Metformin Use and Long-term Outcomes Including Aneurysm Sac Dynamics Following EVAR for Infrarenal Abdominal Aortic Aneurysm: "A Retrospective Study".

PURPOSE: Metformin, widely used for the treatment of diabetes mellitus (DM), has shown potential for inhibiting abdominal aortic aneurysm (AAA) growth by reducing extracellular matrix remodeling and inflammation. However, its influence on clinical outcomes and aneurysm sac dynamics after endovascular aneurysm repair (EVAR) remains uncertain. This retrospective study aims to explore the effects of metformin on long-term outcomes following EVAR. MATERIALS AND METHODS: Patients who underwent elective standard EVAR for infrarenal AAA at a single academic Dutch hospital from 2000 to 2022 were included. We collected baseline patient demographics, comorbid conditions, anatomical and operative characteristics, and 30-day postoperative events. Metformin use was defined as using it preceding EVAR. The primary outcome, the postoperative aneurysm sac volume over time, was investigated using linear mixed-effects modeling. The secondary outcomes, 8-year all-cause mortality and freedom from graft-related events, were evaluated using Kaplan-Meier methods. RESULTS: We analyzed 685 patients, including 634 (93%) non-metformin users and 51 (7%) metformin users. The median follow-up period was similar (4.0 years [IQR=1.5, 6.5] vs 5.0 years [IQR=2.0, 8.0]; p=0.091). Patients on metformin had a preoperative aneurysm sac volume of 153 cc (IQR=114, 195) compared with 178 cc (IQR=133, 240) for non-metformin patients (p=0.054). At 30 days post-EVAR, metformin patients had a comparable mean aneurysm sac volume compared with non-metformin patients (metformin: -19.4 cc [95% confidence interval [CI]: -47.4, 8.5]; p=0.173). The effect of metformin on aneurysm growth over time was not significant (-3.9 cc/year; [95% CI: -22.7, 14.9]; p=0.685). Following risk-adjusted analysis, metformin use was associated with similar rates of all-cause mortality (metformin vs no metformin: 50% vs 44%; hazard ratio [HR]=1.11, 95% CI: 0.66, 1.88; p=0.688) and freedom from graft-related events (metformin vs no metformin: 63% vs 66%; HR=1.82, 95% CI: 0.98, 3.38; p=0.059). CONCLUSION: Although metformin use may reduce preoperative AAA growth, it does not seem to influence overall/long-term post-EVAR AAA sac dynamics, all-cause mortality, or freedom from graft-related events. These findings suggest that the potential protective effect of metformin on AAA may not be sustained after EVAR. Further prospective studies are needed to investigate the mechanisms underlying the potential role of metformin in AAA management following EVAR. CLINICAL IMPACT: There is currently no approved pharmacological treatment available to slow the abdominal aortic aneurysm (AAA) growth rate and reduce the related risk of rupture. In our retrospective analysis including 685 patients undergoing EVAR for infrarenal AAA, we found that metformin use was not associated with improved post-EVAR outcomes, such as a reduction of aneurysm sac volume over time, eight-year all-cause mortality, or freedom of graft-related events. These findings suggest that the potential protective effect of metformin on AAA may not be sustained after EVAR and underscore the need for ongoing research into this area.

Perioperative transfusion study (PETS): Does a liberal transfusion protocol improve outcome in high-risk cardiovascular patients undergoing non-cardiac surgery? A randomised controlled pilot study.

BACKGROUND: Small studies have shown that patients with advanced coronary artery disease might benefit from a more liberal blood transfusion strategy. The goal of this pilot study was to test the feasibility of a blood transfusion intervention in a group of vascular surgery patients who have elevated cardiac troponins in rest. METHODS: We conducted a single-centre, randomised controlled pilot study. Patients with a preoperative elevated high-sensitive troponin T undergoing non-cardiac vascular surgery were randomised between a liberal transfusion regime (haemoglobin >10.4 g/dL) and a restrictive transfusion regime (haemoglobin 8.0-9.6 g/dL) during the first 3 days after surgery. The primary outcome was defined as a composite endpoint of all-cause mortality, myocardial infarction or unscheduled coronary revascularization. RESULTS: In total 499 patients were screened; 92 were included and 50 patients were randomised. Postoperative haemoglobin was different between the intervention and control group; 10.6 versus 9.8, 10.4 versus 9.4, 10.9 versus 9.4 g/dL on day one, two and three respectively (p < 0.05). The primary outcome occurred in four patients (16%) in the liberal transfusion group and in two patients (8%) in control group. CONCLUSION: This pilot study shows that the studied transfusion protocol was able to create a clinically significant difference in perioperative haemoglobin levels. Randomisation was possible in 10% of the screened patients. A large definitive trial should be possible to provide evidence whether a liberal transfusion strategy could decrease the incidence of postoperative myocardial infarction in high risk surgical patients.

Oxygenation during general anesthesia in pediatric patients: A retrospective observational study.

STUDY OBJECTIVE: Protocols are used in intensive care and emergency settings to limit the use of oxygen. However, in pediatric anesthesiology, such protocols do not exist. This study aimed to investigate the administration of oxygen during pediatric general anesthesia and related these values to PaO2, SpO2 and SaO2. DESIGN: Retrospective observational study. SETTING: Tertiary pediatric academic hospital, from June 2017 to August 2020. PATIENTS: Patients aged 0-18 years who underwent general anesthesia for a diagnostic or surgical procedure with tracheal intubation and an arterial catheter for regular blood withdrawal were included. Patients on cardiopulmonary bypass or those with missing data were excluded. Electronic charts were reviewed for patient characteristics, type of surgery, arterial blood gas analyses, and oxygenation management. INTERVENTIONS: No interventions were done. MEASUREMENTS: Primary outcome defined as FiO2, PaO2 and SpO2 values were interpreted using descriptive analyses, and the correlation between PaO2 and FiO2 was determined using the weighted Spearman correlation coefficient. MAIN RESULTS: Data of 493 cases were obtained. Of these, 267 were excluded for various reasons. Finally, 226 cases with a total of 645 samples were analyzed. The median FiO2 was 36% (IQR 31 to 43), with a range from 20% to 97%, and the median PaO2 was 23.6 kPa (IQR 18.6 to 28.1); 177 mmHg (IQR 140 to 211). The median SpO2 level was 99% (IQR 98 to 100%). The study showed a moderately positive association between PaO2 and FiO2 (r = 0.52, p < 0.001). 574 of 645 samples (89%) contained a PaO2 higher than 13.3 kPa; 100 mmHg. CONCLUSIONS: Oxygen administration during general pediatric anesthesia is barely regulated. Hyperoxemia is observed intraoperatively in approximately 90% of cases. Future research should focus on outcomes related to hyperoxemia.

Patient knowledge in anaesthesia: Psychometric development of the RAKQ-The Rotterdam anaesthesia Knowledge questionnaire.

The transition from in-person to digital preoperative patient education requires effective methods for evaluating patients' understanding of the perioperative process, risks, and instructions to ensure informed consent. A knowledge questionnaire covering different anaesthesia techniques and instructions could fulfil this need. We constructed a set of items covering common anaesthesia techniques requiring informed consent and developed the Rotterdam Anaesthesia Knowledge Questionnaire (RAKQ) using a structured approach and Item Response Theory. A team of anaesthetists and educational experts developed the initial set of 60 multiple-choice items, ensuring content and face validity. Next, based on exploratory factor analysis, we identified seven domains: General Anaesthesia-I (regarding what to expect), General Anaesthesia-II (regarding the risks), Spinal Anaesthesia, Epidural Anaesthesia, Regional Anaesthesia, Procedural sedation and analgesia, and Generic Items. This itemset was filled out by 577 patients in the Erasmus MC, Rotterdam, and Albert Schweitzer Hospital, Dordrecht, the Netherlands. Based on factor loadings (≥0.25) and considering clinical relevance this initial item set was reduced to 50 items, distributed over the seven domains. Each domain was processed to produce a separate questionnaire. Through an iterative process of item selection to ensure that the questionnaires met the criteria for Item Response Theory modelling, 40 items remained in the definitive set of seven questionnaires. Finally, we developed an Item Response Theory model for each questionnaire and evaluated its reliability. 1-PL and 2-PL models were chosen based on best model fit. No item misfit (S-χ2, p<0.001 = misfit) was detected in the final models. The newly developed RAKQ allows practitioners to assess their patients' knowledge before consultation to better address knowledge gaps during consultation. Moreover, they can decide whether the level of knowledge is sufficient to obtain digital informed consent without face-to-face education. Researchers can use the RAKQ to compare new methods of patient education with traditional methods.

Targeted proteomics and metabolomics for biomarker discovery in abdominal aortic aneurysm and post-EVAR sac volume.

BACKGROUND AND AIMS: Abdominal aortic aneurysm (AAA) patients undergo uniform surveillance programs both leading up to, and following surgery. Circulating biomarkers could play a pivotal role in individualizing surveillance. We applied a multi-omics approach to identify relevant biomarkers and gain pathophysiological insights. MATERIALS AND METHODS: In this cross-sectional study, 108 AAA patients and 200 post-endovascular aneurysm repair (post-EVAR) patients were separately investigated. We performed partial least squares regression and ingenuity pathway analysis on circulating concentrations of 96 proteins (92 Olink Cardiovascular-III panel, 4 ELISA-assays) and 199 metabolites (measured by LC-TQMS), and their associations with CT-based AAA/sac volume. RESULTS: The median (25th-75th percentile) maximal diameter was 50.0 mm (46.0, 53.0) in the AAA group, and 55.4 mm (45.0, 64.2) in the post-EVAR group. Correcting for clinical characteristics in AAA patients, the aneurysm volume Z-score differed 0.068 (95 %CI: (0.042, 0.093)), 0.066 (0.047, 0.085) and -0.051 (-0.064, -0.038) per Z-score valine, leucine and uPA, respectively. After correcting for clinical characteristics and orthogonalization in the post-EVAR group, the sac volume Z-score differed 0.049 (0.034, 0.063) per Z-score TIMP-4, -0.050 (-0.064, -0.037) per Z-score LDL-receptor, -0.051 (-0.062, -0.040) per Z-score 1-OG/2-OG and -0.056 (-0.066, -0.045) per Z-score 1-LG/2-LG. CONCLUSIONS: The branched-chain amino acids and uPA were related to AAA volume. For post-EVAR patients, LDL-receptor, monoacylglycerols and TIMP-4 are potential biomarkers for sac volume. Additionally, distinct markers for sac change were identified.