Prognostic and Predictive Significance of Ki67 in Primary Non-metastatic or Recurrent Acral Melanoma: Evidence from a Multicenter Retrospective Study.

BACKGROUND: The purpose of this work was to investigate the prognostic significance of Ki67 in acral melanoma (AM). PATIENTS AND METHODS: Ki67 values in primary lesions (pKi67) of 481 patients with primary non-metastatic AM (primary cohort) from three tertiary hospitals and in recurrent lesions (rKi67) of 97 patients (recurrent cohort) were recorded. The associations of p/rKi67 with clinicopathological features and prognosis were analyzed. RESULTS: In the primary cohort, high pKi67 group tended to have more ulceration, pT4, lymph node metastasis (LNM), nodal macrometastases, and recurrence (all P < 0.05). Logistic regression analysis revealed that pKi67 was significantly associated with pT4 and LNM (P = 0.004 and 0.027, respectively). Furthermore, both 5-year overall survival (OS) and recurrence-free survival (RFS) rates in high pKi67 group were significantly worse than those in moderate and low pKi67 groups (OS 47.8% versus 55.7 versus 76.8%, P = 0.002; RFS: 27.1 versus 42.8 versus 61.8%, P < 0.001). Similarly, in the recurrent cohort, the 5-year survival after recurrence (SAR) rates in high rKi67 group was significantly worse than those in moderate and low rKi67 groups (31.7 versus 47.4 versus 75%; P = 0.026). Stratified analysis also indicated a significant survival difference among pKi67 groups within various subgroups. Most importantly, multivariate Cox analysis demonstrated that pKi67 could be independently associated with OS and RFS, as well as rKi67 for SAR (all P < 0.05). CONCLUSIONS: A high Ki67 value was significantly associated with adverse pathological and prognostic features in both primary and recurrent AM cohorts. Ki67 should be routinely evaluated to guide risk stratification and prognostic prediction.

Clinical and pathological findings of chronic actinic dermatitis.

BACKGROUND: Chronic actinic dermatitis (CAD) is a recurrent photosensitive disease occurs predominantly in elderly men on sun-exposed areas, which seriously affect the patient's life quality. The etiology of CAD remains unknown. METHODS: Sixty-six CAD patients, 66 atopic dermatitis (AD) patients, and 46 healthy people were enrolled into this study. Patient-level data were obtained from the electronic medical record and laboratory databases. We also obtained 29 tissue samples including 16 lichenoid lesions, 7 minimal erythematous dose (MED) analysis induced lesions, and 6 normal skin samples. Histopathologic and immunohistochemical analysis were performed. RESULTS: In the clinical characteristics, albumin was lower and uric acid was higher significantly in patients diagnosed as CAD. The infection rate of CAD patient after skin biopsy was considerably high (23.3%). The serum allergen test was prone to be negative in CAD patients. Lymphocytes were the dominate infiltrating cells in early and late CAD lesions, while more CD4+, CD8+, CD69+, and CD103 + cells were found in the late lesions. There is no difference in CD4+/CD8 + ratio and CD69+/CD103 + ratio among groups. More mast cells were observed in the early-stage lesions, and more dendritic cell was observed in the late-stage lesions. CONCLUSIONS: CAD patients have certain oxidative stress and are prone to be infected after skin biopsy. Serum allergen detection is of little significance for CAD diagnosis. Mast cells may be involved in the early process of CAD, while dendritic cells and tissue-resident memory T cell (TRM) may be related to the chronic process of the disease.

Case report: Rubella virus-associated cutaneous granuloma in an adult with TAP1 deficiency.

Rubella virus-associated granulomas commonly occur in immunocompromised individuals, exhibiting a diverse range of clinical presentations. These manifestations can vary from predominantly superficial cutaneous plaques or nonulcerative nodules to more severe deep ulcerative lesions, often accompanied by extensive necrosis and significant tissue destruction. TAP1 deficiency, an exceedingly rare primary immune-deficiency disorder, presents with severe chronic sino-pulmonary infection and cutaneous granulomas. This report highlights the occurrence of rubella virus-associated cutaneous granulomas in patients with TAP1 deficiency. Notably, the pathogenic mutation responsible for TAP1 deficiency stems from a novel genetic alteration that has not been previously reported. This novel observation holds potential significance for the field of diagnosis and investigative efforts in the context of immunodeficiency disorders.

Evaluation of ensemble strategy on the development of multiple view ankle fracture detection algorithm.

OBJECTIVE: To identify the feasibility and efficiency of deep convolutional neural networks (DCNNs) in the detection of ankle fractures and to explore ensemble strategies that applied multiple projections of radiographs.Ankle radiographs (AXRs) are the primary tool used to diagnose ankle fractures. Applying DCNN algorithms on AXRs can potentially improve the diagnostic accuracy and efficiency of detecting ankle fractures. METHODS: A DCNN was trained using a trauma image registry, including 3102 AXRs. We separately trained the DCNN on anteroposterior (AP) and lateral (Lat) AXRs. Different ensemble methods, such as "sum-up," "severance-OR," and "severance-Both," were evaluated to incorporate the results of the model using different projections of view. RESULTS: The AP/Lat model's individual sensitivity, specificity, positive-predictive value, accuracy, and F1 score were 79%/84%, 90%/86%, 88%/86%, 83%/85%, and 0.816/0.850, respectively. Furthermore, the area under the receiver operating characteristic curve (AUROC) of the AP/Lat model was 0.890/0.894 (95% CI: 0.826-0.954/0.831-0.953). The sum-up method generated balanced results by applying both models and obtained an AUROC of 0.917 (95% CI: 0.863-0.972) with 87% accuracy. The severance-OR method resulted in a better sensitivity of 90%, and the severance-Both method obtained a high specificity of 94%. CONCLUSION: Ankle fracture in the AXR could be identified by the trained DCNN algorithm. The selection of ensemble methods can depend on the clinical situation which might help clinicians detect ankle fractures efficiently without interrupting the current clinical pathway. ADVANCES IN KNOWLEDGE: This study demonstrated different ensemble strategies of AI algorithms on multiple view AXRs to optimize the performance in various clinical needs.

Case Report: Pemphigus in Young Patients With Thymic Anomalies.

Pemphigus is an autoimmune disease that occurs mainly in elderly individuals. Young patients with pemphigus are rare, and the risk factors are unclear. The thymus is associated with a variety of autoimmune diseases, and there have been reports of pemphigus complicated with thymic diseases. Here, we report three cases of young patients with pemphigus that were associated with thymic anomalies. We suggest that thymic anomalies may be a risk factor for the early onset of pemphigus and may be associated with increased severity of the disease. Interventions for thymic diseases have certain benefits for improving the effect of treatments and prognosis of these patients.

Methicillin-resistant Staphylococcus aureus nasal carriage and infection among patients with diabetic foot ulcer.

PURPOSE: To evaluate the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) nasal carriage in patients with diabetic foot ulcer (DFU) in Taiwan, and to assess the concordance between colonizing and clinical MRSA isolates from the patients. METHOD: A total of 354 nasal specimens were collected from 112 to 242 diabetic patients with and without foot ulcer, respectively. MRSA clinical isolates from DFU wound cultures were collected for comparison. RESULTS: Nasal carriage rate of S. aureus and MRSA was similar between diabetic patients with and without foot ulcer (15.2% vs. 16.9% for S. aureus and 5.4% vs. 1.7% for MRSA). Nasal S. aureus colonization was an independent predictor for wound S. aureus infection (Odds ratio [OR]: 5.33, 95% confidence interval [CI]: 1.61-17.59), so did nasal MRSA colonization (OR: 19.09, 95% CI: 2.12-171.91). The levels of glycated hemoglobin, and the usage with immunosuppressant agent were associated with S. aureus nasal colonization while oral hypoglycemic agent usage a protective factor. Sequence type 59/staphylococcal chromosome cassette mec IV or V, the local endemic community-associated clone, accounted for 42% and 70% of the clinical and colonizing isolates, respectively. Six of 10 patients with paired colonizing and clinical isolates, either MRSA or methicillin-sensitive S. aureus, had a genetically identical strain from a single patient. CONCLUSION: Less than one-fifth of patients with DFU have nasal S. aureus, including MRSA, colonization; however, the colonization is significantly associated with S. aureus diabetic foot infection. Screening for S. aureus colonizing status in DFU patients might have a potential clinical implication.

Usefulness of miRNA-338-3p in the diagnosis of pemphigus and its correlation with disease severity.

BACKGROUND: Pemphigus is a common life-threatening, autoimmune bullous disease effecting both cutaneous and mucous membranes. Previous diagnosis of pemphigus is based on clinical presentations, histopathology, immunofluorescence and enzyme-linked immunosorbent assay. Furthermore, no laboratory parameters could be used to indicate disease severity. MicroRNAs are endogenous small RNAs, which could be used as diagnostic biomarkers for some autoimmune diseases. Previously, miR-338-3p has been proven significantly up-regulated in pemphigus patients. METHODS: Pemphigus patients (including pemphigus vulgaris and pemphigus foliaceus) with active lesions and with remission, patients diagnosed as bullous pemphigoid and healthy volunteers were recruited, and miR-338-3p expression level was measured using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Active pemphigus patients accepting treatment were followed up for at least 2 weeks to investigate the expression change of miR-338-3p during treatment period. Target genes of miR-338-3p were screened through computer-aided algorithm and verified by RT-qPCR, Western blot and Luciferase activity assay. RESULTS: MiR-338-3p was specifically increased in patients diagnosed as pemphigus with active lesions. The expression level of miR-338-3p gradually decreased after effective treatment. MiR-338-3p expression was independently correlated with disease severity defined by PDAI (Pemphigus Disease Area Index) or ABSIS (Autoimmune Bullous Skin Disorder Intensity Score) criteria. Up-regulation of miR-338-3p could significantly suppress RNF114 expression at mRNA and protein level in vitro. DISCUSSION: MiR-338-3p could be used as a diagnostic biomarker of pemphigus in addition to other traditional methods. Up-regulation of MiR-338-3p was associated with more severe condition in pemphigus. RNF114 is the target gene of miR-338-3p, which probably participates in the regulation of disease activity of pemphigus.