Predictors of Response to Hydroxyurea and Switch to Ruxolitinib in HU-Resistant Polycythaemia VERA Patients: A Real-World PV-NET Study

: In polycythemia vera (PV), the prognostic relevance of an ELN-defined complete response (CR) to hydroxyurea (HU), the predictors of response, and patients' triggers for switching to ruxolitinib are uncertain. In a real-world analysis, we evaluated the predictors of response, their impact on the clinical outcomes of CR to HU, and the correlations between partial or no response (PR/NR) and a patient switching to ruxolitinib. Among 563 PV patients receiving HU for ≥12 months, 166 (29.5%) achieved CR, 264 achieved PR, and 133 achieved NR. In a multivariate analysis, the absence of splenomegaly (p = 0.03), pruritus (p = 0.002), and a median HU dose of ≥1 g/day (p < 0.001) remained associated with CR. Adverse events were more frequent with a median HU dose of ≥1 g/day. Overall, 283 PR/NR patients (71.3%) continued HU, and 114 switched to ruxolitinib. In the 449 patients receiving only HU, rates of thrombosis, hemorrhages, progression, and overall survival were comparable among the CR, PR, and NR groups. Many PV patients received underdosed HU, leading to lower CR and toxicity rates. In addition, many patients continued HU despite a PR/NR; however, splenomegaly and other symptoms were the main drivers of an early switch. Better HU management, standardization of the criteria for and timing of responses to HU, and adequate intervention in poor responders should be advised

HEBE project: Healthy aging versus inflamm-aging: The role of physical exercise in modulating the biomarkers of age-associated and environmentally determined chronic diseases, study protocol

Inflamm-aging refers to the chronic low-grade inflammation that occurs with aging and cellular senescence, and it is linked to various diseases. Understanding the markers involved in inflammation and aging, as well as their interaction with environmental factors and bodily control mechanisms, can provide crucial tools for assessing the resilience (i.e. the ability to adapt and improve) of the human body, particularly in the presence of chronic degenerative conditions or vulnerable life stages, that place the individual and the community to which he belongs in a state of potential fragility. HEBE focuses on physical exercise, along with nutritional and lifestyle recommendations, to reduce systemic inflammation and promote healthy aging. HEBE encompasses multiple research lines (LR). In the ongoing LR1 (“proof of concept”), healthy lifestyle recommendations were provided to University of Milan employees, and changes in quality of life and well-being were assessed using a specialized questionnaire. The first 100 eligible subjects, who expressed their willingness to participate, underwent a personalized physical exercise protocol based on clinical and objective assessments. Biomedical samples were collected at baseline (T0) and follow-up (T1) to establish a shared biobank and identify non-invasive biomarkers that monitor the impact of physical exercise on individual characteristics such as cardiovascular and metabolic health. Subsequently (LR2-LR10), the proof of concept findings will be expanded to include various conditions of vulnerability such as obesity, cancer, endocrine disorders, cardiovascular diseases, infertility, functional syndromes, respiratory disorders, neurodegenerative diseases, and autoimmune conditions. The research lines will leverage the expertise of the 94 participating investigators to form a collaborative network that maximizes the potential for investigation and knowledge exchange. This approach fosters a culture of health promotion and disease prevention

A Computational Thermo-Fluid Dynamics Simulation of Slot Jet Impingement Using a Generalized Two-Equation Turbulence Model

In this study, a computational thermo-fluid dynamics simulation of a wide-slot jet impingement heating process is performed. The present configuration consists of a turbulent incompressible air jet impinging orthogonally on an isothermal cold plate at a Reynolds number of around 11,000. The two-dimensional mean turbulent flow field is numerically predicted by solving Reynolds-averaged Navier–Stokes (RANS) equations, where the two-equation eddy viscosity k-ω model is utilized for turbulence closure. As the commonly used shear stress transport variant overpredicts heat transfer at the plate due to excessive turbulent diffusion, the recently developed generalized k-ω (GEKO) model is considered for the present analysis, where the primary model coefficients are suitably tuned. Through a comparative analysis of the various solutions against one another, in addition to reference experimental and numerical data, the effectiveness of the generalized procedure in predicting both the jet flow characteristics and the heat transfer at the plate is thoroughly evaluated, while determining the optimal set of model parameters. By improving accuracy within the RANS framework, the importance of model adaptability and parameter tuning for this specific fluid engineering application is demonstrated. This study offers valuable insights for improving predictive capability in turbulent jet simulations with broad engineering implications, particularly for industrial heating or cooling systems relying on wide-slot jet impingement

Foreign Body Aspiration in Children—Diagnostic Clues through a Clinical Case

Foreign body aspiration is common in the pediatric age group, especially in males. Despite the high frequency of this potentially life-threatening event, it is not always easy to recognize it given the high variability of the clinical presentation and the potential of “pauci-symptomatic” inhalation. Moreover, a variable latency of the onset of symptoms since the moment of aspiration may be possible determining difficulties in the identification of the inhalation on an anamnestic basis. We describe the case of a 19-month-old boy who accessed the emergency room initially for a head trauma. The clinical evaluation, however, revealed an unexplained serious respiratory distress needing tracheal intubation. After our evaluation, we hypothesized that the severe respiratory distress determined an altered state of consciousness with following head trauma. The radiological findings raised the suspicion of foreign body aspiration for the presence of an atelectasis of the entire left lung. The computed tomography showed an abrupt interruption of the main bronchus at 12 mm from the hull. The following bronchoscopy identified an almond of 2 cm. We will review the literature to underline the diagnostic issues behind foreign body aspiration in children by highlighting the diagnostic clues that are helpful for emergency clinicians in the management of this condition.</jats:p

Foreign Body Aspiration in Children&mdash;Diagnostic Clues through a Clinical Case

Foreign body aspiration is common in the pediatric age group, especially in males. Despite the high frequency of this potentially life-threatening event, it is not always easy to recognize it given the high variability of the clinical presentation and the potential of &ldquo;pauci-symptomatic&rdquo; inhalation. Moreover, a variable latency of the onset of symptoms since the moment of aspiration may be possible determining difficulties in the identification of the inhalation on an anamnestic basis. We describe the case of a 19-month-old boy who accessed the emergency room initially for a head trauma. The clinical evaluation, however, revealed an unexplained serious respiratory distress needing tracheal intubation. After our evaluation, we hypothesized that the severe respiratory distress determined an altered state of consciousness with following head trauma. The radiological findings raised the suspicion of foreign body aspiration for the presence of an atelectasis of the entire left lung. The computed tomography showed an abrupt interruption of the main bronchus at 12 mm from the hull. The following bronchoscopy identified an almond of 2 cm. We will review the literature to underline the diagnostic issues behind foreign body aspiration in children by highlighting the diagnostic clues that are helpful for emergency clinicians in the management of this condition

Risk of burnout and stress in physicians working in a COVID team: A longitudinal survey

Background and aims The COVID-19 pandemic represents a source of stress and potential burnout for many physicians. This single-site survey aimed at assessing perceived stress and risk to develop burnout syndrome among physicians operating in COVID wards. Methods This longitudinal survey evaluated stress and burnout in 51 physicians operating in the COVID team of Gemelli Hospital, Italy. Participants were asked to complete the Maslach Burnout Inventory (MBI) and the Perceived Stress Questionnaire on a short run (PSQs) (referring to the past 7 days) at baseline (T0) and then for four weeks (T1-T4). Perceived Stress Questionnaire on a long run (PSQl) (referring to the past 2 years) was completed only at T0. Results Compared with physicians board-certified in internal medicine, those board-certified in other disciplines showed higher scores for the Emotional Exhaustion (EE) score of the MBI scale (P &lt; .001). Depersonalisation (DP) score showed a reduction over time (P = .002). Attending physicians scored lower than the resident physicians on the DP scale (P = .048) and higher than resident physicians on the Personal Accomplishment (PA) scale (P = .04). PSQl predicted higher scores on the EE scale (P = .003), DP scale (P = .003) and lower scores on the PA scale (P &lt; .001). PSQs showed a reduction over time (P = .03). Attending physicians had a lower PSQs score compared with the resident physicians (P = .04). Conclusions Medical specialty and clinical position could represent risk factors for the development of burnout in a COVID team. In these preliminary results, physicians board-certified in internal medicine showed lower risk of developing EE during the entire course of the study

Make Mission Impossible Feasible: The Experience of a Multidisciplinary Team Providing Treatment for Alcohol Use Disorder to Homeless Individuals

Abstract Aim People experiencing homelessness are often excluded from treatment programs for alcohol use disorder (AUD). The goal of this study was to describe the impact of a multidisciplinary treatment program on alcohol consumption and social reintegration in individuals with AUD experiencing homelessness. Methods Thirty-one individuals with AUD experiencing homelessness were admitted to an inpatient unit for 5–6 days for clinical evaluation and to treat potential alcohol withdrawal syndrome. A group of volunteers, in collaboration with the Community of Sant’Egidio, provided social support aimed to reintegrate patients. After inpatient discharge, all patients were followed as outpatients. Alcohol intake (number drinks/day), craving and clinical evaluation were assessed at each outpatient visit. Biological markers of alcohol use were evaluated at enrollment (T0), at 6 months (T1) and 12 months (T2). Results Compared with T0, patients at T1 showed a significant reduction in alcohol consumption [10 (3–24) vs 2 (0–10); P = 0.015] and in γ-glutamyl-transpeptidase [187 (78–365) vs 98 (74–254); P = 0.0021]. The reduction in alcohol intake was more pronounced in patients with any housing condition [10 (3–20) vs 1 (0–8); P = 0.008]. Similarly, compared with T0, patients at T2 showed significant reduction in alcohol consumption [10 (3–24) vs 0 (0–15); P = 0.001], more pronounced in patients with any housing condition [10 (3–20) vs 0 (0–2); P = 0.006]. Moreover, at T2 patients showed a significant reduction in γ-glutamyl-transpeptidase [187 (78–365) vs 97 (74–189); P = 0.002] and in mean cell volume [100.2 (95–103.6) vs 98.3 (95–102); P = 0.042]. Conclusion Patients experiencing homelessness may benefit from a multidisciplinary treatment program for AUD. Strategies able to facilitate and support their social reintegration and housing can improve treatment outcomes. </jats:sec