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Open Access
Defining modern iatrogenic flatback syndrome: examination of segmental lordosis in short lumbar fusion patients undergoing thoracolumbar deformity correction
(European Spine Journal, 2024-01-01) Diebo, BG; Singh, M; Balmaceno-Criss, M; Daher, M; Lenke, LG; Ames, CP; Burton, DC; Lewis, SM; Klineberg, EO; Lafage, R; Eastlack, RK; Gupta, MC; Mundis, GM; Gum, JL; Hamilton, KD; Hostin, R; Passias, PG; Protopsaltis, TS; Kebaish, KM; Kim, HJ; Shaffrey, CI; Line, BG; Mummaneni, PV; Nunley, PD; Smith, JS; Turner, J; Schwab, FJ; Uribe, JS; Bess, S; Lafage, V; Daniels, AH
Purpose: Understanding the mechanism and extent of preoperative deformity in revision procedures may provide data to prevent future failures in lumbar spinal fusion patients. Methods: ASD patients without prior spine surgery (PRIMARY) and with prior short (SHORT) and long (LONG) fusions were included. SHORT patients were stratified into modes of failure: implant, junctional, malalignment, and neurologic. Baseline demographics, spinopelvic alignment, offset from alignment targets, and patient-reported outcome measures (PROMs) were compared across PRIMARY and SHORT cohorts. Segmental lordosis analyses, assessing under-, match, or over-correction to segmental and global lordosis targets, were performed by SRS-Schwab coronal curve type and construct length. Results: Among 785 patients, 430 (55%) were PRIMARY and 355 (45%) were revisions. Revision procedures included 181 (23%) LONG and 174 (22%) SHORT corrections. SHORT modes of failure included 27% implant, 40% junctional, 73% malalignment, and/or 28% neurologic. SHORT patients were older, frailer, and had worse baseline deformity (PT, PI-LL, SVA) and PROMs (NRS, ODI, VR-12, SRS-22) compared to primary patients (p < 0.001). Segmental lordosis analysis identified 93%, 88%, and 62% undercorrected patients at LL, L1-L4, and L4-S1, respectively. SHORT patients more often underwent 3-column osteotomies (30% vs. 12%, p < 0.001) and had higher ISSG Surgical Invasiveness Score (87.8 vs. 78.3, p = 0.006). Conclusions: Nearly half of adult spinal deformity surgeries were revision fusions. Revision short fusions were associated with sagittal malalignment, often due to undercorrection of segmental lordosis goals, and frequently required more invasive procedures. Further initiatives to optimize alignment in lumbar fusions are needed to avoid costly and invasive deformity corrections. Level of evidence: IV: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.
Open Access
Characteristics and outcomes of patients with symptomatic chronic myocardial injury in a Tanzanian emergency department: A prospective observational study.
(PloS one, 2024-01) Rahim, Faraan O; Sakita, Francis M; Coaxum, Lauren A; Kweka, Godfrey L; Loring, Zak; Mlangi, Jerome J; Galson, Sophie W; Tarimo, Tumsifu G; Temu, Gloria; Bloomfield, Gerald S; Hertz, Julian T
Background
Chronic myocardial injury is a condition defined by stably elevated cardiac biomarkers without acute myocardial ischemia. Although studies from high-income countries have reported that chronic myocardial injury predicts adverse prognosis, there are no published data about the condition in sub-Saharan Africa.
Methods
Between November 2020 and January 2023, adult patients with chest pain or shortness of breath were recruited from an emergency department in Moshi, Tanzania. Medical history and point-of-care troponin T (cTnT) assays were obtained from participants; those whose initial and three-hour repeat cTnT values were abnormally elevated but within 11% of each other were defined as having chronic myocardial injury. Mortality was assessed thirty days following enrollment.
Results
Of 568 enrolled participants, 81 (14.3%) had chronic myocardial injury, 73 (12.9%) had acute myocardial injury, and 412 (72.5%) had undetectable cTnT values. Of participants with chronic myocardial injury, the mean (± sd) age was 61.5 (± 17.2) years, and the most common comorbidities were CKD (n = 65, 80%) and hypertension (n = 60, 74%). After adjusting for CKD, thirty-day mortality rates (38% vs. 36%, aOR 1.03, 95% CI: 0.52-2.03, p = 0.931) were similar between participants with chronic myocardial injury and those with acute myocardial injury, but significantly greater (38% vs. 13.6%, aOR 3.63, 95% CI: 1.98-6.65, p<0.001) among participants with chronic myocardial injury than those with undetectable cTnT values.
Conclusion
In Tanzania, chronic myocardial injury is a poor prognostic indicator associated with high risk of short-term mortality. Clinicians practicing in this region should triage patients with stably elevated cTn levels in light of their increased risk.
Open Access
Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors.
(The New England journal of medicine, 2016-09) Connolly, Stuart J; Milling, Truman J; Eikelboom, John W; Gibson, C Michael; Curnutte, John T; Gold, Alex; Bronson, Michele D; Lu, Genmin; Conley, Pamela B; Verhamme, Peter; Schmidt, Jeannot; Middeldorp, Saskia; Cohen, Alexander T; Beyer-Westendorf, Jan; Albaladejo, Pierre; Lopez-Sendon, Jose; Goodman, Shelly; Leeds, Janet; Wiens, Brian L; Siegal, Deborah M; Zotova, Elena; Meeks, Brandi; Nakamya, Juliet; Lim, W Ting; Crowther, Mark; ANNEXA-4 Investigators
Background
Andexanet alfa (andexanet) is a recombinant modified human factor Xa decoy protein that has been shown to reverse the inhibition of factor Xa in healthy volunteers.
Methods
In this multicenter, prospective, open-label, single-group study, we evaluated 67 patients who had acute major bleeding within 18 hours after the administration of a factor Xa inhibitor. The patients all received a bolus of andexanet followed by a 2-hour infusion of the drug. Patients were evaluated for changes in measures of anti-factor Xa activity and were assessed for clinical hemostatic efficacy during a 12-hour period. All the patients were subsequently followed for 30 days. The efficacy population of 47 patients had a baseline value for anti-factor Xa activity of at least 75 ng per milliliter (or ≥0.5 IU per milliliter for those receiving enoxaparin) and had confirmed bleeding severity at adjudication.
Results
The mean age of the patients was 77 years; most of the patients had substantial cardiovascular disease. Bleeding was predominantly gastrointestinal or intracranial. The mean (±SD) time from emergency department presentation to the administration of the andexanet bolus was 4.8±1.8 hours. After the bolus administration, the median anti-factor Xa activity decreased by 89% (95% confidence interval [CI], 58 to 94) from baseline among patients receiving rivaroxaban and by 93% (95% CI, 87 to 94) among patients receiving apixaban. These levels remained similar during the 2-hour infusion. Four hours after the end of the infusion, there was a relative decrease from baseline of 39% in the measure of anti-factor Xa activity among patients receiving rivaroxaban and of 30% among those receiving apixaban. Twelve hours after the andexanet infusion, clinical hemostasis was adjudicated as excellent or good in 37 of 47 patients in the efficacy analysis (79%; 95% CI, 64 to 89). Thrombotic events occurred in 12 of 67 patients (18%) during the 30-day follow-up.
Conclusions
On the basis of a descriptive preliminary analysis, an initial bolus and subsequent 2-hour infusion of andexanet substantially reduced anti-factor Xa activity in patients with acute major bleeding associated with factor Xa inhibitors, with effective hemostasis occurring in 79%. (Funded by Portola Pharmaceuticals; ANNEXA-4 ClinicalTrials.gov number, NCT02329327 .).
Open Access
A Multi-Center International Analysis of Lung Transplantation Outcomes in Patients With COVID-19.
(Clinical transplantation, 2024-09) Kashem, Mohammed Abul; Loor, Gabriel; Emtiazjoo, Amir; Hartwig, Matthew; Van Raemdonck, Dirk; Calvelli, Hannah; Leon Pena, Andres; Salan-Gomez, Marcelo; Zhao, Huaqing; Warnick, Michael; Villavicencio, Mauricio; Ius, Fabio; Ghadimi, Kamrouz; Salman, Jawad; Chandrashekaran, Satish; Machuca, Tiago; Sanchez, Pablo G; Subramaniam, Kathirvel; Neyrinck, Arne; Huddleston, Stephen; Ceulemans, Laurens; Osho, Asishana; D'Silva, Ethan; Ramamurthy, Uma; Shaffer, Andrew; Langer, Nathaniel; Toyoda, Yoshiya
Introduction
Lung transplantation has become increasingly utilized in patients with COVID-19. While several single-center and UNOS database studies have been published on lung transplants (LTs) for end-stage lung disease (ESLD) from Coronavirus disease 2019 (COVID-19), there is a lack of multi-center and international data.
Methods
This is a multicenter analysis from 11 high-volume lung transplant centers in the United States and Europe. Data were collected through the Multi-Institutional ECLS Registry and stratified by ESLD due to COVID-19 versus other etiologies. Demographics and clinical variables were compared using Chi-square test and Fisher's exact test. Survival was assessed by Kaplan-Meier curves and compared by log-rank test with propensity score matching.
Results
Of 1606 lung transplant recipients, 46 (2.9%) were transplanted for ESLD from COVID-19 compared to 1560 (97.1%) without a history of COVID-19. Among COVID-19 patients, 30 (65.2%) had COVID-19-associated ARDS and 16 (34.8%) had post-COVID-19 fibrosis. COVID-19 patients had higher lung allocation scores (78.0 vs. 44.4, p < 0.0001), had severely limited functional status (37.0% vs. 2.9%, p < 0.0001), had higher preoperative ECMO usage (65.2% vs. 5.4%, p < 0.0001), and spent less time on the waitlist (32 vs. 137 days, p < 0.0001). A 30-day survival was comparable between COVID-19 and non-COVID-19 patients before (100% vs. 98.7%, p = 0.39) and after propensity matching (p = 0.15).
Conclusions
Patients who received LTs due to COVID-19 had short-term survival comparable to that of patients without COVID-19. Our findings support the idea that lung transplantation should be considered for select patients with ESLD due to COVID-19.
Open Access
Ensuring equity in psychosocial risk assessment for solid organ transplantation: a review
(Current Opinion in Organ Transplantation) Obayemi, Joy E; Shaw, Brian I; Greenberg, Goni-Katz; Henson, Jackie; McElroy, Lisa M
Purpose of review This review summarizes the different instruments for evaluating the psychosocial health of transplant candidates, the evidence demonstrating how these instruments relate to probability of transplant waitlisting and transplant outcomes, and the critical knowledge gaps that exist in the causal pathway between psychosocial health and clinical transplant trajectory. Recent findings The current literature reveals that psychosocial assessments are a common reason for racial and ethnic minorities to be denied access to the transplant list. Given evidence that a lack of clinician consensus exists regarding the definition of, importance of, and reproducibility of psychosocial support evaluations, this facet of the holistic evaluation process may create a unique challenge for already vulnerable patient populations. Though recent evidence shows that psychosocial evaluation scores predict select transplant outcomes, these findings remain inconsistent. Summary Multiple instruments for psychosocial transplant evaluation exist, though the utility of these instruments remains uncertain. As equity becomes an increasingly urgent priority for the transplant system, rigorous interrogation of the causal pathway between psychosocial health and transplant longevity is still needed.
Open Access
Cost-effectiveness Improves for Operative vs Nonoperative Treatment of Adult Symptomatic Lumbar Scoliosis at Eight-Year Follow-up.
(Spine, 2024-10) Carreon, Leah Y; Glassman, Steven D; Smith, Justin S; Kelly, Michael P; Yanik, Elizabeth L; Baldus, Christine R; Lurie, Jon D; Edwards, Charles; Lenke, Lawrence G; Buchowski, Jacob M; Crawford, Charles H; Koski, Tyler; Lafage, Virginie; Gupta, Munish; Kim, Han Jo; Ames, Christopher P; Bess, Shay; Schwab, Frank J; Shaffrey, Christopher I; Bridwell, Keith H
Study design
Secondary data analysis of the NIH sponsored study on Adult Symptomatic Lumbar Scoliosis (ASLS).
Objectives
The purpose of this study is to perform a cost-effectiveness analysis comparing operative versus non-operative care for ASLS eight years after enrollment.
Summary of background data
A prior cost-effectiveness analysis of the current cohort comparing operative to non-operative care at five years after enrollment showed and ICER of $44,033 in the As-Treated analysis and a ICER of $27,480 in the Intent-to-treat analysis.
Methods
Data was collected every three months for the first two years, then every six months for the remainder of the study. Data included use of non-operative modalities, medications and employment status. Costs for index and revision surgeries and non-operative modalities were determined using Medicare Allowable rates. Medication costs were determined using the RedBook and indirect costs were calculated based on reported employment status and income. Quality Adjusted Life Years (QALY) was determined using the SF6D.
Results
There were 101 cases in the Operative (Op) and 103 in the Non-operative (Non-Op) group with complete eight year data. Thirty-eight patients (37%) in the Non-Op group had surgery from 3 to 72 months after enrollment. An As-Treated analysis including only cases who never had surgery (N=65) or cases with complete eight-year post-operative data (N=101) showed that operative treatment was favored with an ICER of $20,569 per QALY gained which is within Willingness-to-Pay (WTP) thresholds. An Intent-to-Treat analysis demonstrated greater QALY gains and lower cost in the Op group (ICER = $-13,911). However, Intent-to-Treat analysis is influenced by Non-Op patients who crossed over to operative treatment at variable times during follow-up.
Conclusion
Operative treatment was more cost-effective than non-operative treatment for ASLS at eight-year follow-up. The ICER continued to improve as compared to the five-year values ($20,569 vs. $44,033).
Open Access
Have We Made Advancements in Optimizing Surgical Outcomes and Enhancing Recovery for Patients With High-Risk Adult Spinal Deformity Over Time?
(Oper Neurosurg (Hagerstown), 2024-11-04) Passias, Peter G; Passfall, Lara; Tretiakov, Peter S; Das, Ankita; Onafowokan, Oluwatobi O; Smith, Justin S; Lafage, Virginie; Lafage, Renaud; Line, Breton; Gum, Jeffrey; Kebaish, Khaled M; Than, Khoi D; Mundis, Gregory; Hostin, Richard; Gupta, Munish; Eastlack, Robert K; Chou, Dean; Forman, Alexa; Diebo, Bassel; Daniels, Alan H; Protopsaltis, Themistocles; Hamilton, D Kojo; Soroceanu, Alex; Pinteric, Raymarla; Mummaneni, Praveen; Kim, Han Jo; Anand, Neel; Ames, Christopher P; Hart, Robert; Burton, Douglas; Schwab, Frank J; Shaffrey, Christopher; Klineberg, Eric O; Bess, Shay; International Spine Study Group
BACKGROUND AND OBJECTIVES: The spectrum of patients requiring adult spinal deformity (ASD) surgery is highly variable in baseline (BL) risk such as age, frailty, and deformity severity. Although improvements have been realized in ASD surgery over the past decade, it is unknown whether these carry over to high-risk patients. We aim to determine temporal differences in outcomes at 2 years after ASD surgery in patients stratified by BL risk. METHODS: Patients ≥18 years with complete pre- (BL) and 2-year (2Y) postoperative data from 2009 to 2018 were categorized as having undergone surgery from 2009 to 2013 [early] or from 2014 to 2018 [late]. High-risk [HR] patients met ≥2 of the criteria: (1) ++ BL pelvic incidence and lumbar lordosis or SVA by Scoliosis Research Society (SRS)-Schwab criteria, (2) elderly [≥70 years], (3) severe BL frailty, (4) high Charlson comorbidity index, (5) undergoing 3-column osteotomy, and (6) fusion of >12 levels, or >7 levels for elderly patients. Demographics, clinical outcomes, radiographic alignment targets, and complication rates were assessed by time period for high-risk patients. RESULTS: Of the 725 patients included, 52% (n = 377) were identified as HR. 47% (n = 338) had surgery pre-2014 [early], and 53% (n = 387) underwent surgery in 2014 or later [late]. There was a higher proportion of HR patients in Late group (56% vs 48%). Analysis by early/late status showed no significant differences in achieving improved radiographic alignment by SRS-Schwab, age-adjusted alignment goals, or global alignment and proportion proportionality by 2Y (all P > .05). Late/HR patients had significantly less poor clinical outcomes per SRS and Oswestry Disability Index (both P < .01). Late/HR patients had fewer complications (63% vs 74%, P = .025), reoperations (17% vs 30%, P = .002), and surgical infections (0.9% vs 4.3%, P = .031). Late/HR patients had lower rates of early proximal junctional kyphosis (10% vs 17%, P = .041) and proximal junctional failure (11% vs 22%, P = .003). CONCLUSION: Despite operating on more high-risk patients between 2014 and 2018, surgeons effectively reduced rates of complications, mechanical failures, and reoperations, while simultaneously improving health-related quality of life.
Open Access
Prevalence and Prognosis of Coronal Malalignment Following Lateral Lumbar Interbody Fusion for Minimally Invasive Treatment of Adult Spinal Deformity.
(Spine, 2024-11) Chan, Andrew K; Sampath, Shailen G; Mummaneni, Praveen V; Park, Paul; Uribe, Juan S; Turner, Jay D; Le, Vivian P; Eastlack, Robert K; Fessler, Richard G; Than, Khoi D; Fu, Kai-Ming; Wang, Michael Y; Kanter, Adam S; Okonkwo, David O; Nunley, Pierce D; Anand, Neel; Mundis, Gregory M; Passias, Peter G; Bess, Shay; Shaffrey, Christopher I; Chou, Dean; International Spine Study Group
Study design
Retrospective analysis of prospective multicenter adult spinal deformity (ASD) database.
Objective
To determine the prevalence and prognosis of postoperative coronal malalignment following LLIF for ASD with Qiu type A coronal alignment.
Summary of background data
Qiu Type A coronal alignment is defined as coronal vertical axis (CVA) <30mm.1 There is concern that circumferential minimally invasive surgery (cMIS) with lateral lumbar interbody fusion (LLIF) is associated with postoperative coronal malalignment in ASD with preoperative Qiu type A patients.
Methods
Qui type A patients undergoing cMIS with LLIF for ASD were included, with ASD defined with at least: maximum CC≥20°, SVA>5 cm, PI-LL≥10°, or PT>20°. Two year (2Y) clinical outcomes were compared for type A with 2Y CVA≥30 mm (MAL) versus <30 mm (ALIGN) and were adjusted for factors reaching P<0.05 on univariate comparisons (age, BMI, and ODI).
Results
43 patients met inclusion criteria, of which 12 (27.9%) developed coronal malalignment and 31 (72.1%) remained coronally aligned at 2Y. At baseline, MAL were older (73.0 vs. 69.0, P=0.045), had a lower BMI (26.09 vs. 29.45, P=0.047), and were less disabled (ODI 42.83 vs. 51.69, P=0.016). Otherwise, the groups were well-matched for baseline characteristics. At 2Y, MAL had a greater 2Y SVA (mean 54.08 vs 19.00 mm, P=0.01). Clinically, MAL was associated with inferior 2Y SF-36 PCS (34.78 vs. 37.42, adj P=0.043) and 2Y SRS-22r function/activity domain (3.03 vs. 3.36, adj P=0.040), but otherwise similar in other patient-reported-outcome-metrics (adj P>0.05 for all). 2Y complications were similar between groups, including for reoperations and major and minor complications (adj P>0.05 for all).
Conclusions
In Qui type A patients undergoing cMIS with LLIF for ASD, 27.9% develop coronal malalignment, which was associated with worse SF-36 PCS and SRS-22r function/activity. Despite radiographic malalignment, malalignment was not associated with higher 2-year complication rates including reoperations.
Open Access
Proximal Lumbar Anterior Column Realignment for Iatrogenic Sagittal Plane Adult Spinal Deformity Correction: A Retrospective Case Series.
(World neurosurgery, 2024-11) Frerich, Jason M; Dibble, Christopher F; Park, Christine; Bergin, Stephen M; Goodwin, C Rory; Abd-El-Barr, Muhammad M; Shaffrey, Christopher I; Than, Khoi D
Background
Anterior column realignment (ACR) is a powerful minimally invasive surgery technique to restore sagittal alignment in adult spinal deformity (ASD). This can accomplish similar segmental lordosis restoration as 3-column osteotomy with less blood loss and comparable complication rates. ACR can be performed at adjacent disease segments in the proximal lumbar spine in revision cases. However, two thirds of physiologic lordosis occurs between L4-S1, and concerns remain about altered lumbar morphology. We evaluated patients who underwent proximal lumbar ACR for iatrogenic flatback deformity.
Methods
A total of 19 consecutive patients who underwent L1-2 or L2-3 ACR were retrospectively analyzed. All patients were treated with lateral minimally invasive surgery interbody technique, followed by posterior reconstruction with Smith-Peterson osteotomy. Preoperative and postoperative radiographic and clinical outcomes were obtained.
Results
Mean follow-up was 19 months. All but 1 patient had a history of prior lumbar or lumbo-sacral fusion. Sagittal vertical axis and pelvic incidence-lumbar lordosis decreased from 11.9 cm to 6.1 cm (P < 0.0001) and 34.2° to 12.8° (P < 0.0001). Segmental lordosis increased from -2.7° to 21.9° (P < 0.0001). Proximal lumbar lordosis increased from -0.4° to 22.6° (P < 0.0001), and lordosis distribution index decreased from 79.5% to 48.9% (P < 0.0001). Mean Oswestry Disability Index and numeric pain rating scale back pain scores decreased from 58.0 to 36.2 (P = 0.0041) and 7.9 to 3.4 (P < 0.0001), respectively. Patient-Reported Outcomes Measurement Information System Physical and Mental Health T-scores increased from 34.1 to 43.3 (P = 0.0049) and 40.4 to 45.0 (P = 0.0993), respectively. Major complication rate was 15.8%. One patient required revision for mechanical failure. There were no permanent neurological or vascular injuries.
Conclusions
Proximal lumbar ACR plus Smith-Peterson osteotomy can achieve sagittal correction with low major complication rates in patients with ASD and prior distal fusion. Differentially increasing proximal lumbar lordosis and lowering lumbar distribution index did not have deleterious effects on radiographic or clinical outcomes. Further work is needed to understand the effect of proximal ACR in the surgical management of ASD.
Open Access
When is staging complex adult spinal deformity advantageous? Identifying subsets of patients who benefit from staged interventions.
(Journal of neurosurgery. Spine, 2024-11) Passias, Peter G; Tretiakov, Peter; Onafowokan, Oluwatobi O; Das, Ankita; Lafage, Renaud; Smith, Justin S; Line, Breton G; Nayak, Pratibha; Diebo, Bassel; Daniels, Alan H; Gum, Jeffrey L; Hamilton, D Kojo; Buell, Thomas J; Soroceanu, Alex; Scheer, Justin K; Eastlack, Robert K; Mullin, Jeffrey P; Schoenfeld, Andrew J; Mundis, Gregory M; Hosogane, Naobumi; Yagi, Mitsuru; Mummaneni, Praveen V; Chou, Dean; Fu, Kai-Ming; Than, Khoi D; Anand, Neel; Okonkwo, David O; Wang, Michael Y; Klineberg, Eric; Kebaish, Khaled M; Lewis, Stephen; Hostin, Richard; Gupta, Munish; Lenke, Lawrence; Kim, Han Jo; Ames, Christopher P; Shaffrey, Christopher I; Bess, Shay; Schwab, Frank; Lafage, Virginie; Burton, Douglas
Objective
The objective of this study was to identify baseline patient and surgical factors predictive of optimal outcomes in staged versus same-day combined-approach surgery.
Methods
Adult spinal deformity (ASD) patients with baseline and perioperative (by 6 weeks) data were stratified based on single-stage (same-day) or multistage (staged) surgery, excluding planned multiple hospitalizations. Means comparison analyses were used to assess baseline demographic, radiographic, and surgical differences between cohorts. Backstep logistic regression and conditional inference tree analysis were used to identify variable thresholds associated with study-specific definitions of an optimal outcome in each cohort, defined as no intraoperative or surgery-related in-hospital adverse event.
Results
There were 439 patients with complex ASD in the dataset (mean age 64.0 ± 9.3 years, 68% female, mean BMI 28.7 ± 5.5 kg/m2). Overall, 58.8% of patients were in the same-day group, while 41.2% were in the staged group. Demographically, cohorts were not significantly different (p > 0.05), but staged patients were more frail per total Edmonton Frail Scale score (p = 0.043). Staged patients also reported greater numeric rating scale scores for back pain than same-day patients (p = 0.002). Cohorts were comparable in magnitude of planned correction of C7-S1 sagittal vertical axis, pelvic incidence-lumbar lordosis (PI-LL) mismatch, and T4-12 kyphosis (all p > 0.05). Controlling for baseline age, frailty, and number of levels fused, staged patients reported significantly higher PROMIS Discretionary Social Activities scores by 6 weeks (p = 0.029). Radiographic outcomes by 6 weeks were comparable between cohorts, in terms of both magnitude of change from baseline and overall result (all p > 0.05). Same-day patients were significantly more likely to experience in-hospital complications (p = 0.013). When considering frailty thresholds for staging, only a Charlson Comorbidity Index ≤ 1.0 was associated with optimal outcome in same-day patients, while Edmonton Frail Scale score ≥ 7 (p = 0.036), ≥ 9 levels fused (p = 0.016), and baseline PI-LL mismatch ≥ 15.3° (p = 0.028) were associated with optimal outcome for staged patients. Yet, staging alone was not significantly associated with an optimal outcome perioperatively (p = 0.056).
Conclusions
While staged and same-day combined-approach surgeries yield comparable radiographic and patient-reported outcomes, certain subsets of complex ASD patients may benefit from staged surgery despite the invariably increased hospital length of stay. Individuals with increased frailty, moderate to severe PI-LL mismatch, and increased anticipated number of levels fused may experience a lower risk of perioperative adverse events if they undergo a staged procedure. Clinical trial registration no.: NCT04194138 (ClinicalTrials.gov).
Unknown
Small Extracellular Vesicle-Associated MiRNAs in Polarized Retinal Pigmented Epithelium.
(Investigative ophthalmology & visual science, 2024-11) Hernandez, Belinda J; Strain, Madison; Suarez, Maria Fernanda; Stamer, W Daniel; Ashley-Koch, Allison; Liu, Yutao; Klingeborn, Mikael; Bowes Rickman, Catherine
Purpose
Oxidative stress in the retinal pigmented epithelium (RPE) has been implicated in age-related macular degeneration by impacting endocytic trafficking, including the formation, content, and secretion of extracellular vesicles (EVs). Using our model of polarized primary porcine RPE (pRPE) cells under chronic subtoxic oxidative stress, we tested the hypothesis that RPE miRNAs packaged into EVs are secreted in a polarized manner and contribute to maintaining RPE homeostasis.
Methods
Small EVs (sEVs) enriched for exosomes were isolated from apical and basal conditioned media from pRPE cells grown for up to four weeks with or without low concentrations of hydrogen peroxide using two sEV isolation methods, leading to eight experimental groups. The sEV miRNA expression was profiled using miRNA-Seq with Illumina MiSeq, followed by quality control and bioinformatics analysis for differential expression using the R computing environment. Expression of selected miRNAs were validated using qRT-PCR.
Results
We identified miRNA content differences carried by sEVs isolated using two ultracentrifugation-based methods. Regardless of the sEV isolation method, miR-182 and miR-183 were enriched in the cargo of apically secreted sEVs, and miR-122 in the cargo of basally secreted sEVs from RPE cells during normal homeostatic conditions. After oxidative stress, miR-183 levels were significantly decreased in the cargo of apically released sEVs from stressed RPE cells.
Conclusions
We curated RPE sEV miRNA datasets based on cell polarity and oxidative stress. Unbiased miRNA analysis identified differences based on polarity, stress, and sEV isolation methods. These findings suggest that miRNAs in sEVs may contribute to RPE homeostasis and function in a polarized manner.
Unknown
Philibert de l’Orme’s Divine Proportions and the Composition of the Premier tome de l’Architecture
(Architectural Histories, 2014) Galletti, S
Open Access
Philibert de L’Orme’s Dome in the Chapel of the Château d’Anet: The Role of Stereotomy
(Architectural History, 2021) Galletti, Sara
Open Access
Natural history of adult spinal deformity: how do patients with suboptimal surgical outcomes fare relative to nonoperative counterparts?
(Journal of neurosurgery. Spine, 2023-07) Passias, Peter G; Joujon-Roche, Rachel; Mir, Jamshaid M; Williamson, Tyler K; Tretiakov, Peter S; Imbo, Bailey; Krol, Oscar; Passfall, Lara; Ahmad, Salman; Lebovic, Jordan; Owusu-Sarpong, Stephane; Lanre-Amos, Tomi; Protopsaltis, Themistocles; Lafage, Renaud; Lafage, Virginie; Park, Paul; Chou, Dean; Mummaneni, Praveen V; Fu, Kai-Ming G; Than, Khoi D; Smith, Justin S; Janjua, M Burhan; Schoenfeld, Andrew J; Diebo, Bassel G; Vira, Shaleen
Objective
Management of adult spinal deformity (ASD) has increasingly favored operative intervention; however, the incidence of complications and reoperations is high, and patients may fail to achieve idealized postsurgical results. This study compared health-related quality of life (HRQOL) metrics between patients with suboptimal surgical outcomes and those who underwent nonoperative management as a proxy for the natural history (NH) of ASD.
Methods
ASD patients with 2-year data were included. Patients who were offered surgery but declined were considered nonoperative (i.e., NH) patients. Operative patients with suboptimal outcome (SOp)-defined as any reoperation, major complication, or ≥ 2 severe Scoliosis Research Society (SRS)-Schwab modifiers at follow-up-were selected for comparison. Propensity score matching (PSM) on the basis of baseline age, deformity, SRS-22 Total, and Charlson Comorbidity Index score was used to match the groups. ANCOVA and stepwise logistic regression analysis were used to assess outcomes between groups at 2 years.
Results
In total, 441 patients were included (267 SOp and 174 NH patients). After PSM, 142 patients remained (71 SOp 71 and 71 NH patients). At baseline, the SOp and NH groups had similar demographic characteristics, HRQOL, and deformity (all p > 0.05). At 2 years, ANCOVA determined that NH patients had worse deformity as measured with sagittal vertical axis (36.7 mm vs 21.3 mm, p = 0.025), mismatch between pelvic incidence and lumbar lordosis (11.9° vs 2.9°, p < 0.001), and pelvic tilt (PT) (23.1° vs 20.7°, p = 0.019). The adjusted regression analysis found that SOp patients had higher odds of reaching the minimal clinically important differences in Oswestry Disability Index score (OR [95% CI] 4.5 [1.7-11.5], p = 0.002), SRS-22 Activity (OR [95% CI] 3.2 [1.5-6.8], p = 0.002), SRS-22 Pain (OR [95% CI] 2.8 [1.4-5.9], p = 0.005), and SRS-22 Total (OR [95% CI] 11.0 [3.5-34.4], p < 0.001).
Conclusions
Operative patients with SOp still experience greater improvements in deformity and HRQOL relative to the progressive radiographic and functional deterioration associated with the NH of ASD. The NH of nonoperative management should be accounted for when weighing the risks and benefits of operative intervention for ASD.
Open Access
Should Global Realignment Be Tailored to Frailty Status for Patients Undergoing Surgical Intervention for Adult Spinal Deformity?
(Spine, 2023-07) Passias, Peter G; Williamson, Tyler K; Krol, Oscar; Tretiakov, Peter S; Joujon-Roche, Rachel; Imbo, Bailey; Ahmad, Salman; Bennett-Caso, Claudia; Owusu-Sarpong, Stephane; Lebovic, Jordan B; Robertson, Djani; Vira, Shaleen; Dhillon, Ekamjeet; Schoenfeld, Andrew J; Janjua, Muhammad B; Raman, Tina; Protopsaltis, Themistocles S; Maglaras, Constance; O'Connell, Brooke; Daniels, Alan H; Paulino, Carl; Diebo, Bassel G; Smith, Justin S; Schwab, Frank J; Lafage, Renaud; Lafage, Virginie
Study design
Retrospective cohort study.
Objective
Assess whether modifying spinal alignment goals to accommodate frailty considerations will decrease mechanical complications and maximize clinical outcomes.
Summary of background data
The Global Alignment and Proportion (GAP) score was developed to assist in reducing mechanical complications, but has had less success predicting such events in external validation. Higher frailty and many of its components have been linked to the development of implant failure. Therefore, modifying the GAP score with frailty may strengthen its ability to predict mechanical complications.
Materials and methods
We included 412 surgical ASD patients with two-year follow-up. Frailty was quantified using the modified Adult Spinal Deformity Frailty Index (mASD-FI). Outcomes: proximal junctional kyphosis and proximal junctional failure (PJF), major mechanical complications, and "Best Clinical Outcome" (BCO), defined as Oswestry Disability Index<15 and Scoliosis Research Society 22-item Questionnaire Total>4.5. Logistic regression analysis established a six-week score based on GAP score, frailty, and Oswestry Disability Index US Norms. Logistic regression followed by conditional inference tree analysis generated categorical thresholds. Multivariable logistic regression analysis controlling for confounders was used to assess the performance of the frailty-modified GAP score.
Results
Baseline frailty categories: 57% not frail, 30% frail, 14% severely frail. Overall, 39 of patients developed proximal junctional kyphosis, 8% PJF, 21% mechanical complications, 22% underwent reoperation, and 15% met BCO. The mASD-FI demonstrated a correlation with developing PJF, mechanical complications, undergoing reoperation, and meeting BCO at two years (all P <0.05). Regression analysis generated the following equation: Frailty-Adjusted Realignment Score (FAR Score)=0.49×mASD-FI+0.38×GAP Score. Thresholds for the FAR score (0-13): proportioned: <3.5, moderately disproportioned: 3.5-7.5, severely disproportioned: >7.5. Multivariable logistic regression assessing FAR score demonstrated associations with mechanical complications, reoperation, and meeting BCO by two years (all P <0.05), whereas the original GAP score was only significant for reoperation.
Conclusion
This study demonstrated adjusting alignment goals in adult spinal deformity surgery for a patient's baseline frailty status and disability may be useful in minimizing the risk of complications and adverse events, outperforming the original GAP score in terms of prognostic capacity.
Level of evidence
III.
Open Access
Surgical costs in adult cervical Deformity: Do higher cost surgeries lead to better Outcomes?
(Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 2023-07) Joujon-Roche, Rachel; Dave, Pooja; Tretiakov, Peter; Mcfarland, Kimberly; Mir, Jamshaid; Williamson, Tyler K; Imbo, Bailey; Krol, Oscar; Lebovic, Jordan; Schoenfeld, Andrew J; Vira, Shaleen; Passias, Peter G
Background
As our focus on delivering cost effective healthcare increases, interventions like cervical deformity surgery, which are associated with high resource utilization, have received greater scrutiny. The purpose of this study was to assess relationship between surgical costs, deformity correction, and patient reported outcomes in ACD surgery.
Methods
ACD Patients ≥ 18 years with baseline (BL) and 2-year (2Y) data were included. Cost of surgery was calculated by applying average Medicare reimbursement rates by CPT code to surgical details of each patient in the cohort. CPT codes for corpectomy, ACDF, osteotomy, decompression, levels fused, and instrumentation were considered in the analysis. Costs of complications and reoperations were intentionally excluded from the cost analysis. Patients were ranked into two groups by surgical cost: lowest cost (LC) and highest cost (HC). ANCOVA assessed differences in outcomes while accounting for covariates as appropriate.
Results
113 met inclusion criteria. While mean age, frailty, BMI and gender composition were similar between cost groups, mean CCI was significantly higher in the HC group compared to that of the LC group (p=.014). At baseline, LC and HC groups had similar HRQLs and radiographic deformity (all p >.05). Logistic regression accounting for baseline age, deformity and CCI found that HC patients had significantly lower odds of undergoing reoperation within 2-years (OR: 0.309, 95 % CI: 0.193 - 0.493, p <.001). Furthermore, logistic regression accounting for baseline age, deformity and CCI found odds of DJF were significantly lower for those in the HC group (OR: 0.163, 95 % CI: 0.083 - 0.323, p <.001). At 2-years, logistic regression accounting for age and baseline TS-CL found HC patients still had significantly higher odds of reaching a "0″ TS-CL modifier at 2-years (OR: 3.353, 95 % CI: 1.081 - 10.402, p=.036). Logistic regression accounting for age and baseline NDI score found HC patients had significantly higher odds of reaching MCID in NDI at 2-years (OR: 4.477, 95 % CI: 1.507 - 13.297, p=.007). A similar logistic regression accounting for age and baseline mJOA score found odds of reaching MCID in mJOA significantly higher for high-cost patients (OR: 2.942, 95 % CI: 1.101 - 7.864, p=.031).
Conclusions
While patient presentation influences surgical planning and costs, this study attempted to control for such variations to assess impact of surgical costs on outcomes. Despite continued scrutiny over healthcare costs, we found that more costly surgical interventions can produce superior radiographic alignment as well as patient reported outcomes for patients with cervical deformity.
Open Access
Long-term Morbidity in Patients After Surgical Correction of Adult Spinal Deformity: Results From a Cohort With Minimum 5-year Follow-up.
(Spine, 2023-08) Imbo, Bailey; Williamson, Tyler; Joujon-Roche, Rachel; Krol, Oscar; Tretiakov, Peter; Ahmad, Salman; Bennett-Caso, Claudia; Schoenfeld, Andrew J; Dinizo, Michael; De La Garza-Ramos, Rafael; Janjua, M Burhan; Vira, Shaleen; Ihejirika-Lomedico, Rivka; Raman, Tina; O'Connell, Brooke; Maglaras, Constance; Paulino, Carl; Diebo, Bassel; Lafage, Renaud; Lafage, Virginie; Passias, Peter G
Study design
Retrospective.
Objective
The objective of this study is to describe the rate of postoperative morbidity before and after two-year (2Y) follow-up for patients undergoing surgical correction of adult spinal deformity (ASD).
Summary of background data
Advances in modern surgical techniques for deformity surgery have shown promising short-term clinical results. However, the permanence of radiographic correction, mechanical complications, and revision surgery in ASD surgery remains a clinical challenge. Little information exists on the incidence of long-term morbidity beyond the acute postoperative window.
Methods
ASD patients with complete baseline and five-year (5Y) health-related quality of life and radiographic data were included. The rates of adverse events, including proximal junctional kyphosis (PJK), proximal junctional failure (PJF), and reoperations up to 5Y were documented. Primary and revision surgeries were compared. We used logistic regression analysis to adjust for demographic and surgical confounders.
Results
Of 118 patients eligible for 5Y follow-up, 99(83.9%) had complete follow-up data. The majority were female (83%), mean age 54.1 years and 10.4 levels fused and 14 undergoing three-column osteotomy. Thirty-three patients had a prior fusion and 66 were primary cases. By 5Y postop, the cohort had an adverse event rate of 70.7% with 25 (25.3%) sustaining a major complication and 26 (26.3%) receiving reoperation. Thirty-eight (38.4%) developed PJK by 5Y and 3 (4.0%) developed PJF. The cohort had a significantly higher rate of complications (63.6% vs. 19.2%), PJK (34.3% vs. 4.0%), and reoperations (21.2% vs. 5.1%) before 2Y, all P <0.01. The most common complications beyond 2Y were mechanical complications.
Conclusions
Although the incidence of adverse events was high before 2Y, there was a substantial reduction in longer follow-up indicating complications after 2Y are less common. Complications beyond 2Y consisted mostly of mechanical issues.
Open Access
Outcomes of Surgical Treatment for Patients With Mild Scoliosis and Age-Appropriate Sagittal Alignment With Minimum 2-Year Follow-up.
(Neurospine, 2023-09) Scheer, Justin K; Smith, Justin S; Passias, Peter G; Kim, Han Jo; Bess, Shay; Burton, Douglas C; Klineberg, Eric O; Lafage, Virginie; Gupta, Munish; Ames, Christopher P; International Spine Study Group
Objective
The goal of this study was to determine if patients with mild scoliosis and age-appropriate sagittal alignment have favorable outcomes following surgical correction.
Methods
Retrospective review of a prospective, multicenter adult spinal deformity database. Inclusion criteria: operative patients age ≥18 years, and preoperative pelvic tilt, mismatch between pelvic incidence and lumbar lordosis (PI-LL), and C7 sagittal vertical axis all within established age-adjusted thresholds with minimum 2-year follow-up. Health-related quality of life (HRQoL) scores: Oswestry Disability Index (ODI), 36-item Short Form health survey (SF-36), Scoliosis Research Society-22R (SRS22R), back/leg pain Numerical Rating Scale and minimum clinically important difference (MCID)/substantial clinical benefit (SCB). Two-year and preoperative HRQoL radiographic data were compared. Patients with mild scoliosis (Mild Scoli, Max coronal Cobb 10°-30°) were compared to those with larger curves (Scoli).
Results
One hundred fifty-one patients included from 667 operative patients (82.8% women; average age, 56.4 ± 16.2 years). Forty-two patients (27.8%) included in Mild Scoli group. Mild Scoli group had significantly worse baseline leg pain, ODI, and physical composite scores (p < 0.02). Mean 2-year maximum coronal Cobb angle was significantly improved compared to baseline (p < 0.001). All 2-year HRQoL measures were significantly improved compared to (p < 0.001) except mental composite score, SRS activity and SRS mental for the Mild Scoli group (p > 0.05). From the mild Scoli group, 36%-74% met either MCID or SCB for the HRQoL measures. Sixty-four point three percent had minimum 1 complication, 28.6% had a major complication, 35.7% had reoperation.
Conclusion
Mild scoliosis patients with age-appropriate sagittal alignment benefit from surgical correction, decompression, and stabilization at 2 years postoperative despite having a high complication rate.
Open Access
Impact of Frailty on the Development of Proximal Junctional Failure: Does Frailty Supersede Achieving Optimal Realignment?
(Spine, 2023-10) Krol, Oscar; McFarland, Kimberly; Owusu-Sarpong, Stephane; Sagoo, Navraj; Williamson, Tyler; Joujon-Roche, Rachel; Tretiakov, Peter; Imbo, Bailey; Dave, Pooja; Mir, Jamshaid; Lebovic, Jordan; Onafowokan, Oluwatobi O; Schoenfeld, Andrew J; De la Garza Ramos, Rafael; Janjua, Muhammad Burhan; Sciubba, Daniel M; Diebo, Bassel G; Vira, Shaleen; Smith, Justin S; Lafage, Virginie; Lafage, Renaud; Passias, Peter G
Background
Patients undergoing surgery for adult spinal deformity (ASD) are often elderly, frail, and at elevated risk of adverse events perioperatively, with proximal junctional failure (PJF) occurring relatively frequently. Currently, the specific role of frailty in potentiating this outcome is poorly defined.
Purpose
To determine if the benefits of optimal realignment in ASD, with respect to the development of PJF, can be offset by increasing frailty.
Study design
Retrospective cohort.
Materials and methods
Operative ASD patients (scoliosis >20°, SVA>5 cm, pelvic tilt>25°, or TK>60°) fused to the pelvis or below with available baseline and 2-year (2Y) radiographic and HRQL data were included. The Miller Frailty Index (FI) was used to stratify patients into 2 categories: Not Frail (FI <3) and Frail (>3). Proximal Junctional Failure (PJF) was defined using the Lafage criteria. "Matched" and "unmatched" refers to ideal age-adjusted alignment postoperatively. Multivariable regression determined the impact of frailty on the development of PJF.
Results
Two hundred eighty-four ASD patients met inclusion criteria [62.2yrs±9.9, 81%F, BMI: 27.5 kg/m 2 ±5.3, ASD-FI: 3.4±1.5, Charlson Comorbidity Index (CCI): 1.7±1.6]. Forty-three percent of patients were characterized as Not Frail (NF) and 57% were characterized as Frail (F). PJF development was lower in the NF group compared with the F group (7% vs . 18%; P =0.002). F patients had 3.2 × higher risk of PJF development compared to NF patients (OR: 3.2, 95% CI: 1.3-7.3, P =0.009). Controlling for baseline factors, F unmatched patients had a higher degree of PJF (OR: 1.4, 95% CI:1.02-1.8, P =0.03); however, with prophylaxis, there was no increased risk. Adjusted analysis shows F patients, when matched postoperatively in PI-LL, had no significantly higher risk of PJF.
Conclusions
An increasingly frail state is significantly associated with the development of PJF after corrective surgery for ASD. Optimal realignment may mitigate the impact of frailty on eventual PJF. Prophylaxis should be considered in frail patients who do not reach ideal alignment goals.
Open Access
Predictors of reoperation for spinal disorders in Chiari malformation patients with prior surgical decompression.
(Journal of craniovertebral junction & spine, 2023-10) Onafowokan, Oluwatobi O; Das, Ankita; Mir, Jamshaid M; Alas, Haddy; Williamson, Tyler K; Mcfarland, Kimberly; Varghese, Jeffrey; Naessig, Sara; Imbo, Bailey; Passfall, Lara; Krol, Oscar; Tretiakov, Peter; Joujon-Roche, Rachel; Dave, Pooja; Moattari, Kevin; Owusu-Sarpong, Stephane; Lebovic, Jordan; Vira, Shaleen; Diebo, Bassel; Lafage, Virginie; Passias, Peter Gust
Background
Chiari malformation (CM) is a cluster of related developmental anomalies of the posterior fossa ranging from asymptomatic to fatal. Cranial and spinal decompression can help alleviate symptoms of increased cerebrospinal fluid pressure and correct spinal deformity. As surgical intervention for CM increases in frequency, understanding predictors of reoperation may help optimize neurosurgical planning.
Materials and methods
This was a retrospective analysis of the prospectively collected Healthcare Cost and Utilization Project's California State Inpatient Database years 2004-2011. Chiari malformation Types 1-4 (queried with ICD-9 CM codes) with associated spinal pathologies undergoing stand-alone spinal decompression (queried with ICD-9 CM procedure codes) were included. Cranial decompressions were excluded.
Results
One thousand four hundred and forty-six patients (29.28 years, 55.6% of females) were included. Fifty-eight patients (4.01%) required reoperation (67 reoperations). Patients aged 40-50 years had the most reoperations (11); however, patients aged 15-20 years had a significantly higher reoperation rate than all other groups (15.5% vs. 8.2%, P = 0.048). Female gender was significantly associated with reoperation (67.2% vs. 55.6%, P = 0.006). Medical comorbidities associated with reoperation included chronic lung disease (19% vs. 6.9%, P < 0.001), iron deficiency anemia (10.3% vs. 4.1%, P = 0.024), and renal failure (3.4% vs. 0.9%, P = 0.05). Associated significant cluster anomalies included spina bifida (48.3% vs. 34.8%, P = 0.035), tethered cord syndrome (6.9% vs. 2.1%, P = 0.015), syringomyelia (12.1% vs. 5.9%, P = 0.054), hydrocephalus (37.9% vs. 17.7%, P < 0.001), scoliosis (13.8% vs. 6.4%, P = 0.028), and ventricular septal defect (6.9% vs. 2.3%, P = 0.026).
Conclusions
Multiple medical and CM-specific comorbidities were associated with reoperation. Addressing them, where possible, may aid in improving CM surgery outcomes.