Self-Supervised Learning for Feature Extraction from Glomerular Images and Disease Classification with Minimal Annotations.

BACKGROUND: Deep learning has great potential in digital kidney pathology. However, its effectiveness depends heavily on the availability of extensively labeled datasets, which are often limited due to the specialized knowledge and time required for their creation. This limitation hinders the widespread application of deep learning for the analysis of kidney biopsy images. METHODS: We applied self-distillation with no labels (DINO), a self-supervised learning method, to a dataset of 10,423 glomerular images obtained from 384 PAS-stained kidney biopsy slides. Glomerular features extracted from the DINO-pretrained backbone were visualized using principal component analysis (PCA). We then performed classification tasks by adding either k-nearest neighbor (kNN) classifiers or linear head layers to the DINO-pretrained or ImageNet-pretrained backbones. These models were trained on our labeled classification dataset. Performance was evaluated using metrics such as the area under the receiver operating characteristic curve (ROC-AUC). The classification tasks encompassed four disease categories (minimal change disease, mesangial proliferative glomerulonephritis, membranous nephropathy, and diabetic nephropathy) as well as clinical parameters such as hypertension, proteinuria, and hematuria. RESULTS: PCA visualization revealed distinct principal components corresponding to different glomerular structures, demonstrating the capability of the DINO-pretrained backbone to capture morphological features. In disease classification, the DINO-pretrained transferred model (ROC-AUC = 0.93) outperformed the ImageNet-pretrained fine-tuned model (ROC-AUC = 0.89). When the labeled data were limited, the ImageNet-pretrained fine-tuned model's ROC-AUC dropped to 0.76 (95% confidence interval [CI], 0.72-0.80), whereas the DINO-pretrained transferred model maintained superior performance (ROC-AUC 0.88, 95% CI 0.86-0.90). The DINO-pretrained transferred model also exhibited higher AUCs for the classification of several clinical parameters. External validation using two independent datasets confirmed DINO pre-training's superiority, particularly when labeled data were limited. CONCLUSIONS: The application of DINO to unlabeled PAS-stained glomerular images facilitated the extraction of histological features that can be effectively utilized for disease classification.

Deep Learning Analysis of Histologic Images from Intestinal Specimen Reveals Adipocyte Shrinkage and Mast Cell Infiltration to Predict Postoperative Crohn Disease.

Most patients with Crohn disease (CD), a chronic inflammatory gastrointestinal disease, experience recurrence despite treatment, including surgical resection. However, methods for predicting recurrence remain unclear. This study aimed to predict postoperative recurrence of CD by computational analysis of histopathologic images and to extract histologic characteristics associated with recurrence. A total of 68 patients who underwent surgical resection of the intestine were included in this study and were categorized into two groups according to the presence or absence of postoperative disease recurrence within 2 years after surgery. Recurrence was defined using the CD Activity Index and the Rutgeerts score. Whole-slide images of surgical specimens were analyzed using deep learning model EfficientNet-b5, which achieved a highly accurate prediction of recurrence (area under the curve, 0.995). Moreover, subserosal tissue images with adipose cells enabled highly accurate prediction. Adipose cell morphology showed significant between-group differences in adipose cell size, cell-to-cell distance, and cell flattening values. These findings suggest that adipocyte shrinkage is an important histologic characteristic associated with recurrence. Moreover, there was a significant between-group difference in the degree of mast cell infiltration in the subserosa. These findings show the importance of mesenteric adipose tissue in patient prognosis and CD pathophysiology. These findings also suggest that deep learning-based artificial intelligence enables the extraction of meaningful histologic features.

Efficacy of downtitration or treatment withdrawal compared with continuous dosing after successful treatment with baricitinib in patients with moderate-to-severe atopic dermatitis in a randomized substudy from the long-term extension study BREEZE-AD3.

BACKGROUND: Baricitinib, an oral, selective Janus kinase 1/2 inhibitor, demonstrated long-term efficacy in moderate-to-severe atopic dermatitis in an ongoing double-blind, phase III, long-term extension study, BREEZE-AD3 (NCT03334435). OBJECTIVES: To evaluate the efficacy and safety of downtitration and treatment withdrawal in a substudy of BREEZE-AD3. METHODS: The substudy included patients (N = 526) treated with baricitinib 4 mg or 2 mg at entry into BREEZE-AD3 who achieved a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD®) scale score of 0 (clear), 1 (almost clear) or 2 (mild) at week 52. Patients treated with baricitinib 4 mg were rerandomized to baricitinib 4 mg (continuous dosing), baricitinib 2 mg (downtitration) or placebo (treatment withdrawal, 4-mg cohort), and patients treated with baricitinib 2 mg were rerandomized to baricitinib 2 mg (continuous dosing), baricitinib 1 mg (downtitration), or placebo (treatment withdrawal, 2-mg cohort). After 16 weeks, we assessed the proportion of patients with vIGA-AD® 0/1, vIGA-AD® 0/1/2, vIGA-AD® ≥ 3 (loss of response; criterion to readminister the original baricitinib dose) and for patients who were readministered the original baricitinib dose, we assessed the proportion of patients who recaptured vIGA-AD® 0/1/2 within 16 weeks of treatment readministration (patients in the continuous dosing maintained the same dose). RESULTS: For the continuous dosing, downtitration, and treatment withdrawal groups 51%, 45% and 30% of patients in the 4-mg cohort achieved vIGA-AD® 0/1 and 87%, 61% and 50% of patients achieved vIGA-AD® 0/1/2, respectively. For the 2-mg cohort, the respective proportions of patients were 48%, 42% and 25% for vIGA-AD® 0/1 and 92%, 71% and 45% for vIGA-AD® 0/1/2. The respective proportions of patients with vIGA-AD® ≥ 3 were 39%, 49% and 56% in the 4-mg cohort and 41%, 41% and 64% in the 2-mg cohort. Of those who were readministered the original baricitinib dose, the proportions of patients who recaptured vIGA-AD® 0/1/2 among the continuous dosing, downtitration, and treatment withdrawal groups were 80%, 85% and 88% in the 4-mg cohort and 90%, 56% and 86% in the 2-mg cohort, respectively. CONCLUSIONS: Baricitinib allows flexibility for patients to downtitrate or stop treatment. For patients who downtitrated treatment, the majority maintained efficacy through 16 weeks. Most patients who lost efficacy with downtitration or treatment withdrawal achieved clinically relevant efficacy upon readministration of their original dose.

Development and validation of an infant facial skin assessment tool: a prospective observational study.

BACKGROUND: Severe infant eczema on the face should be treated early because it may lead to allergic diseases in the future. However, caregivers find it difficult to assess. A visual tool for caregivers is needed to easily determine infants' facial skin condition severity based on the tool's scores. We developed an infant facial skin assessment tool (IFSAT) and evaluated its reliability and validity. METHODS: The IFSAT draft was developed based on results of a previous literature review and qualitative sketch. Panels including medical professionals and a caregiver checked the draft's content and face validity, and the IFSAT was finalized. To test the IFSAT's reliability and validity, caregivers and one-month-old infants were recruited. Two scoring methods were additionally created based on the relation between the items and cure period. The relationships between scores and cure period, and the ability to predict whether the infant needed medical treatment were examined by each scoring method. For the predictive validity, scores for infants requiring medical treatment and those for infants who did not were also compared. For the intra-examiner reliability analysis, two pediatricians rated the scores separately twice using photographs. Inter-rater reliabilities were analyzed among pediatricians, nurses, and caregivers. RESULTS: Altogether, 113 infant-caregiver pairs participated in the testing phase. Of the two scoring methods created (versions 1 and 2), pediatricians' and caregivers' scores using versions 1 and 2 were related to the cure period. These scores predict whether the infant needed medical treatment. We then selected version 2 based on the medical professionals' opinions. The scores of caregivers of infants requiring medical treatment were higher than those of caregivers of infants not requiring treatment (p < 0.001). The intraclass correlation coefficient (ICC) of intra-examiner reliability was 0.87. The ICC of inter-rater reliabilities between pediatricians' and caregivers' scores and between nurses' and caregivers' scores were 0.66, and 0.66, respectively. CONCLUSIONS: The proposed IFSAT may be used to assess whether infants need medical treatment and whether to extend the cure period. The tool's reliability and validity were confirmed.

Validity of skin blot examination for albumin and nerve growth factor ß to detect itching of the skin in Indonesian older adults.

AIM: Itching, a common skin disorder, impacts the quality of life of individuals. Itchy skin occurs more with increasing age and the prediction of itchy skin prognosis is necessary to provide good skincare. This study validated biomarkers in skin blotting to identify and measure itching sensation as well as conventional methods to measure skin barrier function. MATERIALS AND METHODS: From a cross-sectional study conducted in Long-term Care (LTC) facilities in Indonesia itching symptoms were obtained through a questionnaire. Skin conditions were assessed using photographs, stratum corneum (SC) hydration, skin pH, and skin blotting for biomarkers: albumin, interleukin 2 (IL2), nerve growth factor ß (NGFß), and thymic stromal lymphopoietin (TSLP). Association of skin measurements with the presence of skin blotting and trends analysis were conducted. RESULTS: Altogether, 564 LTC residents (average age, 70 years) participated. The SC hydration, skin pH, albumin, and NGFß were associated with the presence of itch (p value= <0.001, <0.001, <0.001, and <0.001, respectively). The signal levels of skin blotting biomarkers were higher in itch group than in the non-itch group. Additionally, the higher quantile of SC hydration was significantly associated with a lower intensity level of NGFß and TSLP (p value = 0.005, 0.003, respectively). The lower quantile of skin pH (better skin condition) was significantly associated with lower albumin, NGFß, and TSLP (p value = 0.048, 0.035, and <0.001, respectively). CONCLUSION: The albumin, NGFß, and TSLP could be a candidate for measurement of itchy skin among older adult with disrupted skin barrier function and local skin inflammation.

Skin characteristics associated with foot callus in people with diabetes: A cross-sectional study focused on desmocollin1 in corneocytes.

AIM: The purpose of this study was to investigate the degradation of desmocollin-1 (DSC1), a member of the desmosomal cadherin family in patients with diabetes, as well as the factors associated with the suppression of DSC1 degradation. METHODS: This cross-sectional study included 60 cases of foot callus involving 30 patients with diabetes (DM) and 30 matched volunteers without diabetes (non-DM). DSC1 degradation in samples from debrided calluses was analysed using western blotting. Skin hydration, a factor reported to suppress DSC1 degradation, was measured using a mobile moisture device. RESULTS: Full-length DSC1 (approximately 100 kDa) was detected in six participants only in the DM group, and no relationship was found between the suppression of DSC1 degradation and decreased skin hydration in the DM group. There was no significant difference in skin hydration values between the DM and non-DM groups. CONCLUSION: DSC1 degradation was suppressed in the DM group. There was no relationship between the suppression of DSC1 degradation and decreased skin hydration in the DM group. Current external force callus care would not be sufficient. This study highlights the need to develop novel callus care to enhance the degradation of DSC1.

Exploring the prevalence of skin tears and skin properties related to skin tears in elderly patients at a long-term medical facility in Japan.

The identification of appropriate skin tear prevention guidelines for the elderly requires clinicians to focus on local risk factors such as structural alterations of the epidermis and dermis related to skin tears. The aim of this cross-sectional study is to explore the prevalence of skin tears and to explore skin properties related to skin tears in elderly Japanese patients at a long-term medical facility. After doing the prevalence study, 18 participants with skin tears and 18 without were recruited and an evaluation of their skin properties using 20-MHz ultrasonography, skin blotting and also Corneometer CM-825, Skin-pH-meterPH905, VapoMeter, Moisture Meter-D and CutometerMPA580 was undertaken. A total of 410 patients were examined, the median age was 87 years and 73·2% were women. The prevalence of skin tears was 3·9%, and 50% of skin tears occurred on the dorsal forearm. The changes in skin properties associated with skin tears included increased low-echogenic pixels (LEP) by 20-MHz ultrasonography, decreased type IV collagen and matrix metalloproteinase-2, and increased tumour necrosis factor-α by skin blotting. In conclusion, this study suggests that increased dermal LEP, including solar elastosis, may represent a risk factor for skin tears; this indicates that skin tear risk factors might not only represent chronological ageing but also photoageing.

Consistent Efficacy of Apremilast in Patients with Psoriasis Regardless of Baseline Disease Severity or Special Area Involvement: Subgroup Analysis from PROMINENT.

INTRODUCTION: Psoriasis involvement in special areas (e.g., scalp or nails) is associated with a great disease burden yet it is often inadequately treated with topical treatments. The efficacy and tolerability of apremilast plus existing topical therapy in Japanese patients with mild to moderate plaque psoriasis were demonstrated in PROMINENT, a phase 3b, multicenter, open-label, single-arm study. We evaluated the efficacy of apremilast across disease severities and special areas involved in these patients. METHODS: In PROMINENT, patients received apremilast 30 mg twice daily for 16 weeks in addition to their existing topical therapy, with the option of topical therapy reduction at the discretion of their physician while continuing apremilast treatment from Weeks 16 to 32. We performed a post hoc analysis, assessing apremilast efficacy and safety in Japanese patients stratified by baseline static Physician Global Assessment (sPGA) score (2 [mild] or 3 [moderate]) and special area involvement. RESULTS: Of patients with baseline sPGA = 2 and sPGA = 3, 62.7% and 30.7%, respectively, achieved sPGA score 0 or 1 at Week 32. At Week 32, improvements in skin, nail, scalp, and quality of life assessments were observed regardless of baseline sPGA score. Improvements in these endpoints at Week 32 were also observed in patients with special area (scalp or nail) involvement (n = 134). Incidence of adverse events was similar between patients with baseline sPGA = 2 and sPGA = 3. CONCLUSIONS: Apremilast in combination with topical therapy may be a beneficial treatment for Japanese patients, who have limited systemic treatment options for mild to moderate psoriasis or psoriasis in special areas. TRIAL REGISTRATION: NCT03930186.

Safety and effectiveness of apremilast in Japanese patients with psoriatic disease: Results of a post-marketing surveillance study.

The safety and efficacy of apremilast in psoriatic disease has been demonstrated in clinical trials, including in Japanese patients. This post-marketing surveillance study was conducted after approval of apremalast in Japan in 2016 to evaluate the safety and effectiveness of the drug in Japanese patients with plaque psoriasis (PsO) and psoriatic arthritis (PsA) in routine clinical practice. Patients (enrolled between September 1, 2017, and August 31, 2019), were observed for 12 months after apremilast treatment initiation or until discontinuation or withdrawal. Safety was assessed by evaluating adverse reactions (ARs) and serious ARs. Effectiveness measures in PsO included the proportion of patients who achieved global improvement and Physician's Global Assessment (PGA) scores of 0/1 and the change from baseline in the Dermatology Life Quality Index (DLQI) after 6 and 12 months treatment. The safety analysis set included 1063 patients (PsO, n = 992; PsA, n = 127). ARs and serious ARs were reported in 29.4% and 0.7% of patients, respectively; most occurred <1 month after apremilast initiation. There were no reports of fatal ARs, serious infections, hypersensitivity, or vasculitis. No new safety signals were identified. Among the key survey items, gastrointestinal disorders were the most common ARs (21.3%). In patients with PsO, after 6 and 12 months of treatment, effectiveness rates of achieving highly effective or effective global improvement of were 90.9% and 93.8%; PGA 0/1 was achieved by 42.7% and 58.1% of patients; mean decrease from baseline in total DLQI score was 4.2 (p < 0.0001) and 5.7 (p < 0.0001), respectively. Effectiveness was evaluated in a small number of patients with PsA for some measures; after 6 and 12 months of treatment, improvements were observed in global improvement effectiveness rates, Disease Activity Score in 28 Joints score, Visual Analog Scale score, and DLQI score. We conclude that orally administered apremilast was well tolerated and effective in Japanese patients with PsO and/or PsA enrolled in this post-marketing surveillance study.

Expert consensus on systemic therapy for plaque psoriasis with limited skin involvement in JAPAN: Results from a DELPHI study.

Our objective was to establish consensus on (1) which patients with plaque psoriasis and limited skin involvement (body surface area [BSA] <10%) are suitable for systemic treatment, and (2) a definition of 'topical therapy failure'. A steering committee refined 13 statements drawn from literature related to the study objectives. An independent panel of 45 clinical experts from Japan indicated their agreement to each statement using a 10-point Likert scale (Round 1; strong consensus, ≥70% of responses = 7-10 and median value ≥8). The steering committee reviewed Round 1 results and refined the statements for Round 2, as necessary. In Round 2, the panel indicated their agreement to each statement using a 3-point scale (strong consensus, ≥70% of responses and median value of 3) and were shown Round 1 responses before voting. Forty-five clinicians participated in Round 1 and 41 of those (91%) participated in Round 2. Consensus was achieved on the criteria of eligibility for systemic treatment among patients with limited skin involvement as disease involvement at special or difficult to treat areas, psoriasis-induced psychological distress, uncontrolled symptoms (e.g., scaling, bleeding, pruritus, insomnia) affecting their social life, psoriatic arthritis, or failure of topical therapy. Consensus on criteria for topical failure were persistent symptoms (e.g., itchiness, pain) and plaques, poor patient satisfaction with treatment, a need to increase medication quantity or application time after treatment with two topicals for 4 weeks; or if the Psoriasis Area Severity Index score of >3 or Physician Global Assessment Score of ≥2 after 8 weeks treatment. Our Delphi panel proposes criteria to help physicians identify patients with psoriasis and limited skin involvement who would benefit from systemic therapy and suggests a definition for topical therapy 'failure' which could indicate a move to systemic treatment is warranted.

Exploratory Efficacy Evaluation of Apremilast for the Treatment of Japanese Patients with Palmoplantar Pustulosis: 32-Week Results from a Phase 2, Randomized, Placebo-Controlled Study.

INTRODUCTION: Palmoplantar pustulosis (PPP) is a pruritic, painful, chronic dermatitis that greatly impacts functioning and quality of life and can be difficult to treat. Approved treatment options for PPP are limited, and many patients do not fully respond to current treatments. METHODS: This was a randomized, double-blind, placebo-controlled, phase 2 study in Japanese patients with moderate to severe PPP and inadequate response to topical treatment. Patients were randomized 1:1 to receive apremilast 30 mg twice daily or placebo for 16 weeks followed by an extension phase where all patients received apremilast through week 32. PPP Area and Severity Index (PPPASI), modified PPPASI (which evaluates pustules and vesicles separately), and Palmoplantar Severity Index (PPSI) total scores and subscores (erythema, pustules/vesicles, and desquamation/scales) were evaluated over 32 weeks of apremilast treatment. Achievement of ≥ 50% improvement in PPPASI (PPPASI-50) was evaluated at week 16 among baseline demographic and clinical characteristic subgroups. RESULTS: At week 16, improvements in total score and subscores for PPPASI, modified PPASI, and PPSI, as well as rates of PPPASI-50 were at least moderately greater with apremilast than placebo. Mean PPPASI total score decreased by - 68.3% from baseline to week 32 with continued apremilast treatment. At week 32, mean change from baseline in PPPASI/modified PPPASI subscores ranged from - 58.5% to - 77.0% with apremilast. At week 32, PPSI total score for physician and patient assessments decreased by - 51.3% and - 40.0%, respectively, with continued apremilast treatment. PPPASI-50 response at week 16 was greater with apremilast versus placebo in most demographic and baseline characteristic subgroups. CONCLUSIONS: Improvements in all PPPASI and PPSI total scores and subscores observed with apremilast over 16 weeks were maintained through 32 weeks in patients with moderate to severe PPP and inadequate response to topical treatment. Rates of PPPASI-50 response at week 16 were mostly consistent across patient subgroups. CLINICALTRIALS: GOV: NCT04057937.

Combination of a Topical Anti-Inflammatory Drug and a Moisturizer, Both with a Lamellar Structure Containing Synthetic Pseudo-Ceramides, for the Treatment of Patients with Mild-to-Moderate Atopic Dermatitis.

Purpose: Atopic dermatitis is characterized by chronic inflammation and dryness accompanied by severe itching. The combined use of moisturizers and topical anti-inflammatory drugs is essential for alleviating atopic dermatitis. We have developed a topical anti-inflammatory drug with a steroid and a moisturizer with heparinoid, both in lamellar structure-based formulations containing synthetic pseudo-ceramides. Here, assessed the efficacy of this combination in the treatment of atopic dermatitis. Methods: We included 22 patients with mild to moderate atopic dermatitis and subjected them to a seven-week treatment with the test formulations, followed by a four-week post-treatment period. Results: Clinical findings and the quality of life of participants remarkably improved after one week of treatment. Furthermore, skin hydration and transepidermal water loss considerably improved at weeks one and three, respectively. The Cer [NP]/[NS] ratio, an indicator of epidermal turnover, substantially increased during the treatment period and remained elevated even thereafter. The improvement in stratum corneum function was distinctive in participants with lower barrier function. Conclusion: These findings indicated that the combined use of the anti-inflammatory drug and moisturizer, both in lamellar structure-based formulations, is effective in treating atopic dermatitis in patients with fragile barrier function.

Evaluation of the efficacy of maintenance therapy for acne vulgaris using adapalene 0.1%/benzoyl peroxide 2.5% gel and benzoyl peroxide 2.5% gel for 24 weeks and assessment of atrophic acne scars using three-dimensional image analysis.

Maintenance therapy after remission of inflammation is strongly recommended in the guideline for the treatment of acne vulgaris published by the Japanese Dermatological Association. One advantage of continuing maintenance therapy is the alleviation of atrophic scarring. This study investigated the efficacy of maintenance therapy using adapalene 0.1%/benzoyl peroxide 2.5% gel and benzoyl peroxide 2.5% gel, and its effects on atrophic scarring. Overall, 126 patients were randomized to the adapalene/benzoyl peroxide group (n = 40), benzoyl peroxide group (n = 44), and control group (without maintenance treatment drugs; n = 42), and 111 of these completed a trial lasting 24 weeks. As the primary endpoint, the treatment success rate (the percentage of patients in whom the number of inflammatory lesions was maintained at ≤10) was 89.2% in the adapalene/benzoyl peroxide group, 87.5% in the benzoyl peroxide group, and 47.4% in the control group. Compared with the control group, the success rates were significantly higher in the adapalene/benzoyl peroxide and benzoyl peroxide groups (P = 0.0006 for both). As one of the secondary endpoints, the rate of change in the number of atrophic scars showed significant improvement from the baseline in the adapalene/benzoyl peroxide and benzoyl peroxide groups at week 24 (P = 0.0004 and P < 0.0001, respectively). Although the three-dimensional image analysis parameters did not change significantly from the baseline in the adapalene/benzoyl peroxide and benzoyl peroxide groups at week 24, significant worsening was noted in the control group (P = 0.0276 for affected area, P = 0.0445 for volume, and P = 0.0182 for maximum depth). Adverse drug reactions were noted in three patients in the adapalene/benzoyl peroxide group (7.5%) but not in the benzoyl peroxide group. These findings suggest that maintenance therapy using adapalene 0.1%/benzoyl peroxide 2.5% gel and benzoyl peroxide 2.5% gel is effective in preventing the worsening of scars in Japanese patients with acne vulgaris.

The Role and Benefits of Dermocosmetics in Acne Management in Japan.

In Japan, as in other countries around the world, acne vulgaris is a common disease and a frequent reason for patients to consult dermatologists. For optimal management of acne, it is important to understand how available products to support skin health can be used both with and without prescription products. Dermocosmetics can be defined as skincare agents with dermatologically active ingredients that directly support or care for the symptoms of various skin conditions (distinct from vehicle effects). There are products with active ingredients-including familiar ones such as niacinamide, retinol derivatives, and salicylic acid-that target important aspects of acne pathophysiology. Others, including ceramides, glyercin, thermal spring water, and panthenols, may have positive effects on skin barrier function that are useful in managing acne. This publication will discuss the roles of dermocosmetics in acne either as monotherapy to manage the milder forms of acne and help prevent relapses, or as adjuncts to prescription therapy to increase efficacy or adherence and assist in prevention of local adverse effects. Dermocosmetics may also have active ingredients that positively impact the skin microbiome.

Application of deep learning as an ancillary diagnostic tool for thyroid FNA cytology.

BACKGROUND: Several studies have used artificial intelligence (AI) to analyze cytology images, but AI has yet to be adopted in clinical practice. The objective of this study was to demonstrate the accuracy of AI-based image analysis for thyroid fine-needle aspiration cytology (FNAC) and to propose its application in clinical practice. METHODS: In total, 148,395 microscopic images of FNAC were obtained from 393 thyroid nodules to train and validate the data, and EfficientNetV2-L was used as the image-classification model. The 35 nodules that were classified as atypia of undetermined significance (AUS) were predicted using AI training. RESULTS: The precision-recall area under the curve (PR AUC) was >0.95, except for poorly differentiated thyroid carcinoma (PR AUC = 0.49) and medullary thyroid carcinoma (PR AUC = 0.91). Poorly differentiated thyroid carcinoma had the lowest recall (35.4%) and was difficult to distinguish from papillary thyroid carcinoma, medullary thyroid carcinoma, and follicular thyroid carcinoma. Follicular adenomas and follicular thyroid carcinomas were distinguished from each other by 86.7% and 93.9% recall, respectively. For two-dimensional mapping of the data using t-distributed stochastic neighbor embedding, the lymphomas, follicular adenomas, and anaplastic thyroid carcinomas were divided into three, two, and two groups, respectively. Analysis of the AUS nodules showed 94.7% sensitivity, 14.4% specificity, 56.3% positive predictive value, and 66.7% negative predictive value. CONCLUSIONS: The authors developed an AI-based approach to analyze thyroid FNAC cases encountered in routine practice. This analysis could be useful for the clinical management of AUS and follicular neoplasm nodules (e.g., an online AI platform for thyroid cytology consultations).

English version of Japanese guidance for the use of oral Janus kinase (JAK) inhibitors in the treatments of atopic dermatitis.

This is the English version of guidance for the use of oral Janus kinase (JAK) inhibitors in the treatment of atopic dermatitis. Several cytokines, such as interleukin (IL)-4, IL-13, IL-22, IL-31, thymic stromal lymphopoietin, and interferon-γ, are involved in the pathogenesis of atopic dermatitis. As oral JAK inhibitors hinder the JAK-signal transducers and activators of transcription signal transduction routes involved in the signal transduction of these cytokines, they may be effective for the treatment of atopic dermatitis. In Japan, as oral JAK inhibitors for atopic dermatitis, a JAK1/2 inhibitor, baricitinib, expanded its authorized indications for atopic dermatitis in 2020. Consequentially, a JAK1 inhibitor, upadacitinib, also expanded its indications to atopic dermatitis in 2021, followed by new approval of another JAK1 inhibitor, abrocitinib, for the use under the Japanese health insurance system. Physicians who intend to use them should sufficiently understand and comply with contents of guidelines prepared by the Japanese Ministry of Health, Labour and Welfare to promote optimal use of these drugs. In the treatment with oral JAK inhibitors, it is important to sufficiently consider disease factors, treatment factors and patient backgrounds, and share them with patients to choose treatment options. Points to be considered for drug selection include the efficacy and safety of drugs, age of patients, and dosage and administration of the drug. This guidance was developed for board certified dermatologists, who are specialized in the treatment of atopic dermatitis, and for promoting proper use of oral JAK inhibitors, taking into account a variety of factors in individual patients.

Skin properties of itching without symptoms and associated factors among older adults in long-term care facilities.

Since itching without rash frequently among older adults' population, study about skin properties of itching without rash is important to develop prevention methods. Therefore, this study explored the skin properties related to itching without rash and the factors associated with them. A correlation, predictive designs study was conducted at Indonesian Long-term Care (LTC) facilities. Skin properties including skin barrier function and skin inflammation were examined by photographs (macroscopic and microscopic), stratum corneum (SC) hydration, skin Potential of Hydrogen (pH), and skin blotting. Itching experience and skincare behavior were obtained by questionnaire. The itching-related skin properties and associated factors were analyzed. A total of 405 residents participated in this study, with mean age was 74 years. The prevalence of itching on the whole body was 69.1%, and 50.3% of those manifesting itching on the left forearm involved itching without macroscopic abnormalities (itching without rash). SC hydration, skin pH, albumin and nerve growth factor ß (NGFß) were associated with itching without rash (p = 0.007, 0.012, < 0.001, and < 0.001, respectively). Additionally, factors associated with skin properties were age, sex, sun exposure experience, skincare, and hygiene care in the linear regression analysis. Measurement of skin biomarkers using skin blotting was a possible objective measurement of itching skin properties without rash regardless of the environmental condition.

English version of Japanese guidance for biologics in treating atopic dermatitis.

This is the English version of the Japanese guidance for biologics in treating atopic dermatitis (AD). The signaling pathway mediated by interleukin (IL)-4 and IL-13 contributes to type 2 inflammatory responses and plays an important role in the pathogenesis of AD. IL-31 is a cytokine mainly produced by activated T cells and is known to be involved in the pruritus of AD. Biologics for AD have been approved, including dupilumab, an anti-IL-4 receptor α antibody that was approved for expanded use in AD in 2018. In 2022, nemolizumab, an anti-IL-31 receptor α antibody, was approved for pruritus of AD, and tralokinumab, an anti-IL-13 antibody, was approved for AD. Physicians who intend to use these drugs should sufficiently understand and comply with the contents of the guidelines prepared by the Japanese Ministry of Health, Labour, and Welfare to promote the optimal use of the drugs. In treatment with biologics, it is important to consider disease factors (activity and severity), treatment factors (dosage and administration as well as the efficacy and safety), and patients' background characteristics (age and comorbidities) and share this information with patients when choosing treatment options. This guidance was developed for board-certified dermatologists who specialize in treating AD, and for promoting the proper use of biologics, taking into account the variety of factors in individual patients.

English version of Japanese guidance for use of biologics for psoriasis (the 2022 version).

This is the English version of Japanese guidance for use of biologics for psoriasis (the 2022 version). As the first biologics for psoriasis in Japan, infliximab and adalimumab, anti-tumor necrosis factor-α antibodies, became available in the field of dermatology in 2010, followed by ustekinumab, an anti-interleukin (IL)-12/IL-23p40 antibody, which was launched in Japan in 2011. Moreover, after 2015, three IL-17 inhibitors, the IL-17A antibody preparations secukinumab and ixekizumab, and an anti-IL-17 receptor antibody preparation brodalumab were marketed. Furthermore, after 2018, the anti-IL23p19 antibody preparations guselkumab and risankizumab, the TNF inhibitor certolizumab pegol, the IL-23 inhibitor tildrakizumab, and the anti-IL-17A/F antibody bimekizumab were marketed. It is important for physicians to select appropriate biologic therapy for each psoriatic patient after due consideration of disease factors, treatment factors, and patient background factors, sharing such information with patients. The followings can be listed as points to be considered for the selection of biologics: drug effects (e.g., strength of effectiveness, time to onset of effectiveness, effectiveness against arthritis, primary failure, secondary failure), safety (e.g., infections, administration-related reactions, and relationships with other comorbidities), convenience for patients (e.g., hospital visit intervals, self-injection, maintenance therapy at clinics, feasibility of drug discontinuation/re-administration), and payment (medical costs) borne by patients. This guidance has been prepared with the aim of allowing dermatologists experienced in the treatment of psoriasis to use biologics appropriately according to the circumstances of individual patients after consideration of the above-mentioned factors.

Efficacy and Safety of Apremilast for the Treatment of Japanese Patients with Palmoplantar Pustulosis: Results from a Phase 2, Randomized, Placebo-Controlled Study.

BACKGROUND: Palmoplantar pustulosis (PPP) is a pruritic, painful, recurrent, and chronic dermatitis with limited therapeutic options. OBJECTIVE: To evaluate the efficacy and safety of apremilast for the treatment of Japanese patients with PPP and inadequate response to topical treatment. METHODS: This phase 2, randomized, double-blind, placebo-controlled study enrolled patients with Palmoplantar Pustulosis Area and Severity Index (PPPASI) total score ≥ 12 and moderate or severe pustules/vesicles on the palm or sole (PPPASI pustule/vesicle severity score ≥ 2) at screening and baseline with an inadequate response to topical treatment. Patients were randomized (1:1) to apremilast 30 mg twice daily or placebo for 16 weeks, followed by a 16-week extension phase during which all patients received apremilast. The primary endpoint was achievement of PPPASI-50 response (≥ 50% improvement from baseline in PPPASI). Key secondary endpoints included change from baseline in PPPASI total score, Palmoplantar Pustulosis Severity Index (PPSI), and patient's visual analog scale (VAS) for PPP symptoms (pruritus and discomfort/pain). RESULTS: A total of 90 patients were randomized (apremilast: 46; placebo: 44). A significantly greater proportion of patients achieved PPPASI-50 at week 16 with apremilast versus placebo (P = 0.0003). Patients receiving apremilast showed greater improvement in PPPASI at week 16 versus placebo (nominal P = 0.0013), as well as PPSI and patient-reported pruritus and discomfort/pain (nominal P ≤ 0.001 for all). Improvements were sustained through week 32 with apremilast treatment. The most common treatment-emergent adverse events included diarrhea, abdominal discomfort, headache, and nausea. CONCLUSIONS: Apremilast treatment demonstrated greater improvements in disease severity and patient-reported symptoms versus placebo at week 16 in Japanese patients with PPP with sustained improvements through week 32. No new safety signals were observed. CLINICALTRIALS: GOV: NCT04057937.