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.

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.

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%.

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.

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.

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.

Supervised Exercise Therapy is Effective for Patients With Intermittent Claudication Regardless of Psychological Constructs.

OBJECTIVE: According to current guidelines, supervised exercise therapy (SET) is the treatment of choice for intermittent claudication (IC). Little is known about the potential consequences of psychological factors on the effectiveness of treatment. The aim of this study was to determine possible associations between a set of psychological constructs and treatment outcomes, and to investigate whether self efficacy increased after SET. METHODS: This was a substudy of the ELECT Registry, a multicentre Dutch prospective cohort study in patients with IC receiving primary SET. A complete set of validated questionnaires scoring extraversion, neuroticism, conscientiousness, anxiety, depression, self control, optimism, and self efficacy was obtained in 237 patients (median age 69 years, 40% female). Anxiety and depression were dichotomised using established cutoff scores, whereas other scores were analysed as continuous measures. Multiple linear regression analyses determined possible associations between these independent variables and maximum and functional walking distances (MWD and FWD, respectively), Six Minute Walk Test (6MWT), and VascuQol-6 (dependent variables). Self efficacy during 12 months of SET was analysed using a linear mixed model. RESULTS: Neuroticism and anxiety were associated with lower overall VascuQol-6 scores (estimate -1.35 points [standard error (SE) 0.57; p = .018] and -1.98 points [SE 0.87, p = .023], respectively). Optimism and self efficacy demonstrated higher overall 6MWT (5.92 m [SE 2.34; p = .012] and 1.35 m [SE 0.42; p = .001], respectively). Self control was associated with lower overall log MWD (-0.02 [SE 0.01; p = .038] and log FWD (-0.02 [SE 0.01; p = .080), whereas self efficacy had a higher overall log MWD (0.01 [SE 0.003; p = .009]) and log FWD (0.01 [SE 0.003; p = .011]). Depressive patients with IC demonstrated a greater improvement in 6MWT during follow up (17.56 m [SE 8.67; p = .044]), but this small effect was not confirmed in sensitivity analysis. Self efficacy did not increase during follow up (0.12% [SE 0.49; p = .080]). CONCLUSIONS: The beneficial effects of SET occur regardless of the psychological constructs, supporting current guidelines recommending a SET first strategy in each patient with IC.

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.

Rotational Thromboelastometry-Guided Transfusion Protocol to Reduce Allogeneic Blood Transfusion in Proximal Aortic Surgery With Deep Hypothermic Circulatory Arrest.

OBJECTIVES: To determine the impact of a rotational thromboelastometry (ROTEM)-guided transfusion protocol on the use of blood products, patient outcomes, coagulation factor concentrates, and costs. DESIGN: A single-center retrospective cohort study. SETTING: A tertiary university hospital. PATIENTS: Adults undergoing proximal aortic surgery with deep hypothermic circulatory arrest. INTERVENTION: ROTEM-guided transfusion protocol compared with clinically-guided transfusion. MEASUREMENTS AND MAIN RESULTS: Two hundred seventeen patients were included; seventy-one elective and 24 emergency patients in the clinically-guided group, and 59 elective and 63 emergency patients in the ROTEM-guided transfusion protocol group. In the ROTEM-guided transfusion protocol group, a significant reduction in transfusion of red blood cells (5 [3-8] v 2 [0-4], p < 0.001), platelet concentrate (2 [2-3] v 1 [1-2], p < 0.001), and plasma (1,980 mL [1,320-3,300] v 800 mL [0-1,000], p < 0.001) was seen in elective surgery. Emergency patients received fewer red blood cells (7 [5-10] v 5 [2-10], p = 0.040), platelet concentrate (3 [2-4] v 2 [2-3], p = 0.023), and plasma (3,140 mL [1,980-3,960] v 1,000 mL [0-1,400], p < 0.001). Prothrombin complex concentrate and fibrinogen concentrate were increased significantly in elective and emergency patients. The surgical reexploration for bleeding rate was decreased in elective patients 33.8% v 5.1%. CONCLUSION: The implementation of a ROTEM-guided transfusion protocol might have the potential to decrease blood product transfusion and may improve patient 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.

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.

Impact of body mass index on growth hormone stimulation tests in children and adolescents: a systematic review and meta-analysis.

Peak stimulated growth hormone (GH) levels are known to decrease with increasing body mass index (BMI), possibly leading to overdiagnosis of GH deficiency (GHD) in children with overweight and obesity. However, current guidelines do not guide how to interpret the peak GH values of these children. This systematic review and meta-analysis aimed to study the effect of the BMI standard deviation score (SDS) on stimulated peak GH values in children, to identify potential moderators of this association, and to quantify the extent to which peak GH values in children with obesity are decreased. This systematic review was performed by the PRISMA guidelines. Medline, Embase, Cochrane, Web of Science, and Google Scholar databases were searched for studies reporting the impact of weight status on peak GH in children. Where possible, individual participant data was extracted and/or obtained from authors. Quality and risk of bias were evaluated using the Scottish Intercollegiate Guidelines Network (SIGN) checklists. The primary outcome was the association between peak GH values and BMI SDS. The pooled correlation coefficient r, 95% confidence interval (CI), and heterogeneity statistic I2 were calculated under a multilevel, random-effects model. In addition, exploratory moderator analyses and meta-regressions were performed to investigate the effects of sex, pubertal status, presence of syndromic obesity, mean age and mean BMI SDS on the study level. For the individual participant dataset, linear mixed-models regression analysis was performed with BMI SDS as the predictor and ln(peak GH) as the outcome, accounting for the different studies and GH stimulation agents used. In total, 58 studies were included, providing data on n = 5135 children (576 with individual participant data). Thirty-six (62%) studies had high, 19 (33%) medium, and 3 (5%) low risks of bias. Across all studies, a pooled r of -0.32 (95% CI -0.41 to -0.23, n = 2434 patients from k = 29 subcohorts, I2 = 75.2%) was found. In meta-regressions, larger proportions of males included were associated with weaker negative correlations (p = 0.04). Pubertal status, presence of syndromic obesity, mean age, and mean BMI SDS did not moderate the pooled r (all p > 0.05). Individual participant data analysis revealed a beta of -0.123 (95% CI -0.160 to -0.086, p < 0.0001), i.e. per one-point increase in BMI SDS, peak GH decreases by 11.6% (95% CI 8.3-14.8%). To our knowledge, this is the first systematic review and meta-analysis to investigate the impact of BMI SDS on peak GH values in children. It showed a significant negative relationship. Importantly, this relationship was already present in the normal range of BMI SDS and could lead to overdiagnosis of GHD in children with overweight and obesity. With the ever-rising prevalence of pediatric obesity, there is a need for BMI (SDS)-specific cutoff values for GH stimulation tests in children. Based on the evidence from this meta-analysis, we suggest the following weight status-adjusted cutoffs for GH stimulation tests that have cutoffs for children with normal weight of 5, 7, 10, and 20 µg/L: for overweight children: 4.6, 6.5, 9.3, and 18.6 µg/L; and for children with obesity: 4.3, 6.0, 8.6, and 17.3 µg/L.

Risk Factors, Dynamics, and Clinical Consequences of Aortic Neck Dilatation after Standard Endovascular Aneurysm Repair.

OBJECTIVE: Aortic neck dilatation (AND) occurs after endovascular aneurysm repair (EVAR) with self expanding stent grafts (SESs). Whether it continues, ultimately exceeding the endograft diameter leading to abdominal aortic aneurysm (AAA) rupture, remains uncertain. Dynamics, risk factors, and clinical relevance of AND were investigated after EVAR with standard SESs. METHODS: All intact EVAR patients treated from 2000 to 2015 at a tertiary institution were included. Demographic, anatomical, and device related characteristics were investigated as risk factors for AND. Outer to outer diameters were measured at a single standardised aortic level on reconstructed computed tomography (CT) images. RESULTS: A total of 460 patients were included (median follow up 5.2 years, interquartile range [IQR] 3.0, 7.7 years; CT imaging follow up 3.3 years, IQR 1.3, 5.4). Baseline neck diameter was 24 mm (IQR 22, 26) and increased 11.1% (IQR 1.5%, 21.9%) at last CT imaging. Endograft oversizing was 20.0% (IQR 13.6, 28.0). AND was greater during the first year (5.2% [IQR 0, 11.7]) decreasing subsequently (two to four years to 1.4%/year [IQR 0.0, 4.5%], p ≤ .001) and was associated with suprarenal fixation endografts (t value = 7.9, p < .001) and oversizing (t value = 4.4, p < .001). AND exceeding the endograft was 3.5% (95% CI 2.2% - 4.8%) and 14.4% (95% CI 11.0% - 17.8%) at five and eight years, respectively. Excessive AND was associated with baseline neck diameter (OR 1.2/mm, 95% CI 1.05 - 1.41) while the Excluder endograft had a protective effect (OR 0.15, 95% CI 0.04 - 0.58). Excessive AND was associated with type 1A endoleak (HR 3.3, 95% CI 1.1 - 9.7) and endograft migration > 5 mm (HR 3.1, 95% CI 1.4 - 6.9). CONCLUSION: AND after EVAR with SES is associated with endograft oversizing and radial force but decelerates after the first post-operative year. Baseline aortic neck diameter and suprarenal stent bearing endografts were associated with an increased risk of AND beyond nominal stent graft diameter. However, it remains unclear whether patient selection, differences in endograft radial force or the suprarenal stent are accountable for this difference.

Postoperative Hypotension after Noncardiac Surgery and the Association with Myocardial Injury.

BACKGROUND: Intraoperative hypotension has been associated with postoperative morbidity and early mortality. Postoperative hypotension, however, has been less studied. This study examines postoperative hypotension, hypothesizing that both the degree of hypotension severity and longer durations would be associated with myocardial injury. METHODS: This single-center observational cohort was comprised of 1,710 patients aged 60 yr or more undergoing intermediate- to high-risk noncardiac surgery. Frequent sampling of hemodynamic monitoring on a postoperative high-dependency ward during the first 24 h after surgery was recorded. Multiple mean arterial pressure (MAP) absolute thresholds (50 to 75 mmHg) were used to define hypotension characterized by cumulative minutes, duration, area, and time-weighted-average under MAP. Zero time spent under a threshold was used as the reference group. The primary outcome was myocardial injury (a peak high-sensitive troponin T measurement 50 ng/l or greater) during the first 3 postoperative days. RESULTS: Postoperative hypotension was common, e.g., 2 cumulative hours below a threshold of 60 mmHg occurred in 144 (8%) patients while 4 h less than 75 mmHg occurred in 824 (48%) patients. Patients with myocardial injury had higher prolonged exposures for all characterizations. After adjusting for confounders, postoperative duration below a threshold of 75 mmHg for more than 635 min was associated with myocardial injury (adjusted odds ratio, 2.68; 95% CI, 1.46 to 5.07, P = 0.002). Comparing multiple thresholds, cumulative durations of 2 to 4 h below a MAP threshold of 60 mmHg (adjusted odds ratio, 3.26; 95% CI, 1.57 to 6.48, P = 0.001) and durations of more than 4 h less than 65 mmHg (adjusted odds ratio, 2.98; 95% CI, 1.78 to 4.98, P < 0.001) and 70 mmHg (adjusted odds ratio, 2.18; 95% CI, 1.37 to 3.51, P < 0.001) were also associated with myocardial injury. Associations remained significant after adjusting for intraoperative hypotension, which independently was not associated with myocardial injury. CONCLUSIONS: In this study, postoperative hypotension was common and was independently associated with myocardial injury.

Survival After Uncomplicated EVAR in Octogenarians is Similar to the General Population of Octogenarians Without an Abdominal Aortic Aneurysm.

OBJECTIVE: Long term survival after endovascular aortic aneurysm repair (EVAR) in octogenarians remains unclear. This was evaluated by comparing octogenarians after EVAR with a matched group of octogenarians without an abdominal aortic aneurysm (AAA) from the Rotterdam Study (RS). The influence of complications after EVAR on survival was also studied with the aim of identifying risk factors for the development of complications in octogenarians. METHODS: Using propensity score matching (PSM), 83 EVAR octogenarians were matched for comorbidities with 83 octogenarians from the RS, and survival was compared between these two groups using Cox proportional hazard analysis. Then, complications were studied, defined as cardiac or pulmonary, renal deterioration, access site bleeding, acute limb ischaemia or bowel ischaemia, within 30 days of surgery between 83 EVAR octogenarians and 475 EVAR non-octogenarians. Also, the difference in baseline characteristics between the octogenarians with and without complications after EVAR were studied, and survival was compared between the RS controls and the complicated and uncomplicated EVAR octogenarians separately. RESULTS: The total EVAR octogenarian population did not show an increased mortality risk compared with RS octogenarian controls (hazard ratio [HR] 1.28, 95% confidence interval [CI] 0.84-1.97). Post-operative complications occurred in 22 octogenarians (27%) and 59 non-octogenarians (12.4%, p < .001), mainly cardiac, pulmonary, and bleeding complications. All baseline characteristics were similar in the complicated EVAR octogenarians compared with the uncomplicated EVAR octogenarians. After uncomplicated EVAR, octogenarians had a similar survival compared with the RS controls (HR 1.09, 95% CI 0.68-1.77), but after complicated EVAR their mortality risk increased significantly (HR 1.93, 95% CI 1.06-3.54). CONCLUSION: After standard EVAR, the life expectancy of octogenarians is the same as that of a matched group from the general population without an AAA, provided they do not develop early post-operative complications. Patient selection and meticulous peri-operative care are key.

Immediate postoperative high-sensitivity troponin T concentrations and long-term patient-reported health-related quality of life: A prospective cohort study.

BACKGROUND: Myocardial injury after noncardiac surgery is associated with mortality and major adverse postoperative cardiovascular events. The effect of postoperative troponin concentrations on patient-reported health-related quality of life (HRQoL) is unknown. OBJECTIVE: The study examined the association between immediate postoperative troponin concentrations and self-reported HRQoL 1 year after surgery. DESIGN: Prospective cohort study. SETTING: Single-centre tertiary care hospital in the Netherlands between July 2012 and 2015. PATIENTS: Patients aged at least 60 years undergoing moderate and major noncardiac surgery. INTERVENTION: None. MAIN OUTCOME MEASURES: HRQoL total score was assessed with the EuroQol five-dimensional questionnaire. Tobit regression analysis was used to determine the association between postoperative troponin concentrations and 1-year HRQoL. Peak high-sensitivity troponin T values were divided into four categories: less than 14, 14 to 49, 50 to 149 and at least 150 ng l. RESULTS: A total of 3085 patients with troponin measurements were included. 2634 (85.4%) patients were alive at 1-year follow-up of whom 1297 (49.2%) returned a completed questionnaire. The median score for HRQoL was 0.82 (0.85, 0.81, 0.77 and 0.71 per increasing troponin category). Multivariable analysis revealed betas of -0.06 [95% confidence interval (CI) -0.09 to -0.02], -0.11 (95% CI -0.18 to -0.04) and -0.18 (95% CI -0.29 to -0.07) for troponin levels of 14 to 49, 50 to 149 and at least 150 ng l when compared with values less than 14 ng l. Other independent predictors for lower HRQoL were chronic obstructive pulmonary disease, female sex, peripheral arterial disease and increasing age. CONCLUSION: Higher levels of postoperative troponin measured immediately after surgery were independently associated with lower self-reported HRQoL total score at 1-year follow-up.

Aminoacyl-tRNA synthetase deficiencies in search of common themes.

PURPOSE: Pathogenic variations in genes encoding aminoacyl-tRNA synthetases (ARSs) are increasingly associated with human disease. Clinical features of autosomal recessive ARS deficiencies appear very diverse and without apparent logic. We searched for common clinical patterns to improve disease recognition, insight into pathophysiology, and clinical care. METHODS: Symptoms were analyzed in all patients with recessive ARS deficiencies reported in literature, supplemented with unreported patients evaluated in our hospital. RESULTS: In literature, we identified 107 patients with AARS, DARS, GARS, HARS, IARS, KARS, LARS, MARS, RARS, SARS, VARS, YARS, and QARS deficiencies. Common symptoms (defined as present in ≥4/13 ARS deficiencies) included abnormalities of the central nervous system and/or senses (13/13), failure to thrive, gastrointestinal symptoms, dysmaturity, liver disease, and facial dysmorphisms. Deep phenotyping of 5 additional patients with unreported compound heterozygous pathogenic variations in IARS, LARS, KARS, and QARS extended the common phenotype with lung disease, hypoalbuminemia, anemia, and renal tubulopathy. CONCLUSION: We propose a common clinical phenotype for recessive ARS deficiencies, resulting from insufficient aminoacylation activity to meet translational demand in specific organs or periods of life. Assuming residual ARS activity, adequate protein/amino acid supply seems essential instead of the traditional replacement of protein by glucose in patients with metabolic diseases.

Patients with large neck diameter have a higher risk of type IA endoleaks and aneurysm rupture after standard endovascular aneurysm repair.

OBJECTIVE: Standard endovascular aneurysm repair (EVAR) is the most common treatment of abdominal aortic aneurysms (AAAs). EVAR has been increasingly used in patients with hostile neck features. This study investigated the outcomes of EVAR in patients with neck diameters ≥30 mm in the prospectively maintained Endurant Stent Graft Natural Selection Global Postmarket Registry (ENGAGE). METHODS: This is a retrospective study comparing patients with neck diameters ≥30 mm with patients with neck diameters <30 mm. The primary end point was type IA endoleak (EL1A). Secondary end points included secondary interventions to correct EL1A, aneurysm rupture, and survival. RESULTS: This study included 1257 patients (mean age, 73.1 years; 89.4% male) observed for a median 4.0 years (interquartile range, 2.7-4.8 years). A total of 97 (7.7%) patients had infrarenal neck diameters ≥30 mm and were compared with the remaining 1160 (92.3%) with neck diameters <30 mm. At baseline, there were no differences between groups regarding demographics and comorbidities other than cardiac disease, which was more frequent in the ≥30-mm neck diameter group (P = .037). There were no significant differences between the groups regarding neck length, angulation, thrombus, or calcification. Mean preoperative AAA diameter was 64.6 ± 11.3 mm in the ≥30-mm neck diameter group and 60.0 ± 11.6 mm in the <30-mm neck diameter group (P < .001). Stent graft oversizing was significantly less in the ≥30-mm neck diameter group (12.2% ± 8.9% vs 22.1% ± 11.9%; P <. 001). Five patients (5.2%) in the ≥30-mm neck diameter group and 30 (2.6%) with neck diameters <30 mm developed EL1A, yielding a 4-year freedom from EL1A of 92.4% vs 96.6%, respectively (P = .09). Oversizing was 21.8% ± 13.0% for patients developing EL1A and 21.3% ± 12.4% for the remaining cohort (P = .99). In adjusting for neck length, AAA diameter, and device oversizing, patients with neck diameter ≥30 mm were at greater risk for development of EL1A (hazard ratio, 3.0; 95% confidence interval, 1.0-9.3; P = .05). Secondary interventions due to EL1A did not differ between groups (P = .36). AAA rupture occurred in three patients with neck diameter ≥30 mm (3.1%) and in eight patients with neck diameter <30 mm (0.7%; hazard ratio, 5.1; 95% confidence interval, 1.4-19.2; P = .016); two cases were EL1A related in each group. At 4 years, overall survival was 61.6% for the ≥30-mm neck diameter group and 75.2% for the <30-mm neck diameter group (P = .009), which remained significant on correcting for sex and AAA diameter (P = .016). CONCLUSIONS: In this study, patients with infrarenal neck diameter ≥30 mm had a threefold increased risk of EL1A and fivefold risk of aneurysm rupture after EVAR as well as worse overall survival. This may influence the choice of AAA repair and underlines the need for regular computed tomography-based imaging surveillance in this subset of patients. Furthermore, these results can serve as standards with which new, possibly improved technology, such as EndoAnchors (Medtronic, Santa Rosa, Calif), can be compared.

Anatomic predictors for late mortality after standard endovascular aneurysm repair.

OBJECTIVE: Abdominal aortic aneurysm (AAA) management involves a decision process that takes into account anatomic characteristics, surgical risks, patients' preferences, and expected survival. Whereas larger AAA diameter has been associated with increased mortality after both standard endovascular aneurysm repair (EVAR) and open repair, it is unclear whether survival after EVAR is influenced by other anatomic characteristics. The purpose of this study was to determine the importance of baseline anatomic features on survival after EVAR. METHODS: All patients treated at a tertiary teaching center with EVAR for intact standard infrarenal AAA from 2000 to 2014 were included. The civil data registry was queried to determine survival status; causes of death were obtained from death certificates. The primary study end point was to determine the impact of baseline morphologic features on all-cause and cardiovascular mortality after EVAR. RESULTS: This study included 404 EVAR patients (12.1% women; mean age, 73 years) with a median follow-up of 5.8 years (interquartile range, 3.1-7.4 years). The 5- and 10-year overall survival rates for the entire population after EVAR were 70% (95% confidence interval [CI], 66%-75%) and 43% (95% CI, 37%-50%), respectively. Only AAA diameter >70 mm (hazard ratio [HR], 1.75; 95% CI, 1.20-3.56) was identified as an independent anatomic predictor of all-cause mortality. Death due to cardiovascular causes occurred in 60 (38.5%) patients. Aneurysm-related mortality was responsible for six of the cardiovascular-related deaths. In multivariable analysis, both neck diameter ≥30 mm (HR, 2.16; 95% CI, 1.05-4.43) and AAA diameter >70 mm (HR, 2.45; 95% CI, 1.34-4.46) were identified as independent morphologic risk factors for cardiovascular mortality, whereas >25% circumferential neck thrombus (HR, 0.32; 95% CI, 0.13-0.77) was protective. CONCLUSIONS: This study suggests that patients with AAA diameters >70 mm are at increased risk of all-cause and cardiovascular mortality. In addition, patients with infrarenal neck diameters ≥30 mm have a greater risk of cardiovascular mortality, although AAA-related deaths were not more frequent in this group of patients. Consequently, a more aggressive management of cardiovascular medical comorbidities may be warranted to improve survival after standard EVAR in these patients.