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1.
J Am Chem Soc ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39018427

ABSTRACT

Polycyclic aromatic hydrocarbons (PAHs) are found throughout the interstellar medium and are important markers for the evolution of galaxies and both star and planet formation. They are also widely regarded as a major source of carbon, which has implications in the search for extraterrestrial life. Herein we construct a melting point phase diagram for a series of phenanthrene/pyrene binary mixtures to identify the eutectic composition (75 mol % phenanthrene) and its melting point (83 °C). The molten oil obtained on heating this eutectic composition to 90 °C in aqueous solution is homogenized in the presence of a water-soluble polymeric emulsifier. On cooling to 20 °C, polydisperse spherical phenanthrene/pyrene hybrid microparticles are obtained. Varying the stirring rate and emulsifier type enables the mean microparticle diameter to be adjusted from 11 to 279 µm. Importantly, the phenanthrene content of individual microparticles remains constant during processing, as expected for the eutectic composition. These new hybrid microparticles form impact craters and undergo partial fragmentation when fired into a metal target at 1 km s-1 using a light gas gun. When fired into an aerogel target at the same speed, microparticles are located at the ends of characteristic "carrot tracks". Autofluorescence is observed in both types of experiments, which at first sight suggests minimal degradation. However, Raman microscopy analysis of the aerogel-captured microparticles indicates prominent pyrene signals but no trace of the more volatile phenanthrene component. Such differential ablation during aerogel capture is expected to inform the in situ analysis of PAH-rich cosmic dust in future space missions.

2.
Reg Anesth Pain Med ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39019502

ABSTRACT

BACKGROUND: There is potential for adverse events from corticosteroid injections, including increase in blood glucose, decrease in bone mineral density and suppression of the hypothalamic-pituitary axis. Published studies note that doses lower than those commonly injected provide similar benefit. METHODS: Development of the practice guideline was approved by the Board of Directors of American Society of Regional Anesthesia and Pain Medicine with several other societies agreeing to participate. The scope of guidelines was agreed on to include safety of the injection technique (landmark-guided, ultrasound or radiology-aided injections); effect of the addition of the corticosteroid on the efficacy of the injectate (local anesthetic or saline); and adverse events related to the injection. Based on preliminary discussions, it was decided to structure the topics into three separate guidelines as follows: (1) sympathetic, peripheral nerve blocks and trigger point injections; (2) joints; and (3) neuraxial, facet, sacroiliac joints and related topics (vaccine and anticoagulants). Experts were assigned topics to perform a comprehensive review of the literature and to draft statements and recommendations, which were refined and voted for consensus (≥75% agreement) using a modified Delphi process. The United States Preventive Services Task Force grading of evidence and strength of recommendation was followed. RESULTS: This guideline deals with the use and safety of corticosteroid injections for sympathetic, peripheral nerve blocks and trigger point injections for adult chronic pain conditions. All the statements and recommendations were approved by all participants after four rounds of discussion. The Practice Guidelines Committees and Board of Directors of the participating societies also approved all the statements and recommendations. The safety of some procedures, including stellate blocks, lower extremity peripheral nerve blocks and some sites of trigger point injections, is improved by imaging guidance. The addition of non-particulate corticosteroid to the local anesthetic is beneficial in cluster headaches but not in other types of headaches. Corticosteroid may provide additional benefit in transverse abdominal plane blocks and ilioinguinal/iliohypogastric nerve blocks in postherniorrhaphy pain but there is no evidence for pudendal nerve blocks. There is minimal benefit for the use of corticosteroids in trigger point injections. CONCLUSIONS: In this practice guideline, we provided recommendations on the use of corticosteroids in sympathetic blocks, peripheral nerve blocks, and trigger point injections to assist clinicians in making informed decisions.

3.
Neuropsychology ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39023931

ABSTRACT

OBJECTIVE: This study describes trajectories of cognitive aging among American Indian/Alaskan Native (AI/AN) adults with and without HIV and the role of immunosenescence longitudinally. METHOD: We characterized trajectories of cognitive aging in a sample of 333 AI/AN and 309 non-Hispanic White (NHW) adults who were followed longitudinally for up to 20 years by the HIV Neurobehavioral Research Program (HNRP) across six U.S. research sites. We used growth curve modeling with autoregressive Lag-1 structures and heterogeneous residual variances to assess the role of ethnoracial identity and HIV grouping upon decline in trajectories of cognitive aging. RESULTS: HIV- AI/AN adults demonstrated earlier and steeper decline in normative trajectories of cognitive aging on tasks of processing speed, timed tasks of attention/working memory, executive function, and psychomotor speed in comparison to HIV- NHW adults. Accentuated trajectories of cognitive aging were evident in both HIV+ and HIV+ immunosuppressed groups in comparison to HIV- peers and were primarily driven by the role of immunosenescence. CONCLUSIONS: AI/AN disparities in trajectories of cognitive aging are evident and are likely explained by the interplay of biopsychosociocultural factors, including immunosenescence. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

5.
Cureus ; 16(6): e61521, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38957233

ABSTRACT

Reports of mammary Paget's disease (MPD) as a manifestation of breast cancer recurrence are rare. MPD presents a particular challenge when emerging more than two decades after a breast cancer treated with evidence-based therapy. There is a broad spectrum of non-malignant causes for dermatitis of the nipple during the initial presentation that may delay cancer work-up. This case highlights the MPD work-up and management in the context of a personal history of breast cancer. This unique clinical presentation emphasizes the importance of vigilant cancer surveillance for timely intervention, especially for a presumed cured cancer.

6.
Chemistry ; : e202401816, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38989823

ABSTRACT

N-Heterocyclic carbene (NHC)-derived selenoureas comprise a fundamentally important class of NHC derivatives, with key applications in coordination chemistry and the determination of NHC electronic properties. Considering the broad reactivity of chalcogen-containing compounds, it is surprising to note that the use of NHC-derived selenoureas as organic synthons remains essentially unexplored. The present contribution introduces a novel, straightforward transformation leading to azines bearing a guanidine moiety, through the reaction of a wide range of NHC-derived selenoureas with commercially available diazo compounds, in the presence of triphenylphosphine. This transformation offers a new approach to such products, having biological, materials chemistry, and organic synthesis applications. The guanidine-bearing azines are obtained in excellent yields, with all manipulations taking place in air. A reaction mechanism is proposed, based on both experimental mechanistic findings and density functional theory (DFT) calculations. A one-pot, multicomponent transesterification reaction between selenoureas, α-diazoesters, alcohols, and triphenylphosphine was also developed, providing highly functionalized azines.

7.
J Nucl Med ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38991754

ABSTRACT

177Lu-DOTATATE is an effective second-line treatment for metastatic or nonresectable neuroendocrine tumors. This treatment can result in hematologic severe adverse reactions (SARs). Preemptive identification of patients at risk of SARs could mitigate this risk and improve treatment safety and outcomes. Methods: Demographic and oncologic history, pretreatment laboratory values, and SAR frequency were obtained for 126 sequential patients treated with 177Lu-DOTATATE. Univariable and multivariable logistic regression models identified factors correlating with SARs. Results: Relative pretreatment anemia, leukopenia, thrombocytopenia, and elevated mean corpuscular volume (MCV) were significantly correlated with SARs, with an odds ratio of 16 (95% CI, 5-65) in patients with an MCV greater than 95 fL. Conclusion: Pretreatment bone marrow dyscrasias, including an MCV greater than 95 fL, may predict patients at risk for SARs when treated with 177Lu-DOTATATE. Further study is needed to determine whether the risks of SARs outweigh the benefit in these patients.

8.
bioRxiv ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38979340

ABSTRACT

Although innate immunity is critical for antifungal host defense against the human opportunistic fungal pathogen Aspergillus fumigatus, potentially damaging inflammation must be controlled. Adiponectin (APN) is an adipokine produced mainly in adipose tissue that exerts anti-inflammatory effects in adipose-distal tissues such as the lung. We observed 100% mortality and increased fungal burden and inflammation in neutropenic mice with invasive aspergillosis (IA) that lack APN or the APN receptors AdipoR1 or AdipoR2. Alveolar macrophages (AMs), early immune sentinels that detect and respond to lung infection, express both receptors, and APN-/- AMs exhibited an inflammatory/M1 phenotype that was associated with decreased fungal killing. Pharmacological stimulation of AMs with AdipoR agonist AdipoRon partially rescued deficient killing in APN-/- AMs that was dependent on both receptors. Finally, APN-enhanced fungal killing was associated with increased activation of the non-canonical LC3 pathway of autophagy. Thus, our study identifies a novel role for APN in LC3-mediated killing of A.fumigatus.

9.
Article in English | MEDLINE | ID: mdl-39011664

ABSTRACT

PURPOSE OF REVIEW: To provide an evidence-informed review weighing the pros and cons of particulate vs. nonparticulate steroids for lumbar transforaminal epidural steroid injections (TFESI). RECENT FINDINGS: The relative use of nonparticulate vs. particulate steroids for lumbar TFESI has risen recently in light of catastrophic consequences reported for the latter during cervical TFESI. Among various causes of spinal cord infarct, an exceedingly rare event in the lower lumbar spine, embolization of particulate steroid is among the least likely. Case reports have documented cases of spinal cord infarct during lower lumbar TFESI with both particulate and nonparticulate steroids, with database reviews finding no difference in complication rates. There is some evidence for superiority of particulate over nonparticulate steroids in well-designed studies, which could lead to increase steroid exposure (i.e. more injections) and treatment failure resulting in surgical and/or opioid management when nonparticulate steroids are utilized. SUMMARY: Similar to a paradigm shift in medicine, a personalized approach based on a shared decision model and the consequences of treatment failure, should be utilized in deciding which steroid to utilize. Alternatives to ESI include high-volume injections with nonsteroid solutions, and the use of hypertonic saline, which possesses anti-inflammatory properties and has been shown to be superior to isotonic saline in preliminary clinical studies.

10.
Dalton Trans ; 53(28): 11952-11958, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38958393

ABSTRACT

We disclose a novel series of N-heterocyclic carbene (NHC) gold complexes with varied steric and electronic properties, bearing fluorinated alkoxide anions. Early reactivity studies involving these synthons, lead to the synthesis of various complexes of relevance to gold chemistry and catalysis.

11.
Article in English | MEDLINE | ID: mdl-38955616

ABSTRACT

Postcardiotomy shock in the cardiac surgical patient is a highly morbid condition characterized by profound myocardial impairment and decreased systemic perfusion inadequate to meet end-organ metabolic demand. Postcardiotomy shock is associated with significant morbidity and mortality. Poor outcomes motivate the increased use of mechanical circulatory support (MCS) to restore perfusion in an effort to prevent multiorgan injury and improve patient survival. Despite growing acceptance and adoption of MCS for postcardiotomy shock, criteria for initiation, clinical management, and future areas of clinical investigation remain a topic of ongoing debate. This article seeks to (1) define critical cardiac dysfunction in the patient after cardiotomy, (2) provide an overview of commonly used MCS devices, and (3) summarize the relevant clinical experience for various MCS devices available in the literature, with additional recognition for the role of MCS as a part of a modified approach to the cardiac arrest algorithm in the cardiac surgical patient.

12.
J Biomech ; 172: 112213, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38968649

ABSTRACT

Hip fractures are a severe health concern among older adults. While anthropometric factors have been shown to influence hip fracture risk, the low fidelity of common body composition metrics (e.g. body mass index) reduces our ability to infer underlying mechanisms. While simulation approaches can be used to explore how body composition influences impact dynamics, there is value in experimental data with human volunteers to support the advancement of computational modeling efforts. Accordingly, the goal of this study was to use a novel combination of subject-specific clinical imaging and laboratory-based impact paradigms to assess potential relationships between high-fidelity body composition and impact dynamics metrics (including load magnitude and distribution and pelvis deflection) during sideways falls on the hip in human volunteers. Nineteen females (<35 years) participated. Body composition was assessed via DXA and ultrasound. Participants underwent low-energy (but clinically relevant) sideways falls on the hip during which impact kinetics (total peak force, contract area, peak pressure) and pelvis deformation were measured. Pearson correlations assessed potential relationships between body composition and impact characteristics. Peak force was more strongly correlated with total mass (r = 0.712) and lean mass indices (r = 0.510-0.713) than fat mass indices (r = 0.401-0.592). Peak deflection was positively correlated with indices of adiposity (all r > 0.7), but not of lean mass. Contact area and peak pressure were positively and negatively associated, respectively, with indices of adiposity (all r > 0.49). Trochanteric soft tissue thickness predicted 59 % of the variance in both variables, and was the single strongest correlate with peak pressure. In five-of-eight comparisons, hip-local (vs. whole body) anthropometrics were more highly associated with impact dynamics. In summary, fall-related impact dynamics were strongly associated with body composition, providing support for subject-specific lateral pelvis load prediction models that incorporate soft tissue characteristics. Integrating soft and skeletal tissue properties may have important implications for improving the biomechanical effectiveness of engineering-based protective products.

14.
Ann Biomed Eng ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38969955

ABSTRACT

Early diagnosis of kidney disease remains an unmet clinical challenge, preventing timely and effective intervention. Diabetes and hypertension are two main causes of kidney disease, can often appear together, and can only be distinguished by invasive biopsy. In this study, we developed a modelling approach to simulate blood velocity, volumetric flow rate, and pressure wave propagation in arterial networks of ageing, diabetic, and hypertensive virtual populations. The model was validated by comparing our predictions for pressure, volumetric flow rate and waveform-derived indexes with in vivo data on ageing populations from the literature. The model simulated the effects of kidney disease, and was calibrated to align quantitatively with in vivo data on diabetic and hypertensive nephropathy from the literature. Our study identified some potential biomarkers extracted from renal blood flow rate and flow pulsatility. For typical patient age groups, resistive index values were 0.69 (SD 0.05) and 0.74 (SD 0.02) in the early and severe stages of diabetic nephropathy, respectively. Similar trends were observed in the same stages of hypertensive nephropathy, with a range from 0.65 (SD 0.07) to 0.73 (SD 0.05), respectively. Mean renal blood flow rate through a single diseased kidney ranged from 329 (SD 40, early) to 317 (SD 38, severe) ml/min in diabetic nephropathy and 443 (SD 54, early) to 388 (SD 47, severe) ml/min in hypertensive nephropathy, showing potential as a biomarker for early diagnosis of kidney disease. This modelling approach demonstrated its potential application in informing biomarker identification and facilitating the setup of clinical trials.

15.
Ann Biomed Eng ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977528

ABSTRACT

Sporting helmets contain force attenuating materials which reduce traumatic head injury risk and may influence sport-related concussion (SRC) sequelae. The purpose of this study was to examine the association of sport helmet status with SRC-clinical presentation and recovery trajectories in men's collegiate athletes. Sport helmet status was based on the nature of sports being either helmeted/non-helmeted. 1070 SRCs in helmeted (HELM) sports (Men's-Football, Ice Hockey, and Lacrosse), and 399 SRCs in non-helmeted (NOHELM) sports (Men's-Basketball, Cheerleading, Cross Country/Track & Field, Diving, Gymnastics, Soccer, Swimming, Tennis, and Volleyball) were analyzed. Multivariable negative binomial regression models analyzed associations between sport helmet status and post-injury cognition, balance, and symptom severity, adjusting for covariate effects (SRC history, loss of consciousness, anterograde/retrograde amnesia, event type). Kaplan-Meier curves evaluated median days to: initiation of return to play (iRTP) protocol, and unrestricted RTP (URTP) by sport helmet status. Log-rank tests were used to evaluate differential iRTP/URTP between groups. Two independent multivariable Weibull accelerated failure time models were used to examine differential iRTP and URTP between groups, after adjusting for aforementioned covariates and symptom severity score. Overall, the median days to iRTP and URTP was 6.3 and 12.0, respectively, and was comparable across NOHELM- and HELM-SRCs. Post-injury symptom severity was lower (Score Ratio 0.90, 95%CI 0.82, 0.98), and cognitive test performance was higher (Score Ratio 1.03, 95%CI 1.02, 1.05) in NOHELM-compared to HELM-SRCs. Estimated time spent recovering to iRTP/URTP was comparable between sport helmet status groups. Findings suggest that the grouping of sports into helmeted and non-helmeted show slight differences in clinical presentation but not recovery.

16.
Langmuir ; 40(28): 14527-14539, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38954522

ABSTRACT

X-ray photoelectron spectroscopy (XPS) depth-profiling with an argon gas cluster ion source (GCIS) was used to characterize the spatial distribution of chlorophyll a (Chl) within a poly(cysteine methacrylate) (PCysMA) brush grown by surface-initiated atom-transfer radical polymerization (ATRP) from a planar surface. The organization of Chl is controlled by adjusting the brush grafting density and polymerization time. For dense brushes, the C, N, S elemental composition remains constant throughout the 36 nm brush layer until the underlying gold substrate is approached. However, for either reduced density brushes (mean thickness ∼20 nm) or mushrooms grown with reduced grafting densities (mean thickness 6-9 nm), elemental intensities decrease continuously throughout the brush layer, because photoelectrons are less strongly attenuated for such systems. For all brushes, the fraction of positively charged nitrogen atoms (N+/N0) decreases with increasing depth. Chl binding causes a marked reduction in N+/N0 within the brushes and produces a new feature at 398.1 eV in the N1s core-line spectrum assigned to tetrapyrrole ring nitrogen atoms coordinated to Zn2+. For all grafting densities, the N/S atomic ratio remains approximately constant as a function of brush depth, which indicates a uniform distribution of Chl throughout the brush layer. However, a larger fraction of repeat units bound to Chl is observed at lower grafting densities, reflecting a progressive reduction in steric congestion that enables more uniform distribution of the bulky Chl units throughout the brush layer. In summary, XPS depth-profiling using a GCIS is a powerful tool for characterization of these complex materials.

17.
Nature ; 631(8021): 635-644, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38961291

ABSTRACT

Innate immune pattern recognition receptors, such as the Toll-like receptors (TLRs), are key mediators of the immune response to infection and central to our understanding of health and disease1. After microbial detection, these receptors activate inflammatory signal transduction pathways that involve IκB kinases, mitogen-activated protein kinases, ubiquitin ligases and other adaptor proteins. The mechanisms that connect the proteins in the TLR pathways are poorly defined. To delineate TLR pathway activities, we engineered macrophages to enable microscopy and proteomic analysis of the endogenous myddosome constituent MyD88. We found that myddosomes form transient contacts with activated TLRs and that TLR-free myddosomes are dynamic in size, number and composition over the course of 24 h. Analysis using super-resolution microscopy revealed that, within most myddosomes, MyD88 forms barrel-like structures that function as scaffolds for effector protein recruitment. Proteomic analysis demonstrated that myddosomes contain proteins that act at all stages and regulate all effector responses of the TLR pathways, and genetic analysis defined the epistatic relationship between these effector modules. Myddosome assembly was evident in cells infected with Listeria monocytogenes, but these bacteria evaded myddosome assembly and TLR signalling during cell-to-cell spread. On the basis of these findings, we propose that the entire TLR signalling pathway is executed from within the myddosome.


Subject(s)
Macrophages , Signal Transduction , Toll-Like Receptors , Animals , Humans , Mice , Listeria monocytogenes/immunology , Listeriosis/immunology , Listeriosis/microbiology , Listeriosis/metabolism , Macrophages/immunology , Macrophages/metabolism , Macrophages/microbiology , Myeloid Differentiation Factor 88/metabolism , Proteomics , Toll-Like Receptors/metabolism , Microscopy , Immunity, Innate
18.
bioRxiv ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-39026764

ABSTRACT

Background: Individuals with cocaine use disorder (CUD) who attempt abstinence experience craving and relapse, which poses challenges in treatment. Longitudinal studies linking behavioral manifestations in CUD to the blood transcriptome in living individuals are limited. Therefore, we investigated the connection between drug use behaviors during abstinence with blood transcriptomics. Methods: We conducted a comprehensive longitudinal study involving 12 subjects (9 males, 3 females) with CUD and RNA sequencing on blood collected at a drug-free baseline, and 3, 6 & 9 months thereafter. We categorized subjects into 2 responder groups (high-low) based on scores of drug use variables, and 3 responder groups (low-intermediate-high) on days of abstinence. We investigated differential expression and gene-transcript associations across responder groups at each time point. Lastly, we examined genes that are both co-expressed and showed dynamic expression with time. Results: Genes with significant transcript associations between high and. intermediate days of abstinence at 9 months were notably enriched for cannabis use disorder, drinks weekly, and coronary artery disease risk genes. Time-specific gene co-expression analysis prioritized transcripts related to immune processes, cell cycle, RNA-protein synthesis, and second messenger signaling for days of abstinence. Conclusion: We demonstrate that abstinence reflects robust changes in drug use behaviors and the blood transcriptome in CUD. We also highlight the importance of longitudinal studies to capture complex biological processes during abstinence in CUD.

19.
bioRxiv ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-39026842

ABSTRACT

Current treatments for advanced prostate cancer (PCa) primarily target androgen receptor (AR)-pathways. However, the emergence of castration-resistant prostate cancer (CRPC) and resistance to AR signaling inhibitors (ARSI) remains a significant clinical challenge. This study introduces BSJ-5-63, a novel triple degrader targeting cyclin-dependent kinases (CDKs) CDK12, CDK7, and CDK9, with potential to transform CRPC therapy. BSJ-5-63 effectively downregulates homologous recombination repair (HRR) genes, including BRCA1 and BRCA2, through CDK12 degradation, and attenuates AR signaling through CDK7 and CDK9 degradation, further enhancing its therapeutic impact. Importantly, BSJ-5-63 induces a "BRCAness" state that persists for a significant duration, enabling sequential combination therapy with PARP inhibitors (PARPis) while potentially minimizing drug-related toxicity and resistance. In both in vitro and in vivo studies, BSJ-5-63 exhibited potent antiproliferative effects in both AR-positive and AR-negative CRPC models. This study presents a promising multi-pronged approach for CRPC treatment, addressing both DNA repair mechanisms and AR signaling, with the potential to benefit a wide range of patients regardless of their BRCA1/2 mutational status. SIGNIFICANCE: This study introduces BSJ-5-63, a triple degrader designed to target CDK12, CDK7, and CDK9, making a significant advancement in CRPC therapy. The distinctive mechanism of BSJ-5-63 involves downregulating HRR genes and inhibiting AR signaling, thereby inducing a BRCAness state. This enhances sensitivity to PARP inhibition, effectively addressing ARSI resistance and improving the overall efficacy of treatment. The development of BSJ-5-63 represents a promising therapeutic approach, with the potential to benefit a broad spectrum of CRPC patients.

20.
JAMA Netw Open ; 7(6): e2417310, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38888922

ABSTRACT

Importance: A comprehensive review of the evidence exploring the outcomes of enhanced recovery after surgery (ERAS) guidelines has not been completed. Objective: To evaluate if ERAS guidelines are associated with improved hospital length of stay, hospital readmission, complications, and mortality compared with usual surgical care, and to understand differences in estimates based on study and patient factors. Data Sources: MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central were searched from inception until June 2021. Study Selection: Titles, abstracts, and full-text articles were screened by 2 independent reviewers. Eligible studies were randomized clinical trials that examined ERAS-guided surgery compared with a control group and reported on at least 1 of the outcomes. Data Extraction and Synthesis: Data were abstracted in duplicate using a standardized data abstraction form. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Risk of bias was assessed in duplicate using the Cochrane Risk of Bias tool. Random-effects meta-analysis was used to pool estimates for each outcome, and meta-regression identified sources of heterogeneity within each outcome. Main Outcome and Measures: The primary outcomes were hospital length of stay, hospital readmission within 30 days of index discharge, 30-day postoperative complications, and 30-day postoperative mortality. Results: Of the 12 047 references identified, 1493 full texts were screened for eligibility, 495 were included in the systematic review, and 74 RCTs with 9076 participants were included in the meta-analysis. Included studies presented data from 21 countries and 9 ERAS-guided surgical procedures with 15 (20.3%) having a low risk of bias. The mean (SD) Reporting on ERAS Compliance, Outcomes, and Elements Research checklist score was 13.5 (2.3). Hospital length of stay decreased by 1.88 days (95% CI, 0.95-2.81 days; I2 = 86.5%; P < .001) and the risk of complications decreased (risk ratio, 0.71; 95% CI, 0.59-0.87; I2 = 78.6%; P < .001) in the ERAS group. Risk of readmission and mortality were not significant. Conclusions and Relevance: In this meta-analysis, ERAS guidelines were associated with decreased hospital length of stay and complications. Future studies should aim to improve implementation of ERAS and increase the reach of the guidelines.


Subject(s)
Enhanced Recovery After Surgery , Length of Stay , Patient Readmission , Postoperative Complications , Randomized Controlled Trials as Topic , Humans , Length of Stay/statistics & numerical data , Patient Readmission/statistics & numerical data , Postoperative Complications/mortality , Postoperative Complications/epidemiology , Enhanced Recovery After Surgery/standards , Practice Guidelines as Topic , Male , Female , Middle Aged
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