Non-invasive prediction of hepatocellular carcinoma development using serum fibrosis marker in chronic hepatitis C patients

Background

The FIB-4 index is a simple formula to predict liver fibrosis. This study aimed to evaluate the utility of the FIB-4 index and associated time-course changes as a predictor of hepatocellular carcinoma (HCC) development.

Methods

A total of 171 chronic hepatitis C patients who underwent paired liver biopsies and 875 patients who underwent a single liver biopsy (validation group) were investigated during mean follow-up periods of 6.4 and 5.9 years, respectively. All patients had received interferon therapy and had not achieved a sustained virological response. Factors associated with HCC development were analyzed in these patients.

Results

HCC developed in 30 patients in the paired biopsy group and 89 patients in the validation group. Univariate analysis demonstrated that the FIB-4 index >3.25 and change in the FIB-4 index per year (ΔFIB-4/year) ≥0.3 were predictive factors for HCC development in both groups. Multivariate analysis in the combined population revealed that these two factors were independent. The hazard ratio (HR) for the FIB-4 index >3.25 was 2.7 (p < 0.001) and ΔFIB-4/year ≥0.3 was 1.8 (p = 0.003). Patients with a FIB-4 index >3.25 and a ΔFIB-4/year ≥0.3 were defined as high risk, and those with a FIB-4 index ≤3.25 and a ΔFIB-4/year <0.3 were defined as low risk. The HR of HCC development in patients at high risk was 7.3 (95 % confidence interval 4.3–12.5, p < 0.001).

Conclusions

It was possible to define a group at high risk of developing HCC by intermittently measuring the FIB-4 index and considering time-course changes in this index.     

Relationship between surrounding tissue morphology and directional collective migration of the posterior lateral line primordium in zebrafish

Collective cell migration, in which cells assemble and move together, is an essential process in embryonic development, wound healing and cancer metastasis. Chemokine signaling guides cell assemblies to their destinations. In zebrafish posterior lateral line primordium (PLLP), a model system for collective cell migration, it has been proposed that the chemokine ligand Cxcl12a secreted from muscle pioneer cells (MPs) and muscle fast fibers (MFFs), which are distributed along with the horizontal midline, binds to the receptor Cxcr4b in PLLP and that Cxcl12a–Cxcr4b signaling guides the anterior‐to‐posterior migration of PLLP along the horizontal midline. However, how the surrounding tissues affect PLLP migration remains to be elucidated. Here, we investigated the relationship between the PLLP and the surrounding tissues and found that a furrow between the dorsal and ventral myotomes is generated by Sonic hedgehog (Shh) signaling‐dependent MP and MFF differentiation and that the PLLP migrates in this furrow. When transient inhibition of Shh signaling impaired both the furrow formation and differentiation of cxcl12a‐expressing MPs/MFFs, directional PLLP migration was severely perturbed. Furthermore, when differentiated MPs and MFFs were ablated by femtosecond laser irradiations, the furrow remained and PLLP migration was relatively unaffected. These results suggest that the furrow formation between the dorsal and ventral myotomes is associated with the migratory behavior of PLLP.     

Short- and long-term clinical effects of primary directional coronary atherectomy for acute myocardial infarction

We performed primary directional coronary atherectomy (DCA) without antecedent thrombolytic therapy in 21 of 67 patients with acute myocardial infarction within 24 hr of onset between June 1993–March 1994. Reperfusion with primary DCA was successful in 18 patients (85.7%, group D). Results were compared with those of primary balloon angioplasty patients treated between June 1992–May 1993 (group P). Minimum lumen diameter (MLD) values both immediately after reperfusion and in predischarge angiograms were significantly larger in group D than in group P, but were similar in late follow-up angiograms. Although a larger MLD in group D than in group P contributed to the prevention of reocclusion of the coronary artery before discharge in DCA patients, a high rate of restenosis at late follow-up canceled the beneficial effects of primary DCA. © 1996 Wiley-Liss, Inc.     

Identification of novel prognostic factors focusing on clinical outcomes in patients with non-small cell lung cancer after stereotactic body radiotherapy

Stereotactic body radiotherapy (SBRT) has attracted extensive attention as an effective treatment for patients with early-stage non-small cell lung cancer. However, the factors affecting prognosis after SBRT have not been fully elucidated. The aim of the present study was to investigate the prognostic factors associated with overall survival (OS) and local control (LC) after SBRT. Between March 2003 and March 2020, 497 patients with primary or oligo-metastatic lung cancer who underwent SBRT treatment were retrospectively reviewed. Univariate analysis was performed against various factors related to patient and tumor characteristics using Kaplan-Meier method. Furthermore, the factors with statistically significant differences identified via univariate analysis underwent a stratified Cox proportional hazard regression analysis. The median follow-up period for all patients was 26.17 months (range, 0.36-194.37), and the 5-year OS and LC rates were 66.3 and 86.0%, respectively. Multivariate analysis showed that surfactant protein-D (SP-D), tumor CT values (TCTV) and iodine density values (IDV) were independent prognostic factors for OS, and histology, TCTV and IDV were for LC. Although histology was not selected as a prognostic factor related to OS, it was indicated that patients with squamous cell carcinoma were associated with the SP-D high group compared with the SP-D normal group. In addition, TCTV was correlated to water density values, which tended to decrease with increasing IDV. From these findings, SP-D and TCTV were identified as potential new candidate prognostic factors after SBRT, and it is possible that combining SP-D and histology, and TCTV and IDV may improve the accuracy of prognostic prediction.     

An autopsy case of Balamuthia mandrillaris amoebic encephalitis,a rare emerging infectious disease,with a brief review of the cases reported in Japan

Balamuthia mandrillaris is an amoeba found in fresh water and soil that causes granulomatous amoebic encephalitis. We report herein an autopsy case of B. mandrillaris amoebic encephalitis, which was definitely diagnosed by PCR. An 81‐year‐old man, who had Sjögren's syndrome, manifested drowsiness 2 months before his death with progressive deterioration. Neuroimaging demonstrated foci of T2‐ and fluid‐attenuated inversion recovery high and T1 low‐intensity with irregular post‐contrast ring enhancement in the cerebral hemisphere, thalamus and midbrain. Pathologically, multiple hemorrhagic and necrotic lesions were found in the cerebrum, thalamus, midbrain, pons, medulla and cerebellum, which were characterized by liquefactive necrosis, marked edema, hemorrhage and necrotizing vasculitis associated with the perivascular accumulation of amoebic trophozoites, a few cysts, and the infiltration of numerous neutrophils and microglia/macrophages. The trophozoites were ovoid or round, 10–60 μm in diameter, and they showed foamy cytoplasm and a round nucleus with small karyosome in the center. The PCR and immunohistochemistry from paraffin‐embedded brain specimens revealed angioinvasive encephalitis due to B. mandrillaris. Human cases of B. mandrillaris brain infection are rare in Japan, with only a few brief reports in the literature.     

Clinical features of emergency electrocardiography in patients with acute myocardial infarction caused by left main trunk obstruction.

BACKGROUND: To diagnose left main trunk (LMT) infarction by 12-lead standard electrocardiogram (ECG) is an important emergency technique, but the features in LMT infarctions have not been clarified. METHODS AND RESULTS: The study enrolled 140 subjects who were divided into 4 groups according to the location of the culprit artery: 35 with LMT, 35 with left anterior descending artery (LAD), 35 with right coronary artery and 35 with left circumflex artery. Various parameters obtained from the ECGs were analyzed. Average QTc interval (0.51 +/- 0.06 s) in LMT group was markedly longer than that in the 3 other groups. Average QRS axis (-10 +/- 77 degrees) in LMT infarction showed a remarkable left deviation. ST-segment elevation in lead aVR occurred in 28 patients (80.0%) in the LMT group. The ECG features of the LMT group could be classified into 2 main groups: right bundle branch block (RBBB) with a marked left axis deviation (RBBB + LADEV type) and ST-segment elevation in leads V2-5, I and aVL without abnormal axis deviation (LAD type). CONCLUSION: Either ST-segment elevation in lead aVR and marked prolongation of both the QRS width and QTc interval with a prominent abnormal axis deviation or ST-segment elevation in the broad anterior precordial lead with a normal QRS axis strongly suggests LMT infarction.