Analysis of Diffusion-Weighted and T2-Weighted Imaging in the Prediction of Distinct Granulation Patterns of Somatotroph Adenomas.

OBJECTIVE: The heterogeneity of the somatotroph adenomas, especially for sparsely granulated (SG) and densely granulated (DG) subtypes, has attracted great attention in identifying their imaging biomarker. The purpose of the current study was to compare the diagnostic performance of diffusion-weighted and T2-weighted magnetic resonance imaging (MRI) sequences for preoperatively distinguishing the granulation patterns of somatotroph adenomas. METHODS: Thirty-two patients with a clinical diagnosis of somatotroph adenomas from October 2018 to March 2023 were included in this study. Coronal diffusion-weighted imaging (DWI) and T2-weighted MRI sequence data were collected from 3.0T MRI and compared between SG and DG groups. The immunohistochemistry was used to confirm the electron microscopy pathologic subtypes and Ki67 expression levels of somatotroph adenomas postoperatively. RESULTS: Patients in the SG group had significantly higher signal intensity (SI) ratio of DWI (rDWI) (P < 0.001), lower SI ratio of apparent diffusion coefficient (rADC) (P < 0.001), and higher SI ratio of T2-weighted imaging (P = 0.011). The combined diagnosis index of rDWI and rADC had the highest diagnostic efficiency in predicting SG adenomas (sensitivity, 93.3%; specificity, 88.2%; P < 0.001). The rDWI and rADC values had positive and negative correlations with the Ki67 index and tumor maximum diameter, respectively. Lower rADC×103 was an independent predictor for SG adenomas. CONCLUSIONS: Our results indicated that compared with previously used T2-weighted imaging, the DWI sequence, especially the combined diagnosis index of rDWI and rADC, could more efficiently distinguish the granulation patterns of somatotroph adenomas preoperatively.

Patterns of colorectal cancer screening and adherence rates among an average-risk population enrolled in a national health insurance provider during 2009-2018 in the United States.

While colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States (US), outcomes can be improved through timely screening. Despite the benefits and widespread availability of screening tests, adherence to recommended screening strategies is low. The study aimed to provide recent evidence regarding screening rates and adherence to screening recommendations among adults at average risk for CRC in a commercially insured and Medicare Advantage population. De-identified administrative data from a large US research database were examined to determine screening rates for the years 2009 through 2018. The study population included adults aged 50-75 years and annual study population counts ranged from 1,390,594 in 2009 to 1,654,544 in 2018. Incident screening rates were found to be relatively stable across the study years (approximately 15 %) with adherence lowest in the youngest age group (ages 50-54 years). Colonoscopies accounted for approximately 50 % of all screening tests performed, while there was a substantial increase in the use of home-based screening tests over the study timeframe. The use of the fecal immunochemical test increased from 17.2 % in 2009 to 28.9 % in 2018 and the multi-target stool DNA test increased from 0.4 % in 2015 to 9.0 % in 2018. Overall though, CRC screening and adherence rates remain relatively low among adults at average risk for CRC in the US. Improving adherence rates with CRC screening recommendations among individuals at average risk for CRC is required to improve health outcomes.

Does monoclonal antibody treatment for COVID-19 impact short and long-term outcomes in a large generalisable population? A retrospective cohort study in the USA.

OBJECTIVES: To explore whether monoclonal antibodies (MAb) administered to high-risk patients with COVID-19 during the first week of illness prevent postacute sequelae of SARS-CoV-2 infection. DESIGN: Retrospective cohort study. SETTING: USA. PARTICIPANTS: A sample of 3809 individuals who received MAbs and a matched one-to-one comparison group from a set of 327 079 eligible patients who did not receive MAb treatment were selected from a deidentified administrative data set from commercial and Medicare Advantage health plan enrollees in the USA, including claims and outpatient laboratory data. RESULTS: Individuals who received MAb were 28% less likely to be hospitalised (HR=0.72, 95% CI 0.58 to 0.89) and 41% less likely to be admitted to the intensive care unit (HR=0.59, 95% CI 0.38 to 0.89) 30 days from SARS-CoV-2 diagnosis compared with individuals who did not receive MAb. A higher proportion of individuals given MAb therapy received care for clinical sequelae in the postacute phase (p=0.018). CONCLUSIONS: While MAb therapy was associated with benefits in the acute period, the benefit of therapy did not extend into the postacute period and did not reduce risk for clinical sequelae.

Preoperative identification of cytokeratin 19 status of hepatocellular carcinoma based on diffusion kurtosis imaging.

PURPOSE: To explore the potential value of diffusion kurtosis imaging (DKI) for identification of cytokeratin 19 (CK19) status of HCCs. METHODS: This study was approved by the local institute review board and written informed consent was obtained. 73 patients with pathologically confirmed HCCs were included in this prospective study. All the diffusion-weighted (DW) images were acquired using a 3.0-T MR scanner with 4 b-values (0, 800, 1500 and 2000 s/mm2). The mean diffusion value (MD) and mean kurtosis coefficient (MK) from DKI, apparent diffusion coefficient (ADC) from DW imaging (b = 0, 500 s/mm2), and tumor-to-liver signal intensity ratios on ADC map (SIRADC) and DW images with b-value of 500 s/mm2 (SIRb500) were calculated and compared between CK19-positive (n = 23) and CK19-negative (n = 50) HCC groups. Univariate and multivariate logistic regression analyses were used to identify risk factors for the positive expression of CK19. RESULTS: Increased a-fetoprotein level (p = 0.021) and SIRb500 (p = 0.006) and decreased ADC (p = 0.021) and MD (p < 0.001) were significantly correlated with CK19-positive HCCs at univariate analysis. Decreased MD value (odds ratio: 0.042, p = 0.002) and a-fetoprotein level (odds ratio: 5.139, p = 0.015) were the independent risk factors for CK19-positive HCCs at multivariate analysis. The area under the curve of MD value by receiver operating characteristic analysis was 0.823 with a sensitivity of 86.96% and a specificity of 76% for the prediction of CK19-positive HCCs. CONCLUSION: The decreased MD value derived from DKI is potential quantitative biomarker for predicting CK19-positive HCCs.

Gene set proximity analysis: expanding gene set enrichment analysis through learned geometric embeddings, with drug-repurposing applications in COVID-19.

MOTIVATION: Gene set analysis methods rely on knowledge-based representations of genetic interactions in the form of both gene set collections and protein-protein interaction (PPI) networks. However, explicit representations of genetic interactions often fail to capture complex interdependencies among genes, limiting the analytic power of such methods. RESULTS: We propose an extension of gene set enrichment analysis to a latent embedding space reflecting PPI network topology, called gene set proximity analysis (GSPA). Compared with existing methods, GSPA provides improved ability to identify disease-associated pathways in disease-matched gene expression datasets, while improving reproducibility of enrichment statistics for similar gene sets. GSPA is statistically straightforward, reducing to a version of traditional gene set enrichment analysis through a single user-defined parameter. We apply our method to identify novel drug associations with SARS-CoV-2 viral entry. Finally, we validate our drug association predictions through retrospective clinical analysis of claims data from 8 million patients, supporting a role for gabapentin as a risk factor and metformin as a protective factor for severe COVID-19. AVAILABILITY AND IMPLEMENTATION: GSPA is available for download as a command-line Python package at https://github.com/henrycousins/gspa. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Preoperative assessment of microvascular invasion of hepatocellular carcinoma using non-Gaussian diffusion-weighted imaging with a fractional order calculus model: A pilot study.

PURPOSE: To assess the clinical potential of a set of new diffusion parameters (D, ß, and µ) derived from fractional order calculus (FROC) diffusion model in predicting microvascular invasion (MVI) of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Between January 2019 to November 2020, a total of 63 patients with HCC were enrolled in this study. Diffusion-weighted images were acquired by using ten b-values (0-2000 s/mm2). The FROC model parameters including diffusion coefficient (D), fractional order parameter (ß), a microstructural quantity (µ) together with a conventional apparent diffusion coefficient (ADC) were calculated. Intraclass coefficients were calculated for assessing the agreement of parameters quantified by two radiologists. The differences of these values between the MVI-positive and MVI-negative HCC groups were compared by using independent sample t-test or the Mann-Whitney U test. Then the parameters showing significant differences between subgroups, including the ß and D, were integrated to develop a comprehensive predictive model via binary logistic regression. The diagnostic performance was evaluated by receiver operating characteristic (ROC) analysis. RESULTS: Among all the studied diffusion parameters, significant differences were found in D, ß, and ADC between the MVI-positive and MVI-negative groups. MVI-positive HCCs showed significantly higher ß values (0.65 ± 0.17 vs. 0.51 ± 0.13, P = 0.001), along with lower D values (0.84 ± 0.11 µm2/ms vs. 1.03 ± 0.13 µm2/ms, P < 0.001) and lower ADC values (1.38 ± 0.46 µm2/ms vs. 2.09 ± 0.70 µm2/ms, P < 0.001) than those of MVI-negative HCCs. According to the ROC analysis, the combination of D and ß demonstrated the largest area under the ROC curve (0.920) compared with individual parameters (D: 0.912; ß: 0.733; and ADC: 0.831) for differentiating MVI-positive from MVI-negative HCCs. CONCLUSIONS: The FROC parameters can be used as noninvasive quantitative imaging markers for preoperatively predicting the MVI status of HCCs.

Patterns of initial colorectal cancer screenings after turning 50 years old and follow-up rates of colonoscopy after positive stool-based testing among the average-risk population.

OBJECTIVES: Effective colorectal cancer (CRC) screening requires proper adherence beginning at the recommended screening age. For those with positive results on stool-based tests (SBTs), a follow-up colonoscopy is warranted. The objectives of this study were to 1) examine initial screening rates after turning 50 years old; and 2) assess rates of follow-up colonoscopy after a positive SBT. METHODS: This retrospective study used de-identified administrative claims data from 01/01/2006 to 06/30/2020 for commercially insured and Medicare Advantage enrollees. For objective 1, the index year was the year enrollees turned 50. Rates of CRC screening during and after the index year were captured. For objective 2, the index date was the claim date of a fecal immunochemical test (FIT) or multitarget stool DNA test (mt-sDNA) where linked lab data indicated a positive test result. Rates and time to follow-up colonoscopy after a positive SBT were assessed. RESULTS: Approximately 53% of enrollees initiated CRC screening within five years after turning 50 (50+ cohort N = 718,562). Among enrollees with an available lab result indicating a positive SBT (N = 7329; 2110 FIT and 5219 mt-sDNA), overall follow-up colonoscopy within 6 months of the positive result was less than optimal (65%) and varied by modality; 72% vs 46% (p < .001) among enrollees with a positive mt-sDNA test compared to FIT test, respectively. CONCLUSION: There is potential for improving CRC screening among the eligible average-risk population, both to start screening once they reach the screening-eligible age, and to complete the CRC screening paradigm after a positive stool-based screen.

Differentiating Cytokeratin 19 expression of hepatocellular carcinoma by using multi-b-value diffusion-weighted MR imaging with mono-exponential, stretched exponential, intravoxel incoherent motion, diffusion kurtosis imaging and fractional order calculus models.

PURPOSE: To evaluate Cytokeratin 19 expression in hepatocellular carcinoma (HCC) with diffusion parameters derived from mono-exponential model (MEM), stretched exponential model (SEM), diffusion kurtosis imaging (DKI), intravoxel incoherent motion (IVIM) imaging, and fractional order calculus (FROC) model and compare their predictive performance. METHOD: 61 patients with pathologically confirmed primary HCC were included in this prospective study. All the DWIs were acquired using a 3.0 T MR scanner with 10b-values (0-2000 s/mm2). The apparent diffusion coefficient (ADC), distributed diffusion coefficient (DDC), heterogeneity index (α), apparent kurtosis coefficient (AK), apparent diffusion coefficient (AD), pseudo-diffusion coefficient (Dp), true diffusion coefficient (Dt), perfusion fraction (f), diffusion coefficient (D), fractional order parameter (ß), and a microstructural quantity (µ) were calculated. The diagnostic efficacy of various diffusion parameters for predicting CK19 expression of HCC was compared. RESULTS: ADC, DDC, Dt, Dp, AD, and D were significantly lower in CK19-positive HCCs than in CK19-negative HCCs (P ≤ 0.05). ß was significantly higher in CK19-positive group (P = 0.001). AD (AUC = 0.845) had the greatest AUC values in differentiating CK19-positive and CK19-negative HCC with individual parameters. The combination of ß, AD, and Dp generated the highest area under the ROC curve (AUC = 0.881) compared with individual parameters. CONCLUSIONS: ADC, DDC, Dt, Dp, D, and ß may serve as noninvasive and quantitative imaging markers and holds great potential in accurately accessing CK19 status of HCC. More importantly, the combination of different diffusion parameters yielded better diagnostic performance.

Risk of persistent and new clinical sequelae among adults aged 65 years and older during the post-acute phase of SARS-CoV-2 infection: retrospective cohort study.

OBJECTIVE: To characterize the risk of persistent and new clinical sequelae in adults aged ≥65 years after the acute phase of SARS-CoV-2 infection. DESIGN: Retrospective cohort study. SETTING: UnitedHealth Group Clinical Research Database: deidentified administrative claims and outpatient laboratory test results. PARTICIPANTS: Individuals aged ≥65 years who were continuously enrolled in a Medicare Advantage plan with coverage of prescription drugs from January 2019 to the date of diagnosis of SARS-CoV-2 infection, matched by propensity score to three comparison groups that did not have covid-19: 2020 comparison group (n=87 337), historical 2019 comparison group (n=88 070), and historical comparison group with viral lower respiratory tract illness (n=73 490). MAIN OUTCOME MEASURES: The presence of persistent and new sequelae at 21 or more days after a diagnosis of covid-19 was determined with ICD-10 (international classification of diseases, 10th revision) codes. Excess risk for sequelae caused by infection with SARS-CoV-2 was estimated for the 120 days after the acute phase of the illness with risk difference and hazard ratios, calculated with 95% Bonferroni corrected confidence intervals. The incidence of sequelae after the acute infection was analyzed by age, race, sex, and whether patients were admitted to hospital for covid-19. RESULTS: Among individuals who were diagnosed with SARS-CoV-2, 32% (27 698 of 87 337) sought medical attention in the post-acute period for one or more new or persistent clinical sequelae, which was 11% higher than the 2020 comparison group. Respiratory failure (risk difference 7.55, 95% confidence interval 7.18 to 8.01), fatigue (5.66, 5.03 to 6.27), hypertension (4.43, 2.27 to 6.37), memory difficulties (2.63, 2.23 to 3.13), kidney injury (2.59, 2.03 to 3.12), mental health diagnoses (2.50, 2.04 to 3.04), hypercoagulability 1.47 (1.2 to 1.73), and cardiac rhythm disorders (2.19, 1.76 to 2.57) had the greatest risk differences compared with the 2020 comparison group, with similar findings to the 2019 comparison group. Compared with the group with viral lower respiratory tract illness, however, only respiratory failure, dementia, and post-viral fatigue had increased risk differences of 2.39 (95% confidence interval 1.79 to 2.94), 0.71 (0.3 to 1.08), and 0.18 (0.11 to 0.26) per 100 patients, respectively. Individuals with severe covid-19 disease requiring admission to hospital had a markedly increased risk for most but not all clinical sequelae. CONCLUSIONS: The results confirm an excess risk for persistent and new sequelae in adults aged ≥65 years after acute infection with SARS-CoV-2. Other than respiratory failure, dementia, and post-viral fatigue, the sequelae resembled those of viral lower respiratory tract illness in older adults. These findings further highlight the wide range of important sequelae after acute infection with the SARS-CoV-2 virus.

Unmanaged Pharmacogenomic and Drug Interaction Risk Associations with Hospital Length of Stay among Medicare Advantage Members with COVID-19: A Retrospective Cohort Study.

Unmanaged pharmacogenomic and drug interaction risk can lengthen hospitalization and may have influenced the severe health outcomes seen in some COVID-19 patients. To determine if unmanaged pharmacogenomic and drug interaction risks were associated with longer lengths of stay (LOS) among patients hospitalized with COVID-19, we retrospectively reviewed medical and pharmacy claims from 6025 Medicare Advantage members hospitalized with COVID-19. Patients with a moderate or high pharmacogenetic interaction probability (PIP), which indicates the likelihood that testing would identify one or more clinically actionable gene-drug or gene-drug-drug interactions, were hospitalized for 9% (CI: 4-15%; p < 0.001) and 16% longer (CI: 8-24%; p < 0.001), respectively, compared to those with low PIP. Risk adjustment factor (RAF) score, a commonly used measure of disease burden, was not associated with LOS. High PIP was significantly associated with 12-22% longer LOS compared to low PIP in patients with hypertension, hyperlipidemia, diabetes, or chronic obstructive pulmonary disease (COPD). A greater drug-drug interaction risk was associated with 10% longer LOS among patients with two or three chronic conditions. Thus, unmanaged pharmacogenomic risk was associated with longer LOS in these patients and managing this risk has the potential to reduce LOS in severely ill patients, especially those with chronic conditions.

Regio- and enantioselective umpolung gem-difluoroallylation of hydrazones via palladium catalysis enabled by N-heterocyclic carbene ligand.

The enantioselective construction of C-CF2R (R: alkyl or fluoroalkyl) bonds has attracted the attention of synthetic chemists because of the importance of chiral fluorinated compounds in life and materials sciences. Catalytic asymmetric fluoroalkylation has mainly been realized under organocatalysis and Lewis acid catalysis, with substrates limited to carbonyl compounds. Few examples using transition-metal catalysis exist, owing to side reactions including decomposition and isomerization of fluoroalkylating reagents. Herein we report umpolung asymmetric difluoroallylation of hydrazones with 3-bromo-3,3-difluoropropene (BDFP) under palladium catalysis. Difluoroallylation products having quaternary chiral carbon centers are afforded in good yields with high α/γ- and enantioselectivities. The usefulness of the reaction products is demonstrated and an inner-sphere mechanism of the reaction is proposed. The use of chiral N-heterocyclic carbene as ligand is the key for the selectivities as well as the productivity of the reaction.

Risk of clinical sequelae after the acute phase of SARS-CoV-2 infection: retrospective cohort study.

OBJECTIVE: To evaluate the excess risk and relative hazards for developing incident clinical sequelae after the acute phase of SARS-CoV-2 infection in adults aged 18-65. DESIGN: Retrospective cohort study. SETTING: Three merged data sources from a large United States health plan: a large national administrative claims database, an outpatient laboratory testing database, and an inpatient hospital admissions database. PARTICIPANTS: Individuals aged 18-65 with continuous enrollment in the health plan from January 2019 to the date of a diagnosis of SARS-CoV-2 infection. Three comparator groups, matched by propensity score, to individuals infected with SARS-CoV-2: a 2020 comparator group, an historical 2019 comparator group, and an historical comparator group with viral lower respiratory tract illness. MAIN OUTCOME MEASURES: More than 50 clinical sequelae after the acute phase of SARS-CoV-2 infection (defined as the date of first SARS-CoV-2 diagnosis (index date) plus 21 days) were identified using ICD-10 (international classification of diseases, 10th revision) codes. Excess risk in the four months after acute infection and hazard ratios with Bonferroni corrected 95% confidence intervals were calculated. RESULTS: 14% of adults aged ≤65 who were infected with SARS-CoV-2 (27 074 of 193 113) had at least one new type of clinical sequelae that required medical care after the acute phase of the illness, which was 4.95% higher than in the 2020 comparator group. The risk for specific new sequelae attributable to SARS-Cov-2 infection after the acute phase, including chronic respiratory failure, cardiac arrythmia, hypercoagulability, encephalopathy, peripheral neuropathy, amnesia (memory difficulty), diabetes, liver test abnormalities, myocarditis, anxiety, and fatigue, was significantly greater than in the three comparator groups (2020, 2019, and viral lower respiratory tract illness groups) (all P<0.001). Significant risk differences because of SARS-CoV-2 infection ranged from 0.02 to 2.26 per 100 people (all P<0.001), and hazard ratios ranged from 1.24 to 25.65 compared with the 2020 comparator group. CONCLUSIONS: The results indicate the excess risk of developing new clinical sequelae after the acute phase of SARS-CoV-2 infection, including specific types of sequelae less commonly seen in other viral illnesses. Although individuals who were older, had pre-existing conditions, and were admitted to hospital because of covid-19 were at greatest excess risk, younger adults (aged ≤50), those with no pre-existing conditions, or those not admitted to hospital for covid-19 also had an increased risk of developing new clinical sequelae. The greater risk for incident sequelae after the acute phase of SARS-CoV-2 infection is relevant for healthcare planning.

Association of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers With the Risk of Hospitalization and Death in Hypertensive Patients With COVID-19.

Background Despite its clinical significance, the risk of severe infection requiring hospitalization among outpatients with severe acute respiratory syndrome coronavirus 2 infection who receive angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) remains uncertain. Methods and Results In a propensity score-matched outpatient cohort (January-May 2020) of 2263 Medicare Advantage and commercially insured individuals with hypertension and a positive outpatient SARS-CoV-2, we determined the association of ACE inhibitors and ARBs with COVID-19 hospitalization. In a concurrent inpatient cohort of 7933 hospitalized with COVID-19, we tested their association with in-hospital mortality. The robustness of the observations was assessed in a contemporary cohort (May-August). In the outpatient study, neither ACE inhibitors (hazard ratio [HR], 0.77; 0.53-1.13, P=0.18) nor ARBs (HR, 0.88; 0.61-1.26, P=0.48) were associated with hospitalization risk. ACE inhibitors were associated with lower hospitalization risk in the older Medicare group (HR, 0.61; 0.41-0.93, P=0.02), but not the younger commercially insured group (HR, 2.14; 0.82-5.60, P=0.12; P-interaction 0.09). Neither ACE inhibitors nor ARBs were associated with lower hospitalization risk in either population in the validation cohort. In the primary inpatient study cohort, neither ACE inhibitors (HR, 0.97; 0.81-1.16; P=0.74) nor ARBs (HR, 1.15; 0.95-1.38, P=0.15) were associated with in-hospital mortality. These observations were consistent in the validation cohort. Conclusions ACE inhibitors and ARBs were not associated with COVID-19 hospitalization or mortality. Despite early evidence for a potential association between ACE inhibitors and severe COVID-19 prevention in older individuals, the inconsistency of this observation in recent data argues against a role for prophylaxis.

Histological Subtypes Classification of Lung Cancers on CT Images Using 3D Deep Learning and Radiomics.

RATIONALE AND OBJECTIVES: Histological subtypes of lung cancers are critical for clinical treatment decision. In this study, we attempt to use 3D deep learning and radiomics methods to automatically distinguish lung adenocarcinomas (ADC), squamous cell carcinomas (SCC), and small cell lung cancers (SCLC) respectively on Computed Tomography images, and then compare their performance. MATERIALS AND METHODS: 920 patients (mean age 61.2, range, 17-87; 340 Female and 580 Male) with lung cancer, including 554 patients with ADC, 175 patients with lung SCC and 191 patients with SCLC, were included in this retrospective study from January 2013 to August 2018. Histopathologic analysis was available for every patient. The classification models based on 3D deep learning (named the ProNet) and radiomics (named com_radNet) were designed to classify lung cancers into the three types mentioned above according to histopathologic results. The training, validation and testing cohorts counted 0.70, 0.15, and 0.15 of the whole datasets respectively. RESULTS: The ProNet model used to classify the three types of lung cancers achieved the F1-scores of 90.0%, 72.4%, 83.7% in ADC, SCC, and SCLC respectively, and the weighted average F1-score of 73.2%. For com_radNet, the F1-scores achieved 83.1%, 75.4%, 85.1% in ADC, SCC, and SCLC, and the weighted average F1-score was 72.2%. The area under the receiver operating characteristic curve of the ProNet model and com_radNet were 0.840 and 0.789, and the accuracy were 71.6% and 74.7% respectively. CONCLUSION: The ProNet and com_radNet models we developed can achieve high performance in distinguishing ADC, SCC, and SCLC and may be promising approaches for non-invasive predicting histological subtypes of lung cancers.

Association of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers with the Risk of Hospitalization and Death in Hypertensive Patients with Coronavirus Disease-19.

BACKGROUND: Whether angiotensin-converting enzyme (ACE) Inhibitors and angiotensin receptor blockers (ARBs) mitigate or exacerbate SARS-CoV-2 infection remains uncertain. In a national study, we evaluated the association of ACE inhibitors and ARB with coronavirus disease-19 (COVID-19) hospitalization and mortality among individuals with hypertension. METHODS: Among Medicare Advantage and commercially insured individuals, we identified 2,263 people with hypertension, receiving ≥1 antihypertensive agents, and who had a positive outpatient SARS-CoV-2 test (outpatient cohort). In a propensity score-matched analysis, we determined the association of ACE inhibitors and ARBs with the risk of hospitalization for COVID-19. In a second study of 7,933 individuals with hypertension who were hospitalized with COVID-19 (inpatient cohort), we tested the association of these medications with in-hospital mortality. We stratified all our assessments by insurance groups. RESULTS: Among individuals in the outpatient and inpatient cohorts, 31.9% and 29.8%, respectively, used ACE inhibitors and 32.3% and 28.1% used ARBs. In the outpatient study, over a median 30.0 (19.0 - 40.0) days after testing positive, 12.7% were hospitalized for COVID-19. In propensity score-matched analyses, neither ACE inhibitors (HR, 0.77 [0.53, 1.13], P = 0.18), nor ARBs (HR, 0.88 [0.61, 1.26], P = 0.48), were significantly associated with risk of hospitalization. In analyses stratified by insurance group, ACE inhibitors, but not ARBs, were associated with a significant lower risk of hospitalization in the Medicare group (HR, 0.61 [0.41, 0.93], P = 0.02), but not the commercially insured group (HR: 2.14 [0.82, 5.60], P = 0.12; P-interaction 0.09). In the inpatient study, 14.2% died, 59.5% survived to discharge, and 26.3% had an ongoing hospitalization. In propensity score-matched analyses, neither use of ACE inhibitor (0.97 [0.81, 1.16]; P = 0.74) nor ARB (1.15 [0.95, 1.38]; P = 0.15) was associated with risk of in-hospital mortality, in total or in the stratified analyses. CONCLUSIONS: The use of ACE inhibitors and ARBs was not associated with the risk of hospitalization or mortality among those infected with SARS-CoV-2. However, there was a nearly 40% lower risk of hospitalization with the use of ACE inhibitors in the Medicare population. This finding merits a clinical trial to evaluate the potential role of ACE inhibitors in reducing the risk of hospitalization among older individuals, who are at an elevated risk of adverse outcomes with the infection.

Assessing PD-L1 Expression Level by Radiomic Features From PET/CT in Nonsmall Cell Lung Cancer Patients: An Initial Result.

RATIONALE AND OBJECTIVES: To explore the potential value of radiomic features-derived approach in assessing PD-L1 expression status in nonsmall cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: A cohort of 399 stage I-IV NSCLC patients were enrolled. Tumor segmentation was performed to select essential primary lesions of NSCLC cases after PET/CT images acquisition. Features were extracted, then filtered with automatic relevance determination and minimized with LASSO model based on its relevance of PD-L1 expression status. Finally, we built predictive models with features from the CT, the PET, and the PET/CT images, respectively, for differentiating different status of specific PD-L1 types. Five-fold cross validation was practiced to evaluate the signatures' accuracy, and the receiver operating characteristic as well as the corresponding area under the curve (AUC) was reckoned for each model. RESULTS: With the total of 24 selected features which were significantly associated with PD-L1 expression levels, models based on CT-, PET-, PET/CT-derived features were built and compared. For PD-L1 (SP142) expression level over 1% prediction, models that comprised radiomic features from the CT, the PET, and the PET/CT images resulted in an AUC of 0.97, 0.61, and 0.97, respectively; models for over 50% prediction resulted with AUC of 0.80, 0.65, and 0.77. For PD-L1 (28-8) expression level prediction, predictive models of over 1% expression scored at 0.86, 0.62, and 0.85; and signatures of over 50% expression reached the score of AUCs at 0.91, 0.75, and 0.88, respectively. CONCLUSION: The radiomic-based predictive approach, especially CT-derived predictive model, may anticipate PD-L1 expression status in NSCLC patients relatively accurate. It may be helpful in guiding immunotherapy in clinical practice and deserves further analysis.

Assessing EGFR gene mutation status in non-small cell lung cancer with imaging features from PET/CT.

OBJECTIVE: The aim of this study was to investigate whether quantitative and qualitative features extracted from PET/computed tomography (CT) can be used as imaging biomarkers for evaluating epidermal growth factor receptor (EGFR) mutation status in non-small cell lung cancer patients. METHODS: Eighty patients with stage II and III non-small cell lung cancer from January 2017 to December 2017 were included in this study. All patients underwent PET/CT examination before operation. Patients with 30 EGFR positive and 50 EGFR negative were confirmed by pathological verification and gene detection. Least absolute shrinkage and selection operator was used for analysis and selection of imaging features. Support vector machine was used to classify EGFR positive/negative using the selected features. Ten-fold cross validation was used to estimate the accuracy. RESULTS: A total of 512 quantitative features (radiomic features) were extracted from PET/CT (256 for PET and 256 for CT), and 12 qualitative features (semantic features) were extracted from CT. A total of 35 features were finally retained after least absolute shrinkage and selection operator (31 quantitative features and 4 qualitative features). The 35 selected features were significantly associated with EGFR mutation status. A predictive model was built using PET/CT data. Its performance was revealed as 0.953 using the area under the receiver operating characteristic curve. CONCLUSION: A predictive model using PET/CT images might be used to detect EGFR mutation status in non-small cell lung cancer patients.

MRI-based nomogram estimates the risk of recurrence of primary nonmetastatic pancreatic neuroendocrine tumors after curative resection.

BACKGROUND: Accurate estimation of the recurrence of pancreatic neuroendocrine tumors help with prognosis, guide follow-up, and avoid futile treatments. PURPOSE: To investigate whether MRI features could preoperatively estimate the recurrence of pancreatic neuroendocrine tumors (PNETs) and to refine a novel prognostic model through developing a nomogram incorporating various MRI features. STUDY TYPE: Retrospective. POPULATION: In all, 81 patients with clinicopathologically confirmed nonmetastatic PNETs. FIELD STRENGTH/SEQUENCES: 1.5 T MR, including T1 -weighted, T2 -weighted, and diffusion-weighted imaging sequences. ASSESSMENT: Qualitative and quantitative MRI features of PNET were assessed by three experienced radiologists. STATISTICAL TESTS: Uni- and multivariable analyses for recurrence-free survival (RFS) were evaluated using a Cox proportional hazards model. The MRI-based nomogram was then designed based on multivariable logistic analysis in our study and the performance of the nomogram was validated according to C-index, calibration, and decision curve analyses. RESULTS: MRI features, including tumor size (hazard ratio [HR]: 14.131; P = 0.034), enhancement pattern (HR: 21.821, P = 0.032), and the apparent diffusion coefficient (ADC) values (HR: 0.055, P = 0.038) were significant independent predictors of RFS at multivariable analysis. The performance of the nomogram incorporating various MRI features (with a C-index of 0.910) was improved compared with that based on tumor size, enhancement pattern, and ADC alone (with C-index values of 0.672, 0.851, and 0.809, respectively). The calibration curve of the nomogram exhibited perfect consistency between estimation and observation at 0.5, 1, and 2 years after surgery. The decision curve showed that a nomogram incorporating three features had more favorable clinical predictive usefulness than any single feature. DATA CONCLUSION: MRI features can be considered effective recurrence predictors for PNETs after surgery. The preliminary nomogram incorporating various MRI features could assess the risk of recurrence in PNETs and may be used to optimize individual treatment strategies. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:397-409.

Nitidine chloride suppresses epithelial-to-mesenchymal transition in osteosarcoma cell migration and invasion through Akt/GSK-3ß/Snail signaling pathway.

Metastasis is the main cause of death in osteosarcoma. Targeting the process of metastasis is a main strategy for osteosarcoma therapy. As a traditional Chinese medicine, Zanthoxylum nitidum (Roxb) has been applied to treat various diseases, including cancer. However, no evidence has been shown on the anti-metastasis effect of nitidine chloride (NC) that was extracted from Zanthoxylum nitidum (Roxb) on osteosarcoma cells, or its underling mechanisms. In the present study, we aimed to demonstrate the role of NC on the migration and invasion of osteosarcoma cells. Viability and proliferation of osteosarcoma cells were examined by MTT assay. Then, by appling scratch wound healing assay and Transwell assays, we evaluated migratory and invasive ability of the cells, respectively. Moreover, the expression of epithelial-to-mesenchymal transition (EMT) markers were determined after treatment with NC. Furthermore, the expression of Akt, GSK-3ß and Snail were detected by western blot analysis. In addition, the GSK-3ß activity was examined by GSK-3ß kinase assay. Finally, an inhibitor of GSK-3ß, lithium chloride (LiCl) was applied to testify the effect of NC on the expression of EMT markers and Snail. We found that the proliferative, migratory and invasive ability of the U2OS osteosarcoma cells were all suppressed when treated with NC. NC increased the expression of E-cadherin and decreased the expression of N-cadherin, vimentin and fibronectin in a dose-dependent manner. NC also exerted its ability to suppress the phosphorylation of Akt and GSK-3ß so as to activate GSK-3ß. Then, by using an GSK-3ß inhibitor, LiCl, we revealed the effect of GSK-3ß in the expression of EMT markers. The expression of Snail was inhibited when treated with NC and LiCl also reversed the NC-inhibited Snail expression. Taken together, these results revealed that NC suppressed EMT and decreased the invasive ability of osteosarcoma cells via the Akt/GSK-3ß/snail signaling pathway.

[Percutaneous vertebroplasty for senile osteoporotic vertebral compressive fractures with posterior vertebral defect and spinal canal compromise].

OBJECTIVE: To evaluate the curative effect of percutaneous vertebroplasty (PVP) for senile osteoporotic vertebral compressive fractures with posterior vertebral defect and spinal canal compromise.
 METHODS: A total of 50 patients with osteoporotic vertebral compressive fractures (50 vertebrae) underwent PVP from July, 2010 to October, 2013. Subsequent visual analogue scale (VAS) rating, analgesic utilization and mobility were recorded before and after the surgery.
 RESULTS: A total of 42 patients were followed up completely. The median VAS, analgesic administration score and patients' mobility score was significantly decreased at the 2nd hour, the 3rd day, the 1st month, the 3rd month, the 6th month and the 1st year after the surgery compared with those at the pre-operation (P<0.01). Five recurrence fractures were observed after PVP.
 CONCLUSION: PVP is safe and effective and it is worthy for clinical popularization and application.