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1.
Artigo em Inglês | MEDLINE | ID: mdl-33948991

RESUMO

BACKGROUND AND AIM: The evidences for use of postoperative antibiotics (POA) in hepatocellular carcinoma (HCC) patients underwent hepatectomy are controversial. We aimed to explore the relationship between POA and hepatectomy-related infection in an HBV-related HCC population. METHODS: We retrospectively collected 934 HCC patients who underwent hepatectomy for curative intent from three tertiary hospitals in China. The incidences of postoperative infection including surgical site infection (SSI) and remote site infection (RI) were recorded and calculated. Univariable and multivariable logistic regression analyses were performed to explore related factors of postoperative infection and POA. And the relationship between infection rate with different duration of POA was investigated. RESULTS: The overall infection rate was 8.2% (77/934), including 6.5% (61/934) of SSI and 2.0% (19/934) of RI. Multivariable analysis revealed that the administration of POA was negatively related with the incidence of postoperative infection significantly (OR=0.50, 95% CI=0.30 to 0.83; P=0.008). Albumin-bilirubin (ALBI) score, BCLC stage and extent of hepatectomy were independently related to the POA. And 3-day regimen seemed to be the shortest duration of POA to gain the lowest incidence of postoperative infection. CONCLUSIONS: POA is necessary for HBV related HCC patients to prevent postoperative infection, especially for those with higher ALBI score, at BCLC stage B-C or who underwent major hepatectomy. For HBV related HCC patients, postoperative second generation cephalosporins or ceftriaxone for 3 days after surgery might be proper.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33790552

RESUMO

Objective: Patients with chronic obstructive pulmonary disease (COPD) have a higher risk of osteoporosis. Few studies have addressed the prescription patterns in osteoporosis patients with COPD. The purpose of this study was to conduct a retrospective study of the prescription patterns in patients with COPD and osteoporosis in Taiwan. Methods: The study was conducted with data from the Taiwan National Health Insurance Research Database from January 1, 2003, to December 31, 2016. We selected the COPD population in Taiwan older than 40 years with at least one prescription for a bronchodilator. We excluded patients who had osteoporosis, fracture, asthma, or cancer before the diagnosis of COPD. After the diagnosis of COPD, patients who did not have osteoporosis were also excluded. We followed this COPD and osteoporosis cohort until they had been prescribed medication for osteoporosis. Results: There were 13,407 patients with COPD and osteoporosis who received osteoporosis treatment. Among the patients who received treatment, the majority were female (n = 9136), accounting for 68.14% of all treated patients. A total of 53.4% of the patients had been prescribed steroids least once within the last year before receiving a diagnosis of osteoporosis. A total of 34.61% of the patients received systemic corticosteroids with a daily dose equivalent to 5 mg of prednisolone within the 3 months prior to the diagnosis of osteoporosis. The older the patient was, the higher the probability of the prescription of medication for osteoporosis. Patients with depression had a high probability of receiving medication for osteoporosis with adjusted hazard ratio of 1.141 (95% confidence interval, 1.072-1.214). Conclusion: The rate of prescriptions for the treatment of osteoporosis in patients with COPD was low. Physicians need to be aware of this issue and treat osteoporosis more aggressively in patients with COPD.

3.
BMJ Open ; 11(4): e045940, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33837108

RESUMO

OBJECTIVE: To identify theoretical and technical aspects regarding treatment, prevention of spread and protection of staff to inform the development of a comprehensive training curriculum on COVID-19 management. DESIGN: Cross-sectional study. SETTING: Nine hospitals caring for patients with COVID-19 in Wuhan, China. PARTICIPANTS: 134 Chinese healthcare professionals (74 doctors and 60 nurses) who were deployed to Wuhan, China during the COVID-19 epidemic were included. A two-round Delphi process was initiated between March and May 2020. In the first round, the participants identified knowledge, technical and behavioural (ie, non-technical) skills that are needed to treat patients, prevent spread of the virus and protect healthcare workers. In round 2, the participants rated each item according to its importance to be included in a training curriculum on COVID-19. Consensus for inclusion in the final list was set at 80%. PRIMARY OUTCOME MEASURES: Knowledge, technical and behavioural (ie, non-technical) skills that could form the basis of a training curriculum for COVID-19 management. RESULTS: In the first round 1398 items were suggested by the doctors and reduced to 67 items after content analysis (treatment of patients: n=47; infection prevention and control: n=20). The nurses suggested 1193 items that were reduced to 70 items (treatment of patients: n=49; infection prevention and control: n=21). In round 2, the response rates were 82% in doctors and 93% in nurses. Fifty-eight items of knowledge, technical and behavioural skills were agreed on by the doctors to include in the final list. For the nurses, 58 items were agreed on. CONCLUSIONS: This needs assessment process resulted in a comprehensive list of knowledge, technical and behavioural skills for COVID-19 management. Educators can use these to guide decisions regarding content of training curricula not only for COVID-19 management but also in preparation for future viral pandemic outbreaks.


Assuntos
/prevenção & controle , Currículo , Pandemias , China/epidemiologia , Estudos Transversais , Técnica Delfos , Educação Médica , Educação em Enfermagem , Feminino , Humanos , Capacitação em Serviço , Masculino , Enfermeiras e Enfermeiros , Pandemias/prevenção & controle , Médicos
4.
Sci Rep ; 11(1): 7840, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33837282

RESUMO

After traumatic brain injury (TBI), an inflammatory response in the brain might affect the immune system. The risk of pulmonary infection reportedly increases in patients with TBI. We aimed to evaluate the risk of tuberculosis (TB) in patients with TBI in Taiwan. All participants were selected from the intensive care unit (ICU). Patients with TBI were defined as patients in ICU with intracranial injury, and comparison cohort were patients in ICU without TBI diagnosis. There was a significant difference in TB risk between the patients with TBI and the comparison cohort according to age and the Charlson's comorbidity index (CCI) score. Thus, we divided patients based on CCI into three groups for further analysis: mild (CCI = 0), moderate (CCI = 1/2), severe (CCI > 2). Mild-CCI group had a lower TB incidence rate (0.74%) and longer time to TB development (median: 2.43) than the other two groups. Moderate-CCI group had 1.52-fold increased risk of TB infection (p < 0.0001) compared with mild-CCI group. In the severe-CCI group, patients aged ≥ 80 years had 1.91-fold risk of TB compared with mild-CCI group (p = 0.0481). Severe-CCI group had significantly higher mortality than the mild-CCI group (p = 0.0366). Patients with TBI and more comorbidities had higher risk of TB infection with higher mortality rate.

5.
Women Health ; : 1-12, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33902386

RESUMO

This study was designed to explore the association among health literacy and cancer screening behaviors in Taiwanese females. A total of 353 community-dwelling females were recruited in this cross-sectional study from February to October 2015. Demographic, socioeconomic and personal behavior variables including physical activity, community activity, smoking, alcohol consumption, and betel nut chewing were recorded. Health literacy was evaluated using the Mandarin version of the European Health Literacy Survey Questionnaire. Data on screening behaviors for cervical, breast and colorectal cancers were confirmed by the Taiwanese National eHealth Database. Most respondents with inadequate or problematic general health literacy had no or irregular screening behaviors for cervical, breast and colorectal cancers. In multivariable regression analysis, women with inadequate health literacy were at a greater risk (Odds ratio = 5.71; 95% CI: 1.40-23.26) of having no previous Pap smear screening or >3 years screening interval regardless of education level. However, this association was not detected for breast or colorectal cancer. Women with inadequate health literacy were more likely to have irregular cervical cancer screening, however no associations among health literacy and breast or colorectal cancer were detected. The impact of health literacy on cancer screening behavior warrants further attention and research.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33880797

RESUMO

BACKGROUND AND AIM: This study aims to construct a strategy that uses assistance from artificial intelligence (AI) to assist radiologists in the identification of malignant versus benign focal liver lesions (FLLs) using contrast-enhanced ultrasound (CEUS). METHODS: A training set (patients = 363) and a testing set (patients = 211) were collected from our institute. On four-phase CEUS images in the training set, a composite deep learning architecture was trained and tuned for differentiating malignant and benign FLLs. In the test dataset, AI performance was evaluated by comparison with radiologists with varied levels of experience. Based on the comparison, an AI assistance strategy was constructed, and its usefulness in reducing CEUS interobserver heterogeneity was further tested. RESULTS: In the test set, to identify malignant versus benign FLLs, AI achieved an area under the curve of 0.934 (95% CI 0.890-0.978) with an accuracy of 91.0%. Comparing with radiologists reviewing videos along with complementary patient information, AI outperformed residents (82.9-84.4%, P = 0.038) and matched the performance of experts (87.2-88.2%, P = 0.438). Due to the higher positive predictive value (PPV) (AI: 95.6% vs residents: 88.6-89.7%, P = 0.056), an AI strategy was defined to improve the malignant diagnosis. With the assistance of AI, radiologists exhibited a sensitivity improvement of 97.0-99.4% (P < 0.05) and an accuracy of 91.0-92.9% (P = 0.008-0.189), which was comparable with that of the experts (P = 0.904). CONCLUSIONS: The CEUS-based AI strategy improved the performance of residents and reduced CEUS's interobserver heterogeneity in the differentiation of benign and malignant FLLs.

8.
Eur Radiol ; 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33675388

RESUMO

OBJECTIVES: To investigate the inter-reader agreement of contrast-enhanced ultrasound (CEUS) of Liver Imaging Reporting and Data System version 2017 (LI-RADS v2017) categories among radiologists with different levels of experience. MATERIALS AND METHODS: From January 2014 to December 2014, a total of 326 patients at high risk of hepatocellular carcinoma (HCC) who underwent CEUS were included in this retrospective study. All lesions were classified according to LI-RADS v2017 by six radiologists with different levels of experiences: two residents, two fellows, and two specialists. Kappa coefficient was used to assess consistency of LI-RADS categories and major features among radiologists with different levels of experience. The diagnostic performance of HCC was described by accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC). RESULTS: Inter-reader agreement among radiologists of different experience levels was substantial agreement for arterial phase hyperenhancement, washout appearance, and early or late washout. Inter-reader agreement for LI-RADS categories was moderate to substantial. When LR-5 was used as criteria to determinate HCC, the AUC of LI-RADS for HCC was 0.67 for residents, 0.72 for fellows, and 0.78 for specialist radiologists. When compared between residents and specialists, accuracy, sensitivity, and AUC were significantly different (all p < 0.05). However, there were no significant differences in specificity, PPV, and NPV between the two groups. CONCLUSION: CEUS LI-RADS showed good diagnostic consistency among radiologists with different levels of experience, and consistency increased with experience levels. KEY POINTS: • The inter-reader agreement for LI-RADS categories was moderate to substantial agreement (κ, 0.60-0.80). • When compared between residents and specialists, accuracy, sensitivity, and AUC showed significantly different (all p < 0.05). However, there were no significant differences for specificity, PPV, and NPV between these two groups. • Among the radiologists with more than 1 year of experience, there was no significant difference in the diagnostic performance of HCC, suggesting that CEUS LI-RADS is a good standardized categorization system for high-risk patients.

9.
Ann Surg Oncol ; 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33751300

RESUMO

BACKGROUND: The aim of this work is to explore the impact of the number of sampling sites (NuSS) and sampling location on microvascular invasion (MVI) detection rate and long-term survival of hepatocellular carcinoma (HCC), and determine the minimum NuSS for sufficient MVI detection. PATIENTS AND METHODS: From January 2008 to March 2017, 1144 HCC patients who underwent hepatectomy were retrospectively enrolled. Associations between NuSS and MVI positive rates and overall survival were investigated. NuSS thresholds were determined by Chow test and confirmed prospectively in 305 patients from April 2017 to February 2019. In the prospective cohort, the distribution of MVI in different sampling locations and its prognostic effect was evaluated. RESULTS: MVI positive rates increased as NuSS increased, steadily reaching a plateau when NuSS reached a threshold. A threshold of four, six, eight, and eight sampling sites within paracancerous parenchyma ≤ 1 cm from tumor was required for detecting MVI in solitary tumors measuring 1.0-3.0, 3.1-4.9, and ≥ 5.0 cm and multiple tumors. Patients with adequate NuSS achieved longer survival than those with inadequate NuSS [hazard ratio (HR) = 0.75, P = 0.043]. For all MVI-positive patients, MVI could be detected positive in paracancerous parenchyma ≤ 1 cm from tumor. Patients with MVI positive in paracancerous parenchyma > 1 cm had higher recurrence risk than those with MVI positive only in parenchyma ≤ 1 cm (HR = 6.05, P < 0.001). CONCLUSIONS: Adequate NuSS is associated with higher MVI detection rate and better survival of HCC patients. We recommend four, six, eight, and eight as the cut-points for evaluating MVI sampling quality and patients' prognostic stratification in the subgroups of solitary tumors measuring 1.0-3.0 cm, 3.1-4.9 cm and ≥ 5.0 cm and multiple tumors, respectively.

10.
Int J Hyperthermia ; 38(1): 461-470, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33752538

RESUMO

OBJECTIVE: To investigate the risk factors affecting the technical failure of artificial ascites (AA) formation and to evaluate the local control efficacy of percutaneous thermal ablation assisted by the AA for hepatic tumors. METHODS: A total of 341 patients with 362 hepatic tumors who underwent thermal ablation assisted by AA were reviewed retrospectively. The technical success of AA, the volume of liquid, and local efficacy after ablation were assessed. Predictive factors for the technical failure of AA formation and local tumor progression (LTP) were analyzed using univariate and multivariate analysis. RESULTS: The technical success rate of AA formation was 81.8% (296/362). The amount of fluid was higher when the tumor was located in the left lobe of the liver than when it was located in the right lobe (median 950 ml versus 700 ml, p < 0.001). Previous hepatic resection (OR: 12.63, 95% CI: 2.93-54.45, p < 0.001), ablation (OR: 6.48, 95% CI: 1.36-30.92, p = 0.019) and upper-abdomen surgery (OR: 11.34, 95% CI: 1.96-65.67, p = 0.007) were the independent risk factors of AA failure. In the AA success group, the complete ablation rate was higher and the LTP rate was lower than that in the AA failure group (98.7 versus 92.4%, p = 0.012; 8.8 versus 21.2%, p = 0.004). Multivariate analysis identified AA failure (p = 0.004), tumor size (>3.0 cm) (p = 0.002) and metastatic liver tumor (p = 0.008) as independent risk factors for LTP. CONCLUSION: History of hepatic resection, ablation and upper abdomen surgery were significant predictive factors affecting the technical failure of AA formation. Successful introduction of AA before thermal ablation can achieve better local tumor control efficacy.

12.
Physiol Meas ; 42(3)2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33636707

RESUMO

Objective. The aim of this study was to investigate methods for measuring the cardiac efficiency (CE) and internal work (IW) of the left ventricle via reconstructed impedance cardiography (RICG).Approach.On the basis of the physiological context and Bernoulli's equation in physics, methods of measuring the CE and IW were proposed. The CE, IW, internal work index (IWI), and other data from 180 healthy adults and 144 patients with cardiovascular disease were measured.Main results. The CE of 180 healthy adults was 22.5 ± 2.2%, and the IWI was 22.3 ± 5.2 J l-1m-2. CE decreased with age, and the CE of the younger group (23.5 ± 1.9%) was larger than that of the older group (21.5 ± 1.9%),P < 0.01. The IWI increased with age, and the IWI of the younger group (19.0 ± 3.8 J l-1m-2) was smaller than that of the older group (24.8 ± 4.3 J l-1m-2),P < 0.01. There were no significant difference in CE (22.4 ± 2.2% and 22.6 ± 2.2%) or in the IWI (21.9 ± 5.1 J l-1m-2and 22.6 ± 5.2 J l-1m-2) between the male and female groups. The CEs and IWIs of patients with hypertension, coronary heart disease, and heart failure were 17.4 ± 2.4% and 41.8 ± 15.6 J l-1m-2, 17.6 ± 3.0% and 35.1 ± 10.4 J l-1m-2, and 15.8 ± 3.5% and 42.1 ± 15.6 J l-1m-2, respectively. These CEs were all smaller than that (21.6 ± 2.0%) of the healthy contrast groupP < 0.01, while the IWIs were all larger than that (24.6 ± 4.8 J l-1m-2) of the healthy contrast group,P < 0.01.Significance.The CEs and IWIs measured in this study may reflect physiological changes in healthy humans and pathogenic conditions in patients with cardiovascular disease.

13.
Hepatology ; 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33638162

RESUMO

The dynamic N6-methyladenosine (m6 A) mRNA modification is essential for acute stress response and cancer progression. Sublethal heat stress from insufficient radiofrequency ablation (IRFA) has been confirmed to promote hepatocellular carcinoma (HCC) progression, however, whether m6 A machinery is involved in IRFA-induced HCC recurrence remains unknown. Using IRFA HCC orthotopic mouse model, we detected higher level of m6 A reader YTHDF1 in the sublethal-heat-exposed transitional zone close to the ablation center than that in the farther area. In addition, we validated the increased m6 A modification and elevated YTHDF1 protein level in sublethal-heat-treated HCC cell lines, HCC patient-derived xenograft (PDX) mouse model and patients' HCC tissues. Functionally, gain-/loss-of function assays showed that YTHDF1 promotes HCC cell viability and metastasis. Knockdown of YTHDF1 drastically restrains the tumor metastasis evoked by sublethal heat treatment in tail vein injection lung metastasis and orthotopic HCC mouse models. Mechanistically, we found that sublethal heat treatment increases EGFR m6 A modification in the vicinity of 5'UTR region and promotes its binding with YTHDF1, which enhances the translation of EGFR mRNA. The sublethal heat induced up-regulation of EGFR level was further confirmed in IRFA HCC PDX mouse model and patients' tissues. Combination of YTHDF1 silencing and EGFR inhibition suppressed the malignancies of HCC cells synergically. CONCLUSION: The m6 A-YTHDF1-EGFR axis promotes HCC progression after IRFA, supporting the rationale for targeting m6 A machinery in combined with EGFR inhibitors to suppress HCC metastasis after RFA.

14.
Cancer Lett ; 503: 1-10, 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33444692

RESUMO

Ablative treatment evokes antitumor immunity, but knowledge on the emerging irreversible electroporation (IRE)-induced immunity in hepatocellular carcinoma (HCC) is limited. To investigate the immune effects induced by IRE and its role in preventing post-ablation HCC progression, a C57BL/6J mouse model bearing subcutaneous H22 hepatoma was employed. IRE treatment significantly suppresses HCC growth, and treated mice are tumor-free after secondary tumor injection and show increased splenic interferon-gamma (IFN-γ)+CD8+ T cells. Additionally, more CD8+ T and dendritic cells, but not CD4+ T, B or NK cells, infiltrate into peri-ablation zones after IRE at day 7. Depletion of CD8+ T cells induces local tumor regrowth and distant metastasis after IRE. Vaccination using IRE-processed H22 lysates prevents tumorigenesis in mice, suggesting a protective immune response. IRE also alleviates immunosuppression by reducing local and splenic Treg and PD-1+ T cells. Regarding mechanism, IRE induces cell necrosis and significant release of danger-associated molecular patterns including ATP, high mobility group box 1 and calreticulin that are pivotal to CD8+ T cell immunity. Together, IRE is a promising approach to evoke CD8+ T cell immunity, which help prevent post-ablation HCC progression.

15.
Eur Radiol ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33404697

RESUMO

OBJECTIVES: Restricted mean survival time (RMST) has been increasingly used to assess the treatment effect. We aimed to evaluate a treatment effect of radiofrequency ablation (RFA) versus liver transplantation (LT) and surgical resection (SR) for hepatocellular carcinoma (HCC) within Milan criteria by using an adjusted RMST. METHODS: A total of 7,218 HCC patients (RFA, 3,327; LT, 2,332; SR 1,523) within Milan criteria were eligible for this retrospectively study. The RMST using inverse probability of treatment weighting (IPTW) adjustment were applied to estimate the treatment effect between RFA and LT, RFA, and SR groups. RESULTS: The 3-, 5-, and 10-year IPTW-adjusted difference in RMST of OS for LT over RFA were + 4.5, + 12.4, and + 36.3 months, respectively. For SR versus RFA group, the survival benefit was + 2.3, + 6.1, and + 15.8 months at 3, 5, and 10 years, respectively. But the incremental survival benefit of SR over RFA was only half than that of LT over RFA. In the subgroup of solitary tumor ≤ 2 cm, the adjusted RMST of RFA versus SR was comparable with no statistical differences. Beyond that, in comparison with RFA, a notably greater efficacy of LT and SR was consistently across all subgroups with solitary HCC > 2.0 cm, AFP positive or negative, and fibrosis score 0-4 or 5-6. CONCLUSIONS: RMST provides a measure of absolute survival benefit at a specific time point. Using IPTW-adjusted RMST, we showed that the incremental survival benefit of SR over RFA was about half than that of LT over RFA. KEY POINTS: • The restricted mean survival time offers an intuitive, clinically meaningful interpretation to quantify the treatment effect than the hazard ratio. • Liver transplantation and surgical resection provided better overall survival compared to radiofrequency ablation for HCC patients within Milan criteria, but RFA and SR provide equivalent long-term overall survival for solitary HCC ≤ 2 cm. • The incremental survival benefit of surgical resection over radiofrequency ablation was only half than that of liver transplantation over radiofrequency ablation.

16.
Cell Rep ; 34(3): 108631, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33472079

RESUMO

Mitochondria not only serve as a platform for innate immune signaling transduction but also enhance immune responses by releasing mitochondrial DNA and RNA into the cytoplasm. However, whether mitochondrial matrix proteins could be liberated and involved in immune responses remains enigmatic. Here, we identify the mitochondrial protein ERA G-protein-like 1 (ERAL1) as a mitochondrial antiviral signaling protein (MAVS)-interacting protein by using proximity-based labeling technology. ERAL1 deficiency markedly reduces the downstream antiviral signaling triggered by RNA viruses. Moreover, ERAL1-deficient mice are more susceptible to lethality following RNA virus infection than wild-type mice. After virus infection, ERAL1 is released from mitochondria through the BAX/BAK pore. The cytosolic ERAL1 facilitates lysine 63 (K63)-linked ubiquitination of retinoicacid inducible gene-1 (RIG-I)/melanoma differentiation-associated gene 5 (MDA5) and promotes downstream MAVS polymerization, thus positively regulating antiviral responses.

17.
Eur Radiol ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33502556

RESUMO

OBJECTIVES: To evaluate the influence of pathological factors, such as fibrosis stage and histological grade, on the Liver Imaging Reporting and Data System (LI-RADS) v2017 category of contrast-enhanced ultrasonography (CEUS) in patients with high risk of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Between June 2015 and December 2016, 441 consecutive patients at high risk of HCC with 460 pathologically proven HCCs were enrolled in this retrospective study. All patients underwent a CEUS examination. The major features (arterial phase hyperenhancement, late and mild washout) were assessed, and LI-RADS categories were assigned according to CEUS LI-RADS v2017. CEUS LI-RADS categories and major features were compared in different histological grades and fibrosis stages. RESULTS: The CEUS LR-5 category was more frequently assigned in the low-grade group (151/280) than in the high-grade group (66/159) (p = 0.013), whereas the LR-TIV category was more frequently assigned in the high-grade group (36/159) than in the low-grade group (40/280) (p = 0.035). CEUS LI-RADS category was not significantly different among different fibrosis stages (p ≥ 0.05). Arterial phase hyperenhancement (APHE) and the hepatic fibrosis stage showed a significant correlation in HCCs ≥ 2 cm and the low-grade group (p = 0.027 and p = 0.003, respectively). No major features of CEUS LI-RADS showed statistically significant differences between the low- and high-grade groups (p ≥ 0.05). CONCLUSION: Hepatic fibrosis stage can influence APHE but showed no impact on the CEUS LI-RADS classification, whereas the histological grade of HCC influenced the LR-5 and LR-TIV categories. KEY POINTS: • Histological grade influenced CEUS LR-5 and LR-TIV category (p = 0.013 and p = 0.035 respectively). Low-grade HCCs occurred more frequently in LR-5 category whereas high-grade HCCs occurred more frequently in LR-TIV category. • Fibrosis stage shows significant influence on APHE on HCCs of the size ≥ 2 cm and low-grade group (p = 0.027 and p = 0.003, respectively). • Hepatic fibrosis stage and HCC histological grade exhibited limited impact on CEUS LI-RADS. CEUS LI-RADS may be feasible for diagnosing HCC in patients regardless of histological grade and fibrosis stage.

18.
Cell Host Microbe ; 29(2): 222-235.e4, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33388094

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an unprecedented public health crisis. Evidence suggests that SARS-CoV-2 infection causes dysregulation of the immune system. However, the unique signature of early immune responses remains elusive. We characterized the transcriptome of rhesus macaques and mice infected with SARS-CoV-2. Alarmin S100A8 was robustly induced in SARS-CoV-2-infected animal models as well as in COVID-19 patients. Paquinimod, a specific inhibitor of S100A8/A9, could rescue the pneumonia with substantial reduction of viral loads in SARS-CoV-2-infected mice. Remarkably, Paquinimod treatment resulted in almost 100% survival in a lethal model of mouse coronavirus infection using the mouse hepatitis virus (MHV). A group of neutrophils that contributes to the uncontrolled pathological damage and onset of COVID-19 was dramatically induced by coronavirus infection. Paquinimod treatment could reduce these neutrophils and regain anti-viral responses, unveiling key roles of S100A8/A9 and aberrant neutrophils in the pathogenesis of COVID-19, highlighting new opportunities for therapeutic intervention.


Assuntos
Alarminas/farmacologia , Antivirais/farmacologia , Neutrófilos/efeitos dos fármacos , /efeitos dos fármacos , Animais , /virologia , Modelos Animais de Doenças , Feminino , Humanos , Macaca mulatta , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neutrófilos/metabolismo , Transcriptoma , Carga Viral
19.
Radiology ; 298(3): 680-692, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33464183

RESUMO

Background Transarterial chemoembolization (TACE) is the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). It is unknown whether conventional TACE (cTACE) should be continued or abandoned after initial nonresponse for intermediate-stage HCC. The optimal number of sessions before abandoning cTACE remains debated. Purpose To define the number of sessions that patients who do not respond to treatment (hereafter, nonresponders, with stable disease [SD] or progressive disease [PD]) should undergo before abandoning cTACE. Materials and Methods Patients with intermediate-stage HCC and Child-Pugh A liver function who underwent consecutive cTACE sessions between January 2005 and December 2012 were retrospectively included from three centers. Radiologic response rate to each session and its correlation with overall survival were evaluated. Response was assessed by modified Response Evaluation Criteria in Solid Tumors. A nomogram constructed by using tumor size, tumor capsule, and α-fetoprotein to predict patients who responded to treatment (hereafter, responders) was validated with sensitivity and specificity. Results This study evaluated 4154 patients (mean age, 58 years ± 6 [standard deviation]; 3777 men; primary cohort, 3442 patients [mean age, 58 years ± 6; 3129 men]; validation cohort, 712 patients [mean age, 58 years ± 7; 648 men]). Response rate to first cTACE was 35.6% (1227 of 3442, primary cohort) and 36.7% (261 of 712, validation cohort). For patients with SD who were nonresponders to first cTACE, the response rates after second cTACE were 46.1% (719 of 1560) and 48.4% (147 of 304); for patients with SD who were nonresponders to the second cTACE session, the response rates after the third cTACE session were 58.3% (591 of 1014) and 48.5% (98 of 202). For patients with SD who were nonresponders to third, fourth, and fifth cTACE sessions, response rates after fourth, fifth, and sixth cTACE sessions were less than 10%. All response rates in patients with PD who were nonresponders to the next cTACE were less than 5%. Responders to first, second, and third cTACE had higher 5-year overall survival than nonresponders (all P < .001) but responders to the fourth cTACE did not (P = .21). The sensitivity and specificity of a nomogram predicted responders to third cTACE: 75.0% and 79.4% (internal validation) and 78.6% and 87.0% (external validation), respectively. Conclusion Three sessions were recommended before abandoning conventional transarterial embolization (cTACE) for intermediate-stage hepatocellular carcinoma. The nomogram developed in this study identified responders to third cTACE. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Georgiades in this issue.

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