Myeloid dendritic cells are increased in the lesional skin and associated with pruritus in patients with prurigo nodularis.

The number of dermal mDCs (CD11c+ cells) was increased with itch intensity (r = 0.886, p = 0.003) using immunofluorescence (IF). On IF, CD11c+ mDCs expressed IL-31 in lesional PN skin. Fluorescence in situ hybridization combined with IF also confirmed IL-31 mRNA expression by mDCs in PN lesion. Higher population of colocalization of CD11c+ mDCs expressing IL-31 mRNA were more than CD68+ macrophages and CD3+ T cells in consecutive sections of PN skin lesion. HC, healthy control; PN, prurigo nodularis; SPN, PN with severe pruritus (itch NRS score ≥7 points); MPN, PN with mild pruritus (itch NRS score <3 points); NRS, Numeric Rating Scale; AD, atopic dermatitis; mDC, myeloid dendritic cell.

Underlying Systemic Diseases in Interstitial Granulomatous Dermatitis and Palisaded Neutrophilic Granulomatous Dermatitis: A Systematic Review.

BACKGROUND: Interstitial granulomatous dermatitis (IGD) and palisaded neutrophilic granulomatous dermatitis (PNGD) are uncommon presentations of reactive granulomatous dermatitis. Histologic lesions characterized by IGD/PNGD patterns have been associated with systemic diseases, causing an unmet need for revealing clinical correlates. OBJECTIVE: The aim of this study was to unravel the systemic diseases beyond dermatitis of IGD/PNGD. METHODS: This study analyzed data from case studies, case series, and retrospective cohorts by searching PubMed, Embase, Web of Science, and the Cochrane Library, with no start date or language restrictions on Sep 4, 2021. RESULTS: One hundred ninety-six publications were included (458 cases in total, 216 with details). Systemic diseases associated with IGD/PNGD were classified into 5 groups. Autoimmune disorders (n = 103, 47.6%) including rheumatoid arthritis (n = 51, 23.6%), systemic lupus erythematosus (n = 20, 9.3%), and others were the most common across all underlying diseases, followed by drug eruption (n = 52, 24.1%) such as tumor necrotic factor inhibitor reaction (n = 18, 8.3%) and malignancies (n = 27, 12.5%) such as hematologic malignancy (n = 20, 9.3%). The rest were infectious diseases (n = 12, 5.6%) and accidental conditions (n = 3, 1.4%). CONCLUSION: IGD/PNGD might be associated with autoimmune disorders, drug eruption, malignancies, infectious diseases, and accidental conditions. Patients with IGD/PNGD need further follow-up.

Successful Treatment of a Patient with Pyoderma Gangrenosum, Plaque Psoriasis and Palmoplantar Pustulosis with Adalimumab.

Pyoderma gangrenosum (PG) is a rare autoinflammatory skin disorder, which is characterised by rapidly developing and tender cutaneous ulcers. The treatment of PG is challenging. Palmoplantar pustulosis (PPP) is also an autoinflammatory dermatosis with sterile pustules on the palms and/or the soles. We demonstrated a 68-year-old patient with coexisting autoinflammatory diseases including PG, 1-year history of plaque psoriasis and PPP, recovered after treatment with adalimumab. We also reviewed published reports of PG-associated autoinflammatory syndromes with adalimumab.

Atrophic Pigmented Dermatofibrosarcoma Protuberans: A Case Report and Literature Review.

Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue sarcoma characterized by the proliferation of spindle cells arranged in a storiform pattern. Here we report a case of DFSP presenting as a bluish-black atrophic plaque. The tumor had the histopathologic characteristics of both the pigmented and atrophic variants of DFSP. We describe the histopathologic, molecular, and imaging features of this patient and review other cases of DFSP that have been reported in the literature. Early identification of this DFSP variant can help clinicians implement clinical management strategies to prevent recurrence.

Real-World Experience on Omalizumab Treatment for Patients with Normocomplementemic Urticarial Vasculitis.

BACKGROUND: Urticarial vasculitis is a small vessel vasculitis characterized by long-lasting wheals. It was suggested omalizumab is well tolerated and effective in patients with hypocomplementaemic urticarial vasculitis. OBJECTIVE: To evaluate the clinical response and safety of omalizumab for treating patients with normocomplementaemic urticarial vasculitis (NUV) in real-world setting. METHODS: We collected data from a single-center. This study included patients with NUV who was received omalizumab therapy. During a 24-week study period, the clinical efficacy was evaluated by patient's self-assessment instrument urticarial vasculitis activity score and Dermatology Life Quality Index. RESULTS: Five patients with NUV were enrolled. Three patients received 6 doses of 150 or 300 mg omalizumab subcutaneously every 4 weeks. At 24-week follow-up, it was revealed improvement of clinical manifestations and reduction of urticarial vasculitis activity score and Dermatology Life Quality Index. At 24-week visit, mild wheals recurred in one patient who was only administrated with omalizumab for 4 times. One patient did not response to omalizumab therapy. No adverse events were recorded in the 5 patients. CONCLUSION: Omalizumab may be a potential choice in the treatment of patients with NUV in the real-world life.

Effectiveness of Dupilumab for an Elderly Patient with Prurigo Nodularis Who Was Refractory and Contradicted to Traditional Therapy.

Prurigo nodularis (PN) is an intense pruritic skin condition. Treatment of PN is challenging. We described an elderly patient with PN who had contradictions of cyclosporine or methotrexate and achieved significant improvement after treatment with dupilumab. We also reviewed published cases of elderly patients with PN who were refractory to traditional therapy.

Risk of macrophage activation syndrome in patients with adult-onset Still's disease with skin involvement: A retrospective cohort study.

BACKGROUND: Small case series and case reports indicated that atypical persistent pruritic eruptions (PPEs), another type of skin lesions seen in adult-onset Still's disease (AOSD), imply a worse prognosis than typical evanescent rashes. OBJECTIVE: To investigate clinical characteristics and macrophage activation syndrome (MAS) occurrence in AOSD with PPEs. METHODS: A retrospective cohort study analyzed 150 patients with AOSD with rashes at the First Affiliated Hospital of Zhejiang University from January 2013 to December 2019. RESULTS: Patients with AOSD with PPEs had higher lactate dehydrogenase (492.00 U/L vs 382.00 U/L; P < .001) and ferritin (6944.10 ng/ml vs 4286.60 ng/ml; P = .033), and lower fibrinogen (5.05 g/L vs 5.77 g/L; P = .014) than those with evanescent rashes. Patients with AOSD with PPEs had a higher incidence (17.4% vs 3.1%, P = .006) and cumulative event rate for MAS (P = .008) and tended to receive high-dose glucocorticoid (36% vs 20.3%; P = .036). Multivariate analysis indicated that PPEs (hazard ratio [HR], 5.519; 95% confidence interval [CI], 1.138-26.767; P = .034), aspartate aminotransferase of greater than 120 U/L (HR, 8.084; 95% CI, 1.728-37.826; P = .008), and splenomegaly (HR, 21.152; 95% CI, 2.263-197.711; P = .007) were independent risk factors for MAS. LIMITATIONS: Single-center, retrospective nature, small sample size. CONCLUSION: PPEs indicated increased severity and MAS occurrence versus evanescent rashes. PPEs, aspartate aminotransferase of greater than 120 U/L, and splenomegaly were risk factors for MAS in AOSD with skin involvement.

Comparative study of treatment for striae alba stage striae gravidarum: 1565-nm non-ablative fractional laser versus fractional microneedle radiofrequency.

Striae gravidarum is a common dermatologic condition for females caused by multiple factors during pregnancy. It remains a therapeutic challenge especially in the striae alba (SA) stage, generating psychological and emotional distress to those affected. This study aims to compare the efficacy and safety of 1565-nm non-ablative fractional laser (NAFL) and fractional microneedle radiofrequency (MRF) for treatment of SA striae gravidarum. Fourteen Chinese women with SA striae gravidarum were included in this study. Patient abdomens were randomly divided into NAFL and MRF treatment sides, treated three times at 6-week intervals. Treatment efficacy was evaluated by subjective (clinical assessments, patient satisfaction rating, adverse effects assessment) assessments and objective (skin melanin index measurement, histological study) assessments. Clinical assessment suggested MRF was more effective (P = 0.0143) for improving the appearance of SA striae gravidarum. Both NAFL and MRF demonstrated effective improvement (P = 0.0082 and P = 0.0158, respectively), with no significant difference according to patient satisfaction ratings and changes in melanin index (P = 0.5900). Both treatments induced limited adverse reactions, but MRF treatment caused significant pain compared with the more moderate NAFL treatment (P = 0.0003). MRF treatment increased neocollagen and elastic fibers more significantly than NAFL, based on histological assessments (P = 0.0298 and P = 0.0048, respectively). MRF treatment improved collagen regeneration in SA striae gravidarum more than NAFL but caused considerable pain during treatment. Corresponding treatment or therapeutic strategies should be applied according to clinical scenario.

The IL-23/IL-17 Pathway in Inflammatory Skin Diseases: From Bench to Bedside.

Interleukin-17 (IL-17) is an essential proinflammatory cytokine, which is mainly secreted by the CD4+ helper T cells (Th17 cells) and subsets of innate lymphoid cells. IL-17A is associated with the pathogenesis of inflammatory diseases, including psoriasis, atopic dermatitis, hidradenitis suppurativa, alopecia areata, pityriasis rubra pilaris, pemphigus, and systemic sclerosis. Interleukin-23 (IL-23) plays a pivotal role in stimulating the production of IL-17 by activating the Th17 cells. The IL-23/IL-17 axis is an important pathway for targeted therapy for inflammatory diseases. Emerging evidence from clinical trials has shown that monoclonal antibodies against IL-23, IL-17, and tumor necrosis factor are effective in the treatment of patients with psoriasis, atopic dermatitis, hidradenitis suppurativa, pityriasis rubra pilaris, pemphigus, and systemic sclerosis. Here, we summarize the latest knowledge about the biology, signaling, and pathophysiological functions of the IL-23/IL-17 axis in inflammatory skin diseases. The currently available biologics targeting the axis is also discussed.

Randomized trial of electrodynamic microneedle combined with 5% minoxidil topical solution for the treatment of Chinese male Androgenetic alopecia.

Background: In treating androgenetic alopecia, 5% minoxidil is a commonly used topical drug. By using electrodynamic microneedle at the same time may increase absorption of minoxidil and further stimulate hair growth.Objective: A 24-week, randomized, evaluator blinded, comparative study was performed to evaluate the efficacy of treating Chinese male androgenetic alopecia using microneedle combined with 5% minoxidil topical solution. Methods: Randomized subjects received topical 5% minoxidil (group 1, n = 20), local electrodynamic microneedle treatments (group 2, n = 20), or local electrodynamic microneedle treatments plus topical 5% minoxidil (group 3, n = 20). A total of 12 microneedle treatments were performed every 2 weeks with 2ml 5% minoxidil delivery in group three during each microneedle treatment. Patient receiving topical 5% minoxidil applied 1 ml of the solution twice daily over the course of the study. A total of 60 Chinese male subjects with Norwood-Hamilton type III-VI androgenetic alopecia were treated.Results: The mean improvement in total hair density from baseline to 24 weeks was 18.8/cm2 in group 1, 23.4/cm2 in group 2, and 38.3/cm2 in group 3. The hair growth in the three groups was significantly different (P = 0.002), but there were no significant differences in toxicity found between the three groups.Conclusions: Treatment with microneedle plus topical 5% minoxidil was associated with the best hair growth.

Effect of Stress on the Work Ability of Aging American Workers: Mediating Effects of Health.

We examined how stress affects the work ability of an aging workforce, how health mediates this relationship, and how the effects of stress on work ability differ in relation to social status. We analyzed data from the Health and Retirement Survey, namely, 2921 observations in 2010, 2289 observations in 2012, and 2276 observations in 2014. Ongoing chronic stress, social status, health status, and associations with individual work ability were assessed with ordinary least squares regression. Stress was significantly inversely associated with work ability. Health may function as a mediator between individual stress and work ability. The effects of stress and health on work ability decreased as social status increased. To cope with the challenges of aging workforces, future policy-makers should consider job resources and social status.

Analysis of Dynamic Response of an MRI-Guided Magnetically-Actuated Steerable Catheter System.

This paper presents a free-space open-loop dynamic response analysis for an MRI-guided magnetically-actuated steerable intra-vascular catheter system. The catheter tip is embedded with a set of current carrying micro-coils. The catheter is directly actuated via the magnetic torques generated on these coils by the magnetic field of the magnetic resonance imaging (MRI) scanner. The relationship between the input current commands and catheter tip deflection angle presents an inherent nonlinearity in the proposed catheter system. The system nonlinearity is analyzed by utilizing a pendulum model. The pendulum model is used to describe the system nonlinearity and to perform an approximate input-output linearization. Then, a black-box system identification approach is performed for frequency response analysis of the linearized dynamics. The optimal estimated model is reduced by observing the modes and considering the Nyquist frequency of the camera system that is used to track the catheter motion. The reduced model is experimentally validated with 3D open-loop Cartesian free-space trajectories. This study paves the way for effective and accurate free-space closed-loop control of the robotic catheter with real-time feedback from MRI guidance in subsequent research.

Iterative Jacobian-Based Inverse Kinematics and Open-Loop Control of an MRI-Guided Magnetically Actuated Steerable Catheter System.

This paper presents an iterative Jacobian-based inverse kinematics method for an MRI-guided magnetically-actuated steerable intravascular catheter system. The catheter is directly actuated by magnetic torques generated on a set of current-carrying micro-coils embedded on the catheter tip, by the magnetic field of the magnetic resonance imaging (MRI) scanner. The Jacobian matrix relating changes of the currents through the coils to changes of the tip position is derived using a three dimensional kinematic model of the catheter deflection. The inverse kinematics is numerically computed by iteratively applying the inverse of the Jacobian matrix. The damped least square method is implemented to avoid numerical instability issues that exist during the computation of the inverse of the Jacobian matrix. The performance of the proposed inverse kinematics approach is validated using a prototype of the robotic catheter by comparing the actual trajectories of the catheter tip obtained via open-loop control with the desired trajectories. The results of reproducibility and accuracy evaluations demonstrate that the proposed Jacobian-based inverse kinematics method can be used to actuate the catheter in open-loop to successfully perform complex ablation trajectories required in atrial fibrillation ablation procedures. This study paves the way for effective and accurate closed-loop control of the robotic catheter with real-time feedback from MRI guidance in subsequent research.

Experimental Validation of the Pseudo-Rigid-Body Model of the MRI-Actuated Catheter.

An MRI-actuated catheter is a novel robotic catheter system that utilizes the MRI for both remote steering and visualization for catheter ablation of atrial fibrillation. Planning and control of the catheter requires a sufficiently fast yet accurate model of the catheter. The pseudo-rigid-body (PRB) model offers a reasonable trade-off between speed and accuracy by approximating the continuum catheter as rigid links connected by flexible joints, thus reducing the infinite degrees of freedom of the continuum mechanism to a finite one. In this paper, a PRB model of the MRI-actuated catheter is validated experimentally by comparing the deflections of the PRB model with the deflections of the catheter prototype.

Design of a Magnetic Resonance Imaging Guided Magnetically Actuated Steerable Catheter.

This paper presents design optimization of a magnetic resonance imaging (MRI) actuated steerable catheter for atrial fibrillation ablation in the left atrium. The catheter prototype, built over polymer tubing, is embedded with current-carrying electromagnetic coils. The prototype can be deflected to a desired location by controlling the currents passing through the coils. The design objective is to develop a prototype that can successfully accomplish the ablation task. To complete the tasks, the catheter needs to be capable of reaching a set of desired targets selected by a physician on the chamber and keeping a stable contact with the chamber surface. The design process is based on the maximization of the steering performance of the catheter by evaluating its workspace in free space. The selected design is validated by performing a simulation of an ablation intervention on a virtual model of the left atrium with a real atrium geometry. This validation shows that the prototype can reach every target required by the ablation intervention and provide an appropriate contact force against the chamber.

Needle Grasp and Entry Port Selection for Automatic Execution of Suturing Tasks in Robotic Minimally Invasive Surgery.

This paper presents algorithms for selection of needle grasp and for selection of entry ports of robotic instruments, for autonomous robotic execution of the minimally invasive surgical suturing task. A critical issue for automatic execution of surgical tasks, such as suturing, is the choice of needle grasp for the robotic system. Inappropriate needle grasp increases operating time requiring multiple regrasps to complete the desired task. In robotic minimally invasive surgery, the entry port that the surgical robot goes through into the patient's body has a significant role on the performance of the robot. Improper entry port affects the robot's dexterity, manipulability and reachability. The proposed methods use manipulability, dexterity and torque metrics for needle grasp selection, and employ needle grasp robustness and target location robustness metrics for port selection. The results of a case study simulation in thoracoscopic surgery is also presented to demonstrate the proposed methods. Note to Practitioners-This paper is motivated by the problem of automating low-level surgical tasks in robotic surgery, such as, suturing, retraction, dissection, and providing exposure. Specifically, this paper focuses on needle grasp and entry port selection for automating robotic surgical suturing. Selection of an appropriate way of grasping a needle is critical for successfully and robustly completing autonomous suturing. To the best authors' knowledge, there are no earlier studies in the literature which focus on the needle grasp selection problem. The proposed approach determines how to grasp the needle by optimizing the surgical system's manipulation performance. The existing approaches in the literature for selecting entry ports for the robotic surgical tools only consider the teleoperated robotic minimally invasive surgery, in which the surgeons directly control the robotic instruments. However, automated performance of suturing introduces additional challenges due to uncertainties in needle localization and grasping. This paper proposes two new performance metrics on selecting port locations from the perspective of autonomously performing surgical suturing, without direct involvement of the human user. The paper also presents preliminary experiments which demonstrate the effectiveness of the proposed methods.