Right drug, right patient, right time: aspiration or future promise for biologics in rheumatoid arthritis?

Individualising biologic disease-modifying anti-rheumatic drugs (bDMARDs) to maximise outcomes and deliver safe and cost-effective care is a key goal in the management of rheumatoid arthritis (RA). Investigation to identify predictive tools of bDMARD response is a highly active and prolific area of research. In addition to clinical phenotyping, cellular and molecular characterisation of synovial tissue and blood in patients with RA, using different technologies, can facilitate predictive testing. This narrative review will summarise the literature for the available bDMARD classes and focus on where progress has been made. We will also look ahead and consider the increasing use of ‘omics’ technologies, the potential they hold as well as the challenges, and what is needed in the future to fully realise our ambition of personalised bDMARD treatment

Synovial Tissue Heterogeneity in Rheumatoid Arthritis and Changes With Biologic and Targeted Synthetic Therapies to Inform Stratified Therapy

The treatment of rheumatoid arthritis (RA) has been transformed with the introduction of biologic disease modifying anti-rheumatic drugs (bDMARD) and more recently, targeted synthetic DMARD (tsDMARD) therapies in the form of janus-kinase inhibitors. Nevertheless, response to these agents varies such that a trial and error approach is adopted; leading to poor patient quality of life, and long-term outcomes. There is thus an urgent need to identify effective biomarkers to guide treatment selection. A wealth of research has been invested in this field but with minimal progress. Increasingly recognized is the importance of evaluating synovial tissue, the primary site of RA, as opposed to peripheral blood-based investigation. In this mini-review, we summarize the literature supporting synovial tissue heterogeneity, the conceptual basis for stratified therapy. This includes recognition of distinct synovial pathobiological subtypes and associated molecular pathways. We also review synovial tissue studies that have been conducted to evaluate the effect of individual bDMARD and tsDMARD on the cellular and molecular characteristics, with a view to identifying tissue predictors of response. Initial observations are being brought into the clinical trial landscape with stratified biopsy trials to validate toward implementation. Furthermore, development of tissue based omics technology holds still more promise in advancing our understanding of disease processes and guiding future drug selection

Stability of the standard incus coupling of the Carina middle ear actuator after 1.5T MRI

Limited data is available concerning the safety of active middle ear implants (AMEI) during Magnetic Resonance Imaging (MRI). Measurements in temporal bones are the gold standard for preclinical assessment of device safety. In this study the coupling stability of an actuator as used in a fully implantable AMEI was determined in temporal bones. Eleven temporal bones were implanted with the actuator according to the manufacturer’s surgical guidelines. The actuator was coupled on the incus short process as recommended for sensorineural hearing loss. Temporal bones were exposed 10 times to the MRI magnetic field by entering the MRI suite in a clinically relevant way. Computed Tomography (CT) images were acquired before and after the experiment to investigate the risk of actuator dislocation. Based on the electrical impedance of the actuator, the loading of the actuator to the incus was confirmed. Relative actuator displacement was determined on the CT images by comparing the initial with the final actuator position in 3D space. Impedance curves were analyzed after each exposure to check the loading of the actuator to the ossicles. Analysis of CT images with a 0.30.6 mm in-plane resolution indicate no actuator displacement. The maximum detected change in impedance for all actuators was 8.43 Ω at the actuator’s resonance frequency. Impedance curves measured when the actuator was retracted from the short process after the experiment still indicate the presence of a clear resonance peak. No actuator displacement or dislocation could be detected in the analysis of CT images and the measured impedance curves. Impedance curves obtained when the actuator was retracted from the incus short process still show a clear resonance peak, indicating the device is still functional after the MRI exposures.status: Published onlin

Stability of the standard incus coupling of the Carina middle ear actuator after 1.5T MRI.

Limited data is available concerning the safety of active middle ear implants (AMEI) during Magnetic Resonance Imaging (MRI). Measurements in temporal bones are the gold standard for preclinical assessment of device safety. In this study the coupling stability of an actuator as used in a fully implantable AMEI was determined in temporal bones. Eleven temporal bones were implanted with the actuator according to the manufacturer's surgical guidelines. The actuator was coupled on the incus short process as recommended for sensorineural hearing loss. Temporal bones were exposed 10 times to the MRI magnetic field by entering the MRI suite in a clinically relevant way. Computed Tomography (CT) images were acquired before and after the experiment to investigate the risk of actuator dislocation. Based on the electrical impedance of the actuator, the loading of the actuator to the incus was confirmed. Relative actuator displacement was determined on the CT images by comparing the initial with the final actuator position in 3D space. Impedance curves were analyzed after each exposure to check the loading of the actuator to the ossicles. Analysis of CT images with a 0.30.6 mm in-plane resolution indicate no actuator displacement. The maximum detected change in impedance for all actuators was 8.43 Ω at the actuator's resonance frequency. Impedance curves measured when the actuator was retracted from the short process after the experiment still indicate the presence of a clear resonance peak. No actuator displacement or dislocation could be detected in the analysis of CT images and the measured impedance curves. Impedance curves obtained when the actuator was retracted from the incus short process still show a clear resonance peak, indicating the device is still functional after the MRI exposures

Patients with initially unresectable colorectal liver metastases:is there a possibility of cure?

PURPOSE: Although oncosurgical strategies have demonstrated increased survival in patients with unresectable colorectal liver metastases (CLM), their potential for cure is still questioned. The aim of this study was to evaluate long-term outcome after combining downsizing chemotherapy and rescue surgery and to define prognostic factors of cure. PATIENTS AND METHODS: All patients with initially unresectable CLM who underwent rescue surgery and had a minimum follow-up of 5 years were included. Cure was defined as a disease-free interval > or = 5 years from last hepatic or extrahepatic resection until last follow-up. RESULTS: Mean age of 184 patients who underwent resection (April 1988 through July 2002) was 56.9 years. Patients had a mean number of 5.3 metastases (bilobar in 76%), associated to extrahepatic disease in 27%. Surgery was possible after one (74%) or more (26%) lines of chemotherapy. Five- and 10-year overall survival rates were 33% and 27%, respectively. Of 148 patients with a follow-up > or = 5 years, 24 patients (16%) were considered cured (mean follow-up, 118.6 months), six (25%) of whom were considered cured after repeat resection of recurrence. Twelve "cured" patients (50%) had a disease-free interval more than 10 years. Cured patients more often had three or fewer metastases less than 30 mm (P = .03) responding to first-line chemotherapy (P = .05). Multivariate analysis identified maximum size of metastases less than 30 mm at diagnosis, number of metastases at hepatectomy three or fewer, and complete pathologic response as independent predictors of cure. CONCLUSION: Cure can be achieved overall in 16% of patients with initially unresectable CLM resected after downsizing chemotherapy. In addition to increased survival, this oncosurgical approach has real potential for disease eradication