Perioperative quality indicators specific to the practice of anesthesia in noncardiac surgery: an umbrella review.

PURPOSE: Improvement in delivery of perioperative care depends on the ability to measure outcomes that can direct meaningful changes in practice. We sought to identify and provide an overview of perioperative quality indicators specific to the practice of anesthesia in noncardiac surgery. SOURCE: We conducted an umbrella review (a systematic review of systematic reviews) according to Joanna Briggs Institute methodology. We included systematic reviews examining perioperative indicators in patients ≥ 18 yr of age undergoing noncardiac surgery. Our primary outcome was any quality indicator specific to anesthesia. Indicators were classified by the Donabedian system and perioperative phase of care. The quality of systematic reviews was assessed using AMSTAR 2 criteria. Level of evidence of quality indicators was stratified by the Oxford Centre for Evidence-Based Medicine Classification. PRINCIPAL FINDINGS: Our search returned 1,475 studies. After removing duplicates and screening of abstracts and full texts, 23 systematic reviews encompassing 3,164 primary studies met our inclusion criteria. There were 330 unique quality indicators. Process indicators were most common (n = 169), followed by outcome (n = 114) and structure indicators (n = 47). Few identified indicators were supported by high-level evidence (45/330, 14%). Level 1 evidence supported indicators of antibiotic prophylaxis (1a), venous thromboembolism prophylaxis (1a), postoperative nausea/vomiting prophylaxis (1b), maintenance of normothermia (1a), and goal-directed fluid therapy (1b). CONCLUSION: This umbrella review highlights the scarcity of perioperative quality indicators that are supported by high quality evidence. Future development of quality indicators and recommendations for outcome measurement should focus on metrics that are supported by level 1 evidence. Potential targets for evidence-based quality-improvement programs in anesthesia are identified herein. STUDY REGISTRATION: PROSPERO (CRD42020164691); first registered 28 April 2020.

RéSUMé: OBJECTIF: L'amélioration de la prestation des soins périopératoires dépend de la capacité de mesurer les résultats qui peuvent orienter des changements significatifs dans la pratique. Nous avons cherché à identifier et à fournir une vue d'ensemble des indicateurs périopératoires de qualité spécifiques à la pratique de l'anesthésie en chirurgie non cardiaque. SOURCES: Nous avons mené une revue d'ensemble (une revue systématique des revues systématiques) selon la méthodologie de l'Institut Joanna Briggs. Nous avons inclus des revues systématiques examinant les indicateurs périopératoires chez les patient·es âgé·es de 18 ans ou plus bénéficiant d'une chirurgie non cardiaque. Notre critère d'évaluation principal était tout indicateur de qualité spécifique à l'anesthésie. Les indicateurs ont été classés en fonction du système de Donabedian et de la phase périopératoire des soins. La qualité des revues systématiques a été évaluée à l'aide des critères AMSTAR 2. Le niveau de donnée probante des indicateurs de qualité a été stratifié selon l'Oxford Centre for Evidence-Based Medicine Classification. CONSTATATIONS PRINCIPALES: Notre recherche a permis de trouver 1475 études. Après avoir éliminé les doublons et examiné les résumés et les textes intégraux, 23 revues systématiques englobant 3164 études primaires ont répondu à nos critères d'inclusion. Il y avait 330 indicateurs de qualité uniques. Les indicateurs de processus étaient les plus courants (n = 169), suivi des indicateurs de résultats (n = 114) et des indicateurs de structure (n = 47). Peu d'indicateurs identifiés étaient étayés par des données probantes de haut niveau (45/330, 14 %). Les données probantes de niveau 1 ont confirmé les indicateurs de l'antibioprophylaxie (1a), de la prophylaxie pour la thromboembolie veineuse (1a), de la prophylaxie postopératoire pour les nausées/vomissements (1b), du maintien de la normothermie (1a) et de la fluidothérapie ciblée (1b). CONCLUSION: Cet examen d'ensemble met en évidence la rareté des indicateurs périopératoires de qualité qui sont étayés par des données probantes de haute qualité. L'élaboration future d'indicateurs de qualité et de recommandations pour la mesure des résultats devrait être axée sur des paramètres étayés par des données probantes de niveau 1. Les cibles potentielles des programmes d'amélioration de la qualité de l'anesthésie fondés sur des données probantes sont identifiées dans le présent manuscrit. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42020164691); premier enregistrement le 28 avril 2020.

Spectroscopy-based multi-parametric quantification in subjects with liver iron overload at 1.5T and 3T.

PURPOSE: To evaluate the precision profile (repeatability and reproducibility) of quantitative STEAM-MRS and to determine the relationships between multiple MR biomarkers of chronic liver disease in subjects with iron overload at both 1.5 Tesla (T) and 3T. METHODS: MRS data were acquired in patients with known or suspected liver iron overload. Two STEAM-MRS sequences (multi-TE and multi-TE-TR) were acquired at both 1.5T and 3T (same day), including test-retest acquisition. Each acquisition enabled estimation of R1, R2, and FWHM (each separately for water and fat); and proton density fat fraction. The test-retest repeatability and reproducibility across acquisition modes (multi-TE vs. multi-TE-TR) of the estimates were evaluated using intraclass correlation coefficients, linear regression, and Bland-Altman analyses. Multi-parametric relationships between parameters at each field strength, across field strengths, and with liver iron concentration were also evaluated using linear and nonlinear regression. RESULTS: Fifty-six (n = 56) subjects (10 to 73 years, 37 males/19 females) were successfully recruited. Both STEAM-MRS sequences demonstrated good-to-excellent precision (intraclass correlation coefficient ≥ 0.81) for the quantification of R1water , R2water , FWHMwater , and proton density fat fraction at both 1.5T and 3T. Additionally, several moderate (R2 = 0.50 to 0.69) to high (R2 ≥ 0.70) correlations were observed between biomarkers, across field strengths, and with liver iron concentration. CONCLUSIONS: Over a broad range of liver iron concentration, STEAM-MRS enables rapid and precise measurement of multiple biomarkers of chronic liver disease. By evaluating the multi-parametric relationships between biomarkers, this work may advance the comprehensive MRS-based assessment of chronic liver disease and may help establish biomarkers of chronic liver disease.

Airway recommendations for perioperative patients during the COVID-19 pandemic: a scoping review.

PURPOSE: Numerous guideline recommendations for airway and perioperative management during the COVID-19 pandemic have been published. We identified, synthesized, and compared guidelines intended for anesthesiologists. SOURCE: Member society websites of the World Federation of Societies of Anesthesiologists and the European Society of Anesthesiologists were searched. Recommendations that focused on perioperative airway management of patients with proven or potential COVID-19 were included. Accelerated screening was used; data were extracted by one reviewer and verified by a second. Data were organized into themes based on perioperative phase of care. PRINCIPAL FINDINGS: Thirty unique sets of recommendations were identified. None reported methods for systematically searching or selecting evidence to be included. Four were updated following initial publication. For induction and airway management, most recommended minimizing personnel and having the most experienced anesthesiologist perform tracheal intubation. Significant congruence was observed among recommendations that discussed personal protective equipment. Of those that discussed tracheal intubation methods, most (96%) recommended videolaryngoscopy, while discordance existed regarding use of flexible bronchoscopy. Intraoperatively, 23% suggested specific anesthesia techniques and most (63%) recommended a specific operating room for patients with COVID-19. Postoperatively, a minority discussed extubation procedures (33%), or care in the recovery room (40%). Non-technical considerations were discussed in 27% and psychological support for healthcare providers in 10%. CONCLUSION: Recommendations for perioperative airway management of patients with COVID-19 overlap to a large extent but also show significant differences. Given the paucity of data early in the pandemic, it is not surprising that identified publications largely reflected expert opinion rather than empirical evidence. We suggest future efforts should promote coordinated responses and provide suggestions for studying and establishing best practices in perioperative patients. STUDY REGISTRATION: Open Science Framework ( https://osf.io/a2k4u/ ); date created, 26 March 2020.

RéSUMé: OBJECTIF: De nombreuses recommandations ont été publiées pour la prise en charge des voies aériennes et périopératoires pendant la pandémie de COVID-19. Nous avons identifié, synthétisé et comparé les lignes directrices destinées aux anesthésiologistes. SOURCES: Les sites internet des sociétés membres de la Fédération mondiale des sociétés d'anesthésiologistes et de la Société européenne d'anesthésiologie ont été consultés. Les recommandations axées sur la prise en charge périopératoire des voies aériennes des patients atteints de COVID-19 prouvée ou potentielle ont été incluses. Une sélection accélérée a été utilisée; les données ont été extraites par un examinateur et vérifiées par un second. Les données ont été thématiquement organisées en fonction de la phase périopératoire des soins. CONSTATATIONS PRINCIPALES: Trente ensembles uniques de recommandations ont été identifiés. Aucun de ces ensemble n'a fait état de méthodes de recherche ou de sélection systématiques des données probantes à inclure. Quatre ont été mis à jour après leur publication initiale. Pour l'induction et la prise en charge des voies aériennes, la plupart ont recommandé de minimiser le personnel et de demander à l'anesthésiologiste le plus expérimenté de réaliser l'intubation trachéale. Une congruence significative a été observée parmi les recommandations qui portaient sur les équipements de protection individuelle. Parmi les lignes directrices évoquant les méthodes d'intubation trachéale, la plupart (96 %) ont recommandé la vidéolaryngoscopie, alors qu'il existait une discordance concernant l'utilisation de bronchoscopes flexibles. En peropératoire, 23 % ont suggéré des techniques d'anesthésie spécifiques et la plupart (63 %) ont recommandé une salle d'opération spécifique pour les patients atteints de COVID-19. En postopératoire, une minorité a abordé le sujet des procédures d'extubation (33 %) ou des soins en salle de réveil (40 %). Les considérations non techniques ont été traitées dans 27 % des cas et le soutien psychologique aux fournisseurs de soins de santé dans 10 %. CONCLUSION: Les recommandations pour la prise en charge périopératoire des voies aériennes des patients atteints de COVID-19 se chevauchent dans une large mesure, mais montrent également des différences significatives. Compte tenu de la rareté des données au début de la pandémie, il n'est pas surprenant que les publications identifiées reflètent en grande partie l'opinion d'experts plutôt que de se fonder sur des données probantes empiriques. Nous suggérons que les efforts futurs soient déployés de manière à promouvoir des réponses coordonnées et proposer des suggestions pour étudier et établir les meilleures pratiques chez les patients en période périopératoire. ENREGISTREMENT DE L'éTUDE: Open Science Framework ( https://osf.io/a2k4u/ ); date de création, 26 mars 2020.

Optimal Threshold of Controlled Attenuation Parameter for Detection of HIV-Associated NAFLD With Magnetic Resonance Imaging as the Reference Standard.

BACKGROUND: Controlled attenuation parameter (CAP) is an ultrasound-based point-of-care method to quantify liver fat; however, the optimal threshold for CAP to detect pathologic liver fat among persons living with human immunodeficiency virus (HIV; PLWH) is unknown. Therefore, we aimed to identify the diagnostic accuracy and optimal threshold of CAP for the detection of liver-fat among PLWH with magnetic resonance imaging proton-density fat fraction (MRI-PDFF) as the reference standard. METHODS: Patients from a prospective single-center cohort of PLWH at risk for HIV-associated nonalcoholic fatty liver disease (NAFLD) who underwent contemporaneous MRI-PDFF and CAP assessment were included. Subjects with other forms of liver disease including viral hepatitis and excessive alcohol intake were excluded. Receiver operatic characteristic (ROC) curve analysis were performed to identify the optimal threshold for the detection of HIV-associated NAFLD (liver fat ≥ 5%). RESULTS: Seventy PLWH (90% men) at risk for NAFLD were included. The mean (± standard deviation) age and body mass index were 48.6 (±10.2) years and 30 (± 5.3) kg/m2, respectively. The prevalence of HIV-associated NAFLD (MRI-PDFF ≥ 5%) was 80%. The M and XL probes were used for 56% and 44% of patients, respectively. The area under the ROC curve of CAP for the detection of MRI-PDFF ≥ 5% was 0.82 (0.69-0.95) at the cut-point of 285 dB/m. The positive predictive value of CAP ≥ 285 dB/m was 93.2% in this cohort with sensitivity of 73% and specificity of 78.6%. CONCLUSIONS: The optimal cut-point of CAP to correctly identify HIV-associated NAFLD was 285 dB/m, is similar to previously published cut-point for primary NAFLD and may be incorporated into routine care to identify patients at risk of HIV-associated NAFLD.

Linearity and Bias of Proton Density Fat Fraction as a Quantitative Imaging Biomarker: A Multicenter, Multiplatform, Multivendor Phantom Study.

Background Proton density fat fraction (PDFF) estimated by using chemical shift-encoded (CSE) MRI is an accepted imaging biomarker of hepatic steatosis. This work aims to promote standardized use of CSE MRI to estimate PDFF. Purpose To assess the accuracy of CSE MRI methods for estimating PDFF by determining the linearity and range of bias observed in a phantom. Materials and Methods In this prospective study, a commercial phantom with 12 vials of known PDFF values were shipped across nine U.S. centers. The phantom underwent 160 independent MRI examinations on 27 1.5-T and 3.0-T systems from three vendors. Two three-dimensional CSE MRI protocols with minimal T1 bias were included: vendor and standardized. Each vendor's confounder-corrected complex or hybrid magnitude-complex based reconstruction algorithm was used to generate PDFF maps in both protocols. The Siemens reconstruction required a configuration change to correct for water-fat swaps in the phantom. The MRI PDFF values were compared with the known PDFF values by using linear regression with mixed-effects modeling. The 95% CIs were calculated for the regression slope (ie, proportional bias) and intercept (ie, constant bias) and compared with the null hypothesis (slope = 1, intercept = 0). Results Pooled regression slope for estimated PDFF values versus phantom-derived reference PDFF values was 0.97 (95% CI: 0.96, 0.98) in the biologically relevant 0%-47.5% PDFF range. The corresponding pooled intercept was -0.27% (95% CI: -0.50%, -0.05%). Across vendors, slope ranges were 0.86-1.02 (vendor protocols) and 0.97-1.0 (standardized protocol) at 1.5 T and 0.91-1.01 (vendor protocols) and 0.87-1.01 (standardized protocol) at 3.0 T. The intercept ranges (absolute PDFF percentage) were -0.65% to 0.18% (vendor protocols) and -0.69% to -0.17% (standardized protocol) at 1.5 T and -0.48% to 0.10% (vendor protocols) and -0.78% to -0.21% (standardized protocol) at 3.0 T. Conclusion Proton density fat fraction estimation derived from three-dimensional chemical shift-encoded MRI in a commercial phantom was accurate across vendors, imaging centers, and field strengths, with use of the vendors' product acquisition and reconstruction software. © RSNA, 2021 See also the editorial by Dyke in this issue.

Design and evaluation of quantitative MRI phantoms to mimic the simultaneous presence of fat, iron, and fibrosis in the liver.

PURPOSE: To design, construct, and evaluate quantitative MR phantoms that mimic MRI signals from the liver with simultaneous control of three parameters: proton-density fat fraction (PDFF), R2∗ , and T1 . These parameters are established biomarkers of hepatic steatosis, iron overload, and fibrosis/inflammation, respectively, which can occur simultaneously in the liver. METHODS: Phantoms including multiple vials were constructed. Peanut oil was used to modulate PDFF, MnCl2 and iron microspheres were used to modulate R2∗ , and NiCl2 was used to modulate the T1 of water (T1,water ). Phantoms were evaluated at both 1.5 T and 3 T using stimulated-echo acquisition-mode MRS and chemical shift-encoded MRI. Stimulated-echo acquisition-mode MRS data were processed to estimate T1,water , T1,fat , R2,water∗ , and R2,fat∗ for each vial. Chemical shift-encoded MRI data were processed to generate PDFF and R2∗ maps, and measurements were obtained in each vial. Measurements were evaluated using linear regression and Bland-Altman analysis. RESULTS: High-quality PDFF and R2∗ maps were obtained with homogeneous values throughout each vial. High correlation was observed between imaging PDFF with target PDFF (slope = 0.94-0.97, R2 = 0.994-0.997) and imaging R2∗ with target R2∗ (slope = 0.84-0.88, R2 = 0.935-0.943) at both 1.5 T and 3 T. The values of R2,fat∗ and R2,water∗ were highly correlated with slope close to 1.0 at both 1.5 T (slope = 0.90, R2 = 0.988) and 3 T (slope = 0.99, R2 = 0.959), similar to the behavior observed in vivo. The value of T1,water (500-1200 ms) was controlled with varying NiCl2 concentration, while T1,fat (300 ms) was independent of NiCl2 concentration. CONCLUSION: Novel quantitative MRI phantoms that mimic the simultaneous presence of fat, iron, and fibrosis in the liver were successfully developed and validated.

Temperature-corrected proton density fat fraction estimation using chemical shift-encoded MRI in phantoms.

PURPOSE: Chemical shift-encoded MRI (CSE-MRI) is well-established to quantify proton density fat fraction (PDFF) as a quantitative biomarker of hepatic steatosis. However, temperature is known to bias PDFF estimation in phantom studies. In this study, strategies were developed and evaluated to correct for the effects of temperature on PDFF estimation through simulations, temperature-controlled experiments, and a multi-center, multi-vendor phantom study. THEORY AND METHODS: A technical solution that assumes and automatically estimates a uniform, global temperature throughout the phantom is proposed. Computer simulations modeled the effect of temperature on PDFF estimation using magnitude-, complex-, and hybrid-based CSE-MRI methods. Phantom experiments were performed to assess the temperature correction on PDFF estimation at controlled phantom temperatures. To assess the temperature correction method on a larger scale, the proposed method was applied to data acquired as part of a nine-site multi-vendor phantom study and compared to temperature-corrected PDFF estimation using an a priori guess for ambient room temperature. RESULTS: Simulations and temperature-controlled experiments show that as temperature deviates further from the assumed temperature, PDFF bias increases. Using the proposed correction method and a reasonable a priori guess for ambient temperature, PDFF bias and variability were reduced using magnitude-based CSE-MRI, across MRI systems, field strengths, protocols, and varying phantom temperature. Complex and hybrid methods showed little PDFF bias and variability both before and after correction. CONCLUSION: Correction for temperature reduces temperature-related PDFF bias and variability in phantoms across MRI vendors, sites, field strengths, and protocols for magnitude-based CSE-MRI, even without a priori information about the temperature.

Complications as a Mediator of the Perioperative Frailty-Mortality Association.

BACKGROUND: Preoperative frailty is strongly associated with postoperative complications and mortality. However, the pathways between frailty, postoperative complications, and mortality are poorly described. The authors hypothesized that the occurrence of postoperative complications would mediate a substantial proportion of the total effect of frailty on mortality after elective noncardiac surgery. METHODS: Following protocol registration, the authors conducted a retrospective cohort study of intermediate- to high-risk elective noncardiac surgery patients (2016) using National Surgical Quality Improvement Program data. The authors conducted Bayesian mediation analysis of the relationship between preoperative frailty (exposure, using the Risk Analysis Index), serious complications (mediator), and 30-day mortality (outcome), comprehensively adjusting for confounders. The authors estimated the total effect of frailty on mortality (composed of the indirect effect mediated by complications and the remaining direct effect of frailty) and estimated the proportion of the frailty-mortality association mediated by complications. RESULTS: The authors identified 205,051 patients; 1,474 (0.7%) died. Complications occurred in 20,211 (9.9%). A 2 SD increase in frailty score resulted in a total association with mortality equal to an odds ratio of 3.79 (95% credible interval, 2.48 to 5.64), resulting from a direct association (odds ratio, 1.76; 95% credible interval, 1.34 to 2.30) and an indirect association mediated by complications (odds ratio, 2.15; 95% credible interval, 1.58 to 2.96). Complications mediated 57.3% (95% credible interval, 40.8 to 73.8) of the frailty-mortality association. Cardiopulmonary complications were the strongest mediators among complication subtypes. CONCLUSIONS: Complications mediate more than half of the association between frailty and postoperative mortality in elective noncardiac surgery.

Persistent Postoperative Opioid Prescription Fulfillment and Peripheral Nerve Blocks for Ambulatory Shoulder Surgery: A Retrospective Cohort Study.

BACKGROUND: There is need to identify perioperative interventions that decrease chronic opioid use. The authors hypothesized that receipt of a peripheral nerve block would be associated with a lower incidence of persistent postoperative opioid prescription fulfillment. METHODS: This was a retrospective population-based cohort study examining ambulatory shoulder surgery patients in Ontario, Canada. The main outcome measure was persistent postoperative opioid prescription fulfillment. In opioid-naive patients (no opioid prescription fulfillment in 90 days preoperatively), this was present if an individual fulfilled an opioid prescription of at least a 60-day supply during postoperative days 90 to 365. In opioid-exposed (less than 60 mg oral morphine equivalent dose per day within 90 days preoperatively) or opioid-tolerant (60 mg oral morphine equivalent dose per day or above within 90 days preoperatively) patients, this was classified as present if an individual experienced any increase in opioid prescription fulfillment from postoperative day 90 to 365 relative to their baseline use before surgery. The authors' exposure was the receipt of a peripheral nerve block. RESULTS: The authors identified 48,523 people who underwent elective shoulder surgery from July 1, 2012, to December 31, 2017, at one of 118 Ontario hospitals. There were 8,229 (17%) patients who had persistent postoperative opioid prescription fulfillment. Of those who received a peripheral nerve block, 5,008 (16%) went on to persistent postoperative opioid prescription fulfillment compared to 3,221 (18%) patients who did not (adjusted odds ratio, 0.90; 95% CI, 0.83 to 0.97; P = 0.007). This statistically significant observation was not reproduced in a coarsened exact matching sensitivity analysis (adjusted odds ratio, 0.85; 95% CI, 0.71 to 1.02; P = 0.087) or several other subgroup and sensitivity analyses. CONCLUSIONS: This retrospective analysis found no association between receipt of a peripheral nerve block and a lower incidence of persistent postoperative opioid prescription fulfillment in ambulatory shoulder surgery patients.

Frailty as a Predictor of Death or New Disability After Surgery: A Prospective Cohort Study.

OBJECTIVE: To compare the accuracy of the modified Fried Index (mFI) and the Clinical Frailty Scale (CFS) to predict death or patient-reported new disability 90 days after major elective surgery. BACKGROUND: The association of frailty with patient-reported outcomes, and comparisons between preoperative frailty instruments are poorly described. METHODS: This was a prospective multicenter cohort study. We determined frailty status in individuals ≥65 years having elective noncardiac surgery using the mFI and CFS. Outcomes included death or patient-reported new disability (primary); safety incidents, length of stay (LOS), and institutional discharge (secondary); ease of use, usefulness, benefit, clinical importance, and feasibility (tertiary). We measured the adjusted association of frailty with outcomes using regression analysis and compared true positive and false positive rates (TPR/FPR). RESULTS: Of 702 participants, 645 had complete follow up. The CFS identified 297 (42.3%) with frailty, the mFI 257 (36.6%); 72 (11.1%) died or experienced a new disability. Frailty was significantly associated with the primary outcome (CFS adjusted odds ratio, OR, 2.51, 95% confidence interval, CI, 1.50-4.21; mFI adjusted-OR 2.60, 95% CI 1.57-4.31). TPR and FPR were not significantly different between instruments. Frailty was the only significant predictor of death or new disability in a multivariable analysis. Need for institutional discharge, costs and LOS were significantly increased in individuals with frailty. The CFS was easier to use, required less time and had less missing data. CONCLUSIONS: Older people with frailty are significantly more likely to die or experience a new patient-reported disability after surgery. Clinicians performing frailty assessments before surgery should consider the CFS over the mFI as accuracy was similar, but ease of use and feasibility were higher.

Microbiome Signatures Associated With Steatohepatitis and Moderate to Severe Fibrosis in Children With Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: The intestinal microbiome might affect the development and severity of nonalcoholic fatty liver disease (NAFLD). We analyzed microbiomes of children with and without NAFLD. METHODS: We performed a prospective, observational, cross-sectional study of 87 children (age range, 8-17 years) with biopsy-proven NAFLD and 37 children with obesity without NAFLD (controls). Fecal samples were collected and microbiome composition and functions were assessed using 16S ribosomal RNA amplicon sequencing and metagenomic shotgun sequencing. Microbial taxa were identified using zero-inflated negative binomial modeling. Genes contributing to bacterial pathways were identified using gene set enrichment analysis. RESULTS: Fecal microbiomes of children with NAFLD had lower α-diversity than those of control children (3.32 vs 3.52, P = .016). Fecal microbiomes from children with nonalcoholic steatohepatitis (NASH) had the lowest α-diversity (control, 3.52; NAFLD, 3.36; borderline NASH, 3.37; NASH, 2.97; P = .001). High abundance of Prevotella copri was associated with more severe fibrosis (P = .036). Genes for lipopolysaccharide biosynthesis were enriched in microbiomes from children with NASH (P < .001). Classification and regression tree model with level of alanine aminotransferase and relative abundance of the lipopolysaccharide pathway gene encoding 3-deoxy-d-manno-octulosonate 8-phosphate-phosphatase identified patients with NASH with an area under the receiver operating characteristic curve value of 0.92. Genes involved in flagellar assembly were enriched in the fecal microbiomes of patients with moderate to severe fibrosis (P < .001). Classification and regression tree models based on level of alanine aminotransferase and abundance of genes encoding flagellar biosynthesis protein had good accuracy for identifying case children with moderate to severe fibrosis (area under the receiver operating characteristic curve, 0.87). CONCLUSIONS: In an analysis of fecal microbiomes of children with NAFLD, we associated NAFLD and NASH with intestinal dysbiosis. NAFLD and its severity were associated with greater abundance of genes encoding inflammatory bacterial products. Alterations to the intestinal microbiome might contribute to the pathogenesis of NAFLD and be used as markers of disease or severity.

T1 -corrected quantitative chemical shift-encoded MRI.

PURPOSE: To develop and validate a T1 -corrected chemical-shift encoded MRI (CSE-MRI) method to improve noise performance and reduce bias for quantification of tissue proton density fat-fraction (PDFF). METHODS: A variable flip angle (VFA)-CSE-MRI method using joint-fit reconstruction was developed and implemented. In computer simulations and phantom experiments, sources of bias measured using VFA-CSE-MRI were investigated. The effect of tissue T1 on bias using low flip angle (LFA)-CSE-MRI was also evaluated. The noise performance of VFA-CSE-MRI was compared to LFA-CSE-MRI for liver fat quantification. Finally, a prospective pilot study in patients undergoing gadoxetic acid-enhanced MRI of the liver to evaluate the ability of the proposed method to quantify liver PDFF before and after contrast. RESULTS: VFA-CSE-MRI was accurate and insensitive to transmit B1 inhomogeneities in phantom experiments and computer simulations. With high flip angles, phase errors because of RF spoiling required modification of the CSE signal model. For relaxation parameters commonly observed in liver, the joint-fit reconstruction improved the noise performance marginally, compared to LFA-CSE-MRI, but eliminated T1 -related bias. A total of 25 patients were successfully recruited and analyzed for the pilot study. Strong correlation and good agreement between PDFF measured with VFA-CSE-MRI and LFA-CSE-MRI (pre-contrast) was observed before (R2 = 0.97; slope = 0.88, 0.81-0.94 95% confidence interval [CI]; intercept = 1.34, -0.77-1.92 95% CI) and after (R2 = 0.93; slope = 0.88, 0.78-0.98 95% CI; intercept = 1.90, 1.01-2.79 95% CI) contrast. CONCLUSION: Joint-fit VFA-CSE-MRI is feasible for T1 -corrected PDFF quantification in liver, is insensitive to B1 inhomogeneities, and can eliminate T1 bias, but with only marginal SNR advantage for T1 values observed in the liver.

The relationship between liver triglyceride composition and proton density fat fraction as assessed by 1 H MRS.

The aim of this study was to estimate parameters determining liver triglyceride composition (TC) using 1 H MRS and to assess how TC estimability is affected by proton density fat fraction (PDFF) in adults with nonalcoholic fatty liver disease (NAFLD). In this prospective single-site study, 199 adults with known or suspected NAFLD in whom other causes of liver disease were excluded underwent two 1 H MRS STimulated Echo Acquisition Method (STEAM) sequences at 3 T. A respiratory-gated water-suppressed free breathing sequence (TE 10 ms, 16 signal averages) was used to assess TC in terms of the number of double bonds (ndb) and methylene-interrupted double bonds (nmidb), and a single breath-hold-long TR, multi-TE sequence (TR 3500 ms), which acquired five single average spectra over TE 10-30 ms, was used to estimate liver PDFF. Ndb and nmidb estimability was qualitatively assessed for each case and summarized descriptively. The consistency of ndb and nmidb estimation was examined using ROC analysis. The relationship between ndb and nmidb values and PDFF was presented graphically. Quality-of-fit of ndb and nmidb versus PDFF was evaluated by Pearson-r correlation. A significance level of 0.05 was used. In 263 1 H MRS examinations performed on 199 adult participants, ndb and nmidb were successfully estimated in 7/53 (13.2%) examinations with PDFF < 4%, 13/30 (43.3%) examinations with PDFF between 4% and 7%, 33/41 (80.5%) examinations with PDFF between 7% and 10%, and 124/139 (89.2%) examinations with PDFF > 10% (maximum PDFF 38.1%). Liver TC could be estimated consistently for PDFF > 6.7%. Both ndb and nmidb decreased with increasing PDFF (ndb = 2.83-0.0160·PDFF, r = -0.449, P < 0.0001); nmidb = 0.75-0.0088·PDFF, r = -0.350, P < 0.0001). In a cohort of adults with known or suspected NAFLD, liver TC becomes more saturated as PDFF increases.

Prospective comparison of longitudinal change in hepatic proton density fat fraction (PDFF) estimated by magnitude-based MRI (MRI-M) and complex-based MRI (MRI-C).

PURPOSE: To compare longitudinal hepatic proton density fat fraction (PDFF) changes estimated by magnitude- vs. complex-based chemical-shift-encoded MRI during a weight loss surgery (WLS) program in severely obese adults with biopsy-proven nonalcoholic fatty liver disease (NAFLD). METHODS: This was a secondary analysis of a prospective dual-center longitudinal study of 54 adults (44 women; mean age 52 years; range 27-70 years) with obesity, biopsy-proven NAFLD, and baseline PDFF ≥ 5%, enrolled in a WLS program. PDFF was estimated by confounder-corrected chemical-shift-encoded MRI using magnitude (MRI-M)- and complex (MRI-C)-based techniques at baseline (visit 1), after a 2- to 4-week very low-calorie diet (visit 2), and at 1, 3, and 6 months (visits 3 to 5) after surgery. At each visit, PDFF values estimated by MRI-M and MRI-C were compared by a paired t test. Rates of PDFF change estimated by MRI-M and MRI-C for visits 1 to 3, and for visits 3 to 5 were assessed by Bland-Altman analysis and intraclass correlation coefficients (ICCs). RESULTS: MRI-M PDFF estimates were lower by 0.5-0.7% compared with those of MRI-C at all visits (p < 0.001). There was high agreement and no difference between PDFF change rates estimated by MRI-M vs. MRI-C for visits 1 to 3 (ICC 0.983, 95% CI 0.971, 0.99; bias = - 0.13%, p = 0.22), or visits 3 to 5 (ICC 0.956, 95% CI 0.919-0.977%; bias = 0.03%, p = 0.36). CONCLUSION: Although MRI-M underestimates PDFF compared with MRI-C cross-sectionally, this bias is consistent and MRI-M and MRI-C agree in estimating the rate of hepatic PDFF change longitudinally. KEY POINTS: • MRI-M demonstrates a significant but small and consistent bias (0.5-0.7%; p < 0.001) towards underestimation of PDFF compared with MRI-C at 3 T. • Rates of PDFF change estimated by MRI-M and MRI-C agree closely (ICC 0.96-0.98) in adults with severe obesity and biopsy- proven NAFLD enrolled in a weight loss surgery program. • Our findings support the use of either MRI technique (MRI-M or MRI-C) for clinical care or by individual sites or for multi-center trials that include PDFF change as an endpoint. However, since there is a bias in their measurements, the same technique should be used in any given patient for longitudinal follow-up.

Frailty and long-term postoperative disability trajectories: a prospective multicentre cohort study.

BACKGROUND: Frailty is associated with early postoperative outcomes. How frailty influences long-term postoperative recovery is poorly described. Our objective was to evaluate the association of frailty with postoperative disability trajectories in the year after surgery. METHODS: Prespecified 1-yr follow-up of a prospective multicentre cohort study. Patients ≥65 yr were assessed for frailty before major elective noncardiac surgery (Clinical Frailty Scale [CFS] and Fried Phenotype [FP]). The primary outcome was patient-reported disability score (using the WHO Disability Assessment Schedule 2.0) at baseline, 30, 90, and 365 days after surgery. Repeated measures linear regression estimated the association of preoperative frailty with changes in disability scores over time, adjusted for procedure. Group-based trajectory modelling was used to identify subgroup trajectories of people with frailty. RESULTS: One-year follow-up was complete for 687/702 (97.9%) participants. Frailty was associated with a significant difference in disability trajectory (P<0.0001). Compared with baseline, people with frailty experienced a decrease in disability score at 365 days (CFS frailty: -7.3 points, 95% confidence interval [CI] -10.2 to -4.5); (FP frailty: -5.4 points, 95% CI -8.5 to -2.3); people without frailty had no significant change in their disability score from baseline (no CFS frailty: +0.8 points, 95% CI -1.7 to 3.2; no FP frailty: +1.1 points, 95% CI -3.5 to 1.3). More than one-third of people with frailty experienced an early increase in disability before achieving a net decrease in disability. CONCLUSIONS: Decision-making and care planning should integrate the possible trade-offs between early adverse outcomes with longer-term benefit when frailty is present in older surgical patients.

Prospective Comparison of Preoperative Predictive Performance Between 3 Leading Frailty Instruments.

BACKGROUND: Guidelines recommend routine preoperative frailty assessment for older people. However, the degree to which frailty instruments improve predictive accuracy when added to traditional risk factors is poorly described. Our objective was to measure the accuracy gained in predicting outcomes important to older patients when adding the Clinical Frailty Scale (CFS), Fried Phenotype (FP), or Frailty Index (FI) to traditional risk factors. METHODS: This was an analysis of a multicenter prospective cohort of elective noncardiac surgery patients ≥65 years of age. Each frailty instrument was prospectively collected. The added predictive performance of each frailty instrument beyond the baseline model (age, sex, American Society of Anesthesiologists' score, procedural risk) was estimated using likelihood ratio test, discrimination, calibration, explained variance, and reclassification. Outcomes analyzed included death or new disability, prolonged length of stay (LoS, >75th percentile), and adverse discharge (death or non-home discharge). RESULTS: We included 645 participants (mean age, 74 [standard deviation, 6]); 72 (11.2%) participants died or experienced a new disability, 164 (25.4%) had prolonged LoS, and 60 (9.2%) had adverse discharge. Compared to the baseline model predicting death or new disability (area under the curve [AUC], 0.67; R, 0.08, good calibration), prolonged LoS (AUC, 0.73; R, 0.18, good calibration), and adverse discharge (AUC, 0.78; R, 0.16, poor calibration), the CFS improved fit per the likelihood ratio test (P < .02 for death or new disability, <.001 for LoS, <.001 for discharge), discrimination (AUC = 0.71 for death or new disability, 0.76 for LoS, 0.82 for discharge), calibration (good for death or new disability, LoS, and discharge), explained variance (R = 0.11 for death or new disability, 0.22 for LoS, 0.25 for discharge), and reclassification (appropriate directional reclassification) for all outcomes. The FP improved discrimination and R for all outcomes, but to a lesser degree than the CFS. The FI improved discrimination for death or new disability and R for all outcomes, but to a lesser degree than the CFS and the FP. These results were consistent in internal validation. CONCLUSIONS: Frailty instruments provide meaningful increases in accuracy when predicting postoperative outcomes for older people. Compared to the FP and FI, the CFS appears to improve all measures of predictive performance to the greatest extent and across outcomes. Combined with previous research demonstrating that the CFS is easy to use and requires less time than the FP, clinicians should consider its use in preoperative practice.

Diagnostic accuracy of magnetic resonance imaging hepatic proton density fat fraction in pediatric nonalcoholic fatty liver disease.

We assessed the performance of magnetic resonance imaging (MRI) proton density fat fraction (PDFF) in children to stratify hepatic steatosis grade before and after treatment in the Cysteamine Bitartrate Delayed-Release for the Treatment of Nonalcoholic Fatty Liver Disease in Children (CyNCh) trial, using centrally scored histology as reference. Participants had multiecho 1.5 Tesla (T) or 3T MRI on scanners from three manufacturers. Of 169 enrolled children, 110 (65%) and 83 (49%) had MRI and liver biopsy at baseline and at end of treatment (EOT; 52 weeks), respectively. At baseline, 17% (19 of 110), 28% (31 of 110), and 55% (60 of 110) of liver biopsies showed grades 1, 2, and 3 histological steatosis; corresponding PDFF (mean ± SD) values were 10.9 ± 4.1%, 18.4 ± 6.2%, and 25.7 ± 9.7%, respectively. PDFF classified grade 1 versus 2-3 and 1-2 versus 3 steatosis with areas under receiving operator characteristic curves (AUROCs) of 0.87 (95% confidence interval [CI], 0.80, 0.94) and 0.79 (0.70, 0.87), respectively. PDFF cutoffs at 90% specificity were 17.5% for grades 2-3 steatosis and 23.3% for grade 3 steatosis. At EOT, 47% (39 of 83), 41% (34 of 83), and 12% (10 of 83) of biopsies showed improved, unchanged, and worsened steatosis grade, respectively, with corresponding PDFF (mean ± SD) changes of -7.8 ± 6.3%, -1.2 ± 7.8%, and 4.9 ± 5.0%, respectively. PDFF change classified steatosis grade improvement and worsening with AUROCs (95% CIs) of 0.76 (0.66, 0.87) and 0.83 (0.73, 0.92), respectively. PDFF change cut-off values at 90% specificity were -11.0% and +5.5% for improvement and worsening. CONCLUSION: MRI-estimated PDFF has high diagnostic accuracy to both classify and predict histological steatosis grade and change in histological steatosis grade in children with NAFLD. (Hepatology 2018;67:858-872).

Pilot study on longitudinal change in pancreatic proton density fat fraction during a weight-loss surgery program in adults with obesity.

BACKGROUND: Quantitative-chemical-shift-encoded (CSE)-MRI methods have been applied to the liver. The feasibility and potential utility CSE-MRI in monitoring changes in pancreatic proton density fat fraction (PDFF) have not yet been demonstrated. PURPOSE: To use quantitative CSE-MRI to estimate pancreatic fat changes during a weight-loss program in adults with severe obesity and nonalcoholic fatty liver disease (NAFLD). To explore the relationship of reduction in pancreatic PDFF with reductions in anthropometric indices. STUDY TYPE: Prospective/longitudinal. POPULATION: Nine adults with severe obesity and NAFLD enrolled in a weight-loss program. FIELD STRENGTH/SEQUENCE: CSE-MRI fat quantification techniques and multistation-volumetric fat/water separation techniques were performed at 3 T. ASSESSMENT: PDFF values were recorded from parametric maps colocalized across timepoints. STATISTICAL TESTS: Rates of change of log-transformed variables across time were determined (linear-regression), and their significance assessed compared with no change (Wilcoxon test). Rates of change were correlated pairwise (Spearman's correlation). RESULTS: Mean pancreatic PDFF decreased by 5.7% (range 0.7-17.7%) from 14.3 to 8.6%, hepatic PDFF by 11.4% (2.6-22.0%) from 14.8 to 3.4%, weight by 30.9 kg (17.3-64.2 kg) from 119.0 to 88.1 kg, body mass index by 11.0 kg/m2 (6.3-19.1 kg/m2 ) from 44.1 to 32.9 kg/m2 , waist circumference (WC) by 25.2 cm (4.0-41.0 cm) from 133.1 to 107.9 cm, HC by 23.5 cm (4.5-47.0 cm) from 135.8 to 112.3 cm, visceral adipose tissue (VAT) by 2.9 L (1.7-5.7 L) from 7.1 to 4.2 L, subcutaneous adipose tissue (SCAT) by 4.0 L (2.9-7.4 L) from 15.0 to 11.0 L. Log-transformed rate of change for pancreatic PDFF was moderately correlated with log-transformed rates for hepatic PDFF, VAT, SCAT, and WC (ρ = 0.5, 0.47, 0.45, and 0.48, respectively), although not statistically significant. DATA CONCLUSION: Changes in pancreatic PDFF can be estimated by quantitative CSE-MRI in adults undergoing a weight-loss surgery program. Pancreatic and hepatic PDFF and anthropometric indices decreased significantly. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;50:1092-1102.

Assessment of a high-SNR chemical-shift-encoded MRI with complex reconstruction for proton density fat fraction (PDFF) estimation overall and in the low-fat range.

BACKGROUND: Improving the signal-to-noise ratio (SNR) of chemical-shift-encoded MRI acquisition with complex reconstruction (MRI-C) may improve the accuracy and precision of noninvasive proton density fat fraction (PDFF) quantification in patients with hepatic steatosis. PURPOSE: To assess the accuracy of high SNR (Hi-SNR) MRI-C versus standard MRI-C acquisition to estimate hepatic PDFF in adult and pediatric nonalcoholic fatty liver disease (NAFLD) using an MR spectroscopy (MRS) sequence as the reference standard. STUDY TYPE: Prospective. POPULATION/SUBJECTS: In all, 231 adult and pediatric patients with known or suspected NAFLD. FIELD STRENGTH/SEQUENCE: PDFF estimated at 3T by three MR techniques: standard MRI-C; a Hi-SNR MRI-C variant with increased slice thickness, decreased matrix size, and no parallel imaging; and MRS (reference standard). ASSESSMENT: MRI-PDFF was measured by image analysts using a region of interest coregistered with the MRS-PDFF voxel. STATISTICAL TESTS: Linear regression analyses were used to assess accuracy and precision of MRI-estimated PDFF for MRS-PDFF as a function of MRI-PDFF using the standard and Hi-SNR MRI-C for all patients and for patients with MRS-PDFF <10%. RESULTS: In all, 271 exams from 231 patients were included (mean MRS-PDFF: 12.6% [SD: 10.4]; range: 0.9-41.9). High agreement between MRI-PDFF and MRS-PDFF was demonstrated across the overall range of PDFF, with a regression slope of 1.035 for the standard MRI-C and 1.008 for Hi-SNR MRI-C. Hi-SNR MRI-C, compared to standard MRI-C, provided small but statistically significant improvements in the slope (respectively, 1.008 vs. 1.035, P = 0.004) and mean bias (0.412 vs. 0.673, P < 0.0001) overall. In the low-fat patients only, Hi-SNR MRI-C provided improvements in the slope (1.058 vs. 1.190, P = 0.002), mean bias (0.168 vs. 0.368, P = 0.007), intercept (-0.153 vs. -0.796, P < 0.0001), and borderline improvement in the R2 (0.888 vs. 0.813, P = 0.01). DATA CONCLUSION: Compared to standard MRI-C, Hi-SNR MRI-C provides slightly higher MRI-PDFF estimation accuracy across the overall range of PDFF and improves both accuracy and precision in the low PDFF range. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:229-238.

A Population-based Comparative Effectiveness Study of Peripheral Nerve Blocks for Hip Fracture Surgery.

BACKGROUND: Adverse outcomes and resource use rates are high after hip fracture surgery. Peripheral nerve blocks could improve outcomes through enhanced analgesia and decreased opioid related adverse events. We hypothesized that these benefits would translate into decreased resource use (length of stay [primary outcome] and costs), and better clinical outcomes (pneumonia and mortality). METHODS: The authors conducted a retrospective cohort study of hip fracture surgery patients in Ontario, Canada (2011 to 2015) using linked health administrative data. Multilevel regression, instrumental variable, and propensity scores were used to determine the association of nerve blocks with resource use and outcomes. RESULTS: The authors identified 65,271 hip fracture surgery patients; 10,030 (15.4%) received a block. With a block, the median hospital stay was 7 (interquartile range, 4 to 13) days versus 8 (interquartile range, 5 to 14) days without. Following adjustment, nerve blocks were associated with a 0.6-day decrease in length of stay (95% CI, 0.5 to 0.8). This small difference was consistent with instrumental variable (1.1 days; 95% CI, 0.9 to 1.2) and propensity score (0.2 days; 95% CI, 0.2 to 0.3) analyses. Costs were lower with a nerve block (adjusted difference, -$1,421; 95% CI, -$1,579 to -$1,289 [Canadian dollars]), but no difference in mortality (adjusted odds ratio, 0.99; 95% CI, 0.89 to 1.11) or pneumonia (adjusted odds ratio, 1.01; 95% CI, 0.88 to 1.16) was observed. CONCLUSIONS: Receipt of nerve blocks for hip fracture surgery is associated with decreased length of stay and health system costs, although small effect sizes may not reflect clinical significance for length of stay.