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.

Diffusion-weighted imaging (DWI) in diagnosis, staging, and treatment response assessment of multiple myeloma: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the role of diffusion-weighted imaging (DWI) in the initial diagnosis, staging, and assessment of treatment response in patients with multiple myeloma (MM). MATERIALS AND METHODS: A systematic literature review was conducted in PubMed, the Cochrane Library, EMBASE, Scopus, and Web of Science databases. The primary endpoints were defined as the diagnostic performance of DWI for disease detection, staging of MM, and assessing response to treatment in these patients. RESULTS: Of 5881 initially reviewed publications, 33 were included in the final qualitative and quantitative meta-analysis. The diagnostic performance of DWI in the detection of patients with MM revealed pooled sensitivity and specificity of 86% (95% CI: 84-89) and 63% (95% CI: 56-70), respectively, with a diagnostic odds ratio (OR) of 14.98 (95% CI: 4.24-52.91). The pooled risk difference of 0.19 (95% CI: - 0.04-0.42) was reported in favor of upstaging with DWI compared to conventional MRI (P value = 0.1). Treatment response evaluation and ADCmean value changes across different studies showed sensitivity and specificity of approximately 78% (95% CI: 72-83) and 73% (95% CI: 61-83), respectively, with a diagnostic OR of 7.21 in distinguishing responders from non-responders. CONCLUSIONS: DWI is not only a promising tool for the diagnosis of MM, but it is also useful in the initial staging and re-staging of the disease and treatment response assessment. This can aid clinicians with earlier initiation or change in treatment strategy, which could have prognostic significance for patients.

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.

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.

Convolutional neural networks for PET functional volume fully automatic segmentation: development and validation in a multi-center setting.

PURPOSE: In this work, we addressed fully automatic determination of tumor functional uptake from positron emission tomography (PET) images without relying on other image modalities or additional prior constraints, in the context of multicenter images with heterogeneous characteristics. METHODS: In cervical cancer, an additional challenge is the location of the tumor uptake near or even stuck to the bladder. PET datasets of 232 patients from five institutions were exploited. To avoid unreliable manual delineations, the ground truth was generated with a semi-automated approach: a volume containing the tumor and excluding the bladder was first manually determined, then a well-validated, semi-automated approach relying on the Fuzzy locally Adaptive Bayesian (FLAB) algorithm was applied to generate the ground truth. Our model built on the U-Net architecture incorporates residual blocks with concurrent spatial squeeze and excitation modules, as well as learnable non-linear downsampling and upsampling blocks. Experiments relied on cross-validation (four institutions for training and validation, and the fifth for testing). RESULTS: The model achieved good Dice similarity coefficient (DSC) with little variability across institutions (0.80 ± 0.03), with higher recall (0.90 ± 0.05) than precision (0.75 ± 0.05) and improved results over the standard U-Net (DSC 0.77 ± 0.05, recall 0.87 ± 0.02, precision 0.74 ± 0.08). Both vastly outperformed a fixed threshold at 40% of SUVmax (DSC 0.33 ± 0.15, recall 0.52 ± 0.17, precision 0.30 ± 0.16). In all cases, the model could determine the tumor uptake without including the bladder. Neither shape priors nor anatomical information was required to achieve efficient training. CONCLUSION: The proposed method could facilitate the deployment of a fully automated radiomics pipeline in such a challenging multicenter context.

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.

Long-term Implications of Persistent Diverticulitis: A Retrospective Cohort Study of 915 Patients.

BACKGROUND: Persistent (or ongoing) diverticulitis is a well-recognized outcome after treatment for acute sigmoid diverticulitis; however, its definition, incidence, and risk factors, as well as its long-term implications, remain poorly described. OBJECTIVE: The purpose of this study was to assess the incidence, risk factors, and long-term outcomes of persistent diverticulitis. DESIGN: This was a retrospective cohort study. SETTINGS: Two university-affiliated hospitals in Montreal, Quebec, Canada were included. PATIENTS: The study was composed of consecutive patients managed nonoperatively for acute sigmoid diverticulitis. INTERVENTION: Nonoperative management of acute sigmoid diverticulitis was involved. MAIN OUTCOME MEASURES: Persistent diverticulitis, defined as inpatient or outpatient treatment for signs and symptoms of ongoing diverticulitis within the first 60 days after treatment of the index episode, was measured. RESULTS: In total, 915 patients were discharged after an index episode of diverticulitis managed nonoperatively. Seventy-five patients (8.2%; 95% CI, 6.5%-10.2%) presented within 60 days with persistent diverticulitis. Factors associated with persistent diverticulitis were younger age (adjusted OR = 0.98 (95% CI, 0.96-0.99)), immunosuppression (adjusted OR = 2.02 (95% CI, 1.04-3.88)), and abscess (adjusted OR = 2.05 (95% CI, 1.03-3.92)). Among the 75 patients with persistent disease, 42 (56.0%) required hospital admission, 6 (8.0%) required percutaneous drainage, and 5 (6.7%) required resection. After a median follow-up of 39.0 months (range, 17.0-67.3 mo), the overall recurrence rate in the entire cohort was 31.3% (286/910). After excluding patients who were managed operatively for their persistent episode of diverticulitis, the cumulative incidence of recurrent diverticulitis (log-rank: p < 0.001) and sigmoid colectomy (log-rank: p < 0.001) were higher among patients who experienced persistent diverticulitis after the index episode. After adjustment for relevant patient and disease factors, persistent diverticulitis was associated with higher hazards of recurrence (adjusted HR = 1.94 (95% CI, 1.37-2.76) and colectomy (adjusted HR = 5.11 (95% CI, 2.96-8.83)). LIMITATIONS: The study was limited by its observational study design and modest sample size. CONCLUSIONS: Approximately 10% of patients experience persistent diverticulitis after treatment for an index episode of diverticulitis. Persistent diverticulitis is a poor prognostic factor for long-term outcomes, including recurrent diverticulitis and colectomy. See Video Abstract at http://links.lww.com/DCR/B593. REPERCUSIONES A LARGO PLAZO DE LA DIVERTICULITIS PERSISTENTE ESTUDIO DE UNA COHORTE RETROSPECTIVA DE PACIENTES: ANTECEDENTES:La diverticulitis persistente (o continua) es un resultado bien conocido posterior al tratamiento de la diverticulitis aguda del sigmoides; sin embargo, la definición, incidencia y factores de riesgo, así como sus repercusiones a largo plazo siguen estando descritas de manera deficiente.OBJETIVO:Evaluar la incidencia, los factores de riesgo y los resultados a largo plazo de la diverticulitis persistente.DISEÑO:Estudio de una cohorte retrospectiva.AMBITO:Dos hospitales universitarios afiliados en Montreal, Quebec, Canadá.PACIENTES:pacientes consecutivos tratados sin cirugia por diverticulitis aguda del sigmoides.INTERVENCIÓN:Tratamiento no quirúrgico de la diverticulitis aguda del sigmoides.PRINCIPALES RESULTADOS EVALUADOS:Diverticulitis persistente, definida como tratamiento hospitalario o ambulatorio por signos y síntomas de diverticulitis continua dentro de los primeros 60 días posteriores al tratamiento del episodio índice.RESULTADOS:Un total de 915 pacientes fueron dados de alta posterior al episodio índice de diverticulitis tratados sin cirugia. Setenta y cinco pacientes (8,2%; IC del 95%: 6,5-10,2%) presentaron diverticulitis persistente dentro de los 60 días. Los factores asociados con la diverticulitis persistente fueron una edad menor (aOR: 0,98, IC del 95%: 0,96-0,99), inmunosupresión (aOR: 2,02, IC del 95%: 1,04-3,88) y abscesos (aOR: 2,05, IC del 95%: 1,03-3,92). Entre los 75 pacientes con enfermedad persistente, 42 (56,0%) requirieron ingreso hospitalario, 6 (8,0%) drenaje percutáneo y 5 (6,7%) resección. Posterior a seguimiento medio de 39,0 (17,0-67,3) meses, la tasa global de recurrencia de toda la cohorte fue del 31,3% (286/910). Después de excluir a los pacientes que fueron tratados quirúrgicamente por su episodio persistente de diverticulitis, la incidencia acumulada de diverticulitis recurrente (rango logarítmico: p <0,001) y colectomía sigmoidea (rango logarítmico: p <0,001) fue mayor entre los pacientes que experimentaron diverticulitis persistente después el episodio índice. Posterior al ajuste de factores importantes de la enfermedad y del paciente, la diverticulitis persistente se asoció con mayores riesgos de recurrencia (aHR: 1,94, IC 95% 1,37-2,76) y colectomía (aHR: 5,11, IC 95% 2,96-8,83).LIMITACIONES:Diseño de estudio observacional, un modesto tamaño de muestra.CONCLUSIONES:Aproximadamente el 10% de los pacientes presentan diverticulitis persistente después del tratamiento del episodio índice de diverticulitis. La diverticulitis persistente, en sus resultados a largo plazo, es un factor de mal pronóstico, donse se inlcuye la diverticulitis recurente y colectomía. Consulte Video Resumen en http://links.lww.com/DCR/B593.

Surviving COVID-19 in Bergamo province: a post-acute outpatient re-evaluation.

Bergamo province was badly hit by the coronavirus disease 2019 (COVID-19) epidemic. We organised a public-funded, multidisciplinary follow-up programme for COVID-19 patients discharged from the emergency department or from the inpatient wards of 'Papa Giovanni XXIII' Hospital, the largest public hospital in the area. As of 31 July, the first 767 patients had completed the first post-discharge multidisciplinary assessment. Patients entered our programme at a median time of 81 days after discharge. Among them, 51.4% still complained of symptoms, most commonly fatigue and exertional dyspnoea, and 30.5% were still experiencing post-traumatic psychological consequences. Impaired lung diffusion was found in 19%. Seventeen per cent had D-dimer values two times above the threshold for diagnosis of pulmonary embolism (two unexpected and clinically silent pulmonary thrombosis were discovered by investigating striking D-dimer elevation). Survivors of COVID-19 exhibit a complex array of symptoms, whose common underlying pathology, if any, has still to be elucidated: a multidisciplinary approach is fundamental, to address the different problems and to look for effective solutions.

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.

Diagnostic Algorithm to Differentiate Benign Atypical Leiomyomas from Malignant Uterine Sarcomas with Diffusion-weighted MRI.

Background Improving the differentiation of uterine sarcomas from atypical leiomyomas remains a clinical challenge and is needed to avoid inappropriate surgery. Purpose To develop a diagnostic algorithm including diffusion-weighted MRI criteria to differentiate malignant uterine sarcomas from benign atypical leiomyomas. Materials and Methods This case-control retrospective study identified women with an atypical uterine mass at MRI between January 2000 and April 2017, with surgery or MRI follow-up after 1 year or longer. A diagnostic algorithm including T2-weighted MRI and diffusion-weighted imaging (DWI) signal and apparent diffusion coefficient (ADC) values was developed to predict for sarcoma. The training set consisted of 51 sarcomas and 105 leiomyomas. Two external validation sets were used to evaluate interreader reproducibility (16 sarcomas; 26 leiomyomas) and impact of reader experience (29 sarcomas; 30 leiomyomas). Wilson confidence intervals (CIs) were calculated for sensitivity and specificity. Results Evaluated were 156 women (median age, 50 years; interquartile range, 44-63 years). Predictive MRI criteria for malignancy were enlarged lymph nodes or peritoneal implants, high DWI signal greater than that in endometrium, and ADC less than or equal to 0.905 × 10-3 mm2/sec. Conversely, a global or focal area of low T2 signal intensity and a low or an intermediate DWI signal less than that in endometrium or lymph nodes allowed readers to confidently diagnose as benign a uterine mass demonstrating one or more of these signs (P < .001) in 100% cases in all three data sets. The sensitivities and specificities of the algorithm for diagnosis of malignancy were 98% (50 of 51 masses; 95% CI: 90%, 100%) and 94% (99 of 105 masses; 95% CI: 88%, 98%) in the training set; 88% (14 of 16 masses; 95% CI: 64%, 97%) and 100% (26 of 26 masses; 95% CI: 87%, 100%) in the validation set; and 83% (24 of 29 masses; 95% CI: 65%, 92%) and 97% (29 of 30 masses; 95% CI: 83%, 99%) for the less experienced reader, respectively. Conclusion A diagnostic algorithm with predictive features including lymphadenopathy, high diffusion-weighted imaging signal with reference to endometrium, and low apparent diffusion coefficient enabled differentiation of malignant sarcomas from atypical leiomyomas, and it may assist inexperienced readers. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Méndez in this issue.

Family History Is Associated With Recurrent Diverticulitis After an Episode of Diverticulitis Managed Nonoperatively.

BACKGROUND: To date, the impact of family history on diverticulitis outcomes has been poorly described. OBJECTIVE: This study aims to evaluate the association between family history and diverticulitis recurrence after an episode of diverticulitis managed nonoperatively. DESIGN: This is a retrospective cohort study with prospective telephone follow-up. SETTINGS: This study was conducted at 2 McGill University-affiliated tertiary care hospitals in Montreal, Canada. PATIENTS: All immunocompetent patients with CT-proven left-sided diverticulitis who were managed nonoperatively from 2007 to 2017 were included. INTERVENTION: A positive family history for diverticulitis, as assessed by a detailed telephone questionnaire, was obtained. MAIN OUTCOME MEASURES: The primary outcome was diverticulitis recurrence occurring >60 days after the index episode. Secondary outcomes included a complicated recurrence and >1 recurrence (ie, re-recurrence). RESULTS: Of the 879 patients identified in the database, 433 completed the telephone questionnaire (response rate: 48.9%). Among them, 173 (40.0%) had a positive family history of diverticulitis and 260 (60.0%) did not. Compared to patients with no family history, patients with family history had a younger median age (59.0 vs 62.0 years, p = 0.020) and a higher incidence of abscess (24.3% vs 3.5%, p < 0.001). After a median follow-up of 40.1 (17.4-65.3) months, patients with a positive family history had a higher cumulative incidence of recurrence (log-rank test: p < 0.001). On Cox regression, a positive family history remained associated with diverticulitis recurrence (HR, 3.74; 95% CI, 2.67-5.24). Among patients with a positive family history, >1 relative with a history of diverticulitis had a higher hazard of recurrence (HR, 2.93; 95% CI, 1.96-4.39) than patients with only 1 relative with a history of diverticulitis. Positive family history was also associated with the development of a complicated recurrence (HR, 8.30; 95% CI, 3.64-18.9) and >1 recurrence (HR, 2.03; 95% CI, 1.13-3.65). LIMITATIONS: This study has the potential for recall and nonresponse bias. CONCLUSION: Patients with a positive family history of diverticulitis are at higher risk for recurrent diverticulitis and complicated recurrences. See Video Abstract at http://links.lww.com/DCR/B215. LOS ANTECEDENTES FAMILIARES ESTÁN ASOCIADOS CON DIVERTICULITIS RECURRENTE, DESPUÉS DE UN EPISODIO DE DIVERTICULITIS MANEJADA SIN OPERACIÓN: Hasta la fecha, el impacto de los antecedentes familiares en los resultados de la diverticulitis, ha sido mal descrito.Evaluar la asociación entre los antecedentes familiares y la recurrencia de diverticulitis después de un episodio de diverticulitis manejado de forma no operatoria.Estudio de cohorte retrospectivo con seguimiento telefónico prospectivo.Dos hospitales de atención terciaria afiliados a la Universidad McGill en Montreal, Canadá.Todos los pacientes inmunocompetentes con diverticulitis izquierda comprobada por TAC, que fueron manejados sin cirugía desde 2007-2017.Una historia familiar positiva para diverticulitis, según lo evaluado por un detallado cuestionario telefónico.El resultado primario fue la recurrencia de diverticulitis ocurriendo > 60 días después del episodio índice. Resultados secundarios incluyeron una recurrencia complicada y >1 recurrencia (es decir, re-recurrencia).De los 879 pacientes identificados en la base de datos, 433 completaron el cuestionario telefónico (tasa de respuesta: 48,9%). Entre ellos, 173 (40.0%) tenían antecedentes familiares positivos de diverticulitis y 260 (60.0%) no tenían. Comparados con los pacientes sin antecedentes familiares, los pacientes con antecedentes familiares tenían una mediana de edad más joven (59.0 vs 62.0 años, p = 0.020) y una mayor incidencia de abscesos (24.3% vs 3.5%, p < 0.001). Después de una mediana de seguimiento de 40.1 (17.4-65.3) meses, los pacientes con antecedentes familiares positivos tuvieron una mayor incidencia acumulada de recurrencia (prueba de log-rank: p < 0.001). En la regresión de Cox, un historial familiar positivo, permaneció asociado con recurrencia de diverticulitis (HR, 3.74; IC 95%, 2.67-5.24). Entre los pacientes con antecedentes familiares positivos, >1 familiar con antecedentes de diverticulitis, tuvieron mayores riesgos de recurrencia (HR, 2.93; IC 95%, 1.96-4.39) en comparación de los pacientes con solo 1 familiar. La historia familiar positiva también se asoció con el desarrollo de una recurrencia complicada (HR, 8.30; IC 95%, 3.64-18.9) y >1 recurrencia (HR, 2.03; IC 95%, 1.13-3.65).Potencial de recuerdo y sesgo de no respuesta.Los pacientes con antecedentes familiares positivos de diverticulitis tienen un mayor riesgo para diverticulitis recurrente y recurrencias complicadas. Consulte Video Resumen http://links.lww.com/DCR/B215. (Traducción-Dr. Fidel Ruiz Healy).

External validation of a combined PET and MRI radiomics model for prediction of recurrence in cervical cancer patients treated with chemoradiotherapy.

PURPOSE: The aim of this study was to validate previously developed radiomics models relying on just two radiomics features from 18F-fluorodeoxyglucose positron emission tomography (PET) and magnetic resonance imaging (MRI) images for prediction of disease free survival (DFS) and locoregional control (LRC) in locally advanced cervical cancer (LACC). METHODS: Patients with LACC receiving chemoradiotherapy were enrolled in two French and one Canadian center. Pre-treatment imaging was performed for each patient. Multicentric harmonization of the two radiomics features was performed with the ComBat method. The models for DFS (using the feature from apparent diffusion coefficient (ADC) MRI) and LRC (adding one PET feature to the DFS model) were tuned using one of the French cohorts (n = 112) and applied to the other French (n = 50) and the Canadian (n = 28) external validation cohorts. RESULTS: The DFS model reached an accuracy of 90% (95% CI [79-98%]) (sensitivity 92-93%, specificity 87-89%) in both the French and the Canadian cohorts. The LRC model reached an accuracy of 98% (95% CI [90-99%]) (sensitivity 86%, specificity 100%) in the French cohort and 96% (95% CI [80-99%]) (sensitivity 83%, specificity 100%) in the Canadian cohort. Accuracy was significantly lower without ComBat harmonization (82-85% and 71-86% for DFS and LRC, respectively). The best prediction using standard clinical variables was 56-60% only. CONCLUSIONS: The previously developed PET/MRI radiomics predictive models were successfully validated in two independent external cohorts. A proposed flowchart for improved management of patients based on these models should now be confirmed in future larger prospective studies.

Intraobserver and Interobserver Agreement in the Evaluation of Tumor Vascularization With Computed Tomography Perfusion in Cirrhotic Patients With Hepatocellular Carcinoma.

OBJECTIVES: To evaluate intrareader and inter-reader agreement in CT perfusion (Perf) measurements in cirrhotic patients with hepatocellular carcinoma (HCC) lesions. METHODS: Sixteen patients with HCC (9 untreated, 5 recurrence/residual disease after transarterial chemoembolization, and 2 after radiofrequency ablation treatment) underwent standard CT examination and a Perf study; a quantitative map of arterial and portal Perf by means of a color scale was generated. With dedicated Perf software, the following parameters were calculated on untreated and treated HCC lesions and on cirrhotic parenchyma: hepatic Perf, tissue blood volume, hepatic perfusion index, arterial perfusion, and time to peak. Intraobserver and interobserver agreements were assessed for 2 readers with Bland-Altman plots, intraclass correlation coefficients (ICCs), coefficients of variation, and repeatability. RESULTS: In HCC lesions, agreement analysis demonstrated higher intra-agreement values in comparison with interagreement (range of ICC values, 0.26-0.59 between readers and 0.67-0.94 between readings). Lower interagreement was found for treated HCC lesions in comparison with untreated lesions (range of ICC values, respectively, 0.12-0.54 and 0.31-0.89). CONCLUSIONS: For all Perf parameters intra-agreement was higher than interagreement, even though a relatively wide range of 95% limits of agreement was found in both cases.

Endometrial cancer: diagnostic value of quantitative measurements of microvascular changes with DCE-MR imaging.

OBJECT: To assess the diagnostic value of dynamic contrast-enhanced (DCE) perfusion-magnetic resonance imaging (MRI) in detection, characterization and grading of endometrial cancer, using histopathological analysis as the standard of reference. MATERIALS AND METHODS: Eighty patients with histologically proven endometrial carcinoma who underwent MRI (1.5 T magnet) of the pelvis for staging purposes were enrolled in the study. Each MR examination consisted of multiplanar T2 and T1-weighted turbo spin echo (TSE) sequences and T1-weighted gradient echo sequences before, during and after the administration of contrast medium. For each patient colour perfusion maps were derived from the dynamic sequences using a dedicated workstation. On the maps a region of interest was manually drawn both on normal myometrium and on the endometrial lesion. Then the following perfusion parameters were automatically calculated: relative enhancement (RE, %), maximum enhancement (ME, %), maximum relative enhancement (MRE, %) and time to peak (TTP, s). RESULTS: All patients underwent total hysterectomy. Histopathological analysis documented: G1 tumour in 21 patients, G2 tumour in 44 patients, G3 tumour in 14 patients and one squamous cell carcinoma. The following mean value perfusion parameters, with corresponding mean standard deviation, were obtained for endometrial cancer: RE (%) = 59.3 ± 36.3; ME (%) = 862.7 ± 475.9; MRE (%) = 75.3 ± 37.6 and TTP (s) = 164.7 ± 78. RE, ME and MRE were lower in tumour lesions than in normal myometrium (p < 0.001) and significantly higher values (p < 0.001) of perfusion parameters were obtained for G1 (well-differentiated) tumours as compared to those in G2 and G3 (moderately and poorly differentiated) lesions. CONCLUSION: DCE perfusion-MRI can provide quantitative information on tissue vascularity, which may be of help in detecting endometrial cancer and in the assessment of tumour grading.

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.

Gastroenteropancreatic neuroendocrine tumors: role of imaging in diagnosis and management.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of neoplasms that arise from cells of the diffuse neuroendocrine system and are characterized by a wide spectrum of clinical manifestations. All NETs are potentially malignant but differ in their biologic characteristics and the probability of metastatic disease. The pathologic classification of these tumors relies on their proliferation and differentiation. In the past decades, several nomenclatures have been proposed to stratify neuroendocrine tumors, but the World Health Organization classification is the one that is most widely accepted and used. The diagnosis of neuroendocrine tumor relies on clinical manifestation, laboratory parameters, imaging features, and tissue biomarkers in a biopsy specimen. With improved understanding of the natural history and lesion biology, management of GEP-NETs has also evolved. Although surgery remains the only potentially curative therapy for patients with primary GEP-NETs, other available treatments include chemotherapy, interferon, somatostatin analogs, and targeted therapies. Recent improvements in both morphologic and functional imaging methods have contributed immensely to patient care. Morphologic imaging with contrast agent-enhanced multidetector computed tomography and magnetic resonance imaging is most widely used for initial evaluation and staging of disease in these patients, whereas functional imaging techniques are useful both for detection and prognostic evaluation and can change treatment planning.