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Introduction: Lichen sclerosus (LS) is a chronic inflammatory dermatosis predominantly affecting the anogenital area, with potential systemic implications. Objective: Our aim is to elucidate its clinical characteristics and management strategies. Methods: We conducted a retrospective observational study on adult patients with LS referred to our center between January 2022 and December 2023. Results: Forty-six adult subjects affected by LS were enrolled in the present study. The majority of patients presented with genital involvement, but a significant subset exhibited extragenital LS and concomitant immune-mediated disorders. Common symptoms included itching, soreness, and dyspareunia, with characteristic skin findings of erythema and atrophy. Topical corticosteroids were the mainstay of therapy, complemented by alternative treatments in refractory cases. Alternative therapeutic approaches, such as platelet rich plasma or adipose-tissue derived stromal/stem cell-based strategies, were effectively employed in refractory cases, in the absence of major adverse events. Conclusions: Our findings underscore the importance of alternative approaches in the management of LS and highlight the need for further research to elucidate its pathogenesis and optimize therapeutic interventions.

Oral lichen sclerosus (OLS) represents a diagnostic challenge even for expert dermatologists due to its rarity and subtle clinical manifestations. Only few cases have been reported in literature to date. OLS typically presents with whitish macules in the oral cavity. Histopathological examination remains crucial for definitive diagnosis, with characteristic features including epithelial atrophy, subepithelial hyalinization, loss of elastic fibers, and lymphocytic infiltration. Management strategies vary depending on lesion size and symptomatic presentation, with topical or intralesional corticosteroids being the most commonly used treatment modalities. Long-term monitoring is recommended due to the potential for malignant transformation, although no cases have been reported to date. Greater awareness and understanding of OLS are essential for accurate diagnosis and effective management. Based on these findings, we recommend performing an accurate evaluation of the oral mucosa, especially when dealing with patients affected by genital or extragenital lichen sclerosus (LS). Moreover, we emphasize the importance of multidisciplinary collaboration between dermatologists and other specialists of oral disorders, such as dentists. This short review briefly summarizes available data on OLS, highlighting its diverse clinical presentations and diagnostic challenges. Despite its infrequent occurrence, OLS should be considered in the differential diagnosis of white macules in the oral cavity.

Systemic sclerosis (SS) is a complex connective tissue disease characterized by vasculopathy and progressive fibrosis, primarily considered an autoimmune disorder. SS can affect multiple organs and tissues, including the skin, respiratory, gastrointestinal, genitourinary, cardiovascular, and musculoskeletal systems. Skin involvement is common, and SS-related ulcers, especially digital ulcers, occur in roughly 50% of patients. These ulcers not only cause pain but also significantly impact patients' quality of life, and in severe cases, they can lead to infection, gangrene, and amputation. The search for novel therapies for scleroderma-related ulcers remains an ongoing research area. Platelet-rich plasma (PRP) has been investigated as a potential treatment for difficult-to-heal ulcers, including diabetic, pressure, and vascular ulcers. In this study, we share our experience in treating scleroderma ulcers with PRP. Ten patients with confirmed SS and chronic skin ulcers lasting at least six weeks, which had not responded to conventional treatments, were selected for the study. Homologous PRP gel was prepared and applied once a week for up to eight weeks. The ulcers were documented photographically before and after PRP treatment, and pain levels were assessed using a visual analog scale (VAS). We also conducted a systematic review of the literature focusing on the use of PRP in the setting of SS. The results from our casuistry showed that the ten patients, including eight females and two males with a median age of 52.5 years, had ulcer sizes ranging from 0.78 cm2 to 28.26 cm2. The ulcers were located on fingers, legs, and heels, and they were associated with various forms of SS, including limited and diffuse cutaneous involvement. Raynaud's phenomenon was prevalent, and two patients exhibited organ involvement. The average ulcer size at the end of PRP treatment decreased significantly, with a 78% reduction in ulcered area. Pain levels also markedly improved, as indicated by a reduction in VAS scores. With regards to systematic revision of literature, we retrieved 45 cases of SS treated with PRP-based therapeutic regimes. However, only a minority of them (n=16) underwent PRP treatment for the treatment of SS-related ulcers. An improvement in wound size and pain has been documented in all cases. Taken together, these data highlight the potential benefits of using homologous PRP in the treatment of scleroderma ulcers, emphasizing its positive impact on ulcer size reduction and pain relief.

Necrobiosis Lipoidica (NL) is a dermatological condition characterized by the development of granulomatous inflammation leading to the degeneration of collagen and subsequent formation of yellowish-brown telangiectatic plaques usually localized on the pretibial skin of middle-aged females. Due to its rarity and unclear etiopathogenesis, therapeutic options for NL are not well-standardized. Among them, photodynamic therapy (PDT) is an emerging tool, although its efficacy has primarily been evaluated in single case reports or small case series. This study reports the real-life experience of a cohort of NL patients treated with PDT at the Section of Dermatology of the University Hospital of Messina and Reggio-Emilia. From 2013 to 2023, 17 patients were enrolled —5 males (29%) and 12 females (71%) aged between 16 and 56 years (mean age: 42 ± 13 years), with a median duration of NL of 8 years. The overall complete clearance (>75% lesion reduction) was 29%, while the partial clearance (25–75% lesion reduction) was 59%, with 12% being non-responders. This study adds to the little amount of evidence present in the literature regarding the effectiveness of PDT in the treatment of NL. Variability in treatment responses among patients underscores the need for personalized protocols, optimizing photosensitizers, light sources, and dosimetry. The standardization of treatment protocols and consensus guidelines are essential to ensure reproducibility and comparability across studies.

Current methods for the diagnosis of urinary tract infections with antimicrobial susceptibility testing take 2-3 days and require a clinical laboratory. The lack of a rapid, point-of-care antibiotic susceptibility test (AST) has contributed to the misuse of antibiotics when treating urinary tract infections (UTIs) and consequently to the rise of multi-drug-resistant organisms. The current clinical approach has led to reduced treatment options and increased costs of diagnosis and therapy. To address this issue, novel diagnostics are needed for the timely determination of antimicrobial susceptibility. We present a rapid, point-of-care, phenotypic AST device that can report the antibiotic susceptibility/resistance of a uropathogen to a panel of antibiotics in as few as 3 h by utilizing fluorescent-labelling chemistry and a highly sensitive particle-counting instrument. We analysed 744 urine samples from the outpatients and inpatients of two Italian hospitals. The 130 UTI-positive patient urine samples we found were measured using a panel of six common UTI antibiotics plus a growth control. By comparing our results to hospital laboratory urine cultures, we obtained an overall sensitivity = 81%, a specificity = 83%, an SPV (sensitivity predicted value) = 95%, and an RPV (resistance predicted value) = 54%. According to our preliminary data, the sensitivity predicted value for a single antibiotic agent was 95%, thus allowing (in the vast majority of cases) an early (within 3 h) recognition of an effective agent for a single patient.

IntroductionFolliculin, encoded by FLCN gene, plays a role in the mTORC1 autophagy cascade and its alterations are responsible for the Birt–Hogg–Dubé (BHD) syndrome, characterized by follicle hamartomas, kidney tumors and pneumothorax.Patient and resultsWe report a 74-years-old woman diagnosed with dementia and carrying a FLCN alteration in absence of any sign of BHD. She also carried an alteration of MAT1A gene, which is also implicated in the regulation of mTORC1.DiscussionThe MAT1A variant could have prevented the development of a FLCN-related oncological phenotype. Conversely, our patient presented with dementia that, to date, has yet to be documented in BHD. Folliculin belongs to the DENN family proteins, which includes C9orf72 whose alteration has been associated to neurodegeneration. The folliculin perturbation could affect the C9orf72 activity and our patient could represent the first human model of a relationship between FLCN and C9orf72 across the path of autophagy.

The semantic variant of primary progressive aphasia (svPPA), known also as “semantic dementia (SD),” is a neurodegenerative disorder that pertains to the frontotemporal lobar degeneration clinical syndromes. There is currently no approved pharmacological therapy for all frontotemporal dementia variants. Transcranial direct current stimulation (tDCS) is a promising non-invasive brain stimulation technique capable of modulating cortical excitability through a sub-threshold shift in neuronal resting potential. This technique has previously been applied as adjunct treatment in Alzheimer’s disease, while data for frontotemporal dementia are controversial. In this scoped review, we summarize and critically appraise the currently available evidence regarding the use of tDCS for improving performance in naming and/or matching tasks in patients with svPPA. Clinical trials addressing this topic were identified through MEDLINE (accessed by PubMed) and Web of Science, as of November 2022, week 3. Clinical trials have been unable to show a significant benefit of tDCS in enhancing semantic performance in svPPA patients. The heterogeneity of the studies available in the literature might be a possible explanation. Nevertheless, the results of these studies are promising and may offer valuable insights into methodological differences and overlaps, raising interest among researchers in identifying new non-pharmacological strategies for treating svPPA patients. Further studies are therefore warranted to investigate the potential therapeutic role of tDCS in svPPA.

Introduction. The alarming rise in urinary tract infection (UTI) antimicrobial resistance has resulted from a combination of high prevalence, low specificity and the lack of a rapid, point-of-care (POC) antibiotic susceptibility test (AST), which has led to the overuse/inappropriate use of antibiotics.Aim. This study aimed to evaluate the performance of a rapid POC phenotypic AST device in reporting susceptibility information within 2 h.Methodology. Instrument calibration was performed with model bacteria and fluorescent microbeads to determine the dynamic range and limit of detection for quantifying concentrations of bacteria and demonstrate the ability to rapidly differentiate susceptible and resistant model bacteria. We then evaluated 30 presumptive UTI-positive patient urine samples in a clinical pilot study using a panel of 5 common UTI antibiotics plus a growth control and compared our results to the hospital standard of care AST.Results. Our device was able to robustly detect and quantify bacteria concentrations from 50 to 105 colony-forming units (c.f.u.) ml-1. The high sensitivity of this measurement technique enabled the device to differentiate between susceptible and resistant model bacteria with 100 % specificity over a 2 h growth period. In the clinical pilot study, an overall categorical agreement (CA) of 90.7 % was observed (sensitivity=91.4 %, specificity=88.9 %, n=97) with performance for individual drugs ranging from 85 % CA (ceftazidime) to 100 % (nitrofurantoin).Conclusions. By reducing the typical timeframe for susceptibility testing from 2-3 days to 2 h, our POC phenotypic AST can provide critical information to clinicians prior to the administration of antibiotic therapy.

In the last two years, a new severe acute respiratory syndrome coronavirus (SARS-CoV) infection has spread worldwide leading to the death of millions. Vaccination represents the key factor in the global strategy against this pandemic, but it also poses several problems, especially for vulnerable people such as patients with multiple sclerosis. In this review, we have briefly summarized the main findings of the safety, efficacy, and acceptability of Coronavirus Disease 2019 (COVID-19) vaccination for multiple sclerosis patients. Although the acceptability of COVID-19 vaccines has progressively increased in the last year, a small but significant part of patients with multiple sclerosis still has relevant concerns about vaccination that make them hesitant about receiving the COVID-19 vaccine. Overall, available data suggest that the COVID-19 vaccination is safe and effective in multiple sclerosis patients, even though some pharmacological treatments such as anti-CD20 therapies or sphingosine l-phosphate receptor modulators can reduce the immune response to vaccination. Accordingly, COVID-19 vaccination should be strongly recommended for people with multiple sclerosis and, in patients treated with anti-CD20 therapies and sphingosine l-phosphate receptor modulators, and clinicians should evaluate the appropriate timing for vaccine administration. Further studies are necessary to understand the role of cellular immunity in COVID-19 vaccination and the possible usefulness of booster jabs. On the other hand, it is mandatory to learn more about the reasons why people refuse vaccination. This would help to design a more effective communication campaign aimed at increasing vaccination coverage among vulnerable people.

The spread of smartphones and mobile-Health (m-health) has progressively changed clinical practice, implementing access to medical knowledge and communication between doctors and patients. Dedicated software called Applications (or Apps), assists the practitioners in the various phases of clinical practice, from diagnosis to follow-up and therapy management. The impact of this technology is even more important in diseases such as stroke, which are characterized by a complex management that includes several moments: primary prevention, acute phase management, rehabilitation, and secondary prevention. This review aims to evaluate and summarize the available literature on Apps for the clinical management of stroke. We described their potential and weaknesses, discussing potential room for improvement. Medline databases were interrogated for studies concerning guideline-based decision support Apps for stroke management and other medical scenarios from 2007 (introduction of the first iPhone) until January 2022. We found 551 studies. Forty-three papers were included because they fitted the scope of the review. Based on their purpose, Apps were classified into three groups: primary prevention Apps, acute stroke management Apps, and post-acute stroke Apps. We described the aim of each App and, when available, the results of clinical studies. For acute stroke, several Apps have been designed with the primary purpose of helping communication and sharing of patients’ clinical data among healthcare providers. However, interactive systems Apps aiming to assist clinicians are still lacking, and this field should be developed because it may improve stroke patients’ management.

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.

Over the past decades, among all the non-invasive brain stimulation (NIBS) techniques, those aiming for neuromodulatory protocols have gained special attention. The traditional neurophysiological outcome to estimate the neuromodulatory effect is the motor evoked potential (MEP), the impact of NIBS techniques is commonly estimated as the change in MEP amplitude. This approach has several limitations: first, the use of MEP limits the evaluation of stimulation to the motor cortex excluding all the other brain areas. Second, MEP is an indirect measure of brain activity and is influenced by several factors. To overcome these limitations several studies have used new outcomes to measure brain changes after neuromodulation techniques with the concurrent use of transcranial magnetic stimulation (TMS) and electroencephalogram (EEG). In the present review, we examine studies that use TMS-EEG before and after a single session of neuromodulatory TMS. Then, we focused our literature research on the description of the different metrics derived from TMS-EEG to measure the effect of neuromodulation.

We report a 7-year-old boy born with epidermal nevi (EN) arranged according to Blaschko’s lines involving the face and head, right upper limb, chest, and left lower limb, who developed a left paratesticular embryonal rhabdomyosarcoma at 18 months of age. Parallel sequencing identified a gain-of-function variant (c.37G>C, p.Gly13Arg) of HRAS in both epidermal nevus and tumor but not in leukocytes or buccal mucosal epithelial cells, indicating its postzygotic origin. The variant accounted for 33% and 92% of the total reads in the nevus and tumor DNA specimens, respectively, supporting additional somatic hits in the latter. DNA methylation (DNAm) profiling of the tumor documented a signature consistent with embryonal rhabdomyosarcoma and CNV array analysis inferred from the DNAm arrays and subsequent MLPA analysis demonstrated copy number gains of the entire paternal chromosome 11 carrying the mutated HRAS allele, likely as the result of paternal unidisomy followed by subsequent gain(s) of the paternal chromosome in the tumor. Other structural rearrangements were observed in the tumours, while no additional pathogenic variants affecting genes with role in the RAS-MAPK and PI3K-AKT-MTOR pathways were identified. Our findings provide further evidence of the contribution of “gene dosage” to the multistep process driving cell transformation associated with hyperactive HRAS function.

BackgroundCommercially available health devices are gaining momentum and represent a great opportunity for monitoring patients for prolonged periods. This study aimed at testing the feasibility of a smart device-based secondary prevention program in a cohort of patients with cryptogenic stroke.MethodsIn this proof-of-principle study, patients with non-disabling ischemic stroke and transient ischemic attacks (TIA) in the subacute phase were provided with a smartwatch and smart devices to monitor several parameters – i.e., oxygen saturation, blood pressure, steps a day, heart rate and heart rate variability - for a 4-week period (watch group). This group was compared with a standard-of-care group. Our primary endpoint was the compliance with the use of smart devices that was evaluated as the number of measures performed during the observation period.ResultsIn total, 161 patients were recruited, 87 in the WATCH group and 74 in the control group. In the WATCH group, more than 90% of patients recorded the ECG at least once a day. In total, 5,335 ECGs were recorded during the study. The median blood pressure value was 132/78 mmHg and the median oxygen saturation value was 97%. From a clinical standpoint, although not statistically significant, nine atrial fibrillation episodes (10.3%) in the WATCH group vs. 3 (4%) in the control group were detected.ConclusionOur study suggests that prevention programs for cerebrovascular disease may benefit from the implementation of new technologies.

Ischemic stroke is characterized by a complex cascade of events starting from vessel occlusion. The term “penumbra” denotes the area of severely hypo-perfused brain tissue surrounding the ischemic core that can be potentially recovered if blood flow is reestablished. From the neurophysiological perspective, there are local alterations—reflecting the loss of function of the core and the penumbra—and widespread changes in neural networks functioning, since structural and functional connectivity is disrupted. These dynamic changes are closely related to blood flow in the affected area. However, the pathological process of stroke does not end after the acute phase, but it determines a long-term cascade of events, including changes of cortical excitability, that are quite precocious and might precede clinical evolution. Neurophysiological tools—such as Transcranial Magnetic Stimulation (TMS) or Electroencephalography (EEG)—have enough time resolution to efficiently reflect the pathological changes occurring after stroke. Even if they do not have a role in acute stroke management, EEG and TMS might be helpful for monitoring ischemia evolution—also in the sub-acute and chronic stages. The present review aims to describe the changes occurring in the infarcted area after stroke from the neurophysiological perspective, starting from the acute to the chronic phase.

Abstract is missing (Short communication)

Drug-induced photosensitivity (DIP) is a common cutaneous adverse drug reaction, resulting from the interaction of ultraviolet radiations, mostly ultraviolet A, with drugs. DIP includes phototoxicity and photoallergy. A phototoxic reaction is obtained when topical and systemic drugs or their metabolites absorb light inducing a direct cellular damage, while a photoallergic reaction takes place when the interaction between drugs and ultraviolet radiations causes an immune cutaneous response. Clinically, phototoxicity is immediate and appears as an exaggerated sunburn, whereas photoallergy is a delayed eczematous reaction. DIP may show several clinical subtypes. In this mini-review we report the pathogenetic mechanisms and causative drugs of DIP. We offer a detailed description of DIP clinical features in its classical and unusual subtypes, such as hyperpigmentation/dyschromia, pseudoporphyria, photo-onycolysis, eruptive teleangiectasia, pellagra-like reaction, lichenoid reaction, photodistributed erythema multiforme and subacute/chronic cutaneous lupus erythematosus. We described how physicians may early recognize and manage DIP, including diagnostic tests to rule out similar conditions. We made suggestions on how to improve sun exposure behaviors of patients at risk of DIP by means of an aware use of sunscreens, protective clothing and recent technologic tools. We highlighted the lack of sun safety programs addressed to patients at risk of DIP, who need a formal education about their condition.

Necrobiosis Lipoidica (NL) is a dermatological condition characterized by the development of granulomatous inflammation leading to the degeneration of collagen and subsequent formation of yellowish-brown telangiectatic plaques usually localized on the pretibial skin of middle-aged females. Due to its rarity and unclear etiopathogenesis, therapeutic options for NL are not well-standardized. Among them, photodynamic therapy (PDT) is an emerging tool, although its efficacy has primarily been evaluated in single case reports or small case series. This study reports the real-life experience of a cohort of NL patients treated with PDT at the Section of Dermatology of the University Hospital of Messina and Reggio-Emilia. From 2013 to 2023, 17 patients were enrolled —5 males (29%) and 12 females (71%) aged between 16 and 56 years (mean age: 42 ± 13 years), with a median duration of NL of 8 years. The overall complete clearance (>75% lesion reduction) was 29%, while the partial clearance (25–75% lesion reduction) was 59%, with 12% being non-responders. This study adds to the little amount of evidence present in the literature regarding the effectiveness of PDT in the treatment of NL. Variability in treatment responses among patients underscores the need for personalized protocols, optimizing photosensitizers, light sources, and dosimetry. The standardization of treatment protocols and consensus guidelines are essential to ensure reproducibility and comparability across studies. [ABSTRACT FROM AUTHOR]