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.

Effect of late gadolinium enhancement on left atrial impairment in myocarditis patients.

OBJECTIVE: The aims of our study were to investigate the effect of the extent and location of late gadolinium enhancement (LGE) on the left atrium (LA) function in patients with acute myocarditis (AM) using cardiovascular magnetic resonance (CMR). METHOD: This retrospective study performed CMR scans in 113 consecutive patients (89 males, 24 females; mean age 45.8 ± 17.3 years) with AM that met the updated Lake Louise criteria. Reservoir, conduit, and booster LA functions were analyzed by CMR feature tracking using dedicated software. Besides LA strain measurements, myocardial scar location and extent were assigned and quantified by LGE imaging. RESULTS: AM patients with septal LGE had impaired reservoir, conduit, and conduit strain rate function in comparison with AM patients with non-septal LGE (p = 0.001, for all). In fully adjusted multivariable linear regression, reservoir and conduit were significantly associated with left ventricle (LV) LGE location (ß coefficient = 8.205, p = 0.007; ß coefficient = 5.185, p = 0.026; respectively). In addition, LA parameters decreased according to the increase in the extent of LV fibrosis (LGE ≤ 10%; LGE 11-19%; LGE ≥ 20%). After adjustment in multivariable linear regression, the association with LV LGE extent was no longer statistically significant. CONCLUSION: In patients with acute myocarditis, LA function abnormalities are significantly associated with LV LGE location, but not with LGE extent. Septal LGE is paralleled by a deterioration of LA reservoir and conduit function. CLINICAL RELEVANCE STATEMENT: Left atrium dysfunction is associated with the presence of late gadolinium enhancement in the left ventricle septum and can be useful in the clinical prognostication of patients with acute myocarditis, allowing individually tailored treatment. KEY POINTS: • Myocardial fibrosis is related to atrial impairment. • The location of myocardial fibrosis is the main determinant of atrial dysfunction in myocarditis patients. • The quantification of atrial mechanisms may provide more in-depth insight into myocarditis pathophysiology.

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.

An MRI assessment of prostate cancer local recurrence using the PI-RR system: diagnostic accuracy, inter-observer reliability among readers with variable experience, and correlation with PSA values.

OBJECTIVES: The Prostate Imaging for Recurrence Reporting (PI-RR) system has been recently proposed to promote standardisation in the MR assessment of prostate cancer (PCa) local recurrence after radical prostatectomy (RP) and radiation therapy (RT). This study aims to evaluate PI-RR's diagnostic accuracy, assess the inter-observer reliability among readers with variable experience, and correlate imaging results with anatomopathological and laboratory parameters. METHODS: Patients who underwent a pelvic MRI for suspicion of PCa local recurrence after RP or RT were retrospectively enrolled (October 2017-February 2020). PI-RR scores were independently assessed for each patient by five readers with variable experience in prostate MRI (two senior and three junior radiologists). Biochemical data and histopathological features were collected. The reference standard was determined through biochemical, imaging, or histopathological follow-up data. Reader's diagnostic performance was assessed using contingency tables. Cohen's kappa coefficient (κ) and intraclass correlation coefficient (ICC) were calculated to measure inter-observer reliability. RESULTS: The final cohort included 120 patients (median age, 72 years [IQR, 62-82]). Recurrence was confirmed in 106 (88.3%) patients. Considering a PI-RR score ≥ 3 as positive for recurrence, minimum and maximum diagnostic values among the readers were as follows: sensitivity 79-86%; specificity 64-86%; positive predictive value 95-98%; negative predictive value 33-46%; accuracy 79-87%. Regardless of reader's level of experience, the inter-observer reliability resulted good or excellent (κ ranges across all readers: 0.52-0.77), and ICC was 0.8. Prostate-specific antigen (PSA) velocity, baseline-PSA, and trigger-PSA resulted predictive of local recurrence at imaging. CONCLUSIONS: The PI-RR system is an effective tool for MRI evaluation of PCa local recurrence and facilitates uniformity among radiologists. CLINICAL RELEVANCE STATEMENT: This study confirmed the PI-RR system's good diagnostic accuracy for the MRI evaluation of PCa local recurrences. It showed high reproducibility among readers with variable experience levels, validating it as a promising standardisation tool for assessing patients with biochemical recurrence. KEY POINTS: • In this retrospective study, the PI-RR system revealed promising diagnostic performances among five readers with different experience (sensitivity 79-86%; specificity 64-86%; accuracy 79-87%). • The inter-observer reliability among the five readers resulted good or excellent (κ ranges: 0.52-0.77) with an intraclass correlation coefficient of 0.8. • The PI-RR assessment score may facilitate standardisation and generalizability in the evaluation of prostate cancer local recurrence among radiologists.

Diffusion magnetic resonance imaging for kidney cyst volume quantification and non-cystic tissue characterisation in ADPKD.

OBJECTIVES: Beyond total kidney and cyst volume (TCV), non-cystic tissue plays an important role in autosomal dominant polycystic kidney disease (ADPKD) progression. This study aims at presenting and preliminarily validating a diffusion MRI (DWI)-based TCV quantification method and providing evidence of DWI potential in characterising non-cystic tissue microstructure. METHODS: T2-weighted MRI and DWI scans (b = 0, 15, 50, 100, 200, 350, 500, 700, 1000; 3 directions) were acquired from 35 ADPKD patients with CKD stage 1 to 3a and 15 healthy volunteers on a 1.5 T scanner. ADPKD classification was performed using the Mayo model. DWI scans were processed by mono- and segmented bi-exponential models. TCV was quantified on T2-weighted MRI by the reference semi-automatic method and automatically computed by thresholding the pure diffusivity (D) histogram. The agreement between reference and DWI-based TCV values and the differences in DWI-based parameters between healthy and ADPKD tissue components were assessed. RESULTS: There was strong correlation between DWI-based and reference TCV (rho = 0.994, p < 0.001). Non-cystic ADPKD tissue had significantly higher D, and lower pseudo-diffusion and flowing fraction than healthy tissue (p < 0.001). Moreover, apparent diffusion coefficient and D values significantly differed by Mayo imaging class, both in the whole kidney (Wilcoxon p = 0.007 and p = 0.004) and non-cystic tissue (p = 0.024 and p = 0.007). CONCLUSIONS: DWI shows potential in ADPKD to quantify TCV and characterise non-cystic kidney tissue microstructure, indicating the presence of microcysts and peritubular interstitial fibrosis. DWI could complement existing biomarkers for non-invasively staging, monitoring, and predicting ADPKD progression and evaluating the impact of novel therapies, possibly targeting damaged non-cystic tissue besides cyst expansion. CLINICAL RELEVANCE STATEMENT: This study shows diffusion-weighted MRI (DWI) potential to quantify total cyst volume and characterise non-cystic kidney tissue microstructure in ADPKD. DWI could complement existing biomarkers for non-invasively staging, monitoring, and predicting ADPKD progression and evaluating the impact of novel therapies, possibly targeting damaged non-cystic tissue besides cyst expansion. KEY POINTS: • Diffusion magnetic resonance imaging shows potential to quantify total cyst volume in ADPKD. • Diffusion magnetic resonance imaging might allow to non-invasively characterise non-cystic kidney tissue microstructure. • Diffusion magnetic resonance imaging-based biomarkers significantly differ by Mayo imaging class, suggesting their possible prognostic value.

Chest CT opportunistic biomarkers for phenotyping high-risk COVID-19 patients: a retrospective multicentre study.

OBJECTIVE: To assess the value of opportunistic biomarkers derived from chest CT performed at hospital admission of COVID-19 patients for the phenotypization of high-risk patients. METHODS: In this multicentre retrospective study, 1845 consecutive COVID-19 patients with chest CT performed within 72 h from hospital admission were analysed. Clinical and outcome data were collected by each center 30 and 80 days after hospital admission. Patients with unknown outcomes were excluded. Chest CT was analysed in a single core lab and behind pneumonia CT scores were extracted opportunistic data about atherosclerotic profile (calcium score according to Agatston method), liver steatosis (≤ 40 HU), myosteatosis (paraspinal muscle F < 31.3 HU, M < 37.5 HU), and osteoporosis (D12 bone attenuation < 134 HU). Differences according to treatment and outcome were assessed with ANOVA. Prediction models were obtained using multivariate binary logistic regression and their AUCs were compared with the DeLong test. RESULTS: The final cohort included 1669 patients (age 67.5 [58.5-77.4] yo) mainly men 1105/1669, 66.2%) and with reduced oxygen saturation (92% [88-95%]). Pneumonia severity, high Agatston score, myosteatosis, liver steatosis, and osteoporosis derived from CT were more prevalent in patients with more aggressive treatment, access to ICU, and in-hospital death (always p < 0.05). A multivariable model including clinical and CT variables improved the capability to predict non-critical pneumonia compared to a model including only clinical variables (AUC 0.801 vs 0.789; p = 0.0198) to predict patient death (AUC 0.815 vs 0.800; p = 0.001). CONCLUSION: Opportunistic biomarkers derived from chest CT can improve the characterization of COVID-19 high-risk patients. CLINICAL RELEVANCE STATEMENT: In COVID-19 patients, opportunistic biomarkers of cardiometabolic risk extracted from chest CT improve patient risk stratification. KEY POINTS: • In COVID-19 patients, several information about patient comorbidities can be quantitatively extracted from chest CT, resulting associated with the severity of oxygen treatment, access to ICU, and death. • A prediction model based on multiparametric opportunistic biomarkers derived from chest CT resulted superior to a model including only clinical variables in a large cohort of 1669 patients suffering from SARS- CoV2 infection. • Opportunistic biomarkers of cardiometabolic comorbidities derived from chest CT may improve COVID-19 patients' risk stratification also in absence of detailed clinical data and laboratory tests identifying subclinical and previously unknown conditions.

Venous outflow obstruction in pediatric left lateral segment split liver transplantation.

BACKGROUND: Venous outflow obstruction (VOO) is a known cause of graft and patient loss after pediatric liver transplantation (LT). We analyzed the incidence, risk factors, diagnosis, management, and outcome of VOO in a large, consecutive series of left lateral segment (LLS) split LT with end-to-side triangular venous anastomosis. METHODS: We evaluated data collected in our prospective databases relative to all consecutive pediatric liver transplants performed from January 2006 to December 2021. We included in this study children undergoing LLS split liver transplant with end-to-side triangular anastomosis. Diagnosis of VOO was based on clinical suspicion and radiological confirmation. RESULTS: VOO occurred in 24/279 transplants (8.6%), and it was associated with lower graft weight (p = .04), re-transplantation (p = .008), and presence of two hepatic veins (p < .0001). In presence of two segmental veins' orifices, the type of reconstruction (single anastomosis after venoplasty or double anastomosis) was not significantly related to VOO (p = .87). Multivariable analysis indicated VOO as a risk factor for graft lost (hazard ratio 3.21, 95% confidence interval 1.22-8.46; p = .01). Percutaneous Transluminal Angioplasty (PTA) was effective in 17/22 (77%) transplants. Surgical anastomosis was redone in one case. Overall six grafts (25%) were lost. CONCLUSION: VOO after LLS split LT with end-to-side triangular anastomosis is an unusual but critical complication leading to graft loss in a quarter of cases. The occurrence of VOO was associated with lower graft weight, re-transplantation, and presence of two hepatic veins. PTA was safe and effective to restore proper venous outflow in most cases.

CT renal arteriography as a novel imaging guidance for the percutaneous ablation of small renal tumors.

PURPOSE: To report procedural data and outcomes of a novel image guidance technique, CT renal arteriography (CTRA), performed to target and ablate small intraparenchymal renal tumors. MATERIALS AND METHODS: We retrospectively analyzed data of 2 patients undergoing CTRA-guided ablation for 3 renal intraparenchymal tumors, from February to March 2023. We previously evaluated tumor visibility with US/CEUS, and in all cases conspicuity was poor, whereas contrast-enhanced CT (CECT) clearly depicted all hypervascular nodules. Our primary endpoint was CTRA-guidance feasibility for renal ablation, defined as the precise probe deployment inside the target tumor. The secondary endpoint was CTRA-guided ablation technical success, intended as the inclusion of the whole tumor inside the necrotic volume, with 5 mm safety margins. RENAL scores, complications, procedural time, dose length product (DLP), serum creatinine variation and hospital stay length were also recorded. RESULTS: A confident deployment of the probe tip inside the nodule was accomplished in all 3 cases, with a 100% of correct targeting. We observed immediate technical success after all 3 ablations. The 3 nodules had a RENAL score <7 points, and we encountered no complications due to line placement or ablation. The average time from preablative to postablative CTRA was 54 min (50-58min), with a DLP of 3632mGy*cm (2807-4458mGy*cm). Serum creatinine didn't show a significant variation after the procedures; both patients were hospitalized for 2 days. CONCLUSION: Preliminary data showed that CTRA-guidance might provide unique advantages over conventional CECT-guidance to assist the ablation of small renal intraparenchymal tumor not visualized on US/CEUS.

US-guided percutaneous thrombin injection to treat non-femoral artery pseudoaneurysms: preliminary experience and review of the literature.

PURPOSE: To evaluate the clinical outcome of US-guided percutaneous thrombin injection in the treatment of non-femoral artery pseudoaneurysms (NFAP). MATERIALS AND METHODS: Among all pseudoaneurysms treated in our institution, we retrospectively collected NFAP embolized with percutaneous thrombin injections from January 1, 2015, to December 31, 2021. The embolization was prompted for an ongoing antiaggregating/anticoagulation therapy, NFAP optimal US visibility, or high surgery-related risks. Causes, location, size and neck of NFAP, complications, number of repeated treatments, clinical success and patients clinical conditions at discharge were annotated. The endpoint for clinical success was the resolution of NFAP at postprocedural imaging, with no resort to surgery. RESULTS: Eight consecutive patients (5 females, median age 73 years, range 46-84) underwent 16 procedures. Arterial damage was due to catheterization (3), CVC mispositioning (2), trauma, hemorrhagic diathesis and endoprosthesis endoleak. We treated humeral (2), subclavian (2), thyrocervical, anterior tibial, radial and pancreaticoduodenal arteries. Median pseudoaneurysm size was 530 mm2 (range 32-2400 mm2), with a thin (7/8) or non-visible (1/8) neck. No complications occurred. Clinical success was obtained in 7/8 patients (88%), with a single treatment in 4, multiple in 3 cases (4 embolizations, 3 and 2, respectively). One patient underwent surgical suture after the second failed attempt of percutaneous embolization. Seven patients were discharged in good clinical conditions; one died during hospitalization, due to the worsening of the underlying cardiac disease. CONCLUSIONS: Percutaneous US-guided thrombin injection to treat NFAP is feasible in selected cases, with rare complications. Clinical success is often reached, also by repeated injections.

Biliary complications in pediatric liver transplantation: findings of percutaneous transhepatic cholangiography in a large single-center cohort.

BACKGROUND: Although biliary complications after orthotopic liver transplantation represent a common source of morbidity and mortality, decreasing graft survival, consensus is lacking on their management in the pediatric population. OBJECTIVE: The aim of this study was to present the prevalence of such biliary complications and their interventional radiologic management with representative images. MATERIALS AND METHODS: This retrospective study reports our experience with percutaneous transhepatic cholangiography in the management of biliary complications after orthotopic liver transplantation in pediatric patients. This study enrolled all pediatric patients (<18 years old) who underwent percutaneous transhepatic cholangiography for the management of biliary complications after orthotopic liver transplantation at a tertiary care center between January 2010 and December 2020. Diagnosis of biliary complications and indication to perform percutaneous transhepatic cholangiography were based on clinical, laboratory or radiologic data. RESULTS: Among the 301 orthotopic liver transplantations, 78 (26%) developed biliary complications that were managed by interventional radiology: these included 52 (17.3%) biliary strictures, 19 (6.3%) bile leaks, 5 (1.7%) biliary stones, 1 (0.3%) iatrogenic biliary obstruction and 1 (0.3%) vanishing syndrome. The median time interval between orthotopic liver transplantation and the diagnosis of biliary complications was 6.0 years (interquartile range [IQR] 8.2 years). Percutaneous transhepatic cholangiography and biliary duct catheterization were successful in all cases, with low rates of complications that were variable among subgroups. CONCLUSION: A wide spectrum of biliary complications can occur after pediatric orthotopic liver transplantation. In this large single-center experience, we highlight the value of percutaneous transhepatic cholangiography in their diagnosis and management. Percutaneous treatments in pediatric patients are safe and effective, providing resolution or serving as a bridge to surgery, including re-transplantation.

Aortic regurgitation: A multimodality approach.

Aortic regurgitation (AR) is a common valvular pathology. Multimodality noninvasive cardiovascular imaging is routinely used to assess the mechanism of AR, degree, and its hemodynamic impact on the cardiovascular system. Collecting this information is crucial in establishing the prognosis and in guiding patient management and follow-up. While echocardiography remains the primary test to assess AR, a comprehensive assessment of this valvulopathy can be obtained by combining the information from different techniques. This state-of-the-art review is intended to provide an update ed overview of the applications, strengths, and limits of transthoracic echocardiography, cardiac magnetic resonance, and cardiac computed tomography in patients with AR.

Multimodality imaging in acute myocarditis.

The diagnosis of acute myocarditis often involves several noninvasive techniques that can provide information regarding volumes, ejection fraction, and tissue characterization. In particular, echocardiography is extremely helpful for the evaluation of biventricular volumes, strain and ejection fraction. Cardiac magnetic resonance, beyond biventricular volumes, strain, and ejection fraction allows to characterize myocardial tissue providing information regarding edema, hyperemia, and fibrosis. Contemporary cardiac computed tomography angiography (CCTA) can not only be extremely important for the assessment of coronary arteries, pulmonary arteries and aorta but also tissue characterization using CCTA can be an additional tool that can explain chest pain with a diagnosis of myocarditis.

Artificial intelligence, machine learning and deep learning in musculoskeletal imaging: Current applications.

Artificial intelligence is rapidly expanding in all technological fields. The medical field, and especially diagnostic imaging, has been showing the highest developmental potential. Artificial intelligence aims at human intelligence simulation through the management of complex problems. This review describes the technical background of artificial intelligence, machine learning, and deep learning. The first section illustrates the general potential of artificial intelligence applications in the context of request management, data acquisition, image reconstruction, archiving, and communication systems. In the second section, the prospective of dedicated tools for segmentation, lesion detection, automatic diagnosis, and classification of musculoskeletal disorders is discussed.

AI-SCoRE (artificial intelligence-SARS CoV2 risk evaluation): a fast, objective and fully automated platform to predict the outcome in COVID-19 patients.

PURPOSE: To develop and validate an effective and user-friendly AI platform based on a few unbiased clinical variables integrated with advanced CT automatic analysis for COVID-19 patients' risk stratification. MATERIAL AND METHODS: In total, 1575 consecutive COVID-19 adults admitted to 16 hospitals during wave 1 (February 16-April 29, 2020), submitted to chest CT within 72 h from admission, were retrospectively enrolled. In total, 107 variables were initially collected; 64 extracted from CT. The outcome was survival. A rigorous AI model selection framework was adopted for models selection and automatic CT data extraction. Model performances were compared in terms of AUC. A web-mobile interface was developed using Microsoft PowerApps environment. The platform was externally validated on 213 COVID-19 adults prospectively enrolled during wave 2 (October 14-December 31, 2020). RESULTS: The final cohort included 1125 patients (292 non-survivors, 26%) and 24 variables. Logistic showed the best performance on the complete set of variables (AUC = 0.839 ± 0.009) as in models including a limited set of 13 and 5 variables (AUC = 0.840 ± 0.0093 and AUC = 0.834 ± 0.007). For non-inferior performance, the 5 variables model (age, sex, saturation, well-aerated lung parenchyma and cardiothoracic vascular calcium) was selected as the final model and the extraction of CT-derived parameters was fully automatized. The fully automatic model showed AUC = 0.842 (95% CI: 0.816-0.867) on wave 1 and was used to build a 0-100 scale risk score (AI-SCoRE). The predictive performance was confirmed on wave 2 (AUC 0.808; 95% CI: 0.7402-0.8766). CONCLUSIONS: AI-SCoRE is an effective and reliable platform for automatic risk stratification of COVID-19 patients based on a few unbiased clinical data and CT automatic analysis.

Liver injury in COVID-19 and IL-6 trans-signaling-induced endotheliopathy.

BACKGROUND AND AIMS: COVID-19 is associated with liver injury and elevated interleukin-6 (IL-6). We hypothesized that IL-6 trans-signaling in liver sinusoidal endothelial cells (LSECs) leads to endotheliopathy (a proinflammatory and procoagulant state) and liver injury in COVID-19. METHODS: Coagulopathy, endotheliopathy, and alanine aminotransferase (ALT) were retrospectively analyzed in a subset (n = 68), followed by a larger cohort (n = 3,780) of patients with COVID-19. Liver histology from 43 patients with COVID-19 was analyzed for endotheliopathy and its relationship to liver injury. Primary human LSECs were used to establish the IL-6 trans-signaling mechanism. RESULTS: Factor VIII, fibrinogen, D-dimer, von Willebrand factor (vWF) activity/antigen (biomarkers of coagulopathy/endotheliopathy) were significantly elevated in patients with COVID-19 and liver injury (elevated ALT). IL-6 positively correlated with vWF antigen (p = 0.02), factor VIII activity (p = 0.02), and D-dimer (p <0.0001). On liver histology, patients with COVID-19 and elevated ALT had significantly increased vWF and platelet staining, supporting a link between liver injury, coagulopathy, and endotheliopathy. Intralobular neutrophils positively correlated with platelet (p <0.0001) and vWF (p <0.01) staining, and IL-6 levels positively correlated with vWF staining (p <0.01). IL-6 trans-signaling leads to increased expression of procoagulant (factor VIII, vWF) and proinflammatory factors, increased cell surface vWF (p <0.01), and increased platelet attachment in LSECs. These effects were blocked by soluble glycoprotein 130 (IL-6 trans-signaling inhibitor), the JAK inhibitor ruxolitinib, and STAT1/3 small-interfering RNA knockdown. Hepatocyte fibrinogen expression was increased by the supernatant of LSECs subjected to IL-6 trans-signaling. CONCLUSION: IL-6 trans-signaling drives the coagulopathy and hepatic endotheliopathy associated with COVID-19 and could be a possible mechanism behind liver injury in these patients. LAY SUMMARY: Patients with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection often have liver injury, but why this occurs remains unknown. High levels of interleukin-6 (IL-6) and its circulating receptor, which form a complex to induce inflammatory signals, have been observed in patients with COVID-19. This paper demonstrates that the IL-6 signaling complex causes harmful changes to liver sinusoidal endothelial cells and may promote blood clotting and contribute to liver injury.

Whole-body low-dose computed tomography (WBLDCT) in staging and re-staging of multiple myeloma.

The objective of this study is to evaluate the prognostic features of multiple myeloma (MM) using whole-body low-dose computed tomography (WBLDCT). One hundred three patients with biopsy-proven MM who underwent WBLDCT were retrospectively enrolled. The evolution of osteolytic lesions overtime was performed by measuring the maximum axial diameter at the baseline (T0) and the end of follow-up (Te), by using a cut-off value of 10 mm. The location and dimension of up to three lesions were registered. The time-to-fracture (TTF) was recorded. Sixty-three percent of patients presented a focal pattern, 22% a diffuse pattern, and 15% a combined one. Seventy-two percent of patients with lesions ≤ 10 mm presented stability, 27% a dimensional increase, and 1% a decrease. Patients with lesions >10 mm showed a statistically significant difference regarding the mean difference of axial diameter between T0 and Te (p = 0.015). Patients with lesions >10 mm showed an odds ratio (OR) of 29.8 (95%CIs 3.8-230.5) to develop at least one fracture. Mean TTF was significantly lower in patients with lesions >10 mm in comparison with lesions ≤ 10 mm (9 ± 3 vs 23 ± 7 months, respectively, p = 0.011). WBLDCT represents a reliable imaging-based tool for proper management of MM patients, showing that diffuse form or small lytic lesions may deserve a less frequent follow-up.

Chest X-ray for predicting mortality and the need for ventilatory support in COVID-19 patients presenting to the emergency department.

OBJECTIVES: To evaluate the inter-rater agreement of chest X-ray (CXR) findings in coronavirus disease 2019 (COVID-19) and to determine the value of initial CXR along with demographic, clinical, and laboratory data at emergency department (ED) presentation for predicting mortality and the need for ventilatory support. METHODS: A total of 340 COVID-19 patients who underwent CXR in the ED setting (March 1-13, 2020) were retrospectively included. Two reviewers independently assessed CXR abnormalities, including ground-glass opacities (GGOs) and consolidation. Two scoring systems (Brixia score and percentage of lung involvement) were applied. Inter-rater agreement was assessed by weighted Cohen's kappa (κ) or intraclass correlation coefficient (ICC). Predictors of death and respiratory support were identified by logistic or Poisson regression. RESULTS: GGO admixed with consolidation (n = 235, 69%) was the most common CXR finding. The inter-rater agreement was almost perfect for type of parenchymal opacity (κ = 0.90), Brixia score (ICC = 0.91), and percentage of lung involvement (ICC = 0.95). The Brixia score (OR: 1.19; 95% CI: 1.06, 1.34; p = 0.003), age (OR: 1.16; 95% CI: 1.11, 1.22; p < 0.001), PaO2/FiO2 ratio (OR: 0.99; 95% CI: 0.98, 1; p = 0.002), and cardiovascular diseases (OR: 3.21; 95% CI: 1.28, 8.39; p = 0.014) predicted death. Percentage of lung involvement (OR: 1.02; 95% CI: 1.01, 1.03; p = 0.001) and PaO2/FiO2 ratio (OR: 0.99; 95% CI: 0.99, 1.00; p < 0.001) were significant predictors of the need for ventilatory support. CONCLUSIONS: CXR is a reproducible tool for assessing COVID-19 and integrates with patient history, PaO2/FiO2 ratio, and SpO2 values to early predict mortality and the need for ventilatory support. KEY POINTS: • Chest X-ray is a reproducible tool for assessing COVID-19 pneumonia. • The Brixia score and percentage of lung involvement on chest X-ray integrate with patient history, PaO2/FIO2 ratio, and SpO2 values to early predict mortality and the need for ventilatory support in COVID-19 patients presenting to the emergency department.

Computed tomography semi-automated lung volume quantification in SARS-CoV-2-related pneumonia.

OBJECTIVES: To evaluate a semi-automated segmentation and ventilated lung quantification on chest computed tomography (CT) to assess lung involvement in patients affected by SARS-CoV-2. Results were compared with clinical and functional parameters and outcomes. METHODS: All images underwent quantitative analyses with a dedicated workstation using a semi-automatic lung segmentation software to compute ventilated lung volume (VLV), Ground-glass opacity (GGO) volume (GGO-V), and consolidation volume (CONS-V) as absolute volume and as a percentage of total lung volume (TLV). The ratio between CONS-V, GGO-V, and VLV (CONS-V/VLV and GGO-V/VLV, respectively), TLV (CONS-V/TLV, GGO-V/TLV, and GGO-V + CONS-V/TLV respectively), and the ratio between VLV and TLV (VLV/TLV) were calculated. RESULTS: A total of 108 patients were enrolled. GGO-V/TLV significantly correlated with WBC (r = 0.369), neutrophils (r = 0.446), platelets (r = 0.182), CRP (r = 0.190), PaCO2 (r = 0.176), HCO3- (r = 0.284), and PaO2/FiO2 (P/F) values (r = - 0.344). CONS-V/TLV significantly correlated with WBC (r = 0.294), neutrophils (r = 0.300), lymphocytes (r = -0.225), CRP (r = 0.306), PaCO2 (r = 0.227), pH (r = 0.162), HCO3- (r = 0.394), and P/F (r = - 0.419) values. Statistically significant differences between CONS-V, GGO-V, GGO-V/TLV, CONS-V/TLV, GGO-V/VLV, CONS-V/VLV, GGO-V + CONS-V/TLV, VLV/TLV, CT score, and invasive ventilation by ET were found (all p < 0.05). CONCLUSION: The use of quantitative semi-automated algorithm for lung CT elaboration effectively correlates the severity of SARS-CoV-2-related pneumonia with laboratory parameters and the need for invasive ventilation. KEY POINTS: • Pathological lung volumes, expressed both as GGO-V and as CONS-V, can be considered a useful tool in SARS-CoV-2-related pneumonia. • All lung volumes, expressed themselves and as ratio with TLV and VLV, correlate with laboratory data, in particular C-reactive protein and white blood cell count. • All lung volumes correlate with patient's outcome, in particular concerning invasive ventilation.

Chest CT-derived pulmonary artery enlargement at the admission predicts overall survival in COVID-19 patients: insight from 1461 consecutive patients in Italy.

OBJECTIVES: Enlarged main pulmonary artery diameter (MPAD) resulted to be associated with pulmonary hypertension and mortality in a non-COVID-19 setting. The aim was to investigate and validate the association between MPAD enlargement and overall survival in COVID-19 patients. METHODS: This is a cohort study on 1469 consecutive COVID-19 patients submitted to chest CT within 72 h from admission in seven tertiary level hospitals in Northern Italy, between March 1 and April 20, 2020. Derivation cohort (n = 761) included patients from the first three participating hospitals; validation cohort (n = 633) included patients from the remaining hospitals. CT images were centrally analyzed in a core-lab blinded to clinical data. The prognostic value of MPAD on overall survival was evaluated at adjusted and multivariable Cox's regression analysis on the derivation cohort. The final multivariable model was tested on the validation cohort. RESULTS: In the derivation cohort, the median age was 69 (IQR, 58-77) years and 537 (70.6%) were males. In the validation cohort, the median age was 69 (IQR, 59-77) years with 421 (66.5%) males. Enlarged MPAD (≥ 31 mm) was a predictor of mortality at adjusted (hazard ratio, HR [95%CI]: 1.741 [1.253-2.418], p < 0.001) and multivariable regression analysis (HR [95%CI]: 1.592 [1.154-2.196], p = 0.005), together with male gender, old age, high creatinine, low well-aerated lung volume, and high pneumonia extension (c-index [95%CI] = 0.826 [0.796-0.851]). Model discrimination was confirmed on the validation cohort (c-index [95%CI] = 0.789 [0.758-0.823]), also using CT measurements from a second reader (c-index [95%CI] = 0.790 [0.753;0.825]). CONCLUSION: Enlarged MPAD (≥ 31 mm) at admitting chest CT is an independent predictor of mortality in COVID-19. KEY POINTS: • Enlargement of main pulmonary artery diameter at chest CT performed within 72 h from the admission was associated with a higher rate of in-hospital mortality in COVID-19 patients. • Enlargement of main pulmonary artery diameter (≥ 31 mm) was an independent predictor of death in COVID-19 patients at adjusted and multivariable regression analysis. • The combined evaluation of clinical findings, lung CT features, and main pulmonary artery diameter may be useful for risk stratification in COVID-19 patients.

Pathological characteristics of liver sinusoidal thrombosis in COVID-19 patients: A series of 43 cases.

AIM: Coronavirus disease (COVID-19) is characterized by pneumonia with secondary damage to multiple organs including the liver. Liver injury (elevated alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) often correlates with disease severity in COVID-19 patients. The aim of this study is to identify pathological microthrombi in COVID-19 patient livers by correlating their morphology with liver injury, and examine hyperfibrinogenemia and von Willebrand factor (vWF) as mechanisms of their formation. METHODS: Forty-three post-mortem liver biopsy samples from COVID-19 patients were obtained from Papa Giovanni XXIII Hospital in Bergamo, Italy. Three morphological features of microthrombosis (sinusoidal erythrocyte aggregation [SEA], platelet microthrombi [PMT], and fibrous thrombi) were evaluated. RESULTS: We found liver sinusoidal microthrombosis in 23 COVID-19 patients (53%) was associated with a higher serum ALT and AST level compared to those without (ALT: 10-fold, p = 0.04; AST: 11-fold, p = 0.08). Of 43 livers, PMT and SEA were observed in 14 (33%) and 19 (44%) cases, respectively. Fibrous thrombi were not observed. Platelet microthrombi were associated with increased ALT (p < 0.01), whereas SEA was not (p = 0.73). In COVID-19 livers, strong vWF staining in liver sinusoidal endothelial cells was associated with significantly increased platelet adhesion (1.7-fold, p = 0.0016), compared to those with weak sinusoidal vWF (2-fold, p < 0.0001). Sinusoidal erythrocyte aggregation in 19 (83%) liver samples was mainly seen in zone 2. Livers with SEA had significantly higher fibrinogen (1.6-fold, p = 0.031) compared to those without SEA in COVID-19 patients. CONCLUSIONS: Liver PMT is a pathologically important thrombosis associated with liver injury in COVID-19, while SEA is a unique morphological feature of COVID-19 patient livers. Sinusoidal vWF and hyperfibrinogenemia could contribute to PMT and SEA formation.