Publications by Year: 2023

2023

Bernstein, D. N., Hanna, P., Merchan, N., Rodriguez, E. K., Appleton, P. T., Kwon, J. Y., & Wixted, J. J. (2023). Lack of Surgeon Standardization on Implant Selection in Ankle Fracture Fixation May Increase Costs and Decrease Contribution Margin.. Foot & Ankle Specialist, 16(2), 129-134. https://doi.org/10.1177/19386400211009357 (Original work published 2023)

BACKGROUND: Surgical standardization has been shown to decrease costs without impacting quality; however, there is limited literature on this subject regarding ankle fracture fixation. Methods. Between October 5, 2015 and September 27, 2017, a total of 168 patients with isolated ankle fractures who underwent open reduction, internal fixation (ORIF) were analyzed. Financial data were analyzed across ankle fracture classification type, implant characteristics, and surgeons. Bivariate analyses were conducted. One-way analysis of variance was used to compare hardware costs across all 5 surgeons. Linear regression analysis was used to determine if hardware cost differed by surgeon when accounting for fracture type.

RESULTS: The mean contribution margin was $4853 (SD $6446). There was a significant difference in implant costs by surgeon (range, lowest-cost surgeon: $471 [SD $283] to $1609 [SD $819]; P < .001). There was no difference in the use of a suture button or locking plate by fracture type (P = .13); however, the cost of the implant was significantly higher if a suture button or locking plate was used ($1014 [SD $666] vs $338 [SD $176]; P < .001). There was an association between surgeon 3 (β = 200.32 [95% CI 6.18-394.47]; P = .043) and surgeon 4 (β = 1131.07 [95% CI 906.84-1355.30]; P < .001) and higher hardware costs.

CONCLUSIONS: Even for the same ankle fracture type, a wide variation in implant costs exists. The lack of standardization among surgeons accounted for a nearly 3.5-fold difference, on average, between the lowest- and highest-cost surgeons, negatively affecting contribution margin.

LEVELS OF EVIDENCE: Level IV.

Dillon, S. T., Otu, H. H., Ngo, L. H., Fong, T. G., Vasunilashorn, S. M., Xie, Z., Kunze, L. J., Vlassakov, K. , V, Abdeen, A., Lange, J. K., Earp, B. E., Cooper, Z. R., Schmitt, E. M., Arnold, S. E., Hshieh, T. T., Jones, R. N., Inouye, S. K., Marcantonio, E. R., Libermann, T. A., & Group, R. S. (2023). Patterns and Persistence of Perioperative Plasma and Cerebrospinal Fluid Neuroinflammatory Protein Biomarkers After Elective Orthopedic Surgery Using SOMAscan.. Anesthesia and Analgesia, 136(1), 163-175. https://doi.org/10.1213/ANE.0000000000005991 (Original work published 2023)

BACKGROUND: The neuroinflammatory response to surgery can be characterized by peripheral acute plasma protein changes in blood, but corresponding, persisting alterations in cerebrospinal fluid (CSF) proteins remain mostly unknown. Using the SOMAscan assay, we define acute and longer-term proteome changes associated with surgery in plasma and CSF. We hypothesized that biological pathways identified by these proteins would be in the categories of neuroinflammation and neuronal function and define neuroinflammatory proteome changes associated with surgery in older patients.

METHODS: SOMAscan analyzed 1305 proteins in blood plasma (n = 14) and CSF (n = 15) samples from older patients enrolled in the Role of Inflammation after Surgery for Elders (RISE) study undergoing elective hip and knee replacement surgery with spinal anesthesia. Systems biology analysis identified biological pathways enriched among the surgery-associated differentially expressed proteins in plasma and CSF.

RESULTS: Comparison of postoperative day 1 (POD1) to preoperative (PREOP) plasma protein levels identified 343 proteins with postsurgical changes ( P < .05; absolute value of the fold change [|FC|] > 1.2). Comparing postoperative 1-month (PO1MO) plasma and CSF with PREOP identified 67 proteins in plasma and 79 proteins in CSF with altered levels ( P < .05; |FC| > 1.2). In plasma, 21 proteins, primarily linked to immune response and inflammation, were similarly changed at POD1 and PO1MO. Comparison of plasma to CSF at PO1MO identified 8 shared proteins. Comparison of plasma at POD1 to CSF at PO1MO identified a larger number, 15 proteins in common, most of which are regulated by interleukin-6 (IL-6) or transforming growth factor beta-1 (TGFB1) and linked to the inflammatory response. Of the 79 CSF PO1MO-specific proteins, many are involved in neuronal function and neuroinflammation.

CONCLUSIONS: SOMAscan can characterize both short- and long-term surgery-induced protein alterations in plasma and CSF. Acute plasma protein changes at POD1 parallel changes in PO1MO CSF and suggest 15 potential biomarkers for longer-term neuroinflammation that warrant further investigation.

Geiger, E. J., Liu, W., Srivastava, D. K., Bernthal, N. M., Weil, B. R., Yasui, Y., Ness, K. K., Krull, K. R., Goldsby, R. E., Oeffinger, K. C., Robison, L. L., Dieffenbach, B. , V, Weldon, C. B., Gebhardt, M. C., Howell, R., Murphy, A. J., Leisenring, W. M., Armstrong, G. T., Chow, E. J., & Wustrack, R. L. (2023). What Are Risk Factors for and Outcomes of Late Amputation After Treatment for Lower Extremity Sarcoma: A Childhood Cancer Survivor Study Report.. Clinical Orthopaedics and Related Research, 481(3), 526-538. https://doi.org/10.1097/CORR.0000000000002243 (Original work published 2023)

BACKGROUND: Although pediatric lower extremity sarcoma once was routinely treated with amputation, multiagent chemotherapy as well as the evolution of tumor resection and reconstruction techniques have enabled the wide adoption of limb salvage surgery (LSS). Even though infection and tumor recurrence are established risk factors for early amputation (< 5 years) after LSS, the frequency of and factors associated with late amputation (≥ 5 years from diagnosis) in children with sarcomas are not known. Additionally, the resulting psychosocial and physical outcomes of these patients compared with those treated with primary amputation or LSS that was not complicated by subsequent amputation are not well studied. Studying these outcomes is critical to enhancing the quality of life of patients with sarcomas.

QUESTIONS/PURPOSES: (1) How have treatments changed over time in patients with lower extremity sarcoma who are included in the Childhood Cancer Survivor Study (CCSS), and did primary treatment with amputation or LSS affect overall survival at 25 years among patients who had survived at least 5 years from diagnosis? (2) What is the cumulative incidence of amputation after LSS for patients diagnosed with pediatric lower extremity sarcomas 25 years after diagnosis? (3) What are the factors associated with time to late amputation (≥ 5 years after diagnosis) in patients initially treated with LSS for lower extremity sarcomas in the CCSS? (4) What are the comparative social, physical, and emotional health-related quality of life (HRQOL) outcomes among patients with sarcoma treated with primary amputation, LSS without amputation, or LSS complicated by late amputation, as assessed by CCSS follow-up questionnaires, the SF-36, and the Brief Symptom Inventory-18 at 20 years after cancer diagnosis?

METHODS: The CCSS is a long-term follow-up study that began in 1994 and is coordinated through St. Jude Children's Research Hospital. It is a retrospective study with longitudinal follow-up of more than 38,000 participants treated for childhood cancer when younger than 21 years at one of 31 collaborating institutions between 1970 and 1999 in the United States and Canada. Participants were eligible for enrollment in the CCSS after they had survived 5 years from diagnosis. Within the CCSS cohort, we included participants who had a diagnosis of lower extremity sarcoma treated with primary amputation (547 patients with a mean age at diagnosis of 13 ± 4 years) or primary LSS (510 patients with a mean age 14 ± 4 years). The LSS cohort was subdivided into LSS without amputation, defined as primary LSS without amputation at the time of latest follow-up; LSS with early amputation, defined as LSS complicated by amputation occurring less than 5 years from diagnosis; or LSS with late amputation, defined as primary LSS in study patients who subsequently underwent amputation 5 years or more from cancer diagnosis. The cumulative incidence of late amputation after primary LSS was estimated. Cox proportional hazards regression with time-varying covariates identified factors associated with late amputation. Modified Poisson regression models were used to compare psychosocial, physical, and HRQOL outcomes among patients treated with primary amputation, LSS without amputation, or LSS complicated by late amputation using validated surveys.

RESULTS: More study participants were treated with LSS than with primary amputation in more recent decades. The overall survival at 25 years in this population who survived 5 years from diagnosis was not different between those treated with primary amputation (87% [95% confidence interval [CI] 82% to 91%]) compared with LSS (88% [95% CI 85% to 91%]; p = 0.31). The cumulative incidence of amputation at 25 years after cancer diagnosis and primary LSS was 18% (95% CI 14% to 21%). With the numbers available, the cumulative incidence of late amputation was not different among study patients treated in the 1970s (27% [95% CI 15% to 38%]) versus the 1980s and 1990s (19% [95% CI 13% to 25%] and 15% [95% CI 10% to 19%], respectively; p = 0.15). After controlling for gender, medical and surgical treatment variables, cancer recurrence, and chronic health conditions, gender (hazard ratio [HR] 2.02 [95% CI 1.07 to 3.82]; p = 0.03) and history of prosthetic joint reconstruction (HR 2.58 [95% CI 1.37 to 4.84]; p = 0.003) were associated with an increased likelihood of late amputation. Study patients treated with a primary amputation (relative risk [RR] 2.04 [95% CI 1.15 to 3.64]) and LSS complicated by late amputation (relative risk [RR] 3.85 [95% CI 1.66 to 8.92]) were more likely to be unemployed or unable to attend school than patients treated with LSS without amputation to date. The CCSS cohort treated with primary amputation and those with LSS complicated by late amputation reported worse physical health scores than those without amputation to date, although mental and emotional health outcomes did not differ between the groups.

CONCLUSION: There is a substantial risk of late amputation after LSS, and both primary and late amputation status are associated with decreased physical HRQOL outcomes. Children treated for sarcoma who survive into adulthood after primary amputation and those who undergo late amputation after LSS may benefit from interventions focused on improving physical function and reaching educational and employment milestones. Efforts to improve the physical function of people who have undergone amputation either through prosthetic design or integration into the residuum should be supported. Understanding factors associated with late amputation in the setting of more modern surgical approaches and implants will help surgeons more effectively manage patient expectations and adjust practice to mitigate these risks over the life of the patient.

LEVEL OF EVIDENCE: Level III, therapeutic study.

Pinski, J. M., Ryan, S. P., Pittman, J. L., & Tornetta, P. (2023). Is fixation of the medial malleolus necessary in unstable ankle fractures?. Archives of Orthopaedic and Trauma Surgery, 143(6), 2999-3005. https://doi.org/10.1007/s00402-022-04528-9 (Original work published 2023)

INTRODUCTION: It is unclear whether the medial malleolus in unstable bi- and tri- malleolar ankle fractures without medial talar displacement should be addressed surgically. This study reviews a fixation protocol for the medial malleolar component of unstable bi- or tri- malleolar ankle fractures.

MATERIALS AND METHODS: Two hundred fifty-seven patients who sustained bi- (AO/OTA 44-B2) or tri- (AO/OTA 44-B3) malleolar ankle fractures between January 2005 and August 2019 at two Level 1 trauma centers were retrospectively identified. Medial malleolar fractures were defined as anterior, supra or intercollicular fractures based on the exit of the posterior fracture line. Fixation of the medial malleolar component was performed based on surgical algorithm. Only large or significantly displaced medial malleolar fractures were fixed if the soft tissues were amenable. Primary outcome measure was the presence of medial-sided ankle pain after operative or non-operative treatment of the medial malleolar fracture after a minimum follow up of 6 months. Presence of pain was defined by a pain score of 3 or higher on a 10-point VAS pain score at the site of the medial malleolar fracture.

RESULTS: Significantly more patients in the supracollicular group reported the presence of pain when this type was not fixed versus fixed (28 vs 14%, p = 0.0094). Significantly more patients in the anterior collicular subgroup reported the presence of pain when this type was fixed versus not fixed (40 vs 10%, p = 0.0438). There was no difference in the number of patients reporting pain in the intercollicular group when comparing those who were fixed versus not fixed, (21 vs 22%, p = 1.000).

CONCLUSIONS: When examining post-operative pain, not all medial malleolar fractures require fixation when appropriately selected based on fracture pattern. Only 10% of patients with anterior collicular fractures reported pain after non operative management. Unsurprisingly, more patients in the supracollicular fractures reported pain without surgery compared to with surgery. Fracture pattern should be considered in the treatment algorithm for the medial malleolar component in bi- and tri- malleolar fractures.

Berton, A., Salvatore, G., Nazarian, A., Longo, U. G., Orsi, A., Egan, J., Ramappa, A., DeAngelis, J., & Denaro, V. (2023). Combined MPFL reconstruction and tibial tuberosity transfer avoid focal patella overload in the setting of elevated TT-TG distances.. Knee Surgery, Sports Traumatology, Arthroscopy : Official Journal of the ESSKA, 31(5), 1771-1780. https://doi.org/10.1007/s00167-022-07056-6 (Original work published 2023)

PURPOSE: Objectives are (1) to evaluate the biomechanical effect of isolated medial patellofemoral ligament (MPFL) reconstruction in the setting of increased tibial tuberosity-trochlear groove distance (TTTG), in terms of patella contact pressures, contact area and lateral displacement; (2) to describe the threshold of TTTG up to which MPFL reconstruction should be performed alone or in combination with tibial tuberosity transfer.

METHODS: A finite element model of the knee was developed and validated. The model was modified to simulate isolated MPFL reconstruction, tibial tuberosity transfer and MPFL reconstruction combined with tibial tuberosity transfer for patella malalignment. Two TT-TG distances (17 mm and 22 mm) were simulated. Patella contact pressure, contact area and lateral displacement were analysed.

RESULTS: Isolated MPFL reconstruction, at early degrees of flexion, restored normal patella contact pressure when TTTG was 17 mm, but not when TTTG was 22 mm. After 60° of flexion, the TTTG distance was the main factor influencing contact pressure. Isolated MPFL reconstruction for both TTTG 17 mm and 22 mm showed higher contact area and lower lateral displacement than normal throughout knee flexion. Tibial tuberosity transfer, at early degrees of flexion, reduced the contact pressure, but did not restore the normal contact pressure. After 60° of flexion, the TTTG distance was the main factor influencing contact pressure. Tibial tuberosity transfer maintained lower contact area than normal throughout knee flexion. The lateral displacement was higher than normal between 0° and 30° of flexion (< 0.5 mm). MPFL reconstruction combined with tibial tuberosity transfer produced the same contact mechanics and kinematics of the normal condition.

CONCLUSION: This study highlights the importance of considering to correct alignment in lateral tracking patella to avoid focal patella overload. Our results showed that isolated MPFL reconstruction corrects patella kinematics regardless of TTTG distance. However, isolated MPFL reconstruction would not restore normal patella contact pressure when TTTG is 22 mm. For TTTG 22 mm, the combined procedure of MPFL reconstruction and tibial tuberosity transfer provided an adequate patellofemoral contact mechanics and kinematics, restoring normal biomechanics. This data supports the use of MPFL reconstruction when the patient has normal alignment and the use of combined MPFL reconstruction and tibial tuberosity transfer in patients with elevated TT-TG distances to avoid focal overload.

Szapary, H. J., Monárrez, R., Varady, N. H., Hanna, P., Chen, A. F., & Rodriguez, E. K. (2023). Complications and predictors of morbidity for hip fracture surgery in patients with chronic liver disease.. Hip International : The Journal of Clinical and Experimental Research on Hip Pathology and Therapy, 33(4), 771-778. https://doi.org/10.1177/11207000221112923 (Original work published 2023)

BACKGROUND: Despite the fact that patients with chronic liver disease (CLD) are at increased risk of complications after a fracture of the hip, there remains little information about the risk factors for acute postoperative complications and their overall outcome.The aim of this study was to describe inpatient postoperative complications and identify predictors of postoperative morbidity.

METHODS: Patients with CLD who had been treated for a fracture of the hip between April 2005 and August 2019 were identified from a retrospective search of an intramural trauma registry based in the Northeastern United States. Medical records were reviewed for baseline demographics, preoperative laboratory investigations, and outcomes.

RESULTS: The trauma registry contained 110 patients with CLD who had undergone surgery for a fracture of the hip. Of these, patients with a platelet-count of ⩽100,000/µL were 3.81 (95% CI, 1.59-9.12) times more likely to receive a transfusion than those with a platelet-count of >100,000/µL. Those with a Model for End-stage Liver Disease (MELD) score of >9 were 5.54 (2.33-13.16) times more likely to receive a transfusion and 3.97 (1.06-14.81) times more likely to develop postoperative delirium than those with a MELD score of ⩽9.Of patients without chronic kidney disease, those with a creatinine of ⩾1.2 mg/dL were 6.80 (1.79-25.87) times more likely to develop acute renal failure (ARF) than those with a creatinine of <1.2 mg/dL. In a multivariable model, as MELD score was increased, the odds of developing a composite postoperative complication, which included transfusion, ARF, delirium, or deep wound infection, were 1.29 (1.01-1.66). Other tools used to assess surgical risks, Charlson Comorbidity Index, Elixhauser, and American Society of Anesthesiologist scores, were not predictive.

CONCLUSIONS: Patients with CLD who undergo surgery for a hip fracture have a high rate of postoperative complications which can be predicted by the preoperative laboratory investigations identified in this study and MELD scores, but not by other common comorbidity indices.

Nolte, M. T., Gandhi, S. D., Nguyen, A. Q., Siyaji, Z. K., Piracha, A. Z., Khanna, K., Rush, A. J., Sheha, E. D., & Phillips, F. M. (2023). Rates of Postoperative Complications and Approach-related Neurological Symptoms After L4-L5 Lateral Transpsoas Lumbar Interbody Fusion Compared With Upper Lumbar Levels.. Clinical Spine Surgery, 36(7), E294-E299. https://doi.org/10.1097/BSD.0000000000001367 (Original work published 2023)

STUDY DESIGN: This was a retrospective comparative study.

OBJECTIVE: To compare the likelihood of approach-related complications for patients undergoing single-level lateral lumbar interbody fusion (LLIF) at L4-L5 to those undergoing the procedure at upper lumbar levels.

SUMMARY OF BACKGROUND DATA: LLIF has been associated with a number of advantages when compared with traditional interbody fusion techniques. However, potential risks with the approach include vascular or visceral injury, thigh dysesthesias, and lumbar plexus injury. There are concerns of a higher risk of these complications at the L4-L5 level compared with upper lumbar levels.

MATERIALS AND METHODS: A retrospective cohort review was completed for consecutive patients undergoing single-level LLIF between 2004 and 2019 by a single surgeon. Indication for surgery was symptomatic degenerative lumbar stenosis and/or spondylolisthesis. Patients were divided into 2 cohorts: LLIF at L4-L5 versus a single level between L1 and L4. Baseline characteristics, intraoperative complications, postoperative approach-related neurological symptoms, and patient-reported outcomes were compared and analyzed between the cohorts.

RESULTS: A total of 122 were included in analysis, of which 58 underwent LLIF at L4-L5 and 64 underwent LLIF between L1 and L4. There were no visceral or vascular injuries or lumbar plexus injuries in either cohort. There was no significant difference in the rate of postoperative hip pain, anterior thigh dysesthesias, and/or hip flexor weakness between the cohorts (53.5% L4-L5 vs. 37.5% L1-L4; P =0.102). All patients reported complete resolution of these symptoms by 6-month postoperative follow-up.

DISCUSSION: LLIF surgery at the L4-L5 level is associated with a similar infrequent likelihood of approach-related complications and postoperative hip pain, thigh dysesthesias, and hip flexor weakness when compared with upper lumbar level LLIF. Careful patient selection, meticulous use of real-time neuromonitoring, and an understanding of the anatomic location of the lumbar plexus to the working corridor are critical to success.

Lozano-Calderon, S. A., Albergo, J. I., Groot, O. Q., Merchan, N. A., Abiad, J. M. E., Salinas, V., Mier, L. C. G., Montoya, C. S., Ferrone, M. L., Ready, J. E., Linares, F. J., Levin, A. S., Pensado, M. P., Kreilinger, J. J. P., Ruiz, I. B., Ortiz-Cruz, E. J., Gebhardt, M. C., Cote, G. M., Choy, E., … Jeys, L. M. (2023). Complete tumor necrosis after neoadjuvant chemotherapy defines good responders in patients with Ewing sarcoma.. Cancer, 129(1), 60-70. https://doi.org/10.1002/cncr.34506 (Original work published 2023)

BACKGROUND: Survival in patients who have Ewing sarcoma is correlated with postchemotherapy response (tumor necrosis). This treatment response has been categorized as the response rate, similar to what has been used in osteosarcoma. There is controversy regarding whether this is appropriate or whether it should be a dichotomy of complete versus incomplete response, given how important a complete response is for in overall survival of patients with Ewing sarcoma. The purpose of this study was to evaluate the impact that the amount of chemotherapy-induced necrosis has on (1) overall survival, (2) local recurrence-free survival, (3) metastasis-free survival, and (4) event-free survival in patients with Ewing sarcoma.

METHODS: In total, 427 patients who had Ewing sarcoma or tumors in the Ewing sarcoma family and received treatment with preoperative chemotherapy and surgery at 10 international institutions were included. Multivariate Cox proportional-hazards analyses were used to assess the associations between tumor necrosis and all four outcomes while controlling for clinical factors identified in bivariate analysis, including age, tumor volume, location, surgical margins, metastatic disease at presentation, and preoperative radiotherapy.

RESULTS: Patients who had a complete (100%) tumor response to chemotherapy had increased overall survival (hazard ratio [HR], 0.26; 95% CI, 0.14-0.48; p < .01), recurrence-free survival (HR, 0.40; 95% CI, 0.20-0.82; p = .01), metastasis-free survival (HR, 0.27; 95% CI, 0.15-0.46; p ≤ .01), and event-free survival (HR, 0.26; 95% CI, 0.16-0.41; p ≤ .01) compared with patients who had a partial (0%-99%) response.

CONCLUSIONS: Complete tumor necrosis should be the index parameter to grade response to treatment as satisfactory in patients with Ewing sarcoma. Any viable tumor in these patients after neoadjuvant treatment should be of oncologic concern. These findings can affect the design of new clinical trials and the risk-stratified application of conventional or novel treatments.

Turk, R., Shah, S., Chilton, M., Thomas, T. L., Anene, C., Mousad, A., Le Breton, S., Li, L., Pettit, R., Ives, K., & Ramappa, A. (2023). Return to Sport After Anterior Cruciate Ligament Reconstruction Requires Evaluation of >2 Functional Tests, Psychological Readiness, Quadriceps/Hamstring Strength, and Time After Surgery of 8 Months.. Arthroscopy : the Journal of Arthroscopic & Related Surgery : Official Publication of the Arthroscopy Association of North America and the International Arthroscopy Association, 39(3), 790-801.e6. https://doi.org/10.1016/j.arthro.2022.08.038 (Original work published 2023)

PURPOSE: The purpose of this study was to examine the factors commonly used to determine readiness for return to sport (RTS) in the ACL reconstruction (ACL-R) patient population and assess which were most influential to successfully returning to sport and avoiding re-tear.

METHODS: The PUBMED, EMBASE and Cochrane Library databases were queried for studies related to RTS in ACL-R. Inclusion and exclusion criteria were applied to identify studies with greater than 1-year outcomes detailing the rate of return and re-tear given a described RTS protocol. Data of interest were extracted, and studies were stratified based on level of evidence and selected study features. Meta-analysis or subjective synthesis of appropriate studies was used to assess more than 25 potentially significant variables effecting RTS and re-tear.

RESULTS: After initial search of 1503 studies, 47 articles were selected for inclusion in the final data analysis, including a total of 1432 patients (31.4% female, 68.6% male). A meta-analysis of re-tear rate for included Level of Evidence 1 studies was calculated to be 2.8%. Subgroups including protocols containing a strict time until RTS, strength testing, and ≥2 dynamic tests demonstrated decreased RTS and re-tear heterogeneity from the larger group. Time to RTS, strength testing, dynamic functional testing, and knee stability were also found to be among the most prevalent reported criteria in RTS protocol studies.

CONCLUSIONS: This study suggests a multifactorial clinical algorithm for successful evaluation of RTS. The "critical criteria" recommended by the authors to be part of the postoperative RTS criteria include time since surgery of 8 months, use of >2 functional tests, psychological readiness testing, and quadriceps/hamstring strength testing in addition to the modifying patient factors of age and female gender.

LEVEL OF EVIDENCE: Level IV, systematic review of Level I-IV studies.

Hshieh, T. T., Schmitt, E. M., Fong, T. G., Arnold, S., Cavallari, M., Dickerson, B. C., Dillon, S. T., Jones, R. N., Libermann, T. A., Marcantonio, E. R., Pascual-Leone, A., Shafi, M. M., Touroutoglou, A., Travison, T. G., Gou, R. Y., Tommet, D., Abdeen, A., Earp, B., Kunze, L., … Team, S. S. , II. (2023). Successful aging after elective surgery II: Study design and methods.. Journal of the American Geriatrics Society, 71(1), 46-61. https://doi.org/10.1111/jgs.18065 (Original work published 2023)

BACKGROUND: The Successful Aging after Elective Surgery (SAGES) II study was designed to increase knowledge of the pathophysiology and linkages between delirium and dementia. We examine novel biomarkers potentially associated with delirium, including inflammation, Alzheimer's disease (AD) pathology and neurodegeneration, neuroimaging markers, and neurophysiologic markers. The goal of this paper is to describe the study design and methods for the SAGES II study.

METHODS: The SAGES II study is a 5-year prospective observational study of 400-420 community dwelling persons, aged 65 years and older, assessed prior to scheduled surgery and followed daily throughout hospitalization to observe for development of delirium and other clinical outcomes. Delirium is measured with the Confusion Assessment Method (CAM), long form, after cognitive testing. Cognitive function is measured with a detailed neuropsychologic test battery, summarized as a weighted composite, the General Cognitive Performance (GCP) score. Other key measures include magnetic resonance imaging (MRI), transcranial magnetic stimulation (TMS)/electroencephalography (EEG), and Amyloid positron emission tomography (PET) imaging. We describe the eligibility criteria, enrollment flow, timing of assessments, and variables collected at baseline and during repeated assessments at 1, 2, 6, 12, and 18 months.

RESULTS: This study describes the hospital and surgery-related variables, delirium, long-term cognitive decline, clinical outcomes, and novel biomarkers. In inter-rater reliability assessments, the CAM ratings (weighted kappa = 0.91, 95% confidence interval, CI = 0.74-1.0) in 50 paired assessments and GCP ratings (weighted kappa = 0.99, 95% CI 0.94-1.0) in 25 paired assessments. We describe procedures for data quality assurance and Covid-19 adaptations.

CONCLUSIONS: This complex study presents an innovative effort to advance our understanding of the inter-relationship between delirium and dementia via novel biomarkers, collected in the context of major surgery in older adults. Strengths include the integration of MRI, TMS/EEG, PET modalities, and high-quality longitudinal data.