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Neutrophils play a role in cardiovascular (CV) disease. However, relatively scant evidence exists in the setting of peripheral artery disease (PAD). The aims of this study were to measure biomarkers of neutrophil activation in patients with symptomatic chronic PAD compared with healthy controls, to assess their association with PAD severity, and to evaluate their prognostic value in patients with PAD. The following circulating markers of neutrophil degranulation were tested: polymorphonuclear neutrophil (PMN) elastase, neutrophil gelatinase-associated lipocalin (NGAL), and myeloperoxidase (MPO). Neutrophil extracellular traps (NETs) were quantified by measuring circulating MPO–DNA complexes. Patients with PAD underwent a comprehensive series of vascular tests. The occurrence of 6-month major adverse CV (MACE) and limb events (MALE) was assessed. Overall, 110 participants were included, 66 of which had PAD. After adjustment for conventional CV risk factors, PMN-elastase (adjusted odds ratio [OR]: 1.008; 95% confidence interval [CI]: 1.002–1.015; p = 0.006), NGAL (adjusted OR: 1.045; 95%CI: 1.024–1.066; p < 0.001), and MPO (adjusted OR: 1.013; 95%CI: 1.001–1.024; p = 0.028) were significantly associated with PAD presence. PMN-elastase (adjusted hazard ratio [HR]: 1.010; 95%CI: 1.000–1.020; p = 0.040) and MPO (adjusted HR: 1.027; 95%CI: 1.004–1.051; p = 0.019) were predictive of 6-month MACE and/or MALE. MPO displayed fair prognostic performance on receiver operating characteristic (ROC) curve analyses, with an area under the curve (AUC) of 0.74 (95%CI: 0.56–0.91) and a sensitivity and specificity of 0.80 and 0.65, respectively, for a cut-off of 108.37 ng/mL. MPO–DNA showed a weak inverse correlation with transcutaneous oximetry (TcPO2) on proximal foot (adjusted ρ −0.287; p = 0.032). In conclusion, in patients with symptomatic chronic PAD, enhanced neutrophil activity may be associated with an increased risk of acute CV events, rather than correlate with disease severity. Further research is needed to clarify the role of neutrophils in PAD natural history.

Clinical introductionA 74-year-old hypertensive woman presented with shortness of breath. There was no associated coughing, chest pain or fever. ECG identified atrial fibrillation with rapid ventricular response. A transoesophageal echocardiogram was scheduled to exclude thrombus before cardioversion (Figure 1A); however, an echogenic structure was seen (Figure 1B arrow, see online supplementary video 1) between the left atrium, the pulmonary artery and the aortic root.QuestionWhich of the following is the most likely diagnosis? Aortic valve endocarditis with annular abscessLeft atrial appendage thrombusLeft atrial myxomaPulmonary embolismFor the answer see page 727For the question see page 693

The aim of our study was to assess the prevalence of variants and anomalies of the coronary artery tree in patients who underwent 64-slice computed tomography coronary angiography (CT-CA) for suspected or known coronary artery disease. A total of 543 patients (389 male, mean age 60.5 ± 10.9) were reviewed for coronary artery variants and anomalies including post-processing tools. The majority of segments were identified according to the American Heart Association scheme. The coronary dominance pattern results were: right, 86.6%; left, 9.2%; balanced, 4.2%. The left main coronary artery had a mean length of 112 ± 55 mm. The intermediate branch was present in the 21.9%. A variable number of diagonals (one, 25%; two, 49.7%; more than two, 24%; none, 1.3%) and marginals (one, 35.2%; two, 46.2%; more than two, 18%; none, 0.6%) was visualized. Furthermore, CT-CA may visualize smaller branches such as the conus branch artery (98%), the sinus node artery (91.6%), and the septal branches (93%). Single or associated coronary anomalies occurred in 18.4% of the patients, with the following distribution: 43 anomalies of origin and course, 68 intrinsic anomalies (59 myocardial bridging, nine aneurisms), three fistulas. In conclusion, 64-slice CT-CA provides optimal visualization of the variable and complex anatomy of coronary arteries because of the improved isotropic spatial resolution and flexible post-processing tool.

SARS-CoV-2 may lead to a large spectrum of respiratory manifestations, including pulmonary sequelae. We conducted a single-center longitudinal study of survivors from severe COVID-19 cases who underwent a chest CT during hospitalization (CTH). Three months after being discharged, these patients were evaluated by a clinical examination, pulmonary function tests and a chest-CT scan (CTFU). Sixty-two patients were enrolled. At follow-up, 27% complained of exertional dyspnoea and 12% of cough. Dyspnoeic patients had a lower forced expiratory flow (FEF)25–75 (p = 0.015), while a CT scan (p = 0.016 showed that patients with cough had a higher extent of bronchiectasis. Lung volumes and diffusion of carbon monoxide (DLCO) at follow-up were lower in patients who had been invasively ventilated, which correlated inversely with the length of hospitalization and ground-glass extension at CTH. At follow-up, 14.5% of patients had a complete radiological resolution, while 85.5% presented persistence of ground-glass opacities, and 46.7% showed fibrotic-like alterations. Residual ground-glass at CTFU was related to the length of hospitalization (r = 0.48; p = 0.0002) and to the need for mechanical ventilation or high flow oxygen (p = 0.01) during the acute phase. In conclusion, although patients at three months from discharge showed functional impairment and radiological abnormalities, which correlated with a prolonged hospital stay and need for mechanical ventilation, the persistence of respiratory symptoms was related not to parenchymal but rather to airway sequelae.

A 74-year-old hypertensive woman presented with shortness of breath. There was no associated coughing, chest pain or fever. ECG identified atrial fibrillation with rapid ventricular response. A transoesophageal echocardiogram was scheduled to exclude thrombus before cardioversion (Figure 1A); however, an echogenic structure was seen (Figure 1B arrow, see online supplementary video 1) between the left atrium, the pulmonary artery and the aortic root. Which of the following is the most likely diagnosis? A. Aortic valve endocarditis with annular abscess. B. Left atrial appendage thrombus. C. Left atrial myxoma. D. Pulmonary embolism.

Neoplastic lesions of the pancreas represent a heterogeneous group of entities that can be discovered incidentally at imaging or during examinations tailored towards suspected pancreatic disease. Accurate imaging is essential in the differential diagnosis, since prognosis, management, and therapies vary. Imaging of pancreatic neoplasms may help in detection, characterization, and staging. Suitable imaging modalities include ultrasonography (US) and US-related techniques, multislice computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine. A multimodality approach is mandatory and has a synergistic effect in improving diagnostic accuracy. Neoplastic lesions of the pancreas represent a heterogeneous group of entities that can be discovered incidentally at imaging or during examinations tailored towards suspected pancreatic disease. Imaging of pancreatic neoplasms may help in detection, characterization, and staging. Pancreatic ductal adenocarcinoma (PDA) represents up to 90% of all tumours of the exocrine pancreas and is the second most common gastrointestinal malignancy after colorectal cancer. The gross pathological features of PDA are of a mass with irregular ill-defined contours, a significant fibrous component, and, less frequently, necrotic changes. The absence of dilatation of the biliary and pancreatic ducts is observed in nearly 15% of cases of cephalic PDA (34). In these cases, PDA diagnosis is more challenging and there is a wider differential.

We assessed the effect of intra-coronary attenuation on diagnostic accuracy using 64-slice computed tomography coronary angiography (CT-CA). We enrolled 170 patients with suspected coronary artery disease who underwent conventional coronary angiography (CA) and 64-slice CT-CA (100 ml of Iomeprol 400 mg I/ml at 4 ml/s). The study population was divided into two groups (85 patients each based on median attenuation of 326 HU) based on mean arterial attenuation; group 1 with low attenuation and group 2 with high attenuation. Diagnostic accuracy for the detection of significant coronary artery stenosis was determined for both groups using CA as reference standard. Overall, 163 significant stenoses were detected in 1,030 assessable coronary artery segments in group 1 compared with 160 significant stenoses in 1,020 assessable segments in group 2. The average intra-coronary attenuation was significantly ( P  < 0.05) higher for group 2 (388 ± 46 HU) compared with group 1 (291 ± 33 HU). The corresponding sensitivity and specificity values for detection of significant coronary artery stenosis were higher for group 2 (96.3% and 97.6%, respectively) than for group 1 (82.8% and 93.2%, respectively) and were more marked in distal coronary segments than in proximal segments. Higher intra-coronary attenuation on CT-CA results in greater diagnostic accuracy for detection of coronary artery stenosis.

In Europe, highly pathogenic avian influenza (HPAI) virus circulates in avian wildlife, undergoing frequent reassortment, sporadic introductions in domestic birds, and spillover to mammals. An H5N1 clade 2.3.4.4b reassortant, EA-2023-DG, affecting wild and domestic birds was detected in western Europe in November 2023. Six of its RNA segments came from the EA-2021-AB genotype, but the polymerase basic 2 and polymerase acidic segments originated from low pathogenicity avian influenza viruses. Discrete phylogeographic analyses of concatenated genomes and single polymerase basic 2 and polymerase acidic segments suggested reassortment in summer 2023 near the southwestern Baltic Sea. Subsequent continuous phylogeographic analysis of all concatenated EA-2023-DG genomes highlighted circulation in northwestern Europe until June 2024 and long-distance dispersal toward France, Norway, England, Slovakia, Switzerland, and Austria. Those results illustrate the value of phylodynamic approaches to investigate emergence of novel avian influenza virus variants, trace their subsequent dispersal history, and provide vital clues for informing outbreak prevention and intervention policies.

This study is the follow up of the URBAN-MAES pilot implemented in the framework of the EnRoute project. The study aims at mapping and assessing the process of particulate matter (PM10) and tropospheric ozone (O3) removal by various forest and shrub ecosystems. Different policy levels and environmental contexts were considered, namely the Metropolitan city of Rome and, at a wider level, the Latium region. The approach involves characterization of the main land cover and ecosystems using Sentinel-2 images, enabling a detailed assessment of Ecosystem Service (ES), and monetary valuation based on externality values. The results showed spatial variations in the pattern of PM10 and O3 removal inside the Municipality and in the more rural Latium hinterland, reflecting the spatial dynamics of the two pollutants. Evergreen species displayed higher PM10 removal efficiency, whereas deciduous species showed higher O3 absorption in both rural and urban areas. The overall pollution removal accounted for 5123 and 19,074 Mg of PM10 and O3, respectively, with a relative monetary benefit of 161 and 149 Million Euro for PM10 and O3, respectively. Our results provide spatially explicit evidence that may assist policymakers in land-oriented decisions towards improving Green Infrastructure and maximizing ES provision at different governance levels.

PurposeCheckMate 915 (NCT03068455) compared adjuvant nivolumab monotherapy versus combination nivolumab+ipilimumab in patients with resected stage III/IV melanoma. This exploratory analysis was performed to identify biomarkers that correlate with benefit from adjuvant immunotherapy.Patients and methods1,844 patients received nivolumab 480 mg every 4 weeks or nivolumab 240 mg every 2 weeks with ipilimumab 1 mg/kg every 6 weeks. Tumor and peripheral biomarkers were evaluated, including tumor-informed circulating tumor DNA (ctDNA) at postresection baseline and on-treatment, for their association with recurrence-free survival and distant metastases-free survival.ResultsBiomarker analyses were conducted in 60–96% of the intention-to-treat population. ctDNA positivity at baseline (seen in 16.2% of patients) and on-treatment was associated with higher risk of recurrence than ctDNA negativity (HR, 1.97; 95% CI, 1.57 to 2.46), with a high specificity (87%) and modest sensitivity (39%). ctDNA status, tumor mutational burden (TMB) status (TMB < or ≥350 mutations/tumor) and interferon gamma-RNA signature score (< or ≥median) evaluated together, as well as ctDNA status with tumor CD8 or cell programmed death ligand 1 expression, were more predictive of survival than ctDNA alone. Tumor bulk RNA-seq expression patterns identified gene expression at baseline associated with recurrence.ConclusionsThis study represents the largest assessment of ctDNA and other baseline tumor and peripheral biomarkers for predicting recurrence-free survival in patients with resected melanoma receiving adjuvant immunotherapy. ctDNA alone and in combination with more established biomarkers predicted recurrence-free and distant metastasis-free survival and has potential utility for assessing and monitoring the risk of recurrence in patients with resected melanoma treated with immunotherapy in the adjuvant setting.Trial registration numberNCT03068455.