Understanding the Dermoscopic Patterns of Basal Cell Carcinoma Using Line-Field Confocal Tomography.

Basal cell carcinoma (BCC) is the most frequent malignancy in the general population. To date, dermoscopy is considered a key tool for the diagnosis of BCC; nevertheless, line-field confocal optical coherence tomography (LC-OCT), a new non-invasive optical technique, has become increasingly important in clinical practice, allowing for in vivo imaging at cellular resolution. The present study aimed to investigate the possible correlation between the dermoscopic features of BCC and their LC-OCT counterparts. In total, 100 histopathologically confirmed BCC cases were collected at the Dermatologic Clinic of the University of Siena, Italy. Predefined dermoscopic and LC-OCT criteria were retrospectively evaluated, and their frequencies were calculated. The mean (SD) age of our cohort was 65.46 (13.36) years. Overall, BCC lesions were mainly located on the head (49%), and they were predominantly dermoscopically pigmented (59%). Interestingly, all dermoscopic features considered had a statistically significant agreement with the LC-OCT criteria (all p < 0.05). In conclusion, our results showed that dermoscopic patterns may be associated with LC-OCT findings, potentially increasing accuracy in BCC diagnosis. However, further studies are needed in this field.

Advanced Atrioventricular Block in Athletes: Prevalence and Role of Anti-Ro/Sjögren Syndrome-Related Antigen A Antibodies.

BACKGROUND: Advanced atrioventricular block (AVB), that is, higher than second-degree Mobitz-1, is an abnormal finding in athletes. Despite intensive investigation, in several cases the pathogenesis remains unknown, but frequently pacemaker implantation is still indicated. Increasing evidence points to circulating anti-Ro/Sjögren syndrome-related antigen A (SSA) antibodies cross-reacting with L-type calcium channel and inhibiting the related current as an epidemiologically relevant and potentially reversible cause of isolated AVB in adults. The aim of the study was to determine the prevalence of anti-Ro/SSA-associated advanced AVBs in a large sample of young athletes. METHODS AND RESULTS: A total of 2536 consecutive athletes aged <40 years without a history of cardiac diseases/interventions were enrolled in a cross-sectional study. Resting and exercise electrocardiography was performed, and those presenting any AVB were further evaluated by 24-hour Holter ECG. Athletes with second-degree AVBs and their mothers underwent anti-Ro/SSA testing. Moreover, purified immunoglobulin G from subjects with anti-Ro/SSA-positive and anti-Ro/SSA-negative advanced AVB were tested on L-type calcium current and L-type-calcium channel expression using tSA201 cells. The global prevalence of advanced AVB in the overall sample was ≈0.1%, but the risk considerably increased (2%) when intensely trained postpubertal male subjects were selectively considered. While none of the athletes with advanced AVB showed heart abnormalities, in 100% of cases anti-Ro/SSA antibodies were detected. Ex vivo experiments showed that immunoglobulin G from anti-Ro/SSA-positive but not -negative subjects with advanced AVB acutely inhibit L-type calcium current and chronically downregulate L-type-calcium channel expression. CONCLUSIONS: Our study provides evidence that advanced AVB occurs in young athletes, in most cases associated with anti-Ro/SSA antibodies blocking L-type calcium channels. These findings may open new avenues for immunomodulating therapies to reduce the risk of life-threatening events in athletes, avoiding or delaying pacemaker implantation.

Exploring the Susceptibility to Multiple Primary Tumors in Patients with Differentiated Thyroid Cancer.

PURPOSE: It was demonstrated that differentiated thyroid cancer (DTC) patients may develop multiple primary tumors (MPT) during follow-up. Many studies showed an association between reduced telomere length and cancer phenotype; in particular, the short telomeres were associated with the development of a primary tumor. However, the role of altered telomere length in MPT development has not yet been demonstrated. The aim of this study was to evaluate the possible correlation between a short telomere length in blood leukocytes and the risk of developing MPT in DTC patients. PATIENTS AND METHODS: We retrospectively evaluated 167 DTC patients followed up for a median of 13.6 years. Our control group was represented by 105 healthy subjects without any thyroid disease or present or past history of tumors. Our study groups, age-matched, were evaluated for the relative telomere length measured in leukocytes of peripheral venous blood. RESULTS: The relative telomere length (RTL) was significantly different in healthy subjects compared to the total group of differentiated thyroid cancer patients [p < 0.0001]. Shorter telomeres length was observed in DTC patients with (n = 32) and without (n = 135) MPT compared to healthy subjects (p < 0.0001 and p = 0.0002, respectively). At multivariate analysis, the parameters independently associated with the presence of MPT were RTL [OR: 0.466 (0.226-0.817), p = 0.018] and the familial DTC [OR: 2.949 (1.142-8.466), p = 0.032]. CONCLUSIONS: The results of this study suggest a role of the relative telomere length in predicting MPT development in DTC patients. Our results contribute to increasing the knowledge of the genetic mechanisms underlying MPT development in DTC patients, considering relative telomere length as a possible prognostic marker.

Pattern Analysis of Benign and Malignant Atypical Melanocytic Skin Lesions of Palms and Soles: Variations of Dermoscopic Features According to Anatomic Site and Personal Experience.

Background: The differential diagnosis of atypical melanocytic skin lesions localized on palms and soles represents a diagnostic challenge: indeed, this spectrum encompasses atypical nevi (AN) and early-stage melanomas (EN) displaying overlapping clinical and dermoscopic features. This often generates unnecessary excisions or delayed diagnosis. Investigations to date were mostly carried out in specific populations, focusing either on acrolentiginous melanomas or morphologically typical acquired nevi. Aims: To investigate the dermoscopic features of atypical melanocytic palmoplantar skin lesions (aMPPLs) as evaluated by variously skilled dermatologists and assess their concordance; to investigate the variations in dermoscopic appearance according to precise location on palms and soles; to detect the features with the strongest association with malignancy/benignity in each specific site. Methods: A dataset of 471 aMPPLs-excised in the suspect of malignancy-was collected from 10 European Centers, including a standardized dermoscopic picture (17×) and lesion/patient metadata. An anatomical classification into 17 subareas was considered, along with an anatomo-functional classification considering pressure/friction, (4 macroareas). A total of 156 participants (95 with less than 5 years of experience in dermoscopy and 61 with ≥than 5 years) from 17 countries performed a blinded tele-dermoscopic pattern analysis over 20 cases through a specifically realized web platform. Results: A total of 37,440 dermoscopic evaluations were obtained over 94 (20%) EM and 377 (80%) AN. The areas with the highest density of EM compared to AN were the heel (40.3% EM/aMPPLs) of the sole and the "fingers area" (33%EM/aMPPLs) of the palm, both characterized by intense/chronic traumatism/friction. Globally, the recognition rates of 12 dermoscopic patterns were non statistically different between 95 dermatology residents and 61 specialists: aMPPLs in the plantar arch appeared to be the most "difficult" to diagnose, the parallel ridge pattern was poorly recognized and irregular/regular fibrillar patterns often misinterpreted. Regarding the aMPPL of the "heel area", the parallel furrow pattern (p = 0.014) and lattice-like pattern (p = 0.001) significantly discriminated benign cases, while asymmetry of colors (p = 0.002) and regression structures (p = 0.025) malignant ones. In aMPPLs of the "plantar arch", the lattice-like pattern (p = 0.012) was significant for benignity and asymmetry of structures, asymmetry of colors, regression structures, or blue-white veil for malignancy. In palmar lesions, no data were significant in the discrimination between malignant and benign aMPPLs. Conclusions: This study highlights that (i) the pattern analysis of aMPPLs is challenging for both experienced and novice dermoscopists; (ii) the histological distribution varies according to the anatomo-functional classification; and (iii) different dermoscopic patterns are able to discriminate malignant from benign aMPPLs within specific plantar and palmar areas.

Risk of Skin Cancer in Patients with Psoriasis: Single-Center Retrospective Study Comparing Anti-TNFα and Phototherapy.

Background: The risk of developing non-melanoma skin cancers (NMSCs) in patients with psoriasis is highly debated, and, to date, there is no unambiguous consensus opinion. Psoriasis is known to be related to an increased likelihood of other comorbidities such as psoriatic arthritis, obesity, metabolic syndrome, depression, and cardiovascular disease. Regarding cancer risk, previous studies have reported a greater tendency for the development of cutaneous T-lymphomas and colon, breast, kidney, and lung cancers. Furthermore, data from network meta-analyses have shown that patients with psoriasis have a higher risk of developing squamous cell carcinomas (SCCs) and/or basal cell carcinomas (BCCs). Multiple factors may contribute to the development of NMSCs in psoriatic patients, ranging from immunosuppression induced by biologic agents to previous phototherapy. However, the extent to which each factor may impact this risk has not been entirely assessed. The aim of this study was to evaluate the risk of developing NMSCs in patients with psoriasis observed for at least 5 years, by directly comparing patients only treated with phototherapy and patients treated with anti-tumor necrosis factor α (TNFα) agents, naive to other systemic treatments or phototherapy. Methods: We conducted a single-center retrospective study at Siena University Hospital, Italy, on 200 adult patients with psoriasis divided into two groups: (i) group 1, including 100 patients treated with narrow-band UVB phototherapy (nb-UVB), and (ii) group 2, including 100 patients treated with anti-TNFα. The patients included in group 2 had to be naive to cDMARDs and biologics and treated with anti-TNFα continuously for 5 years without loss of efficacy. All patients were observed for 5 years and underwent annual dermatologic examinations to assess for the occurrence of BCC or SCC. Results: A total of 34 out of 100 patients treated with phototherapy had one BCC or one SCC and 10 out of 34 developed two skin cancers. In particular, five had both types (one BCC and one SCC), and five had two BCCs. Conclusions: The results of our study highlight how the risk of developing NMSCs is greater in patients undergoing phototherapy compared to those treated with anti-TNFα. It also draws attention to the consideration that patients with scalp psoriasis might need closer follow-up as they could be more at risk of developing NMSCs.

Right ventricular dysfunction in chronic heart failure: clinical laboratory and echocardiographic characteristics. (the RIVED-CHF registry).

BACKGROUND: Right ventricular dysfunction (RVD) and pulmonary hypertension have been recognized as two important prognostic features in patients with left side heart failure. Current literature does not distinguish between right heart failure (RHF) and RVD, and the two terms are used indiscriminately to describe pulmonary hypertension and RVD as well as clinical sign of RHF. Therefore, the right ventricle (RV) adaptation across the whole spectrum of left ventricular ejection fraction (LVEF) values has been poorly investigated. METHODS: This is a multicenter observational prospective study endorsed by the Italian Society of Cardiology aiming to analyze the concordance between the signs and symptoms of RHF and echocardiographic features of RVD. The protocol will assess patients affected by chronic heart failure in stable condition regardless of the LVEF threshold by clinical, laboratory, and detailed echocardiographic study. During the follow-up period, patients will be observed by direct check-up visit and/or virtual visits every 6 months for a mean period of 3 years. All clinical laboratory and echocardiographic data will be recorded in a web platform system accessible for all centers included in the study. RESULTS: The main study goals are: to investigate the concordance and discordance between clinical signs of RHF and RVD measured by ultrasonographic examination; to evaluate prognostic impact (in terms of cardiovascular mortality and heart failure hospitalization) of RVD and RHF during a mean follow-up period of 3 years; to investigate the prevalence of different right ventricular maladaptation (isolated right ventricular dilatation, isolated pulmonary hypertension, combined pattern) and the related prognostic impact. CONCLUSIONS: With this protocol, we would investigate the three main RVD patterns according to heart failure types and stages; we would clarify different RVD and pulmonary hypertension severity according to the heart failure types. Additionally, by a serial multiparametric analysis of RV, we would provide a better definition of RVD stage and how much is it related with clinical signs of RHF (ClinicalTrials.gov Identifier: NCT06002321).

Design of a new 3D printed all-in-one magnetic smartphone adapter for fundus and anterior segment imaging.

PURPOSE: To describe and validate a 3D-printed adapter tool which could be used with either a slit lamp or a condensing lens, interchangeable between devices through magnetic fastening, in order to provide physicians a quick, easy and effective method of obtaining clinical photos. MATERIALS AND METHODS: Three specialists, with at least 4-year experience in ophthalmology, gave a rate of image quality obtained by our device and the diagnostic confidence grade. The 3 specialists conducted each 13 or 14 examinations with the smartphone and magnetic adapter. At the end of evaluation, they rated with the Likert scale the ease of use of the device in obtaining clinical images of the anterior segment and ocular fundus respectively. RESULTS: Data of quality perception and confidence demonstrated high values not dissimilar to the "de visu" eye examination. Moreover the instrument we designed turned out to be very user friendly. CONCLUSION: Our adapter coupled with a modern smartphone was able to obtain 4k images and videos of anterior segment, central and peripheral fundus, in an easy and inexpensive way.

Ankyloglossia in newborns: incidence and breastfeeding follow-up at 1 and 6 months.

BACKGROUND: Ankyloglossia is an anatomical variation of the lingual frenulum that negatively interferes with the functionality of the tongue. This condition can affect breastfeeding negatively. The aim of this study is to assess the prevalence of ankyloglossia among healthy babies born in Siena Hospital and the correlation between ankyloglossia and breastfeeding difficulties. METHODS: We performed an observational prospective study conducted on healthy and breastfed newborns born in Siena Hospital in the period between January and June 2022. The evaluation of lingual frenulum in the first few days of life was performed by Martinelli's Lingual Frenulum Protocol with scores for Infants (MLFPI), while the clinical assessment of breastfeeding initiation was performed by the Breastfeeding Observation and Evaluation Form according to WHO-UNICEF guidelines. We also compared the reliability in predicting breastfeeding of a tool that measured the features of the tongue frenulum: the Bristol Tongue Assessment Tool (BTT). Breastfeeding at one and six months of babies' age was assessed by telephone interview, and information among children's nutrition, weight growth and difficulties found in breastfeeding was also collected. This study was approved by the Pediatric Ethics Committee for Clinical Trials of the Tuscany Region. RESULTS: One hundred and ninety infants were included in the study; 21 (11.05%) had a MLFPI score ≥13. Data at one month of age showed a statistically higher MLFPI score (P value <0.001) in babies with breastfeeding difficulties (median score 13.0, IQR 5.5-14), than in those without (median score 5.0, IQR 2.0-7.5). Data at 6 months of age showed a similar difference in babies with and without breastfeeding difficulties (median 12.0, IQR 4.0-14.0 vs. 5.0, IQR 2.0-8.0 respectively). A MLFPI score ≥13 is positively associated with breastfeeding difficulties at 1 and 6 months. Also, the BTT was positively a risk factor for problems in breastfeeding at 1 and 6 months. CONCLUSIONS: A high MLFPI score is a risk factor of breastfeeding difficulties. In these cases, a referral to experienced personnel is advisable: they can provide the emotional and professional support to the mother-child dyad, and/or refer for surgical evaluation and frenotomy. In our cohort, the usefulness of either MLFPI score or BTT was evident in predicting breastfeeding difficulties; the rate of surgical removal of the frenulum was nonetheless low.

A European Multicentric Investigation of Atypical Melanocytic Skin Lesions of Palms and Soles: The iDScore-PalmoPlantar Database.

Background: The differential diagnosis of atypical melanocytic palmoplantar skin lesions (aMPLs) represents a diagnostic challenge, including atypical nevi (AN) and early melanomas (MMs) that display overlapping clinical and dermoscopic features. We aimed to set up a multicentric dataset of aMPL dermoscopic cases paired with multiple anamnestic risk factors and demographic and morphologic data. Methods: Each aMPL case was paired with a dermoscopic and clinical picture and a series of lesion-related data (maximum diameter value; location on the palm/sole in 17 areas; histologic diagnosis; and patient-related data (age, sex, family history of melanoma/sunburns, phototype, pheomelanin, eye/hair color, multiple/dysplastic body nevi, and traumatism on palms/soles). Results: A total of 542 aMPL cases-113 MM and 429 AN-were collected from 195 males and 347 females. No sex prevalence was found for melanomas, while women were found to have relatively more nevi. Melanomas were prevalent on the heel, plantar arch, and fingers in patients aged 65.3 on average, with an average diameter of 17 mm. Atypical nevi were prevalent on the plantar arch and palmar area of patients aged 41.33 on average, with an average diameter of 7 mm. Conclusions: Keeping in mind the risk profile of an aMPL patient can help obtain a timely differentiation between malignant/benign cases, thus avoiding delayed and inappropriate excision, respectively, with the latter often causing discomfort/dysfunctional scarring, especially at acral sites.

Detection of infliximab, adalimumab, and anti-drug antibodies: Development and validation of new monotest, automated assays on multiparametric instrument.

Objective: To convert manual ELISA kits to fully automated immunoassays that quantify serum drug levels and anti-drug antibodies levels of infliximab and adalimumab (CHORUS Promonitor kits). Desing and methods: CHORUS Promonitor INFLIXIMAB, CHORUS Promonitor ADALIMUMAB, CHORUS Promonitor ANTI-INFLIXIMAB, and CHORUS Promonitor ANTI-ADALIMUMAB kits were compared with the corresponding Promonitor kits to determine sensitivity and specificity of the assays. For the automated assays, the entire procedure -from samples dilution to final readouts-was performed by CHORUS TRIO instrument (DIESSE, Italy). Residual human serum samples from clinical laboratory investigations and samples resulting from the addition of specific drugs (IFX or ADL) or anti-drug antibodies (anti-IFX or anti-ADL) were used for the characterization and validation of the tests. Results: CHORUS Promonitor kits showed an excellent agreement (Cohen's coefficient = 1) with the Promonitor kits and were linear within predefined ranges. All assays were accurate and repeatable, as an acceptable variability were observed within runs, between runs, lots, and instruments. No difference in detecting the reference drug or biosimilars emerged. Conclusion: During preclinical development, these kits resulted as sensitive, specific, accurate, and able to quantify either the reference drug or the corresponding biosimilars. All these features support their use in clinical practice for therapeutic drug monitoring of patients with inflammatory diseases under treatment with IFX or ADL.

Psoriasis and Fibromyalgia: A Systematic Review.

Psoriasis is a chronic inflammatory cutaneous condition characterized by several comorbidities, including musculoskeletal disorders. While the association with psoriatic arthritis has been widely addressed in literature, the aim of the present systematic review was to identify all available evidence on the relationship between psoriasis and fibromyalgia, a musculoskeletal syndrome primarily characterized by chronic widespread pain. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and MedLine and Web of Science (WOS) databases were searched for literature up to March 2023. After the removal of duplicate records, a total of 11 articles were deemed eligible for inclusion in a qualitative synthesis. Our results suggested that psoriatic patients had a higher prevalence of fibromyalgia (8-30%), with a very high impact on symptoms of psoriasis. Moreover, fibromyalgic patients had a slightly increased prevalence of psoriasis (2.2-6.7%) compared to the control groups. Finally, several studies demonstrated the substantial impact of fibromyalgia on psoriatic outcome measures in patients with concomitant psoriatic arthritis. In conclusion, available data support a potential interplay between psoriasis and fibromyalgia, but further research is encouraged in this area.

Elevated Interleukin-6 Levels Are Associated With an Increased Risk of QTc Interval Prolongation in a Large Cohort of US Veterans.

BACKGROUND: Although accumulating data indicate that IL-6 (interleukin-6) can promote heart rate-corrected QT interval (QTc) prolongation via direct and indirect effects on cardiac electrophysiology, current evidence comes from basic investigations and small clinical studies only. Therefore, IL-6 is still largely ignored in the clinical management of long-QT syndrome and related arrhythmias. The aim of this study was to estimate the risk of QTc prolongation associated with elevated IL-6 levels in a large population of unselected subjects. METHODS AND RESULTS: An observational study using the Veterans Affairs Informatics and Computing Infrastructure was performed. Participants were US veterans who had an ECG and were tested for IL-6. Descriptive statistics and univariate and multivariate regression analyses were performed to study the relationship between IL-6 and QTc prolongation risk. Study population comprised 1085 individuals, 306 showing normal (<5 pg/mL), 376 moderately high (5-25 pg/mL), and 403 high (>25 pg/mL) IL-6 levels. Subjects with elevated IL-6 showed a concentration-dependent increase in the prevalence of QTc prolongation, and those presenting with QTc prolongation exhibited higher circulating IL-6 levels. Stepwise multivariate regression analyses demonstrated that increased IL-6 level was significantly associated with a risk of QTc prolongation up to 2 times the odds of the reference category of QTc (e.g. QTc >470 ms men/480 ms women ms: odds ratio, 2.28 [95% CI, 1.12-4.50] for IL-6 >25 pg/mL) regardless of the underlying cause. Specifically, the mean QTc increase observed in the presence of elevated IL-6 was quantitatively comparable (IL-6 >25 pg/mL:+6.7 ms) to that of major recognized QT-prolonging risk factors, such as hypokalemia and history of myocardial infarction. CONCLUSIONS: Our data provide evidence that a high circulating IL-6 level is a robust risk factor for QTc prolongation in a large cohort of US veterans, supporting a potentially important arrhythmogenic role for this cytokine in the general population.

Prognostic Factors Improving ATA Risk System and Dynamic Risk Stratification in Low- and Intermediate-Risk DTC Patients.

CONTEXT: American Thyroid Association (ATA) guidelines do not consider age at diagnosis as a prognostic factor on the estimation of the risk of persistent/recurrent disease in differentiated thyroid carcinoma (DTC) patients. While age at diagnosis has already been assessed in high-risk patients, it remains to be established in low- and intermediate-risk patients. OBJECTIVE: The aim of our study was to investigate the role of age as a prognostic factor in the short- and long-term outcome of DTC patients classified at low and intermediate risk according to the ATA stratification risk system. METHODS: We retrospectively evaluated 863 DTC patients (mean follow-up: 10 ± 6.2 years) 52% classified as low (449/863) and 48% as intermediate risk (414/863). For each ATA-risk class patients were divided into subgroups based on age at diagnosis (<55 or ≥55 years). RESULTS: In the intermediate-risk group, patients aged 55 years or older had a higher rate of structural disease (11.6% vs 8.9%), recurrent disease (4.1% vs 0.7%), and death (4.1% vs 1%) when compared with younger patients (<55 years) (P = .007). Multivariate analysis confirmed that older age at diagnosis (odds ratio [OR] = 3.9; 95% CI, 1.9-8.6; P < .001) was an independent risk factor for worse long-term outcome together with response to initial therapy (OR = 13.0; 95% CI, 6.3-27.9; P < .001), and T (OR = 32; 95% CI, 1.4-7.1; P = .005) and N category (OR = 2.3; 95% CI, 1.1-5.0; P = .03). Nevertheless, a negative effect of older age was documented only in the subgroup of intermediate DTC patients with persistent structural disease after initial therapy. Indeed, the rate of worse long-term outcome rose from 13.3% in the whole population of intermediate DTC patients to 47.8% in patients with persistent structural disease after initial therapy (P < .001) and to 80% in patients older than 55 years and persistent structural disease after initial therapy (P = .02). CONCLUSION: Our results suggest that age at diagnosis further predict individual outcomes in Intermediate-Risk DTC allowing ongoing management to be tailored accordingly.

Position statement of the EADV Artificial Intelligence (AI) Task Force on AI-assisted smartphone apps and web-based services for skin disease.

BACKGROUND: As the use of smartphones continues to surge globally, mobile applications (apps) have become a powerful tool for healthcare engagement. Prominent among these are dermatology apps powered by Artificial Intelligence (AI), which provide immediate diagnostic guidance and educational resources for skin diseases, including skin cancer. OBJECTIVE: This article, authored by the EADV AI Task Force, seeks to offer insights and recommendations for the present and future deployment of AI-assisted smartphone applications (apps) and web-based services for skin diseases with emphasis on skin cancer detection. METHODS: An initial position statement was drafted on a comprehensive literature review, which was subsequently refined through two rounds of digital discussions and meticulous feedback by the EADV AI Task Force, ensuring its accuracy, clarity and relevance. RESULTS: Eight key considerations were identified, including risks associated with inaccuracy and improper user education, a decline in professional skills, the influence of non-medical commercial interests, data security, direct and indirect costs, regulatory approval and the necessity of multidisciplinary implementation. Following these considerations, three main recommendations were formulated: (1) to ensure user trust, app developers should prioritize transparency in data quality, accuracy, intended use, privacy and costs; (2) Apps and web-based services should ensure a uniform user experience for diverse groups of patients; (3) European authorities should adopt a rigorous and consistent regulatory framework for dermatology apps to ensure their safety and accuracy for users. CONCLUSIONS: The utilisation of AI-assisted smartphone apps and web-based services in diagnosing and treating skin diseases has the potential to greatly benefit patients in their dermatology journeys. By prioritising innovation, fostering collaboration and implementing effective regulations, we can ensure the successful integration of these apps into clinical practice.

Usefulness of Combined Ultrasound Assessment of E/e' Ratio, Pulmonary Pressure, and Cava Vein Status in Patients With Acute Heart Failure.

Congestion is poorly investigated by ultrasound scans during acute heart failure (AHF) and systematic studies evaluating ultrasound indexes of cardiac pulmonary and systemic congestion during early hospital admission are lacking. We aimed to investigate the prevalence of ultrasound cardiac pulmonary and systemic congestion in a consecutive cohort of hospitalized patients with AHF, analyzing the relevance of each ultrasound congestion component (cardiac, pulmonary, and systemic) in predicting the risk of death and rehospitalization. This is a prospective research study of a single center that evaluates patients with an AHF diagnosis who are divided according to the left ventricular ejection fraction in patients with heart failure with preserved ejection fraction or reduced ejection fraction. We performed a complete bedside echocardiography and lung ultrasound analyses within the first 24 hours of hospital admission. The ultrasound congestion score was preliminarily established by measuring the following parameters: cardiac congestion, which was defined as the contemporary presence of E/e' >15 and pulmonary systolic pressure >35 mm Hg and the pulmonary congestion, defined as the total B-line number >25 at the lung ultrasound performed in 8 chest sites; moreover, the systemic congestion was defined if the inferior vena cava (IVC) was >21 mm and if it was associated with a reduced inspiratory collapse >50%. We thoroughly assessed 230 patients and evaluated their results. Of these patients, 135 had heart failure with reduced ejection fraction and there were 95 patients with heart failure with preserved ejection fraction; 122 patients experienced adverse events during the 180-day follow-up. The receiver operating characteristic curve analysis showed that the tricuspid annular peak systolic excursion (TAPSE) (area under the curve [AUC] 0.34 [0.26 to 0.41], p <0.001), E/e' (AUC 0.62 [0.54 to 0.69], p = 0.003), and IVC (AUC 0.70 [0.63 to 0.77], p <0.001) were all significantly related to poor prognosis detection. The univariate Cox regression analysis revealed that cardiac congestion in terms of E/e' and pulmonary systolic pressure (hazard ratio [HR] 1.49 [1.02 to 2.17], p = 0.037), TAPSE (HR 0.90 [0.85 to 0.94], p <0.001), and systemic congestion (HR 2.64 [1.53 to 4.56], p <0.001) were all significantly related to the 180-day outcome. After adjustment for potential confounders, only TAPSE (HR 0.92 [0.88 to 0.98], p = 0.005) and IVC (HR 1.92 [1.07 to 3.46], p = 0.029) confirmed their prognostic role. The multivariable analysis of multiple congestion levels in terms of systemic plus cardiac (HR 1.54 [1.05 to 2.25], p = 0.03), systemic plus pulmonary (HR 2.26 [1.47 to 3.47], p <0.001), and all 3 congestion features (HR 1.53 [1.06 to 2.23], p = 0.02) revealed an incremental prognostic role for each additional determinant. In conclusion, among the ultrasound indexes of congestion, IVC and TAPSE are related to adverse prognosis, and the addition of pulmonary and cardiac congestion indexes increases the risk prediction accuracy. Our data confirmed that right ventricular dysfunction and systemic congestion are the most powerful predictive factors in AHF.

Factors Influencing the Healthcare Workers' Willingness to Receive the COVID-19 Booster Dose in Tuscany (Italy).

BACKGROUND: The World Health Organization has defined vaccine hesitancy as behavior influenced by several factors, including trust in the vaccine itself or its provider or the perceived need for vaccination. The aim of this study was to investigate the factors influencing the willingness to receive the COVID-19 vaccine among the employees and healthcare professionals of the Central Tuscany Local Health Authority (CT-LHA) in Italy. METHODS: From July to October 2022, a cross-sectional study was conducted. An online questionnaire was administered to 7000 employees of the CT-LHA. The questionnaire analyzed the factors that influenced receiving the booster dose of the COVID-19 vaccine. The sample was stratified by gender, age, type of occupation (healthcare or non-healthcare workers), and seniority. Incomplete questionnaires were excluded. A chi-squared test was performed through STATA. The significance level was set at 95%. RESULTS: Of the questionnaires administered, 1885 (26.9%) questionnaires were eligible for the study. In the previous vaccination campaign, the healthcare workers (HCWs) considered the vaccine used by CT-LHA as safe, in contrast to non-healthcare workers (N-HCWs), who considered it less secure (p < 0.05). The HCWs showed a higher propensity for vaccine safety to receive the booster dose than N-HCWs. N-HCWs appeared to be less affected by an updated booster dose than HCWs (p < 0.05). CONCLUSIONS: The factors studied appear to influence HCWs differently from N-HCWs. Both HCWs and N-HCWs would choose an upgraded mRNA vaccine for the booster dose.

Validation, performance, and reliability of two automated tests for vitamin B12 and folate assay.

Background: Deficiency of Vitamin B12 and folate may determine hematological, neurological, and metabolic alterations; therefore, an accurate quantification of their serum levels is required, especially in the presence of symptoms that might suggest a deficiency. CHORUS VIT B12 and CHORUS FOLATE are two automated immunoassays, developed to quantify vitamin B12 and folate, respectively, in human serum. Design and methods: This single-center, non-pharmacological, diagnostic study described the validation and characterization of CHORUS VIT B12 and CHORUS FOLATE, with a specific focus on performance, precision, and reliability. For each assay, 500 serum samples were analyzed. A comparison between CHORUS assays and commercially available kit was also performed. Results: For CHORUS VIT B12 the lower limit of quantification (LLoQ) was 165.0 pg/mL and the upper LoQ (ULoQ) was 1846.8 pg/mL. The assay was linear within the calibration range (150-2000 pg/mL) and the accuracy was described with the International Standard Vitamin B12, Serum Folate, HOLO TC (NIBSC code: 03/178), with a mean recovery on two lots of 111%. For CHORUS FOLATE (calibration range of 2.0-20.0 ng/mL), LLoQ was 2.0 ng/mL and ULoQ 19.6 ng/mL. The linearity was demonstrated from 2.4 to 20.0 ng/mL; the accuracy was described with the International Standard mentioned above, achieving a mean recovery on three lots of 92%. The lowest and highest values of both CHORUS and COBAS kits were similar and the median values did not significantly vary. Conclusion: CHORUS VIT B12 and CHORUS FOLATE performed well, accurately, and reliably in quantifying vitamin B12 and folate in human serum.

Characteristics of Primary Cutaneous Lymphoma in Italy: A Tertiary Care, Single-Center Study.

Data on primary cutaneous lymphomas (PCLs) patients in the Italian population are limited, and, despite the existence of several treatment options, the management of those patients remains challenging. Our study aimed to investigate the clinical and therapeutic features of PCL patients in a referral center in Italy. We conducted a retrospective study on 100 consecutive PCL patients between January 2017 and December 2022. The mean (SD) age of our cohort was 70.33 (14.14) years. Cutaneous T-cell lymphomas (CTCLs) represented 65% of all cases; the majority were mycosis fungoides (42%), followed by cases of Sezary syndrome (10%) and primary cutaneous anaplastic large cell lymphoma (4%). Cutaneous B-cell lymphomas (CBCLs) accounted for 35 % of PCLs, with 15 cases of primary cutaneous follicle center lymphoma, 10 cases of primary cutaneous diffuse large B-cell lymphoma leg type, and 9 cases of marginal zone B-cell lymphoma. A higher frequency of pruritus (p = 0.008) and higher peripheral blood levels of beta-2 microglobulin (p ≤ 0.001) and lactate dehydrogenase (p = 0.025) were found in CTCLs compared to those of CBCLs. Considering all therapeutic lines performed, treatments were extremely heterogeneous and skin-directed therapies represented the most frequently used approach. Our study confirms the distribution of PCL subtypes formerly reported in the literature and highlights the utility of real-life data in treatments to improve the current management of PCL patients.

Unfolding dermatologic spectrum of Behçet's disease in Italy: real-life data from the International AIDA Network Behçet's disease Registry.

Behçet's disease (BD) is a heterogeneous multifactorial autoinflammatory disease characterized by a plethora of clinical manifestations. Cutaneous lesions are considered hallmarks of the disease. However, their evolution over time and a thorough description are scarcely reported in non-endemic regions. The aim of this study was to detail BD skin manifestations and their evolution over time in Italy, as well as the dermatological prognostic impact of specific cutaneous features in long-standing disease. Data were collected in a double fashion, both retrospectively and prospectively, from the AutoInflammatory Disease Alliance (AIDA) international registry dedicated to BD, between January 2022 and December 2022. A total of 458 Italian patients were included. When assessing skin manifestations course, the constant or sporadic presence or absence of cutaneous involvement between onset and follow-up was considered. Oral ulcers (OU) (88.4%) and genital ulcers (GU) (52.6%), followed by skin involvement (53.7%) represented the most common presenting mucocutaneous manifestations at disease onset. Up to the time of enrolment into the AIDA registry, 411 (93.8%) patients had suffered from OU and 252 (57.9%) from GU; pseudofolliculitis (PF) accounted for the most common skin manifestation (170 patients, 37.1%), followed by erythema nodosum (EN) (102 patients, 22.3%), skin ulcers (9 patients, 2%) and pyoderma gangrenosum (4 patients, 0.9%). A prospective follow-up visit was reported in 261/458 patients; 24/148 (16.2%) subjects with skin involvement as early as BD onset maintained cutaneous lesions for the entire period of observation, while 120 (44.1%) patients suffered from sporadic skin involvement. Conversely, 94/113 (83.2%) with no skin involvement at disease onset did not develop skin lesions thereafter. At follow-up visits, cutaneous involvement was observed in 52 (20%) patients, with a statistically significant association between PF and constant skin involvement (p = 0.031). BD in Italy is characterized by a wide spectrum of clinical presentations and skin manifestations in line with what is described in endemic countries. Patients with skin disease at the onset are likely to present persistent cutaneous involvement thereafter; mucocutaneous lesions observed at the onset, especially PF, could represent a warning sign for future persistent skin involvement requiring closer dermatological care.