Incidence of sexually transmitted infections and association with behavioural factors: Time-to-event analysis of a large pre-exposure prophylaxis (PrEP) cohort.

OBJECTIVES: Our objective was to obtain long-term data on the incidence of sexually transmitted infections (STIs) and their association with behavioural factors after widespread pre-exposure prophylaxis (PrEP) implementation. METHODS: This was a time-to-event analysis of a national PrEP cohort in Switzerland (SwissPrEPared study). Participants were people without HIV interested in taking PrEP with at least two STI screening visits. Primary outcomes were incidence rate of gonorrhoea, chlamydia, and syphilis. The association between behavioural factors and STI diagnosis was expressed using hazard ratios. We adjusted for testing frequency and calendar year. RESULTS: This analysis included 3907 participants enrolled between April 2019 and April 2022, yielding 3815.7 person-years of follow-up for gonorrhoea (15 134 screenings), 3802.5 for chlamydia (15 141 screenings), and 3858.6 for syphilis (15 001 screenings). The median age was 39 years (interquartile range [IQR] 32-47), 93.8% (n = 3664) identified as men who have sex with men (MSM). The incidence was 22.8 (95% confidence interval [CI] 21.3-24.4) per 100 person-years for gonorrhoea, 26.3 (95% CI 24.7-28.0) for chlamydia, and 4.4 (95% CI 3.8-5.1) for syphilis. Yearly incidence rates decreased between 2019 (all bacterial STIs: 81.6; 95% CI 59.1-109.9) and 2022 (all bacterial STIs: 49.8; 95% CI 44.6-55.3). Participants reporting chemsex substance use were at higher risk of incident STIs, as were those reporting multiple sexual partners. Younger age was associated with a higher risk of gonorrhoea and chlamydia. CONCLUSIONS: Incidence rates of bacterial STIs decreased over time. Young MSM, those with multiple partners, and those using chemsex substances were at increased risk of STIs.

Differential functionality of fluoropyrimidine nucleosides for safe cancer therapy.

Chemotherapies are standard care for most cancer types. Pyrimidine analogs including 5-fluorouracil, cytosine arabinoside, 5-azacytidine, and gemcitabine are effective drugs that are utilized as part of a number of anticancer regimens. However, their lack of cell-specificity results in severe side effects. Therefore, there is a capacity to improve the efficacy of such therapies, while decreasing unwanted side effects. Here, we report that while 5-fluorocytosine is not chemotherapeutic in itself, incorporated into a ribonucleoside and more importantly into an RNA oligonucleotide, it induces cytotoxic effects on cancer cells in vitro . Interestingly, these effects are rescued by both uridine and thymidine. Similarly, in-vitro 2'-deoxy-5-fluorocytidine inhibits the growth of tumor cells but has the advantage of being less toxic to human primary cells compared with 5-fluorocytidine, suggesting that the deoxyribonucleoside could exhibit less side-effects in vivo . Thus, this work indicates that the potency of 5-fluorocytidine and 2'-deoxy-5-fluorocytidine should be further explored. In particular, oligonucleotides incorporating 5-fluorocytosine could be novel chemotherapeutic drugs that could be formulated in cancer-specific particles for safe and efficacious cancer treatments.

Effects of intranasal oxytocin and positive couple interaction on immune factors in skin wounds.

BACKGROUND: Intimate social relationships improve individual health and longevity, an effect which is supposed to be mediated through stress-sensitive endocrine and immune mechanisms in response to positive interaction behavior. On a neuroendocrine level, oxytocin (OT) buffers stress responses, modulates social attachment behavior and has been associated with cytokine expression. Consequently, the aim of the present study was to investigate instructed positive couple interaction, observed behavior, and OT in their effect on immune function. METHODS: In a 4-group design, 80 healthy couples (N = 160 individuals) received four standard dermal suction blister wounds and were randomized to instructed positive interaction/control and intranasal OT/placebo. Unstimulated cytokines (IL-1ß, IL-6, TNF-α) were assessed from wound liquid at 40 min, 105 min and 24 hrs after wounding. RESULTS: Overall, group assignment did not affect friendly or dominant behavior during the interaction sequence. IL-1ß and IL-6 levels, however, were moderated by group assignment with lowest levels in women in the positive interaction and OT condition in IL-1 and highest levels in IL-6. TNF-α responses to wounding were not affected from group assignment, however observed friendliness in women was associated with lower TNF-α levels. DISCUSSION: These findings support the immune-regulating role of friendly behavior in romantic couples. Above this, the data provide the first empirical evidence that an intervention that simultaneously targets neuroendocrine mediators and behavior could affect immune function in a sex specific manner and with potential long-term health relevance.

The A to I editing landscape in melanoma and its relation to clinical outcome.

RNA editing refers to non-transient RNA modifications that occur after transcription and prior to translation by the ribosomes. RNA editing is more widespread in cancer cells than in non-transformed cells and is associated with tumorigenesis of various cancer tissues. However, RNA editing can also generate neo-antigens that expose tumour cells to host immunosurveillance. Global RNA editing in melanoma and its relevance to clinical outcome currently remain poorly characterized. The present study compared RNA editing as well as gene expression in tumour cell lines from melanoma patients of short or long metastasis-free survival, patients relapsing or not after immuno- and targeted therapy and tumours harbouring BRAF or NRAS mutations. Overall, our results showed that NTRK gene expression can be a marker of resistance to BRAF and MEK inhibition and gives some insights of candidate genes as potential biomarkers. In addition, this study revealed an increase in Adenosine-to-Inosine editing in Alu regions and in non-repetitive regions, including the hyperediting of the MOK and DZIP3 genes in relapsed tumour samples during targeted therapy and of the ZBTB11 gene in NRAS mutated melanoma cells. Therefore, RNA editing could be a promising tool for identifying predictive markers, tumour neoantigens and targetable pathways that could help in preventing relapses during immuno- or targeted therapies.

S2k guideline: Rosacea.

This updated and upgraded S2k guideline deals with the diagnosis and treatment of rosacea, which is a common, chronic inflammatory skin disease mostly affecting the face. Initially, rosacea is characterized by recurrent erythema, telangiectasia and flushing. Later, the inflammatory component predominates, with persistent erythema with follicular papules, papulopustules and pustules. The development of phyma, which usually occurs on the acral localizations, is the most severe manifestation. For the treatment of rosacea, the interdisciplinary guideline committee, with representatives of the German Dermatological Society (DDG), the Professional Association of German Dermatologists (BVDD), the German Opthalmological Society (DOG), the Society for Dermopharmacy (GD), the Swiss Society for Dermatology and Venereology (SGDV) and the German Rosacea Aid e. V., recommends the avoidance of trigger factors and topical applications of metronidazole, azelaic acid or ivermectin. For symptomatic treatment of persistent centrofacial erythema, the topical vasoconstrictors brimonidine or oxymetazoline can also be used. Systemic therapy is recommended for therapy-resistant and severe forms of rosacea papulopustulosa. The drug of choice is low-dose doxycycline. Alternatively, low-dose isotretinoin can be recommended. Ocular rosacea should be treated with lid margin hygiene. For topical treatment, ciclosporin eye drops, azithromycin, ivermectin or metronidazole are suggested.

Moisture-associated skin damage (MASD): A best practice recommendation from Wund-D.A.CH.

Wund-D.A.CH., as the umbrella organization of German-speaking wound treatment societies, has currently developed a best practice recommendation for skin damage caused by body fluids, which is known as moisture-associated skin damage (MASD) in English-speaking countries. In this expert consensus, the diseases incontinence-associated dermatitis (IAD), intertriginous dermatitis, including intertrigo, gram-negative bacterial toe web infection and toxic contact dermatitis, including periwound and peristomal dermatitis are presented in a differentiated manner. A common feature of these clinical diseases is a deterioration of skin integrity due to prolonged exposure to body fluids such as urine, stool, sweat or wound exudate with associated physical-irritative and/or chemical irritation. In addition, other comorbidities and cofactors play an important role. The diagnosis of these interdisciplinary and interprofessionally relevant MASD is difficult in everyday clinical practice because there are currently no uniform definitions and many relevant differential diagnoses. Effective strategies for the prevention and therapy of these skin diseases are, for example, continence management, use of efficient, absorbent aids with good retention as well as consistent skin protection and adequate skin care. Another important aspect is the education of patients and relatives about the origin, treatment and prevention of MASD.

Efficacy of MMP-inhibiting wound dressings in the treatment of chronic wounds: a systematic review.

OBJECTIVE: Matrix metalloproteinases (MMPs) substantially contribute to the development of chronicity in wounds. Thus, MMP-inhibiting dressings may support healing. A systematic review was performed to determine the existing evidence base for the treatment of hard-to-heal wounds with these dressings. METHODS: A systematic literature search in databases and clinical trial registers was conducted to identify randomised controlled trials (RCTs) investigating the efficacy of MMP-inhibiting dressings. Studies were analysed regarding their quality and clinical evidence. RESULTS: Of 721 hits, 16 relevant studies were assessed. There were 13 studies performed with collagen and three with technology lipido-colloid nano oligosaccharide factor (TLC-NOSF) dressings. Indications included diabetic foot ulcers, venous leg ulcers, pressure ulcers or wounds of mixed origin. Patient-relevant endpoints comprised wound size reduction, complete wound closure, healing time and rate. Considerable differences in the quality and subsequent clinical evidence exist between the studies identified. Substantial evidence for significant improvement in healing was identified only for some dressings. CONCLUSION: Evidence for the superiority of some MMP-inhibiting wound dressings exists regarding wound closure, wound size reduction, healing time and healing rate. More research is required to substantiate the existing evidence for different types of hard-to-heal wounds and to generate evidence for some of the different types of MMP-inhibiting wound dressings.

[Sucrose octasulfate-evidence in the treatment of chronic wounds]. / Sucrose Octasulfat ­ Evidenz in der Behandlung chronischer Wunden.

Patients with chronic wounds should receive wound treatment in addition to causative therapy. In this context, the lack of adequate evidence for wound healing products has been repeatedly discussed. Using the example of TLC-sucrose octasulfate (TLC: technology lipido-colloid), the present review shows that there is significant data with good evidence and comparability in this area. One therapeutic approach to promote wound healing is the inhibition of matrix-metalloproteinases, for example by sucrose octasulfate. For wound products containing TLC-sucrose octasulfate, several sequential clinical studies have been conducted in recent years. The WHAT study was an open randomized controlled trial (RCT) with 117 patients with venous leg ulcers (VLU). The CHALLENGE study was a double-blind RCT with 187 patients with VLU. The SPID study was a pilot study with 33 patients with diabetic foot ulcers (DFU). The two prospective, multicenter clinical pilot studies NEREIDES and CASSIOPEE examined a total of 88 patients with VLU in different phases of healing. In the REALITY study, a pooled data analysis was performed on eight observational studies with 10,220 patients with chronic wounds of different genesis. In the double-blind, two-armed EXPLORER RCT, 240 patients with neuro-ischemic DFU were followed from first presentation until complete healing. In all studies, a significant promotion of wound healing could be shown by the use of wound healing products with TLC-sucrose octasulfate.

[Importance of adequate pressure in compression therapy : Basis for successful treatment]. / Bedeutung des adäquaten Drucks in der Kompressionstherapie : Basis der erfolgreichen Behandlung.

BACKGROUND: The pressure exerted by a compression device on a part of the body corresponds to the dosage of the compression therapy. Therefore, the pressure course under compression materials should be investigated in different clinical situations. MATERIAL AND METHODS: Pressure measurements were carried out under different compression materials in lying, standing and walking positions within the framework of training, self-experimentation and in patients with venous leg ulcers. RESULTS: The results showed that the pressure varied considerably depending on the material used, the firmness of application, the local configuration (body position) and the time interval between applications. A loss of pressure occurred under each compression therapy, especially under inelastic short-stretch material, mainly due to movement and edema reduction. This pressure loss is decisive for the timing of dressing changes and a reason for the good tolerance of high-pressure levels in mobile patients. CONCLUSION: Low pressures are particularly suitable for edema reduction. Hemodynamic effects require higher pressures (60-80 mmHg). For this purpose, inelastic materials are preferred which enable lower pressures when lying down (40-60 mmHg). As compression bandages are too loosely applied by many users, pressure indicators on bandages or adaptive bandages with templates are helpful to apply the material with the correct pressure. As a consequence of these findings it is postulated that, at least in studies comparing different compression media, pressure measurements should be carried out in the future, whereby the measuring point and body position should be documented.

[Leg ulcers (ulcus cruris): The frequent macrovascular causes]. / Ulcus cruris: Die häufigen, makrovaskulären Ursachen.

Leg ulcers (ulcus cruris): The frequent macrovascular causes Abstract. Four pathologies make up the macrovascular etiologies of leg uclers: Venous leg ulcers (50 %), mixed venous-arterial leg ulcers (20 %), arterial leg ulcers (5 %), and Martorell hypertensive ischemic leg ulcer (5 %). The remaining 20 % concern a large array of other etiologies. Every leg ulcer requires vascular (arterial and venous) work-up, that can be completed with microbiology, biopsy, and more in-depth internal diagnostics, as indicated. Venous leg ulcers are treated with compression therapy. Incompetent saphenous veins and tributaries are abolished if the deep venous system is patent. Occluded iliac veins are recanalised and stented, as possible. Refractory venous leg ulcers are grafted with split skin or punch grafts, depending on their surface. Extensive dermatolipofasciosclerosis may be tangentially removed by shave therapy or fasciectomy, that can be combined with negative pressure wound treatment (NPWT). Skin equivalents are an alternative to treat superficial venous leg ulcers that fail to epithelialise. Their indication in the treatment of more complex leg ulcers still needs to be better investigated and understood. The use of dermal matrices leads to more stable scars. Mixed venous-arterial leg ulcers heal slower and recur more frequently. Compression needs to be reduced. Refractory cases require arterial revascularisation, to transform the mixed venous-arterial into a venous leg ulcer. Arterial leg ulcers require arterial revascularization and split skin graft. Martorell hypertensive ischemic leg ulcer is still underrecognised and often confounded with with pyoderma gangrenosum, which leads therapy into a wrong direction. Necrosectomy, antibiotic treatment in the presence of relevant bacterial superinfection, and repeated split skin grafts eventually heal the vast majority of these extremely painful and potentially mortal wounds.

Swiss Practice Recommendations for the Management of Hidradenitis Suppurativa/Acne Inversa.

Hidradenitis suppurativa (HS) is a painful, inflammatory, debilitating skin disease with a chronic intermittent course. The central pathogenetic event seems to be the occlusion of the hair follicle. HS has a 1-year prevalence of about 1%. It typically presents after puberty with painful, deep-seated, inflamed lesions in the apocrine gland-bearing areas of the body: most commonly the axillae, inguinal, and anogenital regions. HS has a high negative impact on patients' quality of life even in patients with only limited disease burden, and the diagnosis of HS is often made with a long diagnostic delay. In this practical short version we present diagnostic and therapeutic recommendations which are based on a systematic literature search as well as an informal expert consensus of Swiss dermatologists and dermatosurgeons.

Compression therapy in patients with venous leg ulcers.

Wund-D.A.CH. is the umbrella organization of the various wound care societies in German-speaking countries. The present consensus paper on practical aspects pertinent to compression therapy in patients with venous leg ulcers was developed by experts from Germany, Austria, and Switzerland. In Europe, venous leg ulcers rank among the most common causes of chronic wounds. Apart from conservative and interventional wound and vein treatment, compression therapy represents the basis of all other therapeutic strategies. To that end, there are currently a wide variety of materials and systems available. While especially short-stretch bandages or multicomponent systems should be used in the initial decongestion phase, ulcer stocking systems are recommended for the subsequent maintenance phase. Another - to date, far less common - alternative are adaptive Velcro bandage systems. Medical compression stockings have proven particularly beneficial in the prevention of ulcer recurrence. The large number of treatment options currently available enables therapists to develop therapeutic concepts geared towards their patients' individual needs and abilities, thus resulting in good acceptance and adherence. Compression therapy plays a crucial role in the treatment of patients with venous leg ulcers. In recent years, a number of different treatment options have become available, their use and application differing among German-speaking countries. The present expert consensus is therefore meant to outline concrete recommendations for routine implementation of compression therapy in patients with venous leg ulcers.

Kompressionstherapie bei Patienten mit Ulcus cruris venosum.

Wund-D.A.CH. ist der Dachverband deutschsprachiger Fachgesellschaften, die sich mit den Thematiken der Wundbehandlung beschäftigen. Experten verschiedener Fachgesellschaften aus Deutschland, Österreich und der Schweiz haben nun einen aktuellen Konsens der Kompressionstherapie für Patienten mit Ulcus cruris venosum erstellt. In Europa ist das Ulcus cruris venosum eine der häufigsten Ursachen für chronische Wunden. Neben der konservativen und interventionellen Wund- und Venentherapie, ist die Kompressionstherapie die Basis der Behandlungsstrategien. Die Kompressionstherapie kann heute mit sehr unterschiedlichen Materialien und Systemen durchgeführt werden. Während in der Entstauungsphase insbesondere Verbände mit Kurzzugbinden oder Mehrkomponentensysteme zur Anwendung kommen, sind es anschließend überwiegend Ulkus-Strumpfsysteme. Eine weitere, bislang wenig verbreitete Alternative sind adaptive Kompressionsbandagen. Insbesondere für die Rezidivprophylaxe werden medizinische Kompressionsstrümpfe empfohlen. Durch die Vielzahl der heute zur Verfügung stehenden Behandlungsoptionen, kann für nahezu alle Patienten ein Konzept entwickelt werden, dass sich an den individuellen Bedürfnissen und Fähigkeiten orientiert und daher auch akzeptiert und durchgeführt wird. Die Kompressionstherapie ist für die Behandlung von Patienten mit Ulcus cruris venosum essentiell. In den letzten Jahren sind viele verschiedene Therapieoptionen verfügbar, die in den deutschsprachigen Ländern unterschiedlich angewendet oder durchgeführt werden. Daher soll dieser Expertenkonsens dazu beitragen, konkrete Empfehlungen für die praktische Durchführung der Kompressionstherapie von Patienten mit Ulcus cruris venosum darzustellen.

[Compression therapy for inflammatory dermatoses of the legs]. / Kompressionstherapie bei entzündlichen Dermatosen der Beine.

In addition to venous and lymphatic diseases, there is increasing scientific evidence that inflammatory dermatoses of the legs are also indications for compression therapy. Specifically, diseases such as pyoderma gangrenosum, livedoid vasculopathy, cutaneous vasculitides, necrobiosis lipoidica, psoriasis, or erysipelas are conditions for which adjunctive compression therapy may be used when manifestations occur on the lower extremities. When inflammatory dermatoses are accompanied by edema, compression therapy is not an off-label use. Especially because of the often problematic pain symptoms, compression therapy can be performed with low resting pressures around 20 mmHg, especially in inflammatory dermatoses.In this review article, the current scientific aspects of compression therapy in inflammatory dermatoses of the legs and the corresponding limitations are presented in a differentiated manner.

Synthetic mRNAs Containing Minimalistic Untranslated Regions Are Highly Functional In Vitro and In Vivo.

Synthetic mRNA produced by in vitro transcription (ivt mRNA) is the active pharmaceutical ingredient of approved anti-COVID-19 vaccines and of many drugs under development. Such synthetic mRNA typically contains several hundred bases of non-coding "untranslated" regions (UTRs) that are involved in the stabilization and translation of the mRNA. However, UTRs are often complex structures, which may complicate the entire production process. To eliminate this obstacle, we managed to reduce the total amount of nucleotides in the UTRs to only four bases. In this way, we generate minimal ivt mRNA ("minRNA"), which is less complex than the usual optimized ivt mRNAs that are contained, for example, in approved vaccines. We have compared the efficacy of minRNA to common augmented mRNAs (with UTRs of globin genes or those included in licensed vaccines) in vivo and in vitro and could demonstrate equivalent functionalities. Our minimal mRNA design will facilitate the further development and implementation of ivt mRNA-based vaccines and therapies.

The utility of artificial intelligence platforms for patient-generated questions in Mohs micrographic surgery: a multi-national, blinded expert panel evaluation.

BACKGROUND: Artificial intelligence (AI) and large language models (LLMs) transform how patients inform themselves. LLMs offer potential as educational tools, but their quality depends upon the information generated. Current literature examining AI as an informational tool in dermatology has been limited in evaluating AI's multifaceted roles and diversity of opinions. Here, we evaluate LLMs as a patient-educational tool for Mohs micrographic surgery (MMS) in and out of the clinic utilizing an international expert panel. METHODS: The most common patient MMS questions were extracted from Google and transposed into two LLMs and Google's search engine. 15 MMS surgeons evaluated the generated responses, examining their appropriateness as a patient-facing informational platform, sufficiency of response in a clinical environment, and accuracy of content generated. Validated scales were employed to assess the comprehensibility of each response. RESULTS: The majority of reviewers deemed all LLM responses appropriate. 75% of responses were rated as mostly accurate or higher. ChatGPT had the highest mean accuracy. The majority of the panel deemed 33% of responses sufficient for clinical practice. The mean comprehensibility scores for all platforms indicated a required 10th-grade reading level. CONCLUSIONS: LLM-generated responses were rated as appropriate patient informational sources and mostly accurate in their content. However, these platforms may not provide sufficient information to function in a clinical environment, and complex comprehensibility may represent a barrier to utilization. As the popularity of these platforms increases, it is important for dermatologists to be aware of these limitations.