An IGFBP2-derived peptide promotes neuroplasticity and rescues deficits in a mouse model of Phelan-McDermid syndrome.

We developed an IGFBP2-mimetic peptide fragment, JB2, and showed that it promotes basal synaptic structural and functional plasticity in cultured neurons and mice. We demonstrate that JB2 directly binds to dendrites and synapses, and its biological activity involves NMDA receptor activation, gene transcription and translation, and IGF2 receptors. It is not IGF1 receptor-dependent. In neurons, JB2 induced extensive remodeling of the membrane phosphoproteome. Synapse and cytoskeletal regulation, autism spectrum disorder (ASD) risk factors, and a Shank3-associated protein network were significantly enriched among phosphorylated and dephosphorylated proteins. Haploinsufficiency of the SHANK3 gene on chromosome 22q13.3 often causes Phelan-McDermid Syndrome (PMS), a genetically defined form of autism with profound deficits in motor behavior, sensory processing, language, and cognitive function. We identified multiple disease-relevant phenotypes in a Shank3 heterozygous mouse and showed that JB2 rescued deficits in synaptic function and plasticity, learning and memory, ultrasonic vocalizations, and motor function; it also normalized neuronal excitability and seizure susceptibility. Notably, JB2 rescued deficits in the auditory evoked response latency, alpha peak frequency, and steady-state electroencephalography response, measures with direct translational value to human subjects. These data demonstrate that JB2 is a potent modulator of neuroplasticity with therapeutic potential for the treatment of PMS and ASD.

Intraoperative Surgeon-Administered Adductor Canal Block Is a Safe Alternative to Preoperative Anesthesiologist-Administered Adductor Canal Block in Primary Total Knee Arthroplasty.

BACKGROUND: The shift toward outpatient total knee arthroplasties (TKAs) has led to a demand for effective perioperative pain control methods. A surgeon-performed "low" adductor canal block ("low-ACB") technique, involving an intraoperative ACB, is gaining popularity due to its efficiency and early pain control potential. This study examined the transition from traditional preoperative anesthesiologist-performed ultrasound-guided adductor canal blocks ("high-ACB") to low-ACB, evaluating pain control, morphine consumption, first physical therapy visit gait distance, hospital length-of-stay, and complications. METHODS: There were 2,620 patients at a single institution who underwent a primary total knee arthroplasty between January 1, 2019, and December 31, 2022, and received either a low-ACB or high-ACB. Cohorts included 1,248 patients and 1,372 patients in the low-ACB and high-ACB groups, respectively. Demographics and operative times were similar. Patient characteristics and outcomes such as morphine milligram equivalents (MMEs), Visual Analog Scale pain scores, gait distance (feet), length of stay (days), and postoperative complications (30-day readmission and 30-day emergency department visit) were collected. RESULTS: The low-ACB cohort had higher pain scores over the first 24 hours (5.05 versus 4.86, P < .001) and higher MME at 6 hours (11.49 versus 8.99, P < .001), although this was not clinically significant. There was no difference in pain scores or MME at 12 or 24 hours (20.81 versus 22.07 and 44.67 versus 48.78, respectively). The low-ACB cohort showed longer gait distance at the first physical therapy visit (188.5 versus 165.1 feet, P < .001) and a shorter length of stay (0.88 versus 1.46 days, P < .01), but these were not clinically significant. There were no differences in 30-day complications. CONCLUSIONS: The low-ACB offers effective pain relief and comparable early recovery without increasing operative time or the complication rate. Low-ACB is an effective, safe, and economical alternative to high-ACB. LEVEL OF EVIDENCE: Therapeutic study, Level III (retrospective cohort study).

Surgical Approach Does Not Influence Instability Risk in Revision Total Hip Arthroplasty.

BACKGROUND: Although the direct anterior (DA) approach has increased in popularity for primary total hip arthroplasty (THA), there is limited evidence regarding its use for revision THA. It is unknown whether the dislocation benefit seen in the primary setting translates to revision cases. METHODS: This retrospective review compared the dislocation rates of revision THA performed through DA versus postero-lateral (PL) approaches at a single institution (2011 to 2021). Exclusion criteria included revision for instability, ≥ 2 prior revisions, approaches other than DA or PL, and placement of dual-mobility or constrained liners. There were 182 hips in 173 patients that met the inclusion criteria. The average follow-up was 6.5 years (range, 2 to 8 years). RESULTS: There was a trend toward more both-component revisions being performed through the PL approach. There were no differences in dislocation rates between the DA revision and PL revision cohorts, which were 8.1% (5 of 72) and 7.5% (9 of 120), respectively (P = .999). Dislocation trended lower when the revision approach was discordant from the primary approach compared to cases where primary and revision had a concordant approach (4.9 versus 8.5%), but this was not statistically significant (P = .740). No significant differences were found in return to operating room, 90-day emergency department visits, or 90-day readmissions. However, the length of stay was significantly shorter in patients who had DA revisions after a primary PL procedure (P = .021). CONCLUSIONS: Dislocation rates following revision THA did not differ between the DA and PL approaches irrespective of the primary approach. Surgeons should choose their revision approach based on their experience and the specific needs of the patient.

A Reduction in Body Mass Index From ≥ 40 to < 40 Lowers Emergency Department Visits, but May Increase All-Cause Readmissions After Primary Total Hip Arthroplasty: Conflicting 90-Day Outcomes at a Single Institution.

BACKGROUND: The American Association of Hip and Knee Surgeons tasked a 2013 workgroup to provide obesity-related recommendations in total joint arthroplasty. Morbidly obese patients (body mass index (BMI) ≥ 40) seeking hip arthroplasty were determined to be at increased perioperative risk, and surgeons were recommended to encourage these patients to reduce their BMI <40 presurgery. We report the effect of instituting a 2014 BMI <40 threshold on our primary total hip arthroplasties (THAs). METHODS: We queried our institutional database to select all primary THAs from January 2010 to May 2020. There were 1,383 THAs that were pre-2014 and 3,273 THAs that were post-2014. The 90-day emergency department (ED) visits, readmissions, and returns to operating room (OR) were identified. Patients were propensity score weight-matched according to comorbidities, age, initial surgical consultation (consult) BMI, and sex. We conducted 3 comparisons: A) pre-2014 patients who had a consult and surgical BMI ≥40 against post-2014 patients who had a consult BMI ≥40 and surgical BMI <40; B) pre-2014 patients against post-2014 patients who had a consult and surgical BMI <40; and C) post-2014 patients who had a consult BMI ≥40 and surgical BMI <40 against post-2014 patients who had a consult BMI ≥40 and surgical BMI ≥40. RESULTS: Post-2014 patients who had a consult BMI ≥ 40 and surgical BMI <40 had less ED visits (7.6 versus 14.1%, P = .0007), but similar readmissions (11.9 versus 6.3%, P = .22) and returns to OR (5.4 versus 1.6%, P = .09) compared to pre-2014 patients who had a consult BMI and surgical BMI ≥ 40. Post-2014 BMI <40 had less readmissions (5.9 versus 9.3%, P < .0001), and similar all-cause returns to OR and ED visits than patients pre-2014. Post-2014 patients who had a consult and surgical BMI ≥ 40 had lower readmissions (12.5 versus 12.8%, P = .05), and similar ED visits and returns to OR than consult BMI ≥ 40 and surgical BMI <40. CONCLUSION: Patient optimization prior to total joint arthroplasty is critical. However, the BMI optimization that mitigates risk in primary total knee arthroplasty may not apply to primary THA. We observed a paradoxical increased readmission rate for patients who reduced their BMI before THA. LEVEL OF EVIDENCE: III.

Cemented Femoral Stem Fixation: Back to the Future.

BACKGROUND: Periprosthetic fractures following elective and nonelective hip arthroplasty remain one of the most common modes of early failure. METHODS: This symposium will explore the current role of cemented fixation and periprosthetic fracture, focusing on history and rationale for cemented stem fixation, registry data, and other potential advantages of cemented stem fixation. A meticulous and methodical surgical technique of cemented stem fixation is paramount to the success and will be thoroughly discussed. RESULTS: The role of stem fixation, and its effect on periprosthetic fracture is well-documented in the literature. Yet despite this, the utilization of cemented stem fixation remains low in the United States. This paradox is multifactorial. CONCLUSION: In addition to a notable reduction in the risk of periprosthetic femur fractures, cemented stem fixation has numerous other advantages and is reproducible with a methodical surgical technique.

Institutional Adherence to the American Association of Hip and Knee Surgeons Body Mass Index Guidelines Lowers Perioperative Emergency Department Visits in Primary Total Knee Arthroplasty.

BACKGROUND: In 2013, the American Association of Hip and Knee Surgeons tasked a workgroup to provide obesity-related recommendations in total joint arthroplasty and determined that patients who had body mass index (BMI) ≥ 40 seeking hip/knee arthroplasty were at increased perioperative risk and recommended preoperative weight reduction. Few studies have shown the actual results of instituting this; therefore, we reported the effect of instituting a BMI < 40 threshold in 2014 on our elective, primary total knee arthroplasties (TKAs). METHODS: We queried an institutional database to select all TKAs conducted from January 2010 to May 2020. There were 2,514 TKA pre-2014 and 5,545 TKA post-2014 that were identified. The 90-day emergency department (ED) visits, readmissions, and returns-to-operating room (OR) outcomes were identified. Patients were propensity score weight-matched as per comorbidities, age, initial surgical consultation (consult) BMI, and sex. We conducted 3 outcome comparisons: (1) pre-2014 patients who had a consult and surgical BMI ≥ 40 against post-2014 patients who had a consult BMI ≥ 40 and surgical BMI < 40; (2) pre-2014 patients against post-2014 patients who had a consult and surgical BMI < 40; (3) post-2014 patients who had a consult BMI ≥ 40 and surgical BMI < 40 against post-2014 patients who had a consult BMI ≥ 40 and surgical BMI ≥ 40. RESULTS: Pre-2014 patients who had a consult and surgical BMI ≥ 40 had more ED visits (12.5% versus 6%, P = .002) but similar readmissions and returns-to-OR than post-2014 patients who had a consult BMI ≥ 40 and surgical BMI < 40. Pre-2014 patients who had a consult and surgical BMI < 40 had more readmissions (8.8% versus 6%, P < .0001) but similar ED visits and returns-to-OR when compared to their post-2014 counterparts. Post-2014 patients who had a consult BMI ≥ 40 and surgical BMI < 40 had fewer ED visits (5.8% versus 10.6%) but similar readmissions and returns-to-OR than patients who had a consult BMI ≥ 40 and surgical BMI ≥ 40. DISCUSSION: Patient optimization prior to total joint arthroplasty is essential. Enacting BMI reduction pathways prior to total knee arthroplasty seems to afford morbidly obese patients major risk mitigation. We must continue to ethically balance the pathology, expected improvement after surgery, and the overall risks of complications for each patient. LEVEL OF EVIDENCE: III.

Zelquistinel Is an Orally Bioavailable Novel NMDA Receptor Allosteric Modulator That Exhibits Rapid and Sustained Antidepressant-Like Effects.

BACKGROUND: The role of glutamatergic receptors in major depressive disorder continues to be of great interest for therapeutic development. Recent studies suggest that both negative and positive modulation of N-methyl-D-aspartate receptors (NMDAR) can produce rapid antidepressant effects. Here we report that zelquistinel, a novel NMDAR allosteric modulator, exhibits high oral bioavailability and dose-proportional exposures in plasma and the central nervous system and produces rapid and sustained antidepressant-like effects in rodents by enhancing activity-dependent, long-term synaptic plasticity. METHODS: NMDAR-mediated functional activity was measured in cultured rat brain cortical neurons (calcium imaging), hNR2A or B subtype-expressing HEK cells, and synaptic plasticity in rat hippocampal and medial prefrontal cortex slices in vitro. Pharmacokinetics were evaluated in rats following oral administration. Antidepressant-like effects were assessed in the rat forced swim test and the chronic social deficit mouse model. Target engagement and the safety/tolerability profile was assessed using phencyclidine-induced hyperlocomotion and rotarod rodent models. RESULTS: Following a single oral dose, zelquistinel (0.1-100 µg/kg) produced rapid and sustained antidepressant-like effects in the rodent depression models. Brain/ cerebrospinal fluid concentrations associated with zelquistinel antidepressant-like activity also increased NMDAR function and rapidly and persistently enhanced activity-dependent synaptic plasticity (long-term potentiation), suggesting that zelquistinel produces antidepressant-like effects by enhancing NMDAR function and synaptic plasticity. Furthermore, Zelquistinel inhibited phencyclidine (an NMDAR antagonist)-induced hyperlocomotion and did not impact rotarod performance. CONCLUSIONS: Zelquistinel produces rapid and sustained antidepressant effects by positively modulating the NMDARs, thereby enhancing long-term potentiation of synaptic transmission.

Extensile Acetabular Exposure for the Direct Anterior Approach to the Hip.

The direct anterior approach to the hip is immediately extensile for complex acetabular reconstruction including placement of augments, cages, and bone graft both on the outer and inner table of the iliac wing. This approach is also useful for exposure and removal of intrapelvic implants.

Extensile Femoral Exposure for the Direct Anterior Approach to the Hip.

The direct anterior approach to the hip is immediately extensile to access the entire femur for a wide range of conversion hip replacement and revision hip replacement scenarios. Multiple types of trochanteric osteotomies and complex procedures including proximal femoral replacement can be accomplished through extension of the direct anterior approach distally.

Clinical Outcomes and Survivorship of Hybrid Total Hip Arthroplasty Performed Through the Anterior Approach.

INTRODUCTION: There is growing evidence that cemented femoral stems have lower complication rates in the elderly due to lower rates of periprosthetic fracture. The main objective of this study was to analyze the survival rate of a hybrid total hip arthroplasty (THA) construct utilizing a taper-slip femoral stem implanted through the anterior approach (AA). Secondary outcome measures were the complication rate, the rate of aseptic loosening, coronal plane alignment of the stem, and the grade of the cement mantle. METHODS: Patients who underwent AA hybrid THA from 2013 to 2020 were included. Indications for a cemented stem were age over 70 or patients with poor bone quality. Descriptive statistics were calculated for patient characteristics. Serial radiographs were reviewed for component alignment and for evidence of implant loosening. The survival of the femoral stem was recorded, with failure defined as femoral stem revision for any reason or radiographic evidence of implant loosening. RESULTS: A total of 473 hybrid THA in 426 patients were identified, with a mean age of 76 years. Mean follow-up was 38 months. Femoral stem survival was 99.2%. There were no cases of aseptic loosening of the femoral component. Mean coronal stem alignment was 0.2 degrees varus, and all were within 5 degrees of neutral. Cement mantle grade was either A or B in 94% of cases. CONCLUSION: AA hybrid THA is an excellent option in elderly patients, or patients with poor bone quality, with a femoral stem survival rate of 99.2% and a 0% rate of aseptic loosening.

Ultrasound-Guided Adductor Canal Block Versus Intraoperative Transarticular Saphenous Nerve Block: A Retrospective Analysis.

BACKGROUND: The ultrasound-guided adductor canal block (High-ACB) is an effective option for pain control in total knee arthroplasty (TKA), but its use can add substantial cost and preparatory time to a TKA procedure. An intraoperative adductor canal block (Low-ACB) performed by the operative surgeon has been described as an alternative. The hypothesis of this study is that the Low-ACB would achieve noninferior pain control and opioid utilization postoperatively when compared to the High-ACB. METHODS: This is a retrospective study of a prospectively maintained database comparing the High-ACB vs the Low-ACB. The primary outcome measure was morphine milligram equivalents consumed. Secondary outcome measures included Visual Analog Scale pain scores, postoperative outcomes (Patient-Reported Outcome Measurement Information System, Knee Injury and Osteoarthritis Outcome Score, knee range of motion), length of stay, postoperative speed of mobilization, and complications related to the type of block. RESULTS: There were 139 patients in the study. There was lower opioid use in the first 24 hours in the Low-ACB compared to the High-ACB group respectively (26.3 vs 30, P = .29) but this did not reach statistical significance. There was a statistically significant difference in Visual Analog Scale score on postoperative day 1 in the Low-ACB vs High-ACB groups respectively (4.6 vs 3.7, P = .02) but this did not reach the level of clinical significance. There was no statistical difference in the Patient-Reported Outcome Measurement Information System, Knee Injury and Osteoarthritis Outcome Score, or postoperative range of motion. There were no block-related complications in either group. CONCLUSION: The Low-ACB is a safe, effective, and cost-saving alternative to the traditional High-ACB for pain control in TKA.

Two-stage Treatment for Hip and Knee Periprosthetic Infections.

Two-stage exchange remains the standard of care for treatment of chronic periprosthetic infections in the United States. The strategy involves three steps; a resection arthroplasty with a thorough debridement and placement of a temporary spacer, an extended period of targeted antibiotics, and finally, a second definitive reconstruction procedure. The lengthy period of time between surgeries, where patients have diminished mobility, a long period of IV antibiotics and its considerable side effects, and the need for two large operations and hospitalizations places physiologic and emotional demands on patients and their families. A two-stage exchange has considerable morbidity and mortality, with significant attrition between stages. Nonetheless, it remains the gold standard for treatment of chronic periprosthetic infections, with good historic success rates. In this review, we outline its historical origins, surgical technique, outcomes and current research shaping two-stage exchanges. (Journal of Surgical Orthopaedic Advances 30(4):220-225, 2021).

NYX-2925 induces metabotropic N-methyl-d-aspartate receptor (NMDAR) signaling that enhances synaptic NMDAR and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor.

N-methyl-d-aspartate receptors (NMDARs) mediate both physiological and pathophysiological processes, although selective ligands lack broad clinical utility. NMDARs are composed of multiple subunits, but N-methyl-d-aspartate receptor subunit 2 (GluN2) is predominately responsible for functional heterogeneity. Specifically, the GluN2A- and GluN2B-containing subtypes are enriched in adult hippocampus and cortex and impact neuronal communication via dynamic trafficking into and out of the synapse. We sought to understand if ((2S, 3R)-3-hydroxy-2-((R)-5-isobutyryl-1-oxo-2,5-diazaspiro[3,4]octan-2-yl) butanamide (NYX-2925), a novel NMDAR modulator, alters synaptic levels of GluN2A- or GluN2B-containing NMDARs. Low-picomolar NYX-2925 increased GluN2B colocalization with the excitatory post-synaptic marker post-synaptic density protein 95 (PSD-95) in rat primary hippocampal neurons within 30 min. Twenty-four hours following oral administration, 1 mg/kg NYX-2925 increased GluN2B in PSD-95-associated complexes ex vivo, and low-picomolar NYX-2925 regulated numerous trafficking pathways in vitro. Because the NYX-2925 concentration that increases synaptic GluN2B was markedly below that which enhances long-term potentiation (mid-nanomolar), we sought to elucidate the basis of this effect. Although NMDAR-dependent, NYX-2925-mediated colocalization of GluN2B with PSD-95 occurred independent of ion flux, as colocalization increased in the presence of either the NMDAR channel blocker (5R,10S)-(-)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate or glycine site antagonist 7-chlorokynurenic acid. Moreover, while mid-nanomolar NYX-2925 concentrations, which do not increase synaptic GluN2B, enhanced calcium transients, functional plasticity was only enhanced by picomolar NYX-2925. Thus, NYX-2925 concentrations that increase synaptic GluN2B facilitated the chemical long-term potentiation induced insertion of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor GluA1 subunit levels. Basal (unstimulated by chemical long-term potentiation) levels of synaptic GluA1 were only increased by mid-nanomolar NYX-2925. These data suggest that NYX-2925 facilitates homeostatic plasticity by initially increasing synaptic GluN2B via metabotropic-like NMDAR signaling. Cover Image for this issue: doi: 10.1111/jnc.14735.

Proximal Femoral Replacement Using the Direct Anterior Approach to the Hip.

Proximal femoral replacement is the salvage procedure for the most severe hip arthroplasty problems. We presented a straightforward approach to this complex procedure using the direct anterior approach to the hip. This allows for accurate fluoroscopic confirmation of acetabular implant placement and direct comparison of leg lengths. It also allows the patient to be supine during the surgery which facilitates the anesthesia care of this challenging patient population.

Periprosthetic Fractures and Conversion Hip Replacement Using the Direct Anterior Approach to the Hip.

Periprosthetic fractures of the femur and the acetabulum around a hip replacement are unfortunately relatively common as is failed acetabular and hip fracture fixation. This chapter will detail the use of the direct anterior approach to the hip to manage periprosthetic fractures of the femur and the acetabulum. We will also address the use of the direct anterior approach to the hip for conversion hip replacement in cases of failed femoral and acetabular fracture fixation.

Extensile Direct Anterior Approach to the Hip for Severe Acetabular Defects.

Although total hip arthroplasty (THA) surgery is one of the most successful procedures in orthopaedics, the number of revision procedures is predicted to increase by 137% over the next two decades.1 Implant failure modes such as instability, infection, loosening, and wear are becoming more prevalent.2 Instability, infection, extensive bony defects, and soft-tissue damage are the most important concerns and complications associated with revision surgery. More than 50% of revisions involve the acetabular implant.2 Paprosky et al described a classification of acetabular defects that occur in cases of implant failure.3 Treating type 2 and 3 uncontained defects can be technically challenging because the surgeon has to use extensive reconstruction techniques to adequately restore the biomechanics of the hip, structural stability, and leg length. Furthermore, neurovascular structures can be in jeopardy when complex pelvic reconstructive procedures are being conducted. In an attempt to optimize the access to the pelvic bone, to minimize soft-tissue damage and to protect the pelvic neurovascular structures, we use an extensile anterior approach to the acetabulum. This approach has been described by Ganz et al to conduct periacetabular osteotomies (PAO).4,5 This approach uses the Smith Petersen interval and exposes the anterior column and the acetabulum along with its defects. To our knowledge, the approach has not been used or described yet to conduct complex reconstructive surgeries for extensive acetabular defects in THA. The following is a description of a modified extensile surgical technique for challenging acetabular defects that may be encountered in certain revision THA reconstructions, as well as certain primary THA. This is an enhanced technical description of a technique presented by these authors in a previously described series of 48 patients who underwent revision using these techniques.6.

The Past, Present, and Future of Orthopedic Education: Lessons Learned From the COVID-19 Pandemic.

The COVID-19 global pandemic has upended nearly every medical discipline, dramatically impacted patient care and has had far-reaching effects on surgeon education. In many areas of the country, elective orthopedic surgery has completely stopped to ensure that resources are available for the critically ill and to minimize the spread of disease. COVID-19 is forcing many around the world to re-evaluate existing processes and organizations and adapt to carry out business, of which medicine and education are not immune. Most national and international orthopedic conferences, training programs, and workshops have been postponed or canceled, and we are now critically evaluating the delivery of education to our colleagues as well as residents and fellows. This article describes the evolution of orthopedic education and significant paradigm shifts necessary to continue to teach ourselves and the future leaders of our noble profession.

Positive N-Methyl-D-Aspartate Receptor Modulation by Rapastinel Promotes Rapid and Sustained Antidepressant-Like Effects.

BACKGROUND: Modulation of glutamatergic synaptic transmission by N-methyl-D-aspartate receptors can produce rapid and sustained antidepressant effects. Rapastinel (GLYX-13), initially described as a N-methyl-D-aspartate receptor partial glycine site agonist, exhibits rapid antidepressant effect in rodents without the accompanying dissociative effects of N-methyl-D-aspartate receptor antagonists. METHODS: The relationship between rapastinel's in vitro N-methyl-D-aspartate receptor pharmacology and antidepressant efficacy was determined by brain microdialysis and subsequent pharmacological characterization of therapeutic rapastinel concentrations in N-methyl-D-aspartate receptor-specific radioligand displacement, calcium mobilization, and medial prefrontal cortex electrophysiology assays. RESULTS: Brain rapastinel concentrations of 30 to 100 nM were associated with its antidepressant-like efficacy and enhancement of N-methyl-D-aspartate receptor-dependent neuronal intracellular calcium mobilization. Modulation of N-methyl-D-aspartate receptors by rapastinel was independent of D-serine concentrations, and glycine site antagonists did not block rapastinel's effect. In rat medial prefrontal cortex slices, 100 nM rapastinel increased N-methyl-D-aspartate receptor-mediated excitatory postsynaptic currents and enhanced the magnitude of long-term potentiation without any effect on miniature EPSCs or paired-pulse facilitation responses, indicating postsynaptic action of rapastinel. A critical amino acid within the NR2 subunit was identified as necessary for rapastinel's modulatory effect. CONCLUSION: Rapastinel brain concentrations associated with antidepressant-like activity directly enhance medial prefrontal cortex N-methyl-D-aspartate receptor activity and N-methyl-D-aspartate receptor-mediated synaptic plasticity in vitro. At therapeutic concentrations, rapastinel directly enhances N-methyl-D-aspartate receptor activity through a novel site independent of the glycine coagonist site. While both rapastinel and ketamine physically target N-methyl-D-aspartate receptors, the 2 molecules have opposing actions on N-methyl-D-aspartate receptors. Modest positive modulation of N-methyl-D-aspartate receptors by rapastinel represents a novel pharmacological approach to promote well-tolerated, rapid, and sustained improvements in mood disorders.

Use of Observation Status Versus Readmission in Elective Total Knee and Hip Arthroplasty Returns to Hospital: A Single-Institution Perspective.

BACKGROUND: The Affordable Care Act's Readmission Reduction Program (RRP) and ongoing transparency efforts to promote consumer-driven competition place significant institutional focus on improving 30-day readmission rates. It remains unclear whether the reduction in readmission rates subsequent to the RRP occurred due to improved quality and/or partly due to increased use of observation status in conditions that may have been classified as readmissions prior to the RRP. We hypothesize that a significant percentage of our institution's 30-day readmissions after elective total knee and hip arthroplasty (TKA/THA) overestimate the needs, duration, and complexity of the hospital-based intervention and inaccurately reflect the quality of service provided. METHODS: We performed a retrospective review of prospectively collected quality control data for 30-day returns to hospital after elective TKA/THA at our institution over a 2-year period. After stratification of the readmissions to under 48-hour and over 48-hour length of stay, we calculated the financial implications to our institution if the under 48-hour length of stay admissions were reclassified as an observation by applying discharge-weighted and payment-weighted analyses to the 2017 RRP report. We then calculated the out-of-pocket expenses for the under 48-hour Medicare subpopulation. RESULTS: We found that 16.7% of the 30-day readmissions after elective TKA/THA required a length of stay under 48 hours. If the short length of stay TKA/THA readmissions were reclassified as observations, our institution's 2018 RRP penalty would have been reduced to 39% or $334,512.28. However, this reclassification would result in an increase in out-of-pocket expenses by $540.25 (range $291.56-$1105.08) per patient. CONCLUSION: A subpopulation of 30-day readmissions does not require a level of care consistent with inpatient admission services. Classification of this short length of stay subpopulation as an observation vs an admission per Centers for Medicare and Medicaid Services guidelines would have removed our institution from the TKA/THA-specific RRP penalty. However, this would result in the unintended consequence of shifting costs, particularly self-administered drug costs, to patients.

Medical Malpractice Litigation Following Primary Total Joint Arthroplasty: A Comprehensive, Nationwide Analysis of the Past Decade.

BACKGROUND: The purpose of this study is to (1) characterize the most common reasons of medical malpractice litigation against adult reconstruction surgeons and (2) report on the outcomes of these lawsuits. METHODS: The Westlaw legal research database was queried for cases between 2008 and 2018 related to total hip and knee arthroplasty (THA and TKA) in the United States. Causes of the lawsuit, patient characteristics, demographics, state/outcome of verdict or settlement, and indemnity payments were noted. RESULTS: A total of 148 records (81 females [55%], 67 males [45%]; 83 TKAs [56%], 65 THAs [44%]) were included in the final analysis. For all patients, infection was the leading cause for malpractice litigation (22%) followed by nerve injury (20%). For TKA, infection was the most common cause of lawsuit (33%). In THA cases, nerve injury was the most common reason for lawsuit (38%), followed by leg-length discrepancy (26%). Procedural errors were alleged in 72% of cases, while diagnostic and post-surgical errors were cited in 55% and 32% of cases. A defense verdict occurred in 74% of cases, plaintiff verdict in 21%, and parties settled in 5%. CONCLUSION: Infection and nerve injury were the most common reasons for litigation in TKA and THA, respectively. The most likely outcome of these lawsuits was a jury verdict in favor of the surgeon. Regardless, surgeons should be cognizant of the potential for lawsuit due to these complications and should ensure they inform patients of these potential complications of TJA preoperatively.