Medicine and Pharmacology

Abstract: This study aimed to evaluate whether the Synerjet system can maximize the trans-dermal delivery and skin rejuvenation of nano-NMN. In a 4-week split-face trial (n=21), this combination demonstrated marked clinical superiority over topical nano-NMN alone (p < 0.001), yielding enhanced improvements in wrinkles (170.56% in periorbital and 154.45% in nasolabial, respectively), pore volume (176.62%), and deep hydration (188.02%). Regarding dermal integrity, the test group showed a 111.56% superior increment in skin elasticity and a 149.75% more effective optimization of melanin intensity. Notably, deep-tissue hydration at a 2.5 mm depth demonstrated a 188.02% higher gain, suggesting that the modality significantly fortifies the skin’s physiological moisture reservoir. The test group exhibited a marked improvement over the control across all cutaneous parameters (p < 0.001). Our findings demonstrate that a new combinatorial approach using EP-assisted microjet of Synerjet system after cold plasma pretreatment and a nano-NMN 10% ampoule resulted in significantly greater improvements in wrinkles, pores, elasticity, pigmentation, and deep skin hydration compared to topical application alone. Consequently, these results demonstrated that Synerjet system effectively overcome the inherent lim-itations of nano-delivery technologies, offering a promising modality for advanced cutaneous rejuvenation and a robust framework for future professional dermatological treatments.

Abstract: The role of IgE‑mediated allergy in atopic dermatitis (AD) has been progressively downplayed as contemporary models emphasize barrier dysfunction, type‑2 cytokine–driven inflammation, pruritus pathways, immune dysregulation, and microbial imbalance. This shift, however, has obscured a defining feature of extrinsic AD: a functional IgE‑dependent amplification loop operating across the epidermal and dermal immune network and extending into the draining lymph node. Emerging evidence shows that Langerhans cells, inflammatory dermal dendritic cells, inflammatory dendritic epidermal cells (IDECs), mast cells, and basophils can acquire environmental allergens through FcεRI‑bound IgE, enabling efficient antigen capture, processing, and T‑cell activation. Among these, IDECs appear central to IgE‑mediated delayed‑type hypersensitivity and the development of spongiosis following epicutaneous allergen exposure. Integrating these findings, we propose a mechanistic model in which IgE‑bearing antigen‑presenting cells initiate and sustain a positive feedback circuit that reinforces type‑2 inflammation and contributes to the chronicity of extrinsic AD. Re‑positioning this IgE‑dependent circuit within the broader pathophysiology of AD provides a revised framework that reconciles classical atopy with modern immunologic insights and highlights new therapeutic opportunities targeting IgE–FcεRI signaling, IDEC biology, and allergen‑driven epidermal immune activation.

Abstract: Lipedema is a painful, chronic and progressive disorder of subcutaneous adipose tissue characterized by disproportionate, symmetrical fat accumulation in the extremities—typically the legs and less often the arms—while sparing hands and feet. It is clinically distinct from obesity and lymphoedema, affects almost exclusively women, and often exacerbates during hormonal transition phases. This paper proposes a unifying pathophysiological concept in which lipedema reflects a regenerative imbalance of adipose tissue. A genetically and estrogen-modulated increase in endothelial permeability (“leaky vessels”) is suggested to activate perivascular/mural adipose-derived stem cells (ADSCs), thereby initiating coupled angiogenesis and adipogenesis. The stromal vascular fraction (SVF) is described as a central mediator, with SVF-derived extracellular vesicles and characteristic microRNAs promoting adipocyte hyperplasia and hypertrophy and leading to large, metabolically less active adipocytes. The organism attempts to counterbalance this surplus through inflammatory activation of mast cells and macrophages; however, inefficient clearance of excess adipocytes (including “crown-like” structures) sustains inflammation and pain. Progressive adipose expansion may compress lymphatic capillaries and precollectors, resulting in dermal and subdermal lymphatic congestion and contributing to oedema and symptom progression. Increased aromatase activity and local estrogen availability are discussed as additional amplifiers of adipogenesis and inflammatory remodeling. Finally, lymphatic-sparing liposuction is outlined as a mechanistically plausible intervention that can reduce tissue pressure, improve lymphatic drainage, and alleviate key symptoms.

Abstract: Background/Objectives: Several novel biologics and small molecule therapies have emerged for the treatment of antihistamine-refractory chronic spontaneous urticaria (CSU), yet no study has directly compared their speed of response. This study aims to provide indirect evidence on the relative time to meaningful clinical response across approved and investigational therapies using a Bayesian network meta-analysis. Methods: Phase 2 and phase 3 randomized controlled trials reporting UAS7 scores in graphical format for antihistamine-refractory CSU were included. The primary outcome was mean time in weeks to minimal clinically important difference (MCID), defined as a UAS7 reduction of 10 points. Data were extracted using WebPlotDigitizer (v4.7) and analyzed via Bayesian random-effects network meta-analysis in MetaInsight (v6.4.0), with placebo as the reference node. Results: All drugs except rilzabrutinib 400mg daily demonstrated faster mean time to MCID than placebo. Fenebrutinib had the fastest mean time to MCID (0.67–0.76 weeks) and tezepelumab the slowest (5.41–5.65 weeks). Only omalizumab 300mg every 4 weeks, dupilumab 300mg every 2 weeks and ligelizumab 72mg and 120mg every 4 weeks achieved statistically significant reductions compared with placebo. All treatments had wide credible intervals reflecting limited direct comparisons. Conclusions: This is the first network meta-analysis comparing time to meaningful symptom control across therapies for antihistamine-refractory CSU. Omalizumab, dupilumab, and ligelizumab demonstrated statistically significant reductions in time to MCID compared with placebo. Head-to-head trials with standardized outcome reporting would enable more definitive comparative conclusions.

Abstract: Background: Vascular adverse events (VAEs) related to facial filler injections are rare but potentially severe complications. Doppler ultrasound has emerged as an adjunct imaging tool for evaluating vascular compromise; however, Doppler findings in facial VAEs remain insufficiently characterized. Objectives: To characterize Doppler ultrasound findings associated with filler-related facial VAEs and to assess whether Doppler patterns differ according to prior hyaluronidase administration. Methods: This international multicenter retrospective observational study included 100 patients with clinically diagnosed facial VAEs following filler injections between May 2022 and April 2025. Doppler ultrasound findings were analyzed, including absent flow in perforators and major arteries, compensatory flow, abnormal waveforms, increased peak systolic velocity (PSV), and absence of Doppler abnormalities. Patients were categorized according to hyaluronidase administration prior to ultrasound evaluation. Descriptive statistics and comparative analyses were performed. Results: One hundred patients (median age, 38 years IQR: 30–50; 88 women) were evaluated. The most frequent Doppler ultrasound findings were absent flow in perforators (42%) and major arteries (35%), followed by compensatory flow (26%), string sign (18%), flow diversion (16%), and increased peak systolic velocity (16%). No Doppler abnormalities were observed in 12% of cases, while tardus–parvus (9%) and staccato waveform (8%) were less frequent. Doppler ultrasound findings did not differ significantly between patients who received hyaluronidase before imaging and those who did not (all P &gt; .05). The dose of hyaluronidase varied substantially. Livedo reticularis, blanching and pain were the most common clinical findings. Central facial arterial territories, particularly the perioral, nasolabial fold, nasal, and glabellar regions, were most commonly involved. Conclusions: Filler-related facial VAEs show recognizable Doppler ultrasound patterns and the identification of these patterns may improve localization of vascular occlusion and support ultrasound-guided hyaluronidase administration, potentially enhancing treatment precision and clinical outcomes.

Abstract: (1) Background: Retinol has consistently demonstrated efficacy in improving signs of skin aging. However, recent European Union regulations have limited its cosmetic concentration to 0.3%, creating the need for new formulations to be capable of maintaining high efficacy, safety, and tolerance. (2) Material and Methods: This clinical study aimed to evaluate and compare the rejuvenating effects and tolerance of a 0.5% retinol serum with a new equivalent technology, Retinduo®, which previously showed promising preclinical results. A single-center, prospective, randomized, controlled, double-blind, two-arm parallel study was conducted in 40 Caucasian women aged 38–60 years with moderate photoaging (Glogau II). 20 participants applied Retinduo® serum and 20 applied retinol 0.5%, following a progressive ap-plication protocol. Clinical and instrumental assessments measured hydration, firmness, elasticity, tone homogeneity, melanin levels, skin roughness, wrinkle parameters, and stratum corneum thickness. (3) Results: Both formulations signifi-cantly improved hydration, firmness, and elasticity from day 28 onward. Retinduo® showed a significant increase in viscoelasticity (R8) from day 56, while retinol 0.5% did not demonstrate significant changes in this parameter. Melanin reduction was observed with Retinduo® at days 28 and 56 and with retinol 0.5% just at day 28. Although a reduction in melanin was observed with both ingredients, the reduction was more significant with Retinduo® at 56 days. Both treatments reduced the thickness of the stratum corneum; however, with Retinduo®, a significant and more pronounced reduction was achieved after 3 months of treatment (30% (p=0.0001) vs. 12% (p=0.033). Retinduo® demonstrated significant wrinkle depth reduction at day 28 and in wrinkle amplitude (width and length of wrinkles) at the end of treatment, while 0.5% retinol showed a positive trend in this parameter. Both products exhibited excellent tolerance. (4) Conclusions: Overall, Retinduo® achieved comparable or slightly superior anti-aging effects while aligning with current European regulatory limits.

Abstract: Background: In this study, we radiologically assessed potential increases in microvascularity, the extracellular matrix, collagen deposition, and tissue viscoelasticity following carboxytherapy for periorbital hyperpigmentation (POH). We also analyzed the correlation between radiological changes and clinical outcomes and explored implications for future outpatient selection, as well as the potential to predict treatment success based on radiological–clinical correlations. Materials and Methods: The present study included 78 patients (76 women and 2 men) aged over 18 years with Fitzpatrick skin types I-V and moderate-to-severe infraorbital dark circles who applied for treatment at the Dermatology Department in the Cosmetology Unit of Medical Faculty Hospital. Each patient was given manual, pressure-controlled injections of sterile CO2 into the upper and lower eyelids for 7 weeks, with one round of treatment per week. We conducted dermatoclinical and radiological evaluations, including measurements of epidermis–dermis thickness and SWE elastography, musculus orbicularis oculi pars pretarsalis thickness, and cSMI vascular index percentage, as well as SOOF tissue SWE elastography (measured in Kpa). These analyses were performed on both lower eyelids before treatment and at 1 month and 6 months after treatment. Results: After treatment, VAS scores improved significantly. Grayscale ultrasonography showed significant increases in epidermis–dermis and orbicularis oculi thickness at 1 and 6 months (p<0.05). SMI presented a significant increase in vascular index at both follow-ups (p<0.05). SOOF SWE values increased significantly at 1 and 6 months, whereas epidermis–dermis SWE did not. Procedural pain was common, and 25 participants withdrew during the 7-week period due to discomfort. Conclusions: Radiological findings indicated collagen accumulation, increased microvascularity, myocyte proliferation, and enhanced viscoelasticity resulting from carboxytherapy treatment. The continuity of radiological and clinical improvements from the first to sixth months following treatment suggests the enduring benefits of this therapy.

Abstract: Fungal infections remain a major global health challenge, especially when they are long-lasting and resistant to treatment. Previous findings suggested that very dilute, low-dose food-grade hydrogen peroxide (FGHP) at 0.5% and 1% concentrations could be both effective and safe in treating chronic fungal nail infections, even in cases lasting over two decades. These earlier outcomes indicated that hydrogen peroxide might help eliminate fungi and promote nail regeneration. In this study, researchers examined a 45-year-old woman with severe, treatment-resistant fungal infections affecting her palms, soles (with ulcerations), and multiple finger and toenails. Her condition had not improved despite treatment at three hospitals in Accra, Ghana. After informed consent, she was treated with FGHP: 40 ml of 0.5% solution three times daily for one month, followed by 1% for another month, then back to 0.5% for a third month. This three-month cycle was repeated three times over nine months, with one-month breaks between cycles. After sixteen months, her condition improved significantly. The ulcers healed completely, infections cleared from her palms and soles, and most nails regenerated. No adverse effects were reported, suggesting FGHP was both effective and safe. Studies are needed to establish the pharmacokinetics and appropriate dose of FGHP.

Abstract: Hidradenitis suppurativa (HS) is a severe inflammatory dermatosis characterized by profound localized pain. Current pathophysiological models of HS focus primarily on microscopic molecular networks and microbiological dysbiosis. Although the psychosocial and behavioral burdens of the disease are individually well-documented, these factors have not yet been integrated into a single macroscopic feedback model. This self-sustaining system operates across three interacting domains: (1) a biomechanical-metabolic loop, where sustained immobility accelerates the accumulation of visceral adiposity and insulin resistance; (2) a psychosocial-physiological loop, where pain-induced sleep disruption and chronic stress drive neuroendocrine dysregulation and maladaptive coping behaviors; and (3) a socioeconomic loop, where economic instability decreases healthcare security. Consequently, these behavioral, psychological, and socioeconomic burdens feed back into the systemic inflammatory core, perpetuating disease chronicity. Moreover, this review explores kinesiophobia (the anticipatory fear of movement) as a potentially critical and overlooked component of the biomechanical-metabolic feedback loop. Currently, there is a notable absence of primary psychometric data quantifying kinesiophobia in the HS population. Future research should aim to quantify this phenomenon to better establish its prevalence and clinical significance. On a macroscopic level, clinicians should aim to systematically break the broader interconnected behavioral feedback loops through multidisciplinary interventions, including cognitive-behavioral therapy and structured patient education. Ultimately, dismantling these psychological and behavioral barriers may be a critical step to attenuate systemic inflammatory amplification and improve long-term clinical outcomes.

Abstract: Background: Androgenetic alopecia (AGA) is the most prevalent form of non-scarring alopecia, affecting up to 80% of men and 50% of women over a lifetime. Despite the established efficacy of oral finasteride and topical minoxidil, limitations including systemic adverse effects, the requirement for indefinite treatment to maintain benefit, and suboptimal long-term patient compliance have stimulated growing clinical interest in minimally invasive, locally delivered therapeutic approaches targeting the follicular microenvironment directly. Objective: To evaluate and compare the available clinical evidence for six minimally invasive non-surgical interventions in AGA: platelet-rich plasma (PRP), microneedling, mesotherapy, intradermal antiandrogen therapy (dutasteride and finasteride), topical finasteride, and polynucleotide/polydeoxyribonucleotide (PN/PDRN) injections. Methods: A systematic search of PubMed and Scopus was conducted for the period January 2000 to March 2026 using pre-defined Boolean search strings. Studies were eligible if they enrolled adults with clinically or trichoscopically confirmed AGA, evaluated one of the six specified interventions, and reported quantitative hair outcome measures. Due to substantial heterogeneity in study design, intervention protocols, and outcome reporting methods, a formal meta-analysis was not conducted; findings are presented as a structured narrative synthesis following PRISMA 2020 reporting guidance where applicable to a single-author narrative synthesis. Results: Forty-seven studies fulfilled the pre-specified eligibility criteria, comprising 18 randomized controlled trials (RCTs), 22 prospective or controlled cohort studies, and 7 retrospective analyses. The most consistent evidence was identified for PRP, supported by multiple RCTs with objective trichoscopic endpoints, and for topical finasteride, which demonstrated non-inferiority to oral finasteride in a phase III trial with substantially reduced systemic drug absorption. Microneedling in combination with topical minoxidil demonstrated significantly superior outcomes over monotherapy in the largest available RCT. Intradermal dutasteride showed promising follicular efficacy with reduced systemic dihydrotestosterone (DHT) suppression relative to equivalent oral dosing. Mesotherapy and PN/PDRN therapies demonstrated directionally positive results, limited by small sample sizes, heterogeneous intervention protocols, and the absence of adequately powered controlled trials. Conclusion: PRP, microneedling combined with topical minoxidil, and topical finasteride represent evidence-informed treatment options within the contemporary management of AGA. Intradermal dutasteride warrants evaluation in larger, prospectively registered controlled trials. Mesotherapy and PN/PDRN injections require protocol standardisation and rigorous placebo-controlled evidence before definitive clinical recommendations can be issued. The conclusions of this review are constrained by protocol heterogeneity across included studies and the absence of formal risk-of-bias assessment.

Abstract: Background: Hyaluronic acid (HA) fillers are among the most commonly performed aesthetic procedures worldwide. Hyaluronidase is the sole enzymatic antidote capable of reversing HA filler-related vascular occlusion, a rare but potentially vision- and tissue-threatening complication. Established international guidelines uniformly endorse immediate hyaluronidase availability as a non-negotiable safety requirement.Objective: This evidence-informed narrative and perspective review examines the mismatch between clinical standards mandating hyaluronidase availability and the real-world access constraints facing practitioners in 2025, with focus on the European and German regulatory environment.Methods: A review of peer-reviewed literature, clinical guidelines, regulatory documentation, and expert consensus statements was conducted. Grey-literature sources and institutional notifications are incorporated where they constitute the most current available evidence. AI-assisted language tools were used in the preparation of this manuscript for drafting and editorial refinement. All content was reviewed, verified, and approved by the authors, who take full responsibility for the accuracy and integrity of the final text.Results: Access barriers documented in official shortage registers, professional society notifications, and regulatory reports include restrictive prescription frameworks, fragmented supply chains, and regulatory classifications that do not reflect hyaluronidase’s emergency rescue function. These barriers are particularly pronounced in Germany: BfArM officially documented Hylase® Dessau shortages across 2023, and in June 2025 the DGHO notified clinicians that the manufacturer had ceased production entirely. The clinical consequence is a safety paradox: advances in filler technology have not been matched by equivalent improvements in reversal agent accessibility, with direct implications for patient safety, practitioner liability, and the reversibility principle underpinning modern aesthetic medicine.Conclusions: Regulatory frameworks governing hyaluronidase must be re-evaluated in light of its life-saving function. Targeted policy reform, structured access models, and mandatory training integration are needed to align regulatory structures with clinical standards of care.

Abstract: Despite advances in surgical and laser techniques, skin graft scars remain challenging to treat, and conventional interventions frequently yield limited outcomes. The Pinholxell method represents a reconstruction-based laser approach that combines a pinhole procedure—utilizing a CO₂ laser to create deep columns measuring approximately 1 mm in diameter—with an immediate fractional CO₂ laser overlay.This dual-mode system enables simultaneous deep dermal remodeling and superficial epidermal regeneration. The macro-pinhole columns act as controlled zones of injury that initiate a localized cytokine cascade, while the intervening intact tissue serves as a “safety zone,” supporting structured dermal regeneration and epithelial recovery.This study presents five cases of patients with skin graft scars treated using the Pinholxell method. The treatment protocols included repeated sessions of Pinholxell therapy administered at 2-month intervals, supplemented with additional fractional CO₂ laser procedures as clinically indicated. The number of treatment sessions was determined based on the severity and characteristics of the scar, including the degree of hypertrophy and the presence of keloidal features.On average, patients underwent 5 to 10 sessions of Pinholxell therapy, along with 7 to 10 sessions of adjunctive fractional CO₂ laser treatments, tailored to enhance epidermal resurfacing and promote comprehensive dermal remodeling, particularly in cases with extensive fibrosis, elevated vascularity, or nodular keloidal architecture. The treatment period ranged from 18 months to 4 years and 4 months.All patients exhibited marked clinical improvement in pigmentation, thickness, surface texture, and pliability of the scar, along with alleviation of symptoms such as pruritus, pain, and functional limitations caused by contracture. No complications were observed, and patient satisfaction was high.These findings suggest that the Pinholxell method is not merely a resurfacing technique but a structured reconstruction strategy for skin graft scars, offering both structural and symptomatic improvement through targeted tissue remodeling and regeneration.

Abstract: Human skin nicotinamide adenine dinucleotide (NAD+) levels decrease with age, likely contributing to the aging skin phenotype. It is hypothesized that topically applied NAD+ precursors, including niacinamide (nicotinamide) riboside (NR), may benefit skin aging. Three human clinical trials of topical Niagen®, NR chloride, were convened in healthy participants to evaluate its irritation potential; acute cosmetic NR alone and in formulation with Niagen NanoCloudTM sachet (NCS) did not result in significant irritation nor sensitization potential. Acute skin moisture content and skin barrier integrity significantly improved at ≥1.5% and ≥2.5% NR concentrations, respectively. Participant-reported outcomes included improvements to skin redness, moisture, and smoothness. These trials demonstrated that NR was nonirritating when applied topically, as a single ingredient product or when delivered in a dry, multi-ingredient product dissolved in a vehicle. As a single ingredient, NR significantly improved skin moisturization, skin smoothing, and skin barrier integrity, which may support the use of NR as a topical ingredient.

Abstract: Background: Chronic urticaria (CU) is a heterogeneous inflammatory disorder generally attributed to mast cell activation. However, emerging evidence suggests that metabolic reprogramming and systemic immune dysregulation also contribute to the disease pathophysiology. This study aimed to investigate the interplay between epithelial barrier integrity, innate immune regulation, metabolic activity, and mast cell effector mechanisms in CU. Methods: Forty CU patients and 40 healthy controls were evaluated. Clinical parameters included disease severity, disease subtype, antihistamine response, IgE levels, anti-TPO status, gastrointestinal symptoms, and angioedema. Serum levels of histamine, intestinal fatty acid-binding protein (IFABP), soluble CD14 (sCD14), diamine oxidase (DAO), D-lactic acid, endotoxin, zonulin, calprotectin, and related ratios were measured. Disease activity and control were assessed using the UAS7 and UCT scores. Results: CU patients exhibited significantly higher DAO (p = 0.003) and lactic acid (p = 0.004) levels compared to controls, whereas other markers showed no significant differences. In anti-TPO-positive patients, sCD14 levels was reduced (p = 0.024), while histamine/sCD14 (p = 0.005), lactic acid/sCD14 (p = 0.014), IFABP/sCD14 (p = 0.008), and zonulin/sCD14 (p = 0.027) were significantly elevated, suggesting relative amplification of metabolic and barrier-related signals under impaired innate immune regulation. Severe anti-TPO-positive patients exhibited lower sCD14 (p = 0.022) and NLR (p = 0.013) but higher UAS7 (p = 0.032), histamine (p = 0.011), calprotectin (p = 0.041), and CD14-normalized ratios, including histamine (p = 0.003), IFABP (p = 0.028), lactic acid (p = 0.019), zonulin (p = 0.029), and calprotectin (p = 0.011) compared with severe anti-TPO–negative patients, indicating a mast cell–dominant and metabolically active inflammatory phenotype. The lactic acid/DAO ratio was significantly lower in controlled versus uncontrolled CU (p = 0.013) and showed discriminatory potential for disease control. Patients with angioedema had higher CRP (p = 0.038) and UAS7 scores (p < 0.001). Conclusions: CU exhibits markedly immunometabolic heterogeneity. Elevated DAO and lactic acid indicate increased histamine turnover and metabolic activation, whereas altered sCD14-normalized biomarker profiles reveal autoimmune-specific immune dysregulation in anti-TPO-positive patients. Severe autoimmune CU manifests as a mast cell–dominant, metabolically active phenotype with relative suppression of innate immune modulators, contrasting with alternative pathways in non-autoimmune severe CU. The lactic acid/DAO ratio may serve as a candidate biomarker of disease control. These results underscore the importance of phenotype-tailored therapeutic strategies in CU.

Abstract: Background: Since the relationship between coagulation factors and serum blood cell factors has not been extensively studied in patients with angioedema (AE) and urticaria, we wanted to examine them. Methods: This cross-sectional study investigated the relationship between coagulation factors, other serum cells and factors, and clinical disease indicators in patients suffering from chronic AE and urticaria. It involved 102 participants, i.e. three groups: 33 patients with isolated AE, 33 patients AE with urticaria (AE/Urt), and 35 healthy controls. Blood samples were collected to analyze the levels of coagulation factors (D-dimer, fibrinogen, factor VII), as well as other serum parameters such as C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR) and complete blood count (CBC). Clinical data regarding symptoms and disease severity were also collected using the validated AECT questionnaire. Results: Only D-dimer values differed significantly between groups and were higher in patients with AE/Urt than in controls. At the same time, D-dimers were significantly more often elevated in both AE groups than in healthy individuals. Additionally, CRP values in both AE groups were significantly more often elevated than in controls, with significantly higher values in both AE groups (in both groups 85%) than in controls (57%). Conclusion: The results of this study suggest that abnormalities in coagulation factors and other serum parameters may play an important role in the pathophysiology of AE and urticaria. These findings could help improve the understanding of the mechanisms behind these diseases and provide insights into enhancing diagnostic and therapeutic approaches for patients. Further research is needed.

Abstract: Background and Clinical Significance: Basal cell carcinoma (BCC) is the most common malignant tumor of the skin and represents the majority of non-melanoma skin cancers, particularly affecting sun-exposed facial areas. Surgical excision remains the gold standard due to high cure rates, especially for high-risk facial lesions. However, patient refusal of biopsy or surgery may create therapeutic challenges. This case highlights a non-surgical alternative approach and emphasizes its clinical implications; Case Presentation: A 60-year-old Egyptian man with uncontrolled hypertension and type 2 diabetes mellitus presented with an ulcerative lesion located between the left nasal wall and lower eyelid. Clinical examination revealed raised pearly borders and central necrosis, highly suggestive of nodulo-ulcerative basal cell carcinoma. The patient refused biopsy and surgical intervention despite counseling and referral for Mohs micrographic surgery. A non-surgical regimen was initiated consisting of cryotherapy every two weeks using two freeze–thaw cycles of four seconds each with a 2-mm margin, combined with topical imiquimod 5% cream applied three times weekly. Episodic local inflammatory reactions occurred and were managed conservatively with temporary interruption and emollient therapy. Fusidic acid ointment was applied post-cryotherapy. Complete clinical resolution was achieved after five months with residual scarring and no recurrence during one year of follow-up; Conclusions: Combined cryotherapy and topical imiquimod may represent a viable therapeutic alternative in carefully selected patients refusing surgical management. Close monitoring and long-term follow-up remain essential.

Abstract: Introduction: Wound healing, tissue repair, and regeneration are biological processes essential for restoring tissue integrity following injury. Disorders in these processes can lead to complications and the formation of scars, impacting both physical and psychological well-being. Methods: This review synthesizes recent advancements in understanding of the molecular and cellular mechanisms governing these processes. We explore the sequential phases of wound healing, the key cellular and molecular players involved, factors influencing healing outcomes, and emerging therapeutic strategies. Special emphasis is placed on novel biomaterials, cell-based therapies, gene therapies, and physical modalities. Modern therapeutic approaches aim to accelerate healing while minimizing complications such as scarring, infection, or chronic inflammation. Among the commercially available topical agents, Dermatix Ultra, Epicyn, Flosteron, and Contractubex are widely used and studied. Results: This review provides a contemporary analysis in the context of wound healing, tissue repair, and scar management, with an evidence-based comparison of these agents, focusing on their composition, mechanisms of action, clinical applications, and a comparative perspective on their efficacy in improving scar outcomes. Conclusion: Thus, this review aims to provide clinicians and patients with an up-to-date understanding of these treatments to facilitate informed decision-making in scar management. Finally, we discuss current challenges and future directions in the field, highlighting the potential for personalized medicine and translational research.

Abstract: Skin inflammation is characterized by oxidative stress, excessive keratinocyte activa-tion, and the overproduction of pro-inflammatory cytokines. In a previous study, we demonstrated that the hydroalcoholic extract from Posidonia oceanica leaves (POE) mit-igates psoriasis-like skin inflammation in a mouse model. In the present study, we in-vestigated the cellular mechanisms underlying these effects in human HaCaT keratinocytes. Non-cytotoxic lipopolysaccharide (LPS) stimulation reproduced key in-flammatory features, including impaired cell proliferation, increased production of ROS and NO, and the upregulation of IL-1β, IL-6, TNF-α and CXCL8/IL-8. Co-treatment with POE significantly attenuated these alterations by restoring cell pro-liferation, suppressing oxidative stress, particularly NOS2/NO, and normalizing both cytokine expression and release. POE alone did not affect cell viability or inflammatory markers, confirming its favorable safety profile. However, POE alone induced a mild pro-apoptotic response, which may contribute to overcoming the apoptosis re-sistance typically observed in psoriatic keratinocytes. These in vitro findings are con-sistent with our previous in vivo results and demonstrate that POE exerts antioxidant and anti-inflammatory activities. Overall, these results support the POE as a promising marine-derived candidate for complementary strategies in the management of psoria-sis-associated inflammatory skin disorders.

Abstract: Chronic urticaria (CU) is a mast cell–driven inflammatory skin disorder characterized by recurrent wheals, angioedema, or both lasting more than six weeks, often resulting in significant impairment of quality of life. Although CU has traditionally been re-garded as a predominantly histamine-mediated condition, evidence accumulated over the past decade has redefined chronic spontaneous urticaria (CSU) as a complex im-mune-mediated disease with marked biological heterogeneity.. Distinct pathogenic mechanisms involving autoimmune pathways, dysregulated mast cell activation, and chronic inflammatory networks have been identified, providing a mechanistic basis for disease persistence, variable severity, and therapeutic refractoriness. This review syn-thesizes current concepts in CSU pathophysiology, with emphasis on mast cell biology, autoimmune endotypes, and inflammatory amplification mechanisms.. We further discuss emerging biomarkers with potential relevance for disease stratification and treatment prediction, as well as established and novel therapeutic strategies targeting key pathogenic pathways. By integrating mechanistic insights with clinical implica-tions, this review highlights the transition toward endotype-driven and bi-omarker-guided management of chronic urticaria.

Abstract: Background: Assessing the national burden of chronic wounds is a complex data an-alytics challenge. Robust estimates in Eastern Europe are scarce, highlighting the need for computational methods to validate cases in large-scale health databases. Methods: We applied a large-scale data analytics approach to Romania’s National Inpatient Database (public hospitals, 2017–2022). A computational case-ascertainment algorithm (validated “≥2 admissions” rule) was used to identify recurrently hospitalised patients, establishing a cohort of 18,856 patients (65,771 hospitalisations). We computed annual prevalence, incidence, and mortality per 100,000 adults, stratified by ulcer categories, age, and sex. Results: Annual prevalence peaked in 2018 (56.14/100,000) and dropped sharply during the COVID-19 pandemic (22.64/100,000 in 2021), with partial recovery in 2022 (30.61/100,000). Incidence followed a similar trend, peaking in 2018 (28.80/100,000) and rebounding modestly in 2022 (7.17/100,000). Mortality remained low but variable (0.21–0.38/100,000). Venous ulcers were the most common category. Pressure ulcers, though least prevalent, had the highest mortality. Adults aged ≥65 years and men had the highest prevalence and incidence. Conclusions: Our data an-alytics framework successfully characterized Romania’s hospital-treated chron-ic-wound burden, revealing that it is substantial, sensitive to pandemic-related dis-ruptions, and disproportionately affects adults aged ≥65 years and men while venous ulcers were the predominant wound category and pressure ulcers carried the highest mortality risk. Clinical implications: Early detection and dedicated care pathways should prioritize these high-risk strata to reduce readmissions and preventable deaths.