Procoagulant phenotype of virus-infected pericytes is associated with portal thrombosis and intrapulmonary vascular dilations in fatal COVID-19.

BACKGROUND & AIMS: Mechanisms and clinical impact of portal microthrombosis featuring severe COVID-19 are unknown. Intrapulmonary vascular dilation (IPVD)-related hypoxia has been described in severe liver diseases. We hypothesized that portal microthrombosis is associated with IPVD and fatal respiratory failure in COVID-19. METHODS: Ninety-three patients who died from COVID-19, were analysed for portal microvascular damage (histology), IPVD (histology and chest-computed tomography, CT), and hypoxemia (arterial blood gas). Seventeen patients who died from COVID-19-unrelated pneumonia served as controls. Vascular lesions and microthrombi were phenotyped for endothelial (vWF) and pericyte (αSMA/PDGFR-ß) markers, tissue factor (TF), viral spike-protein and nucleoprotein (SP, NP), fibrinogen, platelets (CD41a). Viral particles in vascular cells were assessed by transmission electron microscopy (TEM). Cultured pericytes were infected with SARS-CoV-2 to measure TF expression and tubulisation of human pulmonary microvascular endothelial cells (HPMEC) was assessed upon vWF treatment. RESULTS: IPVD was present in 16/66 COVID-19 patients with both liver and lung histology, with a younger age (62 vs 78yo), longer illness (25 vs 14 days), worsening hypoxemia (PaO2/FiO2 from 209 to 89), and more ventilatory support (63 vs 22%) compared to COVID-19/Non-IPVD. IPVD, absent in controls, were confirmed by chest-CT. COVID-19/IPVD liver histology showed portal microthrombosis in >82.5% of portal areas, with a thicker wall of αSMA/PDGFR-ß+/ SP+/NP+ pericytes compared with COVID-19/Non-IPVD. Thrombosed portal venules correlated with αSMA+ area, whereas infected SP+/NP+ pericytes expressed TF. SARS-CoV-2 viral particles were observed in portal pericytes. In-vitro SARS-CoV-2 infection of pericytes up-regulated TF and induced endothelial cells to overexpress vWF, which expanded HPMEC tubules. CONCLUSIONS: SARS-CoV-2 infection of liver pericytes elicits a local procoagulant response associated with extensive portal microthrombosis, IPVD and worsening respiratory failure in fatal COVID-19. IMPACT AND IMPLICATIONS: Vascular involvement of the liver represents a serious complication of COVID-19 infection that must be considered in the work-up of patients with long-lasting and progressively worsening respiratory failure, as it may associate with the development of intrapulmonary vascular dilations. This clinical picture is associated with a pro-coagulant phenotype of portal venule pericytes, which is induced by SARS-CoV-2 infection of pericytes. Both observations provide a model that may apply, at least in part, to other vascular disorders of the liver, featuring obliterative portal venopathy, similarly characterized at the clinical level by development of hypoxemia and at the histological level, by phlebosclerosis and reduced caliber of the portal vein branches in the absence of cirrhosis. Moreover, our findings bring light to an as yet overlooked player of thrombosis pathophysiology, i.e. pericytes, which may provide novel therapeutic tools to halt prothrombotic mechanisms.

Abnormal Uterine Bleeding: A Pictorial Review on Differential Diagnosis and Not-So-Common Cases of Interventional Radiology Management.

Abnormal uterine bleeding (AUB) poses a multifaceted challenge in women's health, necessitating an integrated approach that addresses its diverse etiologies and clinical presentations. The International Federation of Gynecology and Obstetrics PALM-COEIN classification system provides a systematic approach to the diagnosis of AUB in non-pregnant women, based on clinical and imaging-based categorization of causes into structural (Polyps, Adenomyosis, Leiomyomas and Malignancy; PALM), and non-structural causes (Coagulopathies, Ovulatory disorders, primary Endometrial disorders, Iatrogenic and Not otherwise classified; COEIN). On the other hand, placental disorders, uterine rupture, ectopic pregnancy and retained products of conceptions are the main causes of uterine bleeding during pregnancy and in the peripartum period. Ultrasound is usually the first-line imaging technique for the differential diagnosis of causes of AUB. Computed Tomography may be useful if ultrasound findings are unclear, especially in emergency settings. Magnetic resonance imaging, when indicated, is an excellent second-line diagnostic tool for a better non-invasive characterization of the underlying cause of AUB. This pictorial review aims to illustrate the main causes of AUB from the point of view of diagnostic imaging and to show not-so-common cases that can be treated by means of interventional radiology.

Gas exchange abnormalities in Long COVID are driven by the alteration of the vascular component.

BACKGROUND: There are uncertainties whether the impairment of lung diffusing capacity in COVID-19 is due to an alteration in the diffusive conductance of the alveolar membrane (Dm), or an alteration of the alveolar capillary volume (Vc), or a combination of both. The combined measurement DLNO and DLCO diffusion, owing to NO higher affinity and faster reaction rate with haemoglobin compared to CO, enables the simultaneous and rapid determination of both Vc and Dm. The aim of the present study was to better identify the precise cause of post-COVID-19 diffusion impairment. METHODS: Using the combined NO and CO gas transfer techniques (DLNO and DLCO), it is possible to better understand whether gas exchange abnormalities are due to membrane or alveolar capillary volume components. The present study was aimed at evaluating pulmonary gas exchange one year after severe COVID-19.  Results: The cohort included 33 survivors to severe COVID-19 (median age 67 years, 70% male) with no pre-existing lung disease, who underwent clinical, lung function and imaging assessments at 12 months due to persistence of respiratory symptoms or radiological impairment. The gas exchange abnormalities were mainly determined by the compromise of the vascular component as demonstrated by vascular pattern of gas exchange impairment (i.e., DLNO/DLCO≥110%, 76% of the sample), and by a reduction of the Vc (73%), while the Dm was reduced only in 9% of the entire sample. We did not find a correlation between the gas exchange impairment and the extent of the chest CT alterations (DLCO p = 0.059 and DLNO p = 0.054), which on average were found to be mild (11% of the parenchyma). CONCLUSION: In COVID-19 survivors who are still symptomatic or have minimal CT findings at one year, gas exchange abnormalities are determined by impairment of the vascular component, rather than the diffusive component of the alveolar membrane.

Atrial and ventricular strain using cardiovascular magnetic resonance in the prediction of outcomes of pericarditis patients: a pilot study.

OBJECTIVE: Our study aimed to explore with cardiovascular magnetic resonance (CMR) the impact of left atrial (LA) and left ventricular (LV) myocardial strain in patients with acute pericarditis and to investigate their possible prognostic significance in adverse outcomes. METHOD: This retrospective study performed CMR scans in 36 consecutive patients with acute pericarditis (24 males, age 52 [23-52]). The primary endpoint was the combination of recurrent pericarditis, constrictive pericarditis, and surgery for pericardial diseases defined as pericardial events. Atrial and ventricular strain function were performed on conventional cine SSFP sequences. RESULTS: After a median follow-up time of 16 months (interquartile range [13-24]), 12 patients with acute pericarditis reached the primary endpoint. In multivariable Cox regression analysis, LA reservoir and LA conduit strain parameters were all independent determinants of adverse pericardial diseases. Conversely, LV myocardial strain parameters did not remain an independent predictor of outcome. With receiving operating characteristics curve analysis, LA conduit and reservoir strain showed excellent predictive performance (area under the curve of 0.914 and 0.895, respectively) for outcome prediction at 12 months. CONCLUSION: LA reservoir and conduit mechanisms on CMR are independently associated with a higher risk of adverse pericardial events. Including atrial strain parameters in the management of acute pericarditis may improve risk stratification. CLINICAL RELEVANCE STATEMENT: Atrial strain could be a suitable non-invasive and non-contrast cardiovascular magnetic resonance parameter for predicting adverse pericardial complications in patients with acute pericarditis. KEY POINTS: • Myocardial strain is a well-validated CMR parameter for risk stratification in cardiovascular diseases. • LA reservoir and conduit functions are significantly associated with adverse pericardial events. • Atrial strain may serve as an additional non-contrast CMR parameter for stratifying patients with acute pericarditis.

Pseudoaneurysms embolization with glue via percutaneous direct puncture: a multicenter experience on 54 patients.

BACKGROUND: This retrospective multicentric study aims to report on technical safety and effectiveness of pseudoaneurysms embolization with glue (N-butyl cyanoacrylate) adopting a percutaneous direct puncture approach. RESULTS: Fifty-four patients data were collected from five centers. All patients at the time of treatment presented with unruptured PAs and were hemodynamically stable. True aneurysms and lesions treated with embolics other than glue were excluded. Pseudoaneurysms diagnosis was based on CT and anamnestic data; initial investigation with digital-subtracted arteriography was acquired in all cases; then, percutaneous embolizations were performed in the angio-suite (ultrasound, fluoroscopy, ConeBeam CT guidance) or in CT. Technical success was considered as complete pseudoaneurysm embolization at final imaging with sole percutaneous strategy, without need for additional endovascular embolization. Clinical success was intended as pseudoaneurysm resolution within one week follow-up with stabilization or restored clinical conditions. Pseudoaneurysms origins were traumatic (57.4%), inflammatory (24.1%) or spontaneous (18.5%); 39 patients (72.2%) were symptomatic, presenting with pain and/or pulsatile mass. Mean lesions diameter was 19.3 mm (range: 7-30); pseudoaneurysms were located in abdomen (48.1%), limbs (42.6%) and thorax (9.3%). Coagulation function was impaired in 16.6% and 48.1% was under antiplatelets/anticoagulation therapy. In 16.6% the percutaneous approach followed previous treatments failure. The image-guidance modality for percutaneous puncture was most often ultrasound combined with fluoroscopy (38%). Clinical success was obtained in all patients while technical success occurred in 94.4% because 3 patients required an additional endovascular embolization. Complications were registered in 14.8%, all of low grade without clinical sequelae neither prolonged recovery (7 non target embolizations, 1 post-embolization syndrome). CONCLUSIONS: In this study, pseudoaneurysms embolization with glue via percutaneous direct puncture was safe and effective with a low rate of minor complications.

CT Coronary Angiography: Technical Approach and Atherosclerotic Plaque Characterization.

Coronary computed tomography angiography (CCTA) currently represents a robust imaging technique for the detection, quantification and characterization of coronary atherosclerosis. However, CCTA remains a challenging task requiring both high spatial and temporal resolution to provide motion-free images of the coronary arteries. Several CCTA features, such as low attenuation, positive remodeling, spotty calcification, napkin-ring and high pericoronary fat attenuation index have been proved as associated to high-risk plaques. This review aims to explore the role of CCTA in the characterization of high-risk atherosclerotic plaque and the recent advancements in CCTA technologies with a focus on radiomics plaque analysis.

Chest X-ray at Emergency Admission and Potential Association with Barotrauma in Mechanically Ventilated Patients: Experience from the Italian Core of the First Pandemic Peak.

Barotrauma occurs in a significant number of patients with COVID-19 interstitial pneumonia undergoing mechanical ventilation. The aim of the current study was to investigate whether the Brixia score (BS) calculated on chest-X-rays acquired at the Emergency Room was associated with barotrauma. We retrospectively evaluated 117 SARS-CoV-2 patients presented to the Emergency Department (ED) and then admitted to the intensive care unit (ICU) for mechanical ventilation between February and April 2020. Subjects were divided into two groups according to the occurrence of barotrauma during their hospitalization. CXRs performed at ED admittance were assessed using the Brixia score. Distribution of barotrauma (pneumomediastinum, pneumothorax, subcutaneous emphysema) was identified in chest CT scans. Thirty-eight subjects (32.5%) developed barotrauma (25 pneumomediastinum, 24 pneumothorax, 24 subcutaneous emphysema). In the barotrauma group we observed higher Brixia score values compared to the non-barotrauma group (mean value 12.18 vs. 9.28), and logistic regression analysis confirmed that Brixia score is associated with the risk of barotrauma. In this work, we also evaluated the relationship between barotrauma and clinical and ventilatory parameters: SOFA score calculated at ICU admittance and number of days of non-invasive ventilation (NIV) prior to intubation emerged as other potential predictors of barotrauma.

Technical and Clinical Outcomes of Laparoscopic-Laparotomic Hepatocellular Carcinoma Thermal Ablation with Microwave Technology: Case Series and Review of Literature.

PURPOSE: To evaluate technical and clinical outcomes of intraoperative (laparoscopic/laparotomic) microwave ablation on HCC. MATERIALS AND METHODS: This is a retrospective single-center study evaluating consecutive patients treated for very early/early-stage HCC with intraoperative microwave ablation from 1 July 2017 to 30 June 2023. In these patients, a percutaneous US-guided approach was excluded due to the nodule's suboptimal visibility or harmful location and liver resection for a deep position or adherences. Data about the clinical stage, surgical approach, liver pathology and nodules characteristics, technical success, complications, and follow-up were collected. Technical success was intended as the absence of locoregional persistence at follow-up CT/MRI controls. RESULTS: A total of 36 cirrhotic patients (M:F = 30:6, median age 67 years) were enrolled; 18/36 (50%) had a single nodule, 13/36 (36%) had two, 4/36 had three (11%), and 1/36 had four (3%). Among the patients, 24 (67%) were treated with laparoscopy, and 12/36 (33%) with a laparotomic approach. Sixty HCCs of 16.5 mm (6-50 mm) were treated for 7 min (2-30 min) with 100 W of power. A total of 55 nodules (92%) were treated successfully and showed no residual enhancement at the first postoperative follow-up; the other 5/60 (8%) underwent chemo/radioembolization. There was one complication (3%): a biliary fistula treated with percutaneous drainage and glue embolization. The average hospital stay was 3.5 days (1-51 days), and patients were followed up on average for 238 days (13-1792 days). During follow-up, 5/36 patients (14%) underwent liver transplantation, 1/36 (2%) died during hospitalization and 1 after discharge. CONCLUSIONS: Laparoscopic/laparotomic intraoperative HCC MW ablation is feasible in patients unsuitable for percutaneous approach or hepatic resection, with rare complications and with good technical and clinical outcomes.