Label-free electrochemical immunosensor as a reliable point-of-care device for the detection of Interleukin-6 in serum samples from patients with psoriasis

Interleukin-6 (IL-6) plays a crucial role in autoimmunity and chronic inflammation. This study aims to develop a low-cost, simple-to-manufacture, and user-friendly label-free electrochemical point-of-care device for the rapid detection of IL-6 in patients with psoriasis. Precisely, a sandwich-based format immunosensor was developed using two primary antibodies (mAb-IL6 clone-5 and clone-7) and screen-printed electrodes modified with an inexpensive recycling electrochemical enhancing material, called biochar. mAb-IL6 clone-5 was used as a covalently immobilized capture bioreceptor on modified electrodes, and mAb-IL6 clone-7 was used to recognize the immunocomplex (Anti-IL6 clone-5 and IL-6) and form the sandwich. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to conduct electrochemical characterization of the layer-by-layer assembly of the immunosensor, while square wave voltammetry (SWV) was used to perform the sensing. The developed immunosensor demonstrated robust analytical performance in buffer solution, with a wide linear range (LR) by varying from 2 to 250 pg/mL, a good limit of detection (LOD) of 0.78 pg/mL and reproducibility (RSD<7%). In addition, a spectrophotometric ELISA kit was employed to validate the results obtained with the label-free device by analyzing twenty-five serum samples from control and patients affected by psoriasis. A strong correlation in terms of pg/mL concentration of IL-6 was found comparing the two methods, with the advantage for our label-free biosensor of an ease use and a quicker detection time. Based on IL-6 levels, the proposed immunosensor is a dependable, non-invasive screening device capable of predicting disease onset, progression, and treatment efficacy

Detection of Merkel Cell Polyomavirus (MCPyV) DNA and Transcripts in Merkel Cell Carcinoma (MCC)

Merkel cell polyomavirus (MCPyV) is the etiological agent of the majority of Merkel cell carcinoma (MCC): a rare skin tumor. To improve our understanding of the role of MCPyV in MCCs, the detection and analysis of MCPyV DNA and transcripts were performed on primary tumors and regional lymph nodes from two MCC patients: one metastatic and one non-metastatic. MCPyV-DNA was searched by a quantitative polymerase chain reaction (qPCR), followed by the amplification of a Large T Antigen (LTAg), Viral Protein 1 (VP1) and Non-Coding Control Region (NCCR). LTAg and VP1 transcripts were investigated by reverse-transcription PCR (RT-PCR). Viral integration was also studied, and full-length LTAg sequencing was performed. qPCR revealed that the primary tumor of both patients and the lymph node of one patient was positive for the small t-antigen, with an average value of 7.0 × 102 copies/µg. The same samples harbored LTAg, NCCR and VP1 DNA. Sequencing results showed truncated LTAg with the conserved retinoblastoma (Rb) protein binding motif and VP1 and NCCR sequences identical to the MCC350 strain. RT-PCR detected LTAg but not VP1 transcripts. The MCPyV genome was integrated into the primary tumor of both patients. The results confirmed the connection between MCPyV and MCC, assuming integration, LTAg truncation and Rb sequestration as key players in MCPyV-mediated oncogenesis

Dermoscopy and Reflectance Confocal Microscopy in the Diagnosis and Management of Nail Fold Squamous Cell Carcinoma

The management and prognosis of squamous cell carcinoma largely depend on its invasiveness and grade of differentiation. Pigmented nail fold squamous cell carcinoma represents a therapeutic challenge, needing careful treatment to preserve nail function. Here, we report the use of dermoscopy and Reflectance Confocal Microscopy to monitor nail fold squamous cell carcinoma in situ and its response to treatment with topical imiquimod

Predictive role of vitamin A serum concentration in psoriatic patients treated with IL-17 inhibitors to prevent skin and systemic fungal infections

The use of biological drugs in psoriasis is replacing traditional therapies due to their specific mechanism and limited side effects. However, the use of Interleukin 17 inhibitors and the modification of its cytokine pathway could favor the risk of fungal infections.All-trans retinoic acid is an active metabolite of vitamin A with anti-inflammatory and immunoregulatory properties through its capacity to stimulate both innate and adaptive immunity and to its effects on proliferation, differentiation and apoptosis in a variety of immune cells. Furthermore, it has been recently discovered that All-trans retinoic acid has a direct fungistatic effect against Candida and Aspergillus Fumigatus.On the basis of these new insights, in the current review, we suggest that the evaluation of serum level of All-trans retinoic acid or vitamin A should be considered as a predictive marker for the development of fungal infections among psoriatic patients treated with Interleukin 17 inhibitors.In clinical practice, vitamin A test could be added in the routine hospital diagnostic management for a better selection of psoriatic patients eligible to Interleukin 17 inhibitors

From In Silico Simulation between TGF-β Receptors and Quercetin to Clinical Insight of a Medical Device Containing Allium cepa: Its Efficacy and Tolerability on Post-Surgical Scars

1) objective: keloid and hypertrophic scars are a challenge in clinical management, causing functional and psychological discomfort. these pathological scars are caused by a proliferation of dermal tissue following skin injury. the TGF-beta/smad signal pathway in the fibroblasts and myofibroblasts is involved in the scarring process of skin fibrosis. today, multiple therapeutic strategies that target the TGF-beta/smad signal pathway are evaluated to attenuate aberrant skin scars that are sometimes difficult to manage. we performed a head-to-head, randomized controlled trial evaluating the appearance of the post-surgical scars of 64 subjects after two times daily topical application to compare the effect of a class I pullulan-based medical device containing allium cepa extract 5% and hyaluronic acid 5% gel versus a class I medical device silicone gel on new post-surgical wounds. (2) methods: objective scar assessment using the vancouver scar scale (VSS), POSAS, and other scales were performed after 4, 8, and 12 weeks of treatment and statistical analyses were performed. the trial was registered in clinical trials.gov ( NCT05412745). In parallel, molecular docking simulations have been performed to investigate the role of allium cepa in TGF-beta/smad signal pathway. (3) results: we showed that VSS, POSAS scale, itching, and redness reduced significantly at week 4 and 8 in the subjects using devices containing allium cepa and HA. no statistically significant differences in evaluated scores were noted at 12 weeks of treatment. safety was also evaluated by gathering adverse events related to the application of the gel. subject compliance and safety with the assigned gel were similar between the two study groups. molecular docking simulations have shown how allium cepa could inhibit fibroblasts proliferation and contraction via TGF- beta/smad signal pathway. (4) conclusions: the topical application of a pullulan-based medical device containing allium cepa and HA showed a clear reduction in the local inflammation, which might lead to a reduced probability of developing hypertrophic scars or keloids

Preliminary Evidence of Efficacy, Safety, and Treatment Satisfaction with Tirbanibulin 1% Ointment: A Clinical Perspective on Actinic Keratoses

background: actinic keratosis is a common precancerous skin lesion that can progress into invasive squamous cell carcinomas. many topical treatments for actinic keratoses often have poor tolerability and prolonged duration. Tirbanibulin is a novel synthetic drug with potent antitumor and antiproliferative activities. methods: we conducted a single-center, prospective and observational study using tirbanibulin ointment on a 25 cm2 area for 5 consecutive days on 30 participants with AKs on the face or scalp. They were followed for at least 57 days to assess the safety profile and efficacy of the drug as well as treatment satisfaction. we evaluated six signs of local skin reaction (LSR): erythema, scaling, crusting, swelling, blisters/pustules, and erosions/ulcerations, grading the severity as mild, moderate, or severe. The effectiveness was evaluated both clinically and dermoscopically. the treatment satisfaction was assessed using the treatment satisfaction questionnaire for medication (TSQM 1.4). results: on day 57, 70% of the patients showed a complete clinical and dermoscopic response. The highest scores obtained from the TSQM 1.4 were more evident in the convenience and side effects domains. most LSRs, including erythema (83.3%), scaling (30%), and swelling (3.3%), occurred on day 8 but resolved spontaneously. Conclusion: Tirbanibulin is a viable therapeutic option with a short regimen treatment and good tolerability, which favors therapy adherence

Pyodermitis during Nivolumab Treatment for Non-Small Cell Lung Cancer: A Case Report and Review of the Literature

Immunotherapy in oncology is replacing traditional therapies due to it specific action and limited side effects. Despite the high efficacy of immunotherapy, side effects such as bacterial infection have been reported. Bacterial skin and soft tissue infections represent one of the most important differential diagnoses in patients presenting with reddened and swollen skin and soft tissue. Among these infections, cellulitis (phlegmon) and abscesses are the most frequent. In most cases, these infections occur locally with possible contiguous spread, or as a multifocal manifestation, especially in immunocompromised patients. Herein, we report a case of pyodermitis in an immunocompromised district in a patient treated with nivolumab for non-small cell lung cancer. A 64-year-old, smoker male patient showed cutaneous lesions at a different evolution level in the left arm, all in a tattooed area, with one phlegmon and two ulcerated lesions. Microbiological cultures and gram staining revealed an infection caused by a methicillin-susceptible but erythromycin-resistant (ER-R), clindamycin-resistant (CL-R), and gentamicin-resistant (GE-R) Staphylococcus aureus strain. Despite immunotherapy becoming a milestone in oncologic treatment, more than the spectrum of immune-mediated toxicities of these agents needs to be investigated. This report highlights the importance of considering lifestyle and cutaneous background before starting immunotherapy for cancer treatment, with an emphasis on pharmacogenomics and the possibility of modified skin microbiota predisposing to cutaneous infections in patients treated with PD-1 inhibitors

Clinical efficacy and reflectance confocal microscopy monitoring in moderate-severe skin aging treated with a polyvinyl gel containing retinoic and glycolic acid: An assessor-blinded 1-month study proof-of-concept trial

Background Retinoids and alpha-hydroxy acids are commonly used topically as anti-aging substances. Current medical devices contain retinoic acid (0.02%) and glycolic acid (4%) in a polyvinyl gel vehicle (R-G gel). There are still no clinical data nor objective evaluation of the anti-aging effect this product has in the short term. Aims To assess in a prospective 1-month, noncomparative, primary outcome assessor-blinded proof-of-concept trial the clinical efficacy, tolerability, and the skin cells modification (evaluated through reflectance confocal microscopy; RCM), of R-G gel in skin aging treatment. Methods Twelve women with moderate-severe skin aging (Glogau score >= 3) were enrolled. The product was applied on the face three times a week for 4 weeks. Study visits were performed at baseline and after 2 and 4 weeks. RCM evaluation was performed openly at each visit using Viva Scope 1500 to evaluate the left cheek (5 mm below the zygomatic process). Results Eleven subjects concluded the trial. At baseline, the Glogau score was 3.4 +/- 0.5 and decreased significantly at week 4 (P = .0001; ANOVA test) to 2.7 +/- 0.6. Significant reductions of dark spots (-40%) and severity of wrinkles (-12%) were observed at week 4 compared to baseline. The RCM score improved significantly at week 4 with the recovery of the polygonal keratinocytes pattern as the central aspect observed. Conclusion The gel containing retinoic acid and glycolic acid showed significant improvements of the clinical signs of severe skin aging with a concomitant improvement of epidermal and dermal structures evaluated via RCM

Efficacy of a Topical Product Containing Purified Omental Lipids and Three Anti-Itching Compounds in the Treatment of Chronic Pruritus/Prurigo Nodularis in Elderly Subjects: A Prospective, Assessor-Blinded, 4-Week Trial with Transepidermal Water Loss and Optical Coherence Tomography Assessments

Purpose: To investigate the efficacy of a cream containing purified omental lipids 10% and three anti-itching substances (polidocanol/stimutex/palmitoylethanolamine) in elderly subjects with chronic pruritus/prurigo nodularis (CP/CPN). Patients and methods: Thirty-five subjects (6 men; mean age 67±4 years) with CP/CPN were enrolled in a prospective, assessor-blinded, 4-week study. The cream was applied twice daily in the most affected body area. The primary endpoints were the evolution of the 10-cm visual analogue itch severity scale (VAS) and the 4-point verbal itching rating scale (VRS) (from 0 to 3). Secondary endpoints were the evolution of optical coherence tomography (OTC) of four skin parameters (acanthosis/hyperkeratosis/scale/dermal vascular pattern), assessed in a target lesioned area, and the transepidermal water loss (TEWL). Study endpoints were evaluated at baseline and after 2 and 4 weeks by an investigator unaware of the type of treatment. Results: All the enrolled subjects concluded the trial. At baseline, the mean±SD scores for VAS and VRS were 4.9±2.2 and 1.7±0.7, respectively. The treatment was associated with a significant reduction (p=0.0001) of VAS score of 60% at week 2 and of 86% at week 4. VRS score was significantly reduced by 49% after 2 weeks and by 81% after 4 weeks, in comparison with baseline. TEWL (expressed as g/m2/h) mean values were 18±5.4 at baseline and 12.7±4.4 at week 2 and 9.8±4.7 at week 4 (P=0.0001 vs baseline). All the OCT parameters evaluated improved during active treatment; acanthosis grade was 0.22 mm at baseline, 0.19 mm at week 2 and 0.17 mm at week 4 (p=0.0005), representing a 23% reduction in comparison with baseline. The product was very well tolerated. Conclusion: This purified omental lipid with three anti-itching components cream reduces significantly itch intensity in subjects with chronic pruritus/prurigo nodularis, improving the skin barrier function and skin structure. Trial number: ISRCTN869561669

Reflectance Confocal Microscopy Applied to Linear (en Coup de Sabre) Morphea

En coup de sabre morphea is a clinical variant of morphea, presenting as a linear depressed, atrophic area in the paramedian forehead or the frontoparietal scalp, resembling a stroke from a sword. It affects the skin and subcutaneous connective tissues, with possible extension to the underlying musculature, cartilage, and bone and variable association with neurologic symptoms. A 50-year-old woman presented to our clinic for evaluation of an atrophic lesion on her forehead and scalp appearing 1 year before, progressively extending over time. An alopecic atrophic area involving the skin and subcutaneous tissues of her right forehead and scalp arranged in a linear fashion with an "en coup de sabre" appearance was observed in relation with hair loss in the affected area. Reflectance confocal microscopy showed marked hyperreflective areas with severe eccrine gland atrophy. All sebaceous glands had disappeared, with sporadic follicular persistence reduction. Histopathological examination of a punch biopsy specimen taken from a central parietal alopecic area was consistent with a diagnosis of morphea. To our knowledge, this is the first report regarding the use of reflectance confocal microscopy as an ancillary diagnostic technique in linear localized morphea of the scalp and face. This noninvasive technique may represent a useful tool in distinguishing between early stages of the disease, with prevalence of inflammatory lymphocytic infiltrate, and late stages characterized by more prominent sclerosis with mild or absent signs of inflammation