Medicine and Pharmacology

Abstract: A scar is the fibrous tissue that replaces normal skin after the proliferative and remodeling phases of wound healing. When healing is dysregulated, the result is a pathological scar: hypertrophic scars, which remain within the original wound margins, and keloids, which invade adjacent unwounded skin and behave as benign dermal tumors. Both arise when injury reaches the reticular dermis and provokes sustained inflammation and mechanical tension that drive the differentiation of fibroblasts into contractile myofibroblasts and the disorganized over-deposition of collagen and elastin. These lesions cause pain, pruritus, contracture, disfigurement, and considerable psychological distress, and they account for a multibillion-dollar global treatment burden. This review synthesizes the structural, cellular, and molecular basis of cutaneous scarring, distinguishes hypertrophic, keloid, atrophic, and fine-line scars by their clinical and histological features, and organizes the therapeutic landscape into conservative, topical, minimally invasive, surgical, and emerging modalities. We emphasize the convergent signaling axes, TGF-β/Smad, mechanotransduction through integrins and Rho/ROCK, and TNF-α/NF-κB inflammation, that represent rational therapeutic targets, and we highlight why combination and stepwise regimens outperform monotherapy while recurrence remains the central unmet challenge. Finally, we evaluate the feasibility of delivering the anti-fibrotic statin atorvastatin from a calcium-enhanced keratin hydrogel fabricated from residual human hair, an approach developed by our group that couples sustainable biomaterial sourcing with localized, sustained release. We argue that biomaterial-mediated, mechanism-targeted local delivery is a promising direction for converting the broad pleiotropic anti-fibrotic activity of statins into a practical scar therapy.

Abstract: Background: Onychomycosis is a common nail disorder caused by a wide range of pathogenic organisms and is often associated with underlying non-dermatological conditions and lifestyle-related factors. Emerging evidence suggests an increasing role of non-dermatophyte moulds (NDMs), previously regarded as contaminants. However, data describing the epidemiology and causative organisms of onychomycosis in South Africa remain limited. Methods: A retrospective cross-sectional study was conducted at the Dermatology Department of Livingstone Hospital, Gqeberha, from 01 January 2019 to 31 December 2023. Clinical and laboratory records of patients with suspected onychomycosis were reviewed, and only mycologically confirmed cases were included. Diagnosis was established using potassium hydroxide microscopy, fungal culture, and/or Periodic Acid–Schiff staining. Demographic, clinical, and mycological data were analyzed using descriptive and inferential statistical methods. Results: Of 112 clinically suspected cases, 103 were laboratory confirmed. The median age was 57 years, with a slight female predominance (54.4%). Toenail involvement (70.9%) was more frequent than fingernail involvement (43.7%). Nearly all patients (95.1%) had at least one clinical risk factor or comorbidity. Nail discoloration (98.1%), particularly hyperpigmentation, was the most consistent clinical feature, followed by subungual hyperkeratosis (77.7%), onycholysis (59.2%), and nail dystrophy (52.4%). NDMs were the predominant pathogens (57.3%), followed by yeasts (36.9%) and dermatophytes (8.7%). Alternaria, Penicillium, and Aspergillus were the most common NDMs, while Candida parapsilosis, Candida albicans, and Trichosporon species were the leading yeasts. Dermatophyte infections were significantly associated with younger age (p = 0.035) and the presence of tinea (p = 0.025). Non-dermatophyte infections were significantly associated with dermatitis (p = 0.035) and toenail involvement (p = 0.023). Yeast infections were strongly associated with paronychia (p < 0.001) and fingernail involvement (p = 0.026). No independent predictors were identified on multivariable analysis. Conclusions: Nail discoloration remains the most consistent clinical feature of onychomycosis. The high burden of comorbidities underscores the strong association between the condition and underlying conditions. Non-dermatophyte moulds predominate as causative organisms in this setting, highlighting the importance of accurate laboratory diagnosis to guide appropriate management.

Abstract: Rosacea and topical corticosteroid-induced rosacea-like dermatitis (TCIRD) are cutaneous conditions that manifest as erythema, telangiectasia, papules and pustules on the face, accompanied by impairment of the skin barrier. Platelet rich plasma (PRP) constitutes a therapeutic procedure that utilizes a centrifuge to separate a concentrated platelets fraction from a low-volume plasma specimen. Use of PRP has expanded beyond wound healing and skin rejuvenation to include the treatment of inflammatory dermatological conditions. This review explores the clinical ramifications of PRP in the treatment of rosacea and TCIRD, conditions marked by inflammation in the skin. The study places particular emphasis on the effect of PRP on the pathogenesis of rosacea. A comprehensive search of the literature was conducted in this review to identify the efficacy of PRP as a therapeutic modality for rosacea and TCIRD. The effectiveness of PRP in the patient's clinic and the pathogenesis of these skin conditions have been thoroughly documented. Treatment outcomes demonstrated efficacy in addressing symptoms related to rosacea and TCIRD, with improvements observed and symptoms alleviated in these cases following PRP intervention. PRP may represent a potential therapeutic option for rosacea and TCIRD; however, further well-designed studies are required to establish its efficacy and optimal treatment protocols.

Abstract: Plerixafor is a clinically approved CXCR4 antagonist that mobilizes hematopoietic stem cells by disrupting CXCL12/CXCR4 retention signaling. However, its biochemical effects on melanocytes and pigmentation remain unexplored. We investigated how plerixafor modulates CXCR4 sig-naling in melanocytes and evaluated its potential as a pro-melanogenic agent using in vitro and in vivo approaches. Human PIG1 melanocytes were treated with 10 nM plerixafor with or without hydro-quinone (HQ), followed by qPCR for MITF and tyrosinase expression, flow cytometry for CXCR4/CXCR7 and integrin profiling, transwell migration assays, β-arrestin siRNA knockdown, Western blotting, subcellular fractionation, and ChIP-qPCR for β-catenin binding to MITF regu-latory regions. A murine HQ-induced depigmentation model was used to test topical plerixafor on pigmentation, hair follicles, melanogenic gene expression, and systemic safety markers. Plerixafor significantly increased MITF and tyrosinase mRNA and enhanced melanocyte migration, while counteracting HQ-induced suppression of melanogenic genes. Plerixafor reduced cell-surface CXCR4 (consistent with β-arrestin–mediated receptor internalization) without altering CXCR7, c-KIT, or N-cadherin. β-arrestin knockdown abolished plerixafor-induced ERK phosphorylation and melanogenic responses, confirming β-arrestin dependence. Plerixafor promoted β-catenin nuclear translocation and direct β-catenin occupancy at MITF promoter/enhancer TCF/LEF motifs. In vivo, topical plerixafor restored HQ-induced depigmentation, increased hair follicle number and melanin content, and upregulated cutaneous MITF and tyrosinase without hepatic, renal, or inflammatory toxicity. Plerixafor functions as a biased CXCR4 ligand in melanocytes, engaging a β-arrestin–β-catenin–MITF signaling axis to drive melanogenesis and repigmentation. These findings identify β-arrestin–dependent CXCR4 signaling as a tractable pharmacologic mechanism for therapeutic repigmentation in pigmentary disorders.

Abstract: Objectives: Psoriasis is a chronic systemic inflammatory disease associated with an increased risk of cardiovascular disease (CVD). Although this association is well established in moderate-to-severe psoriasis, data on cardiovascular risk in patients with mild psoriasis without metabolic or cardiovascular comorbidities are limited. This study aimed to assess cardiovascular risk and its determinants in patients with mild plaque psoriasis without comorbidities. Methods: This case-control study included 31 adults with mild plaque psoriasis and 17 healthy controls. Patients with metabolic disorders or other inflammatory conditions, cardiovascular disease, malignancies, or heart, kidney, or liver failure were excluded. Clinical assessment included anthropometric measurements, blood pressure, and biochemical blood tests. Ten-year cardiovascular risk was estimated using the Framingham Risk Score (FRS). Group comparisons were performed using nonparametric tests, and correlations were analyzed using Spearman’s correlation coefficient. Results: Patients with mild psoriasis had significantly higher total cholesterol (205.09 vs. 185.07 mg/dL, p = 0.047), non-HDL cholesterol (144.75 vs. 117.50 mg/dL, p = 0.005), LDL cholesterol (124.71 vs. 102.04 mg/dL, p = 0.011), and HbA1c (284.00 vs. 127.77 ng/mL, p = 0.016) than controls. Mean FRS was approximately threefold higher in patients with psoriasis than in controls (2.24% vs. 0.67%, p = 0.013). Male patients had significantly higher FRS than female patients (3.46% vs. 0.71%, p < 0.05). FRS correlated strongly with alanine aminotransferase (ALT; r = 0.63) and moderately with body weight, non-HDL cholesterol, waist circumference, triglycerides, LDL cholesterol, and insulin. Conclusions: Mild psoriasis is associated with increased cardiovascular risk even in the absence of overt metabolic or cardiovascular comorbidities. Early cardiometabolic screening and preventive interventions should be considered in all patients with psoriasis, regardless of disease severity.

Abstract: Conventional dermatological therapies primarily target downstream inflammatory mediators or rely on antioxidant strategies, often without directly addressing the upstream electrophilic chemistry that contributes to tissue damage. Here, we propose a unifying framework based on the Electrophilic Flux (e-Flux) theory, in which a single class of topically applicable agents—Passive Electron Donors (PEDs)—may address diverse dermatological and mucosal conditions by nucleophilically neutralizing pathogenic electrophiles at Stage III of the e-Flux cascade. We review the electrophilic mechanisms underlying five representative conditions: neurogenic skin inflammation driven by 4-hydroxynonenal (4-HNE)-mediated TRPA1 activation, retinoid dermatitis associated with retinaldehyde-induced irritation, aging-related body odor linked to 2-nonenal accumulation, allergic rhinitis mediated by TRPA1-dependent neurogenic inflammation in the nasal mucosa, and migraine involving trigeminal TRPA1 sensitization. For each condition, we outline how upstream electrophile neutralization by PEDs may provide mechanistic advantages over conventional approaches that act further downstream. This perspective positions PED-based topical formulations as a rational, multi-target therapeutic platform grounded in electrophilic chemistry, rather than in empirical antioxidant or anti-inflammatory paradigms.

Abstract: Chronic wounds are a persistent clinical and public health challenge. Natural polyphenols such as curcumin and resveratrol, alongside mesenchymal stem cell (MSC) secretome, have demonstrated complementary anti-inflammatory, antioxidant, and pro-angiogenic properties with potential for wound healing. This study reports two complementary in vitro investigations evaluating the release profiles of curcumin and resveratrol from two polymeric platforms: poly(vinyl alcohol)/sodium alginate/carboxymethylcellulose films (Study 1) and an acrylate copolymer-based hydrogel incorporating MSC secretome (Study 2). UV-Vis spectrophotometric analysis confirmed analytical selectivity with no interference from excipients. In Study 1, films containing curcumin alone exhibited low structural stability and early disintegration in aqueous medium, whereas resveratrol-only films (2% w/w) demonstrated sustained and reproducible release profiles. Combined formulations showed that curcumin compromised polymer matrix integrity and reduced resveratrol release efficiency. In Study 2, resveratrol exhibited progressive and consistent release from the hydrogel, reaching 14.31 µg/mL (isolated control) and 12.60 µg/mL (combined with curcumin) at 120 min. Curcumin showed unsatisfactory release in both systems, attributed to its low aqueous solubility. These results support resveratrol-loaded polymeric matrices as promising sustained-release platforms for bioactive wound dressings and highlight the need for nanoencapsulation strategies to improve curcumin bioavailability.

Abstract: Melasma is a chronic hyperpigmentation disorder that significantly impacts quality of life. Given the persistent challenges in melasma management, there is a need to evaluate therapies that may offer long-term treatment. This review analyzes placebo- and hydroquinone (HQ)-controlled interventional studies of melasma published between January 1, 2014, and December 31, 2024. Screening, data extraction, and discussion synthesis were performed with artificial intelligence assistance under human oversight. Treatments were grouped into five categories: HQ-based Standard Treatments, Isolated Molecules as Depigmenting Therapies, Botanical and Antioxidant-Based Therapies, Regenerative and Microenvironment-Modulating Therapies, and Procedure-Assisted and Combination Treatments. HQ remained a key benchmark, although recurrence and tolerability limitations were frequently observed. Several non-HQ or adjunctive approaches demonstrated benefit when administered orally, topically, intradermally, or via iontophoresis. Botanical antioxidants, synbiotics, epidermal growth factor, and platelet-rich plasma also showed promising efficacy. Nevertheless, the evidence base was constrained by small sample sizes, heterogeneous comparators, inconsistent endpoints, mixed objective and subjective assessments, and variable follow-up durations, which prevented meta-analysis. Research on melasma treatment is growing worldwide, with several promising non-HQ and adjunctive strategies emerging. However, standardization of outcomes, comparator selection, and longer follow-up periods is needed to clarify efficacy, tolerability, and relapse prevention throughout diverse skin tones.

Abstract: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease characterized by substantial clinical and immunological heterogeneity. Traditionally considered a disorder of epidermal barrier dysfunction primarily, AD is now increasingly recognized as a complex systemic inflammatory condition involving dysregulated immune responses, epithelial-derived signaling, neuroimmune interactions, and diverse molecular endotypes. Advances in molecular immunology have significantly expanded current understanding of the cytokine networks underlying disease pathogenesis and have accelerated the transition toward precision medicine approaches in AD. This narrative review summarizes current evidence regarding the immunopathogenesis of AD, with particular emphasis on the interplay between classical and emerging cytokines, biomarker development, and recent therapeutic innovations. Classical type 2 cytokines, including interleukin (IL)-4 and IL-13, remain central drivers of allergic inflammation and epidermal barrier impairment, whereas emerging mediators such as IL-31, IL-33, IL-22, thymic stromal lymphopoietin (TSLP), and OX40/OX40L signaling pathways contribute significantly to chronic inflammation, neuroimmune activation, epidermal remodeling, and pruritus. Comparative analysis of these cytokine pathways highlights the molecular heterogeneity of AD and supports the identification of distinct immunological endotypes. The review additionally discusses current and emerging biomarkers associated with disease severity, therapeutic responsiveness, and inflammatory profiling, including cytokine signatures, serum biomarkers, and transcriptomic approaches. Furthermore, major therapeutic advances involving biologic agents and Janus kinase (JAK) inhibitors are examined within the context of mechanism-based and biomarker-guided therapeutic strategies. Importantly, this review proposes a conceptual precision medicine framework integrating immunopathogenesis, cytokine profiling, molecular endotyping, and targeted therapeutic innovation in AD. Continued advances in biomarker discovery, multi-omics technologies, and individualized therapeutic algorithms may further refine disease stratification and improve personalized management strategies for patients with AD.

Abstract: Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is a CD30-positive T-cell lymphoproliferative disorder that can clinically resemble various non-melanoma skin cancers, making diagnosis challenging. Although histopathology remains the di-agnostic gold standard, non-invasive imaging modalities such as dermoscopy and re-flectance confocal microscopy (RCM) are increasingly used as complementary tools to support the differential diagnosis. To date, no data on RCM features of C-ALCL have been described. Herein, we report the case of an 80-year-old man presenting with a rapidly enlarging nodule on the lateral aspect of his right eyelid, providing a detailed account of dermoscopic and RCM findings integrated with clinicopathological correlation. Dermoscopy revealed a red-orange ho-mogeneous background with white streaks, rosettes, and polymorphic vascular struc-tures, while subsequent RCM (Vivascope 3000 probe) demonstrated marked architectural disarray of the epidermis and dermoepidemal junction, with prominent epidermal in-volvement characterized by aggregates of highly reflective cells. In the absence of al-ternative diagnostic patterns, these features raised suspicion for a cutaneous lym-phoproliferative disorder, which was later confirmed by histopathological and im-munohistochemical analyses. Overall, our findings support the value of RCM as a practical tool in guiding differential diagnosis and biopsy, particularly for rapidly growing lesions located in anatomically sensitive areas.

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.