Platelet-Rich Plasma (PRP) and Adipose-Derived Stem Cell (ADSC) Therapy in the Treatment of Genital Lichen Sclerosus: A Comprehensive Review

Lichen sclerosus (LS) is a chronic inflammatory dermatosis mostly localized in the genital area, characterized by vulvar alterations that can severely impact a patient's quality of life. Current treatment modalities often provide incomplete relief, and there is a need for innovative approaches to manage this condition effectively. Platelet-rich plasma (PRP) and adipose-derived stem cells (ADSCs) have emerged as potential regenerative therapies for LS, offering promising results in clinical practice. This comprehensive review explores the utilization of PRP and ADSC therapy in the treatment of genital LS, highlighting their mechanisms of action, safety profiles, and clinical outcomes. PRP is a blood product enriched in growth factors and cytokines, which promotes tissue regeneration, angiogenesis, and immune modulation. ADSC regenerative potential relies not only in their plasticity but also in the secretion of trophic factors, and modulation of the local immune response. Numerous studies have reported the safety of PRP and ADSC therapy for genital LS. Adverse events are minimal and typically involve mild, self-limiting symptoms, such as transient pain and swelling at the injection site. Long-term safety data are encouraging, with no significant concerns identified in the literature. PRP and ADSC therapy have demonstrated significant improvements in LS-related symptoms, including itching, burning, dyspareunia, and sexual function. Additionally, these therapies enable many patients to discontinue the routine use of topical corticosteroids. Several studies have explored the efficacy of combining PRP and ADSC therapy for LS. In combination, PRP and ADSCs seem to offer a synergistic approach to address the complex pathophysiology of LS, particularly in the early stages. The use of PRP and ADSC therapy for genital lichen sclerosus represents a promising and safe treatment modality. These regenerative approaches have shown significant improvements in LS-related symptoms, tissue trophism, and histological features. Combination therapy, which harnesses the synergistic effects of PRP and ADSCs, is emerging as a preferred option, especially in early-stage LS cases. Further research, including randomized controlled trials and long-term follow-up, is warranted to elucidate the full potential and mechanisms of PRP and ADSC therapy in the management of genital LS. These regenerative approaches hold great promise in enhancing the quality of life of individuals suffering from this challenging condition

Squamous Cell Carcinoma and Ledderhose Disease: A Case Report

Ledderhose disease is disorder of the plantar aponeurosis. This disease is not so common and can be tackled with a surgical or conservative approach. A case of a 73-year-old man came to our attention who had a 26-year history of painless bilateral plantar nodules coalescing into an indurated mass. An ulcerative nodule had been noted in the last 16 months on the right foot, in the absence of trauma, not responsive to conservative treatment, so we decided to perform a biopsy. The histopatologic examination showed squamous cell carcinoma, with warty, well-differentiated, low-grade malignancy. Surgical treatment was suggested, so, in pneumoischemia, we made a surgical incision including the skin lesion. Then we proceeded to sculpture the anterolateral thigh fasciacutaneous flap to obtain adequate soft tissue coverage. The tumor was completely removed. Current reconstructive possibilities comprise a good anatomofunctional recovery even in the case of large demolition requests for the therapy of advanced cases of the disease described in this article. Correlation between Ledderhose disease and the formation of malignant tumors has not been made as yet, but perhaps an element that could unite these pathologies can be researched in the lively cell proliferation that characterizes both. It would be interesting to analyze the biological substrate, as well as the systemic and local levels, in patients where both diseases are manifested

Exploring the Prognostic Role of Ki67 Proliferative Index in Merkel Cell Carcinoma of the Skin: Clinico-Pathologic Analysis of 84 Cases and Review of the Literature.

The exact prediction of outcome of patients with Merkel cell carcinoma (MCC) of the skin is difficult to determine, although several attempts have been made to identify clinico-pathologic prognostic factors. The Ki67 proliferative index is a well-known marker routinely used to define the prognosis of patients with neuroendocrine neoplasms. However, its prognostic value has been poorly investigated in MCC, and available published results are often contradictory mainly because restricted to small series in the absence of standardized methods for Ki67 evaluation. For this reason, we explored the potential prognostic role of Ki67 proliferative index in a large series of MCCs using the WHO standardized method of counting positive cells in at least 500 tumor cells in hot spot areas on camera-captured printed images. In addition, since MCC may be considered as the cutaneous counterpart of digestive neuroendocrine carcinomas (NECs), we decided to stratify MCCs using the available and efficient Ki67 threshold of 55%, which was found prognostic in digestive NECs. This choice was also supported by the Youden index analysis. In addition, we analyzed the prognostic value of other clinico-pathologic parameters using both univariate and multivariate analysis. Ki67 index appeared significantly associated with prognosis at univariate analysis together with stage IV, lack of MCPyV, and p63 expression, but not at the multivariate analysis, where survival resulted independently influenced by p63 expression and tumor stage, only

FAM123A Binds to Microtubules and Inhibits the Guanine Nucleotide Exchange Factor ARHGEF2 to Decrease Actomyosin Contractility

The FAM123 gene family comprises three members, FAM123A, the tumor suppressor WTX(FAM123B) and FAM123C. WTX is required for normal development and causally contributes to human disease, in part through its regulation of β-catenin-dependent WNT signaling. The roles of FAM123A and FAM123C in signaling, cell behavior and human disease remain less understood. We defined and compared the protein-protein interaction networks for each member of the FAM123 family by affinity purification and mass spectrometry. Protein localization and functional studies suggest that the FAM123 family members have conserved and divergent cellular roles. In contrast to WTX and FAM123C, we found that microtubule-associated proteins were enriched in the FAM123A protein interaction network. FAM123A interacted with and tracked dynamic microtubules in a plus-end direction. Domain interaction experiments revealed a ‘SKIP’ amino acid motif in FAM123A that mediated interaction with the microtubule tip tracking proteins EB1 and EB3, and therefore with microtubules. Cells depleted of FAM123A showed compartment-specific effects on microtubule dynamics, increased actomyosin contractility, larger focal adhesions and decreased cell migration. These effects required binding of FAM123A to and inhibition of the guanine nucleotide exchange factor ARHGEF2, a microtubule-associated activator of RhoA. Together, these data suggest that the ‘family-unique’ SKIP motif enables FAM123A to bind EB proteins, localize to microtubules and coordinate microtubule dynamics and actomyosin contractility

A 48-week update of a multicentre real-life experience of dupilumab in adult patients with moderate-to-severe atopic dermatitis

The long-term efficacy and safety of dupilumab has been demonstrated in clinical trials and only in few real-world studies. We conducted an extension analysis from a previous 16-week study on 109 adult patients affected by moderate-to-severe atopic dermatitis treated with dupilumab. Eczema-Area-and-Severity-Index (EASI), itch numerical-rating-score (itch-NRS), Dermatology-Life-Quality-Index (DLQI) scores, drug survival rate and occurrence of adverse events after 24 and 48 weeks of dupilumab treatment were retrospectively collected. Dupilumab demonstrated sustained improvement of disease severity, pruritus, and quality of life in our series with an increasing percentage of patients gaining EASI75 and EASI90 response during the study period. Few patients interrupted treatment resulting in a very high drug survival rate. We also confirmed the favorable safety profile of the drug with absence of serious adverse events and serious infections throughout the 48-week period. The prevalence of conjunctivitis was low and mainly occurred in the mid-term with resolution of the majority of cases at 48 weeks

Visual field loss and vision-related quality of life in the Italian Primary Open Angle Glaucoma Study

The aim of this study was to examine the relationship between visual field (VF) loss, vision-related quality of life (QoL) and glaucoma-related symptoms in a large cohort of primary open angle glaucoma (POAG) patients. POAG patients with or without VF defects or "glaucoma suspect" patients were considered eligible. QoL was assessed using the validated versions of the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and glaucoma-related symptoms were assessed using the Glaucoma Symptom Scale (GSS). Patients were classified as having VF damage in one eye (VFD-1), both eyes (VFD-2), or neither eye (VFD-0). 3227 patients were enrolled and 2940 were eligible for the analysis. 13.4% of patients were classified in the VFD-0, 23.7% in the VFD-1, and 62.9% in the VFD-2 group. GSS visual symptoms domain (Func-4) and GSS non-visual symptoms domain (Symp-6) scores were similar for the VFD-0 and VFD-1 groups (p = 0.133 and p = 0.834 for Func-4 and Symp-6, respectively). VFD-0 group had higher scores than VFD-2 both in Func-4 (p < 0.001) and Symp-6 domains (p = 0.035). Regarding the NEI-VFQ-25, our data demonstrated that bilateral VF defects are associated with vision-related QoL deterioration, irrespective of visual acuity

Vision-related quality of life and symptom perception change over time in newly-diagnosed primary open angle glaucoma patients.

To evaluate the change over time of vision-related quality of life (QoL) and glaucoma symptoms in a population of newly-diagnosed primary open angle glaucoma (POAG) patients. Multicenter, prospective study. Consecutive newly-diagnosed POAG patients were enrolled and followed-up for one year. Follow-up visits were scheduled at 6 and 12 months from baseline. At each visit, vision-related QoL and glaucoma-related symptoms were assessed by the means of the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and the Glaucoma Symptom Scale (GSS), respectively. Trends over time for NEI-VFQ-25 and GSS scores were evaluated with longitudinal linear mixed models. One-hundred seventy-eight patients were included in the analysis. At baseline, early to moderate glaucoma stages were associated with higher scores for most GSS and NEI-VFQ-25 items, while lower best-corrected visual acuity was associated with lower scores for 4 of the 12 NEI-VFQ-25 items. During the follow-up, all the GSS scores, the NEI-VFQ-25 total score, and 7 of the 12 NEI-VFQ-25 scores significantly improved (p &lt; 0.05). In multivariate model, higher increases of most GSS and NEI-VFQ-25 scores were modeled in patients with low scores at baseline. Vision-related QoL and glaucoma-related symptom perception significantly improved during the one-year follow-up in this population of newly diagnosed POAG patients