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Pierce D Nunley,1 Timothy R Deer,2 Ramsin M Benyamin,3 Peter S Staats,4 Jon E Block5 1Spine Institute of Louisiana, Shreveport, LA 71101, USA; 2Center for Pain Relief, Charleston, WV 25301, USA; 3Millennium Pain Center, Bloomington, IL 61704, USA; 4National Spine and Pain Centers, Rockville, MD 20852, USA; 5Jon Block, San Francisco, CA 94115, USA Background: Lumbar spinal stenosis (LSS) causes significant pain and functional impairment, and medical management has increasingly included the prescription of opioid-based analgesics. Interspinous process decompression (IPD) provides a minimally-invasive treatment option for LSS.Methods: This study estimated the type, dosage, and duration of opioid medications through 5 years of follow-up after IPD with the Superion Indirect Decompression System (Vertiflex Inc., Carlsbad, CA USA). Data were obtained from the Superion-treatment arm of a randomized controlled noninferiority trial. The prevalence of subjects using opiates was determined at baseline through 60 months. Primary analysis included all 190 patients randomized to receive the Superion device. In a subgroup of 98 subjects, we determined opioid-medication prevalence among subjects with a history of opioid use.Results: At baseline, almost 50% (94 of 190) of subjects were using opioid medication. Thereafter, there was a sharp decrease in opioid-medication prevalence from 25.2% (41 of 163) at 12 months to 13.3% (20 of 150) at 24 months to 7.5% (8 of 107) at 60 months. Between baseline and 5 years, there was an 85% decrease in the proportion of subjects using opioids. A similar pattern was also observed among subjects with a history of opiates prior to entering the trial.Conclusion: Stand-alone IPD is associated with a marked decrease in the need for opioid medications to manage symptoms related to LSS. In light of the current opiate epidemic, such alternatives as IPD may provide effective pain relief in patients with LSS without the need for opioid therapy. Keywords: interspinous spacer, Superion, lumbar spinal stenosis, opioids, neurogenic claudication, indirect decompression

Pierce D Nunley,1 Vikas V Patel,2 Douglas G Orndorff,3 William F Lavelle,4 Jon E Block,5 Fred H Geisler6 1Spine Institute of Louisiana, Shreveport, LA, 2The Spine Center, University of Colorado Hospital, Denver, CO, 3Spine Colorado, Mercy Regional Hospital, Durango, CO, 4Upstate Bone and Joint Center, East Syracuse, NY, 5Independent Consultant, San Francisco, CA, 6Independent Consultant, Chicago, IL, USA Background: Lumbar spinal stenosis is the most common indication for spine surgery in older adults. Interspinous process decompression (IPD) using a stand-alone spacer that functions as an extension blocker offers a minimally invasive treatment option for intermittent neurogenic claudication associated with spinal stenosis.Methods: This study evaluated the 5-year clinical outcomes for IPD (Superion®) from a randomized controlled US Food and Drug Administration (FDA) noninferiority trial. Outcomes included Zurich Claudication Questionnaire (ZCQ) symptom severity (ss), physical function (pf), and patient satisfaction (ps) subdomains, leg and back pain visual analog scale (VAS), and Oswestry Disability Index (ODI).Results: At 5 years, 84% of patients (74 of 88) demonstrated clinical success on at least two of three ZCQ domains. Individual ZCQ domain success rates were 75% (66 of 88), 81% (71 of 88), and 90% (79 of 88) for ZCQss, ZCQpf, and ZCQps, respectively. Leg and back pain success rates were 80% (68 of 85) and 65% (55 of 85), respectively, and the success rate for ODI was 65% (57 of 88). Percentage improvements over baseline were 42%, 39%, 75%, 66%, and 58% for ZCQss, ZCQpf, leg and back pain VAS, and ODI, respectively (all P1.0; all P

Lineage transitions are a central feature of prostate development, tumourigenesis and treatment resistance. While epigenetic changes are well known to drive prostate lineage transitions, it remains unclear how upstream metabolic signalling contributes to the regulation of prostate epithelial identity. To fill this gap, we developed an approach to perform metabolomics on primary prostate epithelial cells. Using this approach, we discovered that the basal and luminal cells of the prostate exhibit distinct metabolomes and nutrient utilization patterns. Furthermore, basal-to-luminal differentiation is accompanied by increased pyruvate oxidation. We establish the mitochondrial pyruvate carrier and subsequent lactate accumulation as regulators of prostate luminal identity. Inhibition of the mitochondrial pyruvate carrier or supplementation with exogenous lactate results in large-scale chromatin remodelling, influencing both lineage-specific transcription factors and response to antiandrogen treatment. These results establish reciprocal regulation of metabolism and prostate epithelial lineage identity.

Vikas V Patel,1 Pierce D Nunley,2 Peter G Whang,3 Thomas R Haley,4 W Daniel Bradley,5 Raphael P Davis,6 Jon E Block,7 Fred H Geisler8 1The Spine Center, University of Colorado Hospital, Denver, CO, 2Spine Institute of Louisiana, Shreveport, LA, 3Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT, 4Performance Spine and Sports Physicians, PC, Pottstown, PA, 5Texas Back Institute, Denton, TX, 6Department of Neurological Surgery, Stony Brook Medicine, Stony Brook, NY, 7Jon Block, Ph.D. San Francisco, CA, 8McLaren Hospital, Petoskey, MI, USA Purpose: This report provides the 3-year clinical outcomes from the randomized, controlled US Food and Drug Administration Investigational Device Exemption trial of the Superion® for the treatment of moderate degenerative lumbar spinal stenosis. Patients and methods: The Superion® was evaluated in the treatment of subjects aged 45 years or older suffering from symptoms of intermittent neurogenic claudication, secondary to a confirmed diagnosis of moderate degenerative lumbar spinal stenosis at one or two contiguous levels from L1 to L5. Patients were treated between June 2008 and December 2011 at 31 investigational sites. Three hundred ninety-one subjects were included in the randomized study group consisting of 190 Superion® and 201 X-STOP® control subjects. The primary composite endpoint was individual patient success based on four components: improvement in two of three domains of the Zurich Claudication Questionnaire, no reoperations at the index level, no major implant/procedure-related complications, and no clinically significant confounding treatments. Results: At 3 years, the proportion of subjects achieving the primary composite endpoint was greater for Superion® (63/120, 52.5%) than for X-STOP® (49/129, 38.0%) (P=0.023) and the corresponding success rates exceeded 80% for each of the individual components of the primary endpoint in the Superion® group (range: 81%–91%). Improvements in back and leg pain severity as well as back- and disease-specific functional outcomes were also maintained through 36 months. Conclusion: The 3-year outcomes from this randomized controlled trial demonstrate durable clinical improvement consistently across all clinical outcomes for the Superion® in the treatment of patients with moderate degenerative lumbar spinal stenosis. Keywords: InterSpinous Spacer, lumbar spinal stenosis, Superion®, neurogenic claudication

Abstract Background The current report investigates fusion rates and patient-reported outcomes following lumbar spinal surgery using cellular bone allograft (CBA) in patients with risk factors for non-union. Methods A prospective, open label study was conducted in subjects undergoing lumbar spinal fusion with CBA (NCT 02969616) to assess fusion success rates and patient-reported outcomes in subjects with risk factors for non-union. Subjects were categorized into low-risk (≤ 1 risk factors) and high-risk (> 1 risk factors) groups. Radiographic fusion status was evaluated by an independent review of dynamic radiographs and CT scans. Patient-reported outcome measures included quality of life (EQ-5D), Oswestry Disability Index (ODI) and Visual Analog Scales (VAS) for back and leg pain. Adverse event reporting was conducted throughout 24-months of follow-up. Results A total of 274 subjects were enrolled: 140 subjects (51.1%) were categorized into the high-risk group (> 1 risk factor) and 134 subjects (48.9%) into the low-risk group (≤ 1 risk factors). The overall mean age at screening was 58.8 years (SD 12.5) with a higher distribution of females (63.1%) than males (36.9%). No statistical difference in fusion rates were observed between the low-risk (90.0%) and high-risk (93.9%) groups (p > 0.05). A statistically significant improvement in patient-reported outcomes (EQ-5D, ODI and VAS) was observed at all time points (p

ABSTRACT Filoviruses are some of the most lethal viruses in the modern world, and increasing numbers of filovirus species and genera have been discovered in recent years. Despite the potential severity of filovirus outbreaks in the human population, comparably few sensitive pan-filovirus RT-PCR assays have been described that might facilitate early detection and prevention. Here, we present a new pan-filovirus RT-PCR assay targeting the L polymerase gene for detection of all known mammalian filoviruses. We demonstrate the detection of 10 synthetic filovirus RNA templates with analytical sensitivity ranging from 178 to 3,354 copies/mL, without cross-reactivity on 10 non-filoviral human viral species. We verified assay performance on 10 inactivated filovirus isolates, yielding initial sensitivities of 0.012–44.17 TCID50/mL. We coupled this broadly reactive RT-PCR with a deep sequencing workflow that is amenable to high-throughput pooling to maximize detection and discovery potential. In summary, this pan-filovirus RT-PCR assay targets the most conserved filovirus gene, offers the widest breadth of coverage to date, and may help in the detection and discovery of novel filoviruses.IMPORTANCEFiloviruses remain some of the most mysterious viruses known to the world, with extremely high lethality rates and significant pandemic potential. Yet comparably few filovirus species and genera have been discovered to date and questions surround the definitive host species for zoonotic infections. Here, we describe a novel broadly reactive RT-PCR assay targeting the conserved L polymerase gene for high-throughput screening for filoviruses in a variety of clinical and environmental specimens. We demonstrate the assay can detect all known mammalian filoviruses and determine the sensitivity and specificity of the assay on synthetic RNA sequences, inactivated filovirus isolates, and non-filoviral species.

Background: This retrospective cohort study compared short-term complication rates following total ankle arthroplasty (TAA), alone or with concomitant procedures. Secondary independent risk factors were also examined as they related to postoperative outcomes. Methods: The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database was queried using Current Procedural Terminology ( CPT ) codes to identify patients who underwent TAA (27702) between 2010 to 2021. Patients were divided into cohorts based on the presence or absence of ancillary procedures. Propensity score matching was employed to account for demographic differences, and statistical analyses were performed to compare short-term complication rates between matched cohorts. Results: A total of 2225 patients were identified, with 1432 (64.4%) receiving TAA alone and 793 (35.6%) with ancillary procedure(s). After matching, 793 patients were included in each cohort. The ancillary cohort had longer operative times ( P

Background: As lung transplant candidates are older with increased comorbidities, we sought to examine the prevalence and outcomes of lung transplant recipients after prior cardiac surgery. Methods: Lung transplants were identified from the United Network for Organ Sharing/Organ Procurement and Transplantation Network Database. Patients were stratified based on prior cardiac surgery (no surgery [NS], prior coronary artery bypass grafting [CABG], prior valve [Valve]). Unadjusted comparisons were performed among all groups, and propensity matching was utilized for adjusted comparisons. Survival was examined with Kaplan-Meier methods. Results: A total of 28,710 patients were identified, 467 (1.6%) had prior CABG and 84 (0.3%) had prior valvular surgery. Before matching, the NS group was significantly younger, less commonly male, and had lower lung allocation scores. There were significantly fewer bilateral lung transplants in the CABG and Valve groups. Length of stay was shortest in the CABG group, but there were no significant differences in postoperative stroke, dialysis, or in-hospital mortality. There was an increased incidence of cardiac/cerebrovascular cause of death in CABG recipients (18.3%) and malignancy death in Valve recipients (23.3%). Following matching, CABG 5-year survival was lower than NS (p

IntroductionThe 21-point Brain Care Score (BCS) is a novel tool designed to motivate individuals and care providers to take action to reduce the risk of stroke and dementia by encouraging lifestyle changes. Given that late-life depression is increasingly recognized to share risk factors with stroke and dementia, and is an important clinical endpoint for brain health, we tested the hypothesis that a higher BCS is associated with a reduced incidence of future depression. Additionally, we examined its association with a brain health composite outcome comprising stroke, dementia, and late-life depression.MethodsThe BCS was derived from the United Kingdom Biobank baseline evaluation in participants with complete data on BCS items. Associations of BCS with the risk of subsequent incident late-life depression and the composite brain health outcome were estimated using multivariable Cox proportional hazard models. These models were adjusted for age at baseline and sex assigned at birth.ResultsA total of 363,323 participants were included in this analysis, with a median BCS at baseline of 12 (IQR: 11-14). There were 6,628 incident cases of late-life depression during a median follow-up period of 13 years. Each five-point increase in baseline BCS was associated with a 33% lower risk of incident late-life depression (95% CI: 29%-36%) and a 27% lower risk of the incident composite outcome (95% CI: 24%-30%).DiscussionThese data further demonstrate the shared risk factors across depression, dementia, and stroke. The findings suggest that a higher BCS, indicative of healthier lifestyle choices, is significantly associated with a lower incidence of late-life depression and a composite brain health outcome. Additional validation of the BCS is warranted to assess the weighting of its components, its motivational aspects, and its acceptability and adaptability in routine clinical care worldwide.

Background: The incidence of primary total ankle arthroplasty (TAA) is rising, with a corresponding increase in revision surgeries. Despite this, research on risk factors for revision TAA following primary TAA remains limited. Radiographic soft tissue thickness has been explored as a potential predictor for outcomes in hip, knee, and shoulder arthroplasty, but its role in TAA has not been assessed. This study aimed to assess the predictive value of radiographic soft tissue thickness for identifying patients at risk of requiring revision surgery following primary TAA. Methods: A retrospective study was conducted on 323 patients who underwent primary TAA between 2003 and 2019. Radiographic measurements of soft tissue thickness were obtained from preoperative radiographs. Two novel radiographic measures of soft tissue thickness were developed and assessed (tibial tissue thickness and talus tissue thickness). Clinical variables including age, gender, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, diabetes, smoking status, primary diagnosis, and implant type were recorded. Logistic regression analysis was used to assess the predictive value of soft tissue thickness and BMI for revision TAA. Results: The rate of revision surgery was 4.3% (14 of 323 patients). Patients requiring revision had significantly greater tibial tissue (3.54 vs 2.48 cm; P = .02) and talus tissue (2.79 vs 2.42 cm; P = .02) thickness compared with those not requiring revision. Both the tibial tissue thickness (odds ratio 1.16 [1.12-1.20]; P

Not available.

Abstract Background Pedicle screw loosening and breakage are common causes of revision surgery after lumbar fusion. Thus, there remains a continued need for supplemental fixation options that offer immediate stability without the associated failure modes. This finite element analysis compared the biomechanical properties of a novel cortico-pedicular posterior fixation (CPPF) device with those of a conventional pedicle screw system (PSS). Methods The CPPF device is a polyetheretherketone strap providing circumferential cortical fixation for lumbar fusion procedures via an arcuate tunnel. Using a validated finite element model, we compared the stability and load transfer characteristics of CPPF to intact conditions under a 415 N follower load and PSS conditions under a 222 N preload. Depending on the instrumented levels, two different interbody devices were used: a lateral lumbar interbody device at L4–5 or an anterior lumbar interbody device at L5-S1. Primary outcomes included range of motion of the functional spinal units and anterior load transfer, defined as the total load through the disk and interbody device after functional motion and follower load application. Results Across all combinations of interbody devices and lumbar levels evaluated, CPPF consistently demonstrated significant reductions in flexion (ranging from 90 to 98%), extension (ranging from 88 to 94%), lateral bending (ranging from 75 to 80%), and torsion (ranging from 77 to 86%) compared to the intact spine. Stability provided by the CPPF device was comparable to PSS in all simulations (range of motion within 0.5 degrees for flexion–extension, 0.6 degrees for lateral bending, and 0.5 degrees for torsion). The total anterior load transfer was higher with CPPF versus PSS, with differences across all tested conditions ranging from 128 to 258 N during flexion, 89–323 N during extension, 135–377 N during lateral bending, 95–258 N during torsion, and 82–250 N during standing. Conclusion Under the modeled conditions, cortico-pedicular fixation for supplementing anterior or lateral interbody devices between L4 and S1 resulted in comparable stability based on range of motion measures and less anterior column stress shielding based on total anterior load transfer measures compared to PSS. Clinical studies are needed to confirm these finite element analysis findings.

Abstract Background Autologous bone grafts are the gold standard for spinal fusion; however, harvesting autologous bone can result in donor site infection, hematomas, increased operative time, and prolonged pain. Cellular bone allografts (CBAs) are a viable alternative that avoids the need for bone harvesting and may increase fusion success alone or when used as an adjunct material. The present study examined the efficacy and safety of CBA when used as an adjunct graft material to lumbar arthrodesis. Methods A prospective, single-arm, multicenter clinical trial (NCT 02969616) was conducted in adult subjects (> 18 years of age) undergoing lumbar spinal fusion with CBA graft (CBA used as primary (≥ 50% by volume), with augmentation up to 50%). Radiographic fusion status was assessed by an independent review of dynamic radiographs and CT scans. Clinical outcomes were assessed with the Oswestry Disability Index (ODI), and Visual Analog Scales (VAS) score for back and leg pain. Adverse events were assessed through the 24-month follow-up period. The presented data represents an analysis of available subjects (n = 86) who completed 24 months of postoperative follow-up at the time the data was locked for analysis. Results Postoperative 24-month fusion success was achieved in 95.3% of subjects (n = 82/86) undergoing lumbar spinal surgery. Clinical outcomes showed statistically significant improvements in ODI (46.3% improvement), VAS-Back pain (75.5% improvement), and VAS-Leg pain (85.5% improvement) (p

A retrospective review of the UNOS/OPTN Database was performed from 1 October 1987–31 December 2019. Recipients were classified as LSu (15+ years survival without GF/ReTx), normal survival (3–15 years) and short survival (

Introduction: Launched in 2018 for revision total ankle arthroplasty (rTAA), the INVISION talar component addresses subsidence when poor talar bone stock is present. Due to the recency of the market-availability of the INVISION, studies evaluating its efficacy are lacking. This study presents the first analysis of early-term outcomes of patients undergoing rTAA with the INVISION talar component. Methods: This was a single-center, retrospective review of 28 patients undergoing rTAA with the INVISION talar component and INBONE II tibial component performed between 2018 and 2022. Data on preoperative characteristics, postoperative complications, secondary procedures, and survivorship were collected. The primary outcome measures were rates of major complications, re-operation, and implant failure. Secondary outcomes included post-operative changes in varus and valgus alignment of the tibia and talus. Results: The most common secondary procedures performed with rTAA were medial malleolus fixation (n = 22, 78.6%) and gastrocnemius recession (n = 14, 50%). Overall, 10.7% (n = 3) of patients underwent reoperation and 14.3% (n = 4) suffered major complications. Incidence of implant failure was 10.7% (n = 3). All reoperations were caused by infection. Mean varus alignment of the tibia and talus improved from 4.07 degrees and 4.83 degrees to 1.67 degrees and 1.23 degrees, respectively. Mean valgus alignment of the tibia and talus improved from 3.67 degrees and 4.22 degrees to 2.00 degrees and 2.32 degrees, respectively. Conclusions: In a series of 28 patients undergoing rTAA with the INVISION talar component, we discovered comparatively low rates of reoperation, major complication, and implant failure (10.7%, 14.3%, and 10.7%). The INVISION system appears to have a reasonable safety profile, but further studies evaluating long-term outcomes are required to assess the efficacy of the INVISION system.

Background: Primary graft dysfunction (PGD) has detrimental effects on recipients following lung transplantation. Here, we determined the contemporary trends of PGD in a national database, factors associated with the development of PGD grade 3 (PGD3) and ex vivo lung perfusion’s (EVLP) effect on this harmful postoperative complication. Methods: The United Network for Organ Sharing database was queried from 2015 to 2023, and recipients were stratified into No-PGD, PGD1/2, or PGD3. The groups were analyzed with comparative statistics, and survival was determined with Kaplan–Meier methods. Multivariable Cox regression was used to determine factors associated with increased mortality. PGD3 recipients were then stratified based on EVLP use prior to transplantation, and a 3:1 propensity match was performed to determine outcomes following transplantation. Finally, logistic regression models based on select criteria were used to determine risk factors associated with the development of PGD3 and mortality within 1 year. Results: A total of 21.4% of patients were identified as having PGD3 following lung transplant. Those with PGD3 suffered significantly worse perioperative morbidity, mortality, and had worse long-term survival. PGD3 was also independently associated with increased mortality. Matched EVLP PGD3 recipients had significantly higher use of ECMO postoperatively; however, they did not suffer other significant morbidity or mortality as compared to PGD3 recipients without EVLP use. Importantly, EVLP use prior to transplantation was significantly associated with decreased likelihood of PGD3 development, while having no significant association with early mortality. Conclusions: EVLP is associated with decreased PGD3 development, and further optimization of this technology is necessary to expand the donor pool.

Abstract Background Patient-reported outcomes are commonly used to assess patient symptoms. The effect of specific hip pathology on relationships between perceived and objectively measured symptoms remains unclear. The purpose of this study was to evaluate differences of function and pain in patients with FAIS and DDH, to assess the correlation between perceived and objective function, and to determine the influence of pain on measures of function. Methods This prospective cross-sectional study included 35 pre-operative patients (60% female) with femoroacetabular impingement syndrome (FAIS) and 37 pre-operative patients (92% female) with developmental dysplasia of the hip (DDH). Objectively measured function (6-min walk [6MWT], single leg hop [SLHT], Biodex sway [BST], hip abduction strength [HABST], and STAR excursion balance reach [STAR] tests), patient-reported function (UCLA Activity, Hip Outcome Score [HOS], Short Form 12 [SF-12], and Hip Disability and Osteoarthritis Outcome Score [HOOS]), and patient-reported pain (HOOS Pain, visual analogue scale (VAS), and a pain location scale) were collected during a pre-surgical clinic visit. Between-group comparisons of patient scores were performed using Wilcoxon Rank-Sum tests. Within-group correlations were analyzed using Spearman’s rank correlation coefficients. Statistical correlation strength was defined as low (r = ± 0.1–0.3), moderate (r = ± 0.3–0.5) and strong (r > ± 0.5). Results Patients with DDH reported greater pain and lower function compared to patients with FAIS. 6MWT distance was moderately-to-strongly correlated with a number of patient-reported measures of function (FAIS: r = 0.37 to 0.62, DDH: r = 0.36 to 0.55). Additionally, in patients with DDH, SLHT distance was well correlated with patient reported function (r = 0.37 to 0.60). Correlations between patient-reported pain and objectively measured function were sparse in both patient groups. In patients with FAIS, only 6MWT distance and HOOS Pain (r = -0.53) were significantly correlated. In patients with DDH, 6MWT distance was significantly correlated with VAS Average (r = -0.52) and Best (r = -0.53) pain. Conclusion Pain is greater and function is lower in patients with DDH compared to patients with FAIS. Moreover, the relationship between pain and function differs between patient groups. Understanding these differences is valuable for informing treatment decisions. We recommend these insights be incorporated within the clinical continuum of care, particularly during evaluation and selection of surgical and therapeutic interventions.

Abstract Background and Aim Overt obscure gastrointestinal bleeding (OOGIB) is defined as continued bleeding with unknown source despite esophagogastroduodenoscopy (EGD) and colonoscopy evaluation. Small bowel evaluation through video capsule endoscopy (VCE) or double balloon enteroscopy (DBE) is often warranted. We studied the timing of DBE in hospitalized OOGIB patients regarding diagnostic yield, therapeutic yield, and GI rebleeding. Methods We performed a retrospective review of DBEs performed at a tertiary medical center between November 2012 and December 2020. The inclusion criterion was first admission for OOGIB undergoing DBE. Those without previous EGD or colonoscopy were excluded. Patients were stratified into two groups: DBE performed within 72 h of OOGIB (emergent) and beyond 72 h of OOGIB (nonemergent). Propensity score matching was used to adjust for the difference in patients in the two groups. Logistic regression analysis was used to assess factors associated with diagnostic and therapeutic yield. Kaplan–Meir survival curve showed GI bleed‐free survival following initial bleed and was compared using the log rank test. Results A total of 154 patients met the inclusion criterion, of which 62 had emergent DBE and 92 had nonemergent DBE. The propensity‐score‐matched sample consisted of 112 patients, with 56 patients each in the emergent and nonemergent groups. Univariate and multivariable logistic regression analysis showed a significant association between VCE and emergent DBE and diagnostic and therapeutic yield (P

Background: The objective of this study was to evaluate if imbalance influences complication rates, radiological outcomes, and patient-reported outcomes (PROMs) following adult spinal deformity (ASD) surgery. Methods: ASD patients with baseline and 2-year radiographic and PROMs were included. Patients were grouped according to whether they answered yes or no to a recent history of pre-operative loss of balance. The groups were propensity-matched by age, pelvic incidence–lumbar lordosis (PI-LL), and surgical invasiveness score. Results: In total, 212 patients were examined (106 in each group). Patients with gait imbalance had worse baseline PROM measures, including Oswestry disability index (45.2 vs. 36.6), SF-36 mental component score (44 vs. 51.8), and SF-36 physical component score (p < 0.001 for all). After 2 years, patients with gait imbalance had less pelvic tilt correction (−1.2 vs. −3.6°, p = 0.039) for a comparable PI-LL correction (−11.9 vs. −15.1°, p = 0.144). Gait imbalance patients had higher rates of radiographic proximal junctional kyphosis (PJK) (26.4% vs. 14.2%) and implant-related complications (47.2% vs. 34.0%). After controlling for age, baseline sagittal parameters, PI-LL correction, and comorbidities, patients with imbalance had 2.2-times-increased odds of PJK after 2 years. Conclusions: Patients with a self-reported loss of balance/unsteady gait have significantly worse PROMs and higher risk of PJK.

IntroductionThe 21-point Brain Care Score (BCS) was developed through a modified Delphi process in partnership with practitioners and patients to promote behavior changes and lifestyle choices in order to sustainably reduce the risk of dementia and stroke. We aimed to assess the associations of the BCS with risk of incident dementia and stroke.MethodsThe BCS was derived from the United Kingdom Biobank (UKB) baseline evaluation for participants aged 40–69 years, recruited between 2006–2010. Associations of BCS and risk of subsequent incident dementia and stroke were estimated using Cox proportional hazard regressions, adjusted for sex assigned at birth and stratified by age groups at baseline.ResultsThe BCS (median: 12; IQR:11–14) was derived for 398,990 UKB participants (mean age: 57; females: 54%). There were 5,354 incident cases of dementia and 7,259 incident cases of stroke recorded during a median follow-up of 12.5 years. A five-point higher BCS at baseline was associated with a 59% (95%CI: 40-72%) lower risk of dementia among participants aged 59 years. A five-point higher BCS was associated with a 48% (95%CI: 39-56%) lower risk of stroke among participants aged 59.DiscussionThe BCS has clinically relevant and statistically significant associations with risk of dementia and stroke in approximately 0.4 million UK people. Future research includes investigating the feasibility, adaptability and implementation of the BCS for patients and providers worldwide.

Category: Ankle Arthritis; Ankle Introduction/Purpose: Although many patients with postraumatic ankle arthritis are of a younger age, studies evaluating the impact of age on outcomes of primary total ankle arthroplasty (TAA) reveal heterogenous results. The purpose of this study is to determine the effect of age on complication rates and patient reported outcomes after TAA. Methods: This was a retrospective study of 1,185 primary TAA divided into 3 age cohorts (Age < 55, n=219; Age55-70, n=688; Age>70, n=278). Patient demographics, intraoperative variables, postoperative complications, and patient reported outcome measures were compared among groups using univariable analyses. Multivariable Cox regression was performed to assess risk for implant failure by age group. Mean follow-up was 5.7 years. Results: Compared to Age55-70 and Age>70 groups, Age < 55 patients had the lowest mean ASA score (2.2 vs 2.4 vs 2.5; p< 0.001) and highest rates of all complications (33.8% vs 23.1% vs 19.8%; p=0.001), implant failure (9.1% vs 6.0% vs 3.2%; p=0.022), and component removal (5.0% vs 2.8% vs 1.1%; p=0.030). Univariable and multivariable cox regression analysis revealed decreased risk for implant failure for Age>70 compared to Age < 55 patients (HR: 0.43 [95%CI: 0.19-0.94], p=0.034; and HR: 0.42 [95%CI: 0.18-0.95], p=0.038, respectively). Across the AOFAS Hindfoot and all FAOS subscales, Age < 55 group reported the lowest (worst) mean pre and postoperative scores (p < 0.001). The age < 55 group had the highest mean VAS score at final follow-up (22 vs 14 vs 14; p< 0.001). Conclusion: Studies involving large sample sizes with mid-to long-term follow up are critical to reveal age-related impacts on outcomes after TAA. Younger patients had higher rates of complications and implant failure and fared worse on patient reported outcome measures in the largest single-institution series to date evaluating the effect of age on outcomes in TAA.

Category: Ankle Arthritis; Other Introduction/Purpose: Utilization rates of total ankle arthroplasty (TAA) have greatly increased in recent years. For patients with rheumatoid arthritis (RA) undergoing TAA, conflicting data have been reported regarding risk of complications and patient reported outcome (PRO) improvement when compared to patients with osteoarthritis. The purpose of this study is to compare complication rates and PROs of patients with RA to patients with osteoarthritis and posttraumatic arthritis. Methods: This was a retrospective study of 1,071 primary TAA performed at a single institution between 2001 and 2020. Minimum follow-up was two years. Patients were stratified by indication for TAA (osteoarthritis, n=372; posttraumatic arthritis, n=642; RA, n=57). Patient demographics, intraoperative variables, postoperative complications, and PRO measures were compared between groups using univariable statistics. Multivariable Cox regression was performed to assess risk for implant failure. Mean follow-up was 5.6 years (SD: 3.1). Results: Compared to the osteoarthritis and posttraumatic arthritis groups, the RA cohort had the lowest mean age (p < 0.001), lowest percentage of males (p < 0.001), and highest ASA score (p < 0.001). Univariate analysis showed no statistically significant difference for infection rates among groups (p=1.0). The RA cohort had the highest rate of heterotopic ossification postoperatively (2/57, 3.5%, p< 0.001). Multivariable regression analysis showed no increased risk of implant failure for the RA cohort (p=0.23). For the SMFA, SF-36, AOFAS-hindfoot, FAOS-symptoms, and FAOS-ADL the RA group reported the worst scores at final follow-up (p < 0.001). However, the RA cohort demonstrated the largest improvements from preoperative to postoperative scores on the FADI, SF-36, and the symptoms and ADL subscales of the FAOS (p=0.04, 0.01, 0.03, 0.03). Conclusion: In the largest single institution study to date, patients with RA had the worst PRO scores compared to the osteoarthritis and posttraumatic arthritis groups. However, they experienced significantly higher improvements in functional outcomes from their preoperative baseline. Large patient samples with mid- to long-term follow up such as a presented in this series are imperative to fully understand the risk-benefit of TAA in various patient cohorts.

Category: Ankle Arthritis; Ankle Introduction/Purpose: The Scandinavian Total Ankle Replacement (STAR) is a widely used ankle prosthesis, but mid- to long-term follow up remains limited. In thirteen different studies involving 939 STAR total ankle prostheses, the average duration of follow- up for recipients was 3.9 years. Thus, we sought to evaluate the STAR at the mid- to long-term interval with regards to survivorship, complications, and patient reported outcomes (PROs) in one of the largest series with the longest-term follow up to date. Methods: All patients managed with a primary STAR prosthesis at our institution from March 2002 through January 2017 were included in the analysis. Demographic characteristics including gender, race, age, diabetes status, body mass index (BMI), smoking status, American Society of Anesthesiologist (ASA) score, and surgery time were summarized. The cumulative incidence of implant failure was at 5 years and the last recorded time to event (8 years) were reported with 95% confidence intervals (CI). Paired t- tests were used to compare pre-operative and 5 year post-operative (±1 year) for PROs including Visual Analog Scale (VAS), Short Musculoskeletal Function Assessment (SMFA), Short-form-36 (SF-36), and American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot subscales. Additionally, intra- and post-operative complications were recorded. All statistical analysis were conducted in SAS 9.4 (Cary, NC). Statistical significance was assessed at α = 0.05. Results: 247 patients with a unilateral STAR procedure were included in this analysis. Demographics are listed in Table 1. The average number of years of follow-up was 5.71 ± 4.07 years. The cumulative incidence of implant failure at 5 years was 7.7% (95% CI 4.3%-12.5%). The last failure event occurred at 8 years post-implant. The cumulative incidence of implant failure at 8 years was 11.1% (95% CI 6.3%-17.3%) (Table 2, Figure 1). The most common post-operative complications were impingement (N = 39, 15.8%), ankle pain (N = 22, 8.9%), and implant failure (N = 16, 6.5%) (Table 3). With regards to PROs, patients significantly improved between baseline and 5-year follow up in all measures (all p< 0.001; Table 4). Conclusion: At mid- to long-term follow up, patients receiving the STAR prosthesis experienced a significant and durable improvement in PROs across multiple functional indices. Complication and failure rates were lower than those reported in previous series evaluating the STAR, with an observed survivorship of 88.9% at 8-year follow up.

Category: Ankle Arthritis Introduction/Purpose: End stage arthritis is a debilitating condition that significantly affects patients’ quality of life. Ankle arthritis differs from arthritis of the hip and knee in that ankle arthritis is often posttraumatic in nature and affects a younger patient population. Historically, younger age was a contraindication to total ankle arthroplasty (TAA) and ankle arthrodesis was the mainstay of treatment. Advances in TAA implant design and revision implants has expanded indications and increased usage of TAA. Despite this, many surgeons remain hesitant due to the lack of long term data on patient outcomes and survivorship in these patients. The purpose of our study was to evaluate patient reported outcome measures and survivorship after primary TAA in patients < 50 years of age at the time of surgery. Methods: A retrospective chart review was conducted of patients < 50 years of age who underwent primary TAA at a single institution from 2010-2020. Patient demographics, outcome measures, and complications were recorded. All patients had a minimum clinical follow up of 5 years. Patient reported outcome (PRO) measures collected included FADI, VAS, SMFA SF-36, AOFAS hindfoot scores, and FAOS scores. Outcome measures were evaluated preoperative, 1 year postoperative, and at final clinical follow up. Paired t-tests were performed to compare individual patients’ changes in PRO from preoperative to postoperative timepoints. Multiple comparisons correction was performed using the Bonferroni method. Implant survivorship was evaluated based on need for revision of either the tibial or talar component. Results: A total of 59 patients were included in the study. The average age at time of surgery was 43.2 years. All patients had a minimum follow up of 5 years with a mean follow up time of 8.8 years. Mean FADI improved from 53.3 (sd:14.1) preoperatively to 16.1 (sd:11.4) (p < 0.001) at 1-year postoperatively. Mean VAS and SMFA also improved from preoperative to 1-year postoperative timepoints [VAS: 68.2 (sd:27.0) to 10.3(sd:13.1) (p < 0.001); SMFA: 36.1 (sd:12.2) to 14.8 (sd:13.7) (p < 0.001)]. A total of 5 patients required revision of components during the follow up period. Three patients required complete revision of both tibial and talar components, 2 due to aseptic loosening and 1 due to deep infection requiring explant of components. Conclusion: Patients < 50 years undergoing TAA for end stage ankle arthritis have improved patients reported outcomes greater than 5 years after surgery. Despite the increased demands of the younger population, survivorship of total ankle implants in our study was 85% at a mean of 8.8 years postoperative. We believe that TAA is a safe and reliable option for young patients with high patient satisfaction at mid term follow up.

Category: Ankle Arthritis Introduction/Purpose: The Vantage total ankle arthroplasty (TAA) features a design based on careful study of arthritic ankles and current ankle biomechanics, with theoretical advantages of a vertically-oriented tibial fixation and a fully congruent talar dome bone-implant interface. In this design-team, single-institution investigation, we report early-to-intermediate term clinical and radiographic outcomes, implant survivorship, and complications of the Vantage TAA. Methods: We retrospectively reviewed prospectively collected data for 278 consecutive patients undergoing Vantage fixed-bearing TAA. Ankles with coronal plane deformity > 25 degrees and suspected poor bone quality were prospectively excluded. Prospectively collected data includes: PROMIS, SF-36, SMFA, VAS and AOFAS hindfoot-ankle scores. Using previously published and commonly accepted evaluation methods, independent radiographic analysis, performed by a non-design surgeon investigator, included pre-operative, 1-year, and most recent follow-up assessments of 2-plane alignment, component position, and the bone- implant interface. A non-design surgeon investigator with dedicated training in statistics performed the statistical analysis using descriptive statistics to report PROM and radiographic measures and Kaplan-Meier survivorship analysis. Results: Mean patient age was 64.8yrs (range:33-86), 44.2% were female, and mean follow-up was 3.1yrs (2.0-5.5). Mean preoperative and postoperative PROMs were as following: PROMIS-Depression 50.3+/-4.2 and 45.6+/-9.8, PROMIS-Physical Function 39.0+/-3.4 and 45.0+/-7.8, SF-36 total score 55.8+/-15.3 and 73.2+/-20.0, SMFA-Function 29.0+/-13.5 and 15.9+/-5.4, VAS 15.8+/-24.8 and 3.1+/-10.1, and AOFAS hindfoot-ankle 46.3+/-16.5 and 81.1+/-16.3 (Table 1). Radiographic lucency at the bone- implant interface was noted in 33 (18.5%) TAAs at final follow-up; 20 (11.2%) were progressive. Lucency was almost exclusive to the tibial component. Implant survivorship was 99.6% [98.9-100.0] at 1-year and 93.3% [88.7-98.2] at the 5-year mark (Table 2, Figure 1). We identified suboptimal bone preparation, initial component alignment and/or component position in all 11 implant failures (Table 3). Conclusion: At early-to-intermediate followup, we observed favorable clinical outcomes, radiographic results and implant survivorship for the fixed-bearing Vantage TAA, especially with optimal bone preparation and component position. Tibial component lucency remains a concern and warrants further investigation. Suboptimal bone preparation, initial component alignment and/or component position was observed in all implant failures.

Category: Ankle Arthritis; Basic Sciences/Biologics Introduction/Purpose: From 2009-2019, there has been a 120% increase in the incidence of total ankle arthroplasty (TAA) in the United States. With the rise in primary TAA, future increases in revision TAA cases is anticipated. Aseptic loosening with periprosthetic osteolysis continues to account for a significant number of revisions. While several factors may contribute to the pathophysiology of osteolysis, an underlying inflammatory response surrounding TAA implants may play a primary role. It is well known that monosodium urate (gout) and calcium-pyrophosphate (pseudo-gout) crystals evoke a highly inflammatory response and may involve the foot and ankle joints. However, the effect of these conditions following TAA has not yet been reported. We present a small case series of patients with ballooning osteolysis following TAA with confirmed crystalline arthropathy. Methods: This is a retrospective study from a single academic institution looking at patients who underwent TAA revision surgery for periprosthetic osteolysis and concern for aseptic loosening. Revision surgeries were performed by three orthopedic foot and ankle fellowship trained surgeons. Case characteristics, including pre-operative imaging, clinical presentations, intra-operative findings and surgical treatments performed were analyzed and presented in this small case series. Results: We report 5 patients whom underwent revision surgery for ballooning periprosthetic osteolysis following TAA. Intra- operative pathology samples from periprosthetic cysts returned positive for monosodium urate (MSU) or calcium pyrophosphate (CPP) crystalline deposition (1 MSU and 4 CPP) in all 5 patients. Final intra-operative cultures were all negative for infection. Upon gross intra-operative inspection, all polyethylene liners were considered to be normal without abnormal wear characteristics. Periprosthetic cysts were isolated to the tibial component in 2 patients and involved both the tibial and talar components in 3 patients. Staged TAA revision was performed in 2 patients. Bone cyst curettage, bone grafting and polyethylene liner exchange was performed in 3 patients. Conclusion: Periprosthetic osteolysis is a known complication following TAA and often leads to implant loosening, functional disability and subsequent revision surgery. An objective strategy for management of this condition has not been agreed upon amongst orthopedic foot and ankle surgeons, as uncertainty remains surrounding the pathophysiology of osteolysis in TAA. To our knowledge, we are the first to describe a small case series of patients with crystalline arthropathy as a potential cause for periprosthetic osteolysis following TAA. Future prospective studies are warranted to better elucidate this potential cause of TAA failure.

Category: Ankle Arthritis; Ankle Introduction/Purpose: Younger age remains at the forefront of discussion when deciding between total ankle arthroplasty (TAA) and the ankle arthrodesis (AA) for treatment of end stage ankle arthritis. Unlike in the hip and knee, ankle arthritis is typically post-traumatic and presents at a much younger patient age. With the goal of preserving ankle motion, improving function and limiting adjacent joint degeneration, TAA has been shown to be safe and effective in patients < 55 years of age. However, it is not uncommon for debilitating ankle arthritis to occur in individuals within their fourth or even third decade of life resulting in significant patient comorbidity. The purpose of our study was to evaluate patient reported outcome measures and survivorship after primary TAA in patients < 35 years old. Methods: A retrospective chart review was conducted of patients < 35 years old who underwent primary TAA at a single institution from 2007-2020. Patient demographics, outcome measures, and complications were recorded. All patients had a minimum clinical follow up of 2 years. Patient reported outcome measures collected included VAS, SMFA dysfunction index, SF-36 and AOFAS hindfoot scores. Outcome measures were evaluated preoperative, 1 year postoperative, and at final follow up. Paired t-tests were performed to compare individual patients’ changes in PRO from preoperative to postoperative timepoints. Implant survivorship was evaluated as well as complications related to the index procedure. Implant survivorship based on need for complete revision of either the tibial or talar component Results: Twelve patients were included in the study. Average age at surgery was 28.5 years. Mean follow-up was 7.2 years. Mean VAS improved from 53.8 preoperatively to 14.7 (p= 0.152) at 1-year and 12.5 (p= 0.045) at final follow up, respectively. Mean SMFA improved from 40.0 preoperatively to 27.1 (p= 0.018) at 1-year and 24.0 (p= 0.006) at final follow up, respectively. SF-36 and AOFAS hindfoot scores also improved at 1 year and final follow-up compared to preoperative values [SF-36: 45.3 to 60.2 (p=0.06) and 67.0 (p=0.016); AOFAS: 40.6 to 70 (p= 0.08) and 68.9 (p=0.068)]. One patient required talar component revision due to aseptic loosening. One patient required subsequent removal of heterotopic bone due to impingement. No patients developed infection requiring surgical intervention. Conclusion: The onset of ankle arthritis typically occurs at a much younger age compared with that of the hip and knee and has a detrimental impact on patient quality of life. Despite a young age and increased activity demands, our results demonstrated that patients < 35 with end-stage ankle arthritis undergoing TAA demonstrated improved patient-reported outcomes greater than 2 years after surgery. Survivorship of TAA in our study was 91.7% at a mean follow-up of 7.2 years. We believe that TAA is a safe, effective and durable option for very young patients with high patient satisfaction at early to mid-term follow up.

Category: Ankle; Other Introduction/Purpose: The Invision talar component was launched in 2018 as a revision total ankle arthroplasty (TAA) specific option geared towards avoiding further subsidence when poor talar bone stock is present. Due to the recency of the market- availability of the Invision, studies evaluating the efficacy of the implant, even in the short-term, are lacking. Thus, the purpose of this study was to present the early-term outcomes of a series of patients undergoing revision TAA with the use of the Invision talar component. Methods: This was a single-center, retrospective review of 28 patients undergoing revision TAA with the Invision talar component and Inbone II tibial component (Wright Medical; Memphis, Tennessee) performed between 2007 and 2022. Mean follow-up was 1.3 ± 0.93 years. Data on patient preoperative characteristics, postoperative complications, and survivorship were collected. The primary outcome measures were time to major complication, reoperation, and infection. Results: The most common concurrent procedures performed with revision TAA with the Invision talar component were gastrocnemius recession (n=14, 50%), subtalar arthrodesis (n=3, 10.7%) and cotton osteotomy (n = 1, 3.6%). The mean preoperative coronal deformity off the tibia was 4.07 ± 3.06 degrees for varus and 3.67 ± 4.36 degrees for valgus deformities, respectively, and postoperatively, was 1.67 ± 2.16 degrees for varus and 2.00 ± 3.48 degrees for valgus. The mean preoperative coronal plane deformity off the talus was 4.83 ± 6.68 degrees for varus and 4.22 ± 4.21 degrees for valgus, respectively, and postoperatively, was 1.23 ± 2.45 degrees for varus and 2.32 ± 3.93 degrees for valgus. The survivorship from any complication, major complication, reoperation, and infection is shown in Table 2. Conclusion: In a series of 28 patients undergoing revision TAA with the Invision talar component and Inbone II tibial component, we demonstrate a survivorship of 92.7% at 1-year follow up. The Invision appears to have a reasonable safety profile in this non- designer series. The implant compares favorably with others utilized in the revision TAA setting at the early-term, but further studies evaluating mid-and long-term outcomes are required to fully assess the efficacy of the Invision.

Category: Ankle Arthritis Introduction/Purpose: As total ankle arthroplasty (TAA) rises in popularity nationwide, the incidence of major complications and need for revision TAA will continue to increase. A better understanding of the ability to durably correct deformity and improve patient reported outcomes (PROs) in the TAA revision setting is paramount for surgeons facing the impending wave of failed TAA. Thus, the purpose of this study was to present the largest single-center case series of revision TAA to date and to evaluate improvement in PROs and maintenance of correction of coronal plane deformity in patients undergoing this procedure. Methods: This was a single-center, retrospective review of 87 revision TAAs performed between 2007 and 2022. Reoperations for cyst formations only or without metallic component exchange were excluded. The two most common implants used for revision TAA were Inbone II (n=65) and Inbone I (n=14). Mean follow-up was 2.8 ± 2.9 years. Data on patient preoperative characteristics, concurrent procedures, and postoperative complications were collected. The primary outcome measures were time to major complication, reoperation, and infection. Secondary outcomes included PROs and correction of coronal plane deformity measured from both the tibial plafond and talar articulating surface from pre- to post-operatively. Cox regression analyses were performed to compute survivorship. Results: The most common concurrent procedures performed concomitantly with revision TAA were gastrocnemius recession (n=31, 35.6%), subtalar arthrodesis (n=18, 20.7%), and talonavicular arthrodesis (n=5, 5.7%). Mean preoperative coronal plane deformity measured off both the tibial plafond and talar articular surface improved after revision TAA. 1- and 5-year survivorship from major complication, reoperation, and infection is shown in Table 2. Fourteen patients underwent subsequent revision, including TAA (n= 6, 6.9%), arthrodesis (n= 4, 4.6%), below-the-knee amputation (n= 2, 2.3%), or implantation of an antibiotic spacer (n= 2, 2.3%). At one-year postoperatively, mean VAS pain score, SF36, and AOFAS Hindfoot score was 18.2 ± 16.0, 73.0 ± 13.3, and 68.8 ±:9.3, respectively, representing an improvement in PROs after revision TAA. Conclusion: In the largest single-center series of patients undergoing single or double component exchange revision TAA, we demonstrate durable improvements in coronal plane deformity measured off both the tibial plafond and talar articular surface. We also noted 63.0% survivorship with regards to reoperation and improvements in average PROs across the cohort. Overall, revision TAA is a successful procedure, but is associated with higher failure rates at 5 years than primary TAA.

Category: Ankle Arthritis Introduction/Purpose: There is limited data evaluating the effect of obesity on outcomes following total ankle arthroplasty (TAA), especially in adequate sample sizes to detect impacts on patient reported outcomes (PROs). The purpose of this study was to assess the effect of obesity on complication rates and PROs. Methods: This was a single-institution, retrospective study of 1,093 primary TAA performed between 2001 and 2020. Minimum follow-up was 2 years. Patients were stratified by body mass index (BMI) into Control (BMI=18.5-29.9; n=615), Obesity Class I (BMI=30.0-34.9; n=285), and Obesity Class II (BMI>35.0; n=193) groups. Patient information, intraoperative variables, postoperative complications, PRO measures were compared between groups using univariable statistics. Multivariable Cox regression was performed to assess risk for implant failure. Mean follow-up was 5.6 years (sd:3.1). Results: Compared to Control and Class I, Class II patients had the lowest mean age (p=0.001), highest mean ASA score (p < 0.001), and greatest proportion of female sex (p < 0.001) and Black/African American race (p=0.005). There were no statistically significant differences in postoperative complications (infection, implant failure, or impingement) across the BMI classes (p>0.05). Preoperatively, Class II had lower (worse) mean scores for FAOS Pain and ADL subscales than Controls (posthoc pairwise p< 0.001 for both). At final follow-up, both Class II and Class I had lower (worse) mean SMFA (posthoc pairwise p< 0.001 and p=0.030, respectively) and SF36 scores (posthoc pairwise p< 0.001 and p=0.005, respectively) than Controls. Conclusion: At midterm follow-up, obesity was not associated with increased rates of complications after TAA. Patients with obesity reported worse musculoskeletal function and overall quality of life after TAA but there was no differential improvement in PROs across BMI classes. To our knowledge, this is the largest single institution study to date examining the effect of obesity on outcomes after primary TAA.

This study sought to determine whether the deadlift exercise using the 5-by-5 scheme can be performed at a commonly prescribed moderate-to-high load with consistent mechanical output among sets with respect to concentric and eccentric rate of force development [RFD], rate of force attenuation [RFA; i.e., the rate at which the application of force is reduced], total lower limb joint angular work, and the contributions of the individual joints to total lower limb angular work. Twelve resistance-trained males [21 ± 1 y; 1.8 ± 0.56 m; 89.1 ± 15.48 kg] completed five sets of five repetitions of deadlift exercise with a load corresponding to 8 out of 10 on the modified Borg rated perceived exertion (RPE) scale. Body and barbell kinematics [e.g., velocity] and force production [e.g., rate of force development] variables of interest were calculated and averaged across repeated sets. Repeated-measures analyses of variance [α = 0.05] detected no significant differences [p > 0.05] for any variable. Results suggest deadlift exercise using the 5-by-5 scheme at an RPE of 8 can be performed without altered movement or force application across sets. Although these results are preliminary, it appears that deadlift exercise using the current loading scheme can be performed by resistance trained males without concern for movement or mechanical output changes across the five sets.

Summary: Advanced prostate cancers are treated with therapies targeting the androgen receptor (AR) signaling pathway. While many tumors initially respond to AR inhibition, nearly all develop resistance. It is critical to understand how prostate tumor cells respond to AR inhibition in order to exploit therapy-induced phenotypes prior to the outgrowth of treatment-resistant disease. Here, we comprehensively characterize the effects of AR blockade on prostate cancer metabolism using transcriptomics, metabolomics, and bioenergetics approaches. The metabolic response to AR inhibition is defined by reduced glycolysis, robust elongation of mitochondria, and increased reliance on mitochondrial oxidative metabolism. We establish DRP1 activity and MYC signaling as mediators of AR-blockade-induced metabolic phenotypes. Rescuing DRP1 phosphorylation after AR inhibition restores mitochondrial fission, while rescuing MYC restores glycolytic activity and prevents sensitivity to complex I inhibition. Our study provides insight into the regulation of treatment-induced metabolic phenotypes and vulnerabilities in prostate cancer.

Background: Acetabular retention in revision total hip arthroplasty (THA) may be advantageous, yet long-term survival data is limited. Thus, we investigated long-term survivorship of retained acetabular components in revision THA with analysis of rerevision rate, instability risk, and clinical outcomes. Methods: We reviewed 98 hips with polyethylene wear and/or osteolysis that were revised with retained acetabular components. Acetabular inclination and anteversion were measured from prerevision radiographs. A retrospective chart review was performed, collecting outcomes of interest including Harris hip score, instability events, and rerevision surgery. Kaplan-Meier analysis was used to calculate the risk of revision over time. Predictors of survival including acetabular component position were analyzed by multiple logistic regression. Results: Average follow-up was 13 years (range, 5-24). Survivorship rates at 5, 10, 15, and 20 years were 89.7%, 81.6%, 70.8%, and 63.8%, respectively. There was improvement in average Harris hip score (61 to 76, P < .0001). There was a 9% rate of dislocation, and 6 hips (6%) were rerevised for recurrent instability. Overall, there were 23 (23%) rerevisions at an average of 6.1 years with the most common reasons being instability (6%) and aseptic loosening (6%). Use of conventional polyethylene was the only identified independent predictor of rerevision (P = .025). Conclusions: Retention of a well-fixed acetabular component in revision THA provides acceptable long-term outcomes with a 15-year survivorship of 71%. Instability and aseptic loosening were the most common reasons for rerevision. Surgeons may consider retaining the acetabular component at revision surgery if the implant is well-fixed and well-positioned.

Background: Total ankle arthroplasty (TAA) provides a surgical alternative to tibiotalar arthrodesis when treating end-stage ankle arthritis. TAA preserves range of motion at the tibiotalar joint leading to improved postoperative function. Many patients who undergo TAA wish to maintain a high level of activity, including participation in low-impact sports such as golf. There are several studies in the total hip and total knee arthroplasty literature that have looked at the effect of total joint arthroplasty on golf handicap. We hypothesized that similar to hip and knee arthroplasty research, TAA is likely to result in a postoperative increase in golf handicap. Methods: After obtaining institutional review board approval, we retrospectively identified 60 patients (from 140 consecutive TAAs performed between August 2016 and February 2017) who had undergone TAA, played golf pre- and postoperatively, and had at least 1 year of postoperative follow-up. The average postoperative follow-up for the cohort was 28.1 months. Variables including preoperative and postoperative golf handicaps, swing laterality, age, gender, surgical laterality, implant used, and operating surgeon were recorded. Results: The average preoperative and postoperative handicaps were 19.7 and 17.9, respectively, which did not represent a statistically significant difference ( P = .07). Patients who played 3 or more rounds per week had better preoperative and postoperative handicaps compared to patients who played 2 rounds or less; however, the change in their handicap following TAA and the number of rounds played per week was not affected. There was no association between the change in handicap and the follow-up period, handedness of golf shot, surgical laterality, implant used, or the operating surgeon. Conclusion: Our findings showed that golf handicap was not negatively affected following TAA in this series. Level of Evidence: Level IV, case series.

Background: While autologous bone grafts remain the gold standard for spinal fusion procedures, harvesting autologous bone is associated with significant complications, including donor site infection, hematomas, increased operative time, and prolonged pain. Cellular bone allograft (CBA) presents an alternative to autologous bone harvesting, with a favorable efficacy and safety profile. The current study further investigates CBA as an adjunct to lumbar spinal fusion procedures. Methods: A prospective, multicenter, open-label clinical study was conducted in subjects undergoing lumbar spinal fusion with CBA (NCT 02969616). Radiographic fusion status was assessed by an independent review of dynamic radiographs and CT scans. Clinical outcome measures included the Oswestry Disability Index (ODI) and visual analogue scale (VAS) for back and leg pain. Adverse-event reporting was conducted throughout 12 months of follow-up. Available subject data at 12 months were analyzed. Results: A total of 274 subjects were enrolled into the study, with available data from 201 subjects (73.3%) who completed 12 months of postoperative radiographic and clinical evaluation at the time of analysis. Subjects had a mean age of 60.2 ± 11.5 years. A higher number of women (n = 124, 61.7%) than men (n = 77, 38.3%) were enrolled, with a collective mean BMI of 30.6 + 6.5 kg/m2 (range 18.0–51.4). At month 12, successful fusion was achieved in 90.5% of subjects. A significant (p < 0.001) improvement in ODI, VAS-back, and VAS-leg clinical outcomes was also observed compared to baseline scores. One adverse event related to CBA (postoperative radiculopathy) was reported, with surgical exploration demonstrating interbody extrusion of graft material. This subject reported successful fusion at month 12. Conclusions: CBA represents a viable substitute for harvesting of autograft alone with a high rate of successful fusion and significant improvements in subject-reported outcomes, such as pain and disability. Positive benefit was observed in subjects reporting single and multiple risk factors for pseudoarthrosis.

We conducted a genomic analysis of monkeypox virus sequences collected early in the 2022 outbreak, during July–August , in Washington, USA. Using 109 viral genomes, we found low overall genetic diversity, multiple introductions into the state, ongoing community transmission, and potential for co-infections by multiple strains.

Pseudomonas aeruginosa is a common cause of hospital-acquired infections, including central line-associated bloodstream infections and ventilator-associated pneumonia. Unfortunately, effective control of these infections can be difficult, in part due to the prevalence of multi-drug resistant strains of P. aeruginosa. There remains a need for novel therapeutic interventions against P. aeruginosa, and the use of monoclonal antibodies (mAb) is a promising alternative strategy to current standard of care treatments such as antibiotics. To develop mAbs against P. aeruginosa, we utilized ammonium metavanadate, which induces cell envelope stress responses and upregulates polysaccharide expression. Mice were immunized with P. aeruginosa grown with ammonium metavanadate and we developed two IgG2b mAbs, WVDC-0357 and WVDC-0496, directed against the O-antigen lipopolysaccharide of P. aeruginosa. Functional assays revealed that WVDC-0357 and WVDC-0496 directly reduced the viability of P. aeruginosa and mediated bacterial agglutination. In a lethal sepsis model of infection, prophylactic treatment of mice with WVDC-0357 and WVDC-0496 at doses as low as 15 mg/kg conferred 100% survival against challenge. In both sepsis and acute pneumonia models of infection, treatment with WVDC-0357 and WVDC-0496 significantly reduced bacterial burden and inflammatory cytokine production post-challenge. Furthermore, histopathological examination of the lungs revealed that WVDC-0357 and WVDC-0496 reduced inflammatory cell infiltration. Overall, our results indicate that mAbs directed against lipopolysaccharide are a promising therapy for the treatment and prevention of P. aeruginosa infections.

The rise of antimicrobial-resistant bacterial infections is a crucial health concern in the 21st century. In particular, antibiotic-resistant Pseudomonas aeruginosa causes difficult-to-treat infections associated with high morbidity and mortality. Unfortunately, the number of effective therapeutic interventions against antimicrobial-resistant P. aeruginosa infections continues to decline. Therefore, discovery and development of alternative treatments are necessary. Here, we present pre-clinical efficacy studies on an anti-P. aeruginosa therapeutic monoclonal antibody. Using hybridoma technology, we generated a monoclonal antibody and characterized its binding to P. aeruginosa in vitro using ELISA and fluorescence correlation spectroscopy. We also characterized its function in vitro and in vivo against P. aeruginosa. The anti-P. aeruginosa antibody (WVDC-5244) bound P. aeruginosa clinical strains of various serotypes in vitro, even in the presence of alginate exopolysaccharide. In addition, WVDC-5244 induced opsonophagocytic killing of P. aeruginosa in vitro in J774.1 murine macrophage, and complement-mediated killing. In a mouse model of acute pneumonia, prophylactic administration of WVDC-5244 resulted in an improvement of clinical disease manifestations and reduction of P. aeruginosa burden in the respiratory tract compared to the control groups. This study provides promising pre-clinical efficacy data on a new monoclonal antibody with therapeutic potential for P. aeruginosa infections.

Study designA multicenter retrospective review of an adult spinal deformity database.ObjectiveWe aimed to characterize reoperation rates and etiologies of adult spinal deformity surgery with circumferential minimally invasive surgery (cMIS) and hybrid (HYB) techniques.MethodsInclusion criteria were age ≥18 years, and one of the following: coronal Cobb >20°, sagittal vertical axis >5 cm, pelvic tilt >20°, and pelvic incidence-lumbar lordosis >10°. Patients with either cMIS or HYB surgery, ≥3 spinal levels treated with 2-year minimum follow-up were included.ResultsA total of 133 patients met inclusion for this study (65 HYB and 68 cMIS). Junctional failure (13.8%) was the most common reason for reoperation in the HYB group, while fixation failure was the most common reason in the cMIS group (14.7%). There was a higher incidence of proximal junctional failure (PJF) than distal junctional failure (DJF) within HYB (12.3% vs 3.1%), but no significant differences in PJF or DJF rates when compared to cMIS. Early (30 days) reoperations (cMIS = 26.5%; HYB = 27.7%), but early reoperations were more common in the HYB group after propensity matching, largely due to infection rates (10.8% vs 0%, P = .04).ConclusionsAdult spinal deformity correction with cMIS and HYB techniques result in overall reoperation rates of 27.9% and 33.8%, respectively, at minimum 2-year follow-up. Junctional failures are more common after HYB approaches, while pseudarthrosis/fixation failures happen more often with cMIS techniques. Early reoperations were less common than later returns to the operating room in both groups, but cMIS demonstrated less risk of infection and early reoperation when compared with the HYB group.

Study Design:Retrospective, multicenter review of adult scoliosis patients with minimum 2-year follow-up. Objective:Because the fractional curve (FC) of adult scoliosis can cause radiculopathy, we evaluated patients treated with either circumferential minimally invasive surgery (cMIS) or open surgery. Methods:A multicenter retrospective adult deformity review was performed. Patients included: age >18 years with FC >10°, ≥3 levels of instrumentation, 2-year follow-up, and one of the following: coronal Cobb angle (CCA) > 20°, pelvic incidence and lumbar lordosis (PI-LL) > 10°, pelvic tilt (PT) > 20°, and sagittal vertical axis (SVA) > 5 cm. Results:The FC was treated in 118 patients, 79 open and 39 cMIS. The FCs had similar coronal Cobb angles preoperative (17° cMIS, 19.6° open) and postoperative (7° cMIS, 8.1° open), but open had more levels treated (12.1 vs 5.7). cMIS patients had greater reduction in VAS leg (6.4 to 1.8) than open (4.3 to 2.5). With propensity matching 40 patients for levels treated (cMIS: 6.6 levels, N = 20; open: 7.3 levels, N = 20), both groups had similar FC correction (18° in both preoperative, 6.9° in cMIS and 8.5° postoperative). Open had more posterior decompressions (80% vs 22.2%, P < .001). Both groups had similar preoperative (Visual Analogue Scale [VAS] leg 6.1 cMIS and 5.4 open) and postoperative (VAS leg 1.6 cMIS and 3.1 open) leg pain. All cMIS patients had interbody grafts; 35% of open did. There was no difference in change of primary CCA, PI-LL, LL, Oswestry Disability Index, or VAS Back. Conclusion:Patients' FCs treated with cMIS had comparable reduction of leg pain compared with those treated with open surgery, despite significantly fewer cMIS patients undergoing direct decompression.