Imaged capillary isoelectric focusing associated with multivariate analysis: A powerful tool for quality control of therapeutic monoclonal antibodies.

Monoclonal antibodies are increasingly used in cancer therapy. To guarantee the quality of these mAbs from compounding to patient administration, characterization methods are required (e.g. identity). In a clinical setting, these methods must be fast and straightforward. For this reason, we investigated the potential of image capillary isoelectric focusing (icIEF) combined with Principal Component Analysis (PCA) and Partial least squares-discriminant analysis (PLS-DA). icIEF profiles obtained from monoclonals antibodies (mAbs) analysis have been pre-processed and the data submitted to principal component analysis (PCA). This pre-processing method has been designed to avoid the impact of concentration and formulation. Analysis of four commercialized mAbs (Infliximab, Nivolumab, Pertuzumab, and Adalimumab) by icIEF-PCA led to the formation of four clusters corresponding to each mAb. Partial least squares-discriminant analysis (PLS-DA) applied to these data allowed us to build models to predict which monoclonal antibody is analyzed. The validation of this model was obtained from k-fold cross-validation and prediction tests. The selectivity and the specificity of the model performance parameters were assessed by the excellent classification obtained. In conclusion, we established that the combination of icIEF and chemometric approaches is a reliable approach for unambiguously identifying compounded therapeutic monoclonal antibodies (mAbs) before patient administration.

Performance of diagnostic ultrasound to identify causes of hydramnios.

INTRODUCTION: We aimed to assess the diagnostic yield of ultrasonography in the identification of the etiology of hydramnios, and the added value of MRI or amniocentesis. METHODS: We conducted a single-center retrospective study including pregnancies with confirmed hydramnios (defined as deepest pocket ≥8 cm) between January 2013 and May 2017. Twin pregnancies, secondary hydramnios discovered after the diagnosis of a causal pathology, and pregnancies of unknown outcome were excluded. All pregnancies underwent a targeted scan, and selected cases underwent MRI or amniocentesis. RESULTS: A total of 158 patients with confirmed hydramnios were included. Hydramnios was associated with a fetal pathology in 37 cases (23.4%), with diabetes in 39 (24.6%), isolated macrosomia in 16 (10.1%), and considered idiopathic in 66 (41.7%). Ultrasonography established a diagnosis of the underlying pathology in 73% of cases. Amniocentesis was done in 31 cases (20%) and it allowed diagnosis of chromosome anomalies, esophageal atresia, myotonic dystrophy congenital type, Prader-Willi syndrome, and Bartter syndrome. MRI was done in 15 cases (10%) and it allowed one additional diagnosis of esophageal atresia. The diagnostic yields of MRI and amniocentesis were 91.7% and 95.2%, respectively. There were five false positive diagnoses at ultrasonography, and one false positive diagnosis at MRI. CONCLUSION: Hydramnios can be associated with a wide variety of underlying pathologies. Diagnostic ultrasound can attain a diagnosis in the majority of cases. Amniocentesis offers a valuable complementary assessment.

Evaluation of sFlt-1/PlGF Ratio for Predicting and Improving Clinical Management of Pre-eclampsia: Experience in a Specialized Perinatal Care Center.

BACKGROUND: Management of pregnant women at high risk of pre-eclampsia (PE) requires frequent monitoring, with referral to specialized perinatal care centers. Reliable tests are necessary to improve prediction of PE and related complications and to assess disease severity and progression. An imbalance in two biomarkers, soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF), is involved in PE pathogenesis. The sFlt-1 to PlGF ratio is increased in pregnant women before the onset of PE. An elevated ratio is highly predictive of PE, whereas the diagnosis of PE can be ruled out within one week for low ratios. The main objective of this study was to assess whether a low sFlt-1/PlGF ratio, below a cutoff of 38, can predict the absence of PE within one week. METHODS: We performed a prospective, monocentric, observational study to evaluate serum sFlt-1/PlGF ratio (Roche Diagnostics Cobas e411 system) for predicting -PE in a group of 67 high-risk pregnant women (20-37 gestation weeks). RESULTS: Among the 67 patients included, 53 had a sFlt-1/PlGF ratio lower than 38; none developed subsequent PE leading to a negative predictive value of 100%. Eight patients developed clinical PE. The positive predictive value was 21% at one week and 18% at four weeks, in accordance with previous studies. CONCLUSIONS: The serum sFlt-1/PlGF ratio showed highly predictive performances for ruling out PE. Using these biomarkers in routine management of PE may improve clinical care and avoid inappropriate hospitalization, which has a significant economic impact.