Azienda Sanitaria Provinciale 8 - Siracusa

Chemical pollution poses a significant threat to human health, with detrimental effects on various physiological systems, including the respiratory, cardiovascular, mental, and perinatal domains. While the impact of pollution on these systems has been extensively studied, the intricate relationship between chemical pollution and immunity remains a critical area of investigation. The focus of this study is to elucidate the relationship between chemical pollution and human immunity. To accomplish this task, this study presents a comprehensive review that encompasses in vitro, ex vivo, and in vivo studies, shedding light on the ways in which chemical pollution can modulate human immunity. Our aim is to unveil the complex mechanisms by which environmental contaminants compromise the delicate balance of the body’s defense systems going beyond the well-established associations with defense systems and delving into the less-explored link between chemical exposure and various immune disorders, adding urgency to our understanding of the underlying mechanisms and their implications for public health.

Background Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. Methods In this study, 382 infants born at 24⁺⁰–27⁺⁶ weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. The secondary outcomes are BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24⁺⁰ to 25⁺⁶ weeks or 26⁺⁰ to 27⁺⁶ weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). Discussion This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24⁺⁰–27⁺⁶ weeks’ gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks’ postmenstrual age of life. Trial registration ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

BACKGROUND The FIRE trial (Functional Assessment in Elderly Myocardial Infarction Patients With Multivessel Disease) enrolled 1445 older (aged ≥75 years) patients with myocardial infarction and multivessel disease in Italy, Spain, and Poland. Patients were randomized to physiology-guided complete revascularization or treatment of the only culprit lesion. Physiology-guided complete revascularization significantly reduced ischemic adverse events at 1 year. This prespecified analysis investigated the changes between the 2 study groups in angina status, quality of life, physical performance, and frailty. METHODS Patients underwent validated scales at hospital discharge (baseline) and 1 year later. Angina status was evaluated using the Seattle Angina Questionnaire, health-related quality of life by EQ visual analog scale, physical performance by short physical performance battery, and frailty by the clinical frailty scale. Mixed models for repeated measures analysis were used to study the association between the treatment arms, time, and scales. RESULTS Baseline and 1-year Seattle Angina Questionnaire, EQ visual analog scale, short physical performance battery, and clinical frailty scale were collected in around two-thirds of the entire FIRE study population. The mean age was 80.9±4.6 years (female sex, 35.9%). Overall, 35.3% were admitted for ST-segment–elevation myocardial infarction, whereas the others were admitted for non–ST-segment–elevation myocardial infarction. Physiology-guided complete revascularization, compared with culprit-only revascularization, was associated with greater improvement in terms of angina status (Seattle Angina Questionnaire summary score, 7.3 [95% CI, 6.1–8.6] points), health-related quality of life (EQ visual analog scale, 6.2 [95% CI, 4.4–8.1] points), and physical performance (short physical performance battery, 1.1 [95% CI, 0.9–1.3] points). After 1 year, patients randomized to culprit-only revascularization experienced a deterioration in frailty status (clinical frailty scale, 0.2 [95% CI, 0.1–0.3] points), which was not observed in patients randomized to physiology-guided complete revascularization. CONCLUSIONS The present analysis suggested that a physiology-guided complete revascularization is associated with consistent benefits in terms of angina status, quality of life, physical performance, and the absence of further deterioration of the frailty status. REGISTRATION URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03772743.

A recent research project using data from 38 cancer registries has provided new epidemiologic insights into the results of efforts for melanoma control in Italy between the 1990s and the last decade. In this article, the authors present a summary and a commentary of their findings. Incidence increased significantly throughout the study period in both sexes. However, the rates showed a stabilisation or a decrease in men and women aged below 35 years. The risk of disease increased for successive cohorts born until 1973 (women) and 1975 (men) while subsequently tending to decline. The trend towards decreasing tumour thickness and increasing survival has continued, but a novel favourable prognostic factor has emerged since 2013 for patients – particularly for males – with thick melanoma, most likely represented by molecular targeted therapies and immune checkpoint inhibitors. Due to this, the survival gap between males and females has been filled out. In the meanwhile, and despite the incidence increase, dermatologists have not lowered their threshold to perform skin biopsy. Skin biopsy rate has increased because of the increasingly greater volume of dermatologic office visits, but the proportion of skin biopsies out of dermatologic office visits has remained constant. In summary, an important breakthrough in melanoma control in Italy is taking place. Effective interventions have been implemented across the full scope of care, which involve many large local populations – virtually the whole national population. The strategies adopted during the last three decades represent a valuable basis for further steps ahead in melanoma control in Italy.

The present systematic review addresses the influence of occupational exposures on prostate cancer risk. Eleven studies were analyzed for a range of occupational exposures, including but not limited to firefighting, physical activity, night shift work, chemical exposure, and solar ultraviolet radiation. The results of the review reveal that firefighters exposed to harmful substances, individuals engaged in physically strenuous work, and workers with chronic night shift routines showed an increased likelihood of developing prostate cancer. Moreover, the review identified an increased risk associated with exposure to certain chemicals, including alkylphenolic compounds and benzene-related substances. The evidence underscores the importance of considering the cumulative effect of multiple risk factors in a comprehensive risk assessment. However, the conclusions indicate the necessity for further research to deepen these relationships and develop more effective strategies for the prevention of prostate cancer.

(1) Objective: In many Western countries, survival from vulvar squamous cell carcinoma (VSCC) has been stagnating for decades or has increased insufficiently from a clinical perspective. In Italy, previous studies on cancer survival have not taken vulvar cancer into consideration or have pooled patients with vulvar and vaginal cancer. To bridge this knowledge gap, we report the trend in survival from vulvar cancer between 1990 and 2015. (2) Methods: Thirty-eight local cancer registries covering 49% of the national female population contributed the records of 6274 patients. Study endpoints included 1- and 2-year net survival (NS) calculated using the Pohar-Perme estimator and 5-year NS conditional on having survived two years (5|2-year CNS). The significance of survival trends was assessed with the Wald test on the coefficient of the period of diagnosis, entered as a continuous regressor in a Poisson regression model. (3) Results: The median patient age was stable at 76 years. One-year NS decreased from 83.9% in 1990–2001 to 81.9% in 2009–2015 and 2-year NS from 72.2% to 70.5%. Five|2-year CNS increased from 85.7% to 86.7%. These trends were not significant. In the age stratum 70–79 years, a weakly significant decrease in 2-year NS from 71.4% to 65.7% occurred. Multivariate analysis adjusting for age group at diagnosis and geographic area showed an excess risk of death at 5|2-years, of borderline significance, in 2003–2015 versus 1990–2002. (4) Conclusions: One- and 2-year NS and 5|2-year CNS showed no improvements. Current strategies for VSCC control need to be revised both in Italy and at the global level.

Existe una preocupación por investigar la relación entre los síntomas del TDAH y la actividad emprendedora, encontrando un impacto positivo en la intención y acción emprendedora; pero desconociéndose las implicaciones en el rendimiento de estos síntomas. Utilizando una muestra de emprendedores españoles, esta investigación encuentra que los síntomas impulsivos e hiperactivos del TDAH conducen en gran medida al desempeño empresarial a través de la orientación emprendedora, mientras que los síntomas de falta de atención no ayudan a mejorar dicho desempeño. Estos resultados sugieren que las ventajas de rendimiento pueden derivarse de una mayor capacidad innovadora, proactividad y asunción de riesgos.

Background The early crossing of survival curves in randomized clinical trials (RCTs) with immune checkpoint blockers (ICB) suggests an excess of mortality in the first months of treatment. However, the exact estimation of the early death (ED) rate, the comparison between ED upon ICI alone or in combination with other agents and the impact of tumor type and PD-L1 expression on ED are unknown. Methods RCTs comparing ICI alone (ICI-only group) or in combination with other non-ICI therapies (ICI-OT group) (experimental arms) vs non-ICI treatments (control arm) were included. ED was defined as death within the first 3 months of treatment. The primary outcome was the comparison of ED between experimental and control arms, the secondary outcome was the comparison of ED risk between ICI-only and ICI-OT. ED rates estimated by risk-ratio (RR) were pooled by random effect model. Results 56 RCTs (40215 participants, 14 cancer types) were included. ED occurred in 14.2% and 6.7% of patients in ICI-only and ICI-OT groups, respectively. ED risk significantly increased with ICI-only (RR: 1.29, 95% CI 1.05-1.57) versus non-ICI therapies while it was lower with ICI-OT versus non-ICI treatments (RR: 0.81, 95% CI 0.73-0.90). ED risk was significantly higher upon ICI-only compared to ICI-OT (RR: 1.57, 95% CI 1.26-1.95). Gastric and urothelial carcinoma were at higher risk of ED. PD-L1 expression and ICI drug classes were not associated with ED. Conclusions ED upon first-line ICI is a clinically relevant phenomenon across solid malignancies, not predictable by PD-L1 expression, but preventable through the addition of other treatments to ICI.

Background: The number of cancer survivors continues to increase, thanks to advances in cancer diagnosis and treatment. Unfortunately, the incidence of a second primary cancer (SPC) is also increasing, but limited studies reporting incidence data are available regarding multiple cancers. This study presents our observations on multiple primary malignant cancers, the associations between sites, and the inherent sex differences. Patients and methods: We report the data, disaggregated by sex, concerning the SPCs that were recorded in the "Registro Tumori Integrato" (RTI) a population-based cancer registry in Sicily, Italy, as observed in the period from 2003 to 2017, in a total population of approximately 2,300,000. SPCs were divided into synchronous and metachronous cancers. The International Classification of Diseases for Oncology, third edition (ICD-O-3), was used for topographical and morphological classifications. Multiple primary cancers with multi-organ primitiveness were selected from the database of the RTI by extracting patients with more than one diagnosis. SPCs had different histology or morphology from the particular cancer that was considered to be the index cancer case. Multicenter or multifocal cancers, or metastases, were excluded. The percentages of cancer by sex and topography, the average age of incidence, and a breakdown by age were computed. Results: Differences were observed between sexes in terms of incidence and site for SPCs. The most frequent SPC was skin cancer (20% of the SPCs observed). The associations among sites of multiple cancers are reported. Conclusion: There are many gaps in our knowledge of sex differences in cancer. The study of multiple primary cancers could bring more likely opportunities for evaluation of the cancer burden and trends that can be used to identify new research areas by population health programs, as well as for clinical researchers.

Germ cell tumors arise in childhood but peak at around 30 years of age. They are the most common cancers in males under the age of 35. Over 95% arise in the testes while a minority originate in extragonadal sites such as the anterior mediastinum, or mainly in childhood the pineal gland or the sacrococcygeal area. These tumors show an extraordinary sensitivity to chemotherapy (and for seminoma, also to radiation) and cure rates are relatively high even in second or subsequent relapses. Very few data are present in the literature regarding patients diagnosed after 50 years and no specific trials have been conducted in this setting. Nearly all patients reported in the literature had testicular cancers, with occasional reports of extragonadal tumors. Despite the fact that > 50 years may be considered an “elderly” population, these patients are treated with the same cisplatin containing combinations as their younger counterparts with consequent higher toxicity. In this review we will present epidemiological and clinical data from this rare population of patients with testicular cancer.

Background The elderly is characterized by a gradual decline in body function, which represents the clinical situation called "frailty". Prefrailty is the intermediate stage between frailty and the robust condition. L-carnitine (LC) plays an important role in energy production from long-chain fatty acids in mitochondria and its serum level is lower in prefrail and frail subjects. Objective This study aims to evaluate the effect of Acetyl-L-carnitine (ALCAR) in pre frail older patients. Methods We scheduled 3 months of treatment and then 3 months of follow-up. 92 subjects were selected from May 2009 to July 2017 in a randomized, observational, double-blind, placebo-controlled study. We scheduled 3 months of treatment and then 3 months of follow-up. ALCAR (oral 1.5 g/bis in die - BID) or placebo group. Results After the treatment, only the treated group displayed a decrease in C reactive protein (CRP) p<0.001, an increase in serum free carnitine and acetyl carnitine (p<0.05), in Mini Mental state (MMSE) p<0.0001 and 6-walking distance (p<0.0001); ALCAR group vs. placebo group showed a decrease in HDL cholesterol and in CRP (p<0.01), an increase in MMSE score (p< 0.001) and in 6-walking distance (p<0.001) Conclusions ALCAR treatment delays the incidence and severity of onset in prefrail subjects of degenerative disorders of the elderly, with improvement in memory and cognitive processes.

Background: The itAlian pRospective Study on CANGrELOr (ARCANGELO) was aimed to assess the safety of using cangrelor during percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS) in the daily practice. Hypothesis: The safety of cangrelor after the transition to oral P2Y12 inhibitors was evaluated as the incidence of bleeding outcomes in the 30 days following PCI according to postauthorization safety study guidelines. Methods: Adults with ACS who were treated with cangrelor in one of the 28 centers involved in the study. Patients who consented to participate were followed in the 30 days following their PCI. Bleedings (Bleeding Academic Research Consortium [BARC] classification), major adverse cardiac events (MACEs), and adverse events were recorded. The interim results at two-thirds of the enrollment period are presented. Results: A total of 17 bleedings were observed in the 320 patients who completed the study at this stage. All bleedings were classified as BARC Type 1-2, except for one case of Type 3a (vessel puncture site hematoma). Four patients experienced MACEs (2 acute myocardial infarctions, 1 sudden cardiac death, 1 noncardiovascular death due to respiratory distress, and multiorgan failure). None of the bleedings was rated as related to cangrelor. Conclusions: The interim results of the ARCANGELO study provide a preliminary confirmation that the use of cangrelor on patients with ACS undergoing PCI is not associated with severe bleedings.

The case of a 12–year–old male, height 160 cm, weight 46 kg, who practices water polo at a competitive level is reported. Negative family history of cardiovascular pathologies, general and cardiovascular physical examination within the limits of normality. On the electrocardiographic trace (ECG) presence of delta wave from ventricular pre–excitation from intrahyssian accessory pathway (Fig. 1). Echocardiography + color Doppler was normal. The subject underwent a cardiopulmonary stress test with an incremental ramp protocol and steps of 20 watts / min. Shutdown at 190 watts for muscle exhaustion with peak oxygen consumption (VO2) = 43.9 mL / Kg / min, Heart rate = 197 beats / minute, BP = 210/70 mmHg, VE / VCO2 slope = 27.6. Normal course of the cronotropic and pressure curve. The ventricular pre–excitation delta wave persisted for the entire duration of the test and in recovery (Fig. 2, Fig. 3). Secondary disturbances of ventricular repolarization characterized by ST segment sub–leveling and negative T wave appeared at high load and persisted in the first minutes of recovery, delta VO2 / delta WR = 12. Given the non–disappearance of the delta wave from ventricular pre–excitation during the maximal stress test, the subject was sent to an electrophysiological study and subsequent ablation of the accessory pathway. The electrophysiological study was negative for inducibility of atrial fibrillation (AF) and ventricular arrhythmias. Safe ablation was impossible given the intrahyssian position of the accessory pathway. Considering the negativity of the electrophysiological study due to non inducibility of supraventricular and ventricular arrhythmias, eligibility for competitive sports was granted. Open in new tabDownload slide Open in new tabDownload slide Open in new tabDownload slide

Purpose Describe breast cancer in Italy by age, geographical area, stage and sites of metastases. In addition, incident and prevalent cases by region are provided. Patients and Methods This population-based study included all female patients with histologically confirmed breast cancer diagnosed in Italy between 2013 and 2019 in the eight participating Cancer Registries. Cases were described by geographic area (north, center, south), age group (<50, 50–69 and 70+) and site of metastases. In addition, the study also provided an estimate of the cases of metastatic breast cancer per single region. Results Of the total 5731 cases, the number of unknown stage cases (eliminated from our analyses) was 545 (10.5% of cases); therefore, the study was conducted on 5186 cases. Overall, 333 (6.5%) of tumors were metastatic at diagnosis but the distribution by geographical area was different: 5.1% in the north, 7.4% in the center and 7.8% in the south. Related to age, 5.6% were diagnosed before the age of 50 and 5.6% within the screening target group (50–69 years), while in elderly women the percentage rose to 8.1%. As regards the site of the metastases, 27.1% developed metastasis to the bone, 12.4% to the liver, 8.6% to the lung and 2.6% to the brain; in 34.9%, multiple sites were already present at the beginning of the cancer. Overall, 3520 cases of incident mBC are estimated in Italia every year (520 in Lombardy in northern Italy, 350 in Lazio in the center, followed by 330 in Campania in the south), and finally they are out of 52,000 prevalent cases. Conclusion A greater possibility of treating and living with the disease for a long time now requires careful monitoring of these tumors.

To recover impacted canines without esthetic issues, the aligners can be a resolutive tool allowing by pontics the camouflage of absent canines during orthodontic treatment. Knowledge of biomechanics, correct staging of dental movements, and surgery planification are strategic to achieve a good result. To recover impacted canines without esthetic issues, the aligners can be a resolutive tool allowing by pontics the camouflage of absent canines during orthodontic treatment. Knowledge of biomechanics, correct staging of dental movements, and surgery planification are strategic to achieve a good result.

Background The number of patients living after a cancer diagnosis is increasing, especially after thyroid cancer (TC). This study aims at evaluating both the risk of a second primary cancer (SPC) in TC patients and the risk of TC as a SPC. Methods We analyzed two population-based cohorts of individuals with TC or other neoplasms diagnosed between 1998 and 2012, in 28 Italian areas covered by population-based cancer registries. Standardized incidence ratios (SIRs) of SPC were stratified by sex, age, and time since first cancer. Results A total of 38,535 TC patients and 1,329,624 patients with other primary cancers were included. The overall SIR was 1.16 (95% CI: 1.12–1.21) for SPC in TC patients, though no increase was shown for people with follicular (1.06) and medullary (0.95) TC. SPC with significantly increased SIRs was bone/soft tissue (2.0), breast (1.2), prostate (1.4), kidney (2.2), and hemolymphopoietic (1.4) cancers. The overall SIR for TC as a SPC was 1.49 (95% CI: 1.42–1.55), similar for all TC subtypes, and it was significantly increased for people diagnosed with head and neck (2.1), colon–rectum (1.4), lung (1.8), melanoma (2.0), bone/soft tissue (2.8), breast (1.3), corpus uteri (1.4), prostate (1.5), kidney (3.2), central nervous system (2.3), and hemolymphopoietic (1.8) cancers. Conclusions The increased risk of TC after many other neoplasms and of few SPC after TC questions the best way to follow-up cancer patients, avoiding overdiagnosis and overtreatment for TC and, possibly, for other malignancies.

Background & Aims Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) is responsible for coronavirus disease 2019 (COVID‐19), which in males, especially in advanced age, can sometimes evolve into acute respiratory distress syndrome. In addition, mild to moderate alterations in liver function tests (LFTs) have been reported in the worst affected patients. Our review aims to analyse data on the incidence and prognostic value of LFT alterations, the underlying mechanisms and the management of pre‐existing liver disease in COVID‐19 affected patients. Methods We searched available literature through online PubMed database using terms as “SARS‐CoV‐2,” “Liver damage,” “Liver Function tests,” “COVID‐19,” “pre‐existing liver disease,” “drug‐induced liver injury.” Results Available evidence suggest that there could be a relationship between SARS‐CoV‐2 infection and liver damage, although the underlying involved mechanism remains unclear. Cohort studies have shown that high ALT levels, low platelet counts and low albumin levels at admission and during hospitalisation are associated with a high mortality rate. Unfortunately, little is known about the impact of COVID‐19 on pre‐existing liver damage. While chronic viral infections or NAFLD are associated with an increased risk of COVID‐19 progression, patients with cirrhosis may have increased susceptibility to SARS‐CoV‐2 infection due to their systemic immunocompromised status. DILI seems common among hospitalised patient with severe pneumonia. Conclusion Mild to moderate liver impairment during Covid‐19 is common, especially in patients with pre‐existing liver disease. Further studies should be performed in order to understand how pre‐existing liver conditions may influence and worsen progression of liver disease in COVID‐19 patients.

Palliative care arises from the need to provide an assistance response at a particular moment in the patient’s history of illness, when “there is nothing to be done.” PC fills the gap between the active therapeutic phase of poor-prognosis diseases and the patient’s death. The aim is to ensure active care and comprehensive assistance in the terminal phase. The term “palliative” refers to the health and care approach that addresses all condition of patients, to alleviate suffering, to respond to needs, and to improve the quality of life. The palliative approach is global, in that it considers the patient in all contexts: physical, psychological, and spiritual, as well as the family and social dimensions; it also supports and assists families and caregivers. In Italy, since 1999, numerous directives have been issued with relevant regulatory value. PC was born in some Italian regions before the laws that regulated it, thanks to the free initiative of doctors, other voluntary professionals, and citizens, who are sensitive to the discomfort of patients and families affected by oncological diseases. Numerous healthcare professionals are involved; however, a school for doctors and other health professionals specializing in palliative care has not yet been established in Italy. Graduates in the various disciplines can receive a post-graduate master’s degree which follows a unique path for each specific profession. The requirements for the various professionals and their respective skills have been identified and defined within the State-Regions Agreement of July 10, 2014.