Analysis of prognosis and background liver disease in non-advanced hepatocellular carcinoma in two decades.

BACKGROUND/AIM: Antiviral hepatitis and systemic therapies for hepatocellular carcinoma (HCC) remarkably progressed in the recent 10 years. This study aimed to reveal the actual transition and changes in the prognosis and background liver disease in non-advanced HCC in the past 20 years. METHODS: This retrospectively recruited 566 patients who were diagnosed with non-advanced HCC from February 2002 to February 2022. The prognosis was analyzed by subdividing according to the diagnosis date (period I: February 2002-April 2009 and period Ⅱ: May 2009-February 2022). RESULTS: Patients in period II (n = 351) were significantly older, with lower albumin-bilirubin (ALBI) scores and alpha-fetoprotein (AFP) and more anti-viral therapy, systemic therapy, and hepatic arterial infusion chemotherapy as compared with those in period I (n = 215). The etiology ratio of the background liver disease revealed decreased hepatitis C virus from 70.6% to 49.0% and increased non-B, non-C from 17.7% to 39.9% from periods I to Ⅱ. The multivariate analysis revealed older age and higher ALBI score in Barcelona Clinic Liver Cancer (BCLC) 0/A stage, AFP of >20 ng/mL, and higher ALBI score in BCLC B stage as independent prognosis factors. Fine-Gray competing risk model analysis revealed that liver-related deaths significantly decreased in period II as compared to period I, especially for BCLC stage 0/A (HR: 0.656; 95%CI: 0.442-0.972, P = 0.036). CONCLUSION: The characteristics of patients with non-advanced HCC have changed over time. Appropriate background liver management led to better liver-related prognoses in BCLC 0/A.

A case of vaccine-associated myocarditis following pneumococcal immunization leading to acute mitral regurgitation.

Vaccine-associated myocarditis (VAM) is a rare entity but can result in potentially serious sequelae if left untreated. However, the mechanisms of the complications of VAM and its treatment remain unclear. Herein, we report the first case of VAM related to pneumococcal immunization, presenting as a local and systemic inflammatory reaction, in which the patient developed significant secondary mitral regurgitation, resulting in acute heart failure. Finally, the patient recovered completely following corticosteroid treatment. This case highlights the value of cardiac magnetic resonance and the pitfall of endomyocardial biopsy in establishing the definitive diagnosis of VAM and emphasizes the importance of optimal management in understanding the mechanism and instituting the treatment for secondary mitral regurgitation caused by VAM.

Can Deep Learning-Based Volumetric Analysis Predict Oxygen Demand Increase in Patients with COVID-19 Pneumonia?

Background and Objectives: This study aimed to investigate whether predictive indicators for the deterioration of respiratory status can be derived from the deep learning data analysis of initial chest computed tomography (CT) scans of patients with coronavirus disease 2019 (COVID-19). Materials and Methods: Out of 117 CT scans of 75 patients with COVID-19 admitted to our hospital between April and June 2020, we retrospectively analyzed 79 CT scans that had a definite time of onset and were performed prior to any medication intervention. Patients were grouped according to the presence or absence of increased oxygen demand after CT scan. Quantitative volume data of lung opacity were measured automatically using a deep learning-based image analysis system. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of the opacity volume data were calculated to evaluate the accuracy of the system in predicting the deterioration of respiratory status. Results: All 79 CT scans were included (median age, 62 years (interquartile range, 46-77 years); 56 (70.9%) were male. The volume of opacity was significantly higher for the increased oxygen demand group than for the nonincreased oxygen demand group (585.3 vs. 132.8 mL, p < 0.001). The sensitivity, specificity, and AUC were 76.5%, 68.2%, and 0.737, respectively, in the prediction of increased oxygen demand. Conclusion: Deep learning-based quantitative analysis of the affected lung volume in the initial CT scans of patients with COVID-19 can predict the deterioration of respiratory status to improve treatment and resource management.

Phase I clinical study of NMB58, a novel positron emission tomography (PET)-myocardial perfusion imaging tracer, conducted to evaluate its safety and pharmacokinetics in Japanese healthy adult males.

OBJECTIVES: NMB58 is a novel positron emission tomography (PET) tracer containing flurpiridaz as an active ingredient and available as a myocardial perfusion imaging tracer that targets mitochondrial complex 1. A phase I clinical study of NMB58 was conducted to evaluate its safety and pharmacokinetics in healthy volunteers. METHODS: Ten healthy Japanese volunteers received bolus injection of NMB58 (111-167 MBq) intravenously and underwent imaging studies at rest on day 1. Of these subjects, 5 (day 2 cohort 1; exercise stress) and 5 (day 2 cohort 2; pharmacological stress) similarly underwent stress imaging studies on day 2. The safety of NMB58 was evaluated through monitoring of signs/symptoms, electrocardiography, vital signs, and laboratory examinations at baseline and several time points during 3 days. Sequential whole-body positron emission tomography-computed tomography (PET/CT) scan data were acquired for up to 5-h post-injection, with venous blood and urine samples collected for up to 8-h post-injection. Based on the results of the biodistribution study, the absorbed radiation dose (Rad) was estimated by the Medical Internal Radiation Dose method. RESULTS: On day 1, the kidneys were shown to have the highest Rad, followed by the myocardium. On day 2, the myocardium was shown to have the highest Rad, followed by the kidneys. The mean effective doses (EDs) per unit activity administered were 0.021, 0.017 and 0.021 mSv/MBq for overall subjects (day 1), day 2 cohort 1 and day 2 cohort 2, respectively. The estimated exposure dose of NMB58 was similar to or lower than those of radiotracers currently approved for clinical use, including 18F-Fludeoxyglucose. Biodistribution results indicated that NMB58 distributed to the myocardium exhibited high and sustained retention after administration. The cumulative urinary radioactivity excretion rate was shown to be 6.9, 2.3%, and 8.0% of the injected dose in overall subjects (day 1), day 2 cohort 1 and day 2 cohort 2. There were no drug-related adverse events, and the tracer was well tolerated in all subjects. CONCLUSIONS: Based on radiation dosimetry, biodistribution, and safety evaluations, NMB58 was found to be a suitable tracer for clinical use in PET myocardial perfusion imaging during exercise or pharmacological stress.

Late-onset pneumothorax in a COVID-19 patient treated with ventilation and ECMO: A case report and literature review.

Coronavirus disease 2019 (COVID-19) has become a major threat to public health since the outbreak in Wuhan in 2019. Chest computed tomography is recommended for COVID-19 cases for evaluation and follow up of pneumonia and related complication. We report the case of a 66-year-old man with underlying hypertension and a history of smoking 76 packs a year; he was frequently monitored by computed tomography for pulmonary changes during the period from early symptom onset to death. Furthermore, he developed a pneumothorax during the course. The occurrence of pneumothorax in COVID-19 patients is not common, and there have been only a few previous reports. This is a valuable case of pneumothorax in a patient with COVID-19 treated with a ventilator and extracorporeal membrane oxygenation. This case and previous reports suggest that pneumothorax occurs in COVID-19 with a relatively late onset (3-8 weeks). Long-term pneumonia morbidity, steroid therapy, positive pressure ventilation, and extracorporeal membrane oxygenation can cause pneumothorax, leading to capillary and alveolar damage.

Evaluation of the Usefulness of CO-RADS for Chest CT in Patients Suspected of Having COVID-19.

The purpose of this study was to use the Coronavirus Disease 2019 (COVID-19) Reporting and Data System (CO-RADS) to evaluate the chest computed tomography (CT) images of patients suspected of having COVID-19, and to investigate its diagnostic performance and interobserver agreement. The Dutch Radiological Society developed CO-RADS as a diagnostic indicator for assessing suspicion of lung involvement of COVID-19 on a scale of 1 (very low) to 5 (very high). We investigated retrospectively 154 adult patients with clinically suspected COVID-19, between April and June 2020, who underwent chest CT and reverse transcription-polymerase chain reaction (RT-PCR). The patients' average age was 61.3 years (range, 21-93), 101 were male, and 76 were RT-PCR positive. Using CO-RADS, four radiologists evaluated the chest CT images. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated. Interobserver agreement was calculated using the intraclass correlation coefficient (ICC) by comparing the individual reader's score to the median of the remaining three radiologists. The average sensitivity was 87.8% (range, 80.2-93.4%), specificity was 66.4% (range, 51.3-84.5%), and AUC was 0.859 (range, 0.847-0.881); there was no significant difference between the readers (p > 0.200). In 325 (52.8%) of 616 observations, there was absolute agreement among observers. The average ICC of readers was 0.840 (range, 0.800-0.874; p < 0.001). CO-RADS is a categorical taxonomic evaluation scheme for COVID-19 pneumonia, using chest CT images, that provides outstanding performance and from substantial to almost perfect interobserver agreement for predicting COVID-19.

Paravesical space arteriovenous malformation as a specific subgroup of pelvic vascular anomaly: a case series and review of literature.

Treatment of pelvic arteriovenous malformations (AVMs) is frequently challenging because of the complex structures and anatomical diversity among cases. We present a case series of six patients with pelvic AVMs. All patients had a similar anatomical structure consisting of multiple feeders from the unilateral internal iliac artery, collecting into a dilated venous sac in the unilateral paravesical space and draining into a single outflow, eventually joining the pre-prostatic vein or internal iliac vein. Five among these patients were successfully treated by catheter-directed embolo-sclerotherapy. In addition to our six cases, we identified six previous case reports of pelvic AVM with similar anatomical characteristics. Herein, we summarize the clinical and anatomical features of these 12 paravesical AVM cases. In all cases, the patients were men; the AVM was predominantly located at the right paravesical space and demonstrated good therapeutic effect of catheter-directed embolosclerotherapy. These paravesical AVMs may constitute a new subgroup of pelvic vascular anomalies with the same etiology that are treatable by adequate catheter intervention.

Characterization of transgene expression in adenoviral vector-based HIV-1 vaccine candidates.

Recombinant adenovirus vectors have been extensively used in gene therapy clinical studies. More recently, the capability of inducing potent cell-mediated and humoral immunity has made these vectors equally attractive candidates for prophylactic or therapeutic vaccine applications. Merck and Co., Inc., developed HIV-1 vaccine candidates based on adenovirus serotype 5 (Ad5) vectors in which the E1 gene, a critical component for adenovirus replication, was replaced by the cytomegalovirus immediate/early promoter, followed by mutated versions of the HIV-1 gag, pol or nef genes (constructs referred to as MRKAd5gag, MRKAd5pol and MRKAd5nef, respectively). Vaccine performance was evaluated in vitro in a novel assay that measures the level of transgene expression in non-permissive A549 cells. Various combinations of vectors were studied. The results indicate that the vaccine induces a dose-dependent expression of the HIV-1 transgenes in vitro. Furthermore, the gag, pol, and nef transgenes are expressed differentially in A549 cells in an MOI-dependent and formulation-dependent manner, yielding an unexpected enhancement of protein expression in trivalent vs. monovalent formulations. Our data suggest that the presence of additional virus in multivalent formulations increases individual transgene expression in A549 cells, even when the amount of DNA encoding the gene of interest remains constant. This enhancement appears to be controlled at the transcriptional level and related to both the total amount of virus and the combination of transgenes present in the formulation.

Varicella-zoster virus infection induces autophagy in both cultured cells and human skin vesicles.

When grown in cultured cells, varicella-zoster virus (VZV) forms many aberrant light particles and produces low titers. Various studies have explored the reasons for such a phenotype and have pointed to impaired expression of specific late genes and at lysosomal targeting of egressing virions as possible causes. In the studies presented here, we report that the autophagic degradation pathway was induced at late time points after VZV infection of cultured cells, as documented by immunoblot analysis of the cellular proteins LC3B and p62/SQSTM1, along with electron microscopy analysis, which demonstrated the presence of both early autophagosomes and late autophagic compartments. Autophagy was induced in infected cells even in the presence of phosphonoacetic acid, an inhibitor of viral late gene expression, thus suggesting that accumulation of immediate-early and early viral gene products might be the major stimulus for its induction. We also showed that the autophagic response was not dependent on a specific cell substrate, virus strain, or type of inoculum. Finally, using immunofluorescence imaging, we demonstrated autophagosome-specific staining in human zoster vesicles but not in normal skin. Thus, our results document that this innate immune response pathway is a component of the VZV infectious cycle in both cultured cells and the human skin vesicle, the final site of virion formation in the infected human host.