Targeted plasma multi-omics propose glutathione, glycine and serine as biomarkers for abdominal aortic aneurysm growth on serial CT scanning.

BACKGROUND AND AIMS: Abdominal aortic aneurysm (AAA) patients undergo uniform imaging surveillance until reaching the surgical threshold. In spite of the ongoing exploration of AAA pathophysiology, biomarkers for personalized surveillance are lacking. This study aims to identify potential circulating biomarkers for AAA growth on serial CT scans. METHODS: Patients with an AAA (maximal diameter ≥40 mm) were included in this multicentre, prospective cohort study. Participants underwent baseline blood sampling and yearly CT-imaging to determine AAA diameter and volume. Proteins and metabolites were measured using proximity extension assay (Olink Cardiovascular III) or separate ELISA panels, and mass-spectrometry (LC-TQMS), respectively. Linear mixed-effects, orthogonal partial least squares, and Cox regression were used to explore biomarker associations with AAA volume growth rate and the risk of surpassing the surgical threshold, as formulated by current guidelines. RESULTS: 271 biomarkers (95 proteins, 176 metabolites) were measured in 109 (90.8 % male) patients with mean age 72. Median baseline maximal AAA diameter was 47.8 mm, volume 109 mL. Mean annual AAA volume growth rate was 11.5 %, 95 % confidence interval (CI) (10.4, 12.7). Median follow-up time was 23.2 months, 49 patients reached the surgical threshold. Patients with one standard deviation (SD) higher glutathione and glycine levels at baseline had an AAA volume growth rate that respectively was 1.97 %, 95%CI (0.97, 2.97) and 1.74 %, 95%CI (0.78, 2.71) larger, relative to the actual aneurysm size. Serine was associated with the risk of reaching the surgical threshold, independent of age and baseline AAA size (cause-specific hazard ratio per SD difference 1.78, 95%CI (1.30, 2.44)). CONCLUSIONS: Among multiple intertwined biomarkers related to AAA pathophysiology and progression, glutathione, glycine and serine were most promising.

Volume Measurements for Surveillance after Endovascular Aneurysm Repair using Artificial Intelligence.

OBJECTIVE: Surveillance after endovascular aneurysm repair (EVAR) is suboptimal due to limited compliance and relatively large variability in measurement methods of abdominal aortic aneurysm (AAA) sac size after treatment. Measuring volume offers a more sensitive early indicator of aneurysm sac growth or regression and stability, but is more time consuming and thus less practical than measuring maximum diameter. This study evaluated the accuracy and consistency of the artificial intelligence (AI) driven software PRAEVAorta 2 and compared it with an established semi-automated segmentation method. METHODS: Post-EVAR aneurysm sac volumes measured by AI were compared with a semi-automated segmentation method (3mensio software) in patients with an infrarenal AAA, focusing on absolute aneurysm volume and volume evolution over time. The clinical impact of both methods was evaluated by categorising patients as showing either AAA sac regression, stabilisation, or growth comparing the 30 day and one year post-EVAR computed tomography angiography (CTA) images. Inter- and intra-method agreement were assessed using Bland-Altman analysis, the intraclass correlation coefficient (ICC), and Cohen's κ statistic. RESULTS: Forty nine patients (98 CTA images) were analysed, after excluding 15 patients due to segmentation errors by AI owing to low quality CT scans. Aneurysm sac volume measurements showed excellent correlation (ICC = 0.94, 95% confidence interval [CI] 0.88 - 0.99) with good to excellent correlation for volume evolution over time (ICC = 0.85, 95% CI 0.75 - 0.91). Categorisation of AAA sac evolution showed fair correlation (Cohen's κ = 0.33), with 12 discrepancies (24%) between methods. The intra-method agreement for the AI software demonstrated perfect consistency (bias = -0.01 cc), indicating that it is more reliable compared with the semi-automated method. CONCLUSION: Despite some differences in AAA sac volume measurements, the highly consistent AI driven software accurately measured AAA sac volume evolution. AAA sac evolution classification appears to be more reliable than existing methods and may therefore improve risk stratification post-EVAR, and could facilitate AI driven personalised surveillance programmes. While high quality CTA images are crucial, considering radiation exposure is important, validating the software with non-contrast CT scans might reduce the radiation burden.

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.

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.

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.

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.

Opportunities and barriers for prehospital emergency medical services research in the Netherlands; results of a mixed-methods consensus study.

INTRODUCTION: Quality improvement in prehospital emergency medical services (EMS) can only be achieved by high-quality research and critical appraisal of current practices. This study examines current opportunities and barriers in EMS research in the Netherlands. METHODS: This mixed-methods consensus study consisted of three phases. The first phase consisted of semi-structured interviews with relevant stakeholders. Thematic analysis of qualitative data derived from these interviews was used to identify main themes, which were subsequently discussed in several online focus groups in the second phase. Output from these discussions was used to shape statements for an online Delphi consensus study among relevant stakeholders in EMS research. Consensus was met if 80% of respondents agreed or disagreed on a particular statement. RESULTS: Forty-nine stakeholders participated in the study; qualitative thematic analysis of the interviews and focus group discussions identified four main themes: (1) data registration and data sharing, (2) laws and regulations, (3) financial aspects and funding, and (4) organization and culture. Qualitative data from the first two phases of the study were used to construct 33 statements for an online Delphi study. Consensus was reached on 21 (64%) statements. Eleven (52%) of these statements pertained to the storage and use of EMS patient data. CONCLUSION: Barriers for prehospital EMS research in the Netherlands include issues regarding the use of patient data, privacy and legislation, funding and research culture in EMS organizations. Opportunities to increase scientific productivity in EMS research include the development of a national strategy for EMS data and the incorporation of EMS topics in research agendas of national medical professional associations.

Aneurysm Sac Dynamics and its Prognostic Significance Following Fenestrated and Branched Endovascular Aortic Aneurysm Repair.

OBJECTIVE: This study aimed to assess aneurysm sac dynamics and its prognostic significance following fenestrated and branched endovascular aneurysm repair (F/BEVAR). METHODS: Patients undergoing F/BEVAR for degenerative complex aortic aneurysm from 2008 to 2020 at two large vascular centres with two imaging examinations (30 day and one year) were included. Patients were categorised as regression and non-regression, determined by the proportional volume change (> 5%) at one year compared with 30 days. All cause mortality and freedom from graft related events were assessed using Kaplan-Meier methods. Factors associated with non-regression at one year and aneurysm sac volume over time were examined for FEVAR and BEVAR independently using multivariable logistic regression and linear mixed effects modelling. RESULTS: One hundred and sixty-five patients were included: 122 FEVAR, of whom 34% did not regress at one year imaging (20% stable, 14% expansion); and 43 BEVAR, of whom 53% failed to regress (26% stable, 28% expansion). Following F/BEVAR, after risk adjusted analysis, non-regression was associated with higher risk of all cause mortality within five years (hazard ratio [HR] 2.56, 95% confidence interval [CI] 1.09 - 5.37; p = .032) and higher risk of graft related events within five years (HR 2.44, 95% CI 1.10 - 5.26; p = .029). Following multivariable logistic regression, previous aortic repair (odds ratio [OR] 2.56, 95% CI 1.11 - 5.96; p = .029) and larger baseline aneurysm diameter (OR/mm 1.04, 95% CI 1.00 - 1.09; p = .037) were associated with non-regression at one year, whereas smoking history was inversely associated with non-regression (OR 0.21, 95% CI 0.04 - 0.96; p = .045). Overall following FEVAR, aneurysm sac volume decreased significantly up to two years (baseline vs. two year, 267 [95% CI 250 - 285] cm3vs. 223 [95% CI 197 - 248] cm3), remaining unchanged thereafter. Overall following BEVAR, aneurysm sac volume remained stable over time. CONCLUSION: Like infrarenal EVAR, non-regression at one year imaging is associated with higher five year all cause mortality and graft related events risks after F/BEVAR. Following FEVAR for juxtarenal aortic aneurysm, aneurysm sacs generally displayed regression (66% at one year), whereas after BEVAR for thoraco-abdominal aortic aneurysm, aneurysm sacs displayed a concerning proportion of growth at one year (28%), potentially suggesting a persistent risk of rupture and consequently requiring intensified surveillance following BEVAR. Future studies will have to elucidate how to improve sac regression following complex EVAR, and whether the high expansion risk after BEVAR is due to advanced disease extent.

Circulating biomarkers of cardiovascular disease are related to aneurysm volume in abdominal aortic aneurysm.

BACKGROUND: Surveillance programs in abdominal aortic aneurysms (AAA) are mainly based on imaging and leave room for improvement to timely identify patients at risk for AAA growth. Many biomarkers are dysregulated in patients with AAA, which fuels interest in biomarkers as indicators of disease progression. We examined associations of 92 cardiovascular disease (CVD)-related circulating biomarkers with AAA and sac volume. METHODS: In a cross-sectional analysis, we separately investigated (1) 110 watchful waiting (WW) patients (undergoing periodic surveillance imaging without planned intervention) and (2) 203 patients after endovascular aneurysm repair (EVAR). The Cardiovascular Panel III (Olink Proteomics AB, Sweden) was used to measure 92 CVD-related circulating biomarkers. We used cluster analyses to investigate protein-based subphenotypes, and linear regression to examine associations of biomarkers with AAA and sac volume on CT scans. RESULTS: Cluster analyses revealed two biomarker-based subgroups in both WW and EVAR patients, with higher levels of 76 and 74 proteins, respectively, in one subgroup versus the other. In WW patients, uPA showed a borderline significant association with AAA volume. Adjusting for clinical characteristics, there was a difference of -0.092 (-0.148, -0.036) loge mL in AAA volume per SD uPA. In EVAR patients, after multivariable adjustment, four biomarkers remained significantly associated with sac volume. The mean effects on sac volume per SD difference were: LDLR: -0.128 (-0.212, -0.044), TFPI: 0.139 (0.049, 0.229), TIMP4: 0.110 (0.023, 0.197), IGFBP-2: 0.103 (0.012, 0.194). CONCLUSION: LDLR, TFPI, TIMP4, and IGFBP-2 were independently associated with sac volume after EVAR. Subgroups of patients with high levels of the majority of CVD-related biomarkers emphasize the intertwined relationship between AAA and CVD.ClinicalTrials.gov Identifier: NCT03703947.

Intraoperative hypotension in noncardiac surgery patients with chronic beta-blocker therapy: A matched cohort analysis.

STUDY OBJECTIVE: To explore the incidence of intraoperative hypotension in patients with chronic beta-blocker therapy, expressed as time spent, area and time-weighted average under predefined mean arterial pressure thresholds. DESIGN: Retrospective analysis of a prospective observational cohort registry. SETTING: Patients ≥60 years undergoing intermediate- to high-risk noncardiac surgery with routine postoperative troponin measurements on the first three days after surgery. PATIENTS: 1468 matched sets of patients (1:1 ratio with replacement) with and without chronic beta-blocker treatment. INTERVENTIONS: None. MEASUREMENTS: The primary outcome was the exposure to intraoperative hypotension in beta-blocker users vs. non-users. Time spent, area and time-weighted average under predefined mean arterial pressure thresholds (55-75 mmHg) were calculated to express the duration and severity of exposure. Secondary outcomes included incidence of postoperative myocardial injury and thirty-day mortality, myocardial infarction (MI) and stroke. Furthermore, analyses for patient subgroup and beta-blocker subtype were conducted. MAIN RESULTS: In patients with chronic beta-blocker therapy, no increased exposure to intraoperative hypotension was observed for all characteristics and thresholds calculated (all P > .05). Beta-blocker users had lower heart rate before, during and after surgery (70 vs. 74, 61 vs. 65 and 68 vs. 74 bpm, all P < .001, respectively). Postoperative myocardial injury (13.6% vs. 11.6%, P = .269) and thirty-day mortality (2.5% vs. 1.4%, P = .055), MI (1.4% vs. 1.5%, P = .944) and stroke (1.0% vs 0.7%, P =  .474) rates were comparable. The results were consistent in subtype and subgroup analyses. CONCLUSIONS: In this matched cohort analysis, chronic beta-blocker therapy was not associated with increased exposure to intraoperative hypotension in patients undergoing intermediate- to high-risk noncardiac surgery. Furthermore, differences in patient subgroups and postoperative adverse cardiovascular events as a function of treatment regimen could not be demonstrated.

Needle-free pharmacological sedation techniques in paediatric patients for imaging procedures: a systematic review and meta-analysis.

BACKGROUND: Sedation techniques and drugs are increasingly used in children undergoing imaging procedures. In this systematic review and meta-analysis, we present an overview of literature concerning sedation of children aged 0-8 yr for magnetic resonance imaging (MRI) procedures using needle-free pharmacological techniques. METHODS: Embase, MEDLINE, Web of Science, and Cochrane databases were systematically searched for studies on the use of needle-free pharmacological sedation techniques for MRI procedures in children aged 0-8 yr. Studies using i.v. or i.m. medication or advanced airway devices were excluded. We performed a meta-analysis on sedation success rate. Secondary outcomes were onset time, duration, recovery, and adverse events. RESULTS: Sixty-seven studies were included, with 22 380 participants. The pooled success rate for oral chloral hydrate was 94% (95% confidence interval [CI]: 0.91-0.96); for oral chloral hydrate and intranasal dexmedetomidine 95% (95% CI: 0.92-0.97); for rectal, oral, or intranasal midazolam 36% (95% CI: 0.14-0.65); for oral pentobarbital 99% (95% CI: 0.90-1.00); for rectal thiopental 92% (95% CI: 0.85-0.96); for oral melatonin 75% (95% CI: 0.54-0.89); for intranasal dexmedetomidine 62% (95% CI: 0.38-0.82); for intranasal dexmedetomidine and midazolam 94% (95% CI: 0.78-0.99); and for inhaled sevoflurane 98% (95% CI: 0.97-0.99). CONCLUSIONS: We found a large variation in medication, dosage, and route of administration for needle-free sedation. Success rates for sedation techniques varied between 36% and 98%.

Perioperative Mortality in Pediatric Patients: A Systematic Review of Risk Assessment Tools for Use in the Preoperative Setting.

BACKGROUND: There are multiple preoperative risk scores for pediatric mortality. The aim of this study was to systematically describe and compare the existing studies of patient-specific multispecialty risk prediction scores for perioperative mortality in pediatric populations, with the goal of guiding clinicians on which may be most appropriate for use in the preoperative setting. METHODS: This study is a systematic literature review of published journal articles that presented the development, extension/updating, and/or validation of a risk core that predicted all-cause mortality (up to 30 days postoperatively) in pediatric patients undergoing a procedure in which anesthesia was used. Scores needed to be applicable to surgeries in more than one noncardiac surgical specialty and had to be able to be calculated by the anesthesiologist at the time of the preanesthetic assessment. Two investigators independently screened studies for inclusion and assessed study quality in the domains of clinical applicability, feasibility/ease of use in the clinical setting, and risk of bias. RESULTS: A total of 1,681 titles were retrieved. Of these, 10 studies met inclusion criteria: 9 reported the development and validation of scores, and 1 was an external validation of an existing score. Seven studies used varying years of multicenter data from the National Surgical Quality Improvement Program-Pediatric Participant Use File for development and/or validation. The unadjusted rate of mortality in the studies ranged from 0.3 to 3.6%. The preoperative predictors of mortality used in score development included patient demographics, preoperative therapies, and chronic conditions, among others. All models showed good discrimination upon validation (area under the receiver operating characteristics curve greater than 0.8). Most risk scores had high or unclear risks of bias. CONCLUSIONS: There are numerous scores available for the prediction of mortality in pediatric populations, all of which exhibited good performance. However, many have high or unclear risks of bias, and most have not undergone external validation.

Observer Variability as a Determinant of Measurement Error of Ultrasonographic Measurements of the Optic Nerve Sheath Diameter: A Systematic Review.

BACKGROUND: Ultrasonographic measurements of the diameter of the sheath of the optic nerve can be used to assess intracranial pressure indirectly. These measurements come with measurement error. OBJECTIVE: Our aim was to estimate observer's measurement error as a determinant of ultrasonographic measurement variability of the optic nerve sheath diameter. METHODS: A systematic search of the literature was conducted in Embase, Medline, Web of Science, the Cochrane Central Register of Trials, and the first 200 articles of Google Scholar up to April 19, 2021. Inclusion criteria were the following: healthy adults, B-mode ultrasonography, and measurements 3 mm behind the retina. Studies were excluded if standard error of measurement could not be calculated. Nine studies featuring 389 participants (median 40; range 15-100) and 22 observers (median 2; range 1-4) were included. Standard error of measurement and minimal detectable differences were calculated to quantify observer variability. Quality and risk of bias were assessed with the Guidelines for Reporting Reliability and Agreement Studies. RESULTS: The standard error of measurement of the intra- and interobserver variability had a range of 0.10-0.41 mm and 0.14-0.42 mm, respectively. Minimal detectable difference of a single observer was 0.28-1.1 mm. Minimal detectable difference of multiple observers (range 2-4) was 0.40-1.1 mm. Quality assessment showed room for methodological improvement of included studies. CONCLUSIONS: The standard errors of measurement and minimal detectable differences of ultrasonographic measurements of the optic nerve sheath diameter found in this review with healthy participants indicate caution should be urged when interpreting results acquired with this measurement method in clinical context.

Incidence, Prognostic Significance, and Risk Factors of Acute Kidney Injury Following Elective Infrarenal and Complex Endovascular Aneurysm Repair.

OBJECTIVE: Acute kidney injury (AKI) is a well known complication following cardiovascular procedures. The objective was to assess the incidence, risk factors, and prognostic significance of AKI after infrarenal endovascular aneurysm repair (EVAR) and complex EVAR (cEVAR; fenestrated or branched EVAR). METHODS: Consecutive patients undergoing elective infrarenal EVAR or cEVAR between 2000 and 2018 in two large teaching hospitals in the Netherlands were included. AKI was determined by serum creatinine levels increasing > 1.5 times or by an absolute increase of 26.5 mmol/L from baseline value (KDIGO criteria). The primary outcome was incidence of peri-operative AKI development. Secondary outcomes included mid-term renal function (RIFLE criteria), overall survival, and risk factors for AKI development. To determine survival and risk factors for AKI, multivariable Cox regression and logistic regression analyses were performed, accounting for pre-operative renal function and other confounders. RESULTS: In total, 540 patients who underwent infrarenal EVAR with 147 patients who underwent cEVAR also included. The incidence of AKI was 8.7% (n = 47) in infrarenal EVAR patients and 23% (n = 34) in cEVAR patients (fenestrated EVAR 18%; branched EVAR 38%). In contrast to patients without AKI, the renal function of surviving patients with AKI remained significantly reduced at six weeks and did not return to pre-operative values following infrarenal EVAR (three year estimated glomerular filtration rate [eGFR] 59.3 ± 23.1 mL/min/1.73m2vs. pre-operative eGFR 74.0 ± 21.7 mL/min/1.73m2; p = .006) or following cEVAR (three year eGFR 52.0 ± 23.7 mL/min/1.73m2vs. pre-operative eGFR 65.4 ± 18.6 mL/min/1.73m2; p = .082). After risk adjusted analysis, compared with non-AKI, post-operative AKI development was associated with a higher three year mortality rate following both infrarenal and cEVAR (infrarenal EVAR mortality hazard ratio [HR 1.6, 95% confidence interval [CI] 1.01 - 2.7 [p = .046]; cEVAR mortality HR 2.4, 95% CI 1.1 - 5.2 [p = .033]). Following multivariable logistic regression, pre-operative chronic kidney disease (eGFR < 60 mL/min/1.73m2; odds ratio [OR] 2.2, 95% CI 1.03 - 4.8) and neck diameter (OR 1.1, 95% CI 1.01 - 1.2) were significantly associated with AKI following infrarenal EVAR, whereas for cEVAR only contrast volume (OR 1.1, 95% CI 1.0 - 1.2]) was found to be statistically significantly associated with AKI. CONCLUSION: AKI is a well described complication following infrarenal EVAR and is common after cEVAR. As AKI seems to be associated with permanent renal deterioration and lower survival, efforts to prevent AKI are essential. Future studies are required to assess what factors are associated with a higher risk of developing AKI following cEVAR.

Proximal seal dilatation following fenestrated endovascular repair for complex abdominal aortic aneurysms.

OBJECTIVE: Although proximal neck dilatation following infrarenal endovascular aneurysm repair (EVAR) is common and is associated with proximal graft failure, little is known about sealing zone dilatation and its clinical relevance following fenestrated EVAR (FEVAR). We studied proximal seal dilatation (PSD) dynamics following FEVAR and assessed its clinical significance. METHODS: We included all consecutive patients treated for a juxta-/supra-renal aneurysm with fenestrated EVAR using the Zenith Fenestrated Endovascular Graft (Cook Medical, Bloomington, Ind) from 2008 to 2018 in two large teaching hospitals in the Netherlands. The primary outcome was PSD over time and was determined using a linear mixed-effects model. Secondary outcomes included associations for early PSD and difference in aortic dilatation at the level of the covered stent compared with the bare stent. Proximal seal-related adverse events were also obtained. RESULTS: Our cohort included 84 patients with a median computed tomography angiography follow-up time of 24.5 months (interquartile range [IQR], 17-42 months). Maximum aneurysm diameter was 60.1 mm (IQR, 56.9-67.2 mm). Mean proximal seal diameter at baseline was 26.2 mm (standard deviation [SD], ±2.8 mm), mean stent oversizing was 20.1% (SD, ±9.1%), and mean proximal seal length was 29.5 mm (SD, ±11.7 mm). Proximal seal dilatation of 1.7 mm (95% confidence interval [CI], 1.4-2.1 mm) was found in the first year, decelerating thereafter (second year, 0.9 mm/year; 95% CI, 0.7-1.1 mm/y). Over 10% PSD at 1 year occurred in 22 patients (27%) and was associated with stent graft oversizing (odds ratio, 1.1; 95% CI, 1.03-1.2; P = .008) and a lower number of target vessels (four fenestrations/ref two fenestrations: odds ratio, 0.13; 95% CI, 0.02-0.74; P = .029). At last available imaging, dilatation difference was higher at the level of the covered stent compared with the bare stent (3.0 mm [IQR, 1.3-5.1 mm] vs 1.6 mm [IQR, 0.8-2.5 mm]; P < .001). During the study period, only one patient (1.2%) developed a proximal seal-related adverse event (type IA endoleak). CONCLUSIONS: PSD is present following FEVAR, occurring at a faster rate in the first year and subsequently decelerating thereafter, similarly to neck dilatation after standard infrarenal EVAR. Although its clinical implication seems to remain limited in the first years following implantation, further research is required to assess the effect of PSD on long-term FEVAR outcomes.

Validation of a new combined transcutaneous tcPCO2 and tcPO2 sensor in children in the operating theater.

BACKGROUND: Arterial blood gas analysis is the gold standard for monitoring of Pa CO2 and PaO2 during mechanical ventilation. However, continuous measurements would be preferred. Transcutaneous sensors continuously measure blood gases diffusing from the locally heated skin. These sensors have been validated in children mostly in intensive care settings. Accuracy in children during general anesthesia is largely unknown. AIMS: We conducted a study in children undergoing general anesthesia to validate the use and to determine the accuracy of continuous transcutaneous measurements of the partial pressures of PCO2 (tcPCO2 ) and PO2 (tcPO2 ). METHODS: A prospective observational study in a tertiary care pediatric hospital in The Netherlands, from April to October 2018, in children aged 0-18 years undergoing general anesthesia. Patients were included when endotracheally intubated and provided with an arterial catheter for regular blood sampling. Patients with a gestational age <31 weeks, burn victims, and patients with skin disease were excluded. TcPCO2 and tcPO2  measurements were performed with a SenTec OxiVenT™ sensor (SenTec AG). Accuracy was determined with an agreement analysis between arterial and transcutaneous PCO2 and PO2  values, and between arterial and endtidal PCO2 (etCO2 ) values, according to Bland and Altman, accounting for multiple measurements per subject. RESULTS: We included 53 patients (median age 4.1 years, IQR 0.7-14.4 years) and retrieved 175 samples. TcPCO2 -Pa CO2 agreement analysis provided a bias of 0.06 kPa (limits of agreement (LOA) -1.18 to 1.31), the etCO2 -Pa CO2 agreement showed a bias of -0.31 kPa (LOA -1.38 to 0.76). Results of the tcPO2 -PaO2 agreement showed a bias of 3.40 to 0.86* (mean tension) kPa. CONCLUSIONS: This study showed good agreement between Pa CO2 and tcPCO2 in children of all ages during general anesthesia. Both transcutaneous and endtidal CO2  measurements showed good accuracy. TcPO2 is only accurate under 6 months of age.

Intermittent levosimendan infusion in ambulatory patients with end-stage heart failure: a systematic review and meta-analysis of 984 patients.

We sought to synthesize the available evidence regarding safety and efficacy of intermittent levosimendan (LEVO) infusions in ambulatory patients with end-stage heart failure (HF). Safety and efficacy of ambulatory intermittent LEVO infusion in patients with end-stage HF are yet not established. We systematically searched MEDLINE, EMBASE, SCOPUS, Web of Science, and Cochrane databases, from inception to January 30, 2021 for studies reporting outcome of adult ambulatory patients with end-stage HF treated with intermittent LEVO infusion. Fifteen studies (8 randomized and 7 observational) comprised 984 patients (LEVO [N = 727] and controls [N = 257]) met the inclusion criteria. LEVO was associated with improved New York Heart Association (NYHA) functional class (weighted mean difference [WMD] -1.04, 95%CI: -1.70 to -0.38, p < 0.001, 5 studies, I2 = 93%), improved left ventricular (LV) ejection fraction (WMD 4.0%, 95%CI: 2.8% to 5.3%, p < 0.001, 6 studies, I2 = 9%), and reduced BNP levels (WMD -549 pg/mL, 95%CI -866 to -233, p < 0001, 3 studies, I2 = 66%). All-cause death was not different (RR 0.65, 95%CI: 0.38 to 1.093, p = 0.10, 6 studies, I2 = 0), but cardiovascular death was lower on LEVO (RR 0.34, 95%CI: 0.13 to 0.87, p = 0.02, 3 studies, I2 = 0) compared to controls. Furthermore, health-related quality of life (HRQoL) was improved alongside with reduced LV size following LEVO infusions. Major adverse events were not different between LEVO and placebo. In conclusion, intermittent LEVO infusions in ambulatory patients with end-stage HF is associated with less frequent cardiovascular death alongside with improved NYHA class, quality of life, BNP levels, and LV function. However, the current evidence is limited by heterogeneous and relatively small studies.