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Background Preventive dental care, despite its well-established benefits, is underutilized in many jurisdictions, including Italy, where a curative approach often prevails. An international KAP survey (Italy, Switzerland, Serbia, India, Argentina, Spain) was planned to assess the dentists’ knowledge, attitudes, and barriers to preventive care, exploring the influence of age and gender, alongside factors like revenues and time. The present study specifically reports on the data collected from the Italian cohort, serving as a pilot within this broader international endeavour. Methods A cross-sectional survey on Italian dentists was conducted. The questionnaire, originally in English, underwent back-translation to ensure linguistic accuracy before evaluating knowledge, attitudes, and barriers. The data collected via Google Forms were analysed using STATA ® 18.0, with descriptive statistics, contingency table analysis, Cuzick’s test and multinomial logistic regression being used. Results Three-hundred-twenty-two questionnaires were completed (65.8% male, 34.2% female), with the 46–65 age group being the largest (50%). The distribution of participants across dental specialties varied significantly by gender: female dentists predominated in Pediatric Dentistry (84.6%) and Orthodontics (61.1%), while males were more prevalent in Oral Surgery (87.18%). Age significantly impacted knowledge of sugar intake ( p  = 0.04) and fluoride use ( p  < 0.01), with younger dentists showing higher knowledge. Knowledge on sealant application was significantly higher among males compared to females ( p  = 0.04). Age affected attitudes toward smoking cessation and providing oral hygiene instruction ( p  < 0.01). Males reported higher remuneration concerns ( p  = 0.03). Multinomial logistic regression identified female gender, first visit age, sugar consumption knowledge, and perceived knowledge deficit as significant predictors of the age-knowledge interaction. Conclusions Statistically significant age and gender disparities exist in knowledge, attitudes, and barriers to preventive dental care among Italian dentists. Younger dentists demonstrated superior preventive knowledge, while older dentists perceived greater knowledge deficits. Gender influenced knowledge and remuneration concerns. Educational interventions and policy changes are needed to integrate preventive practices, addressing age and gender-specific needs.

In the automotive industry, the measurement, control and reproducibility of certain morphological characteristics of surfaces are important to characterize, qualify, certify and optimize different physical properties, such as the degree of wear, the degree of adhesion by adhesives, glues or paints and optical properties. In this regard, this work is intended demonstrate how it is possible to characterize different surfaces in ABS (Acrylonitrile Butadiene Styrene) and PC-ABS (PolyCarbonate/Acrylonitrile Butadiene Styrene) through a set of morphological parameters defined according to the ISO 25178 standard. These surfaces have been subjected to different etching treatments performed with different chemicals, which can radically modify the morphology of the surface, making it more or less suitable according to the industrial purposes sought. Furthermore, in this work an analytical relationship between the hybrid parameters Sdq and Sdr defined in the ISO-25718 standard is also proposed, valid for many surfaces of general use. This study is based on the use of a confocal optical microscope and a SEM (Scanning Electron Microscope), which allow surface morphology to be studied at the micro/nano scale and the measurements are analyzed with special imaging and three-dimensional scanning software that allows the precise measurement of morphological parameters of the standard ISO-25178.

Recommendations for dyslipidemia management aimed at reducing arterial occlusive events (AOEs) have been recently published. So far, no data have been reported on the management of dyslipidemia in chronic myeloid leukemia (CML) patients treated with nilotinib. We investigated 369 CML adult patients, stratified according to the new Systematic Coronary Risk Evaluation (SCORE) scoring system. Plasma levels of cholesterol, HDL, LDL, and triglycerides were measured prior to the start of nilotinib and after 3, 6, and 12 months. The 5-year cumulative incidence of AOEs was 15.9%. Patients with cholesterol levels > 200 mg/dL and LDL > 70 mg/dL 3 months after treatment showed a significantly higher incidence of AOEs (21.9 ± 4.6% vs 6.2 ± 2.5, P = 0.003). Patients belonging to the high and very high SCORE risk group showed a significant increase of AOEs (34.4 ± 6% vs 10 ± 2.1%, P < 0.001). In multivariate analysis, both high cholesterol and LDL levels and a high and very high SCORE risk remained significantly associated with the risk of AOEs (P = 0.008; HR = 3.5; 95% CI = 1.4–8.7 and P < 0.001; HR = 4.4; 95% CI = 2–9.8, respectively). Overall, 78 patients (21.1%) presented dyslipidemia at the time of CML diagnosis and 88 (23.3%) after starting nilotinib, but only 26 of them (29.5%) were treated with statins.Low LDL and cholesterol plasma levels are associated with a significant lower risk of AOEs in CML patients treated with nilotinib in the real life.

Treatment‐free remission (TFR) by tyrosine kinase inhibitors (TKI) discontinuation in patients with deep molecular response (DMR) is a paramount goal in the current chronic myeloid leukemia (CML) therapeutic strategy. The best DMR level by real‐time quantitative PCR (RT‐qPCR) for TKI discontinuation is still a matter of debate. To compare the accuracy of digital PCR (dPCR) and RT‐qPCR for BCR‐ABL1 transcript levels detection, 142 CML patients were monitored for a median time of 24 months. Digital PCR detected BCR‐ABL1 transcripts in the RT‐qPCR undetectable cases. The dPCR analysis of the samples, grouped by the MR classes, revealed a significant difference between MR4.0 and MR4.5 (P = 0.0104) or MR5.0 (P = 0.0032). The clinical and hematological characteristics of the patients grouped according to DMR classes (MR4.0 vs MR4.5‐5.0) were superimposable. Conversely, patients with dPCR values <0.468 BCR‐ABL1 copies/µL (as we previously described) showed a longer DMR duration (P = 0.0220) and mainly belonged to MR4.5‐5.0 (P = 0.0442) classes compared to patients with higher dPCR values. Among the 142 patients, 111 (78%) discontinued the TKI treatment; among the 111 patients, 24 (22%) lost the MR3.0 or MR4.0. RT‐qPCR was not able to discriminate patients with higher risk of MR loss after discontinuation (P = 0.8100). On the contrary, according to dPCR, 12/25 (48%) patients with BCR‐ABL1 values ≥0.468 and 12/86 (14%) patients with BCR‐ABL1 values <0.468 lost DMR in this cohort, respectively (P = 0.0003). Treatment‐free remission of patients who discontinued TKI with a dPCR <0.468 was significantly higher compared to patients with dPCR ≥ 0.468 (TFR at 2 years 83% vs 52% P = 0.0017, respectively). In conclusion, dPCR resulted in an improved recognition of stable DMR and of candidates to TKI discontinuation. In this study, we compared the accuracy of digital PCR (dPCR) and RT‐qPCR for BCR‐ABL1 transcript levels detection by monitoring 142 CML patients for a median time of 24 months. The clinical and hematological characteristics of the patients grouped according to DMR classes (MR4.0 vs MR4.5‐5.0) were superimposable, while patients with dPCR values <0.468 BCR‐ABL1 copies/µL (as we previously described) showed a longer DMR duration (P = 0.02) and mainly belonged to MR4.5‐5.0 (P = 0.044) classes compared to patients with higher dPCR values. Among the 142 patients, 111 (78%) discontinued the TKI treatment and 24 (22%) among the 111 patients lost the MR3.0 or MR4.0: according to dPCR, 12/25 (48%) and 12/86 (14%) had BCR‐ABL1 values ≥0.468 and <0.468, respectively (P = 0.0003); on the contrary, RT‐qPCR was not able to discriminate patients with higher risk of MR loss after discontinuation (P = 0.81). In conclusion, dPCR resulted in an improved recognition of stable DMR and of candidates to TKI discontinuation.

High Mobility Group 1 protein (HMGB1) is a chromatin component that, when leaked out by necrotic cells, triggers inflammation. HMGB1 can also be secreted by activated monocytes and macrophages, and functions as a late mediator of inflammation. Secretion of a nuclear protein requires a tightly controlled relocation program. We show here that in all cells HMGB1 shuttles actively between the nucleus and cytoplasm. Monocytes and macrophages acetylate HMGB1 extensively upon activation with lipopolysaccharide; moreover, forced hyperacetylation of HMGB1 in resting macrophages causes its relocalization to the cytosol. Cytosolic HMGB1 is then concentrated by default into secretory lysosomes, and secreted when monocytic cells receive an appropriate second signal.

In patients with low-risk polycythemia vera, exposure to low-dose Ropeginterferon alfa-2b (Ropeg) 100 µg every 2 weeks for 2 years was more effective than the standard treatment of therapeutic phlebotomy in maintaining target hematocrit (HCT) (< 45%) with a reduction in the need for phlebotomy without disease progression. In the present paper, we analyzed drug survival, defined as a surrogate measure of the efficacy, safety, adherence, and tolerability of Ropeg in patients followed up to 5 years. During the first 2 years, Ropeg and phlebotomy-only (Phl-O) were discontinued in 33% and 70% of patients, respectively, for lack of response (12 in the Ropeg arm vs. 34 in the Phl-O arm) or adverse events (6 vs. 0) and withdrawal of consent in (3 vs. 10). Thirty-six Ropeg responders continued the drug for up to 3 years, and the probability of drug survival after a median of 3.15 years was 59%. Notably, the primary composite endpoint was maintained in 97%, 94%, and 94% of patients still on drug at 3, 4, and 5 years, respectively, and 60% of cases were phlebotomy-free. Twenty-three of 63 Phl-O patients (37%) failed the primary endpoint and were crossed over to Ropeg; among the risk factors for this failure, the need for more than three bloodletting procedures in the first 6 months emerged as the most important determinant. In conclusion, to improve the effectiveness of Ropeg, we suggest increasing the dose and using it earlier driven by high phlebotomy need in the first 6 months post-diagnosis.

Hypertension is a commonly reported comorbidity in patients diagnosed with chronic myeloid leukemia (CML), and its management represents a challenge in patients treated with 2nd- or 3rd-generation tyrosine kinase inhibitors (TKIs), considering their additional cardiovascular (CV) toxicity. The renin angiotensin system (RAS) contributes to hypertension genesis and plays an important role in atherosclerosis development, proliferation, and differentiation of myeloid hematopoietic cells. We analyzed a cohort of 192 patients with hypertension at CML diagnosis, who were treated with 2nd- or 3rd-generation TKIs, and evaluated the efficacy of RAS inhibitors (angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-II receptor blockers (ARBs)) in the prevention of arterial occlusive events (AOEs), as compared with other drug classes. The 5-year cumulative incidence of AOEs was 32.7 ± 4.2%. Patients with SCORE ≥ 5% (high-very-high) showed a significantly higher incidence of AOEs (33.7 ± 7.6% vs 13.6 ± 4.8%, p = 0.006). The AOE incidence was significantly lower in patients treated with RAS inhibitors (14.8 ± 4.2% vs 44 ± 1%, p < 0.001, HR = 0.283). The difference in the low and intermediate Sokal risk group was confirmed but not in the high-risk group, where a lower RAS expression has been reported. Our data suggest that RAS inhibitors may represent an optimal treatment in patients with hypertension and CML, treated with 2nd or 3rdG TKIs.

We analyzed BCR::ABL1 expression at stop and in the first month after discontinuation in 168 chronic myeloid leukemia patients who stopped imatinib or 2nd generation tyrosine kinase inhibitors (2G‐TKIs) while in sustained deep molecular response. Patients were divided among those who maintained response (group 1, n = 123) and those who lost major molecular response (group 2, n = 45). Mean BCR::ABL1 RNA levels 1 month after discontinuation were higher in group 2 than in group 1 (p = 0.0005) and the difference was more evident 2 months after stop (p < 0.0001). The same trend was found both for imatinib and 2G‐TKIs. A receiver operating characteristic (ROC) analysis to determine a threshold value of BCR::ABL1 at 1 month after discontinuation identified a cut‐off value of 0.0051%, with 92.2% specificity, 31.7% sensitivity and a likelihood ratio of 4.087. We analyzed BCR::ABL1 expression at stop and in the first month after discontinuation in 168 CML patients stopping imatinib or 2G‐TKIs, dividing patients who maintained response (1, n = 123) and those who lost MMR (group 2, n = 45). Mean BCR::ABL1 RNA levels at 1 and 2 months after discontinuation was higher in group 2 than in group 1, with a similar trend for imatinib and 2G‐TKIs. A BCR::ABL1 value <0.0051% at 1 month after discontinuation was the stronger predictor of treatment‐free remission (92.2% specificity).

Patients with chronic myeloid leukemia (CML) treated with nilotinib or ponatinib may experience arterial occlusive events (AOEs). It is currently recommended to thoroughly assess cardiovascular risk factors before treating CML. We identified 455 consecutive CML adult patients, 335 treated with nilotinib and 120 with ponatinib; 380 patients without previous cardiovascular diseases or diabetes were stratified according to the Systematic Coronary Risk Evaluation (SCORE2) and SCORE2-Older Persons (SCORE2-OP). This updated algorithm from the European Society of Cardiology (ESC) estimates a 10-year risk of fatal and non-fatal cardiovascular diseases. It is based on sex, age, smoking habits, systolic blood pressure, non-high-density lipoprotein cholesterol, and European geographical region of cardiovascular risk. The SCORE2/SCORE2-OP algorithm translated more patients (50.2%) to the high–very high cardiovascular risk category than the previous SCORE (25.3%). Patients with a high to very high SCORE2/SCORE2-OP risk showed a significantly higher incidence rate of AOEs (69.2% vs. 46.5%, p < 0.001). The older SCORE was less specific in estimating AOEs in patients classified as low-intermediate risk (69.8 vs. 54.2%). In multivariate analysis, no associations were found between AOEs and gender, age, and type or dose of tyrosine kinase inhibitor. Only the SCORE2/SCORE2-OP risk was confirmed as a significant predictive factor (p = 0.028; hazard ratio = 2.2; 95% confidence interval = 1.1–4.5). Patients with AOEs required, in most cases, imaging diagnostic tests, additional drugs, and sometimes invasive procedures, increasing access to visits and hospital management. This real-life study suggested that the SCORE2 and SCORE2-OP charts could help identify cardiovascular fragility in CML patients providing them with more attention and a proper TKI selection.