Rapid and noninvasive estimation of human arsenic exposure based on 4-photo-set of the hand and foot photos through artificial intelligence.

Chronic exposure to arsenic is linked to the development of cancers in the skin, lungs, and bladder. Arsenic exposure manifests as variegated pigmentation and characteristic pitted keratosis on the hands and feet, which often precede the onset of internal cancers. Traditionally, human arsenic exposure is estimated through arsenic levels in biological tissues; however, these methods are invasive and time-consuming. This study aims to develop a noninvasive approach to predict arsenic exposure using artificial intelligence (AI) to analyze photographs of hands and feet. By incorporating well water consumption data and arsenic concentration levels, we developed an AI algorithm trained on 9988 hand and foot photographs from 2497 subjects. This algorithm correlates visual features of palmoplantar hyperkeratosis with arsenic exposure levels. Four pictures per patient, capturing both ventral and dorsal aspects of hands and feet, were analyzed. The AI model utilized existing arsenic exposure data, including arsenic concentration (AC) and cumulative arsenic exposure (CAE), to make binary predictions of high and low arsenic exposure. The AI model achieved an optimal area under the curve (AUC) values of 0.813 for AC and 0.779 for CAE. Recall and precision metrics were 0.729 and 0.705 for CAE, and 0.750 and 0.763 for AC, respectively. While biomarkers have traditionally been used to assess arsenic exposure, efficient noninvasive methods are lacking. To our knowledge, this is the first study to leverage deep learning for noninvasive arsenic exposure assessment. Despite challenges with binary classification due to imbalanced and sparse data, this approach demonstrates the potential for noninvasive estimation of arsenic concentration. Future studies should focus on increasing data volume and categorizing arsenic concentration statistics to enhance model accuracy. This rapid estimation method could significantly contribute to epidemiological studies and aid physicians in diagnosis.

Clinical Characteristics and Disease Burden of Patients with Moderate-to-Severe Generalized Pustular Psoriasis Flares in Taiwan.

INTRODUCTION: Generalized pustular psoriasis (GPP) is a rare and severe psoriasis subtype characterized by the rapid onset of coalescing sterile pustules over broad body areas and systemic inflammation. Data on its clinical course and outcomes in Taiwan are limited. We evaluated the clinical profile and outcomes of patients with GPP flares in Taiwan. METHODS: This retrospective analysis included adult patients with moderate-to-severe GPP flares occurring in January 2008-December 2021. Data were extracted from medical charts and electronic health records in the Chang Gung Research Database. Statistical analyses were performed using SAS for Windows (version 9.4). Multivariate Poisson regression models were built to investigate different predictors of GPP flare rate. RESULTS: Thirty-four patients with 81 moderate-to-severe GPP flares were identified. Of the 14 patients undergoing genetic analysis, 10 (71.4%) had an IL36RN mutation. Patients' mean age at the index GPP flare was 47.1 ± 16.5 years; 58.0% of the flares were severe, while 42.0% were moderate. Overall, 96.3% of GPP flares were treated with at least one systemic therapy, acitretin being the most prescribed (85.2%), followed by cyclosporine (45.7%) and methotrexate (18.5%). After treatment, the proportion of flares responding positively increased from 0% on day 2 to 6.2% by week 12. Patients were newly diagnosed with psoriasis (23.5%), hypertension (20.6%), diabetes mellitus (14.7%), psoriatic arthritis (2.9%), malignant tumor (8.8%), and depression/anxiety (2.9%) after enrollment. Complications occurring within 12 weeks of GPP flares included arthritis (25.9% of the flares), skin infection (8.6%), and other infections (2.5%). No fatalities were reported. In the multivariate model, former smokers, patients with hepatic disease, and patients with psoriatic arthritis had an increased GPP rate ratio (RR) of 13.33 (95% confidence interval, CI, 2.87-61.78), 14.08 (95% CI 3.04-65.29), and 34.84 (95% CI 4.77- 254.42), respectively. Contrarily, obese and rheumatoid arthritis patients had a lower GPP rate ratio of 0.21 (95% CI 0.08-0.54) and 0.07 (95% CI 0.006-0.78), respectively. CONCLUSIONS: Our findings highlight the complexity of GPP flare presentations and the need for individualized, patient-centered management approaches and continued research to improve affected individuals' care and outcomes.

Deep Deblurring in Teledermatology: Deep Learning Models Restore the Accuracy of Blurry Images' Classification.

Background: Blurry images in teledermatology and consultation increased the diagnostic difficulty for both deep learning models and physicians. We aim to determine the extent of restoration in diagnostic accuracy after blurry images are deblurred by deep learning models. Methods: We used 19,191 skin images from a public skin image dataset that includes 23 skin disease categories, 54 skin images from a public dataset of blurry skin images, and 53 blurry dermatology consultation photos in a medical center to compare the diagnosis accuracy of trained diagnostic deep learning models and subjective sharpness between blurry and deblurred images. We evaluated five different deblurring models, including models for motion blur, Gaussian blur, Bokeh blur, mixed slight blur, and mixed strong blur. Main Outcomes and Measures: Diagnostic accuracy was measured as sensitivity and precision of correct model prediction of the skin disease category. Sharpness rating was performed by board-certified dermatologists on a 4-point scale, with 4 being the highest image clarity. Results: The sensitivity of diagnostic models dropped 0.15 and 0.22 on slightly and strongly blurred images, respectively, and deblurring models restored 0.14 and 0.17 for each group. The sharpness ratings perceived by dermatologists improved from 1.87 to 2.51 after deblurring. Activation maps showed the focus of diagnostic models was compromised by the blurriness but was restored after deblurring. Conclusions: Deep learning models can restore the diagnostic accuracy of diagnostic models for blurry images and increase image sharpness perceived by dermatologists. The model can be incorporated into teledermatology to help the diagnosis of blurry images.

Reduced burden of Arsenic-Related cancers after water mitigation in Taiwan.

BACKGROUND: Epidemiological evidence has demonstrated an association between arsenic in drinking water and increased cancer incidence. This population-based study investigates the impact of a tap water supply system installation in Blackfoot disease-endemic regions of Taiwan on cancer incidence. METHODS: By using the Taiwan Cancer Registry dataset, we enrolled patients aged 40-84 diagnosed with arsenic-related cancers, including hepatocellular carcinoma, small and squamous cell lung cancer, Bowen's disease, basal and squamous cell skin cancer, urothelial bladder cancer, and upper tract urothelial carcinoma between 1995 and 2019. Random-effects age-period-cohort models were used to estimate the cancer incidence data, and a stabilized kriging method was employed to interpolate incidence rates to more precise spatiotemporal units. RESULTS: The results showed that the age-standardized incidence rates of all six types of studied cancers were consistently higher in Blackfoot disease-endemic areas than those in other areas from 1995 to 2019. However, the gap in incidence rates between Blackfoot disease-endemic areas and the remaining regions began to narrow approximately after the 1960 birth cohort when the tap water supply system installation commenced. For small and squamous cell lung cancer, Bowen's disease, and urothelial bladder cancer, the excess incidence rates sharply declined to null for those born after the year of arsenic mitigation. For upper tract urothelial carcinoma, the excess incidence rates decreased more gradually for those born after the year of arsenic mitigation. For hepatocellular carcinoma and basal and squamous cell skin cancer, the excess incidence rates remained constant. Spatiotemporal clusters of high incidence rates were identified in the core townships of Blackfoot disease-endemic areas. These clusters began to dissipate mainly after the 1960 birth cohort. CONCLUSION: Arsenic mitigation from drinking water in Taiwan is associated with a reduced burden of small and squamous cell lung cancers, Bowen's disease, urothelial bladder cancer, and upper tract urothelial carcinoma.

Association of Decreased Bone Density and Hyperlipidemia in a Taiwanese Older Adult Population.

Objective: This study aimed to determine if a combination of 2 abnormal lipid profiles revealed a stronger association with low bone mass than a single blood lipid abnormality alone. Methods: This study enrolled 1373 participants who had received a dual-energy x-ray absorptiometry scan from January 2016 to December 2016 in a medical center in southern Taiwan. Logistic regression was used to examine association between lipid profiles and osteopenia or osteoporosis after adjusting for covariates. Results: Compared to people with total cholesterol (TC) < 200 mg/dL, those with TC ≥ 240 mg/dL tended to have osteopenia or osteoporosis (OR 2.61; 95% CI, 1.44-4.71). Compared to people with low-density lipoprotein cholesterol (LDL-C) < 130 mg/dL, those with LDL-C ≥ 160 mg/dL tended to develop osteopenia or osteoporosis (OR 2.13; 95% CI, 1.21-3.74). The association of increased triglyceride and decreased bone mass was similar, although not statistically significant. Those with the combination of TG ≥ 200 mg/dL and TC ≥ 240 mg/dL had a stronger tendency to have osteopenia or osteoporosis (OR 3.51; 95% CI, 1.11-11.13) than people with only one blood lipid abnormality. Similarly, people with TG ≥ 200 mg/dL and LDL-C ≥ 160 mg/dL had a stronger tendency to have osteopenia or osteoporosis (OR 9.31; 95% CI, 1.15-75.42) than people with only one blood lipid abnormality, after adjustment for the same covariates. Conclusion: Blood levels of TC, LDL-C, and TG were associated with osteopenia or osteoporosis. Results indicate that individuals aged older than 50 years with abnormal lipid profiles should be urged to participate in a bone density survey to exclude osteopenia or osteoporosis.

Targeting antibody-mediated complement-independent mechanism in bullous pemphigoid with diacerein.

BACKGROUND: Bullous pemphigoid (BP) is an antibody-mediated blistering disease predominantly affecting the elderly. The pathogenesis involves both complement-dependent and complement-independent mechanisms. The therapeutic potential of targeting complement-independent mechanism has not yet been determined. The mainstay of treatment, corticosteroid, has many side effects, indicating the needs of better treatments. OBJECTIVE: We tempted to establish an in vitro model of BP which resembles complement-independent mechanism and to examine the therapeutic potential of a novel anti-inflammatory agent, diacerein. METHODS: Cultured HaCaT cells were treated with purified antibodies from BP patients, with or without diacerein to measure the cell interface presence of BP180, protein kinase C, and the production of proinflammatory cytokines. An open-label, randomized, phase 2 trial was conducted to compare topical diacerein and clobetasol ointments in patients with mild-to-moderate BP (NCT03286582). RESULTS: The reduced presentation of BP180 at cell interface after treating with BP autoantibodies was noticed in immunofluorescence and western blotting studies. The phenomenon was restored by diacerein. Diacerein also reduced the autoantibody-induced increase of pro-inflammatory cytokines. Reciprocal changes of BP180 and protein kinase C at the cell interface were found after treating with BP autoantibodies. This phenomenon was also reversed by diacerein in a dose-dependent manner. The phase 2 trial showed that topical diacerein reduced the clinical symptoms which were comparable to those of topical clobetasol. CONCLUSION: Diacerein inhibited BP autoantibody-induced reduction of BP180 and production of proinflammatory cytokines in vitro and showed therapeutic potential in patients with BP. It is a novel drug worthy of further investigations.

Bruton's Tyrosine Kinase Inhibitors with Distinct Binding Modes Reveal Differential Functional Impact on B-Cell Receptor Signaling.

Small molecule inhibitors of Bruton's tyrosine kinase (BTK) have been approved for the treatment of multiple B-cell malignancies and are being evaluated for autoimmune and inflammatory diseases. Various BTK inhibitors (BTKi) have distinct potencies, selectivity profiles, and binding modes within the ATP-binding site. On the basis of the latter feature, BTKis can be classified into those that occupy the back-pocket, H3 pocket, and the hinge region only. Hypothesizing that differing binding modes may have differential impact on the B-cell receptor (BCR) signaling pathway, we evaluated the activities of multiple BTKis in B-cell lymphoma models in vitro and in vivo. We demonstrated that, although all three types of BTKis potently inhibited BTK-Y223 autophosphorylation and phospholipase C gamma 2 (PLCγ2)-Y1217 transphosphorylation, hinge-only binders were defective in inhibiting BTK-mediated calcium mobilization upon BCR activation. In addition, PLCγ2 activation was effectively blocked by back-pocket and H3 pocket binders but not by hinge-only binders. Further investigation using TMD8 cells deficient in Rac family small GTPase 2 (RAC2) revealed that RAC2 functioned as a bypass mechanism, allowing for residual BCR signaling and PLCγ2 activation when BTK kinase activity was fully inhibited by the hinge-only binders. These data reveal a kinase activity-independent function of BTK, involving RAC2 in transducing BCR signaling events, and provide mechanistic rationale for the selection of clinical candidates for B-cell lymphoma indications.

Low-to-Moderate Arsenic Exposure and Urothelial Tract Cancers with a Long Latent Period of Follow-Up in an Arseniasis Area.

BACKGROUND: Arsenic exposure can cause adverse health effects. The effects of long-term low-to-moderate exposure and methylations remain unclear. OBJECTIVE: This study aims to examine the association between low-to-moderate arsenic exposure and urothelial tract cancers while considering the effects of methylation capacity. METHODS: In this study, 5,811 participants were recruited from an arseniasis area in Taiwan for inorganic arsenic metabolite analysis. This follow-up study was conducted between August 1995 and December 2017. We identified 85 urothelial tract cancers in these participants, including 49 bladder and 36 upper urothelial tract cancer cases. A Cox proportional hazards model was employed. RESULTS: The analyses revealed a significant association between concentrations of inorganic arsenic in water > 100 ug/L and bladder cancer occurrence, with a hazard ratio (HR) of 4.88 (95% CI 1.35-17.61). A monotonic trend was observed between concentrations of inorganic arsenic in water (from 0 to > 100 ug/L) and the incidence of urothelial tract cancer, including bladder cancer (p < 0.05) and upper urothelial tract cancers (p < 0.05). Participants with a lower primary methylation index or higher secondary methylation index had a prominent effect. CONCLUSIONS: Rigorous regulations and active interventions should be considered for populations with susceptible characteristics.

Surface-enhanced Raman scattering (SERS) by gold nanoparticle characterizes dermal thickening by collagen in bleomycin-treated skin ex vivo.

PURPOSE: Current skin imaging modalities, including optical, electron, and confocal microscopy, mostly require tissue fixations that could damage proteins and biological molecules. Live tissue or cell imaging such as ultrasonography and optical coherent microscope may not adequately measure the dynamic spectroscopical changes. Raman spectroscopy has been adopted for skin imaging in vivo, mostly for skin cancer imaging. However, whether the epidermal and dermal thickening in skin could be measured and distinguished by conventional Ramen spectroscopy or the surface-enhanced Raman scattering (SERS), a rapid and label-free method for noninvasive measurement remains unknown. METHODS: Human skin sections from patients of atopic dermatitis and keloid, which represent epidermal and dermal thickening, respectively, were measured by conventional Ramen spectroscopy. In mice, skin sections from imiquimod (IMQ)- and bleomycin (BLE)-treated mice, which reflect the epidermal and dermal thickening, respectively, were measured by SERS, that incorporates gold nanoparticles to generate surface plasma and enhance Raman signals. RESULTS: Conventional Ramen spectroscopy failed to consistently show the Raman shift in human samples among the different groups. SERS successfully revealed a prominent peak around 1300 cm-1 in the IMQ-treated skin; and two significant peaks around 1100 and 1300 cm-1 in BLE-treated group. Further quantitative analysis showed 1100 cm-1 peak was significantly accentuated in the BLE-treated skin than that in control skin. SERS identified in vitro a similar 1100 cm-1 peak in solutions of collagen, the major dermal biological molecules. CONCLUSION: SERS distinguishes the epidermal or dermal thickening in mouse skin with rapid and label-free measures. A prominent 1100 cm-1 SERS peak in the BLE-treated skin may result from collagen. SERS might help precision diagnosis in the future.

Liver-specific metastases as an independent prognostic factor in cancer patients receiving hospice care in hospital.

BACKGROUND: Survival prediction is important in cancer patients receiving hospice care. Palliative prognostic index (PPI) and palliative prognostic (PaP) scores have been used to predict survival in cancer patients. However, cancer primary site with metastatic status, enteral feeding tubes, Foley catheter, tracheostomy, and treatment interventions are not considered in aforementioned tools. The study aimed to investigate the cancer features and potential clinical factors other than PPI and PaP to predict patient survival. METHODS: We conducted a retrospective study for cancer patients admitted to a hospice ward between January 2021 and December 2021. We examined the correlation of PPI and PaP scores with survival time since hospice ward admission. Multiple linear regression was used to test the potential clinical factors other than PPI and PaP for predicting survival. RESULTS: A total of 160 patients were enrolled. The correlation coefficients for PPI and PaP scores with survival time were -0.305 and -0.352 (both p < 0.001), but the predictabilities were only marginal at 0.087 and 0.118, respectively. In multiple regression, liver metastasis was an independent poor prognostic factor as adjusted by PPI (ß = -8.495, p = 0.013) or PaP score (ß = -7.139, p = 0.034), while feeding gastrostomy or jejunostomy were found to prolong survival as adjusted by PPI (ß = 24.461, p < 0.001) or PaP score (ß = 27.419, p < 0.001). CONCLUSIONS: Association between PPI and PaP with patient survival in cancer patients at their terminal stages is low. The presence of liver metastases is a poor survival factor independent of PPI and PaP score.

Real-Time Fluorescence Measurement for Droplet Generation and Signal Detection in a Cylindrical Tube.

This study provides an approach for generating droplets in a cylindrical tube. This creative design utilizes a single tube to generate droplets for the emulsion polymerase chain reaction (PCR). We fabricated the multi-layered tube and detected samples in 1 mm microchannel length for the minimum disposable material used for droplet signal analysis. In this research, we verify the validity of the non-planar droplet chip with a single driving pump by experimentally analyzing the light intensity of the liquids during droplet processing in real time. Experimental observation shows that droplet diameter from 150 to 285 µm was obtained by the cylindrical tube with different dispersed liquid and gas pressure settings. Average size of droplets decreased by approximately 37% as the dispersed phase liquids change at the same flow pressure of 50 mbar. In this study, the effects of the laser site, 6-carboxyfluorescein (6-FAM) dye buffer, DNA reagent, and driving pressure are analyzed directly by the signal recorded during droplet generation in the cylindrical tube. Finally, we have developed a real-time detection method to count exon 19 deletion mutations of epidermal growth factor receptor (EGFR) in a droplet using a cylindrical tube. Two digital droplet PCR methods were compared in measuring the copy numbers of EGFR with the same target DNA concentration of 105 copies/µL.

Implantation Mycoses and Invasive Fungal Infections with Cutaneous Involvement in Tropical Taiwan: An 11-Year Retrospective Study of a Medical Center.

BACKGROUND: The rising incidence of implantation mycoses and invasive fungal infections prompts the need for studies describing the latest trends of these diseases; however, the literature remains scarce from tropical Asia in recent years. We shared our 11-year clinical experience at a tertiary center in Southern Taiwan to improve physicians' understanding of the diseases, which could help them assume appropriate management strategies. PATIENTS AND METHODS: Forty cases of pathology-proven cases of implantation mycoses and invasive fungal infections with cutaneous involvement were retrospectively reviewed. The epidemiology, patients' characteristics, initial clinical impressions, fungal species, management, and outcomes were compared and reported. RESULTS: Fonsecaea sp. was the most commonly (14%) involved species in implantation mycoses. The percentages of immunocompromised patients with implantation mycoses and invasive fungal infections were 26% and 60%, respectively. Additionally, 46% of patients with implantation mycoses had type 2 diabetes mellitus. The lesions were commonly mistaken for skin appendage tumors, skin cancers, and hyperkeratotic dermatoses. The prognosis was favorable for the implantation mycoses (83% showed clinical improvement) but bleak for the invasive fungal infections (100% mortality). CONCLUSIONS: Presentations of implantation mycoses and invasive fungal infections vary widely, and immunocompromised status and diabetes mellitus are important associated factors.

Gasdermin A Is Required for Epidermal Cornification during Skin Barrier Regeneration and in an Atopic Dermatitis-Like Model.

Atopic dermatitis is featured with impaired skin barrier. The stratum corneum and the intercellular tight junctions constitute the permeability barrier, which is essential to protect water loss in the host and prevent pathogen entry. The epidermal barrier is constantly renewed by differentiating keratinocytes through cornification, during which autophagy contributes to elimination of organelles and nucleus. The human GSDMA and its mouse homologs Gsdma1-3 are expressed in the suprabasal epidermis. Although a pyroptotic role of GSDMA/Gsdma1 in host defense against Streptococcus pyogenes has been reported, the physiological function of Gsdma1/a2/a3 in epidermal homeostasis remains elusive. Here, through repeated epidermal barrier disruption, we found that tight junction formation and stratum corneum maturation were defective in the Gsdma1/a3-deficient epidermis. Using comparative gene profiling analysis, mitochondrial respiration measurement, and in vivo tracing of mitophagy, our data indicate that Gsdma1/a3 activation leads to mitochondrial dysfunction and subsequently facilitates mitochondrial turnover and epidermal cornification. In calcipotriol (MC903)-induced atopic dermatitis-like animal model, we showed that Gsdma1/a3-deficiency selectively enhanced the T helper type 2 response. Remarkably, the GSDMA expression is reduced in the epidermis of patients with atopic dermatitis compared with that of normal individuals. Gsdma1/a3-deficiency might be involved in atopic dermatitis pathogenesis, likely through GSDMA-mediated epidermal differentiation and cornification.

PD-L1 Enhanced by cis-Urocanic Acid on Langerhans Cells Inhibits Vγ4+ γδT17 Cells in Imiquimod-Induced Skin Inflammation.

Psoriasis is an IL-23/IL-17-mediated inflammatory autoimmune dermatosis, and UVB may contribute to immunosuppression and ameliorate associated symptoms. One of the pathophysiology underlying UVB therapy is the production of cis-urocanic acid (cis-UCA) by keratinocytes. However, the detailed mechanism is yet to be fully understood. In this study, we found FLG expression and serum cis-UCA levels were significantly lower in patients with psoriasis than in healthy controls. We also noted that cis-UCA application inhibited psoriasiform inflammation through the reduction of Vγ4+ γδT17 cells in murine skin and draining lymph nodes. Meanwhile, CCR6 was downregulated on γδT17 cells, which would suppress the inflammatory reaction at a distal skin site. We revealed that the 5-hydroxytryptamine receptor 2A, the known cis-UCA receptor, was highly expressed on Langerhans cells in the skin. cis-UCA also inhibited IL-23 expression and induced PD-L1 on Langerhans cells, leading to the attenuated proliferation and migration of γδT-cells. Compared to the isotype control, α-PD-L1 treatment in vivo could reverse the antipsoriatic effects of cis-UCA. PD-L1 expression on Langerhans cells was sustained through the cis-UCA-induced mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. These findings uncover the cis-UCA-induced PD-L1-mediated immunosuppression on Langerhans cells, which facilitates the resolution of inflammatory dermatoses.

A Review of the Challenges and Nuances in Treating Rosacea in Asian Skin Types Using Cleansers and Moisturizers as Adjuncts.

BACKGROUND: Rosacea is primarily an inflammatory disease of facial skin associated with impaired skin barrier function. While it is commonly thought of as a Caucasian person's disease, it is likely underdiagnosed in people of color, including Asians, leading to missed and delayed diagnoses and increased morbidity. The purpose of this review is to highlight literature on rosacea in Asian people and the role of non-prescription skincare in managing rosacea. METHODS: Four dermatologists (the panel) completed pre-meeting surveys and participated in a web meeting to discuss the role of skin care in treating rosacea in the Asia Pacific (APAC) region. The survey results were summarized, then presented during the virtual meeting. These survey results and relevant papers identified through a literature review were then discussed. This review shows the fruit of these discussions, as well as the advisors' expert opinions and experiences. RESULTS: The panel crafted 5 consensus statements regarding the role of skin care in the treatment of rosacea in the APAC region. The most common forms of rosacea seen by the advisors are mostly erythematous and papulopustular. Among the panel, doxycycline is the most popular treatment for papulopustular rosacea. The panel prioritize gentleness when choosing skincare products for patients with rosacea. CONCLUSIONS: In Asian patients with rosacea, adjunctive skincare is an important part of treatment, maintenance, and prescription treatment. Given the highly sensitive skin of certain Asian patients with rosacea, avoiding potentially irritating substances is crucial. J Drugs Dermatol. 2023;22(1):45-53. doi:10.36849/JDD.7021.

Taiwanese dermatological association (TDA) consensus for the management of pemphigus.

Pemphigus is an uncommon but life-threatening autoimmune blistering disease characterized by the presence of antibodies against desmogleins. Without effective treatment, pemphigus can result in significant morbidity and mortality. Existing consensus statements on pemphigus management from international medical groups provide varying guidelines, especially on treatment. Thus, on January 4, 2020, a panel of seven dermatology experts from the Taiwanese Dermatological Association (TDA) and one rheumatology expert convened to develop a consensus for the management of pemphigus. These experts with extensive experience in pemphigus management were recommended by their respective teaching hospitals and primary care clinics in Taiwan and by the TDA. The meeting reviewed the available consensus statements from international dermatology groups, including the European Dermatology Forum (EDF), the European Academy of Dermatology and Venereology (EADV), and the International Bullous Diseases Consensus Group. Using these guidelines as a basis for discussion and consensus formulation, these experts formulated their consensus statement that provides practical, concise but comprehensive recommendations as to the diagnosis, treatment, and monitoring of pemphigus patients in Taiwan. This consensus serves as a clinical reference for physicians for the management of pemphigus in Taiwan or wherever it may be applicable.

Acute radiation dermatitis among patients with nasopharyngeal carcinoma treated with proton beam therapy: Prognostic factors and treatment outcomes.

A high incidence of severe acute radiation dermatitis (ARD) has been reported for cancer patients treated by proton beam therapy (PBT). This observational study investigated the prognostic factors and treatment outcomes of ARD among patients with nasopharyngeal carcinoma (NPC) treated with PBT. Fifty-seven patients with newly diagnosed NPC and treated with PBT were enrolled. ARD was recorded weekly based on the criteria of Common Terminology Criteria for Adverse Events version 4.0 at treatment visits (1st to 7th weeks) and 1 week (8th week) and 1 month (11th week) after the completion of PBT. The maximum ARD grade was 1, 2, and 3 in 26 (45.6%), 24 (42.1%), and 7 (12.3%) of the patients, respectively. The peak incidence of grade 2 and 3 ARD was observed during the period of the 6th to 8th weeks. Treatment of ARD included topical corticosteroid alone in 24 (42.1%) patients, topical corticosteroid plus silver sulfadiazine in 33 (57.9%) patients, and non-adhering silicone dressing to cover severe skin wound area in 25 (43.8%) patients. In the 11th week, most grade 2 and 3 ARD had disappeared and 93.0% of the patients had ARD of grade 1 or lower. In the binary logistic regression model, we identified habitual smoking (odds ratio [OR]: 5.2, 95% confidence interval [CI]: 1.3-18.8, P = .012) and N2 to N3 nodal status (OR: 4.9, 95% CI: 1.6-15.4, P = .006) as independent predictors of grade 2 and 3 ARD. The results show ARD is a major concern for patients with NPC treated with PBT, especially those with habitual smoking or advanced nodal status. Topical corticosteroid, silver sulfadiazine, and non-adhering silicone dressing are effective for treating ARD induced by PBT.

TIMP3 Gene Polymorphisms of -1296 T > C and -915 A > G Increase the Susceptibility to Arsenic-Induced Skin Cancer: A Cohort Study and In Silico Analysis of Mutation Impacts

Long-term exposure to arsenic may induce several human cancers, including non-melanoma skin cancer. The tissue inhibitor of metalloproteinase (TIMP)-3, encoded by the TIMP3 gene, may inhibit tumor growth, invasion, and metastasis of several cancer types. In this study, we aimed to investigate effects of the TIMP3 -1296 T > C (rs9619311) and -915 A > G (rs2234921) single-nucleotide polymorphisms (SNPs) on skin cancer risk in an arsenic-exposed population, and to evaluate the influence of allele-specific changes by an in silico analysis. In total, 1078 study participants were followed up for a median of 15 years for newly diagnosed skin cancer. New cases were identified through linkage to the National Cancer Registry of Taiwan. A Cox regression analysis was used to evaluate the effects of TIMP3 variants. Transcription factor (TF) profiling of binding sites of allele-specific changes in SNPs was conducted using the JASPAR scan tool. We observed borderline associations between TIMP3 genotypes and skin cancer risk. However, when combined with high arsenic exposure levels, the rs9619311 C allele, rs2234921 G allele, or C-G haplotype groups exhibited a greater risk of developing skin cancer compared to the respective common homozygous genotype group. The in silico analysis revealed several TF motifs located at or flanking the two SNP sites. We validated that the C allele of rs9619311 attenuated the binding affinity of BACH2, MEIS2, NFE2L2, and PBX2 to the TIMP3 promoter, and that the G allele of rs2234921 reduced the affinity of E2F8 and RUNX1 to bind to the promoter. Our findings suggest significant modifications of the effect of the association between arsenic exposure and skin cancer risk by the TIMP3 rs9619311 and rs2234921 variants. The predicted TFs and their differential binding affinities to the TIMP3 promoter provide insights into how TIMP3 interacts with arsenic through TFs in skin cancer formation.