Comparative immunogenicity assessment of biosimilar natalizumab to its reference medicine: a matching immunogenicity profile.

Background: Biosimilar natalizumab (biosim-NTZ) is the first biosimilar monoclonal antibody of reference natalizumab (ref-NTZ) for treatment of relapsing forms of multiple sclerosis (MS). Within the totality of evidence for demonstration of biosimilarity, immunogenicity assessments were performed in healthy subjects and patients with relapsing-remitting MS (RRMS) to confirm a matching immunogenicity profile between biosim-NTZ and ref-NTZ.

Methods: Immunogenicity of biosim-NTZ versus ref-NTZ was evaluated in two pivotal clinical studies.

Introducing the Biosimilar Paradigm to Neurology: The Totality of Evidence for the First Biosimilar Natalizumab.

A biosimilar medicine is a successor to a reference ('originator'/'original-brand') biologic medicine brought to market once the patent and exclusive marketing rights for the reference have expired. Biosimilar natalizumab (PB006 [biosim-NTZ]; developed by Polpharma Biologics S.A.

Efficacy and Safety of Proposed Biosimilar Natalizumab (PB006) in Patients With Relapsing-Remitting Multiple Sclerosis: The Antelope Phase 3 Randomized Clinical Trial.

Importance: Proposed biosimilar natalizumab (biosim-NTZ) PB006 is the first biosimilar monoclonal antibody therapy developed for multiple sclerosis (MS) treatment.

Objective: To evaluate matching efficacy, safety, and immunogenicity between biosim-NTZ and reference natalizumab (ref-NTZ) in patients with relapsing-remitting MS (RRMS).

Design, Setting, And Participants: The Antelope trial was a phase 3, parallel-group, randomized, active-controlled study, conducted between October 2019 and March 2021, with last patient follow-up visit on August 23, 2021.

Propofol Breath Monitoring as a Potential Tool to Improve the Prediction of Intraoperative Plasma Concentrations.

Introduction: Monitoring of drug concentrations in breathing gas is routinely being used to individualize drug dosing for the inhalation anesthetics. For intravenous anesthetics however, no decisive evidence in favor of breath concentration monitoring has been presented up until now. At the same time, questions remain with respect to the performance of currently used plasma pharmacokinetic models implemented in target-controlled infusion systems.

Quantification of propionaldehyde in breath of patients after lung transplantation.

Oxygen-derived free radicals (ROS) have been identified to contribute significantly to ischemia-reperfusion (I/R) injury by initiating chain reactions with polyunsaturated membrane lipids (lipid peroxidation, LPO) resulting in the generation of several aldehydes and ketones. Due to their volatile nature these LPO products can be measured noninvasively in breath. We hypothesized that one of these markers, namely propionaldehyde, will be increased in lung and heart-lung transplant patients where severe oxidative stress due to I/R injury with early graft dysfunction represents one of the major postoperative complications resulting in prolonged ventilation and increased in-hospital morbidity and mortality.

Variability of linezolid concentrations after standard dosing in critically ill patients: a prospective observational study.

Introduction: Severe infections in intensive care patients show high morbidity and mortality rates. Linezolid is an antimicrobial drug frequently used in critically ill patients. Recent data indicates that there might be high variability of linezolid serum concentrations in intensive care patients receiving standard doses.

Liver resection in the elderly: significance of comorbidities and blood loss.

Objective: Liver resection is increasingly performed in elderly patients who are suspected of increased postoperative morbidity (PM) and reduced overall survival (OS). Patient selection based on the identification of age-adjusted risk factors may help to decrease PM and OS.

Design And Participants: Prospectively collected data of 879 patients undergoing elective hepatic resection were analyzed.

Determination of breath isoprene allows the identification of the expiratory fraction of the propofol breath signal during real-time propofol breath monitoring.

Real-time measurement of propofol in the breath may be used for routine clinical monitoring. However, this requires unequivocal identification of the expiratory phase of the respiratory propofol signal as only expiratory propofol reflects propofol blood concentrations. Determination of CO2 breath concentrations is the current gold standard for the identification of expiratory gas but usually requires additional equipment.

Intravenous acetaminophen reduces postoperative nausea and vomiting: a systematic review and meta-analysis.

Opioids are a key risk factor for postoperative nausea and vomiting (PONV). As intravenous (i.v.

Impact of propofol on mid-latency auditory-evoked potentials in children.

Background: Propofol is increasingly used in paediatric anaesthesia, but can be challenging to titrate accurately in this group. Mid-latency auditory-evoked potentials (MLAEPs) can be used to help titrate propofol. However, the effects of propofol on MLAEP in children are unclear.

Breath isoprene concentrations in persons undergoing general anesthesia and in healthy volunteers.

Human breath contains an abundance of volatile organic compounds (VOCs). Analysis of breath VOC may be used for diagnosis of various diseases or for on-line monitoring in anesthesia and intensive care. However, VOC concentrations largely depend on the breath sampling method and have a large inter-individual variability.

Evidence-based analysis of risk factors for postoperative nausea and vomiting.

Background: /st> In assessing a patient's risk for postoperative nausea and vomiting (PONV), it is important to know which risk factors are independent predictors, and which factors are not relevant for predicting PONV.

Methods: /st> We conducted a systematic review of prospective studies (n>500 patients) that applied multivariate logistic regression analyses to identify independent predictors of PONV. Odds ratios (ORs) of individual studies were pooled to calculate a more accurate overall point estimate for each predictor.

Volatile compound profiling for the identification of Gram-negative bacteria by ion-molecule reaction-mass spectrometry.

Aims: Fast and reliable methods for the early detection and identification of micro-organism are of high interest. In addition to established methods, direct mass spectrometry-based analysis of volatile compounds (VCs) emitted by micro-organisms has recently been shown to allow species differentiation. Thus, a large number of pathogenic Gram-negative bacteria, which comprised Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Pseudomonas aeruginosa, Proteus vulgaris and Serratia marcescens, were subjected to headspace VC composition analysis using direct mass spectrometry in a low sample volume that allows for automation.

Volatile organic compound analysis by ion molecule reaction mass spectrometry for Gram-positive bacteria differentiation.

Approximately 50 % of all clinically proven infections in critically ill patients are caused by Gram-positive bacteria. The timely and appropriate treatment of these infections is vital in order to avoid negative outcomes. Hence, fast and reliable methods are needed for the early detection and identification of microorganisms.

Time course of expiratory propofol after bolus injection as measured by ion molecule reaction mass spectrometry.

Propofol in exhaled breath can be detected and monitored in real time by ion molecule reaction mass spectrometry (IMR-MS). In addition, propofol concentration in exhaled breath is tightly correlated with propofol concentration in plasma. Therefore, real-time monitoring of expiratory propofol could be useful for titrating intravenous anesthesia, but only if concentration changes in plasma can be determined in exhaled breath without significant delay.

Effect of an acute consumption of a moderate amount of ethanol on plasma endocannabinoid levels in humans.

Aims: Animal experiments have shown that the endocannabinoid system (ECS) plays an important role in the regulation of ethanol intake. We investigated these effects in healthy volunteers who consumed a moderate amount of ethanol (red wine) and measured plasma levels of the endocannabinoids (ECs) anandamide (AEA) and 2-arachidonoylglycerol (2-AG) to test whether alcohol consumption influences the ECS in humans. Grape juice or plain non-sparkling water served as non-alcoholic control liquids.

Effects of increasing sevoflurane MAC levels on mid-latency auditory evoked potentials in infants, schoolchildren, and the elderly.

Background: Detection of mid-latency auditory evoked potentials (MLAEPs) is a technology to monitor central nervous structures. As seen in adults and children, general anaesthesia influences the MLAEP latencies. MLAEP detection seems to be a promising tool to assess different levels of anaesthesia depth in adults and children.

Pharmacologic management of postoperative nausea and vomiting.

Introduction: As advances in the safety and efficacy of surgery and anesthesia have been made, other complications such as postoperative nausea and vomiting (PONV) have become more apparent. PONV occurs after 30% of all surgeries, and incidences as high as 80% have been reported among patients at high risk.

Areas Covered: This review provides a brief overview of the etiology and mechanisms of emesis and of known risk factors for PONV.

Prevention of pain on injection of propofol: systematic review and meta-analysis.

Objective: To systematically determine the most efficacious approach for preventing pain on injection of propofol.

Design: Systematic review and meta-analysis.

Data Sources: PubMed, Embase, Cochrane Library, www.

Long-term isoflurane therapy for refractory bronchospasm associated with herpes simplex pneumonia in a heart transplant patient.

A 47-year-old man with a history of heart transplant was admitted after severe traumatic brain injury and seizures. During mechanical ventilation, the patient developed bronchospasm that severely compromised respiratory function that led to cardiac arrest. After resuscitation, application of isoflurane through the Anaesthetic Conserving Device (AnaConDa) in the ICU successfully treated bronchospasm, provided adequate sedation, and enabled appropriate ventilation and diagnostic bronchoscopy.

Transdermal scopolamine for the prevention of postoperative nausea and vomiting: a systematic review and meta-analysis.

Background: Transdermal scopolamine (TDS) is a potential long-acting prophylactic antiemetic initially developed to prevent motion sickness. TDS is a centrally acting anticholinergic agent that was approved in 2001 by the US Food and Drug Administration for the prevention of postoperative nausea and vomiting (PONV). Although TDS has been reported to be clinically efficacious in the prevention of PONV, several adverse events (AEs), such as sedation, dry mouth, blurred vision, central cholinergic syndrome, and confusion (particularly in elderly patients with mild cognitive impairment), are potential concerns.

Neurokinin-1 and novel serotonin antagonists for postoperative and postdischarge nausea and vomiting.

Purpose Of Review: This review will address novel options for the prevention and treatment of postoperative and postdischarge nausea and vomiting (PONV and PDNV) after ambulatory anesthesia. In particular, this paper will review the characteristics of neurokinin-1 receptor antagonists (NK1-RAs) and the new serotonin receptor antagonist (5HT3-RA) palonosetron. Finally, we will discuss strategies for prophylaxis and treatment of PONV and PDNV that address the unique concerns in ambulatory surgery patients.

Effect of anaesthesia and cardiopulmonary bypass on blood endocannabinoid concentrations during cardiac surgery.

Background: The endocannabinoid system (ECS) is an endogenous signalling system which includes the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and specific G-protein-coupled endocannabinoid receptors (CB1 and CB2). Recent studies have described important roles of the peripheral ECS in human atherosclerosis, cardiometabolic disorders, heart failure, and systemic inflammation. We sought to study changes in plasma endocannabinoid concentrations during cardiac surgery (CS) under general anaesthesia with isoflurane/sufentanil, and during cardiopulmonary bypass (CPB).

Formation of the N-methylpyridinium ether derivative of propofol to improve sensitivity, specificity and reproducibility of its detection in blood by liquid chromatography-mass spectrometry.

In spite of comparatively high therapeutic concentrations in blood, the quantitation of propofol may cause analytical challenges due to its pharmacokinetic (e.g. short half life, high distribution volume) and physicochemical (significant volatility) particularities.

Molecular breath-gas analysis by online mass spectrometry in mechanically ventilated patients: a new software-based method of CO(2)-controlled alveolar gas monitoring.

Analysis of volatile organic compounds (VOCs) in exhaled breath offers diagnostic potential in research and clinical medicine. Mass spectrometry of expiratory air allows VOC measurements in a concentration range from parts per trillion to parts per million. For the reduction of dilution-related measurement errors due to dead space admixture, the precise identification of the end-expiratory phase of expiration is essential.