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Aims: Sodium-glucose cotransporter inhibitors (SGLT2-i) improve outcomes in patients with heart failure (HF) and reduced ejection fraction (HFrEF). However, evidence in patients with advanced HF is lacking. We aimed to determine the effect of SGLT2-i in advanced HFrEF compared to their effect on a non-advanced population., Methods: Consecutive HFrEF outpatients who started SGLT2-i were observed for 6-months. Patients were categorized as having advanced or non-advanced HFrEF. The primary outcome was the trend of NTproBNP in the two groups. Secondary outcomes included changes in New York Heart Association (NYHA) class, glomerular filtration rate (GFR), and ejection fraction (LVEF). The association between advanced HF diagnosis and including N-terminal pro-brain natriuretic peptide (NTproBNP) reduction was tested using multivariate analysis., Results: Overall, 105 patients (45 advanced, 60 non-advanced) were included. Mean age was 56 ± 10 years, 22 % were female, and 35 % had ischemic heart disease. Median NTproBNP at baseline for advanced and non-advanced patients was 1672pg/ml (IQR 520-3320) vs. 481 pg/ml (IQR 173-917), respectively (p < 0.001). At follow-up, only non-advanced patients reduced their NTproBNP (-32 % (95 % CI -51 to -3), p < 0.001), while advanced patients had an increase in NTproBNP. LVEF and NYHA class improved only in non-advanced patients. GFR was stable in both subgroups. At multivariate analysis a diagnosis of advanced HF was independently associated with a reduced probability of NTproBNP reduction (OR 0.041 (95 % CI 0.002-0.752), p = 0.031). Only one patient discontinued the drug due to side effects., Conclusion: In advanced HFrEF, SGLT2-i do not impact on NTproBNP, LVEF or NYHA class but are well tolerated., Competing Interests: Declaration of competing interest The authors have not any conflict of interest to declare, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To evaluate the anatomical and functional macular results and rate of complications following surgical treatment of primary macular hole (MH) with autologous platelet rich plasma (a-PRP) use., Design: retrospective, interventional, non-randomized case series., Partecipants and Methods: A cohort of 9 consecutive patients from January 1, 2019 to August 31, 2021 who underwent vitrectomy with a-PRP use for primary MH were included. Anatomical results based on spectral domain- optical coherence tomography (SD-OCT) and visual acuity were analyzed., Results: 10 pseudophakic eye of 9 patients were enrolled. Six patients were female and three patients were male. The mean age was 69.9 years ± 1.48. The baseline MH minimum diameter was 486.1 μm ± 37.1, and mean pre operative best-corrected visual acuity (BCVA) was 0.91 ± 0.03 logMAR (Snellen equivalent 20/160). Mean 1 month post operative BCVA was 0.81 ± 0.57 logMAR (Snellen equivalent 20/130; p  = 1.000); mean 3 month post operative BCVA was 0.66 ± 0.04 logMAR (Snellen equivalent 20/90; p  = 0.006); mean 6 month post operative BCVA was 0.6 ± 0.04 logMAR (Snellen equivalent 20/80; p  < 0.001). In all eyes, 10/10 (100%), there was a complete MH closure at 6 months follow up: 5 eyes (50%) with a U-type closure pattern, 4 eyes (40%) with a V-type pattern and 1 eye (10%) with an irregular foveal contour closure at 6 month follow-up. No ocular and systemic complications were reported., Conclusion: The a-PRP use is a successful and promising vitreoretinal surgical technique option for primary MH., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Cardiogenic Shock (CS) complicating acute myocardial infarction (AMI) poses a significant mortality risk, suggesting the opportunity to implement effective mechanical circulatory support strategies. The comparative efficacy of Intra-Aortic Balloon Pump (IABP) and Impella in managing CS-AMI remains a subject of investigation., Objective: This meta-analysis aims to evaluate the comparative effectiveness of Impella and IABP in managing CS-AMI, exploring mortality and adverse events., Methods: A systematic search of major databases from inception to November 2023 identified eight studies, comprising 10,628 patients, comparing Impella and IABP in CS-AMI. Retrospective studies (preferably Propensity-matched) and Randomized Clinical Trials (RCTs) were included., Results: Impella use exhibited significantly higher mortality (57% vs. 46%; OR: 1.44, 95% CI: 1.29-1.60; p < 0.001) and major bleeding (30% vs 15%; OR: 2.93, 95% CI: 1.67-5.13; p < 0.001)., Conclusions: In unselected CS-AMI patients, Impella usage is associated with significantly higher mortality and major bleeding., Competing Interests: Declaration of competing interest Authors have no conflict of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Cancer is the most common cause of death in adult dogs. All dogs would benefit from early diagnosis, but there are no specific guidelines regarding the schedule of cancer screening in companion animals. The aim of this study was to retrospectively evaluate the age at diagnosis in Italian oncological canine patients. A total of 14,636 canine histologically confirmed neoplastic cases were coded according to the Vet-ICD-O-canine-1 and stratified by malignancy, sex, neutering status, breed, cephalic index, body size, and tumor type. Differences in age distribution were analyzed and the influence of these variables on the time of first malignancy diagnosis was assessed using an event history analysis model. The median age at diagnosis for benign and malignant tumors was 9 and 10 years, respectively. Intact and purebred dogs were diagnosed earlier, but the median age differed significantly by breed. The earliest age at diagnosis was recorded for lymphomas and mast cell tumors. The model showed an accelerating effect of large size, brachy- and dolichocephaly, and sexual integrity in female dogs on the time of malignancy diagnosis. Our results confirm that a "one-size-fits-all" approach to cancer screening is not accurate in dogs and provide relevant data that may lead to the establishment of breed-based screening schedules.

Ranolazine is an anti-anginal medication that has demonstrated antiarrhythmic properties by inhibiting both late sodium and potassium currents. Studies have shown promising results for ranolazine in treating both atrial fibrillation and ventricular arrhythmias, particularly when used in combination with other medications. This review explores ranolazine's mechanisms of action and its potential role in cardiac arrhythmias treatment in light of previous clinical studies.

Background: Molecular characterization is pivotal for managing non-small cell lung cancer (NSCLC), although this process is often time-consuming and patients' conditions might worsen while molecular analyses are processed. Our primary aim was to evaluate the performance of "up-front" next-generation sequencing (NGS) through liquid biopsy (LB) of hospitalized patients with newly detected lung neoplasm in parallel with conventional diagnosis. The secondary aim included longitudinal monitoring through LB of patients with oncogenic alterations at baseline., Methods: We enrolled 47 consecutive patients immediately after hospitalization and radiological detection of symptomatic lung neoplasm. LB from peripheral blood was performed at baseline, in parallel with conventional biopsy (CB), when feasible. Additionally, LBs were repeated during treatment in patients with actionable gene alterations at baseline. Oncomine™ Lung cfTNA Research Assay panel was employed for processing plasma samples in NGS., Results: 47 hospitalized patients were enrolled. LB identified 28 patients with gene alterations, including mutations of EGFR (n = 7), KRAS (n = 12), ERBB2 (n = 1), TP53 (n = 2), BRAF (n = 1), one ALK rearrangement, and 4 patients with combined mutations involving EGFR, KRAS and PIK3CA. LB and CB were consistent, except for two patients. Three patients with positive LB for oncogenic drivers did not undergo CB due to contraindications. Median time to molecular results after LB was significantly lower compared to time to molecular report after CB (11 versus 22 days, p < 0.001)., Conclusions: Despite limited numbers, our study supports the role of front-line LB for improving management of symptomatic patients with lung cancer, potentially leading to early targeted therapy initiation., Competing Interests: Declaration of competing interest Chiara Dellepiane has received honoraria for consulting activities of Astra Zeneca, Merck Sharp and Dohme, Bristol-Myers-Squibb, Roche. Francesco Spagnolo has been an advisory boards member for MSD, Novartis, Pierre Fabre, Sun Pharma, Philogen and has received lecture fees/honoraria for consulting activities of BMS, MSD, Novartis, Pierre Fabre, Merck, Sanofi, Sun Pharma, IGEA. Matteo Lambertini reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD and Exact Sciences and speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Knight and Takeda, Travel Grants from Gilead and Daiichi Sankyo, and research support (to the Institution) from Gilead outside the submitted work. Lucia Del Mastro has received honoraria for consulting activities, speaker bureau or advisory boards from Roche, Novartis, Pfizer, Eli Lilly, Astra Zeneca, Merck-Sharp-Dohme, Seagen, Gilead, Pierre Fabre, Eisai, Exact sciences, Ipsen, GSK, Agendia, Stemline Menarini, Daiichi Sakyo. Carlo Genova has received honoraria for consulting activities, speaker bureau or advisory boards from Astra Zeneca, Bristol-Myers-Squibb, Eli Lilly, Janssen, Merck Sharp and Dohme, Novartis, Roche, Sanofi, Takeda. The other authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Maternal obesity has been associated with short- and long-term risks of pregnancy-perinatal adverse events, possibly due to alterations of placental mitochondrial bioenergetics. However, several detrimental mechanisms occurring in the placentas of women with obesity still need to be clarified. Here, we analyzed placental mitochondrial features and oxidative environment of 46 pregnancies in relation to pre-pregnancy BMI. Seventeen Caucasian normal-weight (NW) and twenty-nine women who were obese (OB) were enrolled. The protein expression of mitochondrial CypD and electron transfer chain complexes (C) I-V were measured, as well as ATP production and oxygen consumption rates (OCRs). The protein levels of the pro/anti-oxidant enzymes TXNIP, SOD2, and PON2 were also analyzed. Despite no differences in CypD expression, OCRs were significantly lower in OB vs. NW women. Accordingly, ATP synthase (CV) levels and ATP content were decreased in OB women, positively correlating with placental efficiency, suggesting a link between ATP deficiency and placental dysfunction. SOD2 expression negatively correlated with maternal BMI, indicating a possible impairment of antioxidant defenses with increasing BMI. These changes were worsened in 10 OB women presenting with gestational diabetes mellitus. Overall, these results suggest alterations of placental bioenergetics in pregnancies of women with obesity, possibly leading to placental dysfunction and altered fetal development and programming.

Canine melanoma is a malignant and aggressive neoplasm showing clinical, histological, and molecular features similar to the human counterpart. In human medicine, epidermal growth factor receptors (EGFRs) have already been suggested as prognostic markers and potential therapeutic targets in cutaneous melanoma. The aim of this study was to evaluate the expression of HER-2 and HER-3 in canine melanomas by immunohistochemistry and correlate their expression to the clinicopathological parameters of the examined tumors. Thirty-seven canine melanoma samples were recruited. Data regarding signalment and clinical parameters were also collected. The population was composed of 18 cutaneous, 16 oral/mucosal, and three digital/foot pad melanomas. Histopathological investigations were carried out to analyze histological type, ulceration, and mitotic count. On each sample, immunohistochemistry was performed using an anti-Melan-A or anti-Melanoma antigen, i.e., anti-HER-2 and anti-HER-3 antibodies. HER-2 and HER-3 positivity were classified using already established scoring criteria and a statistical analysis was carried out. The results highlighted that HER-2 expression was observed in 48.6% of the samples and HER-3 expression in 18.9%. The highest HER 2 score (3+) was recorded in 16.2% of the samples, while the coexpression of the two receptors was detected in 13.5% of the samples. A statistically significant association ( p < 0.05) was observed between the expression of HER-2 and HER-3 and the presence of ulceration in oromucosal tumors. This work confirms the expression of HER-2 and HER-3 in canine melanomas and suggests a putative association with negative prognostic parameters. Further studies are necessary to strengthen these data by increasing the samples size and combining pathological examinations with molecular biology in the investigation of EGFR family receptors.

During intrauterine life, external stimuli including maternal nutrition, lifestyle, socioeconomic conditions, anxiety, stress, and air pollution can significantly impact fetal development. The human brain structures begin to form in the early weeks of gestation and continue to grow and mature throughout pregnancy. This review aims to assess, based on the latest research, the impact of environmental factors on fetal and neonatal brain development, showing that oxidative stress and inflammation are implied as a common factor for most of the stressors. Environmental insults can induce a maternal inflammatory state and modify nutrient supply to the fetus, possibly through epigenetic mechanisms, leading to significant consequences for brain morphogenesis and neurological outcomes. These risk factors are often synergic and mutually reinforcing. Fetal growth restriction and preterm birth represent paradigms of intrauterine reduced nutrient supply and inflammation, respectively. These mechanisms can lead to an increase in free radicals and, consequently, oxidative stress, with well-known adverse effects on the offspring's neurodevelopment. Therefore, a healthy intrauterine environment is a critical factor in supporting normal fetal brain development. Hence, healthcare professionals and clinicians should implement effective interventions to prevent and reduce modifiable risk factors associated with an increased inflammatory state and decreased nutrient supply during pregnancy.

Heart rate variability (HRV) is an indicator of autonomic nervous system activity, and high levels of stress and/or depressive symptoms may reduce HRV. Here, we assessed whether (a) parental stress affected HRV in mothers during the perinatal period and whether this is mediated by bonding and (b) whether antenatal maternal mental states, specifically repetitive negative thinking, depressive symptoms, and pregnancy-related anxiety, have an impact on infant HRV, and lastly, we investigated (c) the relationship between maternal HRV and infant HRV. Data are from the Northern Babies Longitudinal Study (NorBaby). In 111 parent-infant pairs, cardiac data were collected 6 months after birth. In the antenatal period, we used the Pregnancy-Related Anxiety Questionnaire-Revised, the Edinburgh Postnatal Depression Scale, and the Perseverative Thinking Questionnaire; in the postnatal period, we used the Parenting Stress Index and the Maternal Postnatal Attachment Scale. Higher levels of perceived parenting stress but not depressive symptoms were associated with lower HRV in mothers (τ = -0.146), and this relationship was not mediated by maternal bonding. Antenatal maternal mental states were not associated with infant HRV. There was no significant correlation between maternal HRV and infant HRV. Our observational data suggest that perceived stress reduces cardiac flexibility. Future studies should measure HRV and parenting stress repeatedly during the perinatal period.

Introduction: The study of the macroscopic appearance of the placenta may represent a useful tool to understand the pathophysiology of adverse pregnancy outcomes. The aim of this study was to evaluate biometry and morphology of placentas in relation to maternal, neonatal and pregnancy course characteristics., Methods: Clinical and placental data (biometry and macroscopic features of chorionic disk and adnexa) from unselected consecutive singleton pregnancies were recorded at the same Institution. Placental efficiency was approximated as ratio between fetal and placental weight (FPR). The total population was grouped according to the presence of any maternal comorbidity or pregnancy complication (group 1), neonatal complications diagnosed only at birth (2) and absence of any comorbidity (3). Multi-adjusted general linear and logistic regression models were performed to analyze associations between groups and placental biometry and morphology., Results: The study population counted 1008 pregnancies: 576 (57.2 %) classified as group 1, 76 (7.5 %) as group 2 and 356 (35.3 %) uncomplicated controls (group 3). In multivariate models adjusted for confounding factors, no significant differences in placental biometry and macroscopic features were observed among the three groups. Maternal BMI was significantly associated with higher placental and birth weight and lower FPR; moreover FPR was significantly higher in pregnancies carrying males compared to female neonates., Discussion: Maternal comorbidity or pregnancy disease was not associated with significant changes in placental macroscopic biometry and morphology. Conversely, maternal pregestational BMI and fetal sex impact on placental biometry and efficiency, suggesting different intrauterine adaptations in obese mothers and in male and female fetuses., 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 article., (Copyright © 2023 Università degli Studi di Milano. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Mitral valve prolapse (MVP) is a common clinical condition in the general population. A subgroup of patients with MVP may experience ventricular arrhythmias and sudden cardiac death ("arrhythmic mitral valve prolapse" [AMVP]) but how to stratify arrhythmic risk is still unclear. Our meta-analysis aims to identify predictive factors for arrhythmic risk in patients with MVP., Methods: We systematically searched Medline, Cochrane, Journals@Ovid, Scopus electronic databases for studies published up to December 28, 2022 and comparing AMVP and nonarrhythmic mitral valve prolapse (NAMVP) for what concerns history, electrocardiographic, echocardiographic and cardiac magnetic resonance features. The effect size was estimated using a random-effect model as odds ratio (OR) and mean difference (MD)., Results: A total of 10 studies enrolling 1715 patients were included. Late gadolinium enhancement (LGE) (OR: 16.67; p = .005), T-wave inversion (TWI) (OR: 2.63; p < .0001), bileaflet MVP (OR: 1.92; p < .0001) and mitral anulus disjunction (MAD) (OR: 2.60; p < .0001) were more represented among patients with AMVP than in NAMVP. Patients with AMVP were shown to have longer anterior mitral leaflet (AML) (MD: 2.63 mm; p < .0001), posterior mitral leaflet (MD: 2.96 mm; p < .0001), thicker AML (MD: 0.49 mm; p < .0001), longer MAD length (MD: 1.24 mm; p < .0001) and higher amount of LGE (MD: 1.41%; p < .0001) than NAMVP. AMVP showed increased mechanical dispersion (MD: 8.04 ms; 95% confidence interval: 5.13-10.96; p < .0001) compared with NAMVP., Conclusions: Our meta-analysis proved that LGE, TWI, bileaflet MVP, and MAD are predictive factors for arrhythmic risk in MVP patients., (© 2023 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Maternal nutritional status represents a pivotal predictor of pregnancy outcome. This prospective observational study investigates the associations between maternal characteristics and nutritional habits at term, hemodynamic parameters, and pregnancy outcomes. Healthy women with singleton uncomplicated pregnancies were enrolled at 36-41 gestational weeks. At enrollment, a nutritional score (0-10) was calculated in order to quantify maternal adherence to a healthy diet and lifestyle. Maternal hemodynamic parameters were assessed by using the Ultrasonic Cardiac Output Monitor (USCOM), including cardiac output (CO), systemic vascular resistance (SVR) and Smith-Madigan inotropy index (SMII). Pregnancy outcomes were recorded at delivery. Associations between maternal characteristics and nutritional score, hemodynamic parameters, and pregnancy outcomes were investigated by using multi-adjusted generalized linear models. In total, 143 pregnancies were enrolled. Pregestational body mass index (BMI) was positively associated with SVR, and negatively associated with CO and SMII. Additionally, a positive association was detected between the nutritional score and SMII. Finally, CO was positively associated with birth and placental weight, while RVS showed a negative association with birth and placental weight. This study shows that maternal derangements in nutritional status and habits are associated with a compromised hemodynamic profile at term, with additional impacts on intrauterine growth.

Background: Lung cancer patients diagnosed following emergency admission often present with advanced disease and poor performance status, leading to suboptimal treatment options and outcomes. This study aimed to investigate the clinical and molecular characteristics, treatment initiation, and survival outcomes of these patients., Methods: We retrospectively analyzed data from 124 patients diagnosed with lung cancer following emergency admission at a single institution. Clinical characteristics, results of molecular analyses for therapeutic purpose, systemic treatment initiation, and survival outcomes were assessed. Correlations between patients' characteristics and treatment initiation were analyzed., Results: Median age at admission was 73 years, and 79.0 % had at least one comorbidity. Most patients (87.1 %) were admitted due to cancer-related symptoms. Molecular analyses were performed in 89.5 % of advanced non-small cell lung cancer (NSCLC) cases. In this subgroup, two-thirds (66.2 %) received first-line therapy. Median overall survival (OS) was 3.9 months for the entire cohort, and 2.9 months for patients with metastatic lung cancer. Among patients with advanced NSCLC, OS was significantly longer for those with actionable oncogenic drivers and those who received first-line therapy. Improvement of performance status during hospitalization resulted in increased probability of receiving first-line systemic therapy., Discussion: Patients diagnosed with lung cancer following emergency admission demonstrated poor survival outcomes. Treatment initiation, particularly for patients with actionable oncogenic drivers, was associated with longer OS. These findings highlight the need for proactive medical approaches, including improving access to molecular diagnostics and targeted treatments, to optimize outcomes in this patient population., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The Authors declare the following potential conflicts of interest. Matteo Lambertini: advisory role for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD and Exact Sciences. Speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Knight, Daiichi Sankyo and Takeda. Research funding (to the Institution) and travel Grants from 10.13039/100005564Gilead outside the submitted work. Francesco Spagnolo: advisory role for Novartis, Pierre Fabre, MSD, Philogen. Speaker honoraria from Novartis, Pierre Fabre, MSD, BMS, Sanofi, Merck, Sun Pharma. Carlo Genova: Advisory role for AstraZeneca, Bristol Myers Squibb, Novartis, Roche, Sanofi, Takeda; Speaker honoraria from AstraZeneca, Bristol Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, Roche, Sanofi, Takeda, Thermofisher. Research Funding from the 10.13039/501100003196Italian Ministry of Health and from Bristol Myers Squibb outside the submitted work. The other Authors declare no conflict of interest., (© 2023 The Authors.)

Heart failure (HF) is a progressive condition with an increasing prevalence, and the scientific evidence of heart failure with reduced ejection fraction (HFrEF) reports a 6% rate of 1-year mortality in stable patients, whereas, in recently hospitalized patients, the 1-year mortality rates exceed 20%. The Sacubitril/Valsartan (S/V), the first angiotensin receptor neprilysin inhibitor (ARNI), significantly reduced both HF hospitalization and cardiovascular mortality., Aim of the Study: to evaluate the effect of S/V in a follow-up period of 5 years from the beginning of the therapy. We compared the one-year outcomes of S/V use with those obtained after 5 years of therapy, monitoring the long-term effects in a real-world population with HFrEF., Methods: Seventy consecutive patients with HFrEF and eligible for ARNI, according to PARADIGM-HF criteria, were enrolled. All patients had an overall follow-up of 60 months, during which time they underwent standard transthoracic echocardiography (TTE) with Global Longitudinal Strain (GLS) evaluation, the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Six Minutes Walking Test (6MWT), and blood tests (NT-pro-BNP and BNP, renal function tests)., Results: NTproBNP values were reduced significantly among the three time-points ( p < 0.001). Among echocardiographic parameters, left ventricle end-diastolic volume (LV EDV) and E/e' significantly were reduced at the first evaluation (12 months), while left ventricle end-systolic volume (LV ESV) decreased during all follow-ups ( p < 0.001). LV EF ( p < 0.001) and GLS ( p < 0.001) significantly increased at both evaluations. The 6MWT ( p < 0.001) and KCCQ scores ( p < 0.001) increased significantly in the first 12 months and remained stable along the other time-points. NYHA class showed an increase in class 1 subjects and a decrease in class 3 subjects during follow-up. NTproBNP, BNP, 6MWT, and KCCQ scores showed a significant change in the first 12 months, while LVEF, GLS, and ESV changed during all evaluations., Conclusions: We verified that the improvements obtained after one year of therapy had not reached a plateau phase but continued to improve and were statistically significant at 5 years. Although our data should be confirmed in larger and multicentre studies, we can state that the utilization of Sacubitril/Valsartan has catalysed substantial transformations in the prognostic landscape of chronic HFrEF, yielding profound clinical implications.

Accidents are the main cause of injury in children, more than half events happen at home. Aims of this study were to assess if SARS-CoV-2 lockdown influence emergency department (ED) visits due to children domestic accident (DAs) and to identify factors associated with hospitalization. This was a multicentre, observational, and retrospective cohort study involving 16 EDs in Italy and enrolling children (3-13 years) receiving a visit in ED during March-June 2019 and March-June 2020. Risk factors for hospitalization were identified by logistic regression models. In total, 8860 ED visits due to domestic accidents in children occurred before (4380) and during (4480) lockdown, with a mean incidence of DA of 5.6% in 2019 and 17.9% in 2020 (p < 0.001) (IRR: 3.16; p < 0.001). The risk of hospitalization was influenced by the type of occurred accident, with fourfold higher for poisoning and twofold lower risk for stab-wound ones. In addition, a higher risk was reported for lockdown period vs 2019 (OR: 1.9; p < 0.001), males (OR: 1.4; p < 0.001), and it increased with age (OR: 1.1; p < 0.001).    Conclusions: The main limitation of this study is the retrospective collection of data, available only for patients who presented at the hospital. This does highlight possible differences in the total number of incidents that truly occurred. In any case, the COVID-19 lockdown had a high impact on the frequency of DAs and on hospitalization. A public health campaign aimed at caregivers would be necessary to minimize possible risks at home. What is Known: • In Italy, domestic accidents are the second leading cause of paediatric mortality after cancer. • During the first SARS-CoV-2 lockdown in 2020, a sharp decrease in the total number of Emergency Departments visits for all causes was observed, both in children and in adults. What is New: • During the first SARS-CoV-2 lockdown in 2020, domestic accidents involving children increased threefold from the previous year. • Higher risk of hospitalization was showed in minors accessing during 2020 vs 2019, in males than in females and it increased with advancing age. Considering the type of injury, a significant higher risk of hospitalization for poisoning was observed., (© 2023. The Author(s).)

Parasite infection is one of the many environmental factors that can significantly contribute to carcinogenesis and is already known to be associated with a variety of malignancies in both human and veterinary medicine. However, the actual number of cancerogenic parasites and their relationship to tumor development is far from being fully understood, especially in veterinary medicine. Thus, the aim of this review is to investigate parasite-related cancers in domestic and wild animals and their burden in veterinary oncology. Spontaneous neoplasia with ascertained or putative parasite etiology in domestic and wild animals will be reviewed, and the multifarious mechanisms of protozoan and metazoan cancer induction will be discussed., (© 2023. The Author(s).)

Chronic rhinosinusitis with nasal polyps (CRSwNP) is defined as a Type 2 eosinophilic disease, while CRSsNP is considered a Type 1 neutrophilic disease. Since neutrophils are also activated in eosinophilic CRSwNP, the eosinophil-neutrophil dualism has been revaluated. Among the inflammatory cells infiltrating sinus-nasal tissues, the role of mast cells (MCs) is not already recognized, although Clinical-Cytological Grading, which defines the severity of CRSwNP, attributes to mixed eosinophil-MC forms of CRSwNP a greater risk of recurrence. We aimed to examine nasal polyps from both a cytological and histopathological point of view, to evaluate the presence and localization of MCs. Cytological and histological examination of 39 samples of nasal polyps were performed. Immunohistochemistry was used to evaluate the presence of Tryptase + CD117 + MCs, which were counted both in the epithelial layer and in the lamina propria. A statistically significant correlation was found between intraepithelial MCs and CRSwNP severity (p < 0.001) and between the total eosinophil count and the total mast cell count (p < 0.001). Cytological examination and immunohistochemistry were comparable in detecting the presence of intraepithelial MCs (p = 0.002). The histological cut-off of 6 intraepithelial MCs was identified to detect severe CRSwNP (p < 0.001). MCs have been shown to be located in the lamina propria of almost all eosinophilic nasal polyps without significantly affecting their severity. Intraepithelial MCs are associated with greater severity of CRSwNP. Histopathological criteria of the eosinophil-MC form of CRSwNP in addition to the eosinophilic one, should be defined to guarantee patients effective and tailored treatments., (© 2023. The Author(s).)

Currently, it is estimated that 15% of human neoplasms globally are caused by infectious agents, with new evidence emerging continuously. Multiple agents have been implicated in various forms of neoplasia, with viruses as the most frequent. In recent years, investigation on viral mechanisms underlying tumoral transformation in cancer development and progression are in the spotlight, both in human and veterinary oncology. Oncogenic viruses in veterinary medicine are of primary importance not only as original pathogens of pets, but also in the view of pets as models of human malignancies. Hence, this work will provide an overview of the main oncogenic viruses of companion animals, with brief notes of comparative medicine., (© 2023. The Author(s).)

Introduction: The aim of our single-center case-control study is to evaluate whether minipuberty occurs in patients with hypoxic ischemic encephalopathy (HIE) who underwent therapeutic hypothermia (TH). We intend to conduct this evaluation by confronting the values of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and the values of testosterone in males and estradiol in females between newborns with HIE and in subsequent TH and healthy controls., Methods: We enrolled 40 patients (age: 56-179 days; 23 males), of whom 20 met the inclusion criteria for the case group and who underwent TH. A blood sample was taken from each patient at approximately 10 weeks of age to evaluate FSH and LH from the serum samples of all patients and to evaluate 17-beta estradiol (E2) and testosterone levels, respectively, from the serum samples of female and male patients., Results: It was found that minipuberty occurred in the case group patients, with no significant differences reported from the control group and with hormonal serum levels comparable to healthy infants of the control group (FSH 4.14 mUI/ml ± 5.81 SD vs. 3.45 mUI/ml ± 3.48 SD; LH 1.41 mUI/ml ±1.29 SD vs. 2.04 mUI/ml ±1.76 SD; testosterone in males 0.79 ng/ml ± 0.43 SD vs. 0.56 ng/ml ± 0.43 SD; 17-beta estradiol in females 28.90 pg/ml ± 16.71 SD vs. 23.66 pg/ml ± 21.29 SD)., Discussion: The results of the present study may pave the way for further research and the evaluation of more possible advantages of TH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Lanciotti, Sica, Penta, Parisi, Argentiero, Radicioni, Di Cara, Di Genova, Verrotti, Troiani and Esposito.)

Introduction: Chemotherapy plus immunotherapy is the standard of care for patients with metastatic NSCLC. No study has evaluated the outcomes of second-line chemotherapy treatments after progression following first-line chemo-immunotherapy., Method: This multicenter retrospective study evaluated the efficacy of second line (2L) chemotherapies after progression under first-line (1L) chemo-immunotherapy, measured by overall survival (2L-OS) and progression free survival (2L-PFS)., Results: A total of 124 patients were included. The mean age was 63.1 years, 30.6 % of the patients were female, 72.6 % had an adenocarcinoma and 43.5 % had a poor ECOG-performance status prior to 2L initiation. Sixty-four (52.0 %) patients were considered resistant to first line chemo-immunotherapy. (1L-PFS < 6 months). In 2L treatments, 57 (46.0 %) patients received taxane monotherapy, 25 (20.1 %) taxane plus anti-angiogenic, 12 (9.7 %) platinum-based chemotherapy and 30 (24.2 %) other chemotherapy. At a median follow-up of 8.3 months (95 %CI: 7.2-10.2), post initiation of 2L treatment, the median 2L-OS was 8.1 months (95 % CI: 6.4-12.7) and the median 2L-PFS was 2.9 months (95 %CI: 2.4-3.3). Overall, the 2L-objective response and 2L-disease control rates were 16.0 %, and 42.5 %, respectively. Taxane plus anti-angiogenic and platinum rechallenge achieved longest median 2L-OS: not reached (95 %CI: 5.8-NR) and 17.6 months (95 %CI 11.6-NR), respectively (p = 0.05). Patients resistant to the 1L treatment had inferior outcomes (2L-OS 5.1 months, 2L-PFS 2.3 months) compared with 1L responders (2L-OS 12.7 months, 2L-PFS 3.2 months)., Conclusion: In this real-life cohort, 2L chemotherapy achieved modest activity following progression under chemo-immunotherapy. 1L-resistant patients remained a refractory population, highlighting a need for new 2L strategies., 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 © 2023. Published by Elsevier B.V.)

During female lifetime and pregnancy, inflammation and cellular senescence are implicated in physiological processes, from ovulation and menstruation, to placental homeostasis and delivery. Several lifestyles, nutritional, and environmental insults, as well as long-lasting pregestational inflammatory diseases may lead to detrimental effects in promoting and sustaining a chronic excessive inflammatory response and inflammaging, which finally contribute to the decay of fertility and pregnancy outcome, with a negative effect on placental function, fetal development, and future health risk profile in the offspring. Maladaptation to pregnancy and obstetric disease may in turn increase maternal inflammaging in a feedback loop, speeding up aging processes and outbreak of chronic diseases. Maternal inflammaging may also impact, through transgenerational effects, on future adult health. Hence, efficacious interventions should be implemented by physicians and healthcare professionals involved in prevention activities to reduce the modifiable factors contributing to the inflammaging process in order to improve public health., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The literature about nervous system lymphoma (NSL) in dogs and cats is fragmentary, based on a few case series and case reports with heterogeneous results. The aim of our study was to retrospectively analyze 45 cases of canine and 47 cases of feline NSL and compare our results with previously reported data, also providing an extensive literature review. Breed, age, gender, clinical signs, type, and neurolocalization were recorded for each case. The pathological patterns and phenotype were assessed by histopathology and immunohistochemistry. The occurrence of central and peripheral NSL was similar between the two species in both primary and secondary types. NSL occurred with a slightly higher prevalence in Labrador Retrievers, and spinal cord lymphoma (SCL) was associated with young age in cats. The most frequent locations were the forebrain in dogs and the thoracolumbar segment in cats. Primary central nervous system lymphoma (CNSL) in cats most frequently involved the forebrain meninges, particularly as a B-cell phenotype. Peripheral NSL mostly affected the sciatic nerve in dogs and had no preferred location in cats. Nine different pathological patterns were identified, with extradural as the most prevalent SCL pattern in both species. Finally, lymphomatosis cerebri was described for the first time in a dog.

Maternal obesity (MO) is expanding worldwide, contributing to the onset of Gestational Diabetes Mellitus (GDM). MO and GDM are associated with adverse maternal and foetal outcomes, with short- and long-term complications. Growing evidence suggests that MO and GDM are characterized by epigenetic alterations contributing to the pathogenesis of metabolic diseases. In this pilot study, plasma microRNAs (miRNAs) of obese pregnant women with/without GDM were profiled at delivery. Nineteen women with spontaneous singleton pregnancies delivering by elective Caesarean section were enrolled: seven normal-weight (NW), six obese without comorbidities (OB/GDM(-)), and six obese with GDM (OB/GDM(+)). miRNA profiling with miRCURY LNA PCR Panel allowed the analysis of the 179 most expressed circulating miRNAs in humans. Data acquisition and statistics (GeneGlobe and SPSS software) and Pathway Enrichment Analysis (PEA) were performed. Data analysis highlighted patterns of significantly differentially expressed miRNAs between groups: OB/GDM(-) vs. NW: n = 4 miRNAs, OB/GDM(+) vs. NW: n = 1, and OB/GDM(+) vs. OB/GDM(-): n = 14. For each comparison, PEA revealed pathways associated with oxidative stress and inflammation, as well as with nutrients and hormones metabolism. Indeed, miRNAs analysis may help to shed light on the complex epigenetic network regulating metabolic pathways in both the mother and the foeto-placental unit. Future investigations are needed to deepen the pregnancy epigenetic landscape in MO and GDM.

Foxp3+ cell counts were evaluated by immunohistochemistry in 59 canine mammary tumors, 20 adenomas, and 39 carcinomas in three different compartments: intratumoral, within the adjacent stroma, and in the distant stroma. Foxp3+ lymphocyte counts were compared with histotype, grading, presence of lymphatic invasion, immunohistochemical expression of estrogen and progesterone receptors, expression of c-erbB-2, and the overall survival (OS). Our findings confirmed that Foxp3+ cells were significantly higher in canine mammary carcinomas compared to adenomas. A significantly higher number of Foxp3+ cells were detected in grade III carcinomas compared to grade II carcinomas, as well as in tumors with lymphatic invasion and loss of ER-expression. Finally, a high number of Foxp3+ cells was associated with poor prognosis. In conclusion, our findings highlighted the association of Foxp3+ lymphocytes with negative clinicopathological features and shorter overall survival (OS), thus confirming the role of Tregs as a negative prognostic marker in canine mammary carcinomas.

Mast cell tumor (MCT) is the most common malignant skin tumor in dogs. In order to gain more information on the prognostic markers in MCT, the role of the eosinophil granulocytes infiltrates was investigated and assessed by the evaluation of tumor-associated tissue eosinophilia (TATE) in 87 canine cutaneous MCTs. In human medicine, high TATE are often described in highly angiogenic tumors: we therefore assessed the vascular endothelial growth factor (VEGF) expression in neoplastic mast cells. TATE and VEGF expression were compared between themselves, with histological grading, immunohistochemical expression of KIT and Ki-67, and with the recurrence. We found a statistically significant correlation between TATE and Patnaik grading ( p = 0.041), Kiupel grading ( p = 0.022), immunohistochemical KIT expression ( p = 0.015), and tumor recurrence ( p = 0.000). No associations were observed with Ki-67 and VEGF expression. This is the first evaluation of TATE and its prognostic value in canine MCTs in veterinary oncology. This study suggest that this investigation could be an important source of information for this tumor and for other neoplasms.

Heart failure (HF) is a complex, multifactorial, progressive clinical condition affecting 64.3 million people worldwide, with a strong impact in terms of morbidity, mortality and public health costs. In the last 50 years, along with a better understanding of HF physiopathology and in agreement with the four main models of HF, many therapeutic options have been developed. Recently, the European Society of Cardiology (ESC) HF guidelines enthusiastically introduced inhibitors of the sodium-glucose cotransporter (SGLT2i) as first line therapy for HF with reduced ejection fraction (HFrEF) in order to reduce hospitalizations and mortality. Despite drugs developed as hypoglycemic agents, data from the EMPA-REG OUTCOME trial encouraged the evaluation of the possible cardiovascular effects, showing SGLT2i beneficial effects on loading conditions, neurohormonal axes, heart cells' biochemistry and vascular stiffness, determining an improvement of each HF model. We want to give a boost to their use by increasing the knowledge of SGLT2-I and understanding the probable mechanisms of this new class of drugs, highlighting strengths and weaknesses, and providing a brief comment on major trials that made Gliflozins a cornerstone in HF therapy. Finally, aspects that may hinder SGLT2-i widespread utilization among different types of specialists, despite the guidelines' indications, will be discussed.

Roe and Fallow deer are common wild ruminants widely distributed in Italy. Infectious diseases of these species can potentially pose health risks to domestic animals and humans. However, few studies have been conducted in which immune system cells in these species were phenotyped. The aims of this study were to determine the cross-reactivity of a wide anti-human panel of commercial antibodies on formalin-fixed and paraffin-embedded (FFPE) samples and to describe the distribution of roe and fallow deer main immune cell subsets in the lymph nodes and spleen. Twenty retromandibular lymph nodes (RLNs) and spleen samples were collected from 10 roe deer and 10 fallow deer and were tested by a panel of 12 commercial anti-human antibodies. The CD79a, CD20, CD3, Iba-1, MAC387, and AM-3K antibodies were successfully labeled cells in cervine tissue, while the Foxp3 and the CD68 did not show suitable immunostaining. This study supplies the first immunohistochemical description of immune cell subpopulations in non-pathological spleen and RLNs from roe and fallow deer and provides an easily repeatable manual IHC protocol to immunolocalize cervine B-, T-cells, and macrophages subsets in FFPE tissue samples.

Introduction: Currently, the adherence to nutritional guidelines is low, with alarming rates of obesity worldwide and micronutrient deficiencies documented even in industrialised countries. As a consequence, nutritional screening and counselling represent a critical subject in early pregnancy, aiming to improve pregnancy outcomes and population health., Methods and Analysis: In this setting, the development of a simple and reproducible nutritional checklist is of utmost importance. The Simple Study is a longitudinal prospective multicentre study aiming to identify the associations between maternal nutritional habits in the first trimester, early markers of placental function and pregnancy outcomes on a large population of singleton pregnancies in Italy.Ongoing healthy singleton pregnancies will be enrolled at the ultrasound scan of the first trimester combined screening test (11 +0 -13 +6 gestational weeks). A nutritional score measuring the adherence to a healthy diet and nutritional deficiencies will be collected at recruitment. Fetal (crown-rump length, nuchal translucency (NT), biparietal diameter, femur length) and utero placental (placental volume, uterine arteries Doppler velocimetry) ultrasound data and biochemical placental markers (pregnancy-associated plasma protein A, free ß-human chorionic gonadotropin) will be collected. Second and third trimester ultrasound records and birth outcomes will be recorded from medical registers. This study will set the stage for introducing a reproducible, time-saving and low-cost nutritional screening in pregnancy. The nutritional score will allow the implementation of specific corrective measures with potential large impact on placentation and pregnancy outcomes., Ethical and Dissemination: Ethical approval for this study was obtained from the Milano Area 1 Ethics Committee (No 46091, 7 November 2018) prior to the commencement of the research.The dissemination plan includes the presentation of abstracts and findings at national and international scientific meetings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Immune checkpoint inhibitors (ICIs) immunotherapy has represented a breakthrough in cancer treatment. Clinical use of ICIs has shown an acceptable safety profile and promising antitumor activity. Nevertheless, some patients do not obtain clinical benefits after ICIs therapy. In order to improve and cure an increasing number of patients, the field has moved toward the discovery of new ICIs expressed by cells of innate immunity with an elevated inherent antitumor activity, such as natural killer cells. This review will focus on the recent findings concerning the role of classical and non-classical immune checkpoint molecules and receptors that regulate natural killer cell function, as potential targets, and their future clinical application.

Introduction: In recent years, immunotherapy has become a pillar in the treatment of advanced, non-oncogene-addicted non-small cell lung cancer (NSCLC). Programmed death ligand 1 (PD-L1) expression is currently the only factor used to predict response to immunotherapy in clinical practice. Specifically, single-agent pembrolizumab as first-line therapy is approved for tumors with high expression of PD-L1 (≥50%) while immunotherapy and chemotherapy are approved for any PD-L1. However, combinations of immune-checkpoint inhibitors (ICIs) and other agents may confer higher benefit than immunotherapy alone in some circumstances., Areas Covered: We reviewed the available data regarding the combined use of ICIs and chemotherapy in patients with advanced, treatment-naïve NSCLC. In light of the benefit demonstrated in advanced disease, these combinations have been subsequently tested in other settings. We collected the most relevant findings regarding efficacy and safety of chemo-immunotherapy combinations in early and locally advanced NSCLC., Expert Opinion: Immune-chemotherapy combinations demonstrated benefit in the advanced setting, and this strategy in now being applied in the early and local advanced settings. A description of clinical and biological predictors of response is required in order to identify patients who may benefit the most from combination therapy.

Background: Maternal nutrition represents a critical risk factor for adverse health outcomes in both mother and offspring. We aimed to investigate associations between maternal nutritional habits, biomarker status, and pregnancy outcome among Italian healthy normal-weight pregnancies. Methods: Multicenter prospective cohort study recruiting Italian healthy normal-weight women with singleton spontaneous pregnancies at 20 ± 2 weeks (T1) in Milan and Naples. All patients underwent nutritional evaluations by our collecting a 7-day weighed dietary record at 25 ± 1 weeks (T2) and a Food Frequency Questionnaire at 29 ± 2 weeks (T3). Maternal venous blood samples were collected at T3 to assess nutritional, inflammatory and oxidative biomarker concentrations (RBCs folate, vitamin D, hepcidin, total antioxidant capacity). Pregnancy outcomes were collected at delivery (T4). General linear models adjusted for confounding factors were estimated to investigate associations between maternal dietary pattern adherence, nutrient intakes, biomarker concentrations and delivery outcomes. Results: 219 healthy normal-weight pregnant women were enrolled. Vitamin D and RBCs folate concentrations, as well as micronutrient intakes, were consistently below the recommended range. In a multi-adjusted model, maternal adherence to the most prevalent 'high meat, animal fats, grains' dietary pattern was positively associated with hepcidin concentrations and negatively associated with gestational age at delivery in pregnancies carrying female fetuses. Hepcidin plasma levels were further negatively associated to placental weight, whereas vitamin D concentrations were positively associated to neonatal weight. Conclusions: A high adherence to an unbalanced 'high meat, animal fats, grains' pattern was detected among Italian normal-weight low-risk pregnancies, further associated with maternal pro-inflammatory status and gestational age at delivery. This evidence underlines the need for a dedicated nutritional counseling even among low-risk pregnancies.

Adolescent health and well-being are of great concern worldwide, and adolescents encounter particular challenges, vulnerabilities and constraints. The dual challenges of adolescent parenthood and obesity are of public health relevance because of the life-altering health and socioeconomic effects on both the parents and the offspring. Prevention and treatment strategies at the individual and population levels have not been successful in the long term, suggesting that adolescent pregnancy and obesity cannot be managed by more of the same. Here, we view adolescent obese pregnancy through the lens of the social contract with youth. The disruption of this contract is faced by today's adolescents, with work, social and economic dilemmas which perpetuate socioeconomic and health inequities across generations. The lack of employment, education and social opportunities, together with obesogenic settings, increase vulnerability and exposure to lifelong health risks, affecting their offspring's life chances too. To break such vicious circles of disadvantage and achieve sustainable solutions in real-world settings, strong efforts on the part of policymakers, healthcare providers and the community must be oriented towards guaranteeing equity and healthy nutrition and environments for today's adolescents. The involvement of adolescents themselves in developing such programs is paramount, not only so that they feel a sense of agency but also to better meet their real life needs.

The mouse mammary tumour virus (MMTV) is implicated in the aetiology of murine mammary carcinomas and a variant of it, the type B leukemogenic virus, can cause murine thymic lymphomas. Interestingly, a MMTV-like virus is suspected to be involved in human breast cancer and feline mammary carcinomas. However, to date, no cases of MMTV-like sequence amplifications have been described in lymphoid neoplasms in veterinary literature. The aim of this study was to investigate the presence of env nucleotide sequences and protein 14 (p14) of a MMTV-like virus in fifty-three feline lymphoma samples. Our results show that MMTV-like sequences were detected in 5/53 tumours (9.4%): three gastrointestinal lymphomas (one B-type diffuse large, one B-type small non-cleaved, and one T-type diffuse mixed lymphoma); and two nasal lymphomas (one B-type diffuse small cleaved lymphoma and one B-type diffuse mixed lymphoma). P14 expression was detected in the cytoplasm, and rarely in nuclei, exclusively of neoplastic cells from PCR-positive tumours. The correlation between the presence of the MMTV-env like sequences (MMTVels) and p14 antigen was statistically significant in nasal lymphomas. All cats with MMTVels-positive lymphoma had a history of contact with the outdoor environment and/or catteries, and two deceased subjects shared their environment with cats that also died of lymphoma. In conclusion, this study succeeds in demonstrating the presence of MMTVels and p14 in feline lymphomas. The characterization of the immunophenotype of MMTVels-positive lymphomas could contribute to the understanding of a possible role of a MMTV-like virus in feline tumour aetiology. The significant association between the presence of the viral sequences in lymphoid tumours and their nasal localization, together with the data collected through supplementary anamnesis, should be further analysed in order to understand the epidemiology of the virus., (© 2022. The Author(s).)

Introduction: Two-dimensional strain echocardiography (2D-SE) is a reliable method for measuring deformation of the left ventricle., Aim of the Study: Aim of the study was to determine changes in 2D-SE parameters over time collected during dipyridamole stress echo-cardiography (dipy-stress) and prognosis of patients with non-diagnostic dipy-stress results., Methods: In the first phase of the study, assessment of a prospective enrolled population with a non-diagnostic dipy-stress test result was conducted, checking through coronary CT angiography (CCTA) the presence of coronary artery disease (CAD). In the follow-up phase, an echocardiographic re-evaluation and outcome analysis during a mean follow-up of 78 months was carried out., Results: In the first phase, Global Circumferential Strain (GCS) values were similar in the CCTA positive and CCTA negative groups at rest and after stress. For Global Longitudinal Strain (GLS), there was a significant reduction (p < .0001) in the CCTA positive group compared to the CCTA negative group. After 78 ± 9 months none of the enrolled patients experimented cardiac events. Values of GCS, both at rest and after stress, did not differ statistically comparing follow-up values with baseline ones. No statistically significant changes were seen in the same analysis for GLS rest and stress values, between baseline and follow-up in the two groups., Conclusions: Performing 2D-SE during dipy-stress can detect mild CAD that conventional stress-tests miss. Patients with mild coronary stenosis may have a favorable mid-term prognosis, but efforts should be made to investigate the decrease trend in GLS, at rest and after stress, reported in this patient group., (© 2022 Wiley Periodicals LLC.)

Since its discovery as a milk factor, mouse mammary tumor virus (MMTV) has been shown to cause mammary carcinoma and lymphoma in mice. MMTV infection depends upon a viral superantigen (sag)-induced immune response and exploits the immune system to establish infection in mammary epithelial cells when they actively divide. Simultaneously, it avoids immune responses, causing tumors through insertional mutagenesis and clonal expansion. Early studies identified antigens and sequences belonging to a virus homologous to MMTV in human samples. Several pieces of evidence fulfill a criterion for a possible causal role for the MMTV-like virus in human breast cancer (BC), though the controversy about whether this virus was linked to BC has raged for over 40 years in the literature. In this review, the most important issues related to MMTV, from its discovery to the present days, are retraced to fully explore such a controversial issue. Furthermore, the hypothesis of an MMTV-like virus raised the question of a potential zoonotic mouse-man transmission. Several studies investigate the role of an MMTV-like virus in companion animals, suggesting their possible role as mediators. Finally, the possibility of an MMTV-like virus as a cause of human BC opens a new era for prevention and therapy.

Hepatitis E virus (HEV) is a common causative agent of acute hepatitis in the world, with a serious public health burden in both developing and industrialized countries. Cervids, along with wild boars and lagomorphs, are the main wild hosts of HEV in Europe and constitute a documented source of infection for humans. The aim of this study was to evaluate the presence of HEV in roe deer ( Capreolus capreolus ) and fallow deer ( Dama dama ) living in Tuscany, Central Italy. Liver samples from 48 roe deer and 60 fallow deer were collected from carcasses during the hunting seasons. Following the results obtained from molecular and histopathologic studies, 5/48 (10.4%) roe deer and 1/60 (1.7%) fallow deer liver samples were positive for the presence of HEV RNA. All PCR-positive livers were also IHC-positive for viral antigen presence, associated with degenerative and inflammatory lesions with predominantly CD3+ cellular infiltrates. This study represents the first identification in Italy of HEV RNA in roe and fallow deer and the first study in literature describing liver alterations associated with HEV infection in cervids. These results demonstrate that HEV is present in wild cervid populations in Italy and confirm the potential zoonotic role of these species.

It is well established that pregnancy induces deep changes in the immune system. This is part of the physiological adaptation of the female organism to the pregnancy and the immunological tolerance toward the fetus. Indeed, over the three trimesters, the suppressive T regulatory lymphocytes are progressively more represented, while the expression of co-stimulatory molecules decreases overtime. Such adaptations relate to an increased risk of infections and progression to severe disease in pregnant women, potentially resulting in an altered generation of long-lived specific immunological memory of infection contracted during pregnancy. How potent is the immune response against SARS-CoV-2 in infected pregnant women and how long the specific SARS-CoV-2 immunity might last need to be urgently addressed, especially considering the current vaccinal campaign. To address these questions, we analyzed the long-term immunological response upon SARS-CoV-2 infection in pregnant women from delivery to a six-months follow-up. In particular, we investigated the specific antibody production, T cell memory subsets, and inflammation profile. Results show that 80% developed an anti-SARS-CoV-2-specific IgG response, comparable with the general population. While IgG were present only in 50% of the asymptomatic subjects, the antibody production was elicited by infection in all the mild-to-critical patients. The specific T-cell memory subsets rebalanced over-time, and the pro-inflammatory profile triggered by specific SARS-CoV-2 stimulation faded away. These results shed light on SARS-CoV-2-specific immunity in pregnant women; understanding the immunological dynamics of the immune system in response to SARS-CoV-2 is essential for defining proper obstetric management of pregnant women and fine tune gender-specific vaccinal plans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fenizia, Cetin, Mileto, Vanetti, Saulle, Di Giminiani, Saresella, Parisi, Trabattoni, Clerici, Biasin and Savasi.)

The photoinduced etiopathology of actinic keratosis and squamous cell carcinoma in feline species is well known. This etiology has also been reported for non-epithelial cutaneous tumors in other species. To date, no cases of auricular non-epithelial cutaneous neoplasms erased in a contest of actinic keratosis in cats have been reported. The aim of this study was to describe feline auricular non-epithelial cutaneous neoplasms associated with typical UV-induced cutaneous lesions and solar elastosis. The study was conducted on five feline cases diagnosed with auricular non-epithelial cutaneous tumors (two fibrosarcomas, one mixosarcoma, one epithelioid melanoma and one hemangiosarcoma), selected from the Tumor Registry of the Department of Veterinary Sciences of the University of Pisa (1998-2018). Ten and six feline auricular biopsies of normal skin and skin with actinic keratosis, respectively, were used as controls. Orcein stain was used to investigate solar elastosis. Histological changes related to chronic solar irradiation were documented in the skin adjacent to the neoplastic lesions in the five cats. Considering the anatomical localization and the results of histopathology, this study suggests that non-epithelial cutaneous neoplasms may have a UV-induced etiopathogenesis in the feline species.

Pregnant women display a higher risk of progression to disease and higher viral loads during infections due to their more permissive, tolerogenic immune system. However, only few studies have focused on SARS-CoV-2 intrapartum vertical transmission via vaginal secretions or faeces. The aim of this study was to investigate the presence of the virus in vaginal, rectal and blood specimens from pregnant women characterized by different COVID-19 disease severity. We enrolled 56 SARS-CoV-2-positive pregnant women, of which 46 (82%) were in the third trimester of pregnancy, 6 (10%) in the second and 4 (7%) in the first. QPCR was performed to detect the virus in vaginal and rectal swabs and in plasma samples. SARS-CoV-2 was detected in 27% of rectal swabs of pregnant women in the third trimester, while no virus particles were detected in vaginal swabs of the same patients. Furthermore, only 4% plasma samples tested positive to SARS-CoV-2. No virus was detected in newborn's nasopharyngeal swabs. Despite the low number of subjects enrolled, our data suggest that, while theoretically possible, intrapartum vaginal or orofecal SARS-CoV-2 transmission seems to be unlikely., (© 2021. The Author(s).)

In the last few years MMTV-like nucleotide sequences were detected in some feline and canine mammary tumours. Due to the confirmed role of cats in the epidemiology of the MMTV-like virus, the aim of this study was to investigate the main pathological features of positive feline mammary carcinomas (FMCs). Twenty-four FMCs were collected at the University of Bologna, submitted to laser microdissection and analysed by nested fluorescence-PCR using primer sets specific for MMTV env sequence. For immunohistochemistry, an antibody against MMTV protein 14 (p14) was used. MMTV-like sequences were detected in three out of 24 FMCs (12.5%), one tubular carcinoma, one tubulopapillary carcinoma and one ductal carcinoma. All PCR-positive tumours were also positive for p14. Multiple nucleotide alignment has shown similarity to MMTV ranging from 98% to 100%. All the 102 examined FMCs were submitted to immunohistochemistry for molecular phenotyping. Of the nine MMTV-like positive FMCs, six were basal-like and three luminal-like. Our results demonstrate MMTV-like sequences and protein in FMCs of different geographic areas. Molecular phenotyping could contribute to understand the possible role of MMTV-like virus in FMC tumor biology.

Women of childbearing age are largely affected by several autoimmune disorders (the estimates range between 1.5 and 10 per 10,000). The increasing number of effective biological agents has dramatically revolutionized the treatment of these clinical conditions, ameliorating the patient's quality of life. The use of these agents by women during pregnancy is growing to ensure the disease activity control and avoid adverse health outcomes. However, for many newer biological agents, the degree of information concerning their use in pregnancy is often incomplete to perform a conclusive risk assessment on fetal and maternal health given the exclusion of this specific population from pharmacological clinical trials. More recently, the COVID-19 pandemic has confirmed the unacceptable inequities of pharmacological research and medical treatment for pregnant and lactating women, exacerbating the need for filling the gaps of quantitative and qualitative pharmacology data in this sensitive population. ere we summarize (i) what is already known about safety and effectiveness of biological agents in this understudied population (with specific focus on pregnancy-related health outcomes), and what we are going to learn from the on-going studies among pregnant women treated with biological agents; (ii) the methodological and ethical considerations that characterize the pharmacological research in pregnancy, also discussing emerging evidence on the use of therapeutic drug monitoring (TDM) in this clinical setting., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

MicroRNAs are gene expression regulators associated with several human pathologies, including those generated by viral infections. Their role in SARS-CoV-2 infection and COVID-19 has been investigated and reviewed in many informative studies; however, a thorough miRNA outline in SARS-CoV-2-infected pregnant women (SIPW), at both systemic and placental levels, is missing. To fill this gap, blood and placenta biopsies collected at delivery from 15 asymptomatic SIPW were immediately analysed for: miRNA expression ( n = 84) (QPCR array), antiviral/immune mRNA target expression ( n = 74) (QGene) and cytokine/chemokines production ( n = 27) (Multiplex ELISA). By comparing these results with those obtained from six uninfected pregnant women (UPW), we observed that, following SARS-CoV-2 infection, the transcriptomic profile of pregnant women is significantly altered in different anatomical districts, even in the absence of clinical symptoms and vertical transmission. This characteristic combination of miRNA and antiviral/immune factors seems to control both the infection and the dysfunctional immune reaction, thus representing a positive correlate of protection and a potential therapeutic target against SARS-CoV-2.