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Background: The Hormonal Bone Effects (HOBOE) study tested whether adjuvant triptorelin plus either letrozole (L) or zoledronic acid (Z) plus L (ZL) was more effective than tamoxifen (T) in premenopausal patients with hormone receptor-positive (HR+) early breast cancer (BC). Here we report the long-term follow-up analysis., Patients and Methods: HOBOE (ClinicalTrials.gov number NCT00412022) is an open-label, three-arm, randomised, phase III trial that involved 16 centres in Italy. One thousand and sixty-five premenopausal patients with HR+ early BC receiving triptorelin were randomly assigned (1 : 1 : 1) to adjuvant T, L or ZL for 5 years. Cancer recurrence, second breast or non-breast cancer and death were considered events for the intention-to-treat disease-free survival (DFS) analysis., Results: As of 24 October 2024 at a median follow-up of 9.2 years, 199 DFS events and 79 deaths were reported. Both ZL and L improved DFS over T, with a hazard ratio (HR) of 0.58 [95% confidence interval (CI) 0.41-0.82; P = 0.002] for ZL versus T and 0.69 (95% CI 0.49-0.97, P = 0.030) for L versus T. No statistically significant difference in OS was reported (global log-rank P = 0.103). The previously reported statistically significant interaction with human epidermal growth factor receptor 2 (HER2) status was confirmed for ZL versus T comparison (P = 0.007)., Conclusion: In this updated analysis, L plus triptorelin, with or without Z, demonstrated a statistically significant DFS improvement over T plus triptorelin for the adjuvant treatment of early BC in premenopausal patients., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The present study aimed to investigate the causal relationships among cognitive impairment, psychopathology, and real-life functioning in a large sample of people with schizophrenia, using a data-driven causal discovery procedure based on partial ancestral graphs (PAGs). This method may provide additional insights for the identification of potential therapeutic targets to promote recovery in people with chronic schizophrenia. State-of-the-art instruments were used to assess the study variables. Two PAGs were generated at baseline and after 4 years of follow-up to model the nature of the causal relationships linking psychopathology, cognition, and functioning. The study sample was composed of more than 600 clinically stable patients with schizophrenia at two time points. The PAGs model indicated that working memory impairment is the first ancestor of the causal links, influencing all the other neurocognitive domains, social cognition, and functional capacity, which in turn affects everyday life functioning. From this domain of functioning a causal link is directed to disorganization and positive symptoms, and another to work skills and interpersonal relationships domains; the latter had a direct link to asociality and the other domains of negative symptoms. The structure of the PAGs did not differ significantly between baseline and follow-up, indicating the stability of the causal relationship model investigated cross-sectionally at both time points. The role of working memory impairment in the pathways to functional outcomes in schizophrenia highlights the importance of implementing integrated pharmacological and cognitive remediation interventions targeting neurocognition. The impact of everyday life and interpersonal functioning on the clinical presentation of schizophrenia suggests that integrated and personalized treatments, promoting relevant skills to improve these functional outcomes, may have a beneficial impact on clinical outcomes., Competing Interests: Competing interests: The authors declare no competing interests. Ethics: The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. All procedures involving human patients were approved by local Ethic Committee “Comitato Etico Università degli Studi della Campania Luigi Vanvitelli - Azienda Ospedaliera Universitaria Luigi Vanvitelli - AORN Ospedali dei Colli (PRIN 2017 project: March 2020, protocol no. 202). Consent to participate/for publication: After receiving a comprehensive explanation of the study procedures and goals, a written informed consent to participate in the study was asked to all subjects., (© 2025. The Author(s).)

Introduction: Renal cell carcinoma (RCC) is one of the most common types of urogenital cancer. The introduction of immune-based combinations, including dual immune-checkpoint inhibitors (ICI) or ICI plus tyrosine kinase inhibitors (TKIs), has radically changed the treatment landscape for metastatic RCC, showing varying efficacy across different prognostic groups based on the International Metastatic RCC Database Consortium (IMDC) criteria., Materials and Methods: This retrospective multicenter study, part of the ARON-1 project, aimed to evaluate the outcomes of favorable-risk metastatic RCC patients treated with immune-based combinations or sunitinib. Patients were assessed for overall survival (OS), progression-free survival (PFS) and overall response rate. We carried out a survival analysis by a Cox regression model., Results: A total of 524 favorable-risk patients were included in the analysis. After a median follow-up of 37.2 months, the median OS in the overall population was 56.1 months. There was no significant difference in OS between patients receiving sunitinib and those receiving TKI + ICI combinations (p = 0.761). Patients on TKI + ICI had significantly longer PFS compared to patient treated with sunitinib (30.7 vs 22.9 months, p = 0.007). Analysis of OS and PFS based on metastatic site revealed that patients with bone metastases benefited more from ICI plus TKI (56 patients with bone metastases receiving IO + TKI, 38 received pembrolizumab plus axitinib, 15 cabozantinib plus nivolumab and 3 pembrolizumab plus lenvatinib), while sunitinib was more effective for pancreatic and glandular metastases. Additionally, the number of metastatic sites played a role, with TKI plus ICI showing superiority in patients with a single metastatic site. The time from RCC diagnosis to metastatic disease also impacted outcomes, with TKI plus ICI being more effective in patients with a shorter interval (i.e., < 36 months)., Conclusions: The choice between upfront combination or monotherapy for metastatic favorable prognosis RCC remains a current issue. While combination therapy offers prolonged PFS, it does not necessarily translate to improve OS compared to sunitinib. This real-world study supports the superiority in terms of PFS of TKI plus ICI vs TKI monotherapy but not in OS. Probable, other clinical factors should be taking into account to make clinical treatment decisions in this setting., Competing Interests: Declarations. Conflicts of Interest: Javier Molina-Cerrillo declares consultant, advisory or speaker roles for IPSEN, Roche, Pfizer, Sanofi, Janssen and BMS. JMC has received research grants from Pfizer, IPSEN and Roche Francesco Massari has received research support and/or honoraria from Astellas, BMS, Janssen, Ipsen, MSD and Pfizer outside the submitted work. Linda Cerbone has received honoraria for advisory boards, speaker engagements and scientific consultancy for educational purposes from AstraZeneca, EISAI, MSD, Ipsen, BMS, A.A.A.; past MSD employee in Medical Affairs. Ondrej Fiala received honoraria from Novartis, Janssen, Merck and Pfizer for consultations and lectures unrelated to this project. Fernando Sabino M. Monteiro has received research support from Janssen, Merck Sharp Dome and honoraria from Janssen, Ipsen, Bristol Myers Squibb and Merck Sharp Dome, all unrelated to the present paper. R. Kanesvaran has received fees for speaker bureau and advisory board activities from the following companies; Pfizer, MSD, BMS, Eisai, Ipsen, Johnson and Johnson, Merck, Amgen, Astellas and Bayer. Camillo Porta has received honoraria from Angelini Pharma, AstraZeneca, BMS, Eisai, Ipsen and MSD and acted as a Protocol Steering Committee Member for BMS, Eisai and MSD. Sebastiano Buti has received honoraria for speaking at scientific events and advisory roles from AstraZeneca, Bristol Myers Squibb, Ipsen, Merck, Eisai, MSD, Novartis and Pfizer and research funding from Novartis and Pfizer. Matteo Santoni has received research support and honoraria from Janssen, Bristol Myers Squibb, Ipsen, MSD, Astellas, A.A.A. and Bayer, all unrelated to the present paper. The other authors declare no conflicts of interest., (© 2024. The Author(s).)

Background and Aims: Circulating proenkephalin (PENK) is a stable endogenous polypeptide with fast response to glomerular dysfunction and tubular damage. This study examined the predictive value of PENK for renal outcomes and mortality in patients with acute coronary syndrome (ACS)., Methods: Proenkephalin was measured in plasma in a prospective multicentre ACS cohort from Switzerland (n = 4787) and in validation cohorts from the UK (n = 1141), Czechia (n = 927), and Germany (n = 220). A biomarker-enhanced risk score (KID-ACS score) for simultaneous prediction of in-hospital acute kidney injury (AKI) and 30-day mortality was derived and externally validated., Results: On multivariable adjustment for established risk factors, circulating PENK remained associated with in-hospital AKI [per log2 increase: adjusted odds ratio 1.53, 95% confidence interval (CI) 1.13-2.09, P = .007] and 30-day mortality (adjusted hazard ratio 2.73, 95% CI 1.85-4.02, P < .001). The KID-ACS score integrates PENK and showed an area under the receiver operating characteristic curve (AUC) of .72 (95% CI .68-.76) for in-hospital AKI and .91 (95% CI .87-.95) for 30-day mortality in the derivation cohort. Upon external validation, KID-ACS achieved similarly high performance for in-hospital AKI (Zurich: AUC .73, 95% CI .70-.77; Czechia: AUC .75, 95% CI .68-.81; Germany: AUC .71, 95% CI .55-.87) and 30-day mortality (UK: AUC .87, 95% CI .83-.91; Czechia: AUC .91, 95% CI .87-.94; Germany: AUC .96, 95% CI .92-1.00), outperforming the contrast-associated AKI score and the Global Registry of Acute Coronary Events 2.0 score, respectively., Conclusions: Circulating PENK offers incremental value for predicting in-hospital AKI and mortality in ACS. The simple six-item KID-ACS risk score integrates PENK and provides a novel tool for simultaneous assessment of renal and mortality risk in patients with ACS., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Mixed signal analog/digital neuromorphic circuits represent an ideal medium for reproducing bio-physically realistic dynamics of biological neural systems in real-time. However, similar to their biological counterparts, these circuits have limited resolution and are affected by a high degree of variability. By developing a recurrent spiking neural network model of the retinocortical visual pathway, we show how such noisy and heterogeneous computing substrate can produce linear receptive fields tuned to visual stimuli with specific orientations and spatial frequencies. Compared to strictly feed-forward schemes, the model generates highly structured Gabor-like receptive fields of any phase symmetry, making optimal use of the hardware resources available in terms of synaptic connections and neuron numbers. Experimental results validate the approach, demonstrating how principles of neural computation can lead to robust sensory processing electronic systems, even when they are affected by high degree of heterogeneity, e.g., due to the use of analog circuits or memristive devices., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Introduction: Few data are available about the forgiveness of two-drug (2DR) or low-barrier three-drug antiretroviral regimens. The aim of this study is to evaluate the real-life forgiveness of lamivudine/dolutegravir (3TC/DTG) and emtricitabine/tenofovir alafenamide/rilpivirine (FTC/TAF/RPV)., Methods: A two center retrospective observational study enrolled all people with HIV (PWH) treated with 3TC/DTG or FTC/TAF/RPV. Adherence was measured as the proportion of days covered (PDC) by drug supply. Binary logistic regression was applied to test the impact of baseline variables and adherence on the achievement of virological suppression., Results: 1258 adult PWH were enrolled, 368 in 3TC/DTG and 890 in RPV/F/TAF. Most were males (71 %), with median age of 51 years (IQR 43-58 years) and median CD4 nadir of 305 cells/mcL (IQR 132-485). The median cohort follow-up totaled 4558 persons/year. Median adherence, as calculated from PDC, was of 0.98 (IQR 0.93-1). Irrespective of the treatment group, a PDC as low as 0.8 was sufficient to obtain HIV-RNA below 200 copies/mL in almost all study participants. The same adherence value also allowed the achievement of HIV-RNA below 50 copies/mL in > 90% of study participants. PDC (P < 0.0001), Italian origin (P < 0.0001) and male sex (P = 0.038) significantly correlated to the achievement of < 200 copies/mL., Conclusions: In this study, we found a similar and high grade of forgiveness in the INSTI-based 2-drug regimen 3TC/DTG and in the NNRTI-based 3-drug regimen FTC/TAF/RPV., Competing Interests: Conflicts of Interest and Source of Funding: Outside the submitted work, LT attended advisory boards and served as consultant for Gilead Sciences and ViiV Healthcare, she received grants for conferences participations from ViiV Healthcare and research grants for her institution from Gilead Sciences; FM has received research funding, fees for scientific advisory boards and speaker honoraria from ViiV Healthcare, Gilead, Janssen and MSD. LC declared conference participation supported by ViiV Healthcare and Gilead Sciences and speaker honoraria from ViiV Healthcare and Gilead Sciences and participation in advisory board for MSD; ADB has received funding for scientific advisory boards, travel and speaker honoraria from ViiV Healthcare, Gilead, Janssen, AbbVie and MSD. For the remaining authors none were declared., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Endometriosis and pelvic inflammatory disease (PID) are gynecological conditions affecting women of reproductive age and causing pain symptoms. The symptoms caused by these conditions are similar; thus, the differential diagnosis may be challenging. The treatment of these conditions is very different because PID is treated with antibiotic therapy, while endometriosis is treated with hormonal therapies suppressing estrogen levels., Areas Covered: A narrative review was conducted through a comprehensive literature search on endometriosis and PID. The search strategy incorporated relevant keywords and MeSH terms related to these topics., Expert Opinion: The antibiotics used to manage PID have high efficacy and safety profiles. Commonly prescribed regimens include a combination of ceftriaxone, doxycycline, and metronidazole. These antibiotics are generally well-tolerated, with most adverse effects being mild and manageable (gastrointestinal disturbances or hypersensitivity reactions). Hormonal therapies are a cornerstone in the management of endometriosis; they include combined oral contraceptives (COCs), progestins, gonadotropin-releasing hormone (GnRH) agonists, and antagonists. COCs and progestins are generally well-tolerated with a favorable safety profile, though they may cause side effects (breakthrough bleeding and mood changes). Oral GnRH antagonists have emerged as a noteworthy option, offering partial estrogen suppression and thereby overcoming the limitations associated with previously used GnRH agonists.

Autism spectrum disorder (ASD) exhibits an ∼4:1 male-to-female sex bias and is characterized by early-onset impairment of social/communication skills, restricted interests, and stereotyped behaviors. Disruption of the Xp22.11 locus has been associated with ASD in males. This locus includes the three-exon PTCHD1, an adjacent multi-isoform long noncoding RNA (lncRNA) named PTCHD1-AS (spanning ∼1 Mb), and a poorly characterized single-exon RNA helicase named DDX53 that is intronic to PTCHD1-AS. While the relationship between PTCHD1/PTCHD1-AS and ASD is being studied, the role of DDX53 has not been comprehensively examined, in part because there is no apparent functional murine ortholog. Through clinical testing, here, we identified 8 males and 2 females with ASD from 8 unrelated families carrying rare, predicted damaging or loss-of-function variants in DDX53. Additionally, we identified a family consisting of a male proband and his affected mother with high-functioning autism, both harboring a gene deletion involving DDX53 and exons of the noncoding RNA PTCHD1-AS. Then, we examined databases, including the Autism Speaks MSSNG and Simons Foundation Autism Research Initiative, as well as population controls. We identified 26 additional individuals with ASD harboring 19 mostly maternally inherited, rare, damaging DDX53 variations, including two variants detected in families from the original clinical analysis. Our findings in humans support a direct link between DDX53 and ASD, which will be important in clinical genetic testing. These same autism-related findings, coupled with the observation that a functional orthologous gene is not found in mice, may also influence the design and interpretation of murine modeling of ASD., Competing Interests: Declaration of interests At the time of this study and its publication, S.W.S. served on the scientific advisory committee of Population Bio. Intellectual property from aspects of his research held at The Hospital for Sick Children are licensed to Athena Diagnostics and Population Bio. These relationships did not influence data interpretation or presentation during this study but are disclosed for potential future considerations. S.V.M. is an employee of GeneDx, LLC. H.F.P. is on the research advisory boards and speaker bureau for Takeda Pharmaceutical, AvroBio, Amicus Therapeutics, Sanofi, Alexion Therapeutics, Denali Therapeutics, and Acer Therapeutics., (Copyright © 2024 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Approximately 40% of patients with Primary Biliary Cholangitis (PBC) show incomplete response to ursodeoxycholic acid, thus needing second-line treatment to prevent disease progression. As no head-to-head comparison study is available, we used a network meta-analysis (NMA) to compare efficacy and safety of available second-line therapies., Methods: We performed a systematic literature review including randomised, placebo-controlled trials of patients with PBC and incomplete response, or intolerance, to ursodeoxycholic acid, and compared relative risks (RRs) for primary (biochemical response at 52-week) and secondary outcomes [incidence of new-onset pruritus and serious adverse events (SAEs)]., Results: The NMA included three studies, each testing obeticholic acid (OCA), seladelpar or elafibranor versus placebo (active therapy/placebo: 379/191 patients). All treatments significantly increased the RR for biochemical response with an advantage of elafibranor versus seladelpar (RR: 4.37, 95% CI: 1.01-18.87). OCA 5-10 mg/10 mg was associated with a higher risk of new-onset pruritus compared to placebo (RR: 1.43; 95% CI: 1.09-1.88/RR: 1.79; 95% CI: 1.37-2.33), while seladelpar decreased this risk (RR: 0.30; 95% CI: 0.12-0.80). Compared to placebo, OCA 5-10 mg/10 mg was associated with an increased risk of SAE (RR: 3.82; 95% CI: 1.46-10.02/RR 2.67; 95% CI: 1.00-7.08)., Conclusions: Among second line therapies for patients with PBC, elafibranor is slightly more effective in obtaining biochemical response than seladelpar that, on the other hand, is the only drug associated with a lower incidence of pruritus. While of similar efficacy, OCA was associated with increased pruritus and SAEs. These findings may help personalise second-line treatment in patients with PBC., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Background: The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) has been validated in many cross-sectional studies. However, longitudinal data on BICAMS subset trajectories and their correlation with disease activity during follow-up are scarce., Objectives: We aimed to (i) assess BICAMS changes in MS patients initiating high-efficacy disease-modifying-treatments (DMTs), (ii) compare these changes based on maintenance of "no-evidence-of-disease-activity" (NEDA-3) status over 24 months, and (iii) determine baseline clinical parameters predictive of cognitive changes., Methods: We enrolled 101 MS patients (mean age:40,45 ± 11; Relapsing-Remitting-MS:81%) initiating highly-effective-DMTs. Patients underwent Expanded Disability Status Scale (EDSS), BICAMS, and Hospital Anxiety and Depression Scale (HADS), at baseline and after 24 months. Regression-based change index (RB-CI) had been used for cognitive change evaluation over follow-up., Results: During follow-up, 78 (77.3%) patients maintained NEDA-3 status. Considering a 90% of confidence levels for RB-CI, 12 (11.9%) improved at SDMT, 13 (12.9%) at CVLT-II and 13 (12.9%) at BVMT-R; while 7 (6.9%) were classified as worsened at SDMT, 11 (10.9%) at CVLT-II and 8 (7.9%) at BVMT-R. SDMT scores significantly improved at follow-up for the entire group (p = 0.003) and in patients maintaining NEDA-3 (p < 0.001). The multivariable regression model assessing the SDMT improvement (n = 12; z = 1.65), was significant and explained 21% of the variance (p = 0.038; Nagelkerke R 2  = 0.212). Lower EDSS proved to be an independent predictor of SDMT reliable improvement (p = 0.027) in our sample., Conclusions: Our findings showed that early disease activity control-especially in patients with low baseline disability-may yield significant benefits even in terms of cognitive performance., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Purpose: We investigated sex-related brain metabolic differences in Amyotrophic Lateral Sclerosis (ALS) and healthy controls (HC)., Methods: We collected two equal-sized groups of male (m-ALS) and female ALS (f-ALS) patients (n = 130 each), who underwent 2-[ 18 F]FDG-PET at diagnosis, matched for site of onset, cognitive status and King's stage. We included 168 age-matched healthy controls, half female (f-HC) and half male (m-HC). We compared brain metabolism of males and females separately for ALS and HC, including age as covariate. A differential network analysis was performed to evaluate brain connectivity., Results: M-ALS showed relative hypometabolism of bilateral medial frontal, parietal and occipital cortices, and left temporal cortex, compared to f-ALS. In node-wise comparison, f-ALS showed significantly higher connectivity in right middle cingulate cortex and left superior and medial frontal gyrus. In HC we did not find any sex-related differences., Conclusion: Sex resulted a major determinant of brain metabolism and connectivity in ALS patients., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Secondary acute myeloid leukemia (s-AML) is associated with inferior outcomes with conventional chemotherapy, and fludarabine combinations (FLAG-Ida) have been tested to improve results. More recently, CPX-351 resulted superior to conventional 3 + 7 in s-AML patients. In the UK NCRI AML19 trial, AML patients were randomized to receive either FLAG-Ida or CPX-351. Subgroup analysis revealed better overall survival (OS) with CPX-351 in patients with MDS-related gene mutations. Unfortunately, minimal residual disease (MRD) was evaluated only in a minority of patients. The aim of this study was to further disclose the mechanisms of higher efficacy of CPX-351 in s-AML, with a focus on MRD. We analyzed 183 consecutive s-AML elderly patients (median age 69, range 60-77) treated with CPX-351 (n = 82) or receiving FLAG-Ida (n = 101). Complete remission (CR) rate and MRD negativity probability were higher among patients receiving CPX-351 (MRD negative CR rate of 40/64, 62.5%, compared to 25/55, 45% in patients who received FLAG-Ida, p < 0.05). Extra-hematological toxicity was lower in CPX-351 arm, and 30 days mortality was 3.6% and 8% in patients receiving CPX-351 or FLAG-Ida, respectively. Notably, 21/64 (32.8%) CR patients treated with CPX 351 underwent allogeneic stem cell transplantation (HSCT), compared to 5/55 with FLAG-Ida (9%, p < 0.05). Overall, CPX-351 treatment resulted in higher OS (median OS 17.7 vs. 11.2 months with FLAG-Ida, p < 0.05). The better outcome of CPX-351 compared to FLAG-Ida in our cohort may be explained by a greater probability of MRD negativity, alongside with an improved tolerance, enabling more s-AML patients to undergo HSCT., (© 2024 John Wiley & Sons Ltd.)

Background: Despite growing evidence of its clinical implications, assessment of coronary microvascular dysfunction (CMD) remains limited in routine clinical practice. Hence, there is an increasing interest in angiography-derived indices to encourage assessment of CMD in the cardiac catheterisation laboratory., Aims: We investigate here an alternative approach, using a combination of pressure-wire-based assessment of distal coronary pressure (P d ) and an angiography-derived surrogate of coronary flow, to derive a hybrid index of microcirculatory resistance (IMR hybrid )., Methods: Patients enroled prospectively under the Oxford Acute Myocardial Infarction (OxAMI) study were included in the OxAMI HYBRID substudy. The accuracy of IMR hybrid was assessed in diagnosing CMD using bolus thermodilution-based Index of Microcirculatory Resistance (IMR) as a reference. The accuracy of IMR hybrid was then compared against a fully angiography-derived index of microvascular resistance (IMR angio )., Results: One hundred and eighty six patients were enroled, of which 121 with acute coronary syndrome and 65 with stable coronary artery disease. A total of 240 vessel analyses were performed. Both IMR hybrid and IMR angio correlated with IMR (rho = 0.71, p < 0.001 and rho = 0.71, p < 0.001 respectively) and showed good and comparable overall diagnostic accuracy in predicting IMR ≥ 25 (80.8% and 83.1% respectively) with a receiver operator curve (ROC) analyses showing similar AUC of 0.86 (95% CI 0.82-0.91, p < 0.001) for IMR hybrid and 0.86 (95% CI 0.809-0.906, p < 0.001) for IMR angio , p for comparison = 0.641., Conclusion: Both approaches, IMR hybrid and IMR angio are viable and comparable indices correlating with bolus thermodilution-based IMR and retaining good diagnostic accuracy. IMR hybrid specifically is a simple alternative to conventional bolus thermodilution-based IMR applicable to any pressure wire system., (© 2024 Wiley Periodicals LLC.)

Objectives: To compare menopausal symptoms of breast cancer survivors on adjuvant endocrine therapy with those of menopausal women., Study Design: In a retrospective nested case-control study menopausal symptoms were compared of breast cancer survivors in pre-, peri- or post-menopause at the time of diagnosis, on tamoxifen or an aromatase inhibitor, plus a gonadotrophin-releasing hormone analogue, if pre- or peri-menopausal, and age-matched control women either in the late peri-menopause, or in surgical or in physiological post-menopause on no hormone replacement therapy. Differences between women on tamoxifen and those on aromatase inhibitors were also evaluated. Weighted and non-weighted t-tests, chi-square tests, and linear or logistic regressions were applied as appropriate., Main Outcome Measures: Score on the Greene's Climacteric Scale and so of its subscales evaluating vasomotor, anxiety, depression, somatisation and sexuality symptoms., Results: A total of 99 breast cancer survivors (45 on tamoxifen, 54 on aromatase inhibitors) and 554 controls (173 in late perimenopause, 353 in natural and 28 in surgical menopause) were enrolled. The score on the Greene's Climacteric Scale was similar in cases and controls (means ± standard deviation) (21.3 ± 10.4 vs. 22.8 ± 11.5, p = 0.199), as were the subscale scores for vasomotor symptoms, anxiety, and somatisation. The depression score was lower (4.63 ± 3.3 vs. 5.98 ± 3.8; p = 0.001) in breast cancer survivors on adjuvant endocrine therapy, mainly due to a lower score of -2.132 (95 % confidence interval - 3.858/-0.407; p = 0.016) for users of aromatase inhibitors. The sexuality score was higher (1.76 ± 1.1 vs. 1.50 ± 1.1, p = 0.011) than in controls. Differences remained significant when corrected for age, menarche, body mass index, menopausal status (peri- or post-), type of menopause (natural, surgical), use of gonadotrophin-releasing hormone analogues, years of amenorrhea, smoking, alcohol use, and for breast radiotherapy, chemotherapy, tamoxifen or aromatase inhibitors. Among breast cancer survivors, women on aromatase inhibitors had lower scores for anxiety (5.75 ± 2.5vs.5.75 ± 2.5; p = 0.045) and depression (3.89 ± 2.5 vs. 5.13 ± 3.6; p = 0.046) than women on tamoxifen., Conclusions: In breast cancer survivors, adjuvant therapy induces symptoms similar in type and intensity to those of symptomatic menopausal women. Compared with menopausal women, breast cancer survivors, particularly those on aromatase inhibitors, appear to experience less severe depressive symptoms., Competing Interests: Declaration of competing interest M. Lambertini reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences; speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Takeda, Gilead; travel Grants from Gilead, Daiichi Sankyo, Roche; research funding (to the Institution) from Gilead all outside the submitted work. Prof. Lucia L. Del Mastro reports advisory role and/or speaker honoraria for Roche, Eli Lilly, Novartis, Pfizer, Pierre Fabre, Eisai, Gilead, Astrazeneca, Daiichi Sankyio, Gilead, Exact sciences, Agendia, Menarini Stemline, Olema, Ipsen, MSD; travel grants from Gilead, daiichi Sankyo, Astrazeneca, Roche; research funding (to the institution) from Pfizer, all outside the submitted work. The other authors declare no conflict of interest with the content of the present article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Pre-hospital emergency nurses, frequently exposed to high-stress situations, are at risk for burnout and stress-related issues, affecting their overall well-being. The Professional Quality of Life (ProQoL) scale, widely used among hospital nurses, remains untested in pre-hospital emergency settings., Aim: To adapt and validate the ProQoL scale for pre-hospital emergency contexts and explore the protective role of emotional intelligence in professional well-being., Methods: A mixed-method study was conducted. The qualitative approach involved semi-structured interviews to inform the modification of items for adapting the ProQoL to the pre-hospital emergency setting. A quantitative method was applied to assess the relationship between emotional intelligence and professional well-being through content and face validity measures., Results: Qualitative interviews suggested refining the ProQoL for pre-hospital emergency settings, emphasising factors such as job satisfaction and professional conduct. The revised 21-item Pre-Hospital Emergency-Professional Quality of Life (PHE-ProQoL) scale demonstrated strong content validity (I-CVI: 0.86-1, S-CVI: 0.9) and face validity. Significant correlations were observed between emotional intelligence and professional well-being, with negative correlations between emotional intelligence and both burnout (Pearson's r = -0.859) and post-traumatic stress (Pearson's r = -0.792), and a positive correlation with compassion satisfaction (Pearson's r = +0.917). Pre-hospital nurses displayed moderate levels of compassion satisfaction (27.3 ± 9.81), high emotional intelligence (28.0 ± 9.58), especially in empathy, and substantial levels of burnout (22.5 ± 6.09) and stress (21.2 ± 4.3)., Discussion: The study found that pre-hospital emergency nurses exhibit moderate compassion satisfaction and above-average emotional intelligence, particularly in perceiving and managing others' emotions. However, they also experience significant levels of burnout and post-traumatic stress., Conclusions: Burnout and post-traumatic stress significantly affect pre-hospital emergency nurses. Enhancing emotional intelligence is crucial for their well-being. Nursing managers now have access to a validated and reliable tool to assess this., (© 2024 The Author(s). Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

Background: RNA polymerase III (POLR3)-related leukodystrophy is a rare, neurodegenerative disorder characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. Despite the challenges of caring for a child with POLR3-related leukodystrophy, few studies have examined parents' disease burden. We sought to investigate quality of life and stress levels amongst parents of children with POLR3-related leukodystrophy. Methods: 43 parents of 32 children completed questionnaires on demographics, stress, quality of life, coping mechanisms, and experience of injustice. Detailed clinical data was collected from all patients. Results: Mothers ( t [27] = -8.66, P  < .001) and fathers (t[16] = -4.47, P  < .001) had lower quality of life scores compared to the normative population, yet 80% of parents' stress scores fell within the normal stress range. Parents' experience of injustice scores were high (>60). Correlations were found between and within parents' scores. Years since disease onset and certain life circumstances correlated to mothers' quality of life scores; however, no correlation was found between modifiable factors and fathers' quality of life scores. Helpful coping mechanisms included those that allowed parents to be involved in their child's life. Conclusions: This is the first study to assess stress and quality of life in this population. These results shed light on the importance of implementing services and social support to improve the well-being of parents., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: EB has been a consultant for Orchard Therapeutics, and Advisory Board for Novartis, PTC, Biogen, Pfizer, Roche. SK is a site investigator for the Ionis Alexander disease clinical trial (2022-present) and BioMarin long-term extension study for CLN2 patients treated with Brineura (2022-present). She was also a consultant for Veristat regarding MLD (2022) and is on the board of directors for the United Leukodystrophy Foundation. ER is a consultant for Taysha Gene Therapies (2023-present) and Acadia (2023-present). She is the PI on the REVEAL trail for Rett syndrome by Taysha Gene Therapies (2022-present). She is/was a subinvestigator on a therapeutic trial by BioMarin (2021-present), Glaxo Smith Kline (2015-2016), Pfizer (2017-2018), and Acadia (2020-2021). AV receives funding from Ionis, Sana, Illumina, Orphan Disease Center, Homology, Affinia, Sanofi, Orchard therapeutics, Takeda, Biogen, Boehringer Ingelhiem, Eli Lilly, Synaptix Bio, and PMD Foundation without any personal compensation. GB is/was a consultant for Orchard Therapeutics (2023), Passage Bio Inc (2020-2022), and Ionis (2019). She is/was a site investigator for the Alexander's disease trial of Ionis (2021-present), Metachromatic leukodystrophy of Shire/Takeda (2020-2021), Krabbe (2021-2023), and GM1 gene therapy trials (2021-present) of Passage Bio, GM1 natural history study from the University of Pennsylvania sponsored by Passage Bio (2021-present) and Adrenoleukodystrophy/Hematopoietic stem cell transplantation natural history study of Bluebird Bio (2019), and a site subinvestigator for the MPS II gene therapy trial of Regenxbio (2021-present) and the MPS II clinical trial of Denali (2022-present). She has received unrestricted educational grants from Takeda (2021-2022). All other authors did not have any potential conflicts of interest with respect to the research or publication of this article.

Contaminants of emerging concern (CEC) pose significant challenges to environmental and human health. The development of the wastewater reuse sector, coupled with progressively stringent regulations, needs innovative systems that integrate advanced treatment processes with in-situ and real-time monitoring of CEC. This study investigates the use of a tryptophan-like fluorescence sensor for real-time and online monitoring of CEC within a pilot plant employing O 3 -based advanced oxidation processes (AOPs). Two tertiary wastewater effluents (WW-1 and WW-2) were tested, placing the pilot system downstream of two different wastewater treatment plants (WWTPs). Priority substances and micropollutants detected in the investigated water matrixes such as pharmaceuticals, per- and polyfluoroalkyl substances (PFAS) were selected as targeted compounds in this study. Fluorescence degradation was detected in real-time by the sensor, showing a high capability to detect fast changes in water quality induced by oxidation. Furthermore, the real-time fluorescence showed better sensitivity than lab-scale fluorescence in detecting the fast action of hydroxyl radicals (·OH) during the O 3 /H 2 O 2 process, highlighting the importance of online monitoring. Selected CEC were degraded by AOPs with different percentages of removal efficiency (RE) (0%3 and ·OH. Fluorescence data by online sensor enabled accurate prediction of the removal of a wide spectrum of CEC during O 3 and O 3 /H 2 O 2 processes (R 2 ≥0.93). Furthermore, real-time fluorescence data were successfully used to predict observed pseudo-first-order rate constants of CEC with O 3 or O 3 /H 2 O 2 . Obtained results suggest that real-time fluorescence monitoring is an excellent tool to control CEC removal during O 3 -based AOPs and monitor the transferred ozone in wastewater (R 2 ≥0.94), contributing to the optimization of reagent dose, energy and costs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Pediatric intestinal pseudo-obstruction (PIPO) is a rare congenital disorder of the enteric nervous system with distal colon aganglionosis potentially leading to intestinal obstruction. Recently, biallelic variants in KIF26A, encoding a crucial motor protein for the migration and differentiation of enteric neural crest cells, have been associated with a neurodevelopmental condition featuring cortical defects and PIPO-like features, though in absence of aganglionosis. So far, only 10 patients have been reported. In this study, we investigated three subjects with congenital hydrocephalus, neurodevelopmental impairment, and intestinal obstruction megacolon syndrome. Brain MRI revealed malformations within cortical dysplasia spectrum, including polymicrogyria and heterotopia. Pathology study of the intestine revealed aganglionosis and elevated acetylcholinesterase activity in parasympathetic nerve fibers. Through trio-exome sequencing (ES), we detected four novel biallelic KIF26A variants, including two missense changes (#1) and two distinct homozygous truncating variants in (#2 and #3). All variants are rare and predicted to be deleterious according to in silico tools. To characterize the impact of the missense variants, we performed 3D protein modeling using Alphafold3 and YASARA. Mutants exhibited increased energy scores compared to wild-type protein, supporting a significant structural destabilization of the protein. Our study expands the genotype and phenotype spectrum of the emerging KIF26A-related disorder., (© 2024 The Author(s). Clinical Genetics published by John Wiley & Sons Ltd.)

Background: This study aimed to assess the distribution of esophageal inflammation in patients with eosinophilic esophagitis (EoE) and its impact on diagnosis and outcome., Aims and Methods: Data from consecutive adult EoE patients who were followed-up at four Italian referral centers from October 2022 to October 2023 were retrospectively collected., Results: One hundred forty-nine patients were included. Proximal EoE was observed in 8.1 % of patients; distal EoE in 27.5 %; and diffuse EoE in 64.4 %. Allergic rhinitis was more prevalent in distal and diffuse than proximal EoE (72.5 % vs. 61.5 % vs 33.3 %; P = 0.049). The prevalence of asthma, atopic dermatitis, oral allergy syndrome, and gastroesophageal reflux disease was not significantly different among the three EoE extent groups. Endoscopic inflammatory features at diagnosis were more prevalent in proximal EoE (91.7 % vs. 53.8 % distal [P = 0.01] vs. 66 % diffuse[P = 0.05]). No significant differences in fibrotic features and esophageal stenoses were observed. The clinical and histological remission rates after first-line therapy were comparable in all groups., Conclusion: Esophageal inflammation in EoE more frequently involves the entire esophagus, followed by isolated distal and proximal involvement. No clear correlation was observed between the histological extent of EoE at diagnosis and comorbidities or treatment response., Competing Interests: Declaration of competing interest Edoardo Vincenzo Savarino has served as speaker for Abbvie, Abivax, Agave, AGPharma, Alfasigma, CaDiGroup, Celltrion, Dr Falk, EG Stada Group, Fenix Pharma, Galapagos, Johnson&Johnson, JB Pharmaceuticals, Innovamedica/Adacyte, Eli Lilly, Malesci, Mayoly Biohealth, Omega Pharma, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots, Unifarco; has served as consultant for Abbvie, Agave, Alfasigma, Biogen, Bristol-Myers Squibb, Celltrion, Dr. Falk, Eli Lilly, Fenix Pharma, Johnson&Johnson, JB Pharmaceuticals, Merck & Co, Nestlè, Pfizer, Reckitt Benckiser, Regeneron, Sanofi, SILA, Sofar, Takeda, Unifarco; he received research support from Bonollo, Difass, Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco, Zeta Farmaceutici; Nicola de Bortoli has served as speaker for: Reckitt-Benkiser, Malesci, Sofar, Dr Falk. Advisory Board: Astra-Zenecahe; the other authors have no disclosures to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Among the tumors with the highest lethality, gliomas are primary brain tumors associated with common recurrence inclined to metastasize along the neuraxis and occasionally out of the central nervous system. Even though metastasis is the main responsible for death in oncological patients, few dedicated treatments are approved. Therefore, the establishment of effective anti-metastasis agents is the final frontier in cancer research. Interestingly, some copper complexes have demonstrated promising efficacy as antimetastatic agents, but they may cause off-site effects such as the alteration of copper homeostasis in healthy tissues. Thus, the incorporation of copper-based antimetastatic agents in rationally designed nano-architectures can increase the treatment localization reducing the side effects. Here, copper complex loaded hybrid nano-architectures (CuLNAs) are presented and employed to assess the impact of an intracellular copper source on glioma cell invasiveness. The novel CuLNAs are fully characterized and exploited for cell migration modulation in a glioma cell line. The results demonstrate that CuLNAs significantly reduce cell migration without impairing cell proliferation compared to standard gold and copper NAs. A concomitant antimigratory-like regulation of the epithelial-to-mesenchymal transition genes confirmed these results, as the gene encoding for the epithelial protein E-cadherin was upregulated and the other explored mesenchymal genes were downregulated. These findings, together with the intrinsic behaviors of NAs, demonstrate that the inclusion of metal complexes in the nano-architectures is a promising approach for the composition of a family of agents with antimetastatic activity., Competing Interests: Declaration of Competing Interest The Authors declare no competing financial interests that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The influence of high positive end-expiratory pressure (PEEP) with recruitment maneuvers on the occurrence of postoperative pulmonary complications after surgery is still not definitively established. Bayesian analysis can help to gain further insights from the available data and provide a probabilistic framework that is easier to interpret. The objective was to estimate the posterior probability that the use of high PEEP with recruitment maneuvers is associated with reduced postoperative pulmonary complications in patients with intermediate-to-high risk under neutral, pessimistic, and optimistic expectations regarding the treatment effect., Methods: Multilevel Bayesian logistic regression analysis was performed on individual patient data from three randomized clinical trials carried out on surgical patients at intermediate to high risk for postoperative pulmonary complications. The main outcome was the occurrence of postoperative pulmonary complications in the early postoperative period. This study examined the effect of high PEEP with recruitment maneuvers versus low PEEP ventilation. Priors were chosen to reflect neutral, pessimistic, and optimistic expectations of the treatment effect., Results: Using a neutral, pessimistic, or optimistic prior, the posterior mean odds ratio for high PEEP with recruitment maneuvers compared to low PEEP was 0.85 (95% credible interval, 0.71 to 1.02), 0.87 (0.72 to 1.04), and 0.86 (0.71 to 1.02), respectively. Regardless of prior beliefs, the posterior probability of experiencing a beneficial effect exceeded 90%. Subgroup analysis indicated a more pronounced effect in patients who underwent laparoscopy (odds ratio, 0.67 [0.50 to 0.87]) and those at high risk for postoperative pulmonary complications (odds ratio, 0.80 [0.53 to 1.13]). Sensitivity analysis, considering severe postoperative pulmonary complications only or applying a different heterogeneity prior, yielded consistent results., Conclusions: High PEEP with recruitment maneuvers demonstrated a moderate reduction in the probability of postoperative pulmonary complication occurrence, with a high posterior probability of benefit observed consistently across various prior beliefs, particularly among patients who underwent laparoscopy., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Background: Transoral robotic surgery (TORS) performed after neoadjuvant chemotherapy (NAC) is a promising treatment for advanced-stage oropharyngeal carcinoma (OPSCC) able to reduce the adjuvant therapy administration rate., Methods: A retrospective bi-centric study was conducted to analyze NAC + TORS versus upfront TORS patients. A 1:1 propensity score matching was used to compare the two groups., Results: Among the 300 patients with stage III-IV OPSCC, 204 patients were matched for comparing NAC + TORS versus upfront TORS. Between the two groups, no significant difference was observed in recurrences and in survival for RFS, OS, and DSS. In the NAC + TORS p16-positive population, adjuvant therapy could be spared in 51% versus 16% in the upfront surgery cohort (p < 0.001) due to the lower frequency of pathological risk factors after NAC., Conclusions: NAC followed by TORS for locoregionally advanced OPSCC demonstrated to achieve non-inferior survival outcomes to upfront surgery, while in the p16-positive population allowed to significantly spare adjuvant therapy., (© 2024 Wiley Periodicals LLC.)

Aim: Gastrointestinal medullary carcinoma is a rare histologic subtype of adenocarcinoma. As nonampullary small bowel medullary carcinomas (SB-MCs) are poorly characterized, we aimed to analyse their clinicopathologic and immunohistochemical features and to compare them with nonmedullary small bowel adenocarcinomas (NM-SBAs)., Methods and Results: Surgically resected SBAs collected through the Small Bowel Cancer Italian Consortium were classified as SB-MCs (carcinomas with ≥50% of tumour fulfilling the typical histologic criteria of MC) or NM-SBAs. Immunohistochemistry for cytokeratin (CK)7, CK20, CDX2, programmed death-ligand 1 (PD-L1) and mismatch repair proteins was performed in both SB-MCs and NM-SBAs. SB-MCs were also tested for CK8/18, synaptophysin, SMARCB1, SMARCA2, SMARCA4, and ARID1A and for Epstein-Barr virus (EBV)-encoded RNAs by in-situ hybridization. MLH1 promoter methylation status was evaluated in MLH1-deficient cases. Eleven SB-MCs and 149 NM-SBAs were identified. One (9%) SB-MC was EBV-positive, while 10 (91%) harboured mismatch repair deficiency (dMMR). MLH1 promoter hypermethylation was found in all eight dMMR SB-MCs tested. Switch/sucrose nonfermentable deficiency was seen in two (18%) SB-MCs, both with isolated loss of ARID1A. Compared with NM-SBAs, SB-MCs exhibited an association with coeliac disease (P < 0.001), higher rates of dMMR (P < 0.001), and PD-L1 positivity by both tumour proportion score and combined positive score (P < 0.001 for both), and a lower rate of CK20 expression (P = 0.024). Survival analysis revealed a better prognosis of SB-MC patients compared to NM-SBA cases (P = 0.02)., Conclusion: SB-MCs represent a distinct histologic subtype, with peculiar features compared to NM-SBAs, including association with coeliac disease, dMMR, PD-L1 expression, and better prognosis., (© 2024 The Author(s). Histopathology published by John Wiley & Sons Ltd.)

Objectives: The revised European Society of Musculoskeletal Radiology (ESSR) consensus guidelines on soft tissue tumor imaging represent an update of 2015 after technical advancements, further insights into specific entities, and revised World Health Organization (2020) and AJCC (2017) classifications. This second of three papers covers algorithms once histology is confirmed: (1) standardized whole-body staging, (2) special algorithms for non-malignant entities, and (3) multiplicity, genetic tumor syndromes, and pitfalls., Materials and Methods: A validated Delphi method based on peer-reviewed literature was used to derive consensus among a panel of 46 specialized musculoskeletal radiologists from 12 European countries. Statements that had undergone interdisciplinary revision were scored online by the level of agreement (0 to 10) during two iterative rounds, that could result in 'group consensus', 'group agreement', or 'lack of agreement'., Results: The three sections contain 24 statements with comments. Group consensus was reached in 95.8% and group agreement in 4.2%. For whole-body staging, pulmonary MDCT should be performed in all high-grade sarcomas. Whole-body MRI is preferred for staging bone metastasis, with [ 18 F]FDG-PET/CT as an alternative modality in PET-avid tumors. Patients with alveolar soft part sarcoma, clear cell sarcoma, and angiosarcoma should be screened for brain metastases. Special algorithms are recommended for entities such as rhabdomyosarcoma, extraskeletal Ewing sarcoma, myxoid liposarcoma, and neurofibromatosis type 1 associated malignant peripheral nerve sheath tumors. Satisfaction of search should be avoided in potential multiplicity., Conclusion: Standardized whole-body staging includes pulmonary MDCT in all high-grade sarcomas; entity-dependent modifications and specific algorithms are recommended for sarcomas and non-malignant soft tissue tumors., Clinical Relevance Statement: These updated ESSR soft tissue tumor imaging guidelines aim to provide support in decision-making, helping to avoid common pitfalls, by providing general and entity-specific algorithms, techniques, and reporting recommendations for whole-body staging in sarcoma and non-malignant soft tissue tumors., Key Points: An early, accurate, diagnosis is crucial for the prognosis of patients with soft tissue tumors. These updated guidelines provide best practice expert consensus for standardized imaging algorithms, techniques, and reporting. Standardization can improve the comparability examinations and provide databases for large data analysis., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is Univ.-Prof. Priv.-Doz. Dr. I.M.N.H. Conflict of interest: A.B. is a member of the European Radiology Editorial Board. He has not taken part in the review or selection process of this article. The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and biometry: No complex statistical methods were necessary for this paper. Informed consent: Written informed consent was not required for this study because patients were not involved. Ethical approval: Institutional Review Board approval was not required because patients were not involved. Study subjects or cohorts overlap: Study subjects or cohorts have not been previously reported. Methodology: Expert consensus is performed by a Delphi process Perspective: not applicable Study design: not applicable Location: multicentre study, (© 2024. The Author(s).)

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., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)