Time-Resolved Analysis Reveals Rapid Dynamics and Broad Scope of the CBP/p300 Acetylome.

The acetyltransferases CBP and p300 are multifunctional transcriptional co-activators. Here, we combined quantitative proteomics with CBP/p300-specific catalytic inhibitors, bromodomain inhibitor, and gene knockout to reveal a comprehensive map of regulated acetylation sites and their dynamic turnover rates. CBP/p300 acetylates thousands of sites, including signature histone sites and a multitude of sites on signaling effectors and enhancer-associated transcriptional regulators. Time-resolved acetylome analyses identified a subset of CBP/p300-regulated sites with very rapid (<30 min) acetylation turnover, revealing a dynamic balance between acetylation and deacetylation. Quantification of acetylation, mRNA, and protein abundance after CBP/p300 inhibition reveals a kinetically competent network of gene expression that strictly depends on CBP/p300-catalyzed rapid acetylation. Collectively, our in-depth acetylome analyses reveal systems attributes of CBP/p300 targets, and the resource dataset provides a framework for investigating CBP/p300 functions and for understanding the impact of small-molecule inhibitors targeting its catalytic and bromodomain activities.

Nuclear export of circular RNA.

Circular RNAs (circRNAs), which are increasingly being implicated in a variety of functions in normal and cancerous cells1-5, are formed by back-splicing of precursor mRNAs in the nucleus6-10. circRNAs are predominantly localized in the cytoplasm, indicating that they must be exported from the nucleus. Here we identify a pathway that is specific for the nuclear export of circular RNA. This pathway requires Ran-GTP, exportin-2 and IGF2BP1. Enhancing the nuclear Ran-GTP gradient by depletion or chemical inhibition of the major protein exporter CRM1 selectively increases the nuclear export of circRNAs, while reducing the nuclear Ran-GTP gradient selectively blocks circRNA export. Depletion or knockout of exportin-2 specifically inhibits nuclear export of circRNA. Analysis of nuclear circRNA-binding proteins reveals that interaction between IGF2BP1 and circRNA is enhanced by Ran-GTP. The formation of circRNA export complexes in the nucleus is promoted by Ran-GTP through its interactions with exportin-2, circRNA and IGF2BP1. Our findings demonstrate that adaptors such as IGF2BP1 that bind directly to circular RNAs recruit Ran-GTP and exportin-2 to export circRNAs in a mechanism that is analogous to protein export, rather than mRNA export.

Enhancers are activated by p300/CBP activity-dependent PIC assembly, RNAPII recruitment, and pause release.

The metazoan-specific acetyltransferase p300/CBP is involved in activating signal-induced, enhancer-mediated transcription of cell-type-specific genes. However, the global kinetics and mechanisms of p300/CBP activity-dependent transcription activation remain poorly understood. We performed genome-wide, time-resolved analyses to show that enhancers and super-enhancers are dynamically activated through p300/CBP-catalyzed acetylation, deactivated by the opposing deacetylase activity, and kinetic acetylation directly contributes to maintaining cell identity at very rapid (minutes) timescales. The acetyltransferase activity is dispensable for the recruitment of p300/CBP and transcription factors but essential for promoting the recruitment of TFIID and RNAPII at virtually all enhancers and enhancer-regulated genes. This identifies pre-initiation complex assembly as a dynamically controlled step in the transcription cycle and reveals p300/CBP-catalyzed acetylation as the signal that specifically promotes transcription initiation at enhancer-regulated genes. We propose that p300/CBP activity uses a "recruit-and-release" mechanism to simultaneously promote RNAPII recruitment and pause release and thereby enables kinetic activation of enhancer-mediated transcription.

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion.

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.

Dynamic lineage priming is driven via direct enhancer regulation by ERK.

Central to understanding cellular behaviour in multi-cellular organisms is the question of how a cell exits one transcriptional state to adopt and eventually become committed to another. Fibroblast growth factor-extracellular signal-regulated kinase (FGF -ERK) signalling drives differentiation of mouse embryonic stem cells (ES cells) and pre-implantation embryos towards primitive endoderm, and inhibiting ERK supports ES cell self-renewal1. Paracrine FGF-ERK signalling induces heterogeneity, whereby cells reversibly progress from pluripotency towards primitive endoderm while retaining their capacity to re-enter self-renewal2. Here we find that ERK reversibly regulates transcription in ES cells by directly affecting enhancer activity without requiring a change in transcription factor binding. ERK triggers the reversible association and disassociation of RNA polymerase II and associated co-factors from genes and enhancers with the mediator component MED24 having an essential role in ERK-dependent transcriptional regulation. Though the binding of mediator components responds directly to signalling, the persistent binding of pluripotency factors to both induced and repressed genes marks them for activation and/or reactivation in response to fluctuations in ERK activity. Among the repressed genes are several core components of the pluripotency network that act to drive their own expression and maintain the ES cell state; if their binding is lost, the ability to reactivate transcription is compromised. Thus, as long as transcription factor occupancy is maintained, so is plasticity, enabling cells to distinguish between transient and sustained signals. If ERK signalling persists, pluripotency transcription factor levels are reduced by protein turnover and irreversible gene silencing and commitment can occur.

Protecting Caribbean patients diagnosed with cancer from compounding disasters.

Caribbean small island developing states are becoming increasingly vulnerable to compounding disasters, prominently featuring climate-related hazards and pandemic diseases, which exacerbate existing barriers to cancer control in the region. We describe the complexities of cancer prevention and control efforts throughout the Caribbean small island developing states, including the unique challenges of people diagnosed with cancer in the region. We highlight potential solutions and strategies that concurrently address disaster adaptation and cancer control. Because Caribbean small island developing states are affected first and worst by the hazards of compounding disasters, the innovative solutions developed in the region are relevant for climate mitigation, disaster adaptation, and cancer control efforts globally. In the age of complex and cascading disaster scenarios, developing strategies to mitigate their effect on the cancer control continuum, and protecting the health and safety of people diagnosed with cancer from extreme events become increasingly urgent. The equitable development of such strategies relies on collaborative efforts among professionals whose diverse expertise from complementary fields infuses the local community perspective while focusing on implementing solutions.

A review of biomedical datasets relating to drug discovery: a knowledge graph perspective.

Drug discovery and development is a complex and costly process. Machine learning approaches are being investigated to help improve the effectiveness and speed of multiple stages of the drug discovery pipeline. Of these, those that use Knowledge Graphs (KG) have promise in many tasks, including drug repurposing, drug toxicity prediction and target gene-disease prioritization. In a drug discovery KG, crucial elements including genes, diseases and drugs are represented as entities, while relationships between them indicate an interaction. However, to construct high-quality KGs, suitable data are required. In this review, we detail publicly available sources suitable for use in constructing drug discovery focused KGs. We aim to help guide machine learning and KG practitioners who are interested in applying new techniques to the drug discovery field, but who may be unfamiliar with the relevant data sources. The datasets are selected via strict criteria, categorized according to the primary type of information contained within and are considered based upon what information could be extracted to build a KG. We then present a comparative analysis of existing public drug discovery KGs and an evaluation of selected motivating case studies from the literature. Additionally, we raise numerous and unique challenges and issues associated with the domain and its datasets, while also highlighting key future research directions. We hope this review will motivate KGs use in solving key and emerging questions in the drug discovery domain.

Outcomes Following Intraoperative Calcar Fractures During Cementless Total Hip Arthroplasty.

BACKGROUND: Intraoperative calcar fractures (IOCFs) are an established complication of cementless total hip arthroplasty (THA). Prompt recognition and management may prevent subsequent postoperative complications. This study aimed to evaluate the outcomes and revision rates of THAs with IOCFs identified and managed intraoperatively. METHODS: There were 11,438 primary cementless THAs performed at a single institution from 2009 to 2022. Prospectively collected data on cases with an IOCF was compared to cases without the complication. The fracture group had a lower body mass index (26.9 versus 28.9 kg/m2; P = .01). Patient age, sex, and mean follow-up (3.2 (0 to 12.8) versus 3.5 years (0 to 14); P = .45) were similar between groups. RESULTS: An IOCF occurred in 62 of 11,438 (0.54%) cases. The THAs done via a direct anterior approach experienced the lowest rate of fractures (31 of 7,505, 0.4%) compared to postero-lateral (27 of 3,759, 0.7%; P = .03) and lateral (4 of 165, 2.4%; P < .01) approaches. Of the IOCFs, 48 of 62 (77%) were managed with cerclage cabling, 4 of 62 (6.5%) with intraoperative stem design change and cabling, 4 of 62 (6.5%) with restricted weight-bearing, and 6 of 62 (9.7%) with no modification to the standard postoperative protocol. The IOCF group experienced one case of postoperative component subsidence. No subjects in the IOCF cohort required revision, and rates were similar between groups (0 of 62, 0% versus 215 of 11,376, 1.9%; P = .63). Postoperative Hip dysfunction and Osteoarthritis Outcome Score for Joint Replacement scores were comparable (85.7 versus 86.4; P = .80). CONCLUSIONS: Cementless THA complicated by IOCF had similar postoperative revision rates and patient-reported outcome measures at early follow-up when compared to patients not experiencing this complication. Surgeons may use these data to provide postoperative counseling on expectations and outcomes following these rare intraoperative events.

The Effect of the COVID Pandemic on the Rate of Same-Day Discharge in Primary Hip and Knee Arthroplasty.

BACKGROUND: Same-day discharge (SDD) following primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) started increasing prior to 2020. The purpose of this study was to evaluate the change in the rate of SDD after the pandemic and determine whether those changes became permanent. METHODS: The annual rate of SDD for 15,208 primary THA and TKA cases performed between January 1, 2015, and September 9, 2022, at a single institution was determined. We also examined changes in SDD patient demographics as well as differences in the 90-day complication rates of SDD and overnight patients. RESULTS: In 2015, the rate of SDD for primary arthroplasty was 24%, which grew annually to 29% in 2019. Postpandemic, the rate of SDD jumped above 50% and continued up to 64% by 2022. The biggest increase was in TKA, which went from under 10% SDD prepandemic to 50% by 2022. The average age and body mass index of SDD cases prepandemic increased significantly to 62 ± 9 years and 29.4 ± 5.3 (P < .01). Overnight patients had higher rates of 90-day postoperative complications (8.4 versus 4.2%, P < .00001). CONCLUSIONS: The pandemic caused major changes in the rate of SDD for primary THA and TKA, increasing in subsequent years. The SDD patients became older and heavier due to the expanded criteria for SDD cases. The 90-day postoperative complication rate was lower for SDD patients since higher risk patients were kept overnight. At the prepandemic rate, 29% of patients currently being sent home would have stayed overnight.

Advanced Concepts in Outpatient Joint Arthroplasty.

As the adoption and utilization of outpatient total joint arthroplasty continues to grow, key developments have enabled surgeons to safely and effectively perform these surgeries while increasing patient satisfaction and operating room efficiency. Here, the authors will discuss the evidence-based principles that have guided this paradigm shift in joint arthroplasty surgery, as well as practical methods for selecting appropriate candidates and optimizing perioperative care. There will be 5 core efficiency principles reviewed that can be used to improve organizational management, streamline workflow, and overcome barriers in the ambulatory surgery center. Finally, future directions in outpatient surgery at the ASC, including the merits of implementing robot assistance and computer navigation, as well as expanding indications for revision surgeries, will be debated.

The CCJR® Charles A. Engh, Sr, MD. Excellence in Hip Research Award: The Evolution of Revision Hip Arthroplasty and Impact on the Trainee's Experience.

BACKGROUND: Advances in total hip arthroplasty (THA) have resulted in evolving revision indications and intraoperative techniques, which can influence the exposure of trainees to complex cases. We report 3 decades of revision experience from a tertiary referral center that trains fellows, comparing the reasons for revision and the complexity of revisions over time. METHODS: We retrospectively reviewed all revision THAs performed at our institution from 1990 to 2022. Revision diagnoses, components revised, types of revision implants used, and exposure techniques were collected. A "complex" revision was defined as a case that involved an extended trochanteric osteotomy, triflange and cup-cage construct, or acetabular augment. RESULTS: A total of 3,556 THA revisions were identified (108 revisions/year). Aseptic loosening was the most common indication in 1990 to 1999 (45 per year), but decreased to 28.3/year in 2010 to 2019. From 1990 to 1999 and 2010 to 2019, fracture increased from 3.1 to 7.3 per year, infection from 2.9/year to 16.9/year, and metallosis from 0.1 to 13.2 per year. Both component revision were common from 1990 to 1994 (42.6 per year), while polyethylene exchange was most common in 2010 to 2019 (43.3 per year). A decrease was observed in "complex" cases over time: 14.8 extended trochanteric osteotomies/year in 2000 to 2004 compared to 5.4 per year in 2018 to 2022, 4.5 triflange and cup-cage constructs/year in 2004 to 2007 compared to 0.8 per year in 2018 to 2022, and 4 acetabular augments per year in 2009 to 2012 compared to 1 per year in 2018 to 2022. CONCLUSIONS: Indications for revision have changed over the decades, while the number of "complex" revisions has gradually decreased, presumably due to advances in implants and materials. If this trend extends to other training institutions, the next generation of arthroplasty surgeons will have less exposure to complex revisions during their training.

A2B-COVID: A Tool for Rapidly Evaluating Potential SARS-CoV-2 Transmission Events.

Identifying linked cases of infection is a critical component of the public health response to viral infectious diseases. In a clinical context, there is a need to make rapid assessments of whether cases of infection have arrived independently onto a ward, or are potentially linked via direct transmission. Viral genome sequence data are of great value in making these assessments, but are often not the only form of data available. Here, we describe A2B-COVID, a method for the rapid identification of potentially linked cases of COVID-19 infection designed for clinical settings. Our method combines knowledge about infection dynamics, data describing the movements of individuals, and evolutionary analysis of genome sequences to assess whether data collected from cases of infection are consistent or inconsistent with linkage via direct transmission. A retrospective analysis of data from two wards at Cambridge University Hospitals NHS Foundation Trust during the first wave of the pandemic showed qualitatively different patterns of linkage between cases on designated COVID-19 and non-COVID-19 wards. The subsequent real-time application of our method to data from the second epidemic wave highlights its value for monitoring cases of infection in a clinical context.

Vernal: a tool for mining fuzzy network motifs in RNA.

MOTIVATION: RNA 3D motifs are recurrent substructures, modeled as networks of base pair interactions, which are crucial for understanding structure-function relationships. The task of automatically identifying such motifs is computationally hard, and remains a key challenge in the field of RNA structural biology and network analysis. State-of-the-art methods solve special cases of the motif problem by constraining the structural variability in occurrences of a motif, and narrowing the substructure search space. RESULTS: Here, we relax these constraints by posing the motif finding problem as a graph representation learning and clustering task. This framing takes advantage of the continuous nature of graph representations to model the flexibility and variability of RNA motifs in an efficient manner. We propose a set of node similarity functions, clustering methods and motif construction algorithms to recover flexible RNA motifs. Our tool, Vernal can be easily customized by users to desired levels of motif flexibility, abundance and size. We show that Vernal is able to retrieve and expand known classes of motifs, as well as to propose novel motifs. AVAILABILITY AND IMPLEMENTATION: The source code, data and a webserver are available at vernal.cs.mcgill.ca. We also provide a flexible interface and a user-friendly webserver to browse and download our results. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

RNAglib: a python package for RNA 2.5 D graphs.

SUMMARY: RNA 3D architectures are stabilized by sophisticated networks of (non-canonical) base pair interactions, which can be conveniently encoded as multi-relational graphs and efficiently exploited by graph theoretical approaches and recent progresses in machine learning techniques. RNAglib is a library that eases the use of this representation, by providing clean data, methods to load it in machine learning pipelines and graph-based deep learning models suited for this representation. RNAglib also offers other utilities to model RNA with 2.5 D graphs, such as drawing tools, comparison functions or baseline performances on RNA applications. AVAILABILITY AND IMPLEMENTATION: The method is distributed as a pip package, RNAglib. Data are available in a repository and can be accessed on rnaglib's web page. The source code, data and documentation are available at https://rnaglib.cs.mcgill.ca. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Physical Versus Virtual Reality-Based Calm Rooms for Psychiatric Inpatients: Quasi-Randomized Trial.

BACKGROUND: Interest in sensory rooms or so-called "calm rooms" in psychiatric inpatient care has increased significantly. In a hospital setting, their purpose is to introduce a relaxing environment to increase well-being as well as to decrease anxiety and aggressive behaviors. Calm rooms can also be used as a tool to provide self-help through a convenient environment for the patients and, at the same time, strengthen the therapeutic relationship between the patient and the professional. Recent developments in virtual reality (VR) have made virtual calm rooms possible, but these have not yet been evaluated in psychiatric inpatient care. OBJECTIVE: This study aimed to compare the effects of VR and physical calm rooms on self-reported well-being and physiological markers of arousal. METHODS: The study was conducted in 2 inpatient psychiatric wards specializing in bipolar disorder from March 2019 to February 2021. Patients who were already admitted were asked if they were interested in using a calm room and willing to provide ratings. This study relied on the quasi-randomized allocation of patients to the wards, which either had a physical or VR calm room. Self-assessment scales (Montgomery-Åsberg Depression Rating Scale-Self Assessment [MADRS-S], Beck Anxiety Scale, and Clinical Global Impression) were used to determine the participants' baseline level of depressive and anxiety symptoms before their use of the physical or VR calm room. The study determined the state of well-being measured using an 11-point visual analog scale (VAS) as well as arousal measured by blood pressure (systolic and diastolic) and heart rate before and after the use of the calm rooms. The primary end point was self-reported well-being using the VAS. RESULTS: A total of 60 participants were included-40 used the VR calm room and 20 used the physical calm room. The mean age of participants was 39 years and the majority were women (35/60, 58%). Analysis of VAS measurement showed improved well-being at the group level from before to after the intervention (P<.05), with no statistically significant difference in effects between the 2 different interventions. Effects were not moderated by baseline depression levels (dichotomized as MADRS-S >20 or ≤20) despite an overall difference in reported well-being between subgroups. CONCLUSIONS: Although the power in this study was low, the findings of this first study indicate comparable effects with respect to well-being and arousal of a VR calm room and a physical calm room. This suggests that a VR calm room can be a viable alternative when the use of a physical calm room is not an option for logistic or other reasons. TRIAL REGISTRATION: ClinicalTrials.gov NCT03918954; https://clinicaltrials.gov/ct2/show/NCT03918954.

Outpatient Total Knee Arthroplasty From a Stand-Alone Surgery Center: Safe as the Hospital?

BACKGROUND: Literature suggests that outpatient arthroplasty may result in low rates of complications and readmissions. There is, however, a dearth of information on the relative safety of total knee arthroplasty (TKA) performed at stand-alone ambulatory surgery centers (ASCs) versus hospital outpatient (HOP) settings. We aimed to compare safety profiles and 90-day adverse events of these 2 cohorts. METHODS: Prospectively collected data were reviewed on all patients who underwent outpatient TKA from 2015 to 2022. The ASC and HOP groups were compared, and differences in demographics, complications, reoperations, revisions, readmissions, and emergency department (ED) visits within 90 days of surgery were analyzed. There were 4 surgeons who performed 4,307 TKAs during the study period, including 740 outpatient cases (ASC = 157; HOP = 583). The ASC patients were younger than HOP patients (ASC = 61 versus HOP = 65; P < .001). Body mass index and sex did not differ significantly between groups. RESULTS: Within 90 days, 44 (6%) complications occurred. No differences were observed between groups in rates of 90-day complications (ASC = 9 of 157, 5.7% versus HOP = 35 of 583, 6.0%; P = .899), reoperations (ASC = 2 of 157, 1.3% versus HOP = 3 of 583, 0.5%; P = .303), revisions (ASC = 0 of 157 versus HOP = 3 of 583, 0.5%; P = 1), readmissions (ASC = 3 of 157, 1.9% versus HOP = 8 of 583, 1.4%; P = .625), and ED visits (ASC = 1 of 157, 0.6% versus HOP = 3 of 583, 0.5%; P = .853). CONCLUSION: These results suggest that in appropriately selected patients, outpatient TKA can be safely performed in both ASC and HOP settings with similar low rates of 90-day complications, reoperations, revisions, readmissions, and ED visits.

Early Practice All-Cause Complications for Fellowship-Trained Anterior Hip Surgeons Are Not Increased When Compared to "Gold Standard" Experienced Posterior Approach Surgeons.

BACKGROUND: Increased complication rates have been reported during the learning curve for direct anterior approach (DAA) total hip arthroplasty (THA). However, emerging literature suggests that complications associated with the learning curve may be substantially reduced with fellowship training. METHODS: Our institutional database was queried to identify 2 groups: (1) 600 THAs comprised of the first 300 consecutive cases performed by 2 DAA fellowship-trained surgeons; and (2) 600 posterolateral approach (PA) THAs, including the most recent 300 primary cases performed by 2 experienced PA surgeons. All-cause complications, revision rates, reoperations, operative times, and transfusion rates were evaluated. RESULTS: Comparing DAA and PA cases, there were no significant differences in rates of all-cause complications (DAA = 18, 3.0% versus PA = 23, 3.8%; P = .43), periprosthetic fractures (DAA = 5, 0.8% versus PA = 10, 1.7%; P = .19), wound complications (DAA = 7, 1.2% versus PA = 2, 0.3%; P = .09), dislocations (DAA = 2, 0.3% versus PA = 8, 1.3%, P = .06), or revisions (DAA = 2, 0.3% versus PL = 5, 0.8%; P = .45) at 120 days postoperatively. There were 4 patients who required reoperation for wound complications, all within the DAA group (DAA = 4, 0.67% versus PA = 0; P = .045). Operative times were shorter in the DAA group (DAA <1.5 hours = 93% versus PA <1.5 hours = 86%; P < .01). No blood transfusions were given in either group. CONCLUSION: In this retrospective study, DAA THAs performed by fellowship-trained surgeons early in practice were not associated with higher complication rates compared to THAs performed by experienced PA surgeons. These results suggest that fellowship training may allow DAA surgeons to complete their learning curve period with complication rates similar to experienced PA surgeons.

Motor Nerve Palsy After Direct Anterior Versus Posterior Total Hip Arthroplasty: Incidence, Risk Factors, and Recovery.

BACKGROUND: There is limited literature on motor nerve palsy in modern total hip arthroplasty (THA). The purpose of this study was to establish the incidence of nerve palsy following THA using the direct anterior (DA) and postero-lateral (PL) approaches, identify risk factors, and describe the extent of recovery. METHODS: Using our institutional database, we examined 10,047 primary THAs performed between 2009 and 2021 using the DA (6,592; 65.6%) or PL (3,455; 34.4%) approach. Postoperative femoral (FNP) and sciatic/peroneal nerve palsies (PNP) were identified. Incidence and time to recovery was calculated, and association between surgical and patient risk factors and nerve palsy were evaluated using Chi-square tests. RESULTS: The overall rate of nerve palsy was 0.34% (34/10,047) and was lower with the DA approach (0.24%) than the PL approach (0.52%), P = .02. The rate of FNPs in the DA group (0.20%) was 4.3 times more than the rate of PNPs (0.05%), while in the PL group the rate of PNPs (0.46%) was 8 times more than that of FNPs (0.06%). Higher rates of nerve palsy were observed with women, shorter patients, and nonosteoarthritis preoperative diagnoses. Full recovery of motor strength occurred in 60% of cases with FNP and 58% of cases with PNP. CONCLUSION: Nerve palsy is rare after contemporary THA through the PL and DA approaches. The PL approach was associated with a higher rate of PNP, whereas the DA approach was associated with a higher rate of FNP. Femoral and sciatic/peroneal palsies had similar rates of complete recovery.

Spinal Anesthesia for Primary Hip and Knee Arthroplasty: Comparative Rates of Transient Neurological Symptoms and Urinary Retention Using Lidocaine, Mepivacaine, and Bupivacaine.

BACKGROUND: Short-acting spinal anesthetics enable rapid recovery after hip and knee arthroplasty; however, concerns with transient neurological symptoms (TNS) cause some to avoid using lidocaine. Postoperative urinary retention (POUR) is also a concern with spinal anesthesia. We sought to study the comparative rates of TNS and POUR between lidocaine, mepivacaine, and bupivacaine in a high-volume hip and knee arthroplasty setting. METHODS: Data for 1,217 primary THA, TKA, and unicompartmental knee arthroplasty cases were reviewed and grouped by spinal anesthetic agent (lidocaine, mepivacaine, or bupivacaine). Of the 1,217 cases, utilization was 523 lidocaine, 573 mepivacaine, and 121 bupivacaine. The incidence of TNS and POUR requiring catheterization was measured both by clinical evaluation as well as a questionnaire sent to patients 14 days postoperatively. RESULTS: The overall rate of TNS was 8%. With the numbers available, there was no difference in rates of TNS between groups (6.9% lidocaine, 9.2% mepivacaine, and 4.1% bupivacaine; P = .297). There was no difference in rates of TNS or POUR between THA and TKA/unicompartmental knee arthroplasty. Bupivacaine had a significantly higher rate of urinary retention (9.1%; P < .001) than mepivacaine (2.8%) or lidocaine (1.5%). CONCLUSION: This study showed no difference in the rate of TNS between the 3 common agents used in spinal anesthesia. Short-acting spinal anesthetics such as lidocaine and mepivacaine can lower the rate of POUR requiring catheterization, helping to enable rapid recovery after hip and knee arthroplasty.