Noninvasive in vivo liver fibrosis evaluation using supersonic shear imaging: a clinical study on 113 hepatitis C virus patients

Supersonic shear imaging (SSI) has recently been demonstrated to be a repeatable and reproducible transient bidimensional elastography technique. We report a prospective clinical evaluation of the performances of SSI for liver fibrosis evaluation in 113 patients with hepatitis C virus (HCV) and a comparison with FibroScan (FS). Liver elasticity values using SSI and FS ranged from 4.50 kPa to 33.96 kPa and from 2.60 kPa to 46.50 kPa, respectively. Analysis of variance (ANOVA) shows a good agreement between fibrosis staging and elasticity assessment using SSI and FS (p < 10⁻⁵). The areas under receiver operating characteristic (ROC) curves for elasticity values assessed from SSI were 0.948, 0.962 and 0.968 for patients with predicted fibrosis levels F ≥ 2, F ≥ 3 and F = 4, respectively. These values are compared with FS area under the receiver operating characteristic curve (AUROC) of 0.846, 0.857 and 0.940, respectively. This comparison between ROC curves is particularly significant for mild and intermediate fibrosis levels. SSI appears to be a fast, simple and reliable method for noninvasive liver fibrosis evaluation.     

Early stages of schizophrenia, challenges and prospects

Despite a relatively extensive treatment armamentarium, the evolution of schizophrenic patients overall remains unfavourable. Early treatment is essential and influences the prognosis. Facilitating access to care through the creation of specialised assessment centres to complement the current system of care is one of the possible avenues for improvement.     

BRCA1/2 mutation analysis in 41 ovarian cell lines reveals only one functionally deleterious BRCA1 mutation

Mutations in BRCA1/2 increase the risk of developing breast and ovarian cancer. Germline BRCA1/2 mutations occur in 8.6–13.7% of unselected epithelial ovarian cancers, somatic mutations are also frequent. BRCA1/2 mutated or dysfunctional cells may be sensitive to PARP inhibition by synthetic lethality. The aim of this study is to comprehensively characterise the BRCA1/2 status of a large panel of ovarian cancer cell lines available to the research community to assist in biomarker studies of novel drugs and in particular of PARP inhibitors.The BRCA1/2 genes were sequenced in 41 ovarian cell lines, mRNA expression of BRCA1/2 and gene methylation status of BRCA1 was also examined. The cytotoxicity of PARP inhibitors olaparib and veliparib was examined in 20 cell lines.The cell line SNU-251 has a deleterious BRCA1 mutation at 5564G > A, and is the only deleterious BRCA1/2 mutant in the panel. Two cell lines (UPN-251 and PEO1) had deleterious mutations as well as additional reversion mutations that restored the protein functionality. Heterozygous mutations in BRCA1/2 were relatively common, found in 14.6% of cell lines. BRCA1 was methylated in two cell lines (OVCAR8, A1847) and there was a corresponding decrease in gene expression. The BRCA1 methylated cell lines were more sensitive to PARP inhibition than wild-type cells. The SNU-251 deleterious mutant was more sensitive to PARP inhibition, but only in a long-term exposure to correct for its slow growth rate. Cell lines derived from metastatic disease are significantly more resistant to veliparib (2.0 fold p = 0.03) compared to those derived from primary tumours. Resistance to olaparib and veliparib was correlated Pearsons-R 0.5393, p = 0.0311.The incidence of BRCA1/2 deleterious mutations 1/41 cell lines derived from 33 different patients (3.0%) is much lower than the population incidence. The reversion mutations and high frequency of heterozygous mutations suggest that there is a selective pressure against BRCA1/2 in cell culture similar to the selective pressure seen in the clinic after treatment with chemotherapy. PARP inhibitors may be useful in patients with BRCA1 deleterious mutations or gene methylation.     

Whole-body muscle MRI to detect myopathies in non-extrapyramidal bent spine syndrome

Objective

Bent spine syndrome (BSS), defined as an abnormal forward flexion of the trunk resolving in supine position, is usually related to parkinsonism, but can also be encountered in myopathies. This study evaluates whole-body muscle MRI (WB-mMRI) as a tool for detecting underlying myopathy in non-extrapyramidal BSS.

Materials and methods

Forty-three patients (90 % women; 53–86 years old) with a non-extrapyramidal BSS were prospectively included. All underwent a 1.5-T WB-mMRI and a nerve conduction study. Muscle biopsy was performed if a myopathy could not be eliminated based on clinical examination and all tests. Systematic MRI interpretation focused on peripheral and axial muscle injury; spinal posture and incidental findings were also reported.

Results

WB-mMRI was completed for all patients, with 13 muscle biopsies ultimately needed and myopathy revealed as the final etiological diagnosis in five cases (12 %). All biopsy-proven myopathies were detected by the WB-mMRI. Relevant incidental MRI findings were made in seven patients.

Conclusions

This study supports WB-mMRI as a sensitive and feasible tool for detecting myopathy in BSS patients. Associated with electroneuromyography, it can better indicate when a muscle biopsy is needed and guide it when required. Rigorous radiological interpretation is mandatory, so as not to miss incidental findings of clinical consequence.     

Assessment of water enema computed tomography: an effective imaging technique for the diagnosis of colon cancer

Aim

The aim of this study was to assess the accuracy of water enema computed tomography (WECT) for the diagnosis of colon cancer.

Methods

A total of 191 patients referred for clinically suspected colon cancer were prospectively evaluated by WECT in a multicenter trial. Examination was contrast enhanced helical CT after colon filling through a rectal tube. For all the cases, final diagnosis was obtained by colonoscopy and/or surgery. CT data were interpreted both locally and at a centralized site by a specialized and general radiologist.

Results

Seventy-one patients were diagnosed with colon cancer. Overall, WECT sensitivity and specificity were 98.6 and 95.0%, respectively. Positive and negative predictive values were 92.1 and 99.1%, respectively. In a subgroup of 33 patients with unclean bowel, the sensitivity and specificity of WECT were 95.0 and 92.3%, respectively. The correlation between local radiologists and the specialized radiologist was excellent (Kappa = 0.87) as was the correlation between the general radiologist and the specialist (Kappa = 0.92).

Conclusion

This prospective analysis demonstrates that WECT is an effective, safe, and simple imaging technique for the diagnosis of colon cancer and can be proposed when a strong clinical suspicion of colon cancer is present, especially in frail patients.     

Cluster analysis using physical performance and self-report measures to identify shoulder injury in overhead female athletes

Objectives

To evaluate the diagnostic validity of the Kerlan-Jobe orthopedic clinic shoulder and elbow score (KJOC) and the Closed kinetic upper extremity stability test (CKCUEST) to assess functional impairments associated with shoulder injury in overhead female athletic populations.

Diagnostic performance of pulmonary ultrasonography and a clinical score for the evaluation of fluid overload in haemodialysis patients

IntroductionThere is no feasible benchmark in daily routine to estimate the hydration status of haemodialysis patients, which is essential to their management.ObjectiveWe performed a study in haemodialysis patients to assess the diagnostic performance of pulmonary ultrasound and clinical examination for the evaluation of fluid overload using transthoracic echocardiography as a gold standard.MethodsThirty-one patients receiving chronic haemodialysis patients were included. Evaluation of hydration status was assessed weekly before haemodialysis sessions using clinical and Echo Comet Score from pulmonary ultrasound and transthoracic echocardiography (reference method).ResultsFive patients had a transthoracic echocardiography overload. Compared with transthoracic echocardiography, the diagnostic performance of the clinical overload score has a sensitivity of 100%, a specificity of 77%, a positive predictive value of 50% and a negative predictive value of 100% with a κ of 0.79. Only orthopnoea (P = 0.008), jugular turgor (P = 0.005) and hepatic-jugular reflux (P = 0.008) were significantly associated with transthoracic echocardiography overload diagnosis. The diagnostic performance of Echo Comet Score by pulmonary ultrasound has a sensitivity of 80%, a specificity of 58%, a positive predictive value of 26% and a negative predictive value of 94%. Ten patients (32.3%) had an increase of extravascular pulmonary water without evidence of transthoracic echocardiography or clinical overload.ConclusionsOur clinical score has a convincing diagnostic performance compared to transthoracic echocardiography and could be easily used in daily clinical routine to adjust dry weight. The evaluation of the overload using pulmonary ultrasound seems poorly correlated with the overload evaluated by transthoracic echocardiography. Extravascular pulmonary water undetected by clinical examination and transthoracic echocardiography remains a parameter that requires further investigation.     

Radioimmunoconjugates for treating cancer: recent advances and current opportunities

Introduction: Radioimmunoconjugates have been used for 30 years to diagnose and treat cancer. For many years, the use of these therapeutic tools has been limited to haematological disorders, such as non-Hodgkin’s lymphoma, given that they have only had a moderate effect on solid tumours.

Areas covered: Recently, several strategies have revived the potential therapeutic application for radioimmunoconjugates. In this review, the authors review the advances in immunological engineering to develop new tools like monoclonal antibodies and their derivatives. Then, the authors summarize the development of radionuclides, the use of recombinant antibodies, pretargeting approaches, and dose fractionation techniques, providing opportunities for both therapeutic and diagnostic applications.

Expert opinion: Radioimmunoconjugates used in nuclear medicine have entered a new era of development. These advances give rise to a variety of opportunities in the management of various cancers, where the radiolabelled antibodies may be particularly useful in immuno-specific phenotypic imaging e.g. companion diagnostics. Concerning therapeutic applications, radioimmunoconjugates have demonstrated their efficacy in the treatment of both haematological malignancies and solid tumours. Recent procedural developments are of great interest in optimising oncological targeted therapies. In the field of cancer theranostics, we believe that radioimmunoconjugated compounds are likely to play a large part in near future.