IRCCS Humanitas Research Hospital

Hemoptysis is a potentially life-threatening symptom that often prompts emergency department (ED) evaluation and hospitalization. Reliable prognostic tools to guide clinical decision-making and optimize resource use are currently lacking. To prospectively validate the Florence Hemoptysis Assessment Score (FLHASc) in patients presenting with hemoptysis to the ED, and to eventually derive and validate an improved version of the score (FLHASc2). We analyzed data from the POPEIHE study (NCT06067997), a multicenter prospective cohort of 546 consecutive adult patients presenting with hemoptysis to 9 Italian EDs. The primary outcome was a composite of in-hospital death, need for ventilatory support, intensive care unit (ICU) admission, blood transfusion, or invasive hemostatic procedures. We evaluated the prognostic performance of the original FLHASc, then derived a new model (FLHASc2) using multivariate logistic regression in a randomly selected derivation cohort (n=321) and validated it in the remaining cohort (n=225). A simplified version of the score was also tested. The original FLHASc demonstrated moderate discriminatory ability (AUC 0.71; 95% CI: 0.65-0.76) and suboptimal calibration. The FLHASc2 showed improved performance (AUC 0.79, 95% CI: 0.73-0.87 in derivation and 0.81, 95% CI: 0.73-0.88, in validation cohorts; Brier score<0.10 in both). The simplified FLHASc2 (sFLHASc2), assigning one point per variable, maintained comparable accuracy (AUC 0.80, 95% CI: 0.72-0.87) and identified 47.8% of patients as low risk (2.7% event rate). When combined with a negative chest X-ray, the observed event rate in this subgroup dropped to 0.87%, with a negative predictive value of 99.1% (CI 95%, 96.5-100%). The FLHASc2 and its simplified version are accurate prognostic tools for identifying hemoptysis patients at low risk of short-term adverse outcomes. Use of the sFLHASc2 combined with chest X-ray may allow safe ED discharge in nearly half of cases. A prospective management trial is warranted to confirm its clinical impact. NCT06067997.

Dopaminergic (DA) neurons of the olfactory bulb (OB) represent one of the largest forebrain DA populations, and increasing evidence highlights their role in shaping odor representations through presynaptic gain control, lateral inhibition, and circuit plasticity. These neurons are heterogeneous, comprising small, axonless cells generated throughout life and larger, axon-bearing cells whose generation is limited to embryonic and perinatal stages. Establishing functional distinctions between these subtypes has been hindered by limited tools for selective targeting. Here, we developed an adeno-associated viral (AAV) strategy using the tyrosine hydroxylase (TH) promoter to drive Cre recombinase expression (AAV-rTH-Cre), enabling temporally controlled labeling of OB DA neurons. Intracerebroventricular injections at embryonic day 14.5 preferentially enriched the targeted DA population in large cells, while adult injections predominantly targeted small DA neurons, consistent with their developmental origins. Neonatal injections yielded reduced specificity, likely reflecting developmental and technical constraints on TH promoter activity. To assess functional properties, we combined AAV-rTH-Cre with Cre-dependent GCaMP7s and performed two-photon calcium imaging in adult mice. Our data revealed significant heterogeneity in spontaneous activity, showing a negative correlation between soma size and both spiking probability and event frequency. Thus, smaller DA neurons exhibited higher spontaneous activity, whereas larger neurons were less active despite their higher intrinsic excitability reported previously. These findings validate AAV-rTH-Cre as a versatile tool for dissecting OB DA subtypes and provide direct in vivo evidence that their morphological diversity translates into distinct spontaneous activity patterns, supporting the hypothesis of complementary roles in olfactory processing.

Asthma is a chronic inflammatory airway disease characterized by variable airflow obstruction and bronchial hyperresponsiveness, affecting millions worldwide and showing heterogeneity in its endotype, clinical presentation, and severity. Following the principles of modern precision medicine, studying an asthmatic patient involves collecting various biomarkers that may assist in diagnosis, management, and characterization of the disease to predict clinical outcomes and treatment responses. Although systemic corticosteroid use should be limited to specific situations, this therapy still plays a crucial role in managing an asthmatic patient, especially during exacerbations. While it is known that steroids can affect biomarkers, the extent of this impact is often unclear. This remains an open issue, particularly in patients with severe asthma, where systemic steroids are more frequently used and biomarker measurement can deeply influence management and even access to therapy. Misinterpreting biomarkers can lead to over- or underestimating asthma severity, potentially resulting in serious consequences. In this comprehensive analysis, we have collected the available literature data on how systemic corticosteroids can affect different biomarkers used in clinical practice and research setting, categorizing them into humoral (eg, blood eosinophil count, total and specific IgE, alfa-1 antitrypsin, interleukins, eosinophil cationic protein, and thymic stromal lymphopoietin), instrumental (eg, spirometry, impulse oscillometry, fractional and multiple flow exhaled nitric oxide, and nasal nitric oxide), and clinical (ear-nose-throat and gastroenterological evaluation). The goal is to provide a practical and concise overview of this impact to assist clinicians in interpreting biomarkers independently of steroid therapy. Research should focus on developing predictive models that adjust individual biomarker readings for steroid dosage and duration, as well as markers less affected by corticosteroid interference. A detailed understanding of steroid-induced biomarker modulation is crucial for accurate asthma phenotyping, personalized treatment choices, and avoiding adverse outcomes caused by both under- and overtreatment. Going forward, integrating improved biomarker correction methods, enhancing patient education on steroid use, and continuing research into new inflammatory markers will be crucial for improving the accuracy and effectiveness of asthma management.

Chronic hand eczema (CHE) is associated with substantial functional impairment and reduced quality of life. Delgocitinib, a pan-Janus kinase (JAK) inhibitor, has emerged as a promising topical treatment for CHE. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to assess the efficacy and safety of topical delgocitinib 20-30 mg/g compared with vehicle in patients with CHE. PubMed, Embase, Cochrane Library, ClinicalTrials.gov, EU CTR, and WHO ICTRP were searched up to 15 February 2026. The primary outcome was treatment success at week 16, defined as clear or almost clear skin with a ≥ 2-point improvement on the Investigator's or Physician's Global Assessment (IGA/PGA). Secondary outcomes included treatment success at weeks 4 and 8, changes in Hand Eczema Symptom Diary (HESD) itch and pain scores, and safety outcomes. Relative risks (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated using random-effects models. Three publications reporting four RCTs involving 1154 patients were included, with 752 receiving delgocitinib and 402 receiving vehicle. At week 16, treatment success was significantly higher with delgocitinib (RR 3.17; 95% CI 1.78-5.65; p < 0.01), corresponding to an absolute risk difference of 16.9% and a number needed to treat (NNT) of 6 (95% CI 3-16). Similar results at weeks 4 and 8. Delgocitinib also led to significantly greater improvements in HESD itch and pain scores. No significant differences were found in overall adverse events (AEs), treatment-related AEs, or serious AEs. Discontinuation due to AEs was lower in the delgocitinib group. Delgocitinib 20-30 mg/g demonstrated greater efficacy than vehicle and a favourable safety profile, supporting its use as a topical treatment for CHE.

Mentalising skills may be conceptualised as composed by both personal and interpersonal competencies, in turn shaped by early adverse experiences and coping strategies. Although cross-sectional observations described a role for mentalising skills in burnout development, large-scale longitudinal studies on the topic remain limited, especially in relation to psychiatry training. The primary aim was to investigate protective and risk factors for higher burnout scores across time. Secondary aims included testing whether psychiatry exhibited different burnout scores across time in comparison to other medical residents. A cohort of 1803 medical residents (1131 psychiatry residents) was assessed for mentalising skills, conceptualised as composed of emotional regulation (Difficulties in Emotion Regulation Scale), interpersonal competencies (Interpersonal Competence Questionnaire), coping strategies (Coping Orientation to Problems Experienced) and burnout dimensions (Maslach Burnout Inventory). One-year follow-up was available for 520 psychiatry residents (73.03% response rate) and 234 other medical residents (35.94% response rate). Longitudinal mixed models and bivariate latent change models were employed. Across all residents, greater levels of burnout were associated with higher scores in insecure attachment, emotional dysregulation and maladaptive coping, as well as lower scores in interpersonal skills. Attending at least one supervision per month was associated with lower burnout scores across time. According to a bivariate latent change model, emotional regulation improvements through years were associated with lower burnout scores across time. In psychiatry residents, lower burnout scores across time were observed as compared to other medical residents. Psychiatry residents benefited from a higher protective effect of interpersonal competencies (group by moderator by time interaction) and coping strategies against burnout. Mentalising skills may mitigate burnout development. Training in psychiatry emerged as a potential mitigating factor against burnout increases. Structured supervisions may foster professional development and emotional resilience.

The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.