Post-treatment cell-free DNA as a predictive biomarker in molecular-targeted therapy of hepatocellular carcinoma

Journal of Gastroenterology - Liquid biopsies, particularly those involving circulating tumor DNA (ctDNA), are rapidly emerging as a non-invasive alternative to tumor biopsies. However, clinical...     

Prospective study of a high-intensity interferon-alpha regimen for chronic hepatitis C virus genotype 1b infection

BACKGROUND/AIMS: To evaluate efficacy of high-intensity interferon administration for patients chronically infected with hepatitis C virus genotype 1b, we administered interferon-alpha with different regimens according to viral load. METHODOLOGY: Eighty-eight patients with hepatitis C virus genotype 1b were treated with recombinant interferon alpha-2b. The 70 patients with pretreatment hepatitis C virus RNA concentration > or = 10(6) copies/mL were given 10(7) units of interferon daily for the first 8 weeks and then three times weekly for 16 weeks (group A). The 18 patients with smaller pretreatment hepatitis C virus RNA concentration received the same dose daily for the first 2 weeks and then three times weekly for 14 weeks (group B). We analyzed tolerance of therapy, responses, and long-term outcome in the two groups. RESULTS: Fifteen of 70 patients (21.4%) in group A could not continue treatment and dropped out, while all patients in group B completed the entire course of therapy. The rate of sustained response in group A was 10.0%, being significantly less than in group B (72.2%; p < 0.0001). However, 12 patients in group A showed a biochemical sustained response despite presence of viremia. Long-term outcome did not differ between groups. CONCLUSIONS: Many patients could not tolerate high-intensity therapy, which showed the limitation of tolerance of patients receiving interferon monotherapy. High-intensity therapy could not improve eradication of hepatitis C virus in patients with high pretreatment hepatitis C virus RNA concentration. However, this therapy may increase the rate of sustained biochemical response, improving long-term outcome.     

CD13/aminopeptidase N, a novel chemoattractant for T lymphocytes in pulmonary sarcoidosis

CD13/aminopeptidase N (E.C.3.4.11.2) is an ectoenzyme located in the outer membrane of a variety of cells. Because aminopeptidase expression was shown to be upregulated by a Th1-related cytokine, IFN-gamma, we examined here the significance of CD13/aminopeptidase N in pulmonary sarcoidosis. The activity of aminopeptidase in bronchoalveolar lavage fluid (BALF) was significantly higher in patients with sarcoidosis than in normal volunteers (NV) and control patients (CP). The activity significantly correlated with lymphocyte percentages and the ratio of CD4+ to CD8+ T lymphocytes in the BALF, and was higher in patients with sarcoidosis with parenchymal involvement than in those without the involvement. CD13/aminopeptidase N protein, which has a molecular mass of approximately 150 kD, was detectable in alveolar macrophages (AM) from patients with sarcoidosis at higher levels than in those from NV. CD13/aminopeptidase N induced in vitro chemotactic migration of human lymphocytes in a concentration range of 10(-)(5) to 10(-)(1) U/ml. The chemotactic activity was greater for CD4+ T lymphocytes than for CD8+ T lymphocytes. The enzymatic activity of CD13/aminopeptidase N was responsible for the chemotactic activity because bestatin, an inhibitor of CD13/aminopeptidase N, abolished the chemotactic activity. Higher chemotactic activity for lymphocytes was detected in the BALF from patients with sarcoidosis than in that from NV, and the activity was significantly decreased by treatment with bestatin. This study indicates that CD13/ aminopeptidase N expressed in AM may have a role in T-lymphocyte involvement in the sarcoid lung and the pathogenesis of alveolitis in this disorder.     

Correction to: Detection of acute rib fractures on CT images with convolutional neural networks: effect of location and type of fracture and reader’s experience

Emergency Radiology -     

Tentative diagnostic criteria and disease severity classification for Castleman disease: A report of the research group on Castleman disease in Japan

Objectives: To determine the tentative diagnostic criteria and disease severity classification for Castleman disease (CD) and describe the clinical and pathologic features among human herpesvirus 8 (HHV-8) negative idiopathic multicentric CD (iMCD) in the Japanese population.

Methods: We established the working groups for the research of CD in Japan and had meetings to discuss and define the tentative diagnostic criteria and disease severity classification for CD. We subsequently analyzed 142 patients classified into iMCD by using the nationwide Japanese patient registry.

Results: We proposed the preliminary diagnostic criteria and disease severity classification for CD based on our discussion. In addition, we made a proposal for the disease activity score. We identified clinical and pathological features of patients with iMCD diagnosed by these diagnostic criteria. In the disease severity classification, 37, 33 and 30% patients were categorized into mild, moderate and severe diseases, respectively.

Conclusion: This is the first proposal for diagnosis and classification of CD by the Japanese group. Further studies are required to validate whether they can distinguish CD from other inflammatory diseases and to determine their sensitivity and specificity.     

Increased incidence of autoantibodies to interleukin-1a in rheumatoid arthritis with interstitial lung disease

OBJECTIVE: To clarify the clinical significance of autoantibodies (auto-Ab) to interleukin-1alpha (IL-1alpha) in rheumatoid arthritis (RA) with interstitial lung disease (ILD), we examined the IL-1alpha auto-Ab level in serum of patients with RA with/without ILD. METHODOLOGY: We investigated the level of IL-1alpha auto-Ab in serum of 70 patients with RA with/without ILD and 40 control patients (CP). Levels of IL-1alpha auto-Ab were measured by radioimmunoassay, and serum was regarded as IL-1alpha auto-Ab positive at an auto-Ab level of more than 5 ng/mL. RESULTS: Interleukin-1alpha auto-Ab was detected in the serum of 30 out of 70 RA patients (42.9%), and six out of 40 CP (15%) (P < 0.05). Interleukin-1alpha auto-Ab were detected in the serum of 18 out of 32 patients with RA with ILD (56.2%) and 12 out of 38 patients with RA without ILD (31.5%). The positive rate of these autoantibodies in RA with ILD was significantly higher than that in RA without ILD (P < 0.05). Although C-reactive protein, immunoglobulin G, rheumatoid factor and rheumatoid arthritis particle agglutination levels in serum from patients with RA with ILD were not significantly different between the IL-1alpha auto-Ab-positive and -negative groups, the lactate dehydrogenase level (LDH) and AaDO, in the IL-1alpha auto-Ab-positive group were significantly higher than those in the negative group (LDH: P < 0.001, AaDO2: P < 0.05). CONCLUSION: These results suggest that IL-1alpha auto-Ab are generated in response to the immunoinflammatory process of ILD in RA, and these autoantibodies may neutralize and regulate the IL-1alpha activity.     

Gore-Tex jump graft for portal vein thrombosis following living donor liver transplantation

Portal vein thrombosis is a rare surgical complication following liver transplantation, which remains a cause of graft loss and death. We describe here the treatment of portal vein thrombosis following living donor liver transplantation using an extended left lobe graft. The patient was treated with a Gore-Tex vascular jump graft extra-anatomically interposed between the recipient superior mesenteric vein and the donor umbilical vein. This technique allowed the hepatic hilum to be left untouched and supplied suitable blood flow to the hepatic allograft. Our experience suggests that this innovative technical solution can be helpful in the effort to rescue cases of hepatic allograft with vascular complications.     

Predictors and Clinical Impact of Prosthesis-Patient Mismatch After Self-Expandable TAVR in Small Annuli

ObjectivesThe aim of this study was to define predictors of prosthesis-patient mismatch (PPM) and its impact on mortality after transcatheter aortic valve replacement (TAVR) with self-expandable valves (SEVs) in patients with small annuli.BackgroundTAVR seems to reduce the risk for PPM compared with surgical aortic valve replacement, especially in patients with small aortic annuli. Nevertheless, predictors and impact of PPM in this population have not been clarified yet.MethodsPredictors of PPM and all-cause mortality were investigated using multivariable logistic regression analysis from the cohort of the TAVI-SMALL (International Multicenter Registry to Evaluate the Performance of Self-Expandable Valves in Small Aortic Annuli) registry, which included patients with severe aortic stenosis and small annuli (annular perimeter <72 mm or area <400 mm² on computed tomography) treated with transcatheter SEVs: 445 patients with (n = 129) and without (n = 316) PPM were enrolled.ResultsIntra-annular valves conferred increased risk for PPM (odds ratio [OR]: 2.36; 95% confidence interval [CI]: 1.16 to 4.81), while post-dilation (OR: 0.46; 95% CI: 0.25–0.84) and valve oversizing (OR: 0.53; 95% CI: 0.28–1.00) seemed to protect against PPM occurrence. At a median follow-up of 354 days, patients with severe PPM, but not those with moderate PPM, had a higher all-cause mortality rate compared with those without PPM (log-rank p = 0.008). Multivariable Cox regression confirmed severe PPM as an independent predictor of all-cause mortality (hazard ratio: 4.27; 95% CI: 1.34 to 13.6).ConclusionsAmong patients with aortic stenosis and small aortic annuli undergoing transcatheter SEV implantation, use of intra-annular valves yielded higher risk for PPM; conversely, post-dilation and valve oversizing protected against PPM occurrence. Severe PPM was independently associated with all-cause mortality.