In situ analysis of neuronal injury and neuroinflammation during HIV-1 infection.

BACKGROUND: Since the introduction of combination antiretroviral therapy (cART) the brain has become an important human immunodeficiency virus (HIV) reservoir due to the relatively low penetration of many drugs utilized in cART into the central nervous system (CNS). Given the inherent limitations of directly assessing acute HIV infection in the brains of people living with HIV (PLWH), animal models, such as humanized mouse models, offer the most effective means of studying the effects of different viral strains and their impact on HIV infection in the CNS. To evaluate CNS pathology during HIV-1 infection in the humanized bone marrow/liver/thymus (BLT) mouse model, a histological analysis was conducted on five CNS regions, including the frontal cortex, hippocampus, striatum, cerebellum, and spinal cord, to delineate the neuronal (MAP2ab, NeuN) and neuroinflammatory (GFAP, Iba-1) changes induced by two viral strains after 2 weeks and 8 weeks post-infection. RESULTS: Findings reveal HIV-infected human cells in the brain of HIV-infected BLT mice, demonstrating HIV neuroinvasion. Further, both viral strains, HIV-1JR-CSF and HIV-1CH040, induced neuronal injury and astrogliosis across all CNS regions following HIV infection at both time points, as demonstrated by decreases in MAP2ab and increases in GFAP fluorescence signal, respectively. Importantly, infection with HIV-1JR-CSF had more prominent effects on neuronal health in specific CNS regions compared to HIV-1CH040 infection, with decreasing number of NeuN+ neurons, specifically in the frontal cortex. On the other hand, infection with HIV-1CH040 demonstrated more prominent effects on neuroinflammation, assessed by an increase in GFAP signal and/or an increase in number of Iba-1+ microglia, across CNS regions. CONCLUSION: These findings demonstrate that CNS pathology is widespread during acute HIV infection. However, neuronal loss and the magnitude of neuroinflammation in the CNS is strain dependent indicating that strains of HIV cause differential CNS pathologies.

Patient Demographic Factors Affect Response Rates to Patient-Reported Outcome Measures for Total Hip Arthroplasty Patients.

BACKGROUND: The Hip Disability and Osteoarthritis Outcome Score (HOOS JR) is a widely used patient-reported outcome measures questionnaire for total hip arthroplasty (THA). However, not all patients choose to complete HOOS JR, and thus, a subset of the THA population may be underrepresented. This study aims to investigate the association between patient demographic factors and HOOS JR response rates. METHODS: This was a retrospective cohort study of adult, English-speaking patients who underwent primary THA by a fellowship-trained arthroplasty surgeon between 2017 and 2023 at a single, high-volume academic institution. The HOOS JR completion status-complete or incomplete-was recorded for each patient within 90 days of surgery. Standard statistical analyses were performed to assess completion against multiple patient demographic factors. RESULTS: Of the 2,908 total patients, 2,112 (72.6%) had complete and 796 (27.4%) had incomplete HOOS JR questionnaires. Multivariate analysis yielded statistical significance (P < .05) for the distribution of patient age, race, insurance, marital status, and income quartile with respect to questionnaire completion. Patient sex or religion did not affect response rates. Failure to complete HOOS JR (all P < .001) was associated with patients aged 18 to 39 (59.8%), who identified as Black (36.4%) or "other" race (39.6%), were never married (38%), and were in the lower half income quartiles (43.9%, 35.9%) when compared to the overall incomplete rate. CONCLUSIONS: Multiple patient demographic factors may affect the HOOS JR response rate. Overall, our analyses suggest that older patients who identify as White and are of higher socioeconomic status are more likely to participate in the questionnaire. Efforts should focus on capturing patient groups less likely to participate to elucidate more generalizable trends in arthroplasty outcomes.

Patients Requiring Both Total Hip Arthroplasty and Lumbar Spinal Fusion Have Lower Hip Functional Outcome Scores: A Matched Case-Control Study.

BACKGROUND: While patients who undergo both lumbar spinal fusion (LSF) and total hip arthroplasty (THA) have increased complication rates compared to patients who have not undergone LSF, there is a paucity of literature evaluating THA functional outcomes in patients with a history of LSF. This study was conducted to determine whether patients undergoing THA with a history of LSF have inferior functional outcomes compared to patients having no history of LSF. METHODS: A retrospective matched case-control study was conducted at an academic center. Patients who underwent both THA and LSF (cases) were matched with controls who underwent THA without LSF. Inclusion criteria required a minimum of 1-year follow-up for the Hip Disability and Osteoarthritis Outcome Score Joint Replacement [HOOS-JR]. Following propensity matching for age, sex, race, body mass index, and comorbidities, 291 cases and 1,164 controls were included, with no demographic differences. RESULTS: Patients who underwent both THA and LSF had a significantly lower preoperative HOOS-JR (47 versus 50; P < .001), postoperative HOOS-JR (77 versus 85; P < .001), a significant lower rate of achieving the patient acceptable symptom state (55 versus 67%; P < .001), with no significant difference in delta HOOS-JR (34 versus 34; P = .834). When comparing patients undergoing THA before LSF or LSF before THA, no differences existed for preoperative HOOS-JR (50 versus 47; P = .304), but patients undergoing THA before LSF had lower postoperative HOOS-JR scores (74 versus 81; P = .034), a lower-delta HOOS-JR (27 versus 35; P = .022), and a lower rate of reaching the HOOS-JR minimal clinically important difference (62 versus 76%; P = .031). CONCLUSIONS: Patients who have a history of LSF experience a similar improvement in hip function when undergoing THA compared to patients who do not have a history of LSF. However, due to lower preoperative function, they may have a lower postoperative functional outcome ceiling. Additionally, patients undergoing THA before LSF have worse hip functional outcomes than patients undergoing LSF before THA.

Rotating Hinge Revision Total Knee Arthroplasty Provides Greater Arc of Motion Gains for Patients Who Have Severe Arthrofibrosis.

BACKGROUND: Arthrofibrosis is a common postoperative total knee arthroplasty (TKA) complication that results in limited range of motion (ROM). There is limited literature on outcomes after revision TKA (rTKA) for arthrofibrosis based on preoperative ROM restriction. The aims of this study were to: (1) examine ROM trajectory after rTKA for arthrofibrosis patients who have severe versus nonsevere limitations; (2) compare ROM gains and final arc of motion (AOM) between severe and nonsevere cohorts; (2a) compare ROM gain in a severe cohort treated with a rotating hinge (RH) versus a non-RH (NRH) construct; and (3) assess the impact of arthrofibrosis severity on patient-reported outcome measures. METHODS: Patients were divided into 2 groups: group A had preoperative ROM < 70° (severe), and group B had preoperative ROM > 70° (non-severe). Patients were assessed clinically using AOM gain, absolute ROM, Knee injury and Osteoarthritis Outcomes Score for Joint Replacement, lower extremity activity scale, and pain scores. Postoperative gains in AOM were compared between both groups. RESULTS: A total of 56 rTKAs (group A (severe): n = 36, group B (non-severe): n = 20) were performed for patients who have postoperative fibrosis. Group B had better ROM at the 1-year time point (group B: 95.9 ± 22.5 degrees versus group A: 83.2 ± 25.7 degrees). Group A had significantly better improvement in absolute AOM than group B (31.1 ± 20.9 versus 11.4 ± 25.0 degrees, P < 0.01). The RH group demonstrated significantly better absolute AOM gain than the NRH group (41.3 ± 19.4 versus 18.3 ± 15.2 degrees, P < 0.001). However, there were no significant differences in patient-reported outcome measures between groups A and B or between RH and NRH groups at the final follow-up. CONCLUSIONS: Final ROM achieved between severe and nonsevere arthrofibrosis groups was similar, and patients who have severe arthrofibrosis can expect greater absolute ROM gains and similar functional outcomes than nonsevere arthrofibrosis patients. The RH rTKAs provided greater AOM gains for patients who have severe arthrofibrosis, with equivalent functional outcomes to non-RH implants. For severe arthrofibrosis patients, RH designs provided twice the overall ROM gain; however, longer follow-up is necessary to determine whether RH designs have inferior overall implant survivorship.

Occupational stressors experienced by healthcare professionals in the course of the COVID-19 crisis.

The novel coronavirus has significantly impacted healthcare systems worldwide, exposing healthcare professionals (HCPs) to work-related stressors to prevent the spread of SARS-CoV-2. This study aimed to assess the occupational stress of HCPs in Lagos State, Nigeria, using a qualitative approach. The study involved nine HCPs from various departments, including doctors, nurses, and medical laboratory technicians. The main causes of stress were workload, policy changes, and extended use of personal protective gear. The study found high levels of occupational stress among HCPs, with workload being the main cause. The impact of the disease outbreak crisis on HCPs' lives and work demands was observed, with occupational demands categorized into safety risk at work and public perceptions. Employers and unions must respond to HCPs' needs for workplace protection and appropriate help to address stressors.

Le nouveau coronavirus a eu un impact significatif sur les systèmes de soins de santé dans le monde entier, exposant les professionnels de la santé (HCP) à des facteurs de stress liés au travail pour empêcher la propagation du SARS-CoV-2. Cette étude visait à évaluer le stress professionnel des HCP dans l'État de Lagos, au Nigeria, en utilisant une approche qualitative. L'étude a impliqué neuf HCP de divers départements, y compris des médecins, des infirmières et des techniciens de laboratoire médical. Les principales causes du stress étaient la charge de travail, les changements de politique et l'utilisation prolongée d'équipements de protection personnelle. L'étude a révélé des niveaux élevés de stress professionnel parmi les HCP, avec la charge de travail étant la principale cause. L'impact de la crise de l'épidémie sur la vie et les exigences professionnelles des HCP a été observé, les demandes de travail étant classées en catégories de risques pour la sécurité au travail et de perceptions du public. Les employeurs et les syndicats doivent répondre aux besoins des HCP en matière de protection des lieux de travail et d'aide appropriée pour faire face aux facteurs de stress.

The usefulness of [68 Ga]Ga-DOTA-JR11 PET/CT in patients with meningioma: comparison with MRI.

PURPOSE: Clinical studies of PET imaging using SSTR2 agonists have demonstrated high accuracy and correlation with SSTR2 expression in meningiomas. However, the usefulness of the SSTR2 antagonist with [68 Ga]Ga-DOTA-JR11 is uncertain. To evaluate the diagnostic performance of [68 Ga]Ga-DOTA-JR11 PET/CT and to clarify tumor characteristics in patients with suspected meningiomas. MATERIALS AND METHODS: Patients with suspected de novo or recurrent meningioma in complex locations or atypical images were enrolled from August 2021 to October 2022 in prospective study. All patients underwent contrast-enhanced MRI (CE-MRI), [68 Ga]Ga-DOTA-JR11 PET/CT, and histopathological evaluation. Tumor uptake of [68 Ga]Ga-DOTA-JR11 was measured by SUVmax and tumor-endocranium ratio (TBR). Diagnostic performance was compared between PET and MRI. RESULTS: Of 36 (50.0 ± 13.0 years of age, 20 women) patients, 32 were histopathologically confirmed meningiomas and four with other tumors. [68 Ga]Ga-DOTA-JR11 uptake was significantly higher in meningioma patients than in those with other tumors (SUVmax: 13.6 ± 7.7 vs. 5.2 ± 3.0, P < 0.001; TBR: 64.2 ± 27.7 vs. 25.0 ± 18.9, P = 0.001). [68 Ga]Ga-DOTA-JR11 PET/CT detected 31 meningiomas, while CE-MRI detected 17 meningiomas of 25 initial diagnosis and 11 recurrent tumors; [68 Ga]Ga-DOTA-JR11 PET had an incremental diagnostic value of 24% (6/25) over MRI in the group of initial diagnosis. There was no statistically significant difference in diagnostic efficacy between PET and MRI (P = 0.45) for all 36 patients. In skull base meningiomas, PET provided a more definitive diagnosis of pituitary involvement (in 12, not in12), compared to MRI (in eight, possible in six, possible not in six, not in four). PET revealed bone involvement in all 14 patients proven by pathology, while MRI identified only 11. CONCLUSIONS: [68 Ga]Ga-DOTA-JR11 PET/CT provided high image quality and presented an ideal diagnostic performance in detecting meningioma and evaluating the involvement of the pituitary and bone. The study provides valuable evidence for the use of [68 Ga]Ga-DOTA-JR11 PET/CT as a complementary imaging modality to CE-MRI in the evaluation of meningiomas.

Penfield and the Founding of the National Institute of Neurological Diseases and Blindness.

As conceived by Wilder Penfield the Montreal Neurological Institute (MNI) integrated neurology, neurosurgery, and allied disciplines within a single institution, where research and teaching complemented patient care. The MNI's success influenced the creation of the National Institute of Neurological Diseases and Blindness (NINDB), as Pearce Bailey, its first Director, sought to replicate the MNI's clinical and research model. He turned to MNI trainees Maitland Baldwin and Milton Shy to head the NINDB's Surgical and Medical Neurology Branches, respectively. They in turn recruited other MNI trainees who continued their work at the NINDB bringing clinical neuroscience to the USA.

The life of the prince of anatomists Jean Riolan, Jr. (the Younger) (1577-1657).

For the first time in the history of anatomy, the important French anatomist Jean Riolan, Jr., clarifies several conditions that anatomy adepts should accomplish during their preparation in his work Anthropographia. Anatomists should be physically, mentally, culturally, and ethically ready for their work. The anatomy teacher should consider three rules: have experience in anatomical dissection, have the essential knowledge and approach to dissection, and use a suitable teaching method.

FRED Jr stent for acute flow diversion in ruptured cerebral aneurysms arising from small-caliber vessels: a clinical case series.

OBJECTIVE: Treatment of ruptured aneurysms arising from small-caliber (< 2.5 mm) or distal vessels beyond the circle of Willis is considered challenging with all treatment modalities. Recently, the Flow Re-Direction Endoluminal Device Junior (FRED Jr) stent, designed for flow diversion in small arteries, was approved in the United States for the treatment of nonruptured aneurysms. Here, the authors report their experience using this device in the setting of subarachnoid hemorrhage (SAH). METHODS: Clinical and radiological records of patients sustaining SAH treated with a FRED Jr stent between June 2020 and October 2022 were reviewed. Treatment course, including antiplatelet therapy, external ventricular drain (EVD) management, and vasospasm, and clinical outcomes were analyzed. Angiographic results were assessed according to the O'Kelly-Marotta (OKM) grading scale. RESULTS: Nine patients at a median age of 62 (range 27-75) years were included. The median Hunt and Hess grade was II (IQR I) and the median modified Fisher grade was 4 (IQR 1). Aneurysm morphology types included saccular (6 patients), blister (1 patient), and dissecting (2 patients), and the aneurysms were located at the anterior communicating artery complex (n = 3) at the A2/A3 (n = 3), M2/M3 (n = 1), V4 (n = 1), and P2 (n = 1) arterial segments. All stents were deployed successfully with no intraprocedural complications. Postoperatively, no rebleeding events were encountered. Vasospasm therapy was initiated in 6 patients, and no symptomatic EVD-related hematomas were observed. Postoperative ischemic events were encountered in 2 patients. The median 3-month modified Rankin Scale score was 2 (IQR 1) for the 7 surviving patients, and 3-month radiographic follow-up revealed OKM grade D in 4 of 7 patients. CONCLUSIONS: Flow diversion using the FRED Jr stent is feasible as a potential treatment strategy for acutely ruptured aneurysms arising from small-caliber vessels. The complication profile reported in this series is comparable to those of historical microsurgical cohorts, and effective protection was conferred by this treatment modality. Therefore, our small cohort provides a glimpse into a new tool for successfully achieving acute flow diversion for this subset of difficult-to-treat aneurysms.

Cross-cultural adaptation and validation of the KOOS, JR questionnaire for assessing knee osteoarthritis in Spanish-speaking patients.

PURPOSE: The present study aims to translate, adapt and validate a Spanish version of the Knee Injury and Osteoarthritis Outcome Score, Joint Replacement (KOOS, JR), including a reliability and validity analysis in patients with knee osteoarthritis (OA). METHODS: This study conducted a prospective validation study following the six stages of the "Guidelines for the Process of Cross-Cultural Adaptation of Self-Report Measures". Psychometric testing was conducted in patients with knee osteoarthritis. Subjects answered the Spanish KOOS, JR (S-KOOS, JR) and a validated Spanish Oxford Knee Score (S-OKS). Retest was conducted at 10 days. Acceptability, floor and ceiling effect, internal consistency (Cronbach's α), reproducibility (mixed-effect model coefficient [MEMC]) and construct validity (Spearman's correlation; p = 0.05) were assessed. RESULTS: Forty-one patients (mean age: 65.6 ± 5.39; 48.8% female) participated in the study. All patients (100%) answered both scores during the first assessment and 38 (92.7%) during the second assessment. All patient-reported outcomes measures were answered completely (100%). The S-KOOS, JR resulted in 100% acceptability when answered. There were no ceiling or floor effects detected. The Cronbach's α for the S-KOOS, JR was 0.927 and its MEMC was 0.852 (CI 95% 0.636-1.078). The Spearman's correlation between the S-KOOS, JR and the S-OKS was 0.711 (CI 0.345-0.608; p < 0.001) and 0.870 (CI 0.444-0.651; p < 0.001) for the first and second assessments, respectively. CONCLUSION: The S-KOOS, JR has very high internal consistency and reproducibility, with a high correlation with the S-OKS; it is a reliable and valid instrument for characterising Spanish-speaking patients suffering from knee OA. LEVEL OF EVIDENCE: IV.

Does design change in total knee arthroplasty implants affect patient-reported outcomes?

PURPOSE: The purpose of this study is to compare the early results of patient-reported outcomes between two generations of a total knee system. METHODS: Between June 2018 and April 2020, 121 first-generation, cemented TKAs (89 patients) and 123 s-generation, cemented TKAs (98 patients) were performed by a single surgeon. Demographic and surgical data were collected from all patients. Starting at the 6-month follow-up, patient-reported outcome measures Knee Injury and Osteoarthritis Outcome Score, Joint Reconstruction (KOOS-JR) and Knee Society (KS) clinical and radiographic scores were prospectively recorded. This study represents a retrospective review of these prospectively collected data. RESULTS: There were no statistically significant differences between the two groups in terms of demographic variables such as age, body mass index, gender and race. KOOS-JR and Knee Society (KS) scores improved significantly (p < 0.001) from their preoperative values in both device generations. There were no differences, pre-operatively, between the two groups in terms of KOOS-JR, KS functional, KS objective, patient satisfaction, and expectation scores; however, there were statistically significant (p < 0.001) lower values of KOOS-JR and KS functional scores for first versus second generation at 6 months (81 vs. 89 and 69 vs. 74, respectively). CONCLUSION: While significant improvement in KS objective, subjective, and patient satisfaction scores were noted with both knee systems, KOOS-JR and KS function scores were significantly higher at the early (6-month) follow-up in the second-generation group. Patients responded acutely to the design change as evidenced by significantly improved patient-reported outcome scores for the second generation.

The Appropriateness of Preoperative Patient Reported Outcome Measures as an Indication for Total Hip Arthroplasty.

BACKGROUND: While Medicare requires patient-reported outcome measures (PROMs) for many quality programs, some commercial insurers have begun requiring preoperative PROMs when determining patient eligibility for total hip arthroplasty (THA). Concerns exist these data may be used to deny THA to patients above a specific PROM score, but the optimal threshold is unknown. We aimed to evaluate outcomes following THA based on theoretical PROM thresholds. METHODS: We retrospectively analyzed 18,006 consecutive primary THA patients from 2016-2019. Hypothesized preoperative Hip Disability and Osteoarthritis Outcome Score, Joint Replacement (HOOS-JR) cutoffs of 40, 50, 60, and 70 points were used. Preoperative scores below each threshold were considered "approved" surgery. Preoperative scores above each threshold were considered "denied" surgery. In-hospital complications, 90-day readmissions, and discharge disposition were evaluated. HOOS-JR scores were collected preoperatively and 1-year postoperatively. Minimum clinically important difference (MCID) achievement was calculated using previously validated anchor-based methods. RESULTS: Using preoperative HOOS-JR thresholds of 40, 50, 60, and 70 points, the percentage of patients who would have been denied surgery was 70.4%, 43.2%, 20.3%, and 8.3%, respectively. For these denied patients, 1-year MCID achievement was 75.9%, 69.0%, 59.1%, and 42.1%, respectively. In-hospital complication rates for approved patients were 3.3%, 3.0%, 2.8%, and 2.7%, while 90-day readmission rates were 5.1%, 4.4%, 4.2%, and 4.1%, respectively. Approved patients had higher MCID achievement (P < .001) but higher nonhome discharge (P = .01) and 90-day readmissions rates (P = .036) than denied patients. CONCLUSION: Most patients achieved MCID at all theoretical PROM thresholds with low complication and readmission rates. Setting preoperative PROM thresholds for THA eligibility did not guarantee clinically successful outcomes.

Preoperative Patient-Reported Outcome Measure Thresholds Should Not be Used for Indicating Total Knee Arthroplasty.

BACKGROUND: While Medicare requires patient-reported outcome measures (PROMs) for many quality programs, some commercial insurers are requiring preoperative PROMs when determining eligibility for total knee arthroplasty (TKA). Concerns exist that these data may be used to deny TKA to patients above a specific PROM score, but the optimal threshold is unknown. We aimed to evaluate TKA outcomes based on theoretical PROM thresholds. METHODS: We retrospectively analyzed 25,246 consecutive primary TKA patients from 2016 to 2019. Hypothesized preoperative knee injury and osteoarthritis outcome score for joint replacement cutoffs of 40, 50, 60, and 70 points were used. Preoperative scores below each threshold were considered "approved" surgery. Preoperative scores above each threshold were considered "denied" surgery. In-hospital complications, 90-day readmissions, and discharge disposition were evaluated. One-year minimum clinically important difference (MCID) achievement was calculated using previously validated anchor-based methods. RESULTS: For "denied" patients below thresholds 40, 50, 60, and 70 points, 1-year MCID achievement was 88.3%, 85.9%, 79.6%, and 77%, respectively. In-hospital complication rates for approved patients were 2.2%, 2.3%, 2.1%, and 2.1%, while 90-day readmission rates were 4.6%, 4.5%, 4.3%, and 4.3%, respectively. Approved patients had higher MCID achievement rates (P < .001) for all thresholds but higher nonhome discharge rates than denied patients for thresholds 40 (P < .001), 50 (P = .002), and 60 (P = .024). Approved and denied patients had similar in-hospital complication and 90-day readmission rates. CONCLUSION: Most patients achieved MCID at all theoretical PROMs thresholds with low complication and readmission rates. Setting preoperative PROM thresholds for TKA eligibility can help optimize patient improvement, but such a policy can create access to care barriers for some patients who would otherwise benefit from a TKA.

Patients Who Have Had Three or More Levels Fused During Lumbar Spinal Fusion Have Worse Functional Outcomes After Total Hip Arthroplasty.

BACKGROUND: Lumbar spinal fusion (LSF) and total hip arthroplasty (THA) are commonly performed in patients who have concomitant spine and hip pathology. While patients who have three or more levels fused during LSF have increased postoperative opioid consumption after undergoing THA, it is unknown whether the number of levels fused during LSF affects THA functional outcomes. METHODS: A retrospective study was conducted at a tertiary academic center for patients who underwent LSF first and then had a primary THA performed with a minimum of one-year follow-up for the Hip Disability and Osteoarthritis Outcome Score Joint Replacement (HOOS-JR). Operative notes were reviewed to determine the number of levels fused during LSF. There were 105 patients who underwent one-level LSF, 55 patients underwent two-level LSF, and 48 patients underwent three-or-more-level LSF. No significant differences existed in age, race, body mass index, and comorbidities between the cohorts. RESULTS: While preoperative HOOS-JR was similar among the three cohorts, patients who had three-or-more-level LSF had significantly lower HOOS-JR scores than patients who had two-level or one-level LSF (71.4 versus 82.4 versus 78.2; P = .010) and a lower delta HOOS-JR (27.2 versus 39.4 versus 35.9; P = .014). Patients who had three-or-more-level LSF had a significantly lower rate of achieving minimal clinically important difference (61.7% versus 87.2% versus 78.7%; P = .011) and the patient acceptable symptom state (37.5% versus 69.1% versus 59.0%; P = .004) for the HOOS-JR, compared to patients who had two-level or one-level LSF, respectively. CONCLUSIONS: Surgeons should counsel patients who have had three-or-more-level LSF that they may have a lower rate of hip function improvement and symptom acceptability after THA, compared to patients who have had a less number of levels fused during LSF.

Hospital Teaching Status and Patient-Reported Outcomes Following Primary Total Hip Arthroplasty: An American Joint Replacement Registry Study.

INTRODUCTION: Previous studies have shown lower morbidity and mortality rates after total hip arthroplasty (THA) at academic teaching hospitals. This study sought to determine the relationship between hospital teaching status and patient-reported outcome measures following primary THA. METHODS: Using American Joint Replacement Registry data from 2012 to 2020, 4,447 primary, elective THAs with both preoperative and one year postoperative Hip disability and Osteoarthritis Outcome Score, Joint Replacement (HOOS, JR) scores were analyzed. The main exposure variable was hospital teaching status, with three cohorts, as follows: major teaching hospitals, minor teaching hospitals, and non-teaching hospitals. Mean preoperative and one year postoperative HOOS, JR scores were compared. RESULTS: Preoperative HOOS, JR scores (nonteaching: 49.69 ± 14.42 versus major teaching: 47.68 ± 15.10 versus minor teaching: 42.46 ± 19.19, P < .001) were significantly higher at non-teaching hospitals than major and minor teaching hospitals, and these differences persisted at one year postoperatively (87.40 ± 15.14 versus 83.87 ± 16.68 versus 80.37 ± 19.27, P < .001). Both preoperative and postoperative differences in HOOS, JR scores were less than the minimum clinically important difference (MCID) at both time points. In multivariate regressions, non-teaching and minor teaching hospitals had similar odds of MCID achievement in HOOS, JR scores compared to major teaching hospitals. CONCLUSION: Using the HOOS, JR score as a validated outcome measure, undergoing primary THA at an academic teaching hospital did not correlate with higher postoperative HOOS, JR scores or greater chances of MCID achievement in HOOS, JR scores compared to non-teaching hospitals. Further work is required to determine the most important factors that may lead to improvement in patient-reported outcomes following THA.

Extensor Mechanism Disruption Remains a Challenging Problem.

BACKGROUND: Extensor mechanism disruption (EMD) following total knee arthroplasty (TKA) is a devastating problem commonly treated with allograft or synthetic reconstruction. Understanding of reconstruction success rates and patient recorded outcomes is lacking. METHODS: Patients who have an EMD after TKA undergoing mesh or whole-extensor allograft reconstruction between 2011 and 2019, with minimum 2-year follow-up were reviewed at two tertiary care centers. Functional failure was defined as extensor lag >30 degrees, amputation, or fusion, as well as revision extensor mechanism reconstruction (EMR). Survivorship was assessed using Kaplan-Meier curves, and factors for success were determined with logistic regressions. RESULTS: Of fifty-six EMRs (49 patients), 50.0% (28/56) were functionally successful at 3.2 years of mean follow-up (range, 0.2 to 7.4). In situ survivorship of the reconstructions at 36 months was 75.0% (42 of 58). There were 50.0% (14 of 28) of functionally failed EMRs that retained their reconstruction at last follow-up. Mean extensor lag among successes and failures was 5.4 and 71.0° (P = .01), respectively. Mean Knee Injury and Osteoarthritis Outcome Score, Joint Replacement scores were 67.1 and 48.8 among successes and failures (P = .01). There were 64.0% (16 of 25) of successes and 1 of 19 failures that obtained a Knee Injury and Osteoarthritis Outcome Score, Joint Replacement score above the minimum patient-acceptable symptom state for TKA. Survivorship and success rates were similar between reconstruction methods (P = .86; P = .76). All-cause mortality was 8.2% (4 of 49), each with EMR failure prior to death. All-cause reoperation rate was 42.9% (24 of 56), with a 14.3% (8 of 56) rate of revision EMR and 10.7% (6 of 56) rate of above-knee-amputation or modular fusion. CONCLUSIONS: This multicenter investigation of mesh or allograft EMR demonstrated modest functional success at 3.2 years. Complication and reoperation rates were high, regardless of EMR technique. Therefore, EMD after TKA remains problematic.

Iduronate-2-sulfatase fused with anti-hTfR antibody, pabinafusp alfa, for MPS-II: A phase 2 trial in Brazil.

In Hunter syndrome (mucopolysaccharidosis II [MPS-II]), systemic accumulation of glycosaminoglycans (GAGs) due to a deficiency of iduronate-2-sulfatase (IDS), caused by mutations in the IDS gene, leads to multiple somatic manifestations and in patients with the severe (neuronopathic) phenotype, also to central nervous system (CNS) involvement. These symptoms cannot be effectively treated with current enzyme-replacement therapies, as they are unable to cross the blood-brain barrier (BBB). Pabinafusp alfa, a novel IDS fused with an anti-human transferrin receptor antibody, was shown to penetrate the BBB and to address neurodegeneration in preclinical studies. Subsequent phase 1/2 and 2/3 clinical studies in Japan have shown marked reduction of GAG accumulation in the cerebrospinal fluid (CSF), along with favorable clinical responses. A 26-week, open-label, randomized, parallel-group phase 2 study was conducted in Brazil to further evaluate the safety and efficacy of intravenously administered pabinafusp alfa at 1.0, 2.0, and 4.0 mg/kg/week in MPS-II patients. The safety profiles in the three dosage groups were similar. Neurodevelopmental evaluation suggested positive neurocognitive signals despite a relatively short study period. The 2.0-mg/kg group, which demonstrated marked reductions in substrate concentrations in the CSF, serum, and urine, was considered to provide the best combination regarding safety and efficacy signals.

Development and Validation of Crosswalks Between the Western Ontario & McMaster Universities Osteoarthritis Index and Hip Disability and Osteoarthritis Outcome Score Joint Replacement/Knee Injury and Osteoarthritis Outcome Score Joint Replacement.

BACKGROUND: The wide variety of patient-reported outcome measures used to assess outcomes following total joint arthroplasty can present a substantial methodological obstacle when attempting to compare information across studies or between institutions. A simple solution is to create crosswalks that reliably convert scores between patient-reported outcome measures. Our goal is to create and validate crosswalks between the commonly used Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) and short-form versions of the Hip Disability and Osteoarthritis Outcome Score Joint Replacement (HOOS JR)/Knee Injury and Osteoarthritis Outcome Score (KOOS JR.). METHODS: Patients in our joint replacement registry were included if they underwent primary total hip arthroplasty (n = 4649) or total knee arthroplasty (n = 3750) for osteoarthritis between May 2007 and February 2012. We used their preoperative and 2-year postoperative HOOS scores (n = 6351) or KOOS scores (n = 4688) to generate the patients' WOMAC and HOOS JR/KOOS JR scores. The equipercentile equating method was applied to create 10 crosswalks: HOOS JR/KOOS JR to WOMAC Total (WOMAC-T), and WOMAC-T, WOMAC Pain (WOMAC-P), WOMAC Stiffness (WOMAC-S), and WOMAC Function (WOMAC-F) to HOOS JR/KOOS JR. Crosswalk validity was assessed by comparing actual and derived scores using Spearman's rank correlation coefficients in a bootstrapped cohort. RESULTS: All 10 crosswalks showed strong positive correlations ranging from 0.846 (WOMAC-S to KOOS JR) to 0.981 (HOOS JR to WOMAC-T). CONCLUSION: We created and validated 10 crosswalks between WOMAC and HOOS JR/KOOS JR. We recommend using the crosswalks between WOMAC-T and HOOS JR/KOOS JR when possible, as they demonstrated the highest correlation. WOMAC-F or WOMAC-P should be used in favor of WOMAC-S if only subscores are available. The HOOS JR/KOOS JR should only be converted to a WOMAC-T. LEVEL OF EVIDENCE: Level III.

Comparison of Patient-Reported Outcomes and Functional Assessment Using a Marker-Less Image Capture System in End-Stage Knee Arthritis.

BACKGROUND: Patient self-assessment of knee function in end-stage osteoarthritis (OA) and following total knee arthroplasty (TKA) using patient-reported outcome measures (PROMs) has become standard for defining disability. The relationship of PROMs to functional performance requires a continued investigation. The purpose of this study was to determine correlations between patient demographics, PROMs, and functional performances using a marker-less image capture system (MICS). METHODS: Patients indicated for elective TKA completed the Knee Injury and Osteoarthritis Score for Joint Replacement (KOOS-JR) and an office-based functional assessment using a MICS. Patient age, body mass index (BMI), and gender were collected. A total of 112 patients were enrolled. Their mean age was 65.0 (±9.7) years, mean BMI was 32.5 (±6.6) kg/m2, and mean KOOS-JR was 14.5 (±5.7). The relationships between patient characteristics, KOOS-JR, MICS Alignment (coronal), MICS Mobility (flexion), and composite Total Joint scores were described using Spearman's correlation coefficients. RESULTS: BMI was weakly correlated with KOOS-JR (ρ = -0.22, P = .024), whereas age was not. Age and BMI were not correlated with performance scores. There were weak to no correlations between KOOS-JR and MICS Alignment (ρ = -0.01, P = .951), Mobility (ρ = 0.33, P < .001), and Total Joint scores (ρ = 0.06, P = .504). CONCLUSION: This study found no strong correlation between KOOS-JR and functional performance using a validated MICS for patients with end-stage knee OA. Further study is warranted in determining the relationship between PROMs and performance to optimize outcomes of patients undergoing nonoperative or surgical interventions for knee OA. The use of high-fidelity functional assessment tools that can be integrated into clinical workflow, such as the MICS used in this study, should permit PROM/functional performance comparisons in large populations.

The AAHKS Clinical Research Award: Are Minimum Two-Year Patient-Reported Outcome Measures Necessary for Accurate Assessment of Patient Outcomes After Primary Total Knee Arthroplasty?

BACKGROUND: The two-year minimum follow-up after total knee arthroplasty (TKA) required by most academic journals is based on implant survivorship studies rather than patient-reported outcome measures (PROMs). Additionally, the COVID-19 pandemic placed an unprecedented burden on patients and staff and halted asymptomatic surveillance clinic visits to minimize exposure. The purpose of this study was to determine if clinically meaningful differences were observed in PROMs beyond one year after TKA. METHODS: A retrospective review was performed on prospectively collected PROMs after 1093 primary TKAs at a suburban academic center. PROMs related to pain, function, activity level, and satisfaction were compared by subsequent follow-up intervals preoperatively, at 4 months, 1 year, and minimum 2 years using paired data analysis techniques. RESULTS: Pain with level walking and while climbing stairs improved from preoperative levels to 4-month, 1-year, and minimum 2-year follow-up. The University of California Los Angeles activity level and Knee Injury and Osteoarthritis Outcome Score for Joint Replacement improved over the same intervals. Patient satisfaction improved over postoperative follow-up intervals (84.0%, 87.3%, and 90.9%). While PROMs improved with statistical and clinical significance preoperatively to 4-month to 1-year follow-up, improvements from 1-year to minimum 2-year follow-up were small and did not reach minimum clinically important differences for nearly all PROMs, demonstrating significant overlap of the 95% confidence intervals. CONCLUSION: While long-term follow-up after TKA remains important for implant survivorship, it appears that one-year PROMs are as clinically reliable and meaningful as two-year PROMs. Therefore, it is reasonable to question the currently accepted 2-year minimum follow-up requirement used in peer-reviewed research involving PROMs. LEVEL OF EVIDENCE: Level III.