Intraindividual comparison of CT and MRI for predicting vessels encapsulating tumor clusters in hepatocellular carcinoma.

OBJECTIVES: To establish and validate scoring models for predicting vessels encapsulating tumor clusters (VETC) in hepatocellular carcinoma (HCC) using computed tomography (CT) and magnetic resonance imaging (MRI), and to intra-individually compare the predictive performance between the two modalities. METHODS: We retrospectively included 324 patients with surgically confirmed HCC who underwent preoperative dynamic CT and MRI with extracellular contrast agent between June 2019 and August 2020. These patients were then divided into a discovery cohort (n = 227) and a validation cohort (n = 97). Imaging features and Liver Imaging Reporting and Data System (LI-RADS) categories of VETC-positive HCCs were evaluated. Logistic regression analyses were conducted on the discovery cohort to identify clinical and imaging predictors associated with VETC-positive cases. Subsequently, separate CT-based and MRI-based scoring models were developed, and their diagnostic performance was compared using generalized estimating equations. RESULTS: On both CT and MRI, VETC-positive HCCs exhibited a higher frequency of size > 5.0 cm, necrosis or severe ischemia, non-smooth tumor margin, targetoid appearance, intratumor artery, and heterogeneous enhancement with septations or irregular ring-like structure compared to VETC-negative HCCs (all p < 0.05). Regarding LI-RADS categories, VETC-positive HCCs were more frequently categorized as LR-M than VETC-negative cases (all p < 0.05). In the validation cohort, the CT-based model showed similar sensitivity (76.7% vs. 86.7%, p = 0.375), specificity (83.6% vs. 74.6%, p = 0.180), and area under the curve value (0.80 vs. 0.81, p = 0.910) to the MRI-based model in predicting VETC-positive HCCs. CONCLUSION: Preoperative CT and MRI demonstrated comparable performance in the identification of VETC-positive HCCs, thus displaying promising predictive capabilities. CLINICAL RELEVANCE STATEMENT: Both computed tomography and magnetic resonance imaging demonstrated promise in preoperatively identifying the vessel-encapsulating tumor cluster pattern in hepatocellular carcinoma, with no statistically significant difference between the two modalities, potentially adding additional prognostic value. KEY POINTS: Computed tomography (CT) and magnetic resonance imaging (MRI) show promise in the preoperative identification of vessels encapsulating tumor clusters-positive hepatocellular carcinoma (HCC). HCC with vessels encapsulating tumor cluster patterns were more frequently LR-M compared to those without. These CT and MRI models showed comparable ability in identifying vessels encapsulating tumor clusters-positive HCC.

The role of enhancing capsule and modified capsule appearances in LI-RADS for diagnosing HCC ≤ 3.0 cm on gadoxetate disodium-enhanced MRI.

OBJECTIVES: To evaluate the value of using enhancing capsule (EC) or modified capsule appearance as a major feature in LI-RADS for diagnosing HCC ≤ 3.0 cm on gadoxetate disodium-enhanced MRI (Gd-EOB-MRI), and to explore the relationship between the imaging features and the histological fibrous capsule. METHODS: This retrospective study enrolled 342 hepatic lesions ≤ 3.0 cm in 319 patients that underwent Gd-EOB-MRIs from January 2018 to March 2021. During dynamic phases and hepatobiliary phase, the modified capsule appearance added the nonenhancing capsule (NEC) (modified LI-RADS + NEC) or corona enhancement (CoE) (modified LI-RADS + CoE) to EC as an alternative capsule appearance. Inter-reader agreement of imaging features was assessed. The diagnostic performances of LI-RADS, LI-RADS with EC ignored, and two modified LI-RADS were compared, followed by Bonferroni correction. Multivariable regression analysis was performed to identify the independent features associated with the histological fibrous capsule. RESULTS: The inter-reader agreement on EC (0.64) was lower than that on the NEC alternative (0.71) but better than that on CoE alternative (0.58). For HCC diagnosis, compared to LI-RADS, LI-RADS with EC ignored showed significantly lower sensitivity (72.7% vs. 67.4%, p < 0.001) with comparable specificity (89.3% vs. 90.7%, p = 1.000). Two modified LI-RADS showed slightly higher sensitivity and lower specificity than LI-RADS, without statistical significance (all p ≥ 0.006). The AUC was highest with modified LI-RADS + NEC (0.82). Both EC and NEC were significantly associated with the fibrous capsule (p < 0.05). CONCLUSION: EC appearance improved the diagnostic sensitivity of LI-RADS for HCC ≤ 3.0 cm on Gd-EOB-MRI. Considering NEC as an alternative capsule appearance allowed for better inter-reader reliability and comparable diagnostic ability. KEY POINTS: • Using the enhancing capsule as a major feature in LI-RADS significantly improved the sensitivity of diagnosing HCC ≤ 3.0 cm without reducing specificity on gadoxetate disodium-enhanced MRI. • Compared to the corona enhancement, the nonenhancing capsule might be a preferable alternative capsule appearance for diagnosing HCC ≤ 3.0 cm. • Capsule appearance should be considered a major feature in LI-RADS for diagnosing HCC ≤ 3.0 cm, regardless whether the capsule appears to be enhancing or nonenhancing.

Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19.

RATIONALE: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. OBJECTIVE: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19. METHODS AND RESULTS: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57-69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19-0.92]; P=0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15-0.89]; P=0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12-0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension. CONCLUSIONS: Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.

Do transition and hepatobiliary phase hypointensity improve LI-RADS categorization as an alternative washout: a systematic review and meta-analysis.

OBJECTIVE: The definition of washout in gadoxetate disodium-enhanced MRI (Gd-EOB-MRI) is controversial. The current Liver Imaging Reporting and Data System (LI-RADS) defines washout only in the portal venous phase on Gd-EOB-MRI, leading to low diagnostic sensitivity for HCC. We performed a meta-analysis to compare the diagnostic performance of Gd-EOB-MRI using conventional (cWO) and modified (mWO) definitions of washout. METHODS: The PubMed and EMBASE databases were searched to identify studies published between January 1, 2010, and August 1, 2021, that compared the diagnostic performance of cWO and mWO for HCC. The mWOs added transition phase (TP) hypointensity (mWO-1), hepatobiliary phase (HBP) hypointensity (mWO-2), or both (mWO-3). The pooled sensitivity and specificity were calculated using a bivariate random-effects model. Study heterogeneity was explored by subgroup analysis and meta-regression analysis. RESULTS: Ten comparative studies with 2391 patients were included. Compared to cWO, the overall mWO yielded significantly higher sensitivity (71% vs. 81%, p = 0.00) and lower specificity (97% vs. 93%, p = 0.01) for diagnosing HCC. The area under the curve (AUC) was 0.90 and 0.94 for the cWO and mWO, respectively. Regarding the three types of mWOs, mWO-2 showed the highest sensitivity (85%) and specificity (96%) for diagnosing HCC. mWO-2 achieved the highest AUC (0.97), followed by mWO-1 (0.90), and mWO-3 (0.89). Average reviewer experience and scanner field strength were significantly associated with study heterogeneity (p < 0.05). CONCLUSIONS: Inclusion of TP and HBP hypointensity in the definition of washout improved the sensitivity with slightly lower specificity for diagnosing HCC in LI-RADS. KEY POINTS: • Compared to the conventional definition of washout, studies using a modified definition had higher sensitivity (71% vs. 81%) but lower specificity (97% vs. 93%) in LI-RADS for the diagnosis of HCC. • Hepatobiliary phase hypointensity may be a preferred alternative washout for HCC diagnosis with the highest area under the curve. • Studies with experienced reviewer or 3.0T MRI showed higher sensitivity and lower specificity for diagnosing HCC when using modified washout (p < 0.05).

The prognostic value of lymph node metastasis and the eighth edition of AJCC for patients with anaplastic thyroid cancer.

OBJECTIVE: The eighth edition of the American Joint Committee on Cancer (AJCC-v8) for anaplastic thyroid cancer (ATC) made a revision in staging for patients with lymph node metastasis (LNM) based on the seventh edition of AJCC (AJCC-v7). Our study aimed to evaluate the predictive ability of AJCC-v8 for survival in patients with ATC by exploring the association between lymph node stage and prognosis of ATC patients. METHODS: Retrospective study of ATC in Surveillance, Epidemiology and End Results (SEER) database. The association between LNM and survival of ATC was estimated by the Kaplan-Meier method and Cox regression model. The predictive performances of the AJCC-v8 and AJCC-v7 were estimated through C-index, Akaike information criterion (AIC) and Bayesian information criterion (BIC). RESULTS: A total of 313 patients with ATC were included in our analysis. Notably, LNM was identified as an independent risk factor for ATC mortality (adjusted HR, 1.47, 95% CI, 1.10-1.96; p = .009), while the risk of mortality in N1a group was comparable to that in N1b group according to univariate (HR, 1.30, 95% CI, 0.92-1.82; p = .133) and multivariate (adjusted HR 0.87, 95% CI, 0.60-1.27; p = .467) cox analyses. Applying the AJCC-v8, the survival of migration population staged T1-3aN1M0 was significantly worse than that of T1-3aN0M0 patients (IVA stage), while was not different from that of T3b-T4bN0/N1M0 patients (IVB stage). With a higher C-index (0.60 vs. 0.59), lower AIC (2728 vs. 2732) and BIC (2732 vs. 2735), AJCC-v8 was demonstrably a more favourable prediction model than AJCC-v7. CONCLUSIONS: This study demonstrated that LNM was independently associated with poor prognosis of ATC, and AJCC-v8 with the modified staging of patients with LNM showed better survival predictive performance in ATC patients than AJCC-v7.

Preoperative MRI features to predict vessels that encapsulate tumor clusters and microvascular invasion in hepatocellular carcinoma.

OBJECTIVE: To estimate the potential of preoperative MRI features in the prediction of the integration patterns of vessels that encapsulate tumor clusters (VETC) and microvascular invasion (MVI) (VM) patterns in hepatocellular carcinoma (HCC) patients after resection and to assess the prognostic value of VM patterns. MATERIALS AND METHODS: Patients who underwent surgical resection for HCC between July 2019 and July 2020 were retrospectively included in the training cohort and validation cohort. In the training cohort, patients were classified into VM-positive HCC (VM-HCC) and VM-negative HCC (non-VM HCC). Predictors associated with VM-HCC were determined by using logistic regression analyses and used to build a prediction model of VM-HCC. The model was tested in the validation cohort by area under the receiver operating characteristic curve (AUC) analysis. Prognostic factors associated with early recurrence of HCC were evaluated by use of Cox logistic regression analyses. RESULTS: Alpha-fetoprotein (AFP) level higher than 400 ng/mL (odds ratio [OR] = 8.0; 95% CI: 2.6-25.2; P < 0.001), non-smooth tumor margin (OR = 3.1; 95% CI: 1.4-6.0; P < 0.001) and peritumoral arterial enhancement (OR = 2.9; 95% CI: 1.4-6.2; P = 0.004) were independent predictors of VM-HCC. The AUCs of the prediction model for VM-HCC were 0.81 for the training cohort and 0.79 for the validation cohort. The high risk of VM-HCC predicted by the three preoperative predictors derived from the prediction model (hazard ratio [HR] 2.0; 95% CI: 1.3, 3.2; P = 0.003) were independently associated with early recurrence, while pathologically confirmed VM-HCC (HR 2.8; 95% CI: 1.6, 3.8; P < 0.001) and satellite nodules (HR 1.8; 95% CI: 1.1, 3.1; P = 0.025) were independently associated with early recurrence after surgical resection. CONCLUSION: The predictive model can be used to predict VM patterns. VM-HCC is associated with increased risk of early recurrence after surgical resection in HCC.

A new classification and regression tree algorithm: Improved diagnostic sensitivity for HCC ≤ 3.0 cm using gadoxetate disodium-enhanced MRI.

PURPOSE: To develop and validate an effective algorithm, based on classification and regression tree (CART) analysis and LI-RADS features, for diagnosing HCC ≤ 3.0 cm with gadoxetate disodium­enhanced MRI (Gd-EOB-MRI). METHOD: We retrospectively included 299 and 90 high-risk patients with hepatic lesions ≤ 3.0 cm that underwent Gd-EOB-MRI from January 2018 to February 2021 in institution 1 (development cohort) and institution 2 (validation cohort), respectively. Through binary and multivariate regression analyses of LI-RADS features in the development cohort, we developed an algorithm using CART analysis, which comprised the targeted appearance and independently significant imaging features. On per-lesion basis, we compared the diagnostic performances of our algorithm, two previously reported CART algorithms, and LI-RADS LR-5 in development and validation cohorts. RESULTS: Our CART algorithm, presenting as a decision tree, included targetoid appearance, HBP hypointensity, nonrim arterial phase hyperenhancement (APHE), and transitional phase hypointensity plus mild-moderate T2 hyperintensity. For definite HCC diagnosis, the overall sensitivity of our algorithm (development cohort 93.2%, validation cohort 92.5%; P < 0.006) was significantly higher than those of Jiang's algorithm modified LR-5 (defined as targetoid appearance, nonperipheral washout, restricted diffusion, and nonrim APHE) and LI-RADS LR-5, with the comparable specificity (development cohort: 84.3%, validation cohort: 86.7%; P ≥ 0.006). Our algorithm, providing the highest balanced accuracy (development cohort: 91.2%, validation cohort: 91.6%), outperformed other criteria for identifying HCCs from non-HCC lesions. CONCLUSIONS: In high-risk patients, our CART algorithm developed with LI-RADS features showed promise for the early diagnosis of HCC ≤ 3.0 cm with Gd-EOB-MRI.

Corona enhancement combined with microvascular invasion for prognosis prediction of macrotrabecular-massive hepatocellular carcinoma subtype.

Objectives: The macrotrabecular-massive (MTM) subtype of hepatocellular carcinoma (HCC) is aggressive and associated with an unfavorable prognosis. This study aimed to characterize MTM-HCC features based on contrast-enhanced MRI and to evaluate the prognosis of imaging characteristics combined with pathology for predicting early recurrence and overall survival after surgery. Methods: This retrospective study included 123 patients with HCC that underwent preoperative contrast-enhanced MRI and surgery, between July 2020 and October 2021. Multivariable logistic regression was performed to investigate factors associated with MTM-HCC. Predictors of early recurrence were determined with a Cox proportional hazards model and validated in a separate retrospective cohort. Results: The primary cohort included 53 patients with MTM-HCC (median age 59 years; 46 male and 7 females; median BMI 23.5 kg/m2) and 70 subjects with non-MTM HCC (median age 61.5 years; 55 male and 15 females; median BMI 22.6 kg/m2) (All P>0.05). The multivariate analysis identified corona enhancement (odds ratio [OR]=2.52, 95% CI: 1.02-6.24; P=0.045) as an independent predictor of the MTM-HCC subtype. The multiple Cox regression analysis identified corona enhancement (hazard ratio [HR]=2.56, 95% CI: 1.08-6.08; P=0.033) and MVI (HR=2.45, 95% CI: 1.40-4.30; P=0.002) as independent predictors of early recurrence (area under the curve=0.790, P<0.001). The prognostic significance of these markers was confirmed by comparing results in the validation cohort to those from the primary cohort. Corona enhancement combined with MVI was significantly associated with poor outcomes after surgery. Conclusions: A nomogram for predicting early recurrence based on corona enhancement and MVI could be used to characterize patients with MTM-HCC and predict their prognosis for early recurrence and overall survival after surgery.

Global Burden of Disease Study 2019 suggests that metabolic risk factors are the leading drivers of the burden of ischemic heart disease.

Metabolic dysfunction is becoming a predominant risk for the development of many comorbidities. Ischemic heart disease (IHD) still imposes the highest disease burden among all cardiovascular diseases worldwide. However, the contributions of metabolic risk factors to IHD over time have not been fully characterized. Here, we analyzed the global disease burden of IHD and 15 associated general risk factors from 1990 to 2019 by applying the methodology framework of the Global Burden of Disease Study. We found that the global death cases due to IHD increased steadily during that time frame, while the mortality rate gradually declined. Notably, metabolic risk factors have become the leading driver of IHD, which also largely contributed to the majority of IHD-related deaths shifting from developed countries to developing countries. These findings suggest an urgent need to implement effective measures to control metabolic risk factors to prevent further increases in IHD-related deaths.

The Neutrophil-to-Lymphocyte Ratio Determines Clinical Efficacy of Corticosteroid Therapy in Patients with COVID-19.

Corticosteroid therapy is now recommended as a treatment in patients with severe COVID-19. But one key question is how to objectively identify severely ill patients who may benefit from such therapy. Here, we assigned 12,862 COVID-19 cases from 21 hospitals in Hubei Province equally to a training and a validation cohort. We found that a neutrophil-to-lymphocyte ratio (NLR) > 6.11 at admission discriminated a higher risk for mortality. Importantly, however, corticosteroid treatment in such individuals was associated with a lower risk of 60-day all-cause mortality. Conversely, in individuals with an NLR ≤ 6.11 or with type 2 diabetes, corticosteroid treatment was not associated with reduced mortality, but rather increased risks of hyperglycemia and infections. These results show that in the studied cohort corticosteroid treatment is associated with beneficial outcomes in a subset of COVID-19 patients who are non-diabetic and with severe symptoms as defined by NLR.

Development and validation of a risk score using complete blood count to predict in-hospital mortality in COVID-19 patients.

BACKGROUND: To develop a sensitive risk score predicting the risk of mortality in patients with coronavirus disease 2019 (COVID-19) using complete blood count (CBC). METHODS: We performed a retrospective cohort study from a total of 13,138 inpatients with COVID-19 in Hubei, China, and Milan, Italy. Among them, 9,810 patients with ≥2 CBC records from Hubei were assigned to the training cohort. CBC parameters were analyzed as potential predictors for all-cause mortality and were selected by the generalized linear mixed model (GLMM). FINDINGS: Five risk factors were derived to construct a composite score (PAWNN score) using the Cox regression model, including platelet counts, age, white blood cell counts, neutrophil counts, and neutrophil:lymphocyte ratio. The PAWNN score showed good accuracy for predicting mortality in 10-fold cross-validation (AUROCs 0.92-0.93) and subsets with different quartile intervals of follow-up and preexisting diseases. The performance of the score was further validated in 2,949 patients with only 1 CBC record from the Hubei cohort (AUROC 0.97) and 227 patients from the Italian cohort (AUROC 0.80). The latent Markov model (LMM) demonstrated that the PAWNN score has good prediction power for transition probabilities between different latent conditions. CONCLUSIONS: The PAWNN score is a simple and accurate risk assessment tool that can predict the mortality for COVID-19 patients during their entire hospitalization. This tool can assist clinicians in prioritizing medical treatment of COVID-19 patients. FUNDING: This work was supported by National Key R&D Program of China (2016YFF0101504, 2016YFF0101505, 2020YFC2004702, 2020YFC0845500), the Key R&D Program of Guangdong Province (2020B1111330003), and the medical flight plan of Wuhan University (TFJH2018006).

A risk score based on baseline risk factors for predicting mortality in COVID-19 patients.

BACKGROUND: To develop a sensitive and clinically applicable risk assessment tool identifying coronavirus disease 2019 (COVID-19) patients with a high risk of mortality at hospital admission. This model would assist frontline clinicians in optimizing medical treatment with limited resources. METHODS: 6415 patients from seven hospitals in Wuhan city were assigned to the training and testing cohorts. A total of 6351 patients from another three hospitals in Wuhan, 2169 patients from outside of Wuhan, and 553 patients from Milan, Italy were assigned to three independent validation cohorts. A total of 64 candidate clinical variables at hospital admission were analyzed by random forest and least absolute shrinkage and selection operator (LASSO) analyses. RESULTS: Eight factors, namely, Oxygen saturation, blood Urea nitrogen, Respiratory rate, admission before the date the national Maximum number of daily new cases was reached, Age, Procalcitonin, C-reactive protein (CRP), and absolute Neutrophil counts, were identified as having significant associations with mortality in COVID-19 patients. A composite score based on these eight risk factors, termed the OURMAPCN-score, predicted the risk of mortality among the COVID-19 patients, with a C-statistic of 0.92 (95% confidence interval [CI] 0.90-0.93). The hazard ratio for all-cause mortality between patients with OURMAPCN-score >11 compared with those with scores ≤ 11 was 18.18 (95% CI 13.93-23.71; p < .0001). The predictive performance, specificity, and sensitivity of the score were validated in three independent cohorts. CONCLUSIONS: The OURMAPCN score is a risk assessment tool to determine the mortality rate in COVID-19 patients based on a limited number of baseline parameters. This tool can assist physicians in optimizing the clinical management of COVID-19 patients with limited hospital resources.

Nonalcoholic Fatty Liver Disease: An Emerging Driver of Hypertension.

Hypertension, a multifactorial disorder resulting from the interplay between genetic predisposition and environmental risk factors, affects ≈30% of adults. Emerging evidence has shown that nonalcoholic fatty liver disease (NAFLD), as an underestimated metabolic abnormality, is strongly associated with an increased risk of incident prehypertension and hypertension. However, the role of NAFLD in the development of hypertension is still obscure and is highly overlooked by the general public. Herein, we highlight the epidemiological evidence and putative mechanisms focusing on the emerging roles of NAFLD in hypertension, with the purpose of reinforcing the notion that NAFLD may serve as an independent risk factor and an important driving force in the development and progression of hypertension. Finally, we also briefly summarize the current potential treatments for NAFLD that might also be beneficial approaches against hypertension.

In-Hospital Use of Statins Is Associated with a Reduced Risk of Mortality among Individuals with COVID-19.

Statins are lipid-lowering therapeutics with favorable anti-inflammatory profiles and have been proposed as an adjunct therapy for COVID-19. However, statins may increase the risk of SARS-CoV-2 viral entry by inducing ACE2 expression. Here, we performed a retrospective study on 13,981 patients with COVID-19 in Hubei Province, China, among which 1,219 received statins. Based on a mixed-effect Cox model after propensity score-matching, we found that the risk for 28-day all-cause mortality was 5.2% and 9.4% in the matched statin and non-statin groups, respectively, with an adjusted hazard ratio of 0.58. The statin use-associated lower risk of mortality was also observed in the Cox time-varying model and marginal structural model analysis. These results give support for the completion of ongoing prospective studies and randomized controlled trials involving statin treatment for COVID-19, which are needed to further validate the utility of this class of drugs to combat the mortality of this pandemic.