Neutrophils activated by membrane attack complexes increase the permeability of melanoma blood vessels.

The microenvironment of malignant melanomas defines the properties of tumor blood vessels and regulates infiltration and vascular dissemination of immune and cancer cells, respectively. Previous research in other cancer entities suggested the complement system as an essential part of the tumor microenvironment. Here, we confirm activation of the complement system in samples of melanoma patients and murine melanomas. We identified the tumor endothelium as the starting point of the complement cascade. Generation of complement-derived C5a promoted the recruitment of neutrophils. Upon contact with the vascular endothelium, neutrophils were further activated by complement membrane attack complexes (MACs). MAC-activated neutrophils release neutrophil extracellular traps (NETs). Close to the blood vessel wall, NETs opened the endothelial barrier as indicated by an enhanced vascular leakage. This facilitated the entrance of melanoma cells into the circulation and their systemic spread. Depletion of neutrophils or lack of MAC formation in complement component 6 (C6)-deficient animals protected the vascular endothelium and prevented vascular intravasation of melanoma cells. Our data suggest that inhibition of MAC-mediated neutrophil activation is a potent strategy to abolish hematogenous dissemination in melanoma.

Tailoring polishing steps for effective removal of polysorbate-degrading host cell proteins in antibody purification.

Ensuring the quality and safety of biopharmaceutical products requires the effective separation of monoclonal antibodies (mAbs) from host cell proteins (HCPs). A major challenge in this field is the enzymatic hydrolysis of polysorbates (PS) in drug products. This study addresses this issue by investigating the removal of polysorbate-degrading HCPs during the polishing steps of downstream purification, an area where knowledge about individual HCP behavior is still limited. We investigated the separation of different mAb formats from four individual polysorbate degrading hydrolases (CES1F, CES2C, LPLA2, and PAF-AH) using cation exchange (CEX) and mixed-mode chromatography (MMC) polishing steps. Our research identified a key challenge: The similar elution behavior of mAbs and HCPs during chromatographic separation. To investigate this phenomenon, we performed high-throughput binding screenings for recombinant polysorbate degrading hydrolases and representative mAb candidates on CEX and MMC chromatography resins. We then employed a three-step strategy that also served as a scale-up process, optimizing separation conditions and leading to the successful removal of specific HCPs while maintaining high mAb recovery rates (>96%). This strategy involved the use of surface response models and miniature columns for screening, followed by validation on larger columns using a chromatography system. Our results highlight the critical role of the inherent properties of mAbs for successful separation from HCPs. These results underscore the need to tailor the purification process to leverage the slight differences in binding behavior and elution profiles between mAbs and specific HCPs. This approach lays the foundation for developing more effective strategies for overcoming the challenge of enzymatic polysorbate degradation, paving the way for improved quality and safety in biopharmaceutical products.

532-nm potassium titanyl-phosphate laser versus 595-nm pulsed dye laser for port-wine birthmarks: A prospective, randomized, split-side study.

BACKGROUND: Pulsed dye lasers (PDL) are currently the first-line treatment of port-wine birthmarks (PWB). Due to high maintenance costs and instable technology, alternative methods are needed. OBJECTIVES: To compare clinical outcomes of a variable-sequenced, long-pulsed 532-nm potassium titanyl-phosphate (KTP) laser and PDL on treating PWB. METHODS: A prospective, randomized, split-side study. Patients were treated with a KTP laser and PDL with 1 to 5 sessions at intervals of 6-8 weeks. A follow-up visit was scheduled 6 weeks post-treatment. Efficacy was evaluated through colorimetric analysis, area reduction measurements and clinical evaluations by two blinded investigators based on photo documentation. Subjects provided rating of pain intensity during treatment, post-treatment reactions and satisfaction. Safety was measured by adverse events. Maintenance issues of the laser systems were documented. RESULTS: A total of 35 patients (mean age 42.1 years) were enrolled. 63% were female. Patients received 2.4 (SD 1.4; 1-5) treatment sessions. Colorimetric analysis indicated a comparable clearance effect in PWB of both KTP laser and PDL. Independent investigators rated clinical appearance to be significantly improved compared to baseline. No significant difference was observed between both laser systems. Regarding post-treatment reactions, the KTP laser caused less swelling, purpura and crusts. 96% would recommend both treatment modalities. Patients were satisfied with both laser systems. During the study, PDL systems malfunctioned for 6.6 months in total. For the KTP laser, we did not observe any system failures. CONCLUSION: Our data indicate that the KTP laser of the latest generation with large-spot sizes, subpulse technology and cryogen cooling has a comparable efficacy to the PDL in treating PWB. In addition, KTP laser is associated with greater tolerability, fewer technical failures and lower repair costs. Further prospective studies are required to determine the true effectiveness of the KTP laser in PWB treatment. This study was preregistered in Clinicaltrials.gov (NCT05771298).

Differential predictive value of tissue-specific PD-L1 expression scores in adjuvant immunotherapy of melanoma.

BACKGROUND: Adjuvant treatment of stage II-IV melanoma with PD-1-based immune checkpoint inhibitors (ICI) has improved relapse-free survival (RFS) and has therefore become a standard-of-care treatment option. Approximately 25%-30% of patients still recur within 1 year. Predictive biomarkers reflecting real-world data are desired. The predictive relevance of tumour tissue PD-L1 expression in the adjuvant setting remains inconclusive. OBJECTIVES: This retrospective, observational study was conducted to evaluate the value of PD-L1 expression scores in different tumour tissue locations in predicting response towards adjuvant immunotherapeutic treatment. METHODS: Tumour tissue taken prior to anti-PD-1 adjuvant ICI in 243 stage II-IV melanoma patients was collected at University Skin Cancer Center Hamburg. PD-L1 expression was evaluated on immune cells (ICS), tumour cells (TPS) and combined (CPS). Scores were determined by independent pathological physician quantification and correlated with therapy outcome at different cut-off (CO) levels (relapse-free survival, RFS) for different tumour tissue locations (primary tumour, metastases). RESULTS: A total of 104 patients were eligible for analysis. Positivity of ICS, TPS and CPS showed no predictive RFS outcome association at different CO levels when analysed irrespective of tissue origin. In primary tumours, ICS at CO 1% showed a significantly improved RFS upon positivity (HR 0.22). In contrast, positivity to TPS (CO 1%) correlated significantly and independently with improved RFS when evaluated in metastatic tumour tissue specimens (HR 0.37). CONCLUSIONS: PD-L1 tumour tissue expression may serve as a predictive biomarker for adjuvant ICI treatment response stratification in melanoma, but caution should be spent on the origin of tumour tissue analysed. The cell-type relevant for the predictive value of PD-L1 expression is tissue-specific with immune cells being important in primary tumours while tumour cells are key in metastases. The present results should be validated in a multicentre cohort.

C-reactive protein flare predicts response to checkpoint inhibitor treatment in melanoma.

BACKGROUND: The treatment of melanoma has been revolutionized by the use of immune checkpoint inhibition (ICI), but many patients do not benefit. Furthermore, immune-related adverse events may occur during therapy. A predictive biomarker is needed to reliably identify patients benefitting. In lung, renal cell and bladder cancer early C-reactive protein (CRP) kinetics were shown to be a predictive biomarker for ICI. OBJECTIVE: Here, we investigate early CRP kinetics as predictive biomarker for ICI in melanoma patients. METHODS: Two independent prospectively collected cohorts were analysed: Cohort 1 (n = 87) with advanced and Cohort 2 (n = 99) with completely resected melanoma. Patients were stratified by in the dynamics of CRP after ICI initiation: A doubling of baseline CRP within 30 days followed by at least a 30% drop within 3 months was classified as a CRP flare. If no doubling of CRP was reported, but a 30% drop within 3 months, patients were classified as CRP responders and all others as CRP non-responders. Analysed factors included clinical characteristics like S100B and LDH. Median follow-up was 1.5 and 1.7 years for Cohorts 1 and 2. RESULTS: In Cohort 1 CRP flare (n = 12), CRP responders (n = 43) and CRP non-responders (n = 32) with a progression-free survival (PFS) of 0.7, 0.6 and 0.2 years (p = 0.017) and an overall survival (OS) of 2.2, 1.5 and 1.0 years (p = 0.014), respectively. Multivariable Cox analysis showed an independent risk reduction of progression for CRP responders by 62% compared to CRP non-responders (p = 0.001). In Cohort 2 CRP flare (n = 13), CRP responders (n = 70) and CRP non-responders (n = 16) the log-rank analysis showed a significant difference between OS and recurrence-free survival (RFS) curves (p = 0.046 and p = 0.049). CONCLUSION: Early CRP kinetics could indicate a response to ICI with improved OS and RFS/PFS. CRP flare and CRP response indicating significantly improved outcomes compared to CRP non-responders.

Mogamulizumab-associated rash - Case series and review of the literature.

Mogamulizumab, a monoclonal antibody directed against CC chemokine receptor 4, is approved as a second-line treatment of mycosis fungoides and Sézary syndrome. One of the most common side effects is mogamulizumab-associated rash (MAR), which can present in a variety of clinical and histological types. Clinically, it can be difficult to differentiate between MAR and progression of the underlying disease, so histological examination is crucial for clinicopathological correlation. Current data analyses suggest that MAR is more common in patients with Sézary syndrome and is associated with a significantly better response to treatment, making the distinction from disease progression particularly important. The management of MAR depends on its severity, and therapy may need to be paused. This article presents three cases from our clinic and reviews the current literature on MAR. It emphasizes the importance of understanding MAR in the management of patients with cutaneous lymphomas.

Telephone follow-up after outpatient nail surgery - a retrospective analysis.

BACKGROUND: One of the areas of care in dermatosurgery is the surgical treatment of diseases of the nail organ. Side effects and complications after nail surgery were investigated by telephone follow-up (TFU), and its suitability for postoperative monitoring and consultation was assessed. PATIENTS AND METHODS: All patients who underwent nail surgery at the Department of Dermatology at the Ludwigshafen City Hospital from October 2019 to December 2021 in outpatient setting were contacted by telephone on the second to third postoperative day and questioned in a standardized manner about postoperative complaints and counselled if necessary. RESULTS: A total of 100 cases were followed up. The most common procedures performed were phenol matricectomy (41%), nail avulsion (16%), and nail matrix biopsies (9%). 50% and 21% of patients reported pain on the day of the procedure and the day after surgery, respectively. After nail avulsion, pain was statistically significantly more frequently reported on the day following the procedure and pain medication was statistically significantly more frequently required (p  =  0.002). Serious adverse events did not occur after nail surgery. 10% of the respondents raised specific questions and needed counseling by TFU. CONCLUSIONS: All nail surgeries were well tolerated in the outpatient setting. Pain was the most common side effect, although only half of all patients reported pain on the day of surgery and only 21% on the day after the procedure. The TFU proved to be an effective and practical as well as easy to establish method for postoperative follow-up and consultation after outpatient nail surgery.

Just-in-time adaptive ecological momentary assessment (JITA-EMA).

Interest in just-in-time adaptive interventions (JITAI) has rapidly increased in recent years. One core challenge for JITAI is the efficient and precise measurement of tailoring variables that are used to inform the timing of momentary intervention delivery. Ecological momentary assessment (EMA) is often used for this purpose, even though EMA in its traditional form was not designed specifically to facilitate momentary interventions. In this article, we introduce just-in-time adaptive EMA (JITA-EMA) as a strategy to reduce participant response burden and decrease measurement error when EMA is used as a tailoring variable in JITAI. JITA-EMA builds on computerized adaptive testing methods developed for purposes of classification (computerized classification testing, CCT), and applies them to the classification of momentary states within individuals. The goal of JITA-EMA is to administer a small and informative selection of EMA questions needed to accurately classify an individual's current state at each measurement occasion. After illustrating the basic components of JITA-EMA (adaptively choosing the initial and subsequent items to administer, adaptively stopping item administration, accommodating dynamically tailored classification cutoffs), we present two simulation studies that explored the performance of JITA-EMA, using the example of momentary fatigue states. Compared with conventional EMA item selection methods that administered a fixed set of questions at each moment, JITA-EMA yielded more accurate momentary classification with fewer questions administered. Our results suggest that JITA-EMA has the potential to enhance some approaches to mobile health interventions by facilitating efficient and precise identification of momentary states that may inform intervention tailoring.

Can you tell people's cognitive ability level from their response patterns in questionnaires?

Questionnaires are ever present in survey research. In this study, we examined whether an indirect indicator of general cognitive ability could be developed based on response patterns in questionnaires. We drew on two established phenomena characterizing connections between cognitive ability and people's performance on basic cognitive tasks, and examined whether they apply to questionnaires responses. (1) The worst performance rule (WPR) states that people's worst performance on multiple sequential tasks is more indicative of their cognitive ability than their average or best performance. (2) The task complexity hypothesis (TCH) suggests that relationships between cognitive ability and performance increase with task complexity. We conceptualized items of a questionnaire as a series of cognitively demanding tasks. A graded response model was used to estimate respondents' performance for each item based on the difference between the observed and model-predicted response ("response error" scores). Analyzing data from 102 items (21 questionnaires) collected from a large-scale nationally representative sample of people aged 50+ years, we found robust associations of cognitive ability with a person's largest but not with their smallest response error scores (supporting the WPR), and stronger associations of cognitive ability with response errors for more complex than for less complex questions (supporting the TCH). Results replicated across two independent samples and six assessment waves. A latent variable of response errors estimated for the most complex items correlated .50 with a latent cognitive ability factor, suggesting that response patterns can be utilized to extract a rough indicator of general cognitive ability in survey research.

Getting the bugs out of AI: Advancing ecological research on arthropods through computer vision.

Deep learning for computer vision has shown promising results in the field of entomology, however, there still remains untapped potential. Deep learning performance is enabled primarily by large quantities of annotated data which, outside of rare circumstances, are limited in ecological studies. Currently, to utilize deep learning systems, ecologists undergo extensive data collection efforts, or limit their problem to niche tasks. These solutions do not scale to region agnostic models. However, there are solutions that employ data augmentation, simulators, generative models, and self-supervised learning that can supplement limited labelled data. Here, we highlight the success of deep learning for computer vision within entomology, discuss data collection efforts, provide methodologies for optimizing learning from limited annotations, and conclude with practical guidelines for how to achieve a foundation model for entomology capable of accessible automated ecological monitoring on a global scale.

Local blood coagulation drives cancer cell arrest and brain metastasis in a mouse model.

Clinically relevant brain metastases (BMs) frequently form in cancer patients, with limited options for effective treatment. Circulating cancer cells must first permanently arrest in brain microvessels to colonize the brain, but the critical factors in this process are not well understood. Here, in vivo multiphoton laser-scanning microscopy of the entire brain metastatic cascade allowed unprecedented insights into how blood clot formation and von Willebrand factor (VWF) deposition determine the arrest of circulating cancer cells and subsequent brain colonization in mice. Clot formation in brain microvessels occurred frequently (>95%) and specifically at intravascularly arrested cancer cells, allowing their long-term arrest. An extensive clot embedded ∼20% of brain-arrested cancer cells, and those were more likely to successfully extravasate and form a macrometastasis. Mechanistically, the generation of tissue factor-mediated thrombin by cancer cells accounted for local activation of plasmatic coagulation in the brain. Thrombin inhibition by treatment with low molecular weight heparin or dabigatran and an anti-VWF antibody prevented clot formation, cancer cell arrest, extravasation, and the formation of brain macrometastases. In contrast, tumor cells were not able to directly activate platelets, and antiplatelet treatments did reduce platelet dispositions at intravascular cancer cells but did not reduce overall formation of BMs. In conclusion, our data show that plasmatic coagulation is activated early by intravascular tumor cells in the brain with subsequent clot formation, which led us to discover a novel and specific mechanism that is crucial for brain colonization. Direct or indirect thrombin and VWF inhibitors emerge as promising drug candidates for trials on prevention of BMs.

Virtual Human-Delivered Interviews for Patients With Chronic Pain: Feasibility, Acceptability, and a Pilot Randomized Trial of Standard Medical, Psychosocial, and Educational Interviews.

OBJECTIVE: Seminal advances in virtual human (VH) technology have introduced highly interactive, computer-animated VH interviewers. Their utility for aiding in chronic pain care is unknown. We developed three interactive telehealth VH interviews-a standard pain-focused, a psychosocial risk factor, and a pain psychology and neuroscience educational interview. We then conducted a preliminary investigation of their feasibility, acceptability, and efficacy. We also experimentally compared a human and a computer-generated VH voice. METHODS: Patients ( N = 94, age = 22-78 years) with chronic musculoskeletal pain were randomly assigned to the standard ( n = 31), psychosocial ( n = 34), or educational ( n = 29) VH interview and one of the two VH voices. Acceptability ratings included patient satisfaction and expectations/evaluations of the VH interview. Outcomes assessed at baseline and about 1-month postinterview were pain intensity, interference, emotional distress, pain catastrophizing, and readiness for pain self-management. Linear mixed-effects models were used to test between- and within-condition effects. RESULTS: Acceptability ratings showed that satisfaction with the VH and telehealth format was generally high, with no condition differences. Study attrition was low ( n = 5). Intent-to-treat-analyses showed that, compared with the standard interview, the psychosocial interview yielded a significantly greater reduction in pain interference ( p = .049, d = 0.43) and a marginally greater reduction in pain intensity ( p = .054, d = 0.36), whereas the educational interview led to a marginally greater yet nonsignificant increase in readiness for change ( p = .095, d = 0.24), as well as several significant improvements within-condition. Results did not differ by VH voice. CONCLUSIONS: Interactive VH interviewers hold promise for improving chronic pain care, including probing for psychosocial risk factors and providing pain-related education.

In vivo characterization of laser-assisted delivery of hyaluronic acid using multiphoton fluorescence lifetime imaging.

Laser-assisted drug delivery (LADD) is a treatment method to enhance the penetration of pharmaceuticals through the skin. The aim of the present study is to track hyaluronic acid (HA) and analyse its effect on human skin in vivo after ablative fractional laser (AFL) treatment. Healthy male and female subjects were recruited. Four areas were marked on their forearms of each volunteer, and each area was assigned to one of the following treatment options: AFL + HA, AFL only, HA only or untreated control. A carbon dioxide laser was used for the AFL treatment. Follow-up measurements were scheduled 30 min and 30 days after treatment using multiphoton tomography equipped with fluorescence lifetime imaging (MPT-FLIM). A total of 11 subjects completed the study. By detecting fluorescence lifetimes, the HA and the anaesthetic ointment were clearly distinguishable from surrounding tissue. After AFL treatment, HA could be visualized in all epidermal and upper dermal layers. In contrast, HA in intact skin was only detected in the superficial layers at distinctly lower levels. The applied HA gel seemed to have beneficial properties for the wound healing process after laser treatment. LADD has proven to be a fast and effective method to increase HA uptake into the skin, allowing for improved hydration and skin rejuvenation over time. Furthermore, LADD could be a beneficial treatment option in laser resurfacing. MPT-FLIM proved to be an appropriate diagnostic tool for drug delivery tracking and monitoring of treatment response for individualized therapy adjustment.

Under pressure-the influence of hypergravity on electrocortical activity and neurocognitive performance.

The effects of hypergravity and the associated increased pressure on the human body have not yet been studied in detail, but are of great importance for the safety of astronauts on space missions and could have a long-term impact on rehabilitation strategies for neurological patients. Considering the plans of international space agencies with the exploration of Mars and Moon, it is important to explore the effects of both extremes, weightlessness and hypergravity. During parabolic flights, a flight manoeuvre that artificially creates weightlessness and hypergravity, electrocortical activity as well as behavioural parameters (error rate and reaction time) and neuronal parameters (event-related potentials P300 and N200) were examined with an electroencephalogram. Thirteen participants solved a neurocognitive task (mental arithmetic task as a primary task and oddball paradigm as a secondary task) within normal as well as hypergravity condition in fifteen consecutive parabolas for 22 s each. No changes between the different gravity levels could be observed for the behavioural parameters and cortical current density. A significantly lower P300 amplitude was observed in 1 G, triggered by the primary task and the target sound of the oddball paradigm. The N200, provoked by the sounds of the oddball paradigm, revealed a higher amplitude in 1.8 G. A model established by Kohn et al. (2018) describing changes in neural communication with decreasing gravity can be used here as an explanatory approach. The fluid shift increases the intracranial pressure, decreases membrane viscosity and influences the open state probability of ion channels. This leads to an increase in the resting membrane potential, and the threshold for triggering an action potential can be reached more easily. The question now arises whether the observed changes are linear or whether they depend on a specific threshold.

Unraveling the initial steps of the ignition chemistry of the hypergolic ionic liquid 1-ethyl-3-methylimidazolium cyanoborohydride ([EMIM][CBH]) with nitric acid (HNO3) exploiting chirped pulse triggered droplet merging.

The composition of the products and the mechanistic routes for the reaction of the hypergolic ionic liquid (HIL) 1-ethyl-3-methylimidazolium cyanoborohydride ([EMIM][CBH]) and nitric acid (HNO3) at various concentrations from 10% to 70% were explored using a contactless single droplet merging within an ultrasonic levitation setup in an inert atmosphere of argon to reveal the initial steps that cause hypergolicity. The reactions were initiated through controlled droplet-merging manipulation triggered by a frequency chirp pulse amplitude modulation. Utilizing the high-speed optical and infrared cameras surrounding the levitation process chamber, intriguing visual images were unveiled: (i) extensive gas release and (ii) temperature rises of up to 435 K in the merged droplets. The gas development was validated qualitatively and quantitatively with Fourier Transform Infrared Spectroscopy (FTIR) indicating the major gas-phase products to be hydrogen cyanide (HCN) and nitrous oxide (N2O). The merged droplet was also probed by pulsed Raman spectroscopy which deciphered features for key functional groups of the reaction products and intermediates (-BH, -BH2, -BH3, -NCO); reaction kinetics revealed that the reaction was initiated by the interaction of the [CBH]- anion of the HIL with the oxidizer (HNO3) through proton transfer. Computations indicate the formation of a van-der-Waals complex between the [CBH]- anion and HNO3 initially, followed by proton transfer from the acid to the anion and subsequent extensive isomerization; these rearrangements were found to be essential for the formation of HCN and N2O. The exoergicity observed during the merging process provides a molar enthalpy change up to 10 kJ mol-1 to the system, which could be sufficient for a significant fraction of the reactants of about 11% to overcome the reaction barriers in the individual steps of the computationally determined minimum energy pathways.

Evaluation of Pressing Issues in Ecological Momentary Assessment.

The use of repeated, momentary, real-world assessment methods known as the Experience Sampling Method and Ecological Momentary Assessment (EMA) has been broadly embraced over the last few decades. These methods have extended our assessment reach beyond lengthy retrospective self-reports as they can capture everyday experiences in their immediate context, including affect, behavior, symptoms, and cognitions. In this review we evaluate nine conceptual, methodological, and psychometric issues about EMA with the goal of stimulating conversation and guiding future research on these matters: the extent to which participants are actually reporting momentary experiences, respondents' interpretation of momentary questions, the use of comparison standards in responding, efforts to increase the EMA reporting period beyond the moment to longer periods within a day, training of EMA study participants, concerns about selection bias of respondents, the impact of missing EMA assessments, the reliability of momentary data, and for which purposes EMA might be considered a gold standard for assessment. Resolution of these issues should have far-reaching implications for advancing the field.

Thermal eye injuries from dermatologic laser treatments-an experimental study.

In recent years, severe ocular complications after dermatological laser therapies have been reported. One hypothesis is thermal damage due to heating of the metal eye shields. The aim of the present study is to evaluate the safety of ocular metal eye shields during laser therapy of the periocular region. For the experimental study, porcine eyelids were exposed to continuously increasing laser energy and multiple pulses using a number of dermatologic laser systems. Temperature differences of the convex and concave surface of metal eye shields were constantly measured using a thermocouple. Maximum increase of the convex surface of shields was + 8.9 °C (± 0.1 °C) provided by the long-pulsed alexandrite laser (20-25-J/cm2 energy, 15-mm spot size, 20-ms pulse duration, 1 Hz). Present data indicate that metal eye shields provide sufficient thermal protection when clinically used laser parameters are applied. Other safety precautions continue to be essential to protect both the patient and the laser operator. These include the use of nonreflective metal eye shields, precise knowledge of laser physics, and a clear understanding of how they interact with ocular and periocular anatomy.

Autologous minced cartilage repair for chondral and osteochondral lesions of the knee joint demonstrates good postoperative outcomes and low reoperation rates at minimum five-year follow-up.

PURPOSE: Minced cartilage is a one-step, autologous procedure with promising short-term results. The aim of the present study was to evaluate mid-term results in a patient cohort with chondral and osteochondral lesions in the knee joint treated with minced cartilage. METHODS: From 2015 through 2016, a total of 34 consecutive patients were treated with a single-step, autologous minced cartilage for knee chondral and osteochondral lesions. Numeric analogue scale (NAS) for pain and knee function were obtained prior to surgery and at 12, 24 and 60 months postoperatively. Secondary outcomes, including Lysholm score, Tegner activity score, and the International Knee Documentation Committee (IKDC) score, were recorded at final follow-up. MRI examinations of patients with unplanned radiological follow-up were analysed using the MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score. RESULTS: A total of 28 patients (44.1% females, age at surgery: 29.5 ± 11.5 years) were available at a mean follow-up of 65.5 ± 4.1 months. Mean defect size was 3.5 ± 1.8 cm2. NAS for pain decreased from a median of 7 (range: 2-10) preoperatively to 2 (0-8) postoperatively. NAS knee function improved from a median of 7 (range: 2-10) to 3 (0-7) after five years, respectively. Satisfactory Lysholm (76.5 ± 12.5), IKDC (71.6 ± 14.8) and Tegner activity (4, range 3-9) scores were reported at final follow-up. Of all patients, 21(75%) and 19 (67.9%) reached or exceeded the PASS for the IKDC- and Lysholm score at final follow-up, respectively. The average overall MOCART 2.0 scores for all postoperatively performed MRIs (n = 23) was 62.3 ± 17.4. Four (14.2%) postoperative complications were directly linked to minced cartilage, one (3.5%) of which required revision surgery. CONCLUSION: One-step, autologous minced cartilage repair of chondral and osteochondral lesions of the knee without the necessity for subchondral bone treatment demonstrated good patient-reported outcomes, low complication rates, and graft longevity at mid-term follow-up. Minced cartilage represents a viable treatment option to more traditional cartilage repair techniques even in mid-term. LEVEL OF EVIDENCE: Level III.

Direct-to-Consumer Teledermatology in Germany: A Retrospective Analysis of 1,999 Teleconsultations Suggests Positive Impact on Patient Care.

Background: There is a high demand for dermatological care in Germany. As use of teledermatology has increased significantly, this study aimed to investigate the impact of teledermatology on patient care. Methods: This retrospective cross-sectional study used data from a direct-to-consumer teledermatology platform using store-and-forward technology available in Germany between July 2021 and April 2022. Additional patient characteristics were collected using a voluntary follow-up questionnaire, 28 days after teleconsultation. Results: Data of 1,999 enrolled patients were evaluated. Patients had a mean age of 36 years, and 61.2% (1,223/1,999) lived in a rural residence. The most common diagnoses included eczema (36.0%, 701/1,946), fungal diseases (15.4%, 299/1,946), and acne (12.5%, 243/1,946). The follow-up questionnaire was answered by 166 patients (8.3%, 166/1,999). In total, 42.8% (71/166) of patients had undergone no previous medical consultation. The most frequent reason for using teledermatology was the waiting time for a dermatology outpatient appointment (62.0%, 103/166). A total of 62.0% (103/166) participants rated the treatment success as good or very good, while 86.1% (143/166) rated the quality of telemedical care as equal or better to that of an outpatient visit. Conclusion: This study showed that patients often use teledermatology because of functional barriers (waiting times). In this cohort, the diagnoses strongly corresponded to reasons for outpatient presentation. Most patients rated the quality of teledermatology service as at least equivalent to that of outpatient physician visits and reported treatment success. Thus, teledermatology can relieve the burden of outpatient care while providing high benefits from the patient's perspective.

A Rejected Hypothesis: Phenomenon of High Treatment Adherence in Direct-to-Consumer Teledermatology Despite Lack of Direct Physician-Patient Interaction.

Background: Adherence to dermatological treatment is described as poor. Empathy and open communication in the physician-patient relationship has been proven to improve adherence. As direct-to-consumer teledermatology enables patients to access dermatological consultations without in-person interactions, we hypothesized treatment adherence in teledermatology to be low. Methods: The objective of the study was to examine treatment adherence in teledermatology. This retrospective cross-sectional study used data from patients treated through a German direct-to-consumer teledermatology platform between July 2021 and April 2022. Additional information was collected through voluntary follow-up questionnaires provided to patients to assess individual treatment success, treatment-related adverse events, and treatment adherence. Results: Data collection included 771 patients; 61.6% (475/771) were women (mean age 35 years). In 46% (355/771), skin disease had been present for <3 months before teleconsultation. Of all patients who answered the follow-up questionnaire (n = 228), 28.5% (65/228) reported treatment-related adverse events, with skin dryness being the most common (56.9%, 37/65). Adverse events resulting in treatment discontinuation were reported in 1.3% (3/228) of all cases. Improvement in skin condition on therapy was described by 75.4% (172/228). In 85.5% (195/228), full treatment adherence was reported. Conclusion: This is the first study worldwide to examine data on treatment adherence in direct-to-consumer-teledermatology. Despite the lack of doctor-patient interaction, the results of our study demonstrate that most patients show high treatment adherence. Possible drivers contributing to high compliance rates could be the high proportion of new-onset skin diseases, the high treatment success of the prescribed therapies, and the low rate of serious adverse events.