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Abstract Design closure and parameter optimisation are crucial in creating cutting-edge antennas. Antenna performance can be improved by fine-tuning preliminary designs created using theoretical considerations and rough dimension adjustment via supervised parameter sweeps. This paper introduces a frequency reconfigurable antenna design that can operate at 28/38 GHz frequencies to meet FCC and Ofcom standards for 5G applications and in the 18 GHz frequency band for K-band radar applications. A PIN diode is used in this design to configure multiple frequency bands. The antenna has a modified rectangular patch-like structure and two optimised plugins on either side. The study that is being presented focuses on maximising the parameters that are subject to optimisation, including length (Ls), width (Ws), strip line width (W1), and height (ht), where the antenna characteristic parameters such as directivity is tuned by a hybrid optimisation scheme called Elephant Clan Updated Grey Wolf Algorithm (ECU-GWA). Here, the performance of gain and directivity are optimally attained by considering parameters such as length, width, ground plane length, width, height, and feed offsets X and Y. The bandwidth of the proposed antenna at − 10 dB is 0.8 GHz, 1.94 GHz, and 7.92 GHz, respectively, at frequencies 18.5 GHz, 28.1 GHz, and 38.1 GHz. Also, according to the simulation results, in the 18 GHz, 28 GHz, and 38 GHz frequencies S11, the return loss is − 60.81 dB, − 56.31 dB, and − 14.19 dB, respectively. The proposed frequency reconfigurable antenna simulation results achieve gains of 4.41 dBi, 6.33 dBi, and 7.70 dBi at 18.5 GHz, 28.1 GHz, and 38.1 GHz, respectively. Also, a microstrip quarter-wave monopole antenna with an ellipsoidal-shaped complementary split-ring resonator-electromagnetic bandgap structure (ECSRR-EBG) structure has been designed based on a genetic algorithm having resonating at 2.9 GHz, 4.7 GHz, 6 GHz for WLAN applications. The gain of the suggested ECSRR metamaterial and EBG periodic structure, with and without the ECCSRR bow-tie antenna. This is done both in the lab and with numbers. The measured result shows that the ECSRR metamaterial boosts gain by 5.2 dBi at 5.9 GHz. At 5.57 GHz, the two-element MIMO antenna achieves its lowest ECC of 0.00081.

Abstract To determine the readmissions trends and the comorbidities of patients with heart failure that most influence hospital readmission rates. Heart failure (HF) is one of the most prevalent health problems as it causes loss of quality of life and increased health-care costs. Its prevalence increases with age and is a major cause of re-hospitalisation within 30 days after discharge. INCA study had observational and ambispective design, including 4,959 patients from 2000 to 2019, with main diagnosis of HF in Extremadura (Spain). The variables examined were collected from discharge reports. To develop the readmission index, capable of discriminating the population with higher probability of re-hospitalisation, a Competing-risk model was generated. Readmission rate have increased over the period under investigation. The main predictors of readmission were: age, diabetes mellitus, presence of neoplasia, HF without previous hospitalisation, atrial fibrillation, anaemia, previous myocardial infarction, obstructive pulmonary disease (COPD) and chronic kidney disease (CKD). These variables were assigned values with balanced weights, our INCA index showed that the population with values greater than 2 for men and women were more likely to be re-admitted. Previous HF without hospital admission, CKD, and COPD appear to have the greatest effect on readmission. Our index allowed us to identify patients with different risks of readmission.

The monitoring of stranded marine mammals represents a strategic method to assess their health, conservation status, and ecological role in the marine ecosystem. Networks worldwide track stranding events for the passive monitoring of mortality patterns, emerging and reemerging pathogens, climate change, and environmental degradation from a One Health perspective. This study summarizes pathogen prevalence data from the Italian Stranding Network (ISN) derived from post-mortem investigations on cetaceans found dead stranded along the Italian coastline between 2015 and 2020. The decomposition of the carcasses and logistics limited the post-mortem examination to 585 individuals, out of 1236 single-stranding reports. The most relevant pathogens identified were Cetacean Morbillivirus, Herpesvirus, Brucella spp., and Toxoplasma gondii, whose roles as environmental stressors are well known, despite their real impact still needing to be investigated in depth. Statistical analysis showed that age and sex seem to be positively related to the presence of pathogens. This study represents the first step in harmonizing post-mortem investigations, which is crucial for evidence-based conservation efforts. Implementing diagnostic and forensic frameworks could offer an indirect insight into the systematic monitoring of diseases to improve the identification of regional and temporal hotspots in which to target specific mitigation, management, and conservation strategies.

Background: The prognostic role of imaging with [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) in oropharynx cancer (OPC) has been demonstrated in the past. The aim of this study was to assess the prognostic impact of both baseline and post-treatment PET/CT in patients with OPC and treated with chemo- and/or radiotherapy. Methods: The PET/CT parameters of scans performed before and after therapy were collected and analyzed to find significant prognosticators for progression-free survival (PFS) and overall survival (OS). Human papillomavirus (HPV) infection’s influence on the prognosis was also taken into account. Results: A total of 66 patients were included in the study. The staging volumetric parameters of PET/CT were significant prognosticators for OS, while the same parameters were affordable predictors for PFS at the restaging evaluation. No significant correlations between HPV infection and PET/CT parameters were reported. Conclusion: The prognostic role of volumetric [18F]FDG PET/CT parameters in patients with OPC was reported.

Key Clinical Message PET‐driven SBRT plus pembrolizumab as first‐line therapy against pleomorphic Pancoast cancer appears beneficial, probably due to high equivalent doses of SBRT on photopenic necrotic core and synergic immune system stimulation of immunoradiotherapy.

Abstract Glucose is a universally available inexpensive biomarker, which is increased as part of the physiological stress response to acute myocardial infarction (AMI) and may therefore help in its early diagnosis. To test this hypothesis, glucose, high-sensitivity cardiac troponin (hs-cTn) T, and hs-cTnI were measured in consecutive patients presenting with acute chest discomfort to the emergency department (ED) and enrolled in a large international diagnostic study (NCT00470587). Two independent cardiologists centrally adjudicated the final diagnosis using all clinical data, including serial hs-cTnT measurements, cardiac imaging and clinical follow-up. The primary diagnostic endpoint was index non-ST-segment elevation MI (NSTEMI). Prognostic endpoints were all-cause death, and cardiovascular (CV) death or future AMI, all within 730-days. Among 5639 eligible patients, NSTEMI was the adjudicated final diagnosis in 1051 (18.6%) patients. Diagnostic accuracy quantified using the area under the receiver-operating characteristics curve (AUC) for the combination of glucose with hs-cTnT and glucose with hs-cTnI was very high, but not higher versus that of hs-cTn alone (glucose/hs-cTnT 0.930 [95% CI 0.922–0.937] versus hs-cTnT 0.929 [95% CI 0.922–0.937]; glucose/hs-cTnI 0.944 [95% CI 0.937–0.951] versus hs-cTnI 0.944 [95% CI 0.937–0.951]). In early-presenters, a dual-marker strategy (glucose

Abstract Researchers often use terminology to define their participant groups that is rooted in a clinical understanding of the group’s shared identity(ies). Such naming often ignores the ways that the individuals who comprise these populations identify themselves. One oft-cited benefit of patient-oriented or community-engaged research is that language is local and relevant to impacted communities. This paper aims to contribute to the literature on how this local and relevant language can best be established. We ask how researchers can identify and implement accurate terminology, even when divergent perspectives exist within the communities involved. We draw from our experience with the Expanding Plasma Donation in Canada study, a community-engaged research study, which explored the views of people impacted by the “men who have sex with men” (MSM) blood donation policies in Canada. We describe the collaborative process through which we came to a consensual naming of this population, the challenges we faced, and a set of guiding principles we used to address them. We did not find an all-encompassing term or acronym that worked for all stages of research. Instead, we offer a set of guiding principles that can aid researchers engaging in a similar process: harm reduction, consent and transparency, collaboration and community involvement, recognition of missing voices, and resisting and/or restructuring oppressive standards.

Background: Fractures through the physis account for 18–30% of all paediatric fractures, leading to growth arrest in up to 5.5% of cases. We have limited knowledge to predict which physeal fractures result in growth arrest and subsequent deformity or limb length discrepancy. The purpose of this study is to identify factors associated with physeal growth arrest to improve patient outcomes. Methods: This prospective cohort study was designed to develop a clinical prediction model for growth arrest after physeal injury. Patients ≤ 18 years old presenting within four weeks of injury were enrolled if they had open physes and sustained a physeal fracture of the humerus, radius, ulna, femur, tibia or fibula. Patients with prior history of same-site fracture or a condition known to alter bone growth or healing were excluded. Demographic data, potential prognostic indicators, and radiographic data were collected at baseline, during healing, and at one- and two-years post-injury. Results: A total of 332 patients had at least six months of follow-up or a diagnosis of growth arrest within six months of injury. In a comparison analysis, patients who developed growth arrest were more likely to be older (12.8 years vs. 9.4 years) and injured on the right side (53.0% vs. 45.7%). Initial displacement and angulation rates were higher in the growth arrest group (59.0% vs. 47.8% and 47.0% vs. 38.8%, respectively), but the amount of angulation was similar (27.0° vs. 28.4°). Rates of growth arrest were highest in distal femoral fractures (86%). Conclusions: The incidence of growth arrest in this patient population appears higher than the past literature reports at 30.1%. However, there may be variances in diagnostic criteria for growth arrest, and the true incidence may be lower. A number of patients were approaching skeletal maturity, and any growth arrest is likely to have less clinical significance in these cases. Further prospective long-term follow-up is required to determine risk factors, incidence, and true clinical impact of growth arrest when it does occur.

Spontaneous smiles in response to politicians can serve as an implicit barometer for gauging electorate preferences. However, it is unclear whether a subtle Duchenne smile-an authentic expression involving the coactivation of the zygomaticus major (ZM) and orbicularis oculi (OO) muscles-would be elicited while reading about a favored politician smiling, indicating a more positive disposition and political endorsement. From an embodied simulation perspective, we investigated whether written descriptions of a politician's smile would trigger morphologically different smiles in readers depending on shared or opposing political orientation. In a controlled reading task in the laboratory, participants were presented with subject-verb phrases describing left and right-wing politicians smiling or frowning. Concurrently, their facial muscular reactions were measured via electromyography (EMG) recording at three facial muscles: the ZM and OO, coactive during Duchenne smiles, and the corrugator supercilii (CS) involved in frowning. We found that participants responded with a Duchenne smile detected at the ZM and OO facial muscles when exposed to portrayals of smiling politicians of same political orientation and reported more positive emotions towards these latter. In contrast, when reading about outgroup politicians smiling, there was a weaker activation of the ZM muscle and no activation of the OO muscle, suggesting a weak non-Duchenne smile, while emotions reported towards outgroup politicians were significantly more negative. Also, a more enhanced frown response in the CS was found for ingroup compared to outgroup politicians' frown expressions. Present findings suggest that a politician's smile may go a long way to influence electorates through both non-verbal and verbal pathways. They add another layer to our understanding of how language and social information shape embodied effects in a highly nuanced manner. Implications for verbal communication in the political context are discussed.

In adolescence individuals enlarge their social relationships and peer groups acquire a strong importance for their identity. Moreover, adolescents can experiment negative relationships with peers, i.e., bullying/cyberbullying. The present study aims to investigate the relationship between the feeling of belonging to a specific group, social identification, the distance that adolescents maintain interacting with others, interpersonal distance, and bullying/cyberbullying behaviors. Adolescents (age range 10-15 years) completed online measures of group identification (social identification with classmates, friends and family), interpersonal distance, and bullying and cyberbullying (perpetration and victimization). Results showed that adolescents with low social identification with classmates and friends chose larger interpersonal distance. Additionally, low scores in social identification with classmates were associated with higher victimization in cyberbullying. In contrast, adolescents with low scores in social identification with family were more involved as bullies in bullying and as victims in cyberbullying. Male adolescents were more likely to be victimized in bullying than females. This study underlines how social identification with peers and family works as a buffer in interfacing strangers, adjusting the distance maintained with them, and as a protective factor against aggressive relationships in adolescence. This study provides new opportunities for psychologists in understanding the psychological dynamics that shape social interactions among adolescents.

Sinonasal tumours are heterogeneous malignancies, presenting different histological features and clinical behaviour. Many studies emphasize the role of specific miRNA in the development and progression of cancer, and their expression profiles could be used as prognostic biomarkers to predict the survival. Recently, using the next-generation sequencing (NGS)-based miRNome analysis the miR-34/miR-449 cluster was identified as miRNA superfamily involved in the pathogenesis of sinonasal cancers (SNCs). In the present study, we established an Argonaute-2 (AGO2): mRNA immunoprecipitation followed by high-throughput sequencing to analyse the regulatory role of miR-34/miR-449 in SNCs. Using this approach, we identified direct target genes (targetome), which were involved in regulation of RNA-DNA metabolic, transcript and epigenetic processes. In particular, the STK3, C9orf78 and STRN3 genes were the direct targets of both miR-34c and miR-449a, and their regulation are predictive of tumour progression. This study provides the first evidence that miR-34/miR-449 and their targets are deregulated in SNCs and could be proposed as valuable prognostic biomarkers.

Background: Infection of Cardiac Implantable Electronic Devices (CIEDI) is a real public health problem. The main aim of this study was to determine the diagnostic performance of 18F-FDG PET/CT in the diagnosis of CIEDI. Methods: A total of 48 patients, who performed 18F-FDG PET/CT for the clinical suspicion of CIEDI were retrospectively analyzed; all patients were provided with a model with procedural recommendations before the exam. Sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy (DA) of 18F-FDG PET/CT were calculated; the reproducibility of qualitative analysis was assessed with Cohen’s κ test. The semi-quantitative parameters (SUVmax, SQR and TBR) were evaluated in CIEDI+ and CIEDI− patients using the Student’ t-test; ROC curves were elaborated to detect cut-off values. The trend of image quality with regards to procedural recommendation adherence was evaluated. Results: Se, Sp, PPV, NPV and DA were respectively 96.2%, 81.8%, 86.2%, 94.7% and 89.6%. The reproducibility of qualitative analysis was excellent (K = 0.89). Semiquantitative parameters resulted statistically different in CIEDI+ and CIEDI− patients. Cut-off values were SUVmax = 2.625, SQR = 3.766 and TBR = 1.29. Trend curves showed increasing image quality due to adherence to procedural recommendations. Conclusions: 18F-FDG-PET/CT is a valid tool in the management of patients suspected of CIEDI and adherence to procedural recommendations improves its image quality.

Background: Petrous apex cholesterol granulomas (PACGs) are benign inflammatory cystic lesions of the temporal bone. Usually, asymptomatic patients may develop symptoms as the lesions expand. The diagnosis is based on both CT and MRI scans and the management relies on “wait and scan” or surgery. This paper aims at evaluating surgical outcomes and proposing a CT-based classification and a management algorithm. Methods: Patients with PACGs who were surgically treated between 2014 and 2024 were included. Symptoms, imaging, approach type and complications were considered. CT scans were classified as Type A (preserved apex cellularity), Type B (erosion of the apex cellularity), and Type C (involvement of the noble structures bone boundaries). The possible connection of the lesion with the infracochlear, perilabyrinthine and sphenoidal cellularity was assessed. Results: Nineteen patients with symptoms like diplopia, headache and sensorineural hearing loss were included. According to our classification, 1/19 patients was Type A, 4/19 were Type B and 14/19 were Type C. Five patients underwent a total resection, seven a subtotal and seven a surgical drainage. Only two complications were recorded, and 17/19 patients showed symptom regression and stability during follow-up. Conclusions: While the management of PACGs is still controversial, according to our classification and surgical outcomes, Type A, being mostly asymptomatic, should be managed with “wait and scan”, Type B should undergo surgery when symptoms are present, while Type C should always undergo surgery because of their invasiveness and potential complications. When possible, a drainage should be attempted; otherwise, a surgical resection is chosen, and its completeness depends on the preoperative general and hearing status.

Amyloidosis is a rare infiltrative condition resulting from the extracellular accumulation of amyloid fibrils at the cardiac level. It can be an acquired condition or due to genetic mutations. With the progression of imaging technologies, a non-invasive diagnosis was proposed. In this study, we discuss the role of CMR in cardiac amyloidosis, focusing on the two most common subtypes (AL and ATTR), waiting for evidence-based guidelines to be published.

Different insights into the connection between kidney [18F]fluorodesoxyglucose ([18F]FDG) uptake at positron emission tomography/computed tomography (PET/CT) and renal function have been proposed in the past. The aim of this study was therefore to assess the presence of a correlation between these two parameters. Kidney uptakes were assessed and compared to the creatinine (Cr) values and estimated glomerular filtration rate (EGFR) among different classes of renal functional impairment or kidney status. A total of 339 patients and 385 different PET/CT scans were included in this study. Significant correlations between kidney uptakes and renal function parameters were reported in most of the groups studied, with the exception of patients with Cr < 1.2 mg/dL and subjects with a kidney transplantation. Strong concordance in the assessment of renal parenchymal uptakes between the different readers was reported. To conclude, strong correlations for renal [18F]FDG uptake with Cr levels and the EGFR were reported, with the exception of the group of patients with a Cr value < 1.2 mg/dL and for the group with a kidney transplantation.

Abstract The “Hypogeum of the Garlands” is a sepulchral site, recently found in Grottaferrata (Lazio, Italy), dating back to the first-second century AD. Two sarcophagi were discovered inside, hosting the human remains of Aebutia Quarta, a rich Roman woman, and her son Carvilius Gemellus. While the body of Carvilius is exceptionally well-preserved, following its embalming and perfect sealing of the sarcophagus, in the case of Aebutia only the bones were preserved because of the sarcophagus’s seal breaking down, although she was covered with perfectly preserved flower garlands. Embalming of the body was a rare ritual in the Imperial Roman times when corpses were more often cremated. The remains of Aebutia showed possible traces of heating. Burned bones from a third individual were discovered on the chamber’s floor and preliminary anthropological survey showed that this individual was a male of 40–50 years old. Here, a combination of spectroscopic techniques, including non-destructive inelastic neutron scattering and Raman spectroscopy, and minimally destructive Fourier transform infrared spectroscopy, were applied to the analysis of these bone samples to give information about ancient Roman funerary practices. The temperature and burning conditions were thus determined, showing that Aebutia Quarta was exposed to mild temperatures (200 °C) only in the upper part of the body, while the third individual was likely cremated as its bones were exposed to temperatures up to 900 °C in quasi-anaerobic conditions.

Abstract Miscarriage is the spontaneous termination of a pregnancy before 24 weeks of gestation. We studied the genome of euploid miscarried embryos from mothers in the range of healthy adult individuals to understand genetic susceptibility to miscarriage not caused by chromosomal aneuploidies. We developed gp , a pipeline that we used to prioritize 439 unique variants in 399 genes, including genes known to be associated with miscarriages. Among the prioritized genes we found STAG2 coding for the cohesin complex subunit, for which inactivation in mouse is lethal, and TLE4 a target of Notch and Wnt, physically interacting with a region on chromosome 9 associated to miscarriages.

IntroductionThe growing demand for plasma protein products has caused concern in many countries who largely rely on importing plasma products produced from plasma collected in the United States and Europe. Optimizing recruitment and retention of a diversity of plasma donors is therefore important for supporting national donation systems that can reliably meet the most critical needs of health services. This series of three systematic reviews aims to synthesize the known barriers and enablers to source plasma donation from the qualitative and survey-based literature and identify which strategies that have shown to be effective in promoting increased intention to, and actual donation of, source plasma.Methods and analysisPrimary studies involving source or convalescent plasma donation via plasmapheresis will be included. The search strategy will capture all potentially relevant studies to each of the three reviews, creating a database of plasma donation literature. Study designs will be subsequently identified in the screening process to facilitate analysis according to the unique inclusion criteria of each review (i.e., qualitative, survey, and experimental designs). The search will be conducted in the electronic databases SCOPUS, MEDLINE, EMBASE, PsycINFO, and CINAHL without date or language restrictions. Studies will be screened, and data will be extracted, in duplicate by two independent reviewers with disagreements resolved through consensus. Reviews 1 and 2 will draw on the Theoretical Domains Framework and Intersectionality, while Review 3 will be informed by Behaviour Change Intervention Ontologies. Directed content analysis and framework analysis (Review 1), and descriptive and inferential syntheses (Reviews 2 and 3), will be used, including meta-analyses if appropriate.DiscussionThis series of related reviews will serve to provide a foundation of what is known from the published literature about barriers and enablers to, and strategies for promoting, plasma donation worldwide.

Graves’ disease (GD) is the leading cause of hyperthyroidism and diffuse toxic goiter in iodine-sufficient geographical areas. GD is associated with classical manifestations such as ophthalmopathy and thyroid dermopathy, in addition to diffuse goiter, which may be the site of carcinomas, as a complication. Case report: A 52-year-old woman presented with goiter and symptoms compatible with hyperthyroidism, such as heat intolerance, weight loss, fatigue, increased sweat, tachycardia, fine tremors, increased intestinal transit, anxiety, emotional lability, insomnia, exophthalmos, and pretibial myxedema. A complementary investigation confirmed the diagnosis of hyperthyroidism (high free T4 and total T3 levels and low thyroid-stimulating hormone - TSH levels). Ultrasound images showed diffuse enlargement of the thyroid lobes by approximately 10 times and the presence of three thyroid nodules, one of which was larger than 2 cm with heterogeneous echogenicity and vascularization throughout the nodule; ultrasound- guided fine needle aspiration revealed cytology compatible with Bethesda IV; scintigraphy revealed a low uptake area (cold nodule) amid a diffuse high-uptake goiter. A thyroidectomy was performed, and the anatomical specimen diagnosis revealed papillary thyroid carcinoma in the right lobe, with adjacent parenchyma compatible with GD. Histopathological examination of the skin showed the presence of myxedema compatible with Graves’ dermopathy. The patient evolved with the normalization of TSH levels and a reduction of cutaneous manifestations. Conclusion: GD abnormalities may not be restricted to the classic clinical manifestations, and a careful investigation may reveal the coexistence of carcinomas.

Growing attention is being given to the European hedgehog (Erinaceus europaeus) because of its synanthropic behaviour and its potential role in harbouring parasites, viruses, fungi and bacteria and disseminating them to several animals and humans. Salmonella are the most frequently detected zoonotic bacteria that hedgehogs could transmit through contaminating water and food sources with faeces. This study aimed to determine the prevalence and distribution of Salmonella spp. in wild hedgehogs in the Emilia-Romagna region (northern Italy). From 2019 to 2022, 212 European hedgehogs that died naturally were tested for Salmonella spp. through culture isolation. Positive samples were subjected to serological typing. A total of 82 samples tested positive for Salmonella spp., with the overall Bayesian posterior estimated prevalence ranging from 35% (95% CI: 23–47%) to a maximum of 45% (95% CI: 31–59%) during the years considered and with an overall prevalence calculated at 39% (95% CI: 33–45%). Salmonella enterica Enteritidis and Veneziana were the most prevalent detected serovars in 65% and 17% of the positive samples, respectively. Since 2021, S. Typhimurium, S. Typhimurium Monofasica, S. Zaiman, S. Hessarek, S. Muenster, S. Isangi serovars, S. enterica subsp. Diarizonae and S. enterica subsp. Houtenae have been detected. These findings show a high prevalence of Salmonella spp. in tested hedgehogs, suggesting an important role of this animal species in the epidemiology of potentially zoonotic serovars circulating in the Emilia-Romagna region.

Abstract Electric fishing is an illegal hunting method, unfortunately widely used by poachers to paralyze fish and to catch many animals in a short time. In Italy, it is authorized only for scientific and conservative purposes. Between 2014 and 2018, the Ferrara section of the Experimental Zooprophylactic Institute of Lombardy and Emilia Romagna, Italy, received nine cases of potentially illegal electric fishing in Po river and its tributary rivers. Necropsies were performed following standard protocols and samples of different tissues were collected and examined using histochemical and immunohistochemical techniques. Gross lesions frequently observed were circulatory alteration phenomena (i.e. multi-organ hyperemia, hemorrhages and congestion, hemopericardium), also found histologically, in addition to multifocal degenerative and necrotic muscular processes that could be attributed to injuries from electric current, as already reported in literature. Immunohistochemical investigations confirmed degenerative and necrotic lesions with myoglobin depletion and a corresponding fibrinogen accumulation. Myoglobin globules were also detected in the renal parenchyma, as consequent of rhabdomyolysis. The results of this study allowed to correlate electric fishing to gross, histologic and immunohistochemical lesions, which together constitute a pathognomonic picture to be considered a reference standard in this type of illegal controversy.

Abstract Background Antiphospholipid Syndrome (APS) is a rare autoimmune disorder with an estimated prevalence of 40–50 cases per 100.000 persons. Patients suffering from low prevalence diseases are more likely to face diagnostic challenges, given the limited knowledge of most clinicians. The main aim of this study was to investigate the time between symptoms occurrence and the diagnosis of APS patients using the Piedmont and Aosta Valley Rare Disease Registry. Secondly, to evaluate the individual impact of the diagnostic gap by gathering patients’ personal experiences through a self-administered questionnaire. Results Data from the Piedmont and Aosta Valley Rare Disease Registry was used. In addition, personal experiences were analyzed through a self-administered questionnaire. A total of 740 APS patients included in the Piedmont and Aosta Valley Rare Disease Registry were analyzed. Diagnostic delay (as defined by time between symptoms’ occurrence and the diagnosis of APS) was significantly reduced over time. In particular, when comparing the diagnostic delay between patients diagnosed between 1983 and 1999 and patients diagnosed between 2000 and 2015, we found a significant statistical difference (Mann-Whithey U Test; mean rank 1216.6 vs. 1066.9, respectively; p

Introduction: Malaysian tuberculosis (TB) clinical practice guideline (CPG) standardises the management of TB to improve the quality of care for TB patients. Not all primary care providers adhere to this guideline, however. This audit aims to improve the management of smear positive adult pulmonary TB by identifying areas of concern and developing action plans. Methods: Data for the audit were gathered from August 2018 to August 2019 from medical records of diagnosed smear positive pulmonary TB patients. Patients were included based on inclusion and exclusion criteria. Results: Forty-eight smear positive pulmonary TB patients were recruited. The majority of patients were male (54.2%) and Malay (33.2%). TB symptoms were assessed for 29.2% of patients at two weeks and then in 81.3% at one month, 97.9% at two months, 16.7% at three months, 95.8% at four months, 22.9% at five months and 95.8% at six months. Medication side effects were assessed at two weeks for only 2.1% of patients, then for 8.3% of patients at one month, 2.1% at two months and 0% at subsequent months. At diagnosis, 25% and 4.2% of patients had their visual acuity and colour vision, respectively, assessed. Only 6.3% of patients were referred to pre-pregnancy counselling. Weights were recorded for 87.5% of patients at diagnosis, then for 27.1% at two weeks, 81.3% at one month, 91.7% at two months, 77.1% at three months, 97.9% at four months, 79.2% at five months and 93.8% at six months. Baseline investigations and Mycobacterium tuberculosis culture and sensitivity were conducted for all patients, but only 81.3% of patients were traced. No patients were referred to pharmacy for medication counselling. Conclusion: This audit shows that there is a difference between current practice and the national guideline. There are some downfalls in management and proper documentation, so interventions should be carried out to improve those aspects.

Abstract In this contribution, we investigated the role of plants in the prehistoric community of Casale del Dolce (Anagni, FR, central Italy), through microparticles recovered from dental calculus. The finding of a great amount of pollen types, even in form of compact lumps, could indicate use of natural substances, such as honeybee products and/or conifer resins. This plant-microremain record also suggested environmental implications relative to the Neolithic and Chalcolithic period. Additionally, the stability of the tartar microenvironment had preserved starches and other microparticles, such as one epidermal trichome, a sporangium, and fragments of plant tissue, rarely detected in ancient dental calculus. The detection of secondary metabolites in the ancient matrix confirmed the familiarity of this community with plant resources. All these data supply various interesting food for thought and expand the knowledge about the potential of dental calculus in archaeological and archaeobotanical fields with a special focus on palaeoecology.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. After first-line therapy, 30–40% of patients relapse or experiment with refractory disease. 18F-FDG PET/CT represents a validated diagnostic tool in post-treatment evaluation of FDG-avid lymphoma, and the Deauville Score (DS), a five-point visual scale, is usually used to assess response. However, the increased number of false positive findings suggested the need to search for new parameters. The aim of this study is to evaluate the prognostic value of End-of-Treatment-PET, comparing DS to the semi-quantitative Lesion-to-Liver ratio (LLR). Methods: newly diagnosed DLBCL patients who underwent 18F-FDG PET/CT were retrospectively analyzed. End-of-Treatment PET findings were assessed first using DS; secondly, assigned the LLR. Results: a total of 105 patients were finally enrolled. ROC analysis showed an LLR of 1.80 as the optimal cutoff value for predicting a disease progression (sensitivity 58%, specificity 95%). Both DS and LLR showed a statistically significant correlation with PFS and OS. LLR resulted in a better diagnostic performance than DS. Conclusions: LLR showed to be a reliable diagnostic method to assess treatment response in DLBCL. The integration of visual and semi-quantitative criteria could help in decision making, improving specificity and PPV.

Solitary fibrous tumor (SFT) of the central nervous system, previously named and classified with the term hemangiopericytoma (HPC), is rare and accounts for less than 1% of all intracranial tumors. Despite its benign nature, it has a malignant behavior due to the high rate of recurrence and distant metastasis, occurring in up to 50% of cases. Surgical resection of the tumor is the treatment of choice. Radiotherapy represents the gold standard in the case of post-surgery residual disease, relapse, and distant metastases. In this context, imaging plays a crucial role in identifying the personalized therapeutic decision for each patient. Although the referring imaging approach in SFT is morphologic, an emerging role of positron emission tomography (PET) has been reported in the literature. However, there is still a debate on which radiotracers have the best accuracy for studying these uncommon tumors because of the histological or biological heterogeneity of SFT.

Abstract Linac‐based STereotactic Arrhythmia Radioablation (STAR) is a safety and effective approach for selected patients with ventricular arrhythmias.

Abstract SARS-CoV-2 is a rapidly evolving pandemic causing great morbimortality. Medical therapy with hydroxicloroquine, azitromycin and protease inhibitors is being empirically used, with reported data of QTc interval prolongation. Our aim is to assess QT interval behaviour in a not critically ill and not monitored cohort of patients. We evaluated admitted and ambulatory patients with COVID-19 patients with 12 lead electrocardiogram at 48 h after treatment initiation. Other clinical and analytical variables were collected. Statistical analysis was performed to assess the magnitude of the QT interval prolongation under treatment and to identify clinical, analytical and electrocardiographic risk markers of QT prolongation independent predictors. We included 219 patients (mean age of 63.6 ± 17.4 years, 48.9% were women and 16.4% were outpatients. The median baseline QTc was 416 ms (IQR 404–433), and after treatment QTc was prolonged to 423 ms (405–438) (P 460 ms, and just one case with QTc > 500 ms. Advanced age, longer QTc basal at the basal ECG and lower potassium levels were independent predictors of QTc interval prolongation. Ambulatory and not critically ill patients with COVID-19 treated with hydroxychloroquine, azithromycin and/or antiretrovirals develop a significant, but not relevant, QT interval prolongation.

Due to marine mammals’ demonstrated susceptibility to SARS-CoV-2, based upon the homology level of their angiotensin-converting enzyme 2 (ACE2) viral receptor with the human one, alongside the global SARS-CoV-2 occurrence and fecal contamination of the river and marine ecosystems, SARS-CoV-2 infection may be plausibly expected to occur also in cetaceans, with special emphasis on inshore species like bottlenose dolphins (Tursiops truncatus). Moreover, based on immune and inflammatory responses to SARS-CoV-2 infection in humans, macrophages could also play an important role in antiviral defense mechanisms. In order to provide a more in-depth insight into SARS-CoV-2 susceptibility in marine mammals, we evaluated the presence of SARS-CoV-2 and the expression of ACE2 and the pan-macrophage marker CD68. Aliquots of tissue samples, belonging to cetaceans stranded along the Italian coastline during 2020-2021, were collected for SARS-CoV-2 analysis by real-time PCR (RT-PCRT) (N = 43) and Immunohistochemistry (IHC) (N = 59); thirty-two aliquots of pulmonary tissue sample (N = 17 Tursiops truncatus, N = 15 Stenella coeruleoalba) available at the Mediterranean Marine Mammal Tissue Bank (MMMTB) of the University of Padua (Legnaro, Padua, Italy) were analyzed to investigate ACE2 expression by IHC. In addition, ACE2 and CD68 were also investigated by Double-Labeling Immunofluorescence (IF) Confocal Laser Microscopy. No SARS-CoV-2 positivity was found in samples analyzed for the survey while ACE2 protein was detected in the lower respiratory tract albeit heterogeneously for age, gender/sex, and species, suggesting that ACE2 expression can vary between different lung regions and among individuals. Finally, double IF analysis showed elevated colocalization of ACE2 and CD68 in macrophages only when an evident inflammatory reaction was present, such as in human SARS-CoV-2 infection.

ABSTRACT Objective To evaluate the therapeutic response to induction treatment in lupus nephritis patients. Methods A total of 29 patients diagnosed with systemic lupus erythematosus and biopsy-proven nephritis were divided into two groups, one with hypertensive individuals and another non-hypertensive patients. The hypertensive patients included were on drugs with antiproteinuric effect. The induction treatment comprised mycophenolate mofetil or cyclophosphamide, based on 24-hour proteinuria and serum creatinine parameters for therapeutic evaluation after 6 months of intervention. The retrospective evaluation of the follow-up was made based on information collected from the medical records. Results Patients with and without hypertension presented similar behaviors of proteinuria (p=0.127) and creatinine (p=0.514) over time. For proteinuria, only the time effect (p=0.007), but not hypertensive effect (p=0.232), was found. There was a reduction in proteinuria levels (reduction by 3.28g/24 hours, on average) from the beginning to the final measurement. As to creatinine, no hypertensive (p=0.757) or time (p=0.154) effects were found. Conclusion Similarity in behavior of proteinuria was observed, after induction treatment for nephritis, taking into account the hypertensive effect. The prior condition did not hinder these patients reaching the recommended proteinuria goal.

Yessotoxins (YTXs) are polycyclic toxic ether compounds produced by phytoplanktonic dinoflagellates which accumulate in filter-feeding organisms. We know that the water temperature in our areas Northwestern Adriatic Sea is optimal for the growth of potentially toxic algae (around 20 °C). In recent years, these temperatures have remained at these levels for longer and longer periods, probably due to global warming, which has led to an excessive increase in toxin levels. The interruption of mussel harvesting caused by algae negatively affects farmers’ revenues and the availability of local fish, causing a major economic loss in Italy’s main shellfish sector. Methods: In the nine years considered, 3359 samples were examined: 1715 marine waters, 73 common clams; 732 mussels; 66 oysters; and 773 veracious clams. Bivalve molluscs were examined for the presence of marine biotoxins, including YTXs, while potentially toxic algae, including those producing YTXs, were searched for and counted in marine waters. The method adopted for the quantification of lipophilic toxins involves the use of an LC-MS/MS system. The enumeration of phytoplankton cells was performed according to the Utermhöl method. Results: Between 2012 and 2020, 706 molluscs were tested for YTXs. In total, 246 samples tested positive, i.e., 34.84%. Of the positive samples, 30 exceeded the legal limit. Conclusion: In this regard, it is essential to develop and activate, as soon as possible, an “early warning” system that allows a better control of the production areas of live bivalve molluscs, thus allowing an optimal management of the plants in these critical situations.

Acute pulmonary embolism (APE) is a cardiovascular emergency, representing the main cause of mortality, morbidity, and hospitalisation in Europe. We aim to evaluate the economic and healthcare impact of lung perfusion scintigraphy (LPS) used in patients with suspected APE, in the event of non-conclusive or contraindicated computed tomography pulmonary angiography (CTPA). We considered two alternative healthcare processes for APE diagnosis, with and without LPS. We performed a cost analysis with the aim of evaluating the average direct healthcare costs for diagnosis, risk assessment, and treatment of APE. We used data from a monocentric trial. Our economic model showed that the strategy with LPS was preferable in terms of costs. The average per-patient costs for the diagnosis and treatment of the acute phase of PE in low-risk patients with a non-conclusive or not-executable CTPA, with and without LPS, are EUR 2145.25 and EUR 4912.45, respectively. LPS is a simple, quick, and economic examination, useful in this setting of patients not only for an early diagnosis but also to exclude APE, demonstrating an advantage in terms of healthcare resources. To the best of our knowledge, this study is the first to analyse the economic and healthcare impact of the use of LPS in the diagnostic pathway of suspected APE.

Abstract The Ceprano calvarium was discovered in fragments on March 1994 near the town of Ceprano in southern Latium (Italy), embedded in Middle Pleistocene layers. After reconstruction, its morphological features suggests that the specimen belongs to an archaic variant of H. heidelbergensis, representing a proxy for the last common ancestor of the diverging clades that respectively led to H. neanderthalensis and H. sapiens. Unfortunately, the calvarium was taphonomically damaged. The postero-lateral vault, in particular, appears deformed and this postmortem damage may have influenced previous interpretations. Specifically, there is a depression on the fragmented left parietal, while the right cranial wall is warped and angulated. This deformation affected the shape of the occipital squama, producing an inclination of the transverse occipital torus. In this paper, after X-ray microtomography (μCT) of both the calvarium and several additional fragments, we analyze consistency and pattern of the taphonomic deformation that affected the specimen, before the computer-assisted retrodeformation has been performed; this has also provided the opportunity to reappraise early attempts at restoration. As a result, we offer a revised interpretation for the Ceprano calvarium’s original shape, now free from the previous uncertainties, along with insight for its complex depositional and taphonomic history.

Abstract The development of crop varieties tolerant to growth temperature fluctuations and improved nutritional value is crucial due to climate change and global population growth. This study investigated the metabolite patterns of developing barley seed as a function of genotype and growth temperature for ideal vegetable protein production and for augmented β-glucan production. Seeds from three barley lines (Bomi, lys3.a and lys5.f) were sampled eight times during grain filling and analysed for metabolites using gas chromatography-mass spectrometry (GC-MS). The lys3.a mutation disrupts a regulator gene, causing an increase in proteins rich in the essential amino acid lysine, while lys5.f carries a mutation in an ADP-glucose transporter gene leading to a significant increase in production of mixed-linkage β-glucan at the expense of α-glucan. Unique metabolic patterns associated with the tricarboxylic acid cycle, shikimate-phenylpropanoid pathway, mevalonate, lipid and carbohydrate metabolism were observed for the barley mutants, whereas growth temperature primarily affected shikimate-phenylpropanoid and lipid metabolism. The study applied recently developed GC-MS metabolomics methods and demonstrated their successful application to link genetic and environmental factors with the seed phenotype of unique and agro-economically important barley models for optimal vegetable protein and dietary fibre production.

Abstract The development of biomaterials able to act against a wide range of bacteria, including antibiotic resistant bacteria, is of great importance since bacterial colonization is one of the main causes of implant failure. In this work, we explored the possibility to functionalize hydroxyapatite (HA) nanocrystals with some monocyclic N-thio-substituted β-lactams. To this aim, a series of non-polar azetidinones have been synthesized and characterized. The amount of azetidinones loaded on HA could be properly controlled on changing the polarity of the loading solution and it can reach values up to 17 wt%. Data on cumulative release in aqueous solution show different trends which can be related to the lipophilicity of the molecules and can be modulated by suitable groups on the azetidinone. The examined β-lactams-HA composites display good antibacterial activity against reference Gram-positive and Gram-negative bacteria. However, the results of citotoxicity and antibacterial tests indicate that HA loaded with 4-acetoxy-1-(methylthio)-azetidin-2-one displays the best performance. In fact, this material strongly inhibited the bacterial growth of both methicillin resistant and methicillin susceptible clinical isolates of S. aureus from surgical bone biopsies, showing to be a very good candidate as a new functional biomaterial with enhanced antibacterial activity.

Sixty barrows (Body Weight-BW- range: 23.9-160 kg) were allotted to two experimental groups (6 pens of 5 pigs each): the control group was kept at a space allowance of 1m2/head; the second group was kept at 1.3m2/head. Behaviour, growth parameters, carcass and meat quality were assessed, as well as fat and cured ham quality. Results showed that pigs raised at 1.3m2/head spent more time laying (particularly in lateral recumbency, P

Background: The early non-invasive discrimination of Type 2 versus Type 1 Myocardial Infarction (T2MI, T1MI) is a major unmet clinical need. We aimed to externally validate a recently derived clinical score (Neumann) combing female sex, no radiating chest pain, and high-sensitivity cardiac troponin I (hs-cTnI) concentration ≤40.8 ng/L. Methods: Patients presenting with acute chest discomfort to the emergency department were prospectively enrolled into an international multicenter diagnostic study. The final diagnoses of T2MI and T1MI were centrally adjudicated by two independent cardiologists using all information including cardiac imaging and serial measurements of hs-cTnT/I according to the fourth universal definition of MI. Model performance for T2MI diagnosis was assessed by formal tests and graphical means of discrimination and calibration. Results: Among 6684 enrolled patients, MI was the adjudicated final diagnosis in 1079 (19%) patients, of which 242 (22%) had T2MI. External validation of the Neumann Score showed a moderate discrimination (C-statistic 0.67 (95%CI 0.64–0.71)). Model calibration showed underestimation of the predicted probabilities of having T2MI for low point scores. Model extension by adding the binary variable heart rate >120/min significantly improved model performance (C-statistic 0.73 (95% CI 0.70–0.76, p < 0.001) and had good calibration. Patients with the highest score values of 3 (Neumann Score, 9.9%) and 5 (Extended Neumann Score, 3.3%) had a 53% and 91% predicted probability of T2MI, respectively. Conclusion: The Neumann Score provided moderate discrimination and suboptimal calibration. Extending the Neumann Score by adding heart rate >120/min improved the model’s performance.

Immunotherapy is a promising therapeutic strategy both for solid and hematologic tumors, such as in Hodgkin (HL) and non-Hodgkin lymphoma (NHL). In particular, immune-checkpoint inhibitors, such as nivolumab and pembrolizumab, are increasingly used for the treatment of refractory/relapsed HL. At the same time, evidence of chimeric antigen receptor (CAR)-T-cell immunotherapy efficacy mostly in NHL is growing. In this setting, the challenge is to identify an appropriate imaging method to evaluate immunotherapy response. The role of 18F-Fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT), especially in early evaluation, is under investigation in order to guide therapeutic strategies, taking into account the possible atypical responses (hyperprogression and pseudoprogression) and immune-related adverse events that could appear on PET images. Herein, we aimed to present a critical overview about the role of 18F-FDG PET/CT in evaluating treatment response to immunotherapy in lymphoma patients.

Objective: The use of nanoparticles (NPs) in cancer diagnosis and treatment is a rapidly developing area of nanotechnology. The main objective of this research work is to synthesize copper oxide (CuO) NPs and to investigate its vitro anticancer and antibacterial property. Methods: The CuO NPs were synthesized via a facile and cost-effective precipitation method using cupric acetate (monohydrate) (CuAc 2 .2H 2 O), sodium hydroxide, and glacial acetic acid. By varying the pH of the precursor solution, the morphology, particle size, and reaction rate of the NPs could be well tailored. The prepared CuO NPs were characterized by X-ray diffraction, ultraviolet-visible spectroscopy, Fourier transform infrared analysis, and scanning electron microscopy. Results: The results revealed a well crystalline structure with leaf-like morphology. By controlling the pH of the solution, particle size and morphology of the NPs are altered. The synthesized CuO NPs have been screened for its antibacterial potency against Gram-positive (Methicillin-resistant Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Salmonella Paratyphi, Klebsiella pneumonia, and Enterobacter aerogenes) bacterial strains. The as-synthesized NPs were found to be remarkable in inhibiting pathogenic bacteria. The anticancer activity reveals the dose-dependent influence of CuO NPs against human breast cancer cell line Michigan Cancer Foundation-7 (MCF-7). Conclusions: The results suggested that CuO NPs have a wide range of antibacterial applications which can be used to control the spread and infection of a variety of bacterial strains. The CuO NPs showed promising anticancer activity against human breast cancer cell line (MCF-7). Overall, CuO NPs are an effective candidate for pharmaceutical, biomedical, and environmental applications.

The presence of a cardiovascular implantable electronic device (CIED) can be burdened by complications such as late infections that are associated with significant morbidity and mortality and require immediate and effective treatment. The aim of this study was to evaluate the role of 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT) in patients with suspected CIED infection. Fifteen patients who performed a 18F-FDG PET/CT for suspicion of CIED infection were retrospectively analyzed; 15 patients, with CIED, that underwent 18F-FDG PET/CT for oncological reasons, were also evaluated. Visual qualitative analysis and semi-quantitative analysis were performed. All patients underwent standard clinical management regardless 18F-FDG PET/CT results. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) resulted as 90.91%, 75%, 86.67%, 90.91% and 75% respectively. Maximum standardized uptake values (SUVmax) and semi-quantitative ratio (SQR) were collected and showed differences statistically significant between CIED infected patients and those who were not. Exploratory cut-off values were derived from receiver operating characteristic (ROC) curves for SUVmax (2.56) and SQR (4.15). This study suggests the clinical usefulness of 18F-FDG PET/CT in patients with CIED infection due to its high sensitivity, repeatability and non-invasiveness. It can help the clinicians in decision making, especially in patients with doubtful clinical presentation. Future large-scale and multicentric studies should be conducted to establish precise protocols about 18F-FDG PET/CT performance.

Spondylodiscitis is a spine infection for which a diagnosis by a magnetic resonance imaging (MRI) is considered the most appropriate imaging technique. The aim of this study was to compare the role of an 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and an MRI in this field. For 56 patients with suspected spondylodiscitis for whom MRI and 18F-FDG PET/CT were performed, we retrospectively analyzed the results. Cohen’s κ was applied to evaluate the agreement between the two techniques in all patients and in subgroups with a different number of spinal districts analyzed by the MRI. Sensitivity, specificity, and accuracy were also evaluated. The agreements of the 18F-FDG PET/CT and MRI in the evaluation of the entire population, whole-spine MRI, and two-districts MRI were moderate (κ = 0.456, κ = 0.432, and κ = 0.429, respectively). In patients for whom one-district MRI was performed, 18F-FDG PET/CT and MRI were both positive and completely concordant (κ = 1). We also separately evaluated patients with suspected spondylodiscitis caused by Mycobacterium tuberculosis for whom the MRI and 18F-FDG PET/CT were always concordant excepting in 2 of the 18 (11%) patients. Sensitivity, specificity, and accuracy of the MRI and 18F-FDG PET/CT were 100%, 60%, 97%, and 92%, 100%, and 94%, respectively. Our results confirmed the 18F-FDG PET/CT diagnostic value in the diagnosis of spondylodiscitis is comparable to that of MRI for the entire spine evaluation. This could be considered a complementary technique or a valid alternative to MRI.

Background: Little is known about clinical outcomes of patients with acute myocardial infraction (AMI) complicated by cardiogenic shock (CS) requiring mechanical ventilation (MV). The aim of this study was to identify the characteristics, risk factors, and outcomes associated with the provision of MV in this specific high-risk population. Methods: Patients with CS complicating AMI and multivessel coronary artery disease from the CULPRIT-SHOCK trial were included. We explored 30 days of clinical outcomes in patients not requiring MV, those with MV on admission, and those in whom MV was initiated within the first day after admission. Results: Among 683 randomized patients included in the analysis, 17.4% received no MV, 59.7% were ventilated at admission and 22.8% received MV within or after the first day after admission. Patients requiring MV had a different risk-profile. Factors independently associated with the provision of MV on admission included higher body weight, resuscitation within 24 h before admission, elevated heart rate and evidence of triple vessel disease. Conclusions: Requiring MV in patients with CS complicating AMI is common and independently associated with mortality after adjusting for covariates. Patients with delayed MV initiation appear to be at higher risk of adverse outcomes. Further research is necessary to identify the optimal timing of MV in this high-risk population.

Angiogenesis represents a key event in cancer development, leading to local invasion e metastatization, and might be considered a basic feature in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) with a high expression of angiogenic molecules. We aimed to analyze the prognostic and predictive role of angiogenic factors in GEP-NENs through the analysis of single nucleotide polymorphisms (SNPs) of VEGF-A, VEGFR2 and VEGFR3. The genomic DNA of 58 consecutive patients with GEP-NENs treated at our Institution was extracted from peripheral blood. Two SNPs were identified respectively in VEGF-A (rs2010963G>C, rs699947A>C), VEGFR-2 (rs2305948C>T, rs1870377T>A), and VEGFR-3 (rs307821T>C, rs307826C>A) gene. Gene polymorphisms were determined by Real-Time PCR using TaqMan assays. Median age was 57 years (range 24-79 years); 32 patients were male and 77.5% of NENs were localized in the pancreas. The allele frequency of VEGFR-2 rs2305948T and of VEGF-A rs2010963C showed a trend of higher frequency than in general population (12.1% vs. 8.0% and 34.5% vs. 31.2%, respectively). Three out SNPs (VEGF-A rs699947C, VEGF-A rs2010963GC and VEGFR-3 rs307821C) showed a correlation with an increased risk of disease relapse. Moreover median PFS changes according to the presence of 0-1 SNPs (20.7% of cases; 61.9 months), 2 SNPs (25.9%; 49.2 months) and 3 SNPs (53.4%; 27.8 months) (p = 0.034). Results suggest, for the first time, that specific SNPs in VEGF-A and VEGFR-3 correlate with poor prognosis in GEP-NENs. The identification of this new prognostic factor might be helpful in order to optimize the management of these heterogeneous neoplasms.