Cranial bone microarchitecture in a mouse model for syndromic craniosynostosis.

Crouzon syndrome is a congenital craniofacial disorder caused by mutations in the Fibroblast Growth Factor Receptor 2 (FGFR2). It is characterized by the premature fusion of cranial sutures, leading to a brachycephalic head shape, and midfacial hypoplasia. The aim of this study was to investigate the effect of the FGFR2 mutation on the microarchitecture of cranial bones at different stages of postnatal skull development, using the FGFR2C342Y mouse model. Apart from craniosynostosis, this model shows cranial bone abnormalities. High-resolution synchrotron microtomography images of the frontal and parietal bone were acquired for both FGFR2C342Y/+ (Crouzon, heterozygous mutant) and FGFR2+/+ (control, wild-type) mice at five ages (postnatal days 1, 3, 7, 14 and 21, n = 6 each). Morphometric measurements were determined for cortical bone porosity: osteocyte lacunae and canals. General linear model to assess the effect of age, anatomical location and genotype was carried out for each morphometric measurement. Histological analysis was performed to validate the findings. In both groups (Crouzon and wild-type), statistical difference in bone volume fraction, average canal volume, lacunar number density, lacunar volume density and canal volume density was found at most age points, with the frontal bone generally showing higher porosity and fewer lacunae. Frontal bone showed differences between the Crouzon and wild-type groups in terms of lacunar morphometry (average lacunar volume, lacunar number density and lacunar volume density) with larger, less dense lacunae around the postnatal age of P7-P14. Histological analysis of bone showed marked differences in frontal bone only. These findings provide a better understanding of the pathogenesis of Crouzon syndrome and will contribute to computational models that predict postoperative changes with the aim to improve surgical outcome.

Searching for a "Window of Opportunity" in the Treatment of Vulvar Lichen Sclerosus: Evidence for Therapeutic Benefits of an Early Corticosteroid Treatment.

INTRODUCTION: Vulvar lichen sclerosus (VLS) is characterized by progressive anatomical changes which become increasingly severe and irreversible. The objective of this study was to investigate if a "window of opportunity" exists in VLS, i.e., to assess if an early treatment may prevent disease progression and facilitate clearance of symptoms and/or signs. METHODS: This retrospective, cohort study included VLS patients treated for the first time with a topical corticosteroid, namely with mometasone furoate 0.1% ointment, for 12 weeks (2016-2021). Scoring of subjective symptoms (global subjective score, GSS, and dyspareunia) and clinical features (global objective score [GOS] and sclerosis-scarring-atrophy) was performed at baseline (T0) and at the control visit (T1). We assessed if the achievement of clearance in GSS, GOS, sclerosis-scarring-atrophy, or dyspareunia depended on the time elapsed between VLS onset and treatment initiation. RESULTS: Among the 168 patients (59.2 ± 13.2 years) included, the median time between VLS onset and first treatment was 14.0 months. At T1, 48.8% of patients achieved clearance of GSS, 28% of GOS and 11.9% of both GSS and GOS, 57.9% of dyspareunia, and 19.2% of sclerosis-scarring-atrophy. The logistic regression model showed that each 10-month increase in treatment initiation adversely affected the clearance of GSS while starting treatment within 6 months of disease onset was significantly associated with clearance of GOS and sclerosis-scarring-atrophy. CONCLUSION: Early treatment is crucial in determining a complete healing of VLS-related symptoms and signs, especially of tissue sclerosis-scarring-atrophy, which appear poorly responsive, or even unresponsive, after the earliest stages of the disease. Thus our findings provide evidence for a "window of opportunity" in VLS treatment.

Short-, mid- and long-term efficacy of dupilumab in moderate to severe atopic dermatitis: a real life multicenter Italian study on 2576 patients.

BACKGROUND: The efficacy and safety of dupilumab in atopic dermatitis (AD) have been defined in clinical trials but limited real-world evidence on long term treatment outcomes are currently available to inform clinical decisions. OBJECTIVES: to describe long-term effectiveness and safety of dupilumab up to 48 months in patients with moderate-to-severe AD. METHODS: a multicenter, retrospective, dynamic cohort study was conducted to assess long term effectiveness and safety of dupilumab in patients with moderate to severe AD in a real-world setting. Predictors of minimal disease activity (MDA) optimal treatment target criteria (defined as the simultaneous achievement of EASI90, itch NRS score ≤1, sleep NRS score ≤1 and DLQI ≤1) were investigated. RESULTS: 2576 patients were enrolled from June 2018 to July 2022. MDA optimal treatment target criteria were achieved by 506 (21.91%), 769 (40.63%), 628 (50.36%), 330 (55.37%) and 58 (54.72%) of those that reached 4, 12, 24, 36 and 48 months of follow-up, respectively. Logistic regression revealed a negative effect on MDA achievement for conjunctivitis and food allergy at all timepoints. Adverse events (AE) were mild and were observed in 373 (15.78%), 166 (7.02%), 83 (6.43%), 27 (4.50%) and 5 (4.55%) of those that reached 4, 12, 24, 36 and 48 months of follow-up. Conjunctivitis was the most frequently reported AE during the available follow-up. AE led to treatment discontinuation in <1% of patients during the evaluated time periods. CONCLUSION: High long-term effectiveness and safety of dupilumab were confirmed in this dynamic cohort of patients with moderate to severe AD, regardless of clinical phenotype and course at baseline. Further research will be needed to investigate the effect of Th2 comorbidities and disease duration on the response to dupilumab and other newer therapeutics for AD.

Surgical strategy in treatment of metopic synostosis in a single centre experience: technical note and quantitative analysis of the outcomes.

PURPOSE: Trigonocephaly is the most common craniosynostosis involving orbits. Although some degree of agreement has been reached regarding surgical timing and indications for treatment, there is no consensus regarding the ideal operative technique to guarantee an optimal morphological outcome. The purpose of this study is to describe both strategies and to compare morphological outcomes by means of morphological surface analysis obtained from three-dimensional (3D) stereophotogrammetry, with two different techniques. METHODS: We retrospectively investigated 43 patients with metopic synostosis surgically treated between 2004 and 2020. Two different techniques were applied, addressed as technique A and B. Ten patients undergone postoperative 3d stereophotogrammetry were enrolled, and cephalometric measurements were taken and compared to a cohort of unaffected patients matched by age and gender. RESULTS: Comparison of the groups demonstrated a hypercorrection of the metopic angle of the second technique, associated with a slightly lower correction of the interfrontoparietal diameter. The metopic angle showed to be significantly undercorrected with the first method. CONCLUSIONS: Alternated barrel staving technique appears to be a quick and satisfactory method in cranial remodelling for metopic synostosis. It guarantees an optimal aesthetic result in the first years after surgery.

Hand eczema in Italian patients referred for patch testing: A retrospective SIDAPA study (2016-2023).

BACKGROUND: Hand eczema (HE) is a common skin disease with a negative impact on patients' quality of life in occupational and non-occupational settings. Up-to-date, data on HE in Italian patients referred for patch testing are lacking. OBJECTIVES: To characterise the profile in terms of demographics, aetiology and patch test results of Italian patients affected by HE referred for patch testing. METHODS: A retrospective descriptive study on consecutive patients affected by HE who underwent patch testing from 2016 to 2023 in eight dermatology clinics was performed. HE patients were divided into two groups according to the exclusive (HE-only group) and not-exclusive (HE+ group) hand involvement, and compared to patients with eczema localised in body areas other than hands (NHE group). RESULTS: One thousand five hundred and ninety-seven patients were affected by HE (35.3% males; mean age 42.7 years), 60.2% belonging to the HE-only group and 39.8% to the HE+ group. Occupational dermatitis was diagnosed in 33.2% of HE-only patients, 25.0% of HE+ patients and 5.2% of NHE patients (p < 0.001). HE-only patients presented: Allergic Contact Dermatitis (ACD), Irritant Contact Dermatitis (ICD), atopic HE in 48.1%, 47.5% and 7.1%, respectively; hyperkeratotic palmar, acute recurrent vesicular and nummular clinical subtypes in 52.2%, 43.9% and 11.9%, respectively; relevant positive patch test reactions in 48.1% (nickel sulphate 18.9%, methylchloroisothiazolinone/methylisothiazolinone 10.6%, methylisothiazolinone 8.6%, p-phenylenediamine 6.0% and potassium dichromate 4.7%). CONCLUSIONS: HE patients, and particularly those with exclusive hand involvement, show a particular profile in terms of demographic and clinical characteristics, etiologies and relevant positive patch test reactions.

Topical Corticosteroid Phobia Among Women Affected With Vulvar Lichen Sclerosus: Results From a Cross-sectional Survey.

OBJECTIVE: Topical corticosteroid (TC) phobia (TCP) is common in subjects affected with chronic inflammatory skin diseases who need prolonged corticosteroid treatments. The aim of this study was to assess TCP in women affected with vulvar lichen sclerosus (VLS). MATERIALS AND METHODS: This observational, cross-sectional study included adult patients with VLS who either started or were undergoing a TC treatment at our vulva unit between May 2022 and May 2023. All patients completed the self-administered TOPICOP questionnaire, which is validated for measuring concerns, worries, and beliefs about TC use. The scores obtained were analyzed in relation to demographic, history, and clinical data. RESULTS: The majority of the 165 (92.1%, 66.5 ± 11.9 years) included patients who had previously undergone TC treatments, mostly for VLS; 81.8% of them had received information about TCs, mainly from dermatologists (86.7%). The median global TOPICOP score was 16.7% (interquartile range. 8.3-30.6), corresponding to a raw median value of 6.0 (interquartile range, 3.0-11.0). The median subscores for the 2 TOPICOP domains, namely, mistaken beliefs and worries about TCs, were equal to each other. At multivariate analysis, none of the collected variables showed a significant association with the degree of TCP. CONCLUSIONS: In our VLS patients, TCP resulted rather low, probably because of the small skin area being treated and the high percentage of women who had already used TCs and who had received information about them from a dermatologist. This latter point suggests that adequate counseling could be a strong basis for greater awareness and serenity in the long-term use of TCs.

A Longitudinal Multiinstitutional Study of Vulvar Lichen Sclerosus: From Childhood to Perimenopause.

OBJECTIVE: The main outcome of this study was the evaluation of clinical characteristics, comorbidities, and therapeutic approaches in patients with vulvar lichen sclerosus (VLS) aged from childhood to perimenopause. Secondly, it was intended to compare these characteristics according to the menarchal status. METHODS: Patients less than 45 years of age with a diagnosis of VLS from January 2002 to June 2022 in 10 referral centers were included in this retrospective longitudinal study. The univariate analysis compared the dependent variables according to menarchal status. RESULTS: One hundred eighty-six patients met the inclusion criteria. At diagnosis, between 25% and 40% of premenarchal patients reported signs related to subepithelial hemorrhage. A significantly greater presence of bleeding ( p < .005), easy bruising ( p = .028), fissures ( p = .008), petechiae/splinter hemorrhages ( p < .001), and bleeding/blistering or open sores ( p = .011) was observed in premenarchal patients with respect to the postmenarchal group. The perineum ( p = .013) and the perianal region ( p < .001) were significantly more involved in the premenarchal group. Topical calcineurin inhibitors were more used in the premenarchal population ( p = .004), whereas vitamin E oil and moisturizers were more used in the postmenarchal population ( p = .047). CONCLUSIONS: Vulvar lichen sclerosus is a chronic condition that can cause vulvar changes that result in severe morbidity and affects sexual function and quality of life, even before menopause. Vulvar lichen sclerosus continues to be misdiagnosed in this population. This may lead to an average delay from symptom onset to diagnosis. Evaluating clinical manifestations of VLS in premenarchal and postmenarchal age allowed us to find different clinical characteristics between the 2 periods suggestive of the diagnosis.

Lack of oral involvement in a large cohort of women with vulvar lichen sclerosus - a multicenter prospective study.

BACKGROUND AND OBJECTIVES: We assessed the prevalence of oral lichen sclerosus in a cohort of women affected with vulvar lichen sclerosus (VLS). PATIENTS AND METHODS: This prospective, observational study included adult female patients with a histologically proven VLS who attended the Vulva Clinics of three Dermatology Units from January 2020 to July 2023. During this period, all VLS patients were asked to be examined in their oral cavities in order to detect any possible sign of oral diseases, which were then biopsied. RESULTS: Three hundred women (mean age 64.5 ± 13.0 years) were included, of whom 21 (7%) had a concurrent extragenital LS. In six (2%) patients, white, non-removable lesions were found at oral inspection and biopsied. All cases were histologically lichen planus. No other clinically relevant oral lesions were found. The six women with histologically proven oral lichen planus had more frequent periodontal and autoimmune diseases than the other included subjects. CONCLUSIONS: Our findings confirm the absolute rarity of oral involvement in patients with VLS. They suggest that the oral mucosa, unlike the genitals, is a setting which weakly leads to development of LS, also in predisposed subjects.

In Vitro Assessment of the Neuro-Compatibility of Fe-20Mn as a Potential Bioresorbable Material for Craniofacial Surgery.

Background and Objectives: Spring-assisted surgery is a popular option for the treatment of non-syndromic craniosynostosis. The main drawback of this procedure is the need for a second surgery for spring removal, which could be avoided if a distractor material could be metabolised over time. Iron-Manganese alloys (FeMn) have a good trade-off between degradation rate and strength; however, their biocompatibility is still debated. Materials and Methods: In this study, the neuro-compatibility of Fe-20Mn (wt.%) was assessed using standard assays. PC-12 cells were exposed to Fe-20Mn (wt.%) and stainless steel via indirect contact. To examine the cytotoxicity, a Cell Tox Green assay was carried out after 1, 2, and 3 days of incubation. Following differentiation, a neurite morphological examination after 1 and 7 days of incubation time was carried out. The degradation response in modified Hank's solution at 1, 3, and 7 days was investigated, too. Results: The cytotoxicity assay showed a higher toxicity of Fe-20Mn than stainless steel at earlier time points; however, at the latest time point, no differences were found. Neurite morphology was similar for cells exposed to Fe-20Mn and stainless steel. Conclusions: In conclusion, the Fe-20Mn alloy shows promising neuro-compatibility. Future studies will focus on in vivo studies to confirm the cellular response to Fe-20Mn.

Suffering and Quality of Life Impairment in Patients with Eczematous Diseases: Results from an Observational Study Assessing the Relevance of the Involvement of Two Sensitive Body Sites, Namely, the Face and Hands.

BACKGROUND: Quality of life (QoL) impairment by eczematous diseases, with reference to body site involvement, has not been deeply addressed. OBJECTIVES: The aims of this study were to assess: (1) the impact on QoL of eczematous diseases affecting the face or hands; (2) any differences in QoL impairment in the case of face versus hand involvement; (3) sensitivity of Pictorial Representation of Illness and Self Measure (PRISM) and Dermatology Life Quality Index (DLQI) in measuring disease-related burden. METHODS: Adults with eczematous diseases of the face or hands were involved. Patients were patch tested and underwent DLQI and PRISM. RESULTS: 143 patients were included, 43.36% with face and 56.64% with hands involvement. PRISM and DLQI scores showed a moderate to strong inverse correlation, but PRISM revealed a higher sensitivity in capturing patients' suffering than DLQI, especially in the case of face involvement. Itching was the sole parameter significantly associated with both PRISM and DLQI scores. CONCLUSIONS: PRISM appeared to be more accurate in detecting the burden of eczematous diseases involving the face, probably due to the interception of the emotional impact, while DLQI, focusing on patient functioning, was more affected by hand involvement. Site involvement could be a criterion for selecting the best QoL assessment tool.

Does Clearance of Vulvar Lichen Sclerosus after a Corticosteroid Treatment Correspond to a Decrease in Disease-Related Burden? Results from a Cohort Study Using Pictorial Representation of Illness and Self-Measure and the Dermatology Life Quality Index.

BACKGROUND AND OBJECTIVES: Complete clearance of vulvar lichen sclerosus (VLS) occurs in a minority of treated patients. Disease persistence may impact patient well-being. The main objective of this study was to assess if achieving a complete clearance with a corticosteroid treatment leads to a benefit in terms of patient suffering and quality-of-life (QoL) impairment. METHODS: We performed an observational study on a cohort of VLS women, who applied mometasone furoate 0.1% ointment for 12 weeks. At treatment completion (T1), we compared the patients who achieved clearance in symptoms (Global Subjective Score [GSS] = 0) or in objective features (Global Objective Score [GOS] = 0) or in both with those who achieved a lower degree of improvement, on the basis of Pictorial Representation of Illness and Self-Measure (PRISM) and Dermatology Life Quality Index (DLQI) scores. RESULTS: In the whole sample (n = 101), GSS, GOS, PRISM, and DLQI scores significantly improved after treatment from baseline; 34 patients (35.8%) achieved GSS = 0, 26 (25.7%) achieved GOS = 0, and 11 (11.5%) clearance of GSS and GOS. PRISM scores at T1 were significantly higher in patients who achieved clearance of symptoms when compared with those who did not, including patients achieving 50-99% GSS improvement from baseline. DLQI scores were lower in patients who achieved clearance of symptoms, signs, or both when compared with the others. CONCLUSIONS: VLS clearance corresponded to a significant improvement in the QoL of VLS patients, also in comparison with those who achieved a substantial but incomplete decrease of symptom and sign scores, and should become an ideal therapeutic goal.

Unravelling the pathogenesis of foramen magnum stenosis in patients with severe achondroplasia: a CT-based comparison with age-matched controls and FGFR3 craniosynostosis syndromes.

OBJECTIVE: Foramen magnum(FM) stenosis can be responsible for acute and chronic damage to the cervicomedullary junction in children with achondroplasia. The bony anatomy and patterns of suture fusion of the FM in this context are incompletely understood, yet becoming increasingly important in the light of novel medical therapies for achondroplasia. The objective of this study was to describe and quantify bony anatomy and fusion patterns of FM stenosis in patients with achondroplasia using CT scans, comparing them to age-matched controls and other FGFR3 craniosynostosis patients. METHODS: Patients with achondroplasia and severe FM stenosis, classified as achondroplasia foramen magnum score(AFMS) grades 3 and 4, were identified from a departmental operative database. All had pre-operative CT scans of the craniocervical junction. Measurements obtained comprised sagittal diameter (SD), transverse diameter (TD), foramen magnum area, and opisthion thickness. Anterior and posterior interoccipital synchondroses (AIOS and PIOS) were graded by the extent of fusion. These measurements were then compared with CT scans from 3 age-matched groups: the normal control group, children with Muenke syndrome, and children with Crouzon syndrome with acanthosis nigricans (CSAN). RESULTS: CT scans were reviewed in 23 cases of patients with achondroplasia, 23 normal controls, 20 Muenke, and 15 CSAN. Children with achondroplasia had significantly smaller sagittal diameter (mean 16.2 ± 2.4 mm) compared to other groups (control 31.7 ± 2.4 mm, p < 0.0001; Muenke 31.7 ± 3.5 mm, p < 0.0001; and CSAN 23.1 ± 3.4 mm, p < 0.0001) and transverse diameters (mean 14.3 ± 1.8 mm) compared with other groups (control 26.5 ± 3.2 mm, p < 0.0001; Muenke 24.1 ± 2.6 mm, p < 0.0001; CSAN 19.1 ± 2.6 mm, p < 0.0001). This translated into a surface area which was 3.4 times smaller in the achondroplasia group compared with the control group. The median grade of the AIOS fusion achondroplasia group was 3.0 (IQR 3.0-5.0), which was significantly higher compared with the control group (1.0, IQR 1.0-1.0, p < 0.0001), Muenke group (1.0, IQR 1.0-1.0, p < 0.0001), and CSAN (2.0, IQR 1.0-2.0, p < 0.0002). Median PIOS fusion grade was also highest in the achondroplasia group (5.0, IQR 4.0-5.0) compared with control (1.0, IQR 1.0-1.0, p < 0.0001), Muenke (2.5, IQR 1.3-3.0, p < 0.0001), and CSAN (4.0, IQR 4.0-4.0, p = 0.2). Distinct bony opisthion spurs projecting into the foramen magnum were seen in achondroplasia patients but not others, resulting in characteristic crescent and cloverleaf shapes. CONCLUSION: Patients with AFMS stages 3 and 4 have significantly reduced FM diameters, with surface area 3.4 times smaller than age-matched controls. This is associated with premature fusion of the AIOS and PIOS in comparison with controls and other FGFR3-related conditions. The presence of thickened opisthion bony spurs contributes to stenosis in achondroplasia. Understanding and quantifying bony changes at the FM of patients with achondroplasia will be important in the future quantitative evaluation of emerging medical therapies.

3-Dimensional Morphometric Outcomes After Endoscopic Strip Craniectomy for Unicoronal Synostosis.

BACKGROUND: Endoscopic strip craniectomy with postoperative helmeting (ESCH) for unicoronal synostosis has shown to be a less morbid procedure when compared with fronto-orbital remodeling (FOR). We aim in this pilot study to report objective methods and quantitative morphologic outcomes of endoscopically treated unicoronal synostosis using 3-dimensional surface scans. METHODS: Our electronic records were reviewed for ophthalmological, neurodevelopmental outcomes, and helmet-related complications. For morphologic outcomes, the following parameters were used: Cranial Index, Cranial Vault Asymmetry Index, Anterior Symmetry Ratio (ASR), and Root Mean Square between the normal and synostotic sides of the head. Three-dimensional stereophotogrammetry scans were evaluated at 3 time points preoperative, 6 months post-op, and at the end of the treatment, which was compared with age-matched scans of normal controls and FOR patients. Nonparametric tests were used for statistical analysis. RESULTS: None of the ESCH cases developed strabismus, major neurodevelopmental delay, or helmet complications. All morphologic parameters improved significantly at 6 months post-op except for the Cranial Vault Asymmetry Index. The ASR was the only parameter to change significantly between 6 months post-op and final scans. At end of helmet treatment, ASR and Root Mean Square differed significantly between the ESCH and both FOR and control groups. CONCLUSIONS: Endoscopic strip craniectomy with postoperative helmeting for single unicoronal synostosis had excellent clinical outcomes. Most of the improvement in head morphology occurred in the first 6 months of treatment. Despite the normalization of the overall head shape, there was residual asymmetry in the frontal and temporal regions of the head.

Does the Mutation Type Affect the Response to Cranial Vault Expansion in Children With Apert Syndrome?

LEVEL OF EVIDENCE: III.

The Accuracy of Computer-Assisted Surgical Planning in Predicting Soft Tissue Responses After Le Fort I Osteotomy: Retrospective Analysis.

PURPOSE: Mismatch between preoperative planning and surgical outcome in maxillofacial surgery relate to on-table replication of presurgical planning and predictive algorithm inaccuracy: software error was hereby decoupled from planning inaccuracy to assess a commercial software. The hypothesis was that soft tissue prediction error would be minimized if the surgical procedure was replicated precisely as planned and is independent of the extent of bone repositioning. MATERIALS AND METHODS: Cone-beam computed tomography scans of 16 Le Fort I osteotomy patients were collected at Boston Children's Hospital. Preoperative and postoperative models of bone and soft tissue were constructed and the maxilla repositioning was replicated. Each model was subdivided into 6 regions: mouth, nose, eyes, and cheeks. Soft tissue prediction (performed using Proplan CMF-Materialise) for each patient was compared with the relative postoperative reconstruction and error was determined. P <0.05 was considered significant. RESULTS: Le Fort I segment repositioning was replicated within 0.70±0.18 mm. The highest prediction error was found in the mouth (1.49±0.77 mm) followed by the cheeks (0.98±0.34 mm), nose (0.86±0.23 mm), and eyes (0.76±0.32). Prediction error on cheeks correlated significantly with mouth ( r =0.63, P < 0.01) and nose ( r =0.67, P < 0.01). Mouth prediction error correlated with total advancement ( r =0.52, P =0.04). CONCLUSIONS: ProPlan CMF is a useful outcome prediction tool; however, accuracy decreases with the extent of maxillary advancement even when errors in surgical replication are minimized.

Incidence of Vulvar Lichen Sclerosus and of Cancer Among Vulvar Lichen Sclerosus Patients: Does Socioeconomic Status Have a Role?

OBJECTIVE: Socioeconomic status (SES) impacts on the incidence of many inflammatory diseases and cancers, but there is no evidence on its implication in vulvar lichen sclerosus (VLS). The authors aimed to assess possible associations between SES and both occurrence of VLS and cancer occurrence among VLS patients. MATERIALS AND METHODS: A retrospective cohort of women resident in the province of Ferrara, Italy, affected with VLS diagnosed between 2001 and 2020, was investigated for assessing any association of SES with VLS and cancer incidence. The SES was expressed through an ecological-based deprivation index identifying 5 subgroups. RESULT: Four-hundred women were diagnosed with VLS during the study period, with double the number of cases in the second decade (2011-2020) compared with the first (2001-2010). More VLS patients belonged to the high rather than the low SES groups (p = .032). From VLS diagnosis to 2018 (1,958.4 total person*years at risk), 22 patients received their first diagnosis of cancer, mainly the skin, breast, and vulva. No significant differences in cancer incidence were found between high/medium-high and low/medium-low SES subjects. CONCLUSIONS: The fact that more VLS patients belonged to the highest socioeconomic classes may be due to a more frequent diagnosis in those with greater health seeking behavior and resources. An involvement of SES-related factors in VLS pathophysiological background can also be taken into consideration. Both the lack of marked social and economic differences in the study area and the availability of free visits and screening may account for the lack of association between SES and cancer development.

Evaluation of the Synovial Effects of Biological and Targeted Synthetic DMARDs in Patients with Psoriatic Arthritis: A Systematic Literature Review and Meta-Analysis.

The aims of this systematic literature review (SLR) were to identify the effects of approved biological and targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) on synovial membrane of psoriatic arthritis (PsA) patients, and to determine the existence of histological/molecular biomarkers of response to therapy. A search was conducted on MEDLINE, Embase, Scopus, and Cochrane Library (PROSPERO:CRD42022304986) to retrieve data on longitudinal change of biomarkers in paired synovial biopsies and in vitro studies. A meta-analysis was conducted by adopting the standardized mean difference (SMD) as a measure of the effect. Twenty-two studies were included (19 longitudinal, 3 in vitro). In longitudinal studies, TNF inhibitors were the most used drugs, while, for in vitro studies, JAK inhibitors or adalimumab/secukinumab were assessed. The main technique used was immunohistochemistry (longitudinal studies). The meta-analysis showed a significant reduction in both CD3+ lymphocytes (SMD -0.85 [95% CI -1.23; -0.47]) and CD68+ macrophages (sublining, sl) (SMD -0.74 [-1.16; -0.32]) in synovial biopsies from patients treated for 4-12 weeks with bDMARDs. Reduction in CD3+ mostly correlated with clinical response. Despite heterogeneity among the biomarkers evaluated, the reduction in CD3+/CD68+sl cells during the first 3 months of treatment with TNF inhibitors represents the most consistent variation reported in the literature.

The Esthetic Perception of Morphological Severity in Scaphocephalic Patients is Correlated With Specific Head Geometrical Features.

OBJECTIVE: To investigate the relationship between perception of craniofacial deformity, geometric head features, and 3D head shape analyzed by statistical shape modeling (SSM). PATIENTS: A total of 18 unoperated patients with scaphocephaly (age = 5.2 ± 1.1m)-6 were followed-up after spring-assisted cranioplasty (SAC) (age = 9.6 ± 1.5m)-and 6 controls (age = 6.7 ± 2.5m). MAIN OUTCOME MEASURES: 3D head shapes were retrieved from 3D scans or computed tomography (CTs). Various geometrical features were measured: anterior and posterior prominence, take-off angle, average anterior and posterior lateral and horizontal curvatures, cranial index (CI) (cranial width over length), and turricephaly index (TI) (cranial height over length). SSM and principal component analysis (PCA) described shape variability. All models were 3D printed; the perception of deformity was blindly scored by 9 surgeons and 1 radiologist in terms of frontal bossing (FB), occipital bulleting (OB), biparietal narrowing (BN), low posterior vertex (LPV), and overall head shape (OHS). RESULTS: A moderate correlation was found between FB and anterior prominence (r = 0.56, P < .01) and take-off angle (r = - 0.57, P < .01). OB correlated with average posterior lateral curvature (r = 0.43, P < 0.01) similarly to BPN (r = 0.55, P < .01) and LPV (r = 0.43, P < .01). OHS showed strong correlation with CI (r = - 0.68, P < .01) and TI (r = 0.63, P< .01). SSM Mode 1 correlated with OHS (r = 0.66, p < .01) while Mode 3 correlated with FB (r = - 0.58, P < .01). CONCLUSIONS: Esthetic cranial appearance in craniofacial patients is correlated to specific geometric parameters and could be estimated using automated methods such as SSM.

Results from an extended study on the reliability of a questionnaire for the diagnosis of sensitive skin: Confirmations and improvements.

OBJECTIVE: A recently proposed self-assessment questionnaire aimed at diagnosing sensitive skin provided promising results in a relatively small population. The main objectives were: (i) to assess the reliability of the aforementioned questionnaire in a larger population and verify the cut-off score previously found to predict skin sensitivity (defined as positivity to LAST, lactic acid stinging test) and (ii) to define a formula that yields the probability of a positive LAST result. METHODS: Adult volunteers were included in this observational, cross-sectional, extended study. Both LAST-positive subjects, who were considered as having sensitive skin ('patients') and negative ones ('controls') completed the questionnaire, which concerned sensitivity to possible triggers of unpleasant skin sensations in real life. A cumulative score (questionnaire-based skin sensitivity score, 0-10) was calculated from the sum of all items. RESULTS: Three hundred and sixty-four subjects were enrolled, 214 patients and 150 controls. The mean questionnaire-based skin sensitivity score was significantly higher among patients than controls. Using two different methods, cut-off values of 4 and 5 were defined for the identification of LAST-positive subjects, with 76.6% and 72.8% accuracy, respectively. Scores below 4 or above 5 showed a high (80% or better) negative or positive predictive value, respectively. The coefficients found that in multivariate analysis for each questionnaire item, gender and age allowed us to calculate the probability of LAST positivity with higher precision taking into account the 'relative weight' of each factor. CONCLUSION: With small variations in the results, the self-assessment questionnaire confirmed its reliability for diagnosing sensitive skin in clinical practice.

INTRODUCTION: Un questionnaire d'auto-évaluation récemment proposé visant à diagnostiquer la peau sensible a fourni des résultats prometteurs dans une population relativement petite. Les principaux objectifs étaient: (i) d'évaluer la fiabilité du questionnaire susmentionné dans une population plus large et de vérifier la valeur du cut-off précédemment trouvé pour prédire la sensibilité cutanée (définie comme la positivité au LAST, de l'anglais « test de piqûre d'acide lactique ¼), et (ii) de définir une formule qui donne la probabilité d'un résultat LAST positif. MÉTHODES: Des volontaires adultes ont été inclus dans cette étude observationnelle, transversale et étendue. Les sujets LAST-positifs, qui étaient considérés comme ayant la peau sensible ('patients'), et les sujets négatifs ('témoins') ont rempli le questionnaire, qui concernait la sensibilité aux possibles déclencheurs de sensations cutanées désagréables dans la vie réelle. Un score cumulatif (score de sensibilité cutanée basé sur un questionnaire, 0-10) a été calculé à partir de la somme de tous les éléments. RÉSULTATS: Trois cent soixante-quatre sujets ont été recrutés, 214 patients et 150 témoins. Le résultat moyen de sensibilité cutanée basé sur le questionnaire était significativement plus élevé chez les patients que chez les témoins. En utilisant deux méthodes différentes, des valeurs seuils de 4 et 5 ont été définies pour l'identification des sujets LAST-positifs, avec une précision de 76,6% et 72,8%, respectivement. Les scores inférieurs à 4 ou supérieurs à 5 ont montré une valeur prédictive négative ou positive élevée (80% ou plus), respectivement. Les coefficients trouvés en différentes analyses pour chaque élément du questionnaire, sexe et âge nous ont permis de calculer la probabilité de positivité LAST avec une plus grande précision en tenant compte du « poids relatif ¼ de chaque facteur. CONCLUSIONS: Avec de faibles variations dans les résultats, le questionnaire d'auto-évaluation a confirmé sa fiabilité pour le diagnostic des peaux sensibles dans la pratique clinique.

Assessment of the perceived burden associated with Malignant Melanoma with Pictorial Representation of Illness and Self Measure (PRISM) and Melanoma Concerns Questionnaire (MCQ-28).

PURPOSE: The impact of malignant melanoma (MM) on patients' psychophysical well-being has been poorly addressed. We aimed to assess the perceived burden in patients with a diagnosis of MM, using two different tools, one generic and one specific for MM, such as Pictorial Representation of Illness and Self Measure (PRISM) and Melanoma Concerns Questionnaire (MCQ-28), respectively. The correlation between PRISM and MCQ-28 subscales and the relevance of disease and patient-related variables were also investigated. METHODS: This single-centre, cross-sectional study included all adult consecutive MM patients who attended our Dermatology Unit from December 2020 to June 2021. Demographics and disease-related data were recorded. PRISM and MCQ-28 were administered. RESULTS: One hundred and seventy-one patients were included (mean age: 59.5 ±14.9 years.; 48.0% males). Median time from MM diagnosis to inclusion was 36 months. Nearly 80% of the patients had in situ or stage I MM. Overall, 22.2% of the patients reported a PRISM score <100mm and similar percentages provided scores indicating impaired quality of life, as assessed with MCQ-28 subscales. A weak, albeit significant, correlation was found between PRISM scores and ACP, CON and SOC2 subscales. The most relevant association found was that between lower PRISM scores and higher-stage MM. CONCLUSIONS: In the study population, mostly affected with superficial MM, their perception of the burden associated with MM did not appear either particularly dramatic or disabling. PRISM seems a reliable system for capturing and quantifying the domains correlated with the emotive dimension of MM, especially MM-related concerns and willingness to face life.