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Background: MatriDerm and Integra are both widely used collagenic acellular dermal matrices (ADMs) in the surgical setting, with similar characteristics in terms of healing time and clinical indication. The aim of the present study is to compare the two ADMs in terms of clinical and histological results in the setting of dermato-oncological surgery., Methods: Ten consecutive patients with medical indications to undergo surgical excision of skin cancers were treated with a 2-step procedure at our Dermatologic Surgery Unit. Immediately after tumor removal, both ADMs were positioned on the wound bed, one adjacent to the other. Closure through split-thickness skin grafting was performed after approximately 3 weeks. Conventional histology, immunostaining and ELISA assay were performed on cutaneous samples at different timepoints., Results: No significant differences were detected in terms of either final clinical outcomes or in extracellular matrix content of the neoformed dermis. However, Matriderm was observed to induce scar retraction more frequently. In contrast, Integra was shown to carry higher infectious risk and to be more slowly reabsorbed into the wound bed. Sometimes foreign body-like granulomatous reactions were also observed, especially in Integra samples., Conclusions: Even in the presence of subtle differences between the ADMs, comparable global outcomes were demonstrated after dermato-oncological surgery.

Background: Hip pain is common in cerebral palsy children, particularly at Gross-Motor Function Classification System level IV-V. It is associated to hip displacement and relates to the migration percentage. Recent literature suggested early reconstructive bone surgery, as the best approach to prevent hip luxation, then hip pain. Still, high rates of hip pain are reported., Aim: To investigate prevalence and determinants of hip pain in an Italian cerebral palsy sample., Design: Single-center retrospective cohort study., Setting: Inpatient and outpatient., Population: Patients with spastic or dyskinetic cerebral palsy, Gross-Motor Function Classification System level IV or V, age 0-18., Methods: A chart review was implemented to report hip pain, as a dichotomous variable (pain/no pain), age, sex, cerebral palsy subtype, Gross-Motor Function level, lumbar scoliosis, migration percentage, previous orthopedic surgery, or botulinum injections, oral or intrathecal baclofen, drug-resistant epilepsy, assistive devices for standing or walking. Descriptive statistics and a multivariate logistic stepwise regression were performed., Results: A total of 504 subjects were included: 302 level V, 209 females, 432 spastics. The mean length of follow-up was 6 years. The overall prevalence of hip pain was 8.9% (6.3% were at level V) and of hip dislocation was 19% (15.9% were at level V). Just 39% of dislocated hips were painful. Children at spastic subtype and level V were predominantly affected. Botulinum and soft tissue surgery related to lower rates of hip pain, without statistical significance. Age (OR 1.19, 95%CI 1.14-1.25, P value 0.000), sex (OR 1.72, 95%CI 1.18-2.52, P value 0.005), migration percentage (OR 1.02, 95%CI 1.02-1.03, P value 0.000) and lumbar scoliosis (OR 1.32, 95%CI 0.86-2.01, P value 0.200) resulted significant independent determinants of hip pain., Conclusions: Hip pain relates with the migration percentage, but not all dislocated hips become painful. Hip pain may be transient and requires a targeted and individualized approach. Children at spastic subtype and level V were predominantly affected. Age and sex are confirmed as determinants. Specific validated measures are to be implemented to assess hip pain., Clinical Rehabilitation Impact: Considering severe non-ambulatory cerebral palsy patients, pain and quality of life should be considered as outcomes, in the management of hip luxation.

Introduction: Mucosal melanoma is a rare neoplasm. Late diagnosis is caused by occult anatomic sites and scarcity of symptoms. Novel biological therapies have now become available. Demographic, therapeutical and survival records on mucosal melanoma are scarce., Objectives: To provide an 11-year retrospective clinical review of real-world data on mucosal melanomas managed in a tertiary referral center in Italy., Methods: We included patients with histopathological mucosal melanoma diagnoses from January 2011 to December 2021. Data were collected until the last known follow-up or death. Survival analysis was performed., Results: Among 33 patients, we found 9 sinonasal, 13 anorectal and 11 urogenital mucosal melanomas (median age 82, females 66.7%). Eighteen cases (54.5%) presented with metastasis (p<0.05). In the urogenital subgroup, only 4 patients (36.4%) had metastasis at diagnosis, all in regional lymph nodes. Sinonasal melanomas were surgically managed with a debulking procedure (44.4%); every case of anorectal and urogenital melanomas underwent radical surgery (30.8% and 45.5%). Fifteen patients were treated with biological therapy (p<0.05). Radiation therapy was used in all melanomas of the sinonasal region (p<0.05). Overall survival was longer for urogenital melanomas (26 months). Univariate analysis showed an increased hazard ratio for death in patients with metastasis. A negative prognostic value of metastatic status was reported by the multivariate model, while administration of first-line immunotherapy demonstrated a protective role., Conclusions: At diagnosis, the absence of metastatic disease is the most relevant factor that influences the survival of mucosal melanomas. Moreover, the use of immunotherapy might prolong the survival of metastatic mucosal melanoma patients.

Background: The role of statins among patients with established cardiovascular diseases (CVDs) who are hospitalized with COVID-19 is still debated. This study aimed at assessing whether the prior use of statins was associated with a less severe COVID-19 prognosis., Methods: Subjects with CVDs infected with SARS-CoV-2 and hospitalized between 20 February 2020 and 31 December 2020 were selected. These were classified into two mutually exclusive groups: statins-users and non-users of lipid-lowering therapies (non-LLT users). The relationship between statins exposure and the risk of Mechanical Ventilation (MV), Intensive Care Unit (ICU) access and death were evaluated by using logistic and Cox regressions models., Results: Of 1127 selected patients, 571 were statins-users whereas 556 were non-LLT users. The previous use of statins was not associated with a variation in the risk of need of MV (Odds Ratio [OR]: 1.00; 95% Confidence Intervals [CI]: 0.38-2.67), ICU access (OR: 0.54; 95% CI: 0.22-1.32) and mortality at 14 days (Hazard Ratio [HR]: 0.42; 95% CI: 0.16-1.10). However, a decreased risk of mortality at 30 days (HR: 0.39; 95% CI: 0.18-0.85) was observed in statins-users compared with non-LLT users., Conclusions: These findings support the clinical advice for patients CVDs to continue their treatment with statins during SARS-CoV-2 infection.

The study's aim was two-fold: to describe the trend of hip subluxation in the largest sample of Italian nonambulatory cerebral palsy (CP) children ever published; to investigate its determinants. This single-centre retrospective cohort study included patients with spastic or dyskinetic CP, Gross Motor Function Classification System (GMFCS) level IV or V, age 0-18 years, having been referred to our unit before March 2020. The hip subluxation was measured by means of the migration percentage (MP). Other data were gathered such as sex, CP subtype, GMFCS level, presence of drug-resistant epilepsy, age, use of walkers with weight relief or standing devices, previous botulinum injection or hip surgery, oral or intrathecal baclofen and hip pain. Multiple linear stepwise regression was performed and descriptive statistics are provided. Spastic CP had MP maximum increase in early ages, with GMFCS level V values persistently higher than level IV. The dyskinetic subtype showed a slower increase of the MP, with GMFCS level IV presenting similar or higher values, compared to level V. Age, CP severity and spastic subtype are the main determinants. The stepwise multiple regression analysis demonstrated that weight relief walking and standing assistive devices, combined with botulinum contributed to reduce the MP progression. Dyskinetic CP showed overall lower MP values and a more variable behaviour relative to age and GMFCS level, compared to the spastic subtype. Standing and walking assistive devices, with partial or total weight relief, combined with individually targeted botulinum injections, should be considered in the management of bilateral nonambulatory CP patients, to prevent hip subluxation or its recurrence after surgery., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Previous studies ruled out the benefits of azithromycin for treatment of patients with COVID-19 who are hospitalized. However, the effects of azithromycin for treatment of patients with positive SARS-CoV-2 test results in the community remains a matter of debate. This study aimed to assess whether azithromycin, when used in subjects with positive test results for SARS-CoV-2, is associated with a reduced risk of hospitalization, in-hospital COVID-19 outcomes, and death., Methods: Two study cohorts were selected. Cohort A included subjects with positive test results for SARS-CoV-2 between February 20, 2020 and December 10, 2020; cohort B included subjects infected with SARS-CoV-2 and hospitalized between February 20, 2020 and December 31, 2020. We compared the risk of hospitalization, intensive care unit access, need for mechanical ventilation, and death in azithromycin users versus nonusers. A clustered Fine-Gray analysis was employed to assess the risk of hospitalization; logistic and Cox regressions were performed to assess the risk of intensive care unit access, mechanical ventilation, and death., Results: In cohort A, among 4861 azithromycin users and 4861 propensity-matched nonusers, azithromycin use was associated with higher risk of hospitalization (hazard ratio [HR] 1.59, 95% confidence interval [CI] 1.45-1.75) compared with nonuse. In cohort B, among 997 subjects selected in both groups, azithromycin use was not significantly associated with intensive care unit access (odds ratio [OR] 1.22, 95% CI 0.93-1.56), mechanical ventilation (OR 1.30, 95% CI 0.99-1.70), 14-day mortality (HR0.88, 95% CI 0.74-1.05), or 30-day mortality (HR 0.89, 95% CI 0.77-1.03)., Conclusion: Our findings confirm the lack of benefits of azithromycin treatment among community patients infected with SARS-CoV-2, raising concern on potential risks associated with its inappropriate use., Competing Interests: Declarations of competing interest ICA, CF, DR, SC, PF, PC, RDP, SK, AZ, GM, AS, GC and GM have no conflicts of interest to declare. LGM reported receiving grants from Bayer, Daiiki-Sankyo, and Boehringer Ingelheim outside the submitted work and speaker fees from Pfizer and Bayer., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Most ELST data in the literature are case studies or limited to small cohorts (< 16 patients). We evaluated the main clinical signs observed at endolymphatic sac tumor (ELST) diagnosis in patients with or without Von Hippel-Lindau disease., Methods: We conducted a comprehensive literature search in PubMed, Scopus, and Web of Science. We included studies with at least 1 patient, of any age, affected by sporadic or VHL-related ELSTs reporting levels of hearing loss and facial nerve function and a comprehensive description of presenting symptoms at ELST diagnosis. We combined data for proportional meta-analysis. p values of 0.05 were considered statistically significant. Methodological quality was evaluated. Analyses were performed with MedCalc 14.8.1 software., Results: A total of 26 studies, including 113 patients and 118 cases of ELSTs were included. Pooled proportion rates (95% CI) of overall hearing loss was 88.7%, (82.4-93.4), severe hearing loss was 21.6% (12.8-32.1) profound hearing loss was 39.8% (28.7-51.5), vertigo/imbalance was 42.0% (33.8-50.5), tinnitus was 61.8% (53.4-69.8) and facial nerve palsy was 30.6% (23.2-38.9). Generally, symptoms were homogeneous or moderately heterogeneous among included studies., Conclusion: This is the first systematic review of clinical presentations at ELST diagnosis. The most serious clinical events include profound hearing loss and facial impairment. Fluctuating hearing loss, tinnitus and vertigo are frequently reported and may confound correct and prompt ELST diagnosis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Eccrine poroma (EP) is a rare benign adnexal tumor that may mimic benign or malignant tumors and differential diagnosis may be difficult under clinical and dermoscopic examination. Reflectance confocal microscopy (RCM) examination may add important information to diagnosis and subsequent management of solitary lesions for which dermoscopy can be challenging. The aim of the present study was to investigate features of EP at RCM in order to detect the characteristics that might aid in the differential diagnosis of EP versus other solitary lesions (benign or malignant). Secondary objective was to correlate the resulting features with histopathological findings. This monocentric retrospective observational case-control study included all EPs registered with RCM between January 2007 and May 2018. Control cases were benign or malignant lesions similar in clinical appearance, morphology, and dermoscopic features to EPs. RCM evaluators were blinded to clinical-dermoscopic images and to final histopathological diagnoses. Finally, RCM-histopathological correlation was performed. A total of 11 EPs and 33 controls were included in the present study. Among RCM parameters, "cords without palisading," "dark holes," "prominent vascularization" and "abundant stroma" resulted positively associated with EP in univariate analysis. RCM features correspond to the histopathological diagnosis of EP in 97% of cases, as illustrated by the cluster analysis. An excellent correlation between diagnostic features of conventional histopathology and RCM was observed. RCM assists in the differential diagnosis of solitary lesions, allowing to reach a correct diagnosis of EP through the identification of its four characteristics., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Nurses dealing with a patient's sexuality must start from an awareness of their own experience, specific attitudes, and possible limits. What emerges from the literature is a conservative tendency in nurses, which underlines the difficulty in this awareness, but even a difficulty in improving the necessary knowledge/skills. It is, therefore, essential to create tools that can raise awareness of these limits., Objective: the present study aims to explore the psychometric properties of the Attitudes and Beliefs about Sexuality Scale, adapted and validated for the Italian context., Method: This is an instrumental, cross-sectional piece of research, whose SABS validation process applies the steps of Beaton and Valmi. The convenience sample collected data from 223 participants in the first approach. This was followed by a retest involving 44 students randomly selected from those who responded in the first phase. Ethical principles were respected., Results: The SABS questionnaire demonstrated good test-retest reliability, good internal consistency, and adequate construct validity., Conclusions: The Italian version of the SABS is valid and reliable for use with nursing students. This is the fourth language in which the SABS is available for research.

Background and Objectives : Solid-organ transplant recipients (SOTRs) are notably considered at risk for developing cutaneous malignancies. However, most of the existing literature is focused on kidney transplant-related non-melanoma skin cancers (NMSCs). Conflicting data have been published so far on NMSC incidence among liver transplant recipients (LTRs), and whether LTRs really should be considered at lower risk remains controversial. The aim of the present study was to prospectively collect data on the incidence of cutaneous neoplasms in an LTR cohort. Materials and Methods: All LTRs transplanted at the Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit of Modena University Hospital from October 2015 to June 2021 underwent a post-transplant periodic skin check at the Dermatology Unit according to our institutional integrated care pathway. Data on the presence of cutaneous malignant and premalignant lesions were collected at every timepoint. Results: A total of 105 patients were enrolled in the present study. Nearly 15% of the patients developed cutaneous cancerous and/or precancerous lesions during the follow-up period. Almost half of the skin cancerous lesions were basal cell carcinomas. Actinic keratoses (AKs) were observed in six patients. Four patients developed in situ squamous cell carcinomas, and one patient was diagnosed with stage I malignant melanoma. Otherwise, well-established risk factors for the occurrence of skin tumors, such as skin phototype, cumulative sun exposure, and familial history of cutaneous neoplasms, seemed to have no direct impact on skin cancer occurrence in our cohort, as well as an immunosuppressive regimen and the occurrence of non-cutaneous neoplasms. Conclusions : Close dermatological follow-up is crucial for LTRs, and shared protocols of regular skin checks in this particular subset of patients are needed in transplant centers.

Background: The aim of this study was to assess long-term macular vascular changes and their correlation with functional recovery in patients successfully treated for Macula-ON and Macula-OFF rhegmatogenous retinal detachment (RRD). Methods: This retrospective observational study included 82 eyes of 82 patients who received primary successful retinal detachment surgery, 33 Macula-ON and 49 Macula-OFF. Superficial and deep capillary plexuses (SCP and DCP) were evaluated by optical coherence tomography angiography (OCTA), and were correlated with visual acuity (VA), surgical technique and tamponade at 12 months after surgery. The fellow eyes were used as controls. Results: At 12-month follow-up, there was a significant decrease in the vessel density (VD) in the SCP in the operated eyes compared to control eyes (p < 0.05) in both the Macula-ON and Macula-OFF groups. Vessel length density (VLD) decrease in SCP was more extended in the Macula-OFF group. No difference in the DCP perfusion parameters was found, compared to controls. Subgroup analysis dependent on the type of surgery or tamponade showed no significant differences of VD and VLD. An inverse correlation was found between the SCP VD and the duration of silicone oil (SO) tamponade (p = 0.039). A significant correlation was observed between parafoveal SCP VD and final best corrected visual acuity (BCVA) (p = 0.028). The multivariate linear regression analysis showed that only the type of tamponade was significantly correlated with the final BCVA in the Macula-ON group (p = 0.004). Conclusions: Our study described long-term perfusion changes in RRD after surgery, with lower SCP VD and VLD in the operated eyes compared to the fellow ones, not influenced by type of surgery or tamponade. The choice of tamponade and SO removal timing may affect functional outcomes, especially in Macula-ON RRD. In conclusion, such functional and perfusion changes can be considered biomarkers that highlight the relevance of careful management of this sight-threatening disease.

Melanoma is the deadliest type of skin cancer characterized by high cellular heterogeneity, which contributes to therapy resistance and unpredictable disease outcome. Recently, by correlating reflectance confocal microscopy morphology with histopathological type, we identified four distinct melanoma subtypes: dendritic cell, round cell, dermal nest, and combined-type melanomas. In this study, each reflectance confocal microscopy melanoma subtype expressed a specific biomolecular profile and biological behavior in vitro. Markers of tumor aggressiveness, including Ki-67, MERTK, nestin, and stemness markers were highest in the most invasive combined-type and dermal nest melanomas than in dendritic cell and round cell melanomas. This was also confirmed in multicellular tumor spheroids. Transcriptomic analysis showed modulation of cancer progression-associated genes from dendritic cell to combined-type melanomas. The switch from E- to N-cadherin expression proved the epithelial-to-mesenchymal transition from dendritic cell to combined-type subtypes. The dermal nest melanoma was predominantly located in the dermis, as also shown in skin reconstructs. It displayed a unique behavior and a molecular profile associated with a high degree of aggressiveness. Altogether, our results show that each reflectance confocal microscopy melanoma subtype has a distinct biological and gene expression profile related to tumor aggressiveness, confirming that reflectance confocal microscopy can be a dependable tool for in vivo detection of different types of melanoma and for early diagnostic screening., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Differential diagnosis of extrafacial flat pigmented lesions with dermoscopic reticular and/or homogeneous pattern is challenging. Dendritic cells upon reflectance confocal microscopy (RCM) still represent a pitfall. This study aims to determine the role of dendritic cells upon RCM in the epidermis and dermo-epidermal junction (DEJ), together with common RCM features for melanoma and nevi, in dermoscopically equivocal extrafacial flat pigmented lesions. A retrospective evaluation of RCM images of melanocytic extrafacial flat pigmented lesions with reticular and/or homogeneous dermoscopic pattern and with histopathological diagnosis, was performed. A multivariate model of RCM features was used to obtain a score of independent risk factors. A total of 698 lesions were included. Increasing patient age, epidermal dendritic cells, many dendritic cells in the DEJ (>30%) and many (>5/mm 2 ) round atypical cells were independent risk factors for melanoma. Edged papillae and melanophages were indicative of nevus. A score based on these features was developed to assist in melanoma differential diagnosis. The RCM observation of abundant (>30%) dendritic cells in the DEJ is highly suggestive of malignity. This independent risk factor should also be considered for improved differential diagnosis of extrafacial melanoma., (© 2022 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

Importance: Previous systematic reviews and meta-analyses have concluded that given data paucity, a comparison of reflectance confocal microscopy (RCM) with dermoscopy is complex. They recommend comparative prospective studies in a real-world setting of suspect lesions., Objective: To test the hypothesis that RCM reduces unnecessary lesion excision by more than 30% and identifies all melanoma lesions thicker than 0.5 mm at baseline., Design, Setting, and Participants: This randomized clinical trial included 3165 patients enrolled from 3 dermatology referral centers in Italy between January 2017 and December 2019, with a mean (SD) follow-up of 9.6 (6.9) months (range, 1.9-37.0 months). The consecutive sample of 3165 suspect lesions determined through dermoscopy were eligible for inclusion (10 patients refused). Diagnostic analysis included 3078 patients (48 lost, 39 refused excision). Data were analyzed between April and September 2021., Interventions: Patients were randomly assigned 1:1 to standard therapeutic care (clinical and dermoscopy evaluation) with or without adjunctive RCM. Information available guided prospective clinical decision-making (excision or follow-up)., Main Outcomes and Measures: Hypotheses were defined prior to study initiation. All lesions excised (baseline and follow-up) were registered, including histopathological diagnoses/no change at dermoscopy follow-up (with or without adjunctive RCM). Number needed to excise (total number of excised lesions/number of melanomas) and Breslow thickness of delayed diagnosed melanomas were calculated based on real-life, prospective, clinical decision-making., Results: Among the 3165 participants, 1608 (50.8%) were male, and mean (SD) age was 49.3 (14.9) years. When compared with standard therapeutic care only, adjunctive RCM was associated with a higher positive predictive value (18.9 vs 33.3), lower benign to malignant ratio (3.7:1.0 vs 1.8:1.0), and a number needed to excise reduction of 43.4% (5.3 vs 3.0). All lesions (n = 15) with delayed melanoma diagnoses were thinner than 0.5 mm., Conclusions and Relevance: This randomized clinical trial shows that adjunctive use of RCM for suspect lesions reduces unnecessary excisions and assures the removal of aggressive melanomas at baseline in a real-life, clinical decision-making application for referral centers with RCM., Trial Registration: ClinicalTrials.gov Identifier: NCT04789421.

Background: In this study we aimed at investigating macular perfusion/anatomical changes in eyes with early onset rhegmatogenous retinal detachment (RRD) after prompt surgery within 24 hours, comparing a bisected macula and not bisected macula RRD. Methods: In this prospective observational study, 14 eyes of 14 patients who underwent within-24 hours vitreoretinal surgery for early onset RRD were enrolled. Patients were further divided into two subgroups: the not bisected macula group (NBM group) and the bisected macula group (BM group). At baseline and 3-month follow up, macular architecture and vessel analysis were assessed using optical coherence tomography angiography (OCTA) imaging. In detail, quantitative and qualitative analyses of the macular area were performed to quantify topographical retinal perfusion changes after surgery, calculating the foveal avascular zone (FAZ), vessel density (VD) and vessel length density (VLD) at the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Results: Most cases (43%) were superotemporal RRD. Primary retinal reattachment was obtained in all cases, without recurrences within 3-month follow up. After surgery, a significant FAZ enlargement was observed at both the SCP and DCP level (p < 0.001; p < 0.05), with a significant effect of time noted between the two time points in the NBM and BM subanalysis (F = 3.68; p < 0.017). An excellent functional outcome was maintained for the whole follow-up. On the other hand, after surgery, perfusion parameters did not change significantly apart from the vessel density of the inferior macular sector at the DCP level (p = 0.03). Conclusions: Our findings suggest that the macular perfusion of eyes with RRD is still preserved if the surgery is performed really promptly, thus highlighting the great importance of a correct timing for surgery. OCTA analysis allows for a better understanding of the pathophysiological mechanisms underneath early vascular microarchitecture modifications of the posterior pole in retinal detachment, differentiating the two types of RRD not completely involving the fovea (BM and NBM).

Background: Basal cell carcinoma can simulate melanoma and specific dermoscopic criteria have not yet been defined in a large cohort., Objective: To identify dermoscopic "trump" characteristics for differential diagnosis, identify cluster groups and assess the clinical impact of this study's findings., Methods: Retrospective, multicentric comparative study of atypical, non-facial basal cell carcinoma (≥1 seven-point checklist criteria) and melanoma (with at least one BCC criteria) at dermoscopy. Observed dermoscopic features were used to develop a proposed score. Lesion clusters were defined with hierarchical analysis. Clinical impact was assessed with a blinded reader study following this study's results., Results: A total of 146 basal cell carcinoma and 76 melanoma were included. Atypical vascular pattern was common to most lesions (74.5%). Twelve trump features were included in the proposed score (sensitivity 94.1% and specificity 79.5%). Cluster analysis identified 3 basal cell carcinoma and 3 melanoma clusters. Findings improved overall diagnostic accuracy and confidence (26.8% and 13.8%, respectively; p < 0.001)., Conclusions: These findings support the notion that atypical vascular pattern should be considered a shared feature of both melanoma and atypical basal cell carcinoma. Our proposed score improves diagnostic accuracy and confidence. Absence of pigmented features was associated with lower diagnostic accuracy and confidence., (© 2022 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

Purpose: The migration percentage is a widely used criterion for surgery in displaced hips. Literature suggests that no hip can spontaneously improve if the migration percentage exceeds 45%, in a mixed population of cerebral palsy children. The aim of the present article was to identify the point of no return of the migration percentage in a selected sample of non-ambulatory cerebral palsy children, being the most exposed to hip luxation., Methods: This single-center retrospective cohort study included patients with spastic or dyskinetic cerebral palsy, Gross Motor Function Classification System level IV or V, age 0-18, having at least three pelvic radiographies, excluding radiographies relative to hips having previously undergone surgery. The following information was collected: sex, cerebral palsy subtype, Gross Motor Function Classification System level, presence of drug-resistant epilepsy, migration percentage, age at assessment, use of walking or standing assistive devices, previous botulinum injection, oral or intrathecal baclofen, and hip pain. Data were analyzed at the level of the individual hips. Descriptive statistics were presented. Receiver operating characteristic curve analysis was conducted to investigate which value of the migration percentage could be adopted as the "point of no return": that is, the cutoff value beyond which no migration percentage reduction, by more than 5%, could be expected., Results: The optimal cutoff value was identified as migration percentage ≥50%, with a sensitivity of 84.5% and a specificity of 100% (p-value <0.001)., Conclusion: Based on the present study, migration percentage ≥50% is the "point of no return" for Gross Motor Function Classification System IV-V cerebral palsy patients, representing the cutoff value beyond which no spontaneous cerebral palsy reduction may be expected, unless addressing surgery., Level of Evidence: level II-retrospective study., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Digital dermoscopy follow up (DDF) is useful in improving the recognition of melanoma, catching early changes over time, although benign nevi can also show changes. Reflectance confocal microscopy (RCM) improves accuracy in diagnosing melanoma and decreases the number of unnecessary resections., Objective: To evaluate dynamic dermoscopic and RCM changes during follow up of equivocal melanocytic lesions and assess the impact of adjunctive RCM to DDF for melanoma diagnosis., Methods: A retrospective, multicenter study of extrafacial atypical melanocytic lesions excised during follow up was performed. Morphologic changes were evaluated, comparing dermoscopy and RCM baseline and follow-up images., Results: One hundred thirty-seven atypical melanocytic lesions were studied, including 14 melanomas and 123 benign nevi. Significantly greater changes in DDF of atypical network, regression, atypical streaks, and asymmetrical growth as well as in dynamic RCM of atypical cells and dermal-epidermal junction disarray were noted in melanomas. With adjunctive dynamic RCM and major changes at DDF, sensitivity reached 100%, with 40.6% specificity., Limitations: Selected series of difficult to recognize lesions, with both DDF and dynamic RCM images., Conclusion: Adjunctive dynamic RCM improves early melanoma recognition sensitivity., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Increasing numbers of individuals suffer from post-acute COVID-19 syndrome (PACS), which manifests with persistent symptoms, the most prevalent being dyspnea, fatigue, and musculoskeletal, cognitive, and/or mental health impairments. This systematic review investigated the effectiveness of rehabilitation interventions for individuals with PACS. We searched the MEDLINE, Embase, Cochrane Register of Controlled Trials, CINHAL, Scopus, Prospero, and PEDro databases and the International Clinical Trials Registry Platform for randomized controlled trials (RCTs) up to November 2021. We screened 516 citations for eligibility, i.e., trials that included individuals with PACS exposed to exercise-based rehabilitation interventions. Five RCTs were included, accounting for 512 participants (aged 49.2-69.4 years, 65% males). Based on the revised Cochrane risk-of-bias tool (RoB 2.0), two RCTs had "low risk of bias", and three were in the "some concerns" category. Three RCTs compared experimental rehabilitation interventions with no or minimal rehabilitation, while two compared two active rehabilitation interventions. Rehabilitation seemed to improve dyspnea, anxiety, and kinesiophobia. Results on pulmonary function were inconsistent, while improvements were detected in muscle strength, walking capacity, sit-to-stand performance, and quality of life. Pending further studies based on qualitatively sound designs, these first findings seem to advocate for rehabilitation interventions to lessen disability due to PACS.

Background: The increasing global burden of melanoma demands efficient health services. Accurate early melanoma diagnosis improves prognosis., Objectives: To assess melanoma prevention strategies and a systematic diagnostic-therapeutical workflow (improved patient access and high-performance technology integration) and estimate cost savings., Methods: Retrospective analysis of epidemiological data of an entire province over a 10-year period of all excised lesions suspicious for melanoma (melanoma or benign), registered according to excision location: reference hospital (DP) or other (NDP). A systematic diagnostic-therapeutical workflow, including direct patient access, primary care physician education and high-performance technology (reflectance confocal microscopy (RCM)) integration, was implemented. Impact was assessed with the number of lesions needed to excise (NNE)., Results: From 40,832 suspicious lesions excised, 7.5% ( n = 3054) were melanoma. There was a 279% increase in the number of melanomas excised ( n = 203 (2009) to n = 567 (2018)). Identification precision improved more than 100% (5.1% in 2009 to 12.0% in 2018). After RCM implementation, NNE decreased almost 3-fold at DP and by half at NDP. Overall NNE for DP was significantly lower (NNE = 8) than for NDP (NNE = 20), p < 0.001. Cost savings amounted to EUR 1,476,392.00., Conclusions: Melanoma prevention strategies combined with systematic diagnostic-therapeutical workflow reduced the ratio of nevi excised to identify each melanoma. Total costs may be reduced by as much as 37%.

Background: The gold standard treatment for solitary medium-sized (1-2 cm) renal stones is not defined by recent guidelines, since management modalities including shockwave lithotripsy (SWL), retrograde intrarenal surgery (RIRS), and percutaneous nephrolithotomy (PNL) are recommended. Improved ability to predict patient outcomes would aid in patients' counseling and decision-making., Objective: To develop a nomogram predicting treatment failure, based on preoperative clinical variables, to be used in the preplanning setting., Design, Setting, and Participants: We recruited 2605 patients from 14 centers and carried out a multicenter retrospective analysis of 699 SWL, 1290 RIRS, and 616 PN L procedures performed as first-line treatment for 1-2-cm kidney stones. The variables evaluated included age, gender, previous renal surgery, body mass index, stone size, location, stone density, skin-to-stone distance, presence of urinary tract infections (UTIs), and hydronephrosis., Outcome Measurements and Statistical Analysis: Multivariate logistic regression was fitted to predict treatment failure, defined as the presence of residual fragments >4 mm. A nomogram was developed based on the coefficients of the logit function., Results and Limitations: A total of 2431 (93.3%) patients were stone free; 174 (6.7%) treatment failures were recorded and considered the event to be predicted. On univariate analysis, type of procedure, preoperative hydronephrosis, stone density, stone location, and laterality turned out to be statistically significant. Skin-to-stone distance, UTIs, and previous renal surgery were predictors of failure on multivariate analysis. Each variable was given a score based on statistical relevance. The main limitation of the current study is its retrospective nature., Conclusions: This nomogram provides a prediction of treatment failure and need of reintervention for medium-sized kidney stones. External validation is needed to determine its reproducibility and validity., Patient Summary: We developed a preoperative model of treatment outcomes for 1-2-cm kidney stones. Its application may assist urologists to counsel patients with regard to stone management modality., (Copyright © 2020. Published by Elsevier B.V.)

Background-Actinic keratoses (AKs) are the most common sun-induced precancerous lesions that can progress to squamocellular carcinoma (SCC). Recently, the grade-independent association between AKs and SCC has been suggested; however, the molecular bases of this potential association have not been investigated. This study has assessed the metabolomic fingerprint of AK I, AK II, AK III and SCC using high resolution magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy in order to evaluate the hypothesis of grade-independent association between AK and SCC. Association between AKs and SCCs has also been evaluated by histopathology. Methods-Metabolomic data were obtained through HR-MAS NMR spectroscopy. The whole spectral profiles were analyzed through multivariate statistical analysis using MetaboAnalyst 5.0. Histologic examination was performed on sections stained with hematoxylin and eosin; statistical analysis was performed using STATA software version 14. Results-A group of 35 patients affected by AKs and/or SCCs and 10 healthy controls were enrolled for metabolomics analysis. Histopathological analysis was conducted on 170 specimens of SCCs and AKs (including the ones that underwent metabolomic analysis). SCCs and AK I were found to be significantly associated in terms of the content of some metabolites. Moreover, in the logistic regression model, the presence of parakeratosis in AKs appeared to be less frequently associated with SCCs, while AKs with hypertrophy had a two-fold higher risk of being associated with SCC. Conclusions-Our findings, derived from metabolomics and histopathological data, support the notion that AK I are different from healthy skin and share some different features with SCCs. This may further support the expanding notion that all AKs should be treated independently from their clinical appearance or histological grade because they may be associated with SCC.

Purpose: To systematically review outcomes of orbital bony wall decompression for Grave's orbitopathy according to the surgical approach., Methods: A systematic search for studies published in "Ovid MEDLINE", "Web of Science" and "Embase" of patients with surgical treatment of Grave's orbitopathy was performed. The overall postoperative change in Hertel exophthalmometry was calculated by random-effect meta-analysis model with 95% confidence interval (CI)., Results: A total of 33 studies, including 1686 patients and 2946 procedures, were included. The weighted mean Hertel value overall reduction was - 4.56 mm (95% CI - 5.05 to - 4.07 mm). According to surgical techniques the reduction was - 4.36 mm (95% CI - 5.22 to - 3.50) for infero-medial technique, - 4.88 mm (- 5.68 to - 4.08) for medial-lateral technique, - 4.32 mm (- 4.80to - 3.84) for lateral technique, - 5.45 mm (- 6.16 to - 4.74) for three-wall technique and - 3.47 mm (- 5.81 to - 1.12) for medial technique. The overall rate of new-onset of primary gaze diplopia was reported in 23 studies. The included procedures were 653 and results were heterogeneous (heterogeneity: Q = 78.8 df = 22, I2 = 72.09%, p < 0.01). The pooled proportion (95% CI) rate of new-onset of primary gaze diplopia was 12% (7-16)., Conclusion: Our metanalysis highlights that orbital bony wall decompression represents an effective surgical procedure. The three wall approach was associated with the best results in terms of exophthalmos reduction. Data suggest that an exclusive lateral approach may help to avoid the new-onset of primary gaze diplopia during the postoperative period., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

A retrospective case-control study was conducted at Modena University Hospital from December 2017 to January 2019 to identify risk factors and predictors of MDR/XDR Pseudomonas aeruginosa (PA) isolation with resistance to ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T), and of mortality among patients infected/colonized. Among 111 PA isolates from clinical/surveillance samples, 60 (54.1%) were susceptible to both drugs (S-CZA-C/T), while 27 (24.3%) were resistant to both (R-CZA-C/T). Compared to patients colonized/infected with S-CZA-C/T, those with R-C/T + CZA PA had a statistically significantly higher Charlson comorbidity score, greater rate of previous PA colonization, longer time before PA isolation, more frequent presence of CVC, higher exposure to C/T and cephalosporins, longer hospital stay, and higher overall and attributable mortality. In the multivariable analysis, age, prior PA colonization, longer time from admission to PA isolation, diagnosis of urinary tract infection, and exposure to carbapenems were associated with the isolation of a R-C/T + CZA PA strain, while PA-related BSI, a comorbidity score > 7, and ICU stay were significantly associated with attributable mortality. C/T and CZA are important therapeutic resources for hard-to-treat PA-related infections, thus specific antimicrobial stewardship interventions should be prompted in order to avoid the development of this combined resistance, which would jeopardize the chance to treat these infections.

Hearing loss is one of the most common congenital sensory disorders. It can be associated with several comorbidities, in particular developmental disabilities (DD). In Emilia-Romagna (ER), a region in Northern Italy, Child and Adolescent Mental Health Services (CAMHS) provide the diagnostic framework and treatment for these conditions. The aim of the present study is to evaluate the prevalence of hearing loss, both isolated or in association with comorbidities, in the juvenile population. The study draws its data from the ER Childhood and Adolescent Neuropsychiatry Information System (SINPIAER), an Administrative Healthcare Database collecting the clinical data of all those who have attended CAMHS since 2010. The most frequent type of hearing loss was bilateral sensorineural hearing loss, which was present in 69-72% of the cases, while bilateral conductive hearing loss was the second most common type, ranging from 8 to 10%. Among DD, congenital malformations, mental retardation, visual impairment, and cerebral palsy were the most common. In particular, autism spectrum disorders show increasing incidence and prevalence among CAMHS users in ER region. In-depth knowledge of hearing loss epidemiology and related conditions, such as developmental disabilities, in the juvenile population is crucial for disease prevention, health planning, and resource allocation.

Background: Psoriasis is a chronic, relapsing disease and most epidemiological studies include selected patients undergoing systemic therapies only. Epidemiological data suggest that psoriasis affects 2-3% of the general population, and that men and women are equally affected. The objective was to identify differences in gender for disease severity, patient characteristics and comorbidities in patients with moderate to severe psoriasis, independent of therapy., Methods: A retrospective medical chart review of consecutive patients diagnosed with moderate-severe psoriasis at a single center between 2004 and 2017, with a complete set of medical records, was undertaken. Both univariate and multivariate regression analyses were performed. Statistical significance was defined as P<0.05., Results: The male-to-female ratio revealed a higher prevalence for male gender (2:1, P<0.05). Whilst no significant differences were found for most factors according to gender, age at first evaluation was significantly higher for women. Logistic regression analysis indicated that autoimmune/autoinflammatory diseases were more frequently observed in women, as well as phenotypes other than plaque psoriasis and hypertension. Inversely, dyslipidemia was more frequently associated with male gender., Conclusions: Our results show that moderate-severe psoriasis is more common in men and suggests a differential gender distribution of some specific comorbidities in the setting of this disease.

Background: Lentigo maligna (LM) and lentigo maligna-melanoma (LMM) are histotypes of melanoma arising in skin with cumulative solar radiation damage. The extension of atypical melanocytes to the hair follicle (folliculotropism) is a histopathological feature of LM/LMM. Its role has not been totally clarified, but it may be correlated to treatment response in LM or to progression in LMM., Objective: This retrospective, multicentric study aims to identify dermatoscopic features associated with folliculotropism in LMs/LMMs., Patients and Methods: We analyzed cases of head and neck LMs/LMMs diagnosed between 2005-2014 at Melanoma Units, University of Bologna/Modena/Florence/Siena (Italy), Nice (France): 25 LMs and 73 LMMs were included., Results: Grey circles (44 %) indicated an isthmic/bulb level of involvement, which were completely absent in the infundibular LM lesions (P = 0.041). In the group of LMMs, light/dark brown pseudonetwork and light brown structureless areas were an indicator of diffuse distribution of malignant melanocytes in the follicular units (P < 0.001 and P = 0.001, respectively), while grey circles indicated focal or diffuse distribution (P < 0.001)., Conclusions: A better understanding of the extension of malignant melanocytes is helpful, aiding clinicians in their decision to perform a radical excision or obtaining a biopsy in the most invasive area of the lesion, which includes potential folliculotropism., (© 2020 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Background: Atopic dermatitis (AD) is a chronic inflammatory disease. Recently, dupilumab was approved for moderate-to-severe AD. D-OCT is a noninvasive tool for the characterization of skin diseases., Objective: To describe the changes observed with D-OCT in lesional and clinically healthy skin of patients with refractory severe AD under dupilumab treatment., Methods: We analyzed AD lesions and healthy skin by D-OCT. Clinical scores of AD severity were assessed at baseline (T0) and after 1 and 3 months of treatment (T1, T2). Descriptive statistics, chi-square test, and t test were used to compare the analyzed parameters over time and between AD lesions and clinically healthy skin., Results: At baseline, average EASI was 45.7. During the follow-up, EASI75 and EASI90 were achieved in 57% and 36% of patients at T1 and 100% and 86% of patients at T2, respectively. Lesional skin D-OCT parameters related to epidermal remodeling and inflammation evidenced a significant improvement after 1 month of treatment. In clinically healthy skin, D-OCT parameters improved significantly after 3 months of treatment, especially for collagen remodeling and inflammation., Conclusion: The study demonstrates that the clinical improvement of severe AD patients under dupilumab treatment is correlated with specific D-OCT changes of patients' lesional and clinically healthy skin., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Purpose: To evaluate the role of magnetic resonance imaging (MRI) performed before and after neoadjuvant chemoradiotherapy (nCRT) in predicting risk of recurrence in rectal cancer and to investigate the prognostic significance of MR-detected extramural venous invasion (mr-EMVI) and of its regression after nCRT., Methods: During 2005-2016, 87 patients with rectal cancer underwent pre- and post-nCRT MRI before surgery. Two radiologists independently reviewed MR examinations retrospectively, assessing T stage, nodal involvement, circumferential resection margin (CRM) status, and mr-EMVI. All four parameters assessed in pre- and post-nCRT MRI were correlated with the risk of recurrence. Correlation with disease-free survival (DFS) was investigated for significant predictive factors in pre-nCRT MRI and for mr-EMVI and its possible regression in post-nCRT MRI., Results: 15 of 87 patients developed recurrence, with a relapse-rate of 17.2%. Statistical analysis showed a significant correlation between CRM involvement and mr-EMVI assessed in pre-nCRT MRI and the risk of recurrence; 3 years-DFS in patients positive for these two parameters was significantly shorter compared with negatives. In post-nCRT MRI, all four parameters correlated significantly with recurrence: mr-EMVI affected significantly 3 years-DFS and its regression after nCRT correlated with a trend toward improvement of survival outcomes, although not statistically significant., Conclusions: CRM involvement and mr-EMVI assessed in pre-nCRT MRI should be considered early predictive factors of recurrence in rectal cancer. MRI performed after nCRT has a significant value in predicting risk of recurrence: mr-EMVI confirmed to be a poor prognosis predictor and its regression or persistence after nCRT could have influences on treatment and follow-up strategies.

The aim of the study was to identify possible predictors of neurological worsening and need of non-invasive ventilation (NIV) in individuals affected by myotonic dystrophy type 1 (DM1), the most common form of adult-onset muscular dystrophy., Methods: A retrospective observational cohort study was undertaken. Thirty-three patients with genetic diagnosis of DM1 were followed at our Neuromuscular unit in Modena. Abnormal trinucleotide repeat (CTG) expansion of dystrophy protein kinase gene (MDPK) on chromosome 19q 13.3 was the prerequisite for inclusion. The number of CTG repeats was determined. All the participants were older than 14 at the time of enrolment, therefore they could be included into the juvenile or adult form of the disease. Participants were neurologically evaluated every 6-8 months up to 18 years. Neurological impairment was assessed by Muscular Impairment Rating (MIRS), Medical Research Council (MRC), and modified Rankin (mRS) scales. The independent variables considered for prognosis were age at first evaluation, duration of the disease, CTG repeat number, gender, and presence of cardiac and vascular morbidities.Male patients were 51.5% and female patients 48.5%. Sixteen patients were younger than the mean age of 30.1 years, while the remaining 17 were up to 65. Twelve subjects (36.4%) underwent NIV before the end of follow-up. Muscle force and disability scores showed statistically significant deterioration (p < 0.001) during follow-up. The worsening was significantly higher among patients carrying higher number of CTG repeats and of younger age. The presence of cardio-vascular involvement has significant impact on neurological and respiratory progression.Neurological worsening is predicted by CTG expansion size, young age and presence of cardio-vascular morbidities., (©2020 Gaetano Conte Academy - Mediterranean Society of Myology, Naples, Italy.)

Background: Everolimus (Eve), which is a mammalian target of Rapamicin (mTOR) inhibitor, is part of the therapeutic armamentarium of neuroendocrine tumors (NETs). Currently, there are no validated biomarkers predicting Eve efficacy in NETs. In this study, we explore whether the expression of phosphorilated (p)-mTOR and p70S6-kinase (S6K), a downstream effector of mTOR, correlates with the outcome of patients with NET that were treated with Eve., Methods: Tissue specimens that were derived from NETs treated with Eve at our Institution were examined for the expression levels of p-mTOR and p-S6K by immunohistochemistry. Response rate (RR), progression-free survival (PFS), and overall survival (OS) were analyzed in two groups: p-mTOR/p-S6K positive (group 1) and p-mTOR/p-S6K negative (group 2). Univariate and multivariate Cox regression analysis were performed., Results: Twenty-four patients with advanced NETs that were treated with Eve were included in the analysis. Eight out 24 (33.3%) patients were both p-mTOR and p-S6K positive. A better median PFS and OS in group 1 (18.2 and 39.9 months) as compared to group 2 (13 and 32.4 months) was depicted, with a toxicity profile that was comparable with data literature., Conclusions: Our study suggests that the activation of mTOR pathway can predict better outcomes in patients with NET treated with Eve. However, these results warrant further confirmation in a prospective setting.

Background: Advances in biologic treatments have led to a new therapeutic frontier for moderate-to-severe psoriasis. Nevertheless, the efficacy of anti-TNFα decreases with time, requiring adjustments to maintain valuable Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) responses., Objectives: To evaluate the efficacy and safety of adalimumab dose escalation (40 mg, subcutaneous, once a week for 24 weeks) in psoriatic adult patients with secondary loss of response (PASI ≥50 to ≤75 or PASI≥75 and DLQI ≥5)., Materials and Methods: A multicentre, observational study involving different Italian third-level referral centres for psoriasis enrolled a total of 64 adult patients with moderate-to-severe psoriasis who were treated with adalimumab and experienced a secondary loss of response. Primary end-points were PASI> 75 or PASI ≥50 to ≤ 75 with DLQI ≤ 5, and the secondary end-point was the ability to maintain a therapeutic response, resuming adalimumab every other week., Results: At Week 16 and Week 24, 29/64 (45.3%) and 35/64 (54.6%) responded based on PASI, and mean DLQI was 4.9 and 4.09, respectively. At Week 36 and Week 48, 45.3% and 28.1% patients achieved the second end-point, respectively. No adverse events were recorded except for one patient with recurrent tonsillitis., Conclusion: Adalimumab escalation could be considered in cases with loss of response before switching to alternative biologic therapy.

Ex vivo fluorescence confocal microscopy (FCM) is an optical technology that provides fast H&E-like images of freshly excised tissues, and it has been mainly used for "real-time" pathological examination of dermatological malignancies. It has also shown to be a promising tool for fast pathological examination of prostatic tissues. We aim to create an atlas for FCM images of prostatic and periprostatic tissues to facilitate the interpretation of these images. Furthermore, we aimed to evaluate the learning curve of images interpretation of this new technology. Eighty fresh and unprepared biopsies obtained from radical prostatectomy specimens were evaluated using the FCM VivaScope® 2500 M-G4 (Mavig GmbH, Munich, Germany; Caliber I.D.; Rochester NY, USA) by two pathologists. Images of FCM with the corresponding H&E are illustrated to create the atlas. Furthermore, the two pathologists were asked to re-evaluate the 80 specimens after 90 days interval in order to assess the learning curve of images' interpretation of FCM. FCM was able to differentiate between different types of prostatic and periprostatic tissues including benign prostatic glands, benign prostatic hyperplasia, high-grade intraepithelial neoplasm, and prostatic adenocarcinoma. As regards the learning curve, FCM demonstrated a short learning curve. We created an atlas that can serve as the base for urologists and pathologists for learning and interpreting FCM images of prostatic and periprostatic tissues. Furthermore, FCM images is easily interpretable; however, further studies are required to explore the potential applications of this new technology in prostate cancer diagnosis and management.

Purpose: In order to understand how thyroid abnormalities emerge over time in adults, we evaluated incidence of thyroid diseases in healthy subjects, after almost 6 years from a previous negative ultrasound. Methods: Anamnestic and physical data were collected. Ultrasound neck evaluation was performed by an experienced endocrinologist, recording detailed thyroid and nodules characteristics. Nodules were classified according to American Thyroid Association classification for prediction of cancer risk. Serum samples were collected for subsequent evaluations (TSH, free thyroid hormones, calcitonin, anti-thyroid antibodies). Anamnestic, clinical, sonographic, and serological characteristics were analyzed with logistic regression analysis for subjects with nodules vs. those without. Results: One hundred and eleven subjects were enrolled (43M, 68F). Half of them developed nodules, mainly smaller than 1 cm and without suspicious characteristics. Ninety-seven percent were euthyroid. Only 4% had serological diagnosis of thyroiditis. Incidence of thyroid diseases was higher in women, especially nulliparous. Comparing clinical characteristics of subjects with and without nodules, the only statistically significant difference concerned thyroid volume adjusted for body weight or surface ( p < 0.05), but not residual volume excluding nodules. Multivariate logistic regression analysis showed that female gender, higher BMI-adjusted thyroid volume and residual thyroid volume excluding nodules, nulliparity, age, and fT3 increase the risk of developing nodules. Conclusions: These results demonstrate that adult thyroid tissue undergoes changes that are already detectable by US after almost 6 years. Half of the enrolled subjects developed de novo nodules or colloid cysts of poor clinical relevance., (Copyright © 2020 Brigante, Monzani, Locaso, Gnarini, Graziadei, Kaleci, De Santis, Tagliavini, Simoni, Rochira and Madeo.)

Background: The melanocortin 1 receptor (MC1R) gene is one of the major determinants of skin pigmentation. It is a highly polymorphic gene and some of its polymorphisms have been related to specific skin phenotypes, increased risk of skin cancers and skin photoageing. Currently, its contribution to changes in dermal features in photo-exposed skin is unknown., Objective: The main objective of this study is to evaluate the potential correlation between MC1R status and specific healthy photo-exposed skin characteristics., Materials and Methods: Skin facial features were estimated by evaluation with standard digital photography with automated features count, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) in 100 healthy women. Skin of the forearms was used as a control., Results: The study found an association between RHC MC1R polymorphisms and dermal features in photo-exposed areas being represented by increased vessel density and pixel density in OCT (P = .025 and P = .001, respectively) and increased coarse collagen in RCM (P = .034), as compared to non-RHC subjects. To our knowledge this is previously unreported. Additionally, previously reported correlations between light hair colour and pigmented spots with MC1R RHC polymorphisms have been confirmed., Conclusions: Our results suggest the role of RHC MC1R variants in dermal variations of facial skin, as compared to non-RHC variants. To our knowledge this is previously unreported., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Liquid biopsy consists in the quantification and qualification of circulating cell-free DNA (cfDNA) and tumor-derived DNA (ctDNA) for cancer recognition. Recently, the characterization of seminal cfDNA (scfDNA) has been reported as a possible biomarker for prostate cancer (PCa) diagnosis., Methods: Thirty patients with histologically proven PCa, 33 with benign prostate hyperplasia (BPH) and 21 healthy controls were enrolled. cfDNA was extracted from seminal fluid samples. cfDNA quantification and analysis were performed using Qubit ssDNA Kit and Agilent 2100 Bioanalyzer. Statistical analysis included: Levene's test, Shapiro-Wilk, Kolmogorov-Smirnov and Kruskal Wallis tests., Results: Median cfDNA was significantly higher in PCa patients 428.45 ng/mL (173.93-1159.62) compared to BPH patients 77.4 ng/mL (18.23-501) and healthy controls 25.4 ng/mL (15.37-76.62). scfDNA fragments longer than 1000 base-pairs were more common in patients with PCa compared to those with BPH and controls., Conclusions: scfDNA concentration and fragment size differed significantly in the three groups of PCa, BPH and healthy controls. Both parameters are potential clinical biomarkers for PCa and can be used in both early diagnosis and follow-up. Using automated systems for high-throughput cfDNA quantification could improve the reproducibility of the method and facilitate the implementation of liquid biopsies in the clinical setting., (Copyright © 2019. Published by Elsevier B.V.)

Background: The treatments of horizontal semicircular canal benign paroxysmal positional vertigo (HSC-BPPV) have low remission rates ranging between 60% and 90%, connected to the difficulty in correctly identifying the affected side of HSC-BPPV. Objective: To propose and compare the efficacy of the latency test (LT) in identifying the affected ear in patients with HSC-BPPV. Materials and methods: Twenty-one subjects diagnosed with HSC-BPPV, as ascertained by head rolling test (HRT), were prospectively identified. Lateralization was assessed with pseudo-spontaneous nystagmus, lying-down nystagmus, bow and lean (BLT), HRT and LT tests. LT is a novel technique involving a 180° movement of the head and the analysis of the time required to reverse the nystagmus. Results: About 57% of patients were diagnosed with geotropic, and 43% with apogeotropic type HSC-BPPV. LT achieved a correct side diagnosis in 86%. Efficacy analysis of the tests compared to HRT revealed a substantial fair level of agreement for lying-down test ( κ  = 0.32, p  < .05), a slight level of agreement for BLT ( κ  = 0.19, p  < .05) and a substantial level of agreement for LT ( κ  = 0.071, p  < .001). Conclusions and significance: LT was proven to show a substantial level of agreement compared to HRT in identifying the affected ear in patients with HSC-BPPV in this pilot study.

Objective: To report the first application of ex vivo fluorescence confocal microscopy (FCM) - a novel optical technology that is capable of providing fast microscopic imaging of unfixed tissue specimens- in the urological field assessing its diagnostic accuracy for non neoplastic and cancerous prostate tissue (prostatic adenocarcinoma) compared to the 'gold standard' histopathological diagnoses., Patients and Methods: In all, 89 specimens from 13 patients with clinically localised prostate cancer were enrolled into the study. All patients underwent robot-assisted laparoscopic radical prostatectomy with fresh prostatic tissue biopsies taken at the end of each intervention using an 18-G biopsy punch. Specimens were randomly assigned to the three collaborating pathologists for evaluation. Intra- and inter-observer agreement was tested by the means of Cohen's κ. The diagnostic performance was evaluated on receiver operating characteristic curve analysis., Results: The overall diagnostic agreement between FCM and histopathological diagnoses was substantial with a 91% correct diagnosis (κ = 0.75) and an area under the curve of 0.884 (95% confidence interval 0.840-0.920), 83.33% sensitivity, and 93.53% specificity., Conclusion: FCM seems to be a promising tool for enhanced specimens' reporting performance, given its simple application and very rapid microscopic image generation (<5 min/specimen). This technique may potentially be used for intraoperative pathological specimens' analysis., (© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)

Purpose: Hormone receptors (HR) status in HER2 + breast cancer (BC) is a recognized stratification factor with relevant clinical implication. According to HR expression, HER2 + BC show different clinical characteristics, treatment sensitivity and prognosis. The interaction between HR and HER2 pathways remains incompletely understood., Methods: Thirty-four HER2 + BC were included: 18 tumors with HER2+/HR + and 16 with HER2+/HR-. The expression of 770 genes and 13 molecular pathways were evaluated using Nanostring PanCancer Pathway panel performed on FFPE BC biopsies., Results: Gene expression analysis identified 127 genes with significantly different expression between the two cohorts. 83% of these genes were overexpressed in HER2+/HR- cohort. Globally, 23% of them belonged to PI3K pathway (41 genes), 15% to Trascriptional regulation (26 genes) and 12% to MAPK (22 genes). Regarding pathway expression, PI3K, MAPK and NOTCH were significantly differently expressed between the two groups (p = 0.003, p = 0.0018 and p = 0.02, respectively), all of them were overexpressed in HER2+/HR- tumors., Conclusions: According to HR status, HER2 + tumors express different pathways profiles: the overexpression of PI3K, MAPK and NOTCH pathways in HER2+/HR- group could justify different survival outcomes and treatment sensitivity. The identification of tumor driver pathways may be a useful instrument for individualized pathway-directed therapies. Further clinical implications are warranted.

Cutaneous melanoma (CM) is one of the most prevalent skin cancers, which lacks both a prognostic marker and a specific and lasting treatment, due to the complexity of the disease and heterogeneity of patients. Reflectance confocal microscopy (RCM) in vivo analysis is a versatile approach offering immediate morphological information, enabling the identification of four primary cutaneous RCM CM types. Whether RCM CM types are associated with a specific protein and molecular genetic profiles at the tissue level remains unclear. The current pilot study was designed to identify potential correlations between RCM CM types and specific biological characteristics, combining immunohistochemistry (IHC) and molecular analyses. Eighty primary CMs evaluated at patient bedside with RCM (type 1 [19, 24%], type 2 [12, 15%], type 3 [7, 9%] and type 4 [42, 52%]) were retrospectively evaluated by IHC stains (CD271, CD20, CD31, cyclin D1), fluorescence in situ hybridization FISH for MYC gain and CDKN2A loss and molecular analysis for somatic mutations (BRAF, NRAS and KIT). RCM CM types correlated with markers of stemness property, density of intra-tumoral lymphocytic B infiltrate and cyclin D1 expression, while no significant association was found with blood vessel density nor molecular findings. RCM CM types show a different marker profile expression, suggestive of a progression and an increase in aggressiveness, according to RCM morphologies., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Atypical basal cell carcinoma (BCC), characterized by equivocal dermoscopic features typical of malignant melanoma (MM), can be difficult to diagnose. Reflectance confocal microscopy (RCM) enables in vivo imaging at nearly histological resolution., Objectives: To evaluate with RCM atypical melanocytic lesions identified in dermoscopy, according to common RCM criteria for the differential diagnosis of BCC, and to identify representative RCM parameters for superficial (sBCCs) and nonsuperficial (nsBCCs) basal cell carcinomas (BCCs)., Methods: A retrospective analysis of consecutive patients evaluated with RCM, selecting excised lesions classified at dermoscopy with ≥1 score from the re visited 7-point checklist, mimicking melanoma, registered between 2010 and 2016. Cluster analysis identified BCC subclassifications., Results: Of 178 atypical lesions, 34 lesions were diagnosed as BCCs with RCM. Lesions were confirmed BCCs with histopathology. Dermoscopic features included atypical network (55.9%) and regression structures (35.5%) associated with sBCCs, and an atypical vascular pattern (58.8%) and irregular blotches (58.8%) with nsBCCs. Hierarchical cluster analysis identified 2 clusters: cluster 1 (100% sBCCs) was characterized by the presence of cords connected to the epidermis (90%, p < 0.001), tumor islands located in the epidermis (100%, p < 0.001), smaller vascular diameter (100%, p < 0.001) and solar elastosis (90%, p = 0.017), and cluster 2 (nsBCCs 85%) was defined by the dermic location of tumor islands (87.5%, p < 0.001) with branch-like structures (70.8%, p = 0.007) and surrounding collagen (83.3%, p = 0.012), peripheral palisading (83.3%, p = 0.012) and coiled vascular morphology (79.2%, p < 0.001) with a larger vascular diameter (50%, p < 0.001)., Conclusions: RCM is able to diagnose BCCs mimicking melanoma at dermoscopy and seems able to identify sBCCs and nsBCCs., (© 2018 S. Karger AG, Basel.)

Background: Malignant melanoma is an aggressive skin cancer, which can lead to metastasis development. Vascularization enhancement is fundamental for tumor growth, worsening the prognosis. Dynamic optical coherence tomography (D-OCT) enables the in vivo evaluation of vascular patterns in skin lesions., Objective: In vivo evaluation of the melanoma vessel morphology by means of D-OCT and correlation with Breslow index., Methods: Retrospective analysis of histologically proven melanomas, evaluated by D-OCT at three different depths (150, 300 and 500 μm), was performed. Vessels were classified according to morphology (dots, blobs, coiled, line, curved, serpiginous), distribution (regular, irregular) and the presence/type of branches. The data were correlated with Breslow thickness., Results: A total of 127 melanomas were evaluated. Dotted vessels were recorded at all depths, and their irregular distribution was associated with lesions thicker than 1.0 mm (from 75% to 91%), compared with thin ones (42%) at 150 μm (P = 0.031), and from 33% to 57% vs 18% at 300 μm (P = 0.021). Serpiginous and branching vessels with bulges were predominantly seen in melanomas thicker than 2 mm at 150 μm (from 14% to 27%, P < 0.001) and 300 μm of depth (from 36% to 54%, P < 0.001)., Limitations: Background noise hampered vessel detection at 500 μm. No correlation with dermoscopy/histology., Conclusion: Vascular pattern evaluation at 150 and 300 μm provided data on tumor microvascular asset and its pattern of progression in accordance with Breslow thickness. Since vascular progression is theoretically linked with tumor aggressiveness, the study of vascular pattern related with melanoma metastatization capability is warranted., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Ex vivo fluorescence confocal microscopy (FCM) is an innovative imaging tool that can be used intraoperatively to obtain real-time images of untreated excised tissue with almost histologic resolution. As inflammatory diseases often share overlapping clinical features, histopathology evaluation is required for dubious cases, delaying definitive diagnoses, and therefore therapy. This study identifies key-features at ex vivo FCM for differential diagnoses of cutaneous inflammatory diseases, in particular, psoriasis, eczema, lichen planus and discoid lupus erythematosus. Retrospective ex vivo FCM and histological evaluations with relevant diagnoses were correlated with prospectively reported histopathologic diagnoses, to evaluate agreement and the level of expertise required for correct diagnoses. We demonstrated that ex vivo FCM enabled the distinction of the main inflammatory features in most cases, providing a substantial concordance to histopathologic diagnoses. Moreover, ex vivo FCM and histological evaluations reached a substantial agreement with histopathologic diagnoses both for all raters and for each operator. After a yet to be defined learning curve, these preliminary results suggest that dermatologists may be able to satisfactorily interpret ex vivo FCM images for correct real-time diagnoses. Despite some limitations mainly related to the equipment of FCM with a single objective lens, our study suggests that ex vivo FCM seems a promising tool in assisting diagnoses of cutaneous inflammatory lesions, with a level of accuracy quite close to that offered by histopathology. This is the first study to investigate ex vivo FCM application in cutaneous inflammatory lesions, and to evaluate the diagnostic capability of this technology., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Temporal bone CSF leak represents a rare condition that may be associated to some particular symptoms as hearing loss, otorrhea and tinnitus. In the opinion of many authors a surgical treatment is mandatory to avoid serious consequences as meningitis. Middle cranial fossa (MCF), transmastoid (TM) and combined approaches are all described to manage this condition. The objective of this paper was firstly to analyze the overall outcomes of this surgery. Our second aim was to make a comparison between different surgical modalities on the basis of their rate of success and complications., Methods: A search thorough Ovid MEDLINE was organized in January 2017 to enroll all eligible articles. A statistical analysis of the obtained data was performed., Results: Thirtythree studies comprising a total of 873 procedures were included. The overall rate of success resulted 95.6% (94.1–96.8). The rate of major complications analyzed for 818 procedures was 3.4% (2.3–4.8). Subgroups analysis showed a success rate of 97.1% (90.7–99.5) for TM approach. A success rate of 94.1% (89.1–97.3) was calculated for MCF approach. Combined procedure (TM + MCF) showed a success rate of 97.9% (92.9–99.7)., Conclusion: The results of our review showed as the surgical treatment for CSF leak of temporal bone origin represents a safe option with high rate of success. Moreover our statistical data suggested that no significant differences are present in terms of outcomes between the analyzed surgical approaches.