The association of vasomotor symptoms with fracture risk and bone mineral density in postmenopausal women: a systematic review and meta-analysis of observational studies.

BACKGROUND/AIMS: Vasomotor symptoms (VMS) adversely affect postmenopausal quality of life. However, their association with bone health has not been elucidated. This study aimed to systematically review and meta-analyze the evidence regarding the association of VMS with fracture risk and bone mineral density (BMD) in peri- and postmenopausal women. METHODS: A literature search was conducted in PubMed, Scopus and Cochrane databases until 31 August 2023. Fracture, low BMD (osteoporosis/osteopenia) and mean change in lumbar spine (LS) and femoral neck (FN) BMD were assessed. The results are presented as odds ratio (OR) and mean difference (MD), respectively, with a 95% confidence interval (95% CI). The I2 index quantified heterogeneity. RESULTS: Twenty studies were included in the qualitative and 12 in the quantitative analysis (n=49,659). No difference in fractures between women with and without VMS was found (n=5, OR 1.04, 95% CI 0.93-1.16, I2 16%). However, VMS were associated with low BMD (n=5, OR 1.54, 95% CI 1.42-1.67, I2 0%). This difference was evident for LS (MD -0.019 g/cm2, 95% CI -0.03 to -0.008, I2 85.2%), but not for FN BMD (MD -0.010 g/cm2, 95% CI -0.021 to 0.001, I2 78.2%). These results were independent of VMS severity, age and study design. When the analysis was confined to studies that excluded menopausal hormone therapy use, the association with BMD remained significant. CONCLUSIONS: The presence of VMS is associated with low BMD in postmenopausal women, although it does not seem to increase fracture risk.

The Natural Evolution of Nevi with Peripheral Globules.

BACKGROUND: Peripheral globules (PG) in melanocytic lesions represent a concerning dermoscopic feature since they might be present in growing nevi and melanomas. Their natural evolution has not been fully elucidated, and an age-based management approach has been recommended. OBJECTIVES: The aim of this study was to calculate the growth rate of lesions with PG and investigate possible association with age, sex, location, and the global dermoscopic pattern. METHODS: We retrospectively selected the lesions of interest from a cohort of Caucasian patients who underwent sequential digital dermoscopy monitoring. Lesions with PG distributed at 75% or more of their circumference with available follow-up images or histopathologic report were included. The surface area was automatically calculated with the help of an incorporated tool used in the acquisition of the images. The images were also evaluated by independent investigators for the presence of pre-defined criteria. Growth-curve models were used to assess the growth rate. The outcome variable was the area of nevi in mm2, and scatterplots with Lowess curves were used to present the mean change of nevi during follow-up. RESULTS: A total of 208 lesions from 98 patients with a median age of 36 years (range 15-75) were included. The median follow-up time was 18 months (range 4-48). The mean growth rate for all nevi was 0.16 mm2/month (95% CI, 0.14-0.18, p < 0.001), ranging from -0.29 to 0.61 mm2/month. The growth rate was higher in nevi with a homogeneous dermoscopic pattern (p < 0.001). The number of peripheral globules during follow-up varied from increasing to complete disappearance. None of the lesions developed any melanoma-specific structure at follow-up. CONCLUSION: Nevi with PG grew at a mean rate of 0.16 mm2/month, and the growth rate was independent of age, gender, or anatomic location. Nevi with homogeneous pattern demonstrated the highest growth rate in our cohort. None of the monitored nevi with PG developed melanoma-specific criteria at follow-up.

Real-Life Data on the Management of Incompletely Excised Basal Cell Carcinoma.

BACKGROUND: The histopathologic presence of basal cell carcinoma (BCC) cells at one or more margins of the specimen after surgical excision is considered suggestive of incomplete tumor clearance. The management of incompletely excised BCC might vary in different clinical scenarios from re-excision to application of other treatments or even watchful waiting. OBJECTIVE: The aims of the study were to report the real-life management of incompletely excised BCC in a tertiary referral center and compare the recurrence rates according to the selected management modality. METHODS: A retrospective study was conducted at a tertiary Dermatology Center in Northern Greece. Our electronic database was scanned over a 5-year period to retrieve all BCCs with available histopathologic assay reporting at least one involved margin (lateral or deep). The included patients were divided into 3 groups according to the selected management after incomplete excision: group 1 included those who underwent immediate re-excision (n = 26), group 2 those who were followed up without any additional therapy (n = 40), and group 3 those who were treated with adjuvant/complementary non-surgical treatment (n = 18). Finally, we recorded the presence or absence of residual tumor in the new histopathologic report of those tumors that were selected to be re-excised (group 1). The primary outcome was the appearance of clinical tumor recurrence. RESULTS: Of 1,689 BCCs recorded in our database, 84 met the inclusion criteria and were included in the analysis. Re-excision had been selected in 26 of 84 patients (group 1), watchful waiting in 40 (group 2), and non-surgical treatments in 18 (group 3). The histopathologic reports of the 26 tumors of group 1 that were re-excised revealed residual tumor in 14 (53.8%) cases. Overall, a clinical recurrence occurred in 14 of 84 patients (16.7%) after a mean follow-up of 17 months. The median time to recurrence was 14 months. Of 40 patients without any treatment, recurrence developed in 10 (25%), while only 2 of 18 patients treated with non-surgical treatments recurred (11.1%). CONCLUSIONS: Our study suggests that positive histopathologic margins after BCC excision result in a clinical recurrence only in a proportion of patients. This percentage is higher when no further treatment is applied and lower when the area is re-excised or treated with imiquimod alone or combined with cryotherapy.

A retrospective multicentric cohort study of checkpoint inhibitors-induced pruritus with focus on management.

BACKGROUND: Limited data on immune checkpoint inhibitor (ICI)-induced pruritus per se and efficacy of different therapeutic modalities in its management exist. OBJECTIVE: To study the quantitative and qualitative characteristics of ICI-induced pruritus per se and to assess the efficacy of the therapeutic modalities usually applied. METHODS: We retrospectively reviewed the records of 91 patients who were under treatment with ICIs for any kind of neoplasia and developed pruritus during treatment. RESULTS: Twenty out of 91 individuals (22.0%) with ICI-induced pruritus had pruritus as the only symptom, while 71/91 (78.0%) presented with pruritus coexisting with an additional cutaneous toxicity. Pruritus was treated with antihistamines (18/20, 90.0%) and/or topical regimens, as first-line choice. In resistant cases, as a second therapeutic intervention, narrow-band UVB (NBUVB), oral steroids and GABA analogs were added (70.0%). Statistical analysis revealed a significant difference in mean pruritus Numerical Rating Scale (NRS) scores between baseline and sequential visits. Moreover, subgroup analysis revealed a significant reduction in mean NRS scores in those treated with phototherapy. LIMITATIONS: Retrospective design, low number of patients and survivorship bias. CONCLUSION: Pruritus per se was present in a substantial portion of our cohort (22.0%). Our study confirms the efficacy of current treatment strategies and suggests NBUVB as a potential steroid-sparing therapeutic alternative.

Dermatoscopic shiny white structures in benign cutaneous tumours.

The dermatoscopic characteristics of shiny white structures (SWS) in malignant skin tumours are well described, but data on benign skin neoplasms are scarce. To evaluate dermatoscopic features of SWS in common benign tumours, we reviewed our database for histopathologically confirmed cases. The dermatoscopic images were evaluated for the presence of any type of SWS. Those images with SWS were further analyzed for their quantity, distribution and shape. Of 2420 evaluated benign tumours, 357 (14.8%) displayed SWS. The highest frequencies were observed in pyogenic granuloma (62/100, 62.0%), angioma (63/113, 55.8%) and adnexal tumours (42/84, 50.0%). The lowest frequency was found in common nevi (16/1032, 1.6%) and solar lentigo (0%). The presence of SWS was not associated with sex or anatomic location. SWS were usually diffuse and multiple. SWS may be present in a broad spectrum of benign tumours. Therefore, they should not be considered as de-facto indicators of malignancy.

The first positive evidence that training improves triage decisions in Greece: evidence from emergency nurses at an Academic Tertiary Care Emergency Department.

BACKGROUND: Triage refers to the process of patient prioritisation in the emergency department (ED). This is based on the severity of the patient's illness and is performed by emergency nurses (ENs). This has a pivotal role in ensuring patient safety and in ensuring that the ED operates smoothly - so continuous and accurate training are essential. As Emergency Nursing has been formally established in Greece since 2019, it is of the uppermost importance that all Greek ENs should be trained in the use of a standardised triage system. The present study aimed to evaluate the effect of triage training of ENs in the use of the Swiss Triage System (STS) after an intervention of one week. METHODS: The effect of triage training was studied experimentally by comparing performance before and one week after training. A sample of thirty-six ENs from the University Department of Emergency Medicine at AHEPA University Hospital took part. The role of training in triage by the STS was assessed by completing the same self-administered questionnaire before and after a 45-minute e-learning program (presentation video of STS but with simulation scenarios) which was available during the period of a week. The post-training test was taken 2 weeks later, after the training process. RESULTS: The most promising finding was that there was a significant improvement in the number of correct answers after the training in triage (p<0.001). A significant improvement was also detected (p<0.001) in the questions that tested vigilance in providing safe health services by ENs, whereas there was no significant association between the number of correct answers and years of emergency experience or level of education, - either before or after the intervention. CONCLUSIONS: Triage training seems to successfully improve effective and efficient triage. To the best of our knowledge, this is the first study that has demonstrated that triage training has a significant positive impact on triage performance by ENs in Greece. It is planned to support these findings by real time studies in an ED.

Dermoscopic Clues of Histopathologically Aggressive Basal Cell Carcinoma Subtypes.

Background: The group of histopathologically aggressive BCC subtypes includes morpheaform, micronodular, infiltrative and metatypical BCC. Since these tumors are at increased risk of recurring, micrographically controlled surgery is considered the best therapeutic option. Although dermoscopy significantly improves the clinical recognition of BCC, scarce evidence exists on their dermoscopic criteria. Aim: To investigate the dermoscopic characteristics of histopathologically aggressive BCC subtypes. Materials and Methods: Dermoscopic images of morpheaform, micronodular, infiltrative and metatypical BCC were analyzed for the presence of predefined variables. Descriptive and analytical statistics were performed. Results: Most histopathologically aggressive BCCs were located on the head and neck. Infiltrative was the most common subtype. All subtypes, except micronodular BCC, rarely displayed dermoscopic pigmentation. The most frequent dermoscopic features of infiltrative BCC were arborizing vessels (67.1%), shiny white structures (48.6%) and ulceration (52.9%). The features prevailing in morpheaform BCC were arborizing vessels (68.4%), ulceration (n = 12, 63.2%) and white porcelain areas (47.4%). Micronodular BCC was typified by milky red structureless areas (53.8%), arborizing vessels (53.8%), short fine telangiectasias (50%), ulceration (46.2%) and blue structures (57.7%). The most common findings in metatypical BCC were arborizing vessels (77.8%), shiny white structures (66.7%), ulceration (62.9%) and keratin mass (29.6%). Limitations: Study population of only white skin and relatively small sample size in some groups. Conclusions: Our study provided data on the clinical, dermoscopic and epidemiological characteristics of histopathologically aggressive BCCs.

Clinical associations and classification of immune checkpoint inhibitor-induced cutaneous toxicities: a multicentre study from the European Academy of Dermatology and Venereology Task Force of Dermatology for Cancer Patients.

BACKGROUND: Cutaneous immune-related adverse events (irAEs) represent the most frequent toxicities induced by immune checkpoint inhibitors (ICIs). OBJECTIVES: To investigate clinical associations of cutaneous toxicities induced by different ICI therapies. METHODS: This was a multicentre retrospective international cohort study of patients with cancer who developed cutaneous irAEs under ICI therapy. Analysis was performed of the rates and basic characteristics of all cutaneous toxicities, and identification of any associations was performed using univariate and multivariate models. RESULTS: In total, 762 patients were included, who developed 993 cutaneous toxicities. Forty different types of skin toxicities were identified. Psoriasis (175 patients, 23·0%) and pruritus (171 patients, 22·4%) were the most common toxicities, followed by macular rash (161 patients, 21·1%) and eczematous-type reactions (150 patients, 19·7%). Multivariate analysis showed that among patients with macular rash, vitiligo or multiple toxicities, patients received ICIs more frequently for melanoma than for NSCLC. Moreover, anti-CTLA4 was less frequent than anti-programmed death 1 treatment in patients with macular rash [odds ratio (OR) 0·11, 95% confidence interval (CI) 0·01-0·76] and vitiligo (OR 0·07, 95% CI 0·006-0·78). A significant association was also seen in patients treated with a combination of ICI and chemotherapy vs. ICI monotherapy. They less frequently developed psoriasis (OR 0·08, 95% CI 0·02-0·31), lichenoid reactions (OR 0·15, 95% CI 0·03-0·77) and eczematous reactions (OR 0·24, 95% CI 0·07-0·78), all compared with pruritic rash. CONCLUSIONS: Our study showed that skin-oriented toxicities do not share a single pattern and are related to several factors, including the specific agent administered and the underlying malignancy treated. Follow-up plans should be individualized in order to minimize the risk for severe reactions that could compromise optimum therapeutic outcome. What is already known about this topic? Patients with cancer treated with different immune checkpoint inhibitors (ICIs) carry an increased risk of developing various types of skin toxicities. What are the clinical implications of this work? In this multicentre cohort study we showed that ICI-related skin toxicities do not share a single pattern and may depend on several factors, including the specific agent administered and the underlying malignancy. Among patients with macular rash, vitiligo or multiple skin toxicities, patients received ICIs more frequently for melanoma than for non-small cell lung cancer. The combination of ICI and chemotherapy compared with ICI monotherapy occurred to a lesser extent in patients with psoriatic rash lichenoid and eczematous reactions, compared with patients with pruritus. Clinical awareness and specialized dermatological consultation should be advocated.

Evaluation of dermatoscopic criteria for early detection of squamous cell carcinoma arising on an actinic keratosis.

BACKGROUND: Advanced squamous cell carcinoma (SCC) can be discriminated easily from actinic keratosis (AK) based on clinical and dermatoscopic features. However, at the initial stage of dermal invasion, SCC might still be clinically flat and discrimination from AK remains challenging, even with the addition of dermatoscopy. OBJECTIVE: The aim of this study was to investigate the clinical and dermatoscopic criteria that could suggest early invasion and serve as potent predictors to discriminate early SCC from AK. METHODS: Clinical and dermatoscopic images of histopathologically diagnosed AKs and early SCCs were evaluated for the presence of predefined criteria by 3 independent investigators. RESULTS: A total of 50 early SCCs and 45 AKs were included. The main positive dermatoscopic predictors of early SCC were dotted/glomerular vessels (odds ratio [OR] 3.83), hairpin vessels (OR 12.12), and white structureless areas (OR 3.58), whereas background erythema represented a negative SCC predictor (OR 0.22). LIMITATIONS: The retrospective evaluation of images. Moreover, the differential diagnosis included in the study is restricted between AK and early SCC. CONCLUSIONS: We identified potent predictors for the discrimination of AK and early SCC that may better guide management decisions in everyday clinical practice.

Dermoscopic Predictors of Benignity and Malignancy in Equivocal Lesions Predominated by Blue Color.

BACKGROUND: Blue color in dermoscopy can be seen in a wide range of benign and malignant lesions, melanocytic or not. Some blue-colored dermoscopic criteria have been associated with specific tumors, such as blue-white veil with melanoma and homogeneous blue with blue nevi. However, when blue color occupies a large part of the lesion's surface, the dermoscopic assessment might be particularly challenging. OBJECTIVE: To identify dermoscopic predictors associated with benignity and malignancy in tumors characterized by a predominant dermoscopic presence of blue color. METHODS: We retrospectively screened our institutional database for tumors exhibiting blue color in at least 50% of their surface with available histopathologic diagnosis. Lesions with blue color covering less than 50% of their extent and lesions not histopathologically assessed were excluded. The dermoscopic images were evaluated for the presence of predefined criteria, including the characteristics of the blue color, coexisting colors, and the vascular structures. RESULTS: Of 91 included tumors, 53 were benign (35 blue nevi, 10 angiomas, and 8 seborrheic keratoses) and 38 malignant (12 melanomas and 26 basal cell carcinomas). Our analysis revealed 3 potent dermoscopic predictors of benignity: extension of blue color in more than 75% of the surface, diffuse distribution of blue color, and absence of vessels, posing a 2.3-fold, 5.6-fold, and 6.7-fold increased probability of benignity, respectively. In contrast, asymmetric distribution of blue color, blue clods, coexistence of gray color and linear vessels were significantly predictive of malignancy, posing a 8.9-fold, 2.8-fold, 13.5-fold, and 10.4-fold increased probability, respectively. CONCLUSION: In predominantly blue tumors, the probability of malignancy is high when blue color is seen in clods or is asymmetrically distributed and when gray color or linear vessels coexist. In contrast, a diffuse distribution of blue color, its expansion in more than 75% of the surface, and the absence of vessels are highly suggestive of a benign tumor.

The dermoscopic inverse approach significantly improves the accuracy of human readers for lentigo maligna diagnosis.

BACKGROUND: A recently introduced dermoscopic method for the diagnosis of early lentigo maligna (LM) is based on the absence of prevalent patterns of pigmented actinic keratosis and solar lentigo/flat seborrheic keratosis. We term this the inverse approach. OBJECTIVE: To determine whether training on the inverse approach increases the diagnostic accuracy of readers compared to classic pattern analysis. METHODS: We used clinical and dermoscopic images of histopathologically diagnosed LMs, pigmented actinic keratoses, and solar lentigo/flat seborrheic keratoses. Participants in a dermoscopy masterclass classified the lesions at baseline and after training on pattern analysis and the inverse approach. We compared their diagnostic performance among the 3 timepoints and to that of a trained convolutional neural network. RESULTS: The mean sensitivity for LM without training was 51.5%; after training on pattern analysis, it increased to 56.7%; and after learning the inverse approach, it increased to 83.6%. The mean proportions of correct answers at the 3 timepoints were 62.1%, 65.5, and 78.5%. The percentages of readers outperforming the convolutional neural network were 6.4%, 15.4%, and 53.9%, respectively. LIMITATIONS: The experimental setting and the inclusion of histopathologically diagnosed lesions only. CONCLUSIONS: The inverse approach, added to the classic pattern analysis, significantly improves the sensitivity of human readers for early LM diagnosis.

Accuracy of dermoscopic criteria for the differential diagnosis between irritated seborrheic keratosis and squamous cell carcinoma.

BACKGROUND: Even with the addition of dermoscopy, a significant morphologic overlap exists between irritated seborrheic keratosis (ISK) and squamous cell carcinoma (SCC). OBJECTIVE: The aim of this study was to investigate the dermoscopic criteria that could serve as potent predictors for the differential diagnosis between ISK and SCC. METHODS: Dermoscopic images of histopathologically diagnosed ISKs and SCCs were evaluated by 3 independent investigators for the presence of predefined criteria. RESULTS: A total of 104 SCCs and 61 ISKs were included. The main dermoscopic predictors of SCC were dotted vessels (odds ratio [OR], 10.4), branched linear vessels (OR, 5.30), white structureless areas (OR, 6.78), white circles surrounding follicles (OR, 23.45), a diffuse irregular (OR, 2.55) or peripheral (OR, 2.8) vessel arrangement, and a central scale arrangement (OR, 3.35). Dermoscopic predictors of ISK were hairpin vessels (OR, 0.38), a diffuse regular vessel arrangement (OR, 0.39 and OR, 0.36), and white halos surrounding vessels covering more than 10% of the lesion (OR, 0.29 and OR, 0.12). LIMITATIONS: First, the retrospective design of the study; second, the differential diagnosis included in the study was restricted to ISK and SCC. CONCLUSIONS: We confirmed the significant morphologic overlap between ISK and SCC, but we also identified potent predictors for the differential diagnosis between these 2 entities.

Immune checkpoint-mediated psoriasis: A multicenter European study of 115 patients from the European Network for Cutaneous Adverse Event to Oncologic Drugs (ENCADO) group.

BACKGROUND: Immune checkpoint inhibitor (ICI)-mediated psoriasis poses significant diagnostic and therapeutic challenges. OBJECTIVE: To report data on ICI-mediated psoriasis, emerging from the largest cohort to date, to our knowledge, and to propose a step-by-step management algorithm. METHODS: The medical records of all patients with ICI-mediated psoriasis were retrospectively reviewed across 9 institutions. RESULTS: We included a cohort of 115 individuals. Grade 1, 2, and 3 disease severity was reported in 60 of 105 (57.1%, 10 missing data), 34 of 105 (32.4%), and 11 of 105 (10.5%), respectively. The ratio between exacerbation and de novo cases was 1:4.3. The most common systemic therapy was acitretin (23 patients, 20.1%), followed by systemic steroids (8 patients, 7%), apremilast (7 patients, 6.1%), methotrexate (5 patients, 4.3%) and biologics (4 patients, 3.6%). Overall, 29 of 112 patients (25.9%) interrupted and 20 of 111 (18%) permanently discontinued ICIs because of psoriasis. Body surface area of greater than 10% at baseline had a 3.6 increased risk for ICI treatment modification (odds ratio, 3.64; 95% confidence interval, 1.27-10.45; P = .03) and a 6.4 increased risk for permanent discontinuation (odds ratio, 6.41; 95% confidence interval, 2.40-17.11; P < .001). Guttate psoriasis and grade 2 or 3 disease were significant positive predictors for antitumor response of ICI, whereas pruritus was a negative predictor. LIMITATIONS: Retrospective design. CONCLUSION: Acitretin, apremilast, and methotrexate are safe and effective modalities for ICI-mediated psoriasis. In most cases, ICI can be completed unhindered. A therapeutic algorithm is proposed.

Second primary melanomas in a cohort of 977 melanoma patients within the first 5 years of monitoring.

BACKGROUND: In retrospective studies, a second primary melanoma (SPM) develops in 2%-20% of melanoma patients. Scarce evidence exists on the usefulness of total-body photography (TBP) and digital dermatoscopic documentation (DDD) for detecting SPMs. OBJECTIVE: The primary aim was to quantify the risk and investigate the time of occurrence of SPMs. Secondary aims were to identify risk factors for SPM and to assess the usefulness of TBP and DDD for SPM detection. METHODS: This prospective cohort included patients with recently diagnosed melanoma that underwent sequential clinical and dermatoscopic examinations for up to 5 years. Life table analysis and Kaplan-Meier survival analysis were performed. Multivariate Cox models were constructed to identify factors affecting the outcome. RESULTS: An SPM developed in 46 of 977 (4.7%) patients. Life table analysis revealed a 5-year cumulative risk of 8.0% for SPM. High nevus count, fair phototype, and occupational sun exposure were potent predictors of SPM. Of all new melanomas, 17.3% were diagnosed by clinical and dermatoscopic examination, 48.1% by TBP, and 34.6% by DDD. LIMITATIONS: All patients followed the same protocol and diagnostic bias associated with sequential dermatoscopic imaging. CONCLUSION: In this cohort, melanoma patients were at 8% risk of an SPM developing within 5 years. TBP and DDD significantly contributed to the early detection of SPM.

Real-life data on basal cell carcinoma treatment: Insights on clinicians' therapeutic choices from an institutional hospital registry.

Basal cell carcinoma (BCC) is the most common skin cancer in white skin individuals. The treatment of choice is surgical excision, but several other therapeutic choices are available and might also be efficient and cost-effective in selected cases of low-risk BCC or when surgery is complicate or contraindicated. The aim of the current study was to analyze the applied treatments for BCC in the real-life practice of a tertiary hospital, and investigate factors associated to the tumor and the patients that might influence the treatment selection of clinicians. Data on all BCCs treated from 1st January 2018 to 31st December 2019 were extracted. A total of 751 BCCs from 585 patients were included. The baseline characteristics of patients and tumors, the type of applied treatment and the histopathologic report when available were analyzed. Most tumors were located on the head/neck (64.2%). The most frequently applied treatment was surgical excision (580/751, 77.2%). In 22.8% of tumors a nonsurgical treatment was selected. The most frequently selected alternative treatments were, imiquimod, cryosurgery, their combination (immunocryosurgery), and vismodegib. A pretreatment diagnosis of superficial BCC was associated with a 12-fold increased probability of selecting a nonsurgical treatment except of vismodegib. Every added year of age increased the probability of selecting a nonsurgical treatment by 3-fold. Every added mm of diameter increased the possibility of vismodegib use by 4%. Surgery is the most frequently applied BCC treatment, but nonsurgical modalities do also have an essential role in real settings.