Purpose: Hypertriglyceridemia (hyperTG) is common among intensive care unit (ICU) patients, but knowledge about hyperTG risk factors is scarce. The present study aims to identify risk factors favoring its development in patients requiring prolonged ICU treatment. Methods: Prospective observational study in the medicosurgical ICU of a university teaching hospital. All consecutive patients staying C4 days were enrolled. Potential risk factors were recorded: pathology, energy intake, amount and type of nutritional lipids, intake of propofol, glucose intake, laboratory parameters, and drugs. Triglyceride (TG) levels were assessed three times weekly. Statistics was based on twoway analysis of variance (ANOVA) and linear regression with potential risk factors. Results: Out of 1,301 consecutive admissions, 220 patients were eligible, of whom 99 (45 %) presented hyperTG (triglycerides [2 mmol/L). HyperTG patients were younger, heavier, with more brain injury and multiple trauma. Intake of propofol (mg/kg/h) and lipids' propofol had the highest correlation with plasma TG (r 2 = 0.28 and 0.26, respectively, both p \ 0.001). Infection and inflammation were associated with development of hyperTG [C-reactive protein (CRP), r 2 = 0.19, p = 0.004]. No strong association could be found with nutritional lipids or other risk factors.Outcome was similar in normo-and hyperTG patients. Conclusions: HyperTG is frequent in the ICU but is not associated with adverse outcome. Propofol and accompanying lipid emulsion are the strongest risk factors. Our results suggest that plasma TG should be monitored at least twice weekly in patients on propofol. The clinical consequences of propofol-related hyperTG should be investigated in further studies.

A randomized, double-blind, controlled vaccine clinical trial was conducted to assess, as the primary outcome, the safety and protective efficacy of the Plasmodium vivax circumsporozoite (CS) protein in healthy malaria-naïve (phase IIa) and semi-immune (phase IIb) volunteers. Participants (n = 35) were randomly selected from a larger group (n = 121) and further divided into naïve (n = 17) and semi-immune (n = 18) groups and were immunized at months 0, 2, and 6 with PvCS formulated in Montanide ISA-51 adjuvant or placebo (adjuvant alone). Specific antibodies and IFN-γ responses to PvCS were determined as secondary outcome; all experimental volunteers developed specific IgG and IFN-γ. Three months after the last immunization, all participants were subjected to controlled human malaria infection. All naive controls became infected and drastic parasitemia reduction, including sterile protection, developed in several experimental volunteers in phase IIa (6/11) (54%, 95% CI 0.25–0.84) and phase IIb (7/11) (64%, 95% CI 0.35–0.92). However, no difference in parasitemia was observed between the phase IIb experimental and control subgroups. In conclusion, this study demonstrates significant protection in both naïve and semi-immune volunteers, encouraging further PvCS vaccine clinical development. Trial registration number NCT 02083068. This trial was funded by Colciencias (grant 529-2009), NHLBI (grant RHL086488 A), and MVDC/CIV Foundation (grant 2014-1206).

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Background CT-P13 is an infliximab biosimilar that was granted market authorization in Switzerland in 2016. Despite the growing literature supporting the equivalence of CT-P13 compared with originator infliximab regarding the efficacy, safety, and immunogenicity and the undeniable cost-saving opportunities, CT-P13 remains widely underused in Switzerland. Objective Leaving aside the phenomenon of a low initiation rate, this study aimed to explore the reasons behind the high discontinuation rate observed among the patients taking CT-P13 in a large tertiary hospital in Western Switzerland. Methods We performed a retrospective cohort study using routinely collected data. Patients were eligible if they received originator infliximab or CT-P13 between September 2017 and December 2020. They were included if they had received at least two CT-P13 infusions during the same period. Patients were excluded if the follow-up was incomplete prior to or 6 months after their first CT-P13 infusion and if they had an oncological main diagnosis. Primary outcomes were the reasons for treatment discontinuation. Results One hundred and fifty-six patients were included and classified into two groups: switchers who were treated with originator infliximab and were switched to CT-P13 ( n = 85, 54%) and initiators who did not receive originator infliximab prior to CT-P13 treatment ( n = 71, 46%). Included patients belonged to three different groups of diagnosis: gastroenterological (67, 43%), rheumatological (61, 39%), and immunological (28, 18%). Twenty-three (27%) switchers and 35 (49%) initiators discontinued CT-P13 after 12 months. Main reasons for CT-P13 discontinuation were lack of efficacy ( n = 21, 36%) and secondary loss of response ( n = 16, 28%); however, objective assessments were not available. Initiators’ probability to discontinue CT-P13 at 12 months was significantly higher than switchers’ ( p < 0.01). Conclusions Lack of efficacy and secondary loss of response were the main reasons for the high CT-P13 discontinuation rate observed in a large tertiary hospital in Western Switzerland. Lack of active training and coordination among healthcare professionals and little education in patients may have exacerbated patients’ subjective complaints and increased the CT-P13 discontinuation rate. Supplementary Information The online version contains supplementary material available at 10.1007/s40801-022-00299-2.

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IntroductionWe previously showed that erythropoietin (EPO) attenuates the morphological signs of spinal cord ischemia/reperfusion (I/R) injury in swine [1] without, however, improving neurological function. The clinical use of EPO has been cautioned most recently due to serious safety concerns arising from an increased mortality in acute stroke patients treated with EPO and simultaneously receiving systemic thrombolysis [2]. Carbamylated EPO (cEPO) is an EPO derivative without erythropoietic activity and devoid of the EPO side eff ects, but with apparently well maintained cytoprotective qualities [3]. We therefore tested the hypothesis whether cEPO may be equally effi cient as EPO in reducing morphological as well as functional aortic occlusion-induced spinal cord I/R injury. Methods In a randomized and blinded trial pigs received either vehicle (control, n = 9), EPO or cEPO, respectively (n = 9 each; 5,000 IU/kg over 30 minutes before and during the fi rst 4 hours of reperfusion). Animals underwent 30 minutes of thoracic aortic balloon occlusion with catheters placed immediately downstream of the A. subclavia and upstream of the aortic trifurcation. Spinal cord function was assessed by motor evoked potentials (MEP as percentage of the amplitude before aortic occlusion) and lower limb refl exes (assessed as the subjective strength of response) for a period of 10 hours after reperfusion. Tissue damage was evaluated using Nissl staining. Results Both EPO-treated and cEPO-treated animals presented with attenuated spinal cord injury in the Nissl staining (median (quartile) percentage of damaged neurons in the thoracic segments: control 27 (25,44), cEPO 8 (4,10), and EPO 5 (5,7), P <0.001 vs control group; in the lumbar segments: control 26 (19,32), cEPO 7 (5,13), EPO 8 (5,10), P <0.001 vs control group). However, while only cEPO treatment was associated with recovery of the MEP amplitude to pre-occlusion values when compared with the control group (P <0.05), lower limb refl ex response was comparably restored stronger in both treatment groups (P <0.05 vs control). Conclusions In a clinically relevant porcine model mimicking aortic crossclamping during vascular surgery repair of thoracic aortic aneurysm, cEPO protected spinal cord function and integrity as eff ective as EPO when applied at equipotent doses. Acknowledgements Supported by the Deutsche Forschungs gemeinschaft (SCHE 899/2-2). References Introduction Unfolded protein response (UPR)-mediated apoptosis plays a pivotal role in ischemia-reperfusion injury. Sodium 4-phenylbutyrate (PBA) has been reported to act as a chemical chaperone inhibiting UPR-mediated apoptosis triggered by ischemia in various organs other than the heart. Therefore we investigated whether PBA reduces UPR-mediated apoptosis and protects against myocardial ischemia-reperfusion injury in mice. Methods C57BL/6 mice were subjected to 30 minutes LAD ischemia followed by reperfusion. PBA (100 mg/kg) or PBS (control) was administrated intraperitoneally just before ischemia. Apoptosis, infarct ...

Tumor necrosis factor-alpha (TNF-⍺) antagonists are biological drugs with multiple authorized biosimilars. Biosimilars are becoming critical to the financial sustainability of health systems. Recent studies emphasize that physicians’ knowledge regarding biosimilars has not yet progressed sufficiently to overcome their concerns regarding biosimilars’ safety and efficacy. To assess the current knowledge, opinions, and attitudes toward TNF-⍺ antagonist biosimilars among postgraduate physicians and specialists, an anonymous, self-administered survey was implemented on SurveyMonkey between February and May 2022. The survey was validated through think-aloud interviews with senior and postgraduate physicians in rheumatology, gastroenterology, and immunoallergology, and a senior epidemiologist. Participant recruitment was conducted with the help of the physicians’ professional societies and departmental head physicians of two university hospitals in Western Switzerland. Most physicians felt more comfortable initiating a TNF-⍺ antagonist biosimilar in biologic-naive patients (BNPs) than switching patients stabilized on the original biologic (originator). However, most participants agreed that BNPs should start treatment with the biosimilar rather than the originator when available. Postgraduate physicians and specialists in rheumatology, gastroenterology, and immunoallergology who participated in this survey were familiar with TNF-⍺ antagonist biosimilars and were confident in prescribing them. Yet, they still preferred to avoid switching a patient already on the originator.