Mass Specthoscope: A Hand-held Extendable Probe for Localized Noninvasive Sampling of Skin Volatome for Online Analysis.

Human skin emits a unique set of volatile organic compounds (VOCs). These VOCs can be probed in order to obtain physiological information about the individuals. However, extracting the VOCs that emanate from human skin for analysis is troublesome and time-consuming. Therefore, we have developed "Mass Specthoscope"─a convenient tool for rapid sampling and detecting VOCs emitted by human skin. The hand-held probe with a pressurized tip and wireless button enables sampling VOCs from surfaces and their transfer to the atmospheric pressure chemical ionization source of quadrupole time-of-flight mass spectrometer. The system was characterized using chemical standards (acetone, benzaldehyde, sulcatone, α-pinene, and decanal). The limits of detection are in the range from 2.25 × 10-5 to 3.79 × 10-5 mol m-2. The system was initially tested by detecting VOCs emanating from porcine skin spiked with VOCs as well as unspiked fresh and spoiled ham. In the main test, the skin of nine healthy participants was probed with the Mass Specthoscope. The sampling regions included the armpit, forearm, and forehead. Numerous skin-related VOC signals were detected. In the final test, one participant ingested a fenugreek drink, and the participant's skin surface was probed using the Mass Specthoscope hourly during the 8 h period. The result revealed a gradual release of fenugreek-related VOCs from the skin. We believe that this analytical approach has the potential to be used in metabolomic studies and following further identification of disease biomarkers─also in noninvasive diagnostics.

Lifetime risk, life expectancy, loss-of-life expectancy and lifetime healthcare expenditure for Stevens-Johnson syndrome/toxic epidermal necrolysis in Taiwan: follow-up of a nationwide cohort from 2008 to 2019.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) not only cause acute, devastating mucocutaneous reactions but also have long-lasting implications on survivors' lives. OBJECTIVES: To quantify the lifetime burden of SJS/TEN. METHODS: The cumulative incidence rate (CIR), life expectancy (LE), loss-of-life expectancy (LoLE) and lifetime healthcare expenditure (HE) for SJS/TEN were estimated over the period from 2008 to 2019 using data from the National Health Insurance Research Database of Taiwan and life tables of vital statistics. RESULTS: In this nationwide cohort of 6552 incident SJS/TEN cases, a trend towards a decrease in the CIR was observed between 2008 and 2019. Compared with the general population, patients with SJS/TEN experience a tremendous loss of 9.43 (1.06) [mean (SEM)] years of LE after diagnosis of SJS/TEN. Male patients with SJS/TEN had higher LoLE [10.74 (1.22) vs. 7.69 (1.43) years] and annual HE than females. Younger age at diagnosis of SJS/TEN was associated with longer LE but greater LoLE and higher lifetime HE. Patients with intensive care unit admission on diagnosis, malignancy, diabetes mellitus, end-stage renal disease and SJS/TEN-associated sequelae experienced substantially greater LoLE and HE per life year. CONCLUSIONS: Patients with SJS/TEN suffer substantial loss-of-LE and HE, particularly young patients, compared with the general population. These data provide a reference estimate of the lifetime burden of SJS/TEN to help health authorities evaluate the cost-effectiveness of future preventive and treatment strategies to minimize the burden of SJS/TEN.

Predictors of time to relapse following ustekinumab withdrawal in patients with psoriasis who had responded to therapy: An 8-year multicenter study.

BACKGROUND: Data on predictors and time to relapse in patients with psoriasis who discontinue therapy in a real-world setting are scarce. OBJECTIVE: To investigate predictors of relapse after withdrawal of ustekinumab in patients with psoriasis. METHOD: This study screened 500 patients with psoriasis who received ustekinumab (669 treatment episodes) between 2011 and 2018. Overall, 202 patients (accounting for 304 treatment episodes) who had responded to therapy and were withdrawn from ustekinumab treatment were included. RESULTS: The cumulative probabilities of being relapse-free at 6, 12, 18, 24, and 36 months after withdrawal from ustekinumab treatment were 49.3%, 12.6%, 5.3%, 4.7%, and 1.6%, respectively. Multivariate regression analyses with a generalized estimating equation showed that after adjustments, biologic-naive status, maximum improvement in Psoriasis Area and Severity Index during ustekinumab treatment, time to achieve a 50% improvement in baseline Psoriasis Area and Severity Index score after initiation of ustekinumab, family history of psoriasis, chronic kidney disease, and immunosuppressant use while not taking ustekinumab were significant predictors of time to relapse following discontinuation of ustekinumab. LIMITATION: Nonrandomized allocation of duration of treatment and follow-up. CONCLUSION: Given the high rates of relapse, withdrawal of ustekinumab from patients with well-controlled psoriasis cannot be recommended.

2022 Taiwanese Dermatological Association (TDA), Taiwanese Association for Psoriasis and Skin Immunology (TAPSI), and Taiwan Society of cardiology (TSOC) joint consensus recommendations for the management of psoriatic disease with attention to cardiovascular comorbidities.

Psoriatic disease is a chronic inflammatory disorder with skin and joint manifestations. Due to the persistent inflammatory state exhibited by patients with psoriasis, multiple systemic comorbidities occur more frequently in patients with psoriasis than in the general population, and the risk of cardiovascular (CV) diseases is significantly increased. As the pathophysiology of psoriatic disease is becoming better understood, the sharing of underlying pathogenic mechanisms between psoriatic and CV diseases is becoming increasingly apparent. Consequently, careful attention to CV comorbidities that already exist or may potentially develop is needed in the management of patients with psoriasis, particularly in the screening and primary prevention of CV disease and in treatment selection due to potential drug-drug and drug-disease interactions. Furthermore, as the use of effective biologic therapy and more aggressive oral systemic treatment for psoriatic disease is increasing, consideration of the potential positive and negative effects of oral and biologic treatment on CV disease is warranted. To improve outcomes and quality of care for patients with psoriasis, the Taiwanese Dermatological Association, the Taiwanese Association for Psoriasis and Skin Immunology, and the Taiwan Society of Cardiology established a Task Force of 20 clinicians from the fields of dermatology, cardiology, and rheumatology to jointly develop consensus expert recommendations for the management of patients with psoriatic disease with attention to CV comorbidities.

Enhancing Cementitious Composites with Functionalized Graphene Oxide-Based Materials: Surface Chemistry and Mechanisms.

Graphene oxide-based materials (GOBMs) have been widely explored as nano-reinforcements in cementitious composites due to their unique properties. Oxygen-containing functional groups in GOBMs are crucial for enhancing the microstructure of cementitious composites. A better comprehension of their surface chemistry and mechanisms is required to advance the potential applications in cementitious composites of functionalized GOBMs. However, the mechanism by which the oxygen-containing functional groups enhance the response of cementitious composites is still unclear, and controlling the surface chemistry of GOBMs is currently constrained. This review aims to investigate the reactions and mechanisms for functionalized GOBMs as additives incorporated in cement composites. A variety of GOBMs, including graphene oxide (GO), hydroxylated graphene (HO-G), edge-carboxylated graphene (ECG), edge-oxidized graphene oxide (EOGO), reduced graphene oxide (rGO), and GO/silane composite, are discussed with regard to their oxygen functional groups and interactions with the cement microstructure. This review provides insight into the potential benefits of using GOBMs as nano-reinforcements in cementitious composites. A better understanding of the surface chemistry and mechanisms of GOBMs will enable the development of more effective functionalization strategies and open up new possibilities for the design of high-performance cementitious composites.

Depilatory laser miniaturizes hair by inducing bystander dermal papilla cell necrosis through thermal diffusion.

OBJECTIVES: Depilatory laser targeting melanin has been widely applied for the treatment of hypertrichosis. Both selective photothermolysis and thermal diffusion have been proposed for its effect, but the exact mechanism of permanent hair reduction remains unclear. In this study, we explore the role of thermal diffusion in depilatory laser-induced permanent hair loss and determine whether nonpigmented cells are injured by thermal diffusion. MATERIALS AND METHODS: C57BL/6 mice in anagen and telogen were treated with alexandrite laser (wavelength 755 nm, pulse duration 3 milliseconds, fluence 12 J/cm2 , spot size 12 mm), respectively. Histological analysis, terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and transmission electron microscopic imaging were employed to evaluate the injury to hair follicle (HF) cells. The proliferation status of HF cells was examined by 5-bromo-2'-deoxyuridine pulse labeling. The number of HF stem cells was quantified by fluorescence-activated cell sorting. The size of the regenerated hair was determined by measuring its length and width. RESULTS: We found that irradiating C57BL/6 mice in anagen with alexandrite laser led to hair miniaturization in the next anagen. In addition to thermal disruption of melanin-containing cells in the precortex region, we also detected necrosis of the adjacent nonpigmented dermal papilla cells due to thermal diffusion. Dermal papilla cells decreased by 24% after laser injury, while the number of bulge stem cells remained unchanged. When the laser was delivered to telogen HFs where no melanin was present adjacent to the dermal papilla, thermal necrosis and cell reduction were not detected in the dermal papilla and no hair miniaturization was observed. CONCLUSION: Our results suggest that depilatory laser miniaturizes hair by inducing thermal necrosis of dermal papilla cells due to secondary thermal diffusion from melanin-containing precortex cells in the anagen hair bulbs.

Severity of periodontitis and salivary interleukin-1ß are associated with psoriasis involvement.

BACKGROUND/PURPOSE: Both psoriasis and periodontal diseases are characterized by an exaggerated immune response to the microbiota residing on epithelial surfaces. This study aimed to explore the associations between the severity of psoriasis and periodontal destruction in patients with psoriasis. METHODS: Thirty-three patients diagnosed with psoriasis were referred from the dermatology clinic of National Taiwan University Hospital. Full-mouth periodontal examination was performed and saliva was collected after patients signed informed consent forms. The Psoriasis Area Severity Index (PASI) as well as clinical periodontal parameters including probing depth (PD), plaque index (PI), gingival index (GI), and clinical attachment level (CAL) were evaluated. Salivary cytokines including interleukin (IL)-1ß, IL-12, IL-17, interferon-γ, and tumor necrosis factor (TNF)-α were tested with the Luminex Bio-Plex system. Anti-inflammatory medication, tobacco use, and underlying comorbidities were included in the analysis. RESULTS: Baseline PASI was significantly associated with PI. PASI at follow-up was positively correlated with CAL ≥ 4 mm (%) and saliva IL-1ß levels. Psoriasis patients who used non-steroidal anti-inflammatory drugs or topical steroids had significantly lower GI, PD ≥ 4 mm (%), and saliva IL-1ß and TNF-α levels. Moreover, a history of tobacco use was associated with higher PD ≥ 4 mm (%). CONCLUSION: PI, CAL, and salivary IL-1ß were associated with PASI. Periodontal severity was associated with psoriasis involvement. Periodontal inflammation in psoriasis may be modified by anti-inflammatory medication and tobacco use. Additional large-scale longitudinal and mechanistic studies are needed.

Predictors of hepatitis B and C virus reactivation in patients with psoriasis treated with biologic agents: a 9-year multicenter cohort study.

BACKGROUND: The increasing use of biologics is accompanied by a risk of hepatitis B (HBV) and C virus (HCV) reactivation. OBJECTIVE: To determine the predictors of HBV and HCV reactivation in patients with psoriasis receiving biologics. METHODS: This study screened 2060 patients with psoriasis (3562 treatment episodes) who were taking biologics from 2009 to 2018. There were 359 patients with psoriasis with HBV (561 treatment episodes) and 61 with HCV infection (112 treatment episodes). RESULTS: During 8809 and 1522 person-months of follow-up, 88 treatment episodes for HBV involved HBV reactivation, and 14 episodes of HCV involved reactivation. The reactivation rate was significantly higher in treatment episodes of chronic HBV infection than in that of occult HBV (34.3% vs 3.2%, P = .001) and resolved HBV (34.3% vs 5.0%, P < .001). The multivariate analysis revealed that being hepatitis B surface antigen seropositive, being hepatitis B e-antigen seropositive, and tumor necrosis factor-α-inhibitor therapy were risk factors for HBV reactivation, whereas antiviral prophylaxis was effective in reducing the risk of HBV reactivation. No predictors were significantly associated with HCV reactivation. LIMITATIONS: Observational design and a lack of a comparison group. CONCLUSION: Patients with psoriasis on biologics have a risk of HBV and HCV reactivations, particularly those who are seropositive for hepatitis B surface antigen and hepatitis B e-antigen and undergoing tumor necrosis factor-α-inhibitor therapy.

Recommendations for psoriatic arthritis management: A joint position paper of the Taiwan Rheumatology Association and the Taiwanese Association for Psoriasis and Skin Immunology.

In Taiwan, the incidence and prevalence of psoriatic arthritis (PsA) have risen significantly in recent years. Moreover, data from the Taiwan National Health Insurance Research Database (NHIRD) show that more than 85% of PsA patients are treated with just non-steroidal anti-inflammatory drugs (NSAIDs) and/or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Taiwanese clinicians have also expressed concerns regarding uncertainties in the diagnosis of PsA and the delayed, interrupted, and/or tapered use of biologics, as well as differences in therapeutic preferences between and within dermatologists and rheumatologists. To address these issues, the Taiwan Rheumatology Association and the Taiwanese Association for Psoriasis and Skin Immunology jointly convened a committee of 28 clinicians from the fields of rheumatology, dermatology, orthopedics, and rehabilitation, to develop evidence-based consensus recommendations for the practical management of PsA in Taiwan. A total of six overarching principles and 13 recommendations were developed and approved, as well as a treatment algorithm with four separate tracks for axial PsA, peripheral PsA, enthesitis, and dactylitis. Psoriasis (PsO) management was not discussed here, as the Taiwanese Dermatological Association has recently published a comprehensive consensus statement on the management of PsO. Together, these recommendations provide an up-to-date, evidence-based framework for PsA care in Taiwan.

Safety Profile of Secukinumab in Treatment of Patients with Psoriasis and Concurrent Hepatitis B or C: A Multicentric Prospective Cohort Study.

Safety data for secukinumab in patients with psoriasis and viral hepatitis are lacking. The aim of this study is to investigate the risk of reactivation of hepatitis B virus (HBV)/hepatitis C virus (HCV) in patients with psoriasis who are receiving secukinumab therapy. This multicentre study screened 284 patients with psoriasis with available HBV and HCV serological data and 63 patients with concurrent HBV/HCV infection were enrolled. In the absence of antiviral prophylaxis, 7 of 46 (15.2%) patients with HBV exhibited HBV reactivation during secukinumab therapy. The risk of reactivation was significantly higher in HBsAg-positive patients, compared with HBsAg-negative/HBcAb-positive patients (24.0% vs. 4.17%, p = 0.047). One of 14 (7.1%) HCV patients showed enhanced replication of HCV with hepatitis. No virus reactivation occurred in patients receiving antiviral prophylaxis. HBsAg-positive and HBsAg-negative/HBcAb-positive psoriasis patients can develop virus reactivation during secukinumab therapy, thus necessitating close monitoring of viral load and considering an antiviral prophylaxis for all HBsAg-positive patients with psoriasis.

Efficacy and Safety of a Low-Level Light Therapy for Androgenetic Alopecia: A 24-Week, Randomized, Double-Blind, Self-Comparison, Sham Device-Controlled Trial.

BACKGROUND: Previous studies have reported the benefits of low-level/light laser therapy (LLLT) for the promotion of hair regrowth. However, the effectiveness of LLLT for the treatment of androgenetic alopecia (AGA) is still a topic of debate. OBJECTIVE: To investigate the efficacy and safety of LLLT on hair regrowth in patients with AGA. METHODS: This 24-week, randomized, double-blind, self-comparison, sham device-controlled trial enrolled 100 patients with AGA. All participants were randomly assigned to receive the investigational LLLT on one side of the head and sham light treatment on the contralateral side, 3 times weekly for 30 minutes each, over a 24-week period. Global scalp photography, phototrichogram assessment, the investigator's global assessment (IGA) of hair regrowth, and the subject's assessment of the treatment satisfaction were used for evaluation. RESULTS: After 24 weeks of treatment, the LLLT-treated scalp exhibited significantly greater hair coverage than the sham light-treated side (14.2% vs. 11.8%, p < .001). A significantly greater improvement from baseline in hair thickness, hair count, hair coverage, and IGA were also observed in the LLLT-treated side than in the sham light-treated side at the 12- and 24-week visits. No serious adverse events were observed. CONCLUSION: The use of LLLT might be an effective, safe, well-tolerated treatment for AGA.

Noninvasive Glucose Monitoring with a Contact Lens and Smartphone.

Diabetes has become a chronic metabolic disorder, and the growing diabetes population makes medical care more important. We investigated using a portable and noninvasive contact lens as an ideal sensor for diabetes patients whose tear fluid contains glucose. The key feature is the reversible covalent interaction between boronic acid and glucose, which can provide a noninvasive glucose sensor for diabetes patients. We present a phenylboronic acid (PBA)-based HEMA contact lens that exhibits a reversible swelling/shrinking effect to change its thickness. The difference in thickness can be detected in a picture taken with a smartphone and analyzed using software. Our novel technique offers the following capabilities: (i) non-enzymatic and continuous glucose detection with the contact lens; (ii) no need for an embedded circuit and power source for the glucose sensor; and (iii) the use of a smartphone to detect the change in thickness of the contact lens with no need for additional photo-sensors. This technique is promising for a noninvasive measurement of the glucose level and simple implementation of glucose sensing with a smartphone.

Probing Skin for Metabolites and Topical Drugs with Hydrogel Micropatches.

Sampling the skin surface is a convenient way to obtain biological specimens bearing clinically relevant information. Hydrogel micropatches enable noninvasive collection of skin excretion specimens, which can subsequently be subjected to rapid mass spectrometric analysis providing insights into the skin metabolome.

Increased risk of avascular necrosis in patients with psoriatic disease: A nationwide population-based matched cohort study.

BACKGROUND: Avascular necrosis (AVN) and psoriasis have some pathogenic mechanisms and associated conditions in common. OBJECTIVE: To examine the association between psoriasis and AVN. METHODS: This study used data from the Taiwan National Health Insurance Research Database for the period 2004-2006 and identified 28,268 patients with psoriasis, who were then matched for age and sex with 113,072 controls without psoriasis from the Taiwan Longitudinal Health Insurance Database 2000. Multivariate Cox proportional hazards models were used for the analysis. RESULTS: The unadjusted risk of AVN was significantly higher for patients with psoriasis than for controls (hazard ratio [HR] 2.29) and remained significant after adjustment for other risk factors (adjusted HR 1.96; 95% confidence interval 1.62-2.38). The risk for AVN increased in relation to psoriasis severity and was higher for patients with psoriasis and arthritis than for patients without arthritis. The adjusted HRs were higher for male patients than for female patients and for patients younger than 30 years compared with older patients. LIMITATIONS: We lacked information on daily tobacco use, alcohol consumption, and physical activity. CONCLUSION: The risk for AVN increased with the disease severity of psoriasis.

Hydrogel Micropatch and Mass Spectrometry-Assisted Screening for Psoriasis-Related Skin Metabolites.

BACKGROUND: Psoriasis is a chronic, immune-mediated inflammatory skin disease. Screening skin metabolites could unravel the pathophysiology of psoriasis and provide new diagnostic approaches. Due to the lack of suitable methodologies for collecting scarce amounts of skin excretions, the psoriatic skin metabolome has not been extensively studied. METHODS: We implemented biocompatible hydrogel micropatch probes combined with mass spectrometry to investigate the skin metabolome. This noninvasive approach was applied to examine samples obtained from 100 psoriatic patients and 100 healthy individuals. We also developed custom data treatment tools and used chemometric and statistical tools to reveal the alterations in the skin metabolome caused by psoriasis. RESULTS: The proposed methodology enabled us to capture alterations in the composition of skin excretions caused by the disease. Chemometric analysis revealed the major differences between the metabolomes of psoriatic skin and healthy skin. Several polar metabolites were positively (choline and glutamic acid) or negatively (urocanic acid and citrulline) correlated with the plaque severity scores. The amounts of these metabolites in the excretions sampled from psoriatic skin were significantly different (P < 0.001) from the excretions sampled from healthy skin. The role of biological variability and various confounding factors, which might affect the skin metabolome, was also investigated. CONCLUSIONS: Sampling lesional and healthy skin with the hydrogel micropatch probes and subsequent direct mass spectrometry scanning provided information on the alterations in the skin metabolome caused by psoriasis, increasing the understanding of the complex pathophysiology of this disease.

Increased risk of aortic aneurysm (AA) in relation to the severity of psoriasis: A national population-based matched-cohort study.

BACKGROUND: Inflammation of systemic and vascular tissues besides the skin in psoriasis is associated with cardiovascular morbidity and mortality. OBJECTIVE: We sought to investigate whether or not patients with psoriasis have an increased risk of aortic aneurysm (AA). METHODS: This population-based cohort study identified 34,301 patients with psoriasis in the Taiwan National Health Insurance Research Database during 2004 to 2006, who were matched for age and sex with 137,204 control subjects without psoriasis from the Taiwan Longitudinal Health Insurance Database 2000. Each individual was individually followed up for 5 years to identify those who subsequently developed AA. RESULTS: After adjusting for medical history and medication use, patients with psoriasis were at increased overall risk of AA (adjusted hazard ratio [HR] 1.80; 95% confidence interval 1.25-2.61). The risk for AA increased with the severity of psoriasis. The adjusted HRs were higher for male than female patients (adjusted HR 1.84 vs 1.56), and for patients younger than 50 years versus older patients (adjusted HR 2.81 vs 1.64). LIMITATIONS: There is a lack of information regarding patients' Psoriasis Area and Severity Index score, daily tobacco use, or alcohol consumption. CONCLUSION: Patients with psoriasis are predisposed to developing AA: this risk increases with psoriasis severity and is independent of established cardiovascular risk factors.

Increased risk of arrhythmia in patients with psoriatic disease: A nationwide population-based matched cohort study.

BACKGROUND: Psoriasis is associated with cardiovascular morbidity and mortality. However, the association between psoriasis and arrhythmia has not been adequately studied. OBJECTIVE: We sought to investigate whether patients with psoriasis have an increased risk of arrhythmia. METHODS: This population-based cohort study identified 40,637 patients with psoriasis and 162,548 subjects without psoriasis matched by age, sex, history of coronary artery disease, hypertension, and diabetes in the Taiwan National Health Insurance Research Database during 2004 through 2006. RESULTS: After adjusting for medical history and medication use, patients with psoriasis were at increased risk of overall arrhythmia (adjusted hazard ratio [aHR] 1.34; 95% confidence interval [CI] 1.29-1.39). The risks of arrhythmia were higher in all subgroups, including patients with severe (aHR 1.25; 95% CI 1.12-1.39) and mild (aHR 1.35; 95% CI 1.30-1.41) psoriasis, and in patients with (aHR 1.46; 95% CI 1.22-1.74) and without (aHR 1.33; 95% CI 1.28-1.39) psoriatic arthritis. LIMITATIONS: The National Health Insurance Research Database did not contain information regarding Psoriasis Area and Severity Index, cigarette smoking, or alcohol consumption. CONCLUSION: Patients with psoriasis were at higher risk of developing arrhythmia, particularly for those with psoriatic arthritis, independent of traditional cardiovascular risk factors.