and E2 in patients with chemotherapy-induced amenorrhea and treated by tamoxifen. AMH is promising biomarker in the field of infertility treatment even in the patients treated by chemotherapy. It might be a possible biomarker to determine the menopausal status for decision-making whether aromatase inhibitor could be applicable or not in hormone positive breast cancer patients with chemotherapy induced amenorrhea or treated by tamoxifen.
Amenorrhea ; Anti-Mullerian Hormone ; Aromatase ; Biomarkers ; Breast Neoplasms* ; Breast* ; Drug Therapy ; Estradiol ; Estrogens ; Female ; Follicle Stimulating Hormone ; Gonads ; Humans ; Infertility ; Inhibins ; Ovarian Reserve* ; Premenopause ; Tamoxifen ; Ultrasonography