Synchronized presentation of a language task to the electrical stimulation of cortical regions during speech mapping in an awake surgery

Intraoperative speech mapping is performed to preserve language function during tumour resections that involve eloquent cortical areas. For this technique the synchronization of the picture presentation to the patient with the electrical stimulation of the cortex is of major importance. During the operative routine images are manually presented by a psychologist or neurologist to the patient and have to be coordinated with the neurosurgeon stimulating the cortex by a neurostimulator, operated by an engineer. To increase the efficiency of this procedure and to minimize the time needed to localize functional cortical areas, images should appear automatically with electrical stimulation. To achieve this synchronization, the potential combination of an existing neurostimulator with commercially available software for image display was studied. A trigger signal was created to induce the presentation of a series of line drawings showing different objects. The software to control the neurostimulator and the software for image displaying were installed on two different computers. A cable was developed to transfer the trigger signal from the neurostimulator to the computer used for picture presentation. It was shown that it is possible to induce the image display via the neurostimulator using square-wave pulses of 5 V and a width of 10 ms. Thus, we present a system that enables the automated picture presentation synchronized to the electrical stimulation of cortical regions

Postprocessing algorithm for automated analysis of pelvic intraoperative neuromonitoring signals

Two dimensional pelvic intraoperative neuromonitoring (pIONM®) is based on electric stimulation of autonomic nerves under observation of electromyography of internal anal sphincter (IAS) and manometry of urinary bladder. The method provides nerve identification and verification of its’ functional integrity. Currently pIONM® is gaining increased attention in times where preservation of function is becoming more and more important. Ongoing technical and methodological developments in experimental and clinical settings require further analysis of the obtained signals. This work describes a postprocessing algorithm for pIONM® signals, developed for automated analysis of huge amount of recorded data. The analysis routine includes a graphical representation of the recorded signals in the time and frequency domain, as well as a quantitative evaluation by means of features calculated from the time and frequency domain. The produced plots are summarized automatically in a PowerPoint presentation. The calculated features are filled into a standardized Excel-sheet, ready for statistical analysis

Best practice: surgeon driven application in pelvic operations

In applied biomedical engineering and medical industry the transfer of established technology towards customers’ needs is essential for successful development and therefore business opportunities. In chronological order, we can show the transfer of scientific results of neurophysiological research into an existing neuromonitoring system and product which can be used by non-experts in medical technology in the operating room environment. All neurophysiology functions were realized in an intuitive graphical user interface. To stimulate the autonomous nerves, a specialized parameter paradigm was used, different from motor nerve stimulation. In the background, a complex signal processing algorithm recorded smooth muscle and bladder manometry data in synchronized time and automatically detected neurophysiological signals. The acquired data was then presented in real-time. With this effort a complex scientific task could be simplified to a Yes/No statement to the end-user. Beside all the reduction of complexity, the scientific challenge was still obtained, as raw-data is still possible to be recorded

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics