Line-field confocal optical coherence tomography, a novel non-invasive tool for the diagnosis of onychomycosis.

BACKGROUND AND OBJECTIVES: Onychomycosis is common and important to distinguish from other nail diseases. Rapid and accurate diagnosis is necessary for optimal patient treatment and outcome. Non-invasive diagnostic tools have increasing potential for nail diseases including onychomycosis. This study evaluated line-field confocal optical coherence tomography (LC-OCT) as a rapid non-invasive tool for diagnosing onychomycosis as compared to confocal laser scanning microscopy (CLSM), optical coherence tomography (OCT), and conventional methods. PATIENTS AND METHODS: In this prospective study 86 patients with clinically suspected onychomycosis and 14 controls were examined using LC-OCT, OCT, and CLSM. KOH-preparation, fungal culture, PCR, and histopathology were used as comparative conventional methods. RESULTS: LC-OCT had the highest sensitivity and negative predictive value of all methods used, closely followed by PCR and OCT. Specificity and positive predictive value of LC-OCT were as high as with CLSM, while OCT scored much lower. The gold standard technique, fungal culture, showed the lowest sensitivity and negative predictive value. Only PCR and culture allowed species differentiation. CONCLUSIONS: LC-OCT enables quick and non-invasive detection of onychomycosis, with advantages over CLSM and OCT, and similar diagnostic accuracy to PCR but lacking species differentiation. For accurate nail examination, LC-OCT requires well-trained and experienced operators.

Precision of Soft-Tissue Filler Injections: An Ultrasound-Based Verification Study.

BACKGROUND: Uncontrolled product spread is an important issue to consider in facial filler injections. Lack of precision can result in reduced effectiveness and surface projection, as well as irregularities and product visibility. OBJECTIVES: The authors sought to assess the precision of soft-tissue filler injections in the face by employing a cannula. METHODS: This single-center observational study investigated soft-tissue filler distribution utilizing real-time non-invasive ultrasound imaging. Outcome parameters included (1) the tissue plane of product distribution, (2) the extent of horizontal as well as vertical product spread at the injection site, and (3) the product surface area taking into account the multifactorial influence of several independent variables. Participants were followed up to 30 days post-injection. RESULTS: A total 100 facial injections were performed in 8 patients (2 males, 6 females) with a mean age of 37.20 (±6.34) years and a mean BMI of 22.21 (±1.39) kg/m.2. The plane of product distribution remained constant in approximately 90% of cases at day 0 (d0), d14, and d30. Mean horizontal product spread was higher compared with vertical spread, and both significantly decreased over all time points (P < .001). Mean product surface area was 22.51 ± 16.34 mm2 at d0, 15.97 ± 11.28 mm2 at d14, and 12.9 ± 9.15 mm2 at d30. Analysis employing generalized linear models revealed that injection volume and injection depth significantly influenced product surface area. CONCLUSIONS: Injection of soft-tissue filler employing a cannula allows precise application of the product within the intended tissue plane. Precision can be improved by injecting less product into deeper tissue layers.

The Impact of Breast Symmetry on Eye Movement and Gaze Pattern: An Eye-Tracking Investigation.

BACKGROUND: The objective assessment of beauty remains challenging despite ongoing research efforts. A new method of objectively determining the aesthetic appeal of body features by analyzing gaze patterns and eye movements has recently been investigated. OBJECTIVES: The objective of this study was to assess, by means of objective eye-tracking technology, differences in the gaze patterns of observers presented with standardized 3-dimensional images showing different degrees of breast asymmetry. METHODS: A total of 83 Caucasian study participants with a mean age of 38.60 (19.8) years were presented with 5 images depicting varying degrees of breast asymmetry. In addition to the assessment of eye movements, participants were asked to rate the aesthetic appeal and the asymmetry of the breasts on a 5-point Likert scale. RESULTS: Overall, the data showed that participants' rating of the breasts' aesthetic appeal was inversely related to the level of asymmetry. The mean [standard deviation] time until fixation was shortest for the image depicting the greatest breast asymmetry (50 cc) at 0.77 [0.7] seconds (P < 0.001). In addition, the mammary region was also viewed longest in this image at 3.76 [0.5] seconds (P < 0.001). A volume difference of 35 cc between breasts deflected the observers' gaze significantly toward the larger of the asymmetric breasts (P < 0.001). CONCLUSIONS: Surgeons should focus on achieving symmetric breast volume (ie, differences <35 cc between breasts) to avoid noticeable asymmetry with regard to breast size.

Onset of occupational hand eczema among healthcare workers during the SARS-CoV-2 pandemic: Comparing a single surgical site with a COVID-19 intensive care unit.

BACKGROUND: As a result of the COVID-19 outbreak, hygiene regulations have been revised and hand sanitation has been intensified. OBJECTIVE: To investigate the onset of hand eczema during the COVID-19 pandemic in healthcare workers (HCWs) directly involved in intensive care of COVID-19 patients and HCWs without direct contact with COVID-19 patients. Hereby, we aim at increasing awareness about occupational hand eczema and preventive measures that can be adopted. METHOD: A survey was distributed amongst 114 HCWs at a single surgical centre and at a COVID-19 intensive care unit of the university hospital Ludwig Maximilian University Munich, Germany. Participants were questioned about the daily frequency of hand hygiene prior to and during the pandemic. Participants self-reported the onset of hand eczema and associated symptoms. RESULTS: Our study revealed a significant increase in hand washing, disinfection, and use of hand cream across all participants (P-value <.001), regardless of having direct contact with COVID-19 patients. A high prevalence of symptoms associated with acute hand dermatitis of 90.4% was found across all HCWs, whereas hand eczema itself was underreported (14.9%). CONCLUSION: The increase in hand sanitation during the COVID-19 pandemic impairs the skin of the hands across all HCWs, independent of direct intensive care of affected patients.

Objective evaluation of the efficacy of a non-ablative fractional 1565 nm laser for the treatment of deliberate self-harm scars.

Scars resulting from deliberate self-harm (DSH) represent therapeutically challenging forms of scarring due to their highly variable patterns, with no official therapeutic guidelines available. In this pilot study, we aimed to evaluate the effectiveness and safety of a non-ablative fractional Er:glass 1565 nm laser, as a potential new, minimal-invasive approach for the improvement of DSH scars. Sixteen Caucasians suffering from mature DSH scars were included in this clinical study. Patients received a total of three treatments using a non-ablative fractional 1565 nm Er:glass laser every 4 weeks, employing two passes (300 µbeams/cm2, 40 mJ, onto the scar; 150 µbeams/cm2, 50 mJ, overall area). Measurements included questionnaires (DLQI, POSAS), digital photography, and objective three-dimensional analysis using PRIMOS and VECTRA software at baseline, 1 and 6 months after treatment. PRIMOS objective measurements showed highly significant changes in scar surface with a reduction of atrophic lesions by 27.5% at 6 months follow-up (FU), a decrease in scar height by 42.7% at 6 months FU, resulting in an overall diminished skin irregularity dropping from 678.3 µm at baseline to 441.6 µm throughout the course of the study (p = <0.001 respectively). Improvements in objective measurements were supported by clinical evaluation of scar parameters and showed a strong correlation with enhanced life quality of treated patients. Procedures were well-tolerated, with no lasting negative side effects and little to no downtime. The use of a fractional non-ablative 1565 nm Er:glass laser represents a promising and safe approach for the therapy of DSH scars. Although these scars will never fully resolve, their appearance can be significantly improved to a cosmetically and socially more acceptable appearance.

Deficit of Omega-3 Fatty Acids in Acne Patients-A Cross-Sectional Pilot Study in a German Cohort.

Omega-3 fatty acids (ω-3 FAs) exert anti-inflammatory effects, including the downregulation of pro-inflammatory cytokines, eicosanoids, and insulin-like growth factor-1. Therefore, they may improve acne severity as an adjunct treatment. However, there is a paucity of data regarding patients' existing deficits. The aim of this study was to determine ω-3 FA levels in acne patients in correlation with self-reported dietary preferences and clinical severity. A single-center, cross-sectional study of 100 acne patients was conducted. Patients' blood parameters, including ω-3 FAs levels, were assessed using the HS-omega-3 Index® in erythrocytes (Omegametrix® GmbH, Martinsried, Germany). Dietary preferences were assessed using a standardized food frequency questionnaire. Clinical dermatologic evaluation was performed using the Investigator Global Assessment (IGA) of acne. The values of the HS-omega-3 Index® were outside the recommended range of 8-11% in 96 patients (mean 5.15%), independent of the clinical severity or affected anatomic sites. A severe deficit (HS-omega-3 Index® < 4%) was seen more commonly in men than in women (p = 0.021). The regular consumption of legumes was significantly associated with higher ω-3 FA levels (p = 0.003), as was oral ω-3 FA supplementation (p = 0.006) and the lack of sunflower oil intake (p = 0.008). This pilot study demonstrated a deficit of ω-3 FAs in a German acne cohort. Higher ω-3 FAs levels were observed in patients with regular legume intake and oral ω-3 FAs supplementation. Further prospective studies are needed to investigate whether the clinical severity of acne improves in patients with normal HS-omega-3 Index®.

Characteristics of Gut Microbiota in Rosacea Patients-A Cross-Sectional, Controlled Pilot Study.

BACKGROUND: Recent studies have suggested a possible connection between rosacea and patients' gut microbiota. OBJECTIVE: To investigate the differences in fecal microbial profiles between patients with rosacea and healthy controls. METHODS: Gut microbiota of 54 rosacea patients (RP) were analyzed using MiSeq 16S rRNA sequencing. Enterotypes, the Firmicutes/Bacteroides (F/B) ratio, the significance of alpha and beta diversity, and differential abundance analysis (DAA) were calculated and compared with age- and gender-matched controls (CP, n = 50). RESULTS: Significant changes in the enterotypes and F/B ratio were observed between the RP and CP (p = 0.017 and p = 0.002, respectively). The RP showed a decreased microbial richness and diversity compared to the CP (Shannon p = 0.012, inverse Simpson p = 0.034). Beta diversity also differed between both groups (PERMANOVA, p = 0.006). Fourteen significantly different taxa were detected according to DAA. Faecalibacterium prausnitzii (coef. -0.0800, p = 0.008), Lachnoospiraceae ND 3007 group sp. (coef. -0.073, p < 0.001), and Ruminococcaceae (coef. -0.072, p = 0.015) were significantly decreased; Oscillobacter sp. (coef. 0.023, p = 0.031), Flavonifractor plautii (coef. 0.011, p = 0.037), and Ruminococccaceae UBA 1819 (coef. 0.010, p = 0.031) were significantly increased in the RP compared to the CP. CONCLUSION: Significant alterations in gut microbiota were present in the RP. Taxonomic shifts and reduced richness and diversity were observed when compared to the CP. Larger prospective studies are needed to investigate correlations with clinical features and to translate these findings into future therapeutic approaches.

[Rosacea-the updated S2k guideline]. / Rosazea ­ die neue S2k-Leitlinie.

Rosacea is a common chronic inflammatory dermatosis of the face, clinically characterized by erythema, telangiectasia, papules, pustules, and rhinophyma. In January 2022, the updated guideline on rosacea was published. Groundbreaking innovations include the new clinical classification according to phenotypes, extended diagnostic and therapeutic recommendations for ocular rosacea and implications of the gut microbiome on rosacea. Furthermore, the guideline encompasses a new chapter on the psychosocial aspects of rosacea and detailed recommendations for approved and off-label therapies.

Dietary Patterns in Acne and Rosacea Patients-A Controlled Study and Comprehensive Analysis.

As the relationship between exposome factors and inflammatory skin diseases is gaining increasing attention, the objective of this study was to investigate dietary patterns among acne and rosacea patients and to establish the disease risk attributable to nutrition. In this cross-sectional, controlled study, patients' dietary habits were assessed via subjective ratings of beneficial and trigger foods, followed by standardized food frequency surveys (FFS). Scores for disease-specific risk stratification based on dietary habits were proposed. Clinical assessments, dermatologic examinations, and laboratory analyses were performed. A total of 296 patients (acne group (AG) n = 120, control group (ACG) n = 32; rosacea group (RG) n = 105, control group (RCG) n = 39) were included. The significant impact of diet on disease severity was self-reported by 80.8% of the AG and 70.5% of the RG. Leading dietary triggers were found in both groups, while beneficial food items were identified more clearly by the AG. FFS revealed significant dietary differences between the AG, RG, and control groups. Disease-specific scores showed greater precision for acne (odds ratio 14.5 AG, 5.5 RG). The AG had higher insulin-like growth factor (IGF)-1 levels correlating with dairy intake (p = 0.006). Overall, this study underlines the influence of diet on acne and rosacea, providing valuable disease-specific scores for dietary risk stratification. Consuming vegetables, legumes, oily fish, olive oil, and nuts, and limiting meat, cheese, and alcohol appear to be beneficial for both acne and rosacea. Future studies can build on these data to further improve preventive and therapeutic strategies.

Cutaneous T-cell Lymphomas: A Single-center Retrospective Analysis.

INTRODUCTION: Cutaneous T-cell lymphomas (CTCLs) are rare diseases characterized by infiltration of malignant T-cells into the skin. We evaluated the prevalence, epidemiology, and therapy of CTCLs, focusing on its most well-known subtypes, namely mycosis fungoides (MF) and Sézary syndrome (SS). PATIENTS AND METHODS: We retrospectively analyzed the medical data of patients with a histologically confirmed diagnosis of CTCL presenting to our outpatient department during a 5-year period from January 2015 to December 2019. RESULTS: We evaluated the files of 102 patients, of whom 67% were men and 33% women. The overall mean age was 59.1±14.1 (24-86) years. Ninety-two patients (90%) were diagnosed with MF and ten patients (10%) with SS. According to ISCL/EORTC, the majority of patients initially classified as stage IA (34%) and IB (45%). Disease frequency decreased at advanced stages (II: 4%; III: 7%; IV: 10%). Forty-five patients (44.1%) received only skin-directed therapy (SDT). Twenty patients (19.6%) progressed from SDT to systemic therapy (ST). Thirty-seven patients (36.3%) received ST combined with SDT (TS) from the start of treatment. Overall, fifty different therapeutic approaches of TS were initiated due to lack of response to therapy or disease progression. CONCLUSION: Management of CTCLs aims to maintain patient quality of life while minimizing side-effects. As CTCLs are usually incurable diseases, the focus of treatment is on symptom control and prevention of disease progression. Due to the large patient group and the long observation period, our study allows for a valid evaluation of the frequency and therapy of MF and SS in a university outpatient clinic in Germany. We favor topical therapies in early stages with more invasive therapies in advanced stages.

Patterns of pseudoprogression across different cancer entities treated with immune checkpoint inhibitors.

BACKGROUND: Pseudoprogression (PsPD) is a rare response pattern to immune checkpoint inhibitor (ICI) therapy in oncology. This study aims to reveal imaging features of PsPD, and their association to other relevant findings. METHODS: Patients with PsPD who had at least three consecutive cross-sectional imaging studies at our comprehensive cancer center were retrospectively analyzed. Treatment response was assessed according to immune Response Evaluation Criteria in Solid Tumors (iRECIST). PsPD was defined as the occurrence of immune unconfirmed progressive disease (iUPD) without follow-up confirmation. Target lesions (TL), non-target lesions (NTL), new lesions (NL) were analyzed over time. Tumor markers and immune-related adverse events (irAE) were correlated. RESULTS: Thirty-two patients were included (mean age: 66.7 ± 13.6 years, 21.9% female) with mean baseline STL of 69.7 mm ± 55.6 mm. PsPD was observed in twenty-six patients (81.3%) at FU1, and no cases occurred after FU4. Patients with iUPD exhibited the following: TL increase in twelve patients, (37.5%), NTL increase in seven patients (21.9%), NL appearance in six patients (18.8%), and combinations thereof in four patients (12.5%). The mean and maximum increase for first iUPD in sum of TL was 19.8 and 96.8 mm (+ 700.8%). The mean and maximum decrease in sum of TL between iUPD and consecutive follow-up was - 19.1 mm and - 114.8 mm (-60.9%) respectively. The mean and maximum sum of new TL at first iUPD timepoint were 7.6 and 82.0 mm respectively. In two patients (10.5%), tumor-specific serologic markers were elevated at first iUPD, while the rest were stable or decreased among the other PsPD cases (89.5%). In fourteen patients (43.8%), irAE were observed. CONCLUSIONS: PsPD occurred most frequently at FU1 after initiation of ICI treatment. The two most prevalent reasons for PsPD were TL und NTL progression, with an increase in TL diameter commonly below + 100%. In few cases, PsPD was observed even if tumor markers were rising compared to baseline. Our findings also suggest a correlation between PsPD and irAE. These findings may guide decision-making of ICI continuation in suspected PsPD.

Ionizing radiation biomarkers for potential use in epidemiological studies.

Ionizing radiation is a known human carcinogen that can induce a variety of biological effects depending on the physical nature, duration, doses and dose-rates of exposure. However, the magnitude of health risks at low doses and dose-rates (below 100mSv and/or 0.1mSvmin(-1)) remains controversial due to a lack of direct human evidence. It is anticipated that significant insights will emerge from the integration of epidemiological and biological research, made possible by molecular epidemiology studies incorporating biomarkers and bioassays. A number of these have been used to investigate exposure, effects and susceptibility to ionizing radiation, albeit often at higher doses and dose rates, with each reflecting time-limited cellular or physiological alterations. This review summarises the multidisciplinary work undertaken in the framework of the European project DoReMi (Low Dose Research towards Multidisciplinary Integration) to identify the most appropriate biomarkers for use in population studies. In addition to logistical and ethical considerations for conducting large-scale epidemiological studies, we discuss the relevance of their use for assessing the effects of low dose ionizing radiation exposure at the cellular and physiological level. We also propose a temporal classification of biomarkers that may be relevant for molecular epidemiology studies which need to take into account the time elapsed since exposure. Finally, the integration of biology with epidemiology requires careful planning and enhanced discussions between the epidemiology, biology and dosimetry communities in order to determine the most important questions to be addressed in light of pragmatic considerations including the appropriate population to be investigated (occupationally, environmentally or medically exposed), and study design. The consideration of the logistics of biological sample collection, processing and storing and the choice of biomarker or bioassay, as well as awareness of potential confounding factors, are also essential.

Clinical clues to identify patients with ocular rosacea - a Germany-wide epidemiologic analysis.

BACKGROUND AND OBJECTIVES: Ocular rosacea is a special manifestation of rosacea with unknown etiology. Eye involvement in rosacea patients is surprisingly common; however, it is often underdiagnosed, resulting in inappropriate treatment. We aimed to provide an updated epidemiologic perspective on ocular rosacea in Germany to improve patient care. PATIENTS AND METHODS: Data of 777 rosacea patients were assessed using a detailed online questionnaire regarding ocular and skin symptoms, previous dermatological and ophthalmological consults, presence of type 1 hypersensitivities, and Demodex testing. All data were statistically analyzed. RESULTS: Most patients reported ocular symptoms (399/777, 51.4%), including red eyes (179/399, 44.9%), itching (187/399, 46.9%), sty or chalazion (309/399, 77.4%), and dryness (108/399, 27.1%). Ocular rosacea was confirmed in 149/309 cases who consulted an ophthalmologist (45.3%). A total of 159/399 (39.8%) had no pre-existing allergies. Eye involvement was significantly associated with the presence of skin symptoms (P < 0.05), impacting patients' general well-being and overall treatment satisfaction. About half of Demodex-positive patients (21/45, 46.7%) showed ocular symptoms. CONCLUSIONS: Eye involvement in rosacea patients was common, often presenting with unspecific symptoms.

Cost-effectiveness of Response-Adapted De-escalation of Immunotherapy in Advanced Melanoma.

Importance: Combination immunotherapy with nivolumab and ipilimumab has markedly improved outcomes for patients with advanced melanoma. However, these therapies pose a considerable financial burden to both patients and the health care system. The ADAPT-IT trial demonstrated comparable progression-free and overall survival for patients with response-adapted ipilimumab discontinuation compared with standard of care (SOC). Objective: To determine the cost-effectiveness of ipilimumab discontinuation for patients with interim imaging-confirmed tumor response in the treatment of advanced melanoma. Design, Setting, and Participants: This cost-effectiveness analysis was performed using data from the ADAPT-IT (follow-up of 33 months) and CheckMate 067 (follow-up of 6.5 years) trials, as well as published literature over the ADAPT-IT trial duration of 33 months. The analysis was performed in a US setting from a US-payer perspective, and the willingness-to-pay (WTP) threshold was set at $100 000/quality-adjusted life-year (QALY). A total of 355 patients with previously untreated melanoma (unresectable stage III or IV metastatic melanoma) were included. Exposure: Response-adapted ipilimumab discontinuation compared with SOC therapy. Main Outcomes and Measures: The primary outcomes of the CheckMate trial were overall survival and progression-free survival, while that of ADAPT-IT was objective response. This informed a decision model to estimate lifetime costs and QALYs associated with both strategies. Incremental cost, effectiveness, and cost-effectiveness ratio were assessed. Sensitivity and scenario analyses were performed to account for variability in trials and input parameters. Results: Of the 355 patients included in the analysis, 41 patients were from the ADAPT-IT trial (median age, 65 years; 28 [68%] male) and 314 patients from the CheckMate 067 trial (median age, 61 years; 206 [66%] male). Response-adapted treatment was the cost-effective option in 94.0% of scenarios based on Monte Carlo simulations, with a dominant incremental cost-effectiveness ratio and an incremental net monetary benefit of $28 849 compared with SOC therapy. Cost savings were estimated at $19 891 per patient compared with SOC. In scenario analyses, current SOC was only considered as a cost-effective option under best survival assumptions and if the willingness-to-pay threshold exceeded $630 000/QALY. Conclusions and Relevance: This economic evaluation demonstrated that response-adapted treatment de-escalation in patients with advanced melanoma may lead to considerable savings in health care costs and could represent the most cost-effective strategy across various resource settings. Future trials should aim to provide further evidence on noninferiority.

Efficacy and tolerability of a detergent and care component for rosacea patients: A split-face, vehicle-controlled, randomized trial.

BACKGROUND: The treatment of facial erythema and subjective symptoms of rosacea patients remains challenging in clinical practice. Cosmeceuticals, care components containing active ingredients such as phytochemicals, play a growing role in treatment plans. However, well-designed studies on their efficacy and limitations are widely missing. OBJECTIVE: A foam and a cream for rosacea patients were assessed based on objective and subjective methodology. The tolerability of skin and eyes was evaluated. METHODS: A randomized, double-blinded, split-face, and vehicle-controlled trial was conducted. At baseline and after four weeks of product use, dermatological and ophthalmological investigations were performed, employing image analysis of facial erythema, clinical assessments, and questionnaires. RESULTS: The patient cohort comprised 33 females with persistent facial erythema due to rosacea. No significant differences were found between the vehicle and the verum. According to the analysis of facial erythema, a "less pronounced" or "much less pronounced" appearance was seen in two thirds of patients comparing V1 to V0. Especially, the dryness of the skin improved by the use of the vehicle and the verum. Adverse subjective skin sensations decreased by 61.3% for the verum side and by 58.6% for the vehicle side. Subjective and objective analysis of ocular manifestation differed, with subjective manifestations reported more frequently, thus highlighting underdiagnosis of ocular rosacea. CONCLUSIONS: As no clear differences between the verum and the vehicle were found, an optimal skin care regime itself seems to have a superior effect in the relief of facial erythema and foremost of subjective symptoms, rather than certain active ingredients.