Pediatric Keloids: A Retrospective, Single-Institution Cohort Analysis in Korea.

BACKGROUND/OBJECTIVES: There are scant established data on the cause, distribution, treatment options, and recurrence rate of pediatric keloids in Asian populations. We characterized clinical features by comprehensively categorizing pediatric keloid patients into prepubertal and postpubertal groups at a single tertiary center. METHODS: We searched the database of Kangbuk Samsung Hospital for pediatric patients (< 18 years) with clinically proven keloids who underwent outpatient-based treatment from 2007 to 2021. Clinical features, including demographics, distribution, underlying cause, treatment modality, and recurrence, were analyzed. RESULTS: Of the 93 patients (total 110 keloids), 42 females (45.2%) and 51 males (54.8%), with a mean age of 14.5 ± 4.1 years (range, 1-18 years), were retrospectively analyzed. The mean length of follow-up was 22.0 ± 14.2 months (range, 6-63). Of the 100 keloids with assessable causes, piercing (22%) and acne (19%) were the most common. In the prepubertal group, the lower and upper limbs (n = 7, 28%; n = 6, 24%) were the two most common locations, suggesting that post-traumatic keloids are common during this developmental period. In the postpubertal group, the ear (n = 25, 29.4%) was the most common site, which corresponds to the frequency of cosmetic piercing at this age. No differences were found between the effects of treatment methods on relapse rate. CONCLUSIONS: Understanding the clinical features of pediatric keloids is important in the therapeutic considerations for pediatric keloids. Future studies should analyze a larger number of children with keloids over longer observation periods.

Immunophenotypic classification regarding prognosis in peripheral T cell lymphoma, NOS, and nodal T follicular helper T cell lymphoma, angioimmunoblastic-type.

This study aimed to determine the clinicopathological predictive factors of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), and nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFH, AI-type). In this single-centered, retrospective study, medical records of 59 patients who were diagnosed with PTCL, NOS, or nTFH, AI-type from March 2007 to September 2022 were reviewed. The clinicopathological variables, including immunohistochemistry(IHC) subgroups, distinguishing TBX21 from the GATA3 subgroups were analyzed. Overall, 28 patients (75.7%) in the TBX21 group were PTCL, NOS. There were 9 (24.3%) patients in the GATA3 group. In univariable analyses, lymphoma subtype, age, and performance status were associated with progression-free survival (PFS), and overall survival (OS). In multivariable analyses, lymphoma subtype, and performance status were related to PFS and OS (P = 0.012, P < 0.001, P = 0.006, and P < 0.001, respectively). The GATA3 subgroup tended to have a worse prognosis in univariable analyses; however, it became more insignificant in multivariable when lymphoma subtype and performance status were adjusted (P = 0.065, P = 0.180, P = 0.972, and P = 0.265, respectively). The double-positive group showed variable prognoses of better PFS and worse OS. PD-1 and PD-L1 were associated with the EBV in situ hybridization (P = 0.027, and P = 0.005), and PD-1 was associated with CD30 expression (P = 0.043). This study demonstrated the potential of IHC classification to predict prognosis for PTCL, NOS, as well as nTFH AI-type, although further validation is necessary. Treatments targeting CD30, PD-1, and PD-L1 appear promising for lymphoma treatment.

Erosive Pustular Dermatosis of the Scalp Arising on Long-Standing Burn Scars: A Report of Three Cases and Brief Review of Literature.

Introduction: Erosive pustular dermatosis of the scalp (EPDS) is a rare and recalcitrant condition in which chronic scalp pustules and erosive patches are diagnosed by nondiagnostic laboratory tests and histopathological tests. Although various precipitating factors including trauma have been reported, erosive pustular dermatosis arising on the long-standing burn scars is rare. Case Presentation: We report three cases of EPDS arising on long-standing burn scars. Based on clinical and histological findings, erosive pustular dermatosis was diagnosed and successfully treated with topical steroid ointment. Conclusion: We propose that chronic burn scar is another precipitating factors for EPDS and clinicians should consider EPDS in differential diagnoses of erosive pustular dermatosis in long-standing burn scars on the scalp.

Comparison of the Characteristics of Three Acellular Dermal Matrices Subjected to Distinct Processing Methods Using Five Types of Histochemical Staining.

BACKGROUND: Acellular dermal matrix (ADM) is treated using various devitalization and aseptic processing methods. The processing effects on ADM were evaluated by histochemical tests. METHODS: From January 2014 to December 2016, 18 patients [average age, 43.0 (range, 30-54) years] who underwent breast reconstruction with an ADM and tissue expander were prospectively enrolled. During the permanent implant replacement, a biopsy of the ADM was performed. We used three different human-derived products, namely, Alloderm®, Allomend®, and Megaderm®. Hematoxylin and eosin, CD68, CD3, CD31, and smooth muscle actin were used to evaluate the collagen structure, inflammation, angiogenesis, and myofibroblast infiltration. Each ADM was semi-quantitatively analyzed. RESULTS: Significant differences in collagen degradation, acute inflammation, and myofibroblast infiltration were observed among the ADMs. Collagen degeneration (p<0.001) and myofibroblast infiltration (smooth muscle actin-positive, p=0.018; CD31-negative, p=0.765) were the most severe in Megaderm®. Acute inflammation, represented by CD68, was most severe in Alloderm® (p=0.024). Both radiation and freeze-drying treatment physically damaged the collagen structure. Collagen degeneration was most severe in Megaderm®, followed by Allomend® and Alloderm®. Since Alloderm® is treated using chemicals, an assessment of the chemical irritation is warranted. CONCLUSIONS: The biopsy results were inconclusive. Therefore, to better interpret processing, more large-scale, serial, histochemical studies of each ADM are needed. LEVEL OF EVIDENCE IV: This journal requires that authors 38 assign a level of evidence to each article. For a full 39 description of these Evidence-Based Medicine ratings, 40 please refer to the Table of Contents or the online 41 Instructions to Authors www.springer.com/00266 .

Clinicopathological Factors Influencing Resection Margin Involvement During Mohs Micrographic Surgery for Skin Tumors.

BACKGROUND/AIM: Mohs micrographic surgery (MMS) is a specialized procedure for removing skin tumors. Intraoperative assessment of the resection margin (RM) status using frozen section examination is a crucial component of MMS. This study aimed to identify significant clinicopathological characteristics that could help surgeons determine the optimal surgical extent. PATIENTS AND METHODS: One hundred and fifty-one patients with primary skin tumors were included. The relationship between RM involvement and the clinico-pathological characteristics was analyzed for each histological type. RESULTS: Basal cell carcinoma (BCC) was significantly more likely to exhibit positive RMs and required additional excision during MMS compared to squamous cell carcinoma. In addition, the probability of RM involvement was significantly higher in high-risk BCC subtypes. CONCLUSION: When planning MMS, considering the histological type and presence of high-risk morphology may help surgeons perform more effective procedures.

Clinicopathological Characterization of Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System.

BACKGROUND/AIM: Primary central nervous system diffuse large B-cell lymphoma (CNS DLBCL) is a rare entity, accounting for 3-4% of intracranial neoplasms. This study aimed to investigate the clinicopathological characteristics of primary CNS DLBCL patients and their prognostic implication. PATIENTS AND METHODS: We collected 74 cases of clinically and pathologically confirmed primary CNS DLBCL from two institutions. Disease-free survival (DFS) and overall survival (OS) were analyzed based on various clinicopathological parameters. RESULTS: Most cases (83.8%) were classified as activated B-cell immunophenotype by Hans algorithm and cell-of-origin classification did not influence the clinical outcome. On univariate analysis, age (>60 years) and ECOG performance status (≥2) were significantly associated with shorter DFS and OS, and MYC/BCL2 co-expression significantly impacted poor DFS. An anaplastic variant was diagnosed in only 2 cases, but it raised possible association with poor outcome. On multivariate analysis, ECOG performance status and age was associated with poor prognosis. CONCLUSION: In primary CNS DLBCL, age and performance status revealed the most significant association with prognosis. Cell-of-origin classification was not a significant prognostic factor in contrast to systemic DLBCL.

Clinicopathological and Prognostic Significance of Programmed Death Ligand-1 SP142 Expression in 132 Patients With Triple-negative Breast Cancer.

BACKGROUND/AIM: The prognostic value of programmed death ligand-1 (PD-L1) expression in triple-negative breast cancer (TNBC) has not been sufficiently investigated. In this study, we examined whether PD-L1 expression status is associated with clinicopathological features and outcomes of patients with TNBC. PATIENTS AND METHODS: Immunostaining for PD-L1 SP142 was performed on tissue microarrays containing 132 TNBC samples. High PD-L1 expression was defined as ≥10% of the tumor area occupied by PD-L1-expressing cells. RESULTS: Thirty-five (26.5%) patients showed high PD-L1 SP142 expression on immune cells (ICs). High IC PD-L1 expression was significantly correlated with smaller tumor size (p=0.030), absence of lymphovascular invasion (p=0.024), and fewer lymph node metastases (p=0.002). Multivariate survival analysis revealed that high IC PD-L1 expression independently predicted better disease-free survival (DFS) of TNBC patients. CONCLUSION: High PD-L1 SP142 expression on ICs was significantly associated with favorable clinicopathological parameters and better outcomes in patients with TNBC. Our observations suggest that high IC PD-L1 expression can be used as an independent prognostic marker for predicting better DFS in patients with TNBC.

Prognostic significance of BLK expression in R-CHOP treated diffuse large B-cell lymphoma.

BACKGROUND: The aim of the present study was to evaluate the prognostic significance of B-cell lymphocyte kinase (BLK) expression for survival outcomes in diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP. METHODS: We retrospectively analyzed the medical records of 89 patients from two tertiary referral hospitals. The expression of BLK, SYK, and CDK1 were evaluated in a semiquantitative method using an H-score, and the proportions of BCL2 and C-MYC were evaluated. RESULTS: A total of 89 patients received R-CHOP chemotherapy as a first-line chemotherapy. The expression rates of BLK in tumor cells was 39.2% (n = 34). BLK expression status was not significantly associated with clinical variables; however, BLK expression in tumor cells was significantly associated with the expression of both C-MYC and BCL2 (p = .003). With a median follow-up of 60.4 months, patients with BLK expression had significantly lower 5-year progression-free survival (PFS) and overall survival rates (49.8% and 60.9%, respectively) than patients without BLK expression (77.3% and 86.7%, respectively). In multivariate analysis for PFS, BLK positivity was an independent poor prognostic factor (hazard ratio, 2.208; p = .040). CONCLUSIONS: Here, we describe the clinicopathological features and survival outcome according to expression of BLK in DLBCL. Approximately 39% of DLBCL patients showed BLK positivity, which was associated as a predictive marker for poor prognosis in patients who received R-CHOP chemotherapy.

Clinicopathologic Characteristics Associated with Prognosis in Ocular Extranodal Marginal Zone B Cell Lymphoma.

Background and Objectives: Extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT) type is the most common subtype of the ocular adnexal lymphoma. Despite its excellent prognosis, some patients experience partial remission or progressive disease. We aimed to evaluate clinicopathologic differences in the treatment responder group by comparing complete remission (CR) and non-complete remission (non-CR). Materials and Methods: This study retrospectively reviewed 48 patients who were diagnosed with ocular adnexal MALT lymphoma at Ulsan University Hospital between March 2002 and August 2018. Patients who were followed up for less than 6 months were excluded. Histologic and clinical features were analyzed. The patients were divided into two groups: CR and non-CR. Results: Among the 48 patients, 33 achieved CR and 15 achieved non-CR during the median follow-up period of 40.00 months (range, 7-109 months). In univariable analysis, more patients tend to undergo treatment in the CR group, and post-radiotherapy (post-RT) SUVmax, PET and serum lactate dehydrogenase (LDH) levels were higher in the non-CR group (p = 0.043, p = 0.016, and p = 0.042, respectively). In a multivariable analysis, only application of treatment, including radiotherapy or chemotherapy with immunotherapy, was related to CR (odd ratio 7.301, 95% confidence interval 1.273-41.862, p = 0.026). In subgroup analysis according to the site of involvement, none of the variables were significant except for the post-RT SUVmax of PET and level of serum LDH in the non-conjunctiva group (p = 0.026, and p = 0.037, respectively). Seven (14.6%) patients had a recurrence, and those with a recurring site other than the primary site had a higher Ki-67 labeling index, although it was not statistically significant (9.56% vs. 18.00%, p = 0.095). Conclusions: Although belonging to the early stages, the non-CR rate was high in patients with high serum LDH levels, and recurred patients had higher Ki-67. Thus, considering active treatment is recommended in this group of patients.

Corticosteroid-induced drug reaction with eosinophilia and systematic symptoms successfully treated with a tumor necrosis factor alpha inhibitor.

BACKGROUND: Despite recent advances in the treatment of drug reaction with eosinophilia and systemic symptoms (DRESS), the mainstay of treatment involves discontinuing the culprit drugs and administering topical or systemic corticosteroid. OBJECTIVE: The clinical use of a tumor necrosis factor (TNF)-alpha inhibitor was rarely explored in treatment of DRESS. METHODS: We present a case of corticosteroid-induced DRESS that was successfully treated with a TNF-alpha inhibitor without sequalae. RESULTS: This is the first case report that showed the clinical use of a TNF alpha inhibitor in treating corticosteroids- induced DRESS and immediate hypersensitivity reactions. The HLA-B*5801 was identified as a possible genetic factor associated with a corticosteroid-induced DRESS. CONCLUSIONS: A TNF-alpha inhibitor could be a primary option in treating DRESS, especially in patients with hypersensitivity reaction to corticosteroids.

Early postoperative treatment of mastectomy scars using a fractional carbon dioxide laser: a randomized, controlled, split-scar, blinded study.

BACKGROUND: Mastectomy leaves unsightly scarring, which can be distressing to patients. Laser therapy for scar prevention has been consistently emphasized in recent studies showing that several types of lasers, including fractional ablation lasers, are effective for reducing scar formation. Nonetheless, there are few studies evaluating the therapeutic efficacy of ablative CO2 fractional lasers (ACFLs). METHODS: This study had a randomized, comparative, prospective, split-scar design with blinded evaluation of mastectomy scars. Fifteen patients with mastectomy scars were treated using an ACFL. Half of each scar was randomized to "A," while the other side was allocated to group "B." Laser treatment was conducted randomly. Scars were assessed using digital photographs of the scar and Vancouver scar scale (VSS) scores. Histological assessments were also done. RESULTS: The mean VSS scores were 2.20±1.28 for the treatment side and 2.96±1.40 for the control side. There was a significant difference in the VSS score between the treatment side and the control side (P=0.002). The mean visual analog scale (VAS) scores were 4.13±1.36 for the treatment side and 4.67±1.53 for the control side. There was a significant difference in VAS score between the treatment side and the control side (P=0.02). CONCLUSIONS: This study demonstrated that early scar treatment using an ACFL significantly improved the clinical results of the treatment compared to the untreated scar, and this difference was associated with patient satisfaction.

Proto-oncogene Pokemon in thyroid cancer: a potential promoter of tumorigenesis in papillary thyroid carcinoma.

BACKGROUND: Pokemon is an oncogenic transcription regulator that plays a critical role in cellular differentiation. Although it has been found to be overexpressed in several types of cancer involving different organs, its role in thyroid gland has yet to be reported. The objective of this study was to evaluate the expression of Pokemon in papillary thyroid carcinoma (PTC) based on clinicopathological parameters. METHODS: Tissue microarray samples derived from patients with PTC or benign thyroid disease were used to evaluate Pokemon expression based on immunohistochemical analysis. Correlations of its expression with various clinicopathological parameters were then analyzed. RESULTS: Pokemon expression was observed in 22.0% of thyroid follicular cells from the normal group, 44.0% from the group with benign thyroid diseases, and 92.1% from the group with PTC (p < .001). The intensity of Pokemon expression was markedly higher in the PTC group. Pokemon expression level and PTC tumor size showed an inverse correlation. T1a tumors showed strong expression levels of Pokemon. However, larger tumors showed weak expression (p = .006). CONCLUSIONS: Pokemon expression is associated with tumorigenesis of PTC, with expression showing an inverse correlation with PTC tumor size. This might be related to the negative regulation of aerobic glycolysis by Pokemon.

Association between skeletal muscle mass and mammographic breast density.

Mammographic density (MD) of the breast and body mass index (BMI) are inversely associated with each other, but have inconsistent associations with respect to the risk of breast cancer. Skeletal muscle mass index (SMI) has been considered to reflect a relatively accurate fat and muscle percentage in the body. So, we evaluated the relation between SMI and MD. A cross-sectional study was performed in 143,456 women who underwent comprehensive examinations from 2012 to 2016. BMI was adjusted to analyze whether SMI is an independent factor predicting dense breast. After adjustment for confounding factors including BMI, the odds ratios for MD for the dense breasts was between the highest and lowest quartiles of SMI at 2.65 for premenopausal women and at 2.39 for postmenopausal women. SMI was a significant predictor for MD, which could be due to the similar growth mechanism of the skeletal muscle and breast parenchymal tissue. Further studies are needed to understand the causal link between muscularity, MD and breast cancer risk.

High BMI1 Expression with Low CD8+ and CD4+ T Cell Activity Could Promote Breast Cancer Cell Survival: A Machine Learning Approach.

BMI1 is known to play a key role in the regulation of stem cell self-renewal in both endogenous and cancer stem cells. High BMI1 expression has been associated with poor prognosis in a variety of human tumors. The aim of this study was to reveal the correlations of BMI1 with survival rates, genetic alterations, and immune activities, and to validate the results using machine learning. We investigated the survival rates according to BMI1 expression in 389 and 789 breast cancer patients from Kangbuk Samsung Medical Center (KBSMC) and The Cancer Genome Atlas, respectively. We performed gene set enrichment analysis (GSEA) with pathway-based network analysis, investigated the immune response, and performed in vitro drug screening assays. The survival prediction model was evaluated through a gradient boosting machine (GBM) approach incorporating BMI1. High BMI1 expression was correlated with poor survival in patients with breast cancer. In GSEA and in in silico flow cytometry, high BMI1 expression was associated with factors indicating a weak immune response, such as decreased CD8+ T cell and CD4+ T cell counts. In pathway-based network analysis, BMI1 was directly linked to transcriptional regulation and indirectly linked to inflammatory response pathways, etc. The GBM model incorporating BMI1 showed improved prognostic performance compared with the model without BMI1. We identified telomerase inhibitor IX, a drug with potent activity against breast cancer cell lines with high BMI1 expression. We suggest that high BMI1 expression could be a therapeutic target in breast cancer. These results could contribute to the design of future experimental research and drug development programs for breast cancer.

Altered Differentiation of Tendon-Derived Stem Cells in Diabetic Conditions Mediated by Macrophage Migration Inhibitory Factor.

The purpose of our study was to evaluate the role of macrophage migration inhibitory factor (MIF) in the differentiation of tendon-derived stem cells (TdSCs) under hyperglycemic conditions. In the in vivo experiment, rats were classified into diabetic (DM) and non-DM groups depending on the intraperitoneal streptozotocin (STZ) or saline injection. Twelve-week after STZ injection, the supraspinatus tendon was harvested and prepared for histological evaluation and real-time reverse transcription polymerase chain reaction for osteochondrogenic (aggrecan, BMP-2, and Sox9) and tenogenic (Egr1, Mkx, scleraxis, type 1 collagen, and Tnmd) markers. For the in vitro experiment, TdSCs were isolated from healthy rat Achilles tendons. Cultured TdSCs were treated with methylglyoxal and recombinant MIF or MIF gene knockdown to determine the effect of hyperglycemic conditions and MIF on the differentiation function of TdSCs. These conditions were classified into four groups: hyperglycemic-control group, hyperglycemic-recombinant-MIF group, hyperglycemic-knockdown-MIF group, and normal-control group. The mRNA expression of osteochondrogenic and tenogenic markers was compared among the groups. In the in vivo experiment, the mRNA expression of all osteochondrogenic and tenogenic differentiation markers in the DM group was significantly higher and lower than that in the non-DM group, respectively. Similarly, in the in vitro experiments, the expression of all osteochondrogenic and tenogenic differentiation markers was significantly upregulated and downregulated, respectively, in the hyperglycemic-control group compared to that in the normal-control group. The hyperglycemic-knockdown-MIF group demonstrated significantly decreased expression of all osteochondrogenic differentiation markers and increased expression of only some tenogenic differentiation markers compared with the hyperglycemic-control group. In contrast, the hyperglycemic-recombinant-MIF group showed significantly increased expression of all osteochondrogenic differentiation markers, but no significant difference in any tenogenic marker level, compared to the hyperglycemic-control group. These results suggest that tendon homeostasis could be affected by hyperglycemic conditions, and MIF appears to alter the differentiation of TdSCs via enhancement of the osteochondrogenic differentiation in hyperglycemic conditions. These are preliminary findings, and must be confirmed in a further study.

Can ultrasound distinguish between dermatofibroma and subcutaneous epidermal tumors? - Imaging features and reproducibility.

BACKGROUND: We evaluated ultrasound (US) features of dermatofibroma and epidermal tumor (ET). We also evaluated the reproducibility of each US findings. MATERIALS AND METHODS: We retrospectively assessed US findings of 30 surgically confirmed dermatofibromas and 44 ETs, measuring the lesion (i.e., the depth and the length of the lesion) and calculating the depth to length ratio (DLR). We then determined the sharpness and the shape of the lesion. Finally, we assessed whether the lesion appeared with a "more-than-half sign" (involving more than 50% of the dermal layer) or a "submarine sign" (focal projection to skin). We used Pearson's chi-squared test to analyze the US findings (i.e., presence of more-than-half sign or submarine sign and margin sharpness) between dermatofibroma and ET. Inter-observer agreement of the image findings was assessed using kappa statistics. RESULTS: The submarine sign and margin sharpness of ET lesions and the more-than-half sign and submarine sign in dermatofibroma, respectively, showed almost perfect agreement. Also, the more-than-half sign and shape of the lesion in ET and the margin sharpness and shape of the lesion in dermatofibroma showed substantial agreement. The measurements of DLRs showed excellent reproducibility. There were no significant differences of DLRs between two groups (p values = 0.512, 0.671, respectively). The more-than-half sign was observed more frequently in the context of dermatofibroma to a statistically significant degree (p < 0.001), while the submarine sign was statistically more common in relation to ET together with greater margin sharpness (p = 0.021 and <0.001, respectively). CONCLUSIONS: More-than-half signs are common in dermatofibroma while submarine sign and sharp margin are common in ET. Each finding showed high reproducibility and can be useful as a sonographic marker for differentiation between ET and dermatofibroma.

High-sensitivity C-reactive Protein and Regression of Low-grade Squamous Intraepithelial Lesion: The Role of Low-grade Inflammation in Cervical Carcinogenesis.

BACKGROUND: Inflammation is emerging as a potential mechanism of cervical carcinogenesis. However, few studies have investigated the association between host inflammatory status and the natural course of cervical precursor lesion. The aim of this study was to assess the probability of LSIL regression, associated with an inflammatory biomarker, high-sensitivity C-reactive protein (hs-CRP). METHODS: In a longitudinal cohort study, female participants were examined annually or biannually using cervical cytology between 2006 and 2015. Incident LSIL cases were included in the analysis, with regression defined as at least one consecutive normal cytologic result. A total of 520 women aged 22-64 years were followed up for LSIL regression. The multivariable-adjusted hazard ratios (HRs) for LSIL regression were estimated using a parametric proportional hazards model. RESULTS: During 827.5 person-years of follow-up, 486 out of 520 subjects (93.5%) showed LSIL regression. After adjusting several important potential confounders, a higher quartile of hs-CRP levels was significantly associated with a lower rate of regression (for quartile 4 vs quartile 1, inverse HR 1.33; 95% CI, 1.04-1.69; P for trend = 0.028). CONCLUSIONS: The low rate of spontaneous regression recorded in women with higher hs-CRP lends support to the role of the perturbated host inflammatory status in cervical carcinogenesis, and suggests that hs-CRP level could help monitor LSIL.

Excessive walking exercise precipitates diabetic neuropathic foot pain: hind paw suspension treadmill exercise experiment in a rat model.

The harmful effects of excessive mechanical loading on diabetic neuropathy and the reason diabetic neuropathic symptoms are common in feet are unclear. In this study, the hind paw suspension treadmill exercise model was used in rats to investigate whether mechanical loading applied to the front paws precipitates neuropathic pain, especially in diabetic conditions. Thirty-two rats were divided into six groups according to the presence of diabetes (DM) and the intensity of mechanical loading applied to the front paws: DM-Hi (high-intensity); DM-Lo (low-intensity); DM-No (non-mechanical loading); Sham-Hi; Sham-Lo; and Sham-No. DM was induced by streptozotocin injection. For high-intensity or low-intensity mechanical loading, treadmill walking exercise was conducted with or without hind paw suspension, respectively. The mechanical withdrawal threshold of the front paw decreased significantly after 8 weeks only in the DM mechanical loading groups (DM-Hi and DM-Lo), and high-intensity loading more significantly decreased the front-paw withdrawal threshold than low-intensity loading. In the DM-Hi group only, macrophage migration inhibitory factor (MIF) increased significantly, and intra-epidermal nerve fibers (IENF) in the front paws decreased significantly. In diabetic conditions, mechanical overloading such as excessive walking is likely to precipitate mechanical allodynia and damage IENF¸ which could explain why diabetic neuropathic symptoms are common in feet. This finding might be related to up-regulation of intracellular signaling cascades such as MIF, rather than inflammatory processes.

Voxel-based Three-dimensional Segmentation of the Capsulo-synovium from Contrast-enhanced MRI Can Represent Clinical Impairments in Adhesive Capsulitis.

The purposes were to calculate total voxel volume of the entire capsulo-synovial enhanced portion on contrast-enhanced (CE) MRI in adhesive capsulitis, and to investigate its association with glenohumeral joint volume and passive range of motions (ROMs), which are a well-known diagnostic reference standard and clinical hallmark of this condition. Medical records of 169 consecutive patients who underwent ultrasound-guided intraarticular injection with adhesive capsulitis and CE-MRI to exclude other mimicking shoulder diseases were retrospectively reviewed. To calculate total voxel volume of entire capsulo-synovial enhanced portion on CE-MRI, voxel-based 3-dimensional (3D) segmentation was obtained semi-automatically using Fiji, an open-source image processing software. Pearson's correlation coefficients were analyzed. Sixty patients who met eligibility criteria were included. Total voxel volume showed a significant inverse correlation with the glenohumeral joint volume (r = -0.528, P < 0.001), forward elevation, external rotation, and abduction (r = -0.407, P = 0.001; r = -0.342, P = 0.007; r = -0.275, P = 0.034, respectively). Intra-observer and inter-observer reliabilities, measured by intraclass correlation coefficients (ICC), were excellent (ICC = 0.87 and 0.77, respectively). This study's results indicate that voxel-based 3D segmentation of entire capsulo-synovial enhanced portion from CE-MRI can represent the severity of clinical impairments, such as obliterated joint volume and limited passive ROMs in adhesive capsulitis.

Expression of UTX Indicates Poor Prognosis in Patients With Luminal Breast Cancer and is Associated With MMP-11 Expression.

Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX) is involved in the epigenetic regulation. A previous mouse xenograft study revealed that UTX knockdown is associated with downregulated expression of matrix metalloproteinase-11 (MMP-11). The authors investigated 224 cases of breast cancer from Kangbuk Samsung Medical Center between 2000 and 2005. Nuclear UTX and cytoplasmic MMP-11 expressions were assessed using immunohistochemistry of tumor tissue microarray specimens. The relationships between the expression of UTX, MMP-11, and patients' outcomes were analyzed. UTX expression was significantly associated with high histologic grade, lymphatic invasion, vascular invasion, and tumoral expression of MMP-11. Survival analysis revealed that patients with UTX expression had a poorer overall survival rate (P=0.010) as well as diminished disease-free survival rate (P=0.001). The prognostic power of UTX expression was significant in patients with luminal-type breast cancer (P=0.027, overall survival; P=0.008, disease-free survival). Validation of UTX can provide further prognostic information beyond traditional indicators and represents a potential therapeutic target for breast cancer.