RESUMEN
Intervertebral disc degeneration is a leading cause of chronic low back pain. Cell-based strategies that seek to treat disc degeneration by regenerating the central nucleus pulposus (NP) hold significant promise, but key challenges remain. One of these is the inability of therapeutic cells to effectively mimic the performance of native NP cells, which are unique amongst skeletal cell types in that they arise from the embryonic notochord. In this study, we use single cell RNA sequencing to demonstrate emergent heterogeneity amongst notochord-derived NP cells in the postnatal mouse disc. Specifically, we established the existence of progenitor and mature NP cells, corresponding to notochordal and chondrocyte-like cells, respectively. Mature NP cells exhibited significantly higher expression levels of extracellular matrix (ECM) genes including aggrecan, and collagens II and VI, along with elevated transforming growth factor-beta and phosphoinositide 3 kinase-protein kinase B signaling. Additionally, we identified Cd9 as a novel surface marker of mature NP cells, and demonstrated that these cells were localized to the NP periphery, increased in numbers with increasing postnatal age, and co-localized with emerging glycosaminoglycan-rich matrix. Finally, we used a goat model to show that Cd9+ NP cell numbers decrease with moderate severity disc degeneration, suggesting that these cells are associated with maintenance of the healthy NP ECM. Improved understanding of the developmental mechanisms underlying regulation of ECM deposition in the postnatal NP may inform improved regenerative strategies for disc degeneration and associated low back pain.
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Degeneración del Disco Intervertebral , Disco Intervertebral , Dolor de la Región Lumbar , Núcleo Pulposo , Ratones , Animales , Núcleo Pulposo/metabolismo , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/metabolismo , Disco Intervertebral/metabolismo , Notocorda/metabolismo , Dolor de la Región Lumbar/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Análisis de Secuencia de ARNRESUMEN
OBJECTIVE: To isolate the impact of subsumed surgery (a shorter procedure completed entirely during overlapping non-critical portions of a longer antecedent procedure) on patient outcomes. SUMMARY BACKGROUND DATA: The American College of Surgeons recently recommended the elimination of "concurrent surgery" with overlap during a procedure's critical portions. Guidelines for non-concurrent overlap have been established, but the safety of subsumed surgery remains to be examined. METHODS: All consecutive procedures from 2013 to 2021 within a multihospital academic medical center were included (n=871,441). Simple logistic regression was performed to compare postoperative events between patients undergoing non-overlap surgery (n=533,032) and completely subsumed surgery (n=11,319). Thereafter, coarsened exact matching was used to match patients with non-overlap and subsumed surgery 1:1 on CPT code, 18 demographic features, baseline health characteristics, and procedural variables (n=7,146). Exact-matched cases were subsequently limited to pairs performed by the same surgeon (n=5,028). Primary outcomes included 30-day readmission, ED visits, and reoperations. RESULTS: Univariate analysis suggested that subsumed surgery had a higher 30-day risk of readmission (OR 1.55, P<0.0001), ED evaluation (OR 1.19, P<0.0001), and reoperation (OR 1.98, P<0.0001). When comparison was limited to the exact same procedure and patients were matched on demographics and health characteristics, there were no outcome differences between patients with subsumed surgery and non-overlapping surgery, even when limiting analyses to the same surgeon. CONCLUSIONS: Similar surgeries for similar patients result in similar outcomes whether there is completely subsumed or no overlap. Individual surgeons performing a specific procedure have no outcome differences with subsumed and non-overlapping cases.
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OBJECTIVE: To conduct a prospective, randomized controlled trial (RCT) of an enhanced recovery after surgery (ERAS) protocol in an elective spine surgery population. BACKGROUND: Surgical outcomes such as length of stay (LOS), discharge disposition, and opioid utilization greatly contribute to patient satisfaction and societal healthcare costs. ERAS protocols are multimodal, patient-centered care pathways shown to reduce postoperative opioid use, reduced LOS, and improved ambulation; however, prospective ERAS data are limited in spine surgery. METHODS: This single-center, institutional review board-approved, prospective RCT-enrolled adult patients undergoing elective spine surgery between March 2019 and October 2020. Primary outcomes were perioperative and 1-month postoperative opioid use. Patients were randomized to ERAS (n=142) or standard-of-care (SOC; n=142) based on power analyses to detect a difference in postoperative opioid use. RESULTS: Opioid use during hospitalization and the first postoperative month was not significantly different between groups (ERAS 112.2 vs SOC 117.6 morphine milligram equivalent, P =0.76; ERAS 38.7% vs SOC 39.4%, P =1.00, respectively). However, patients randomized to ERAS were less likely to use opioids at 6 months postoperatively (ERAS 11.4% vs SOC 20.6%, P =0.046) and more likely to be discharged to home after surgery (ERAS 91.5% vs SOC 81.0%, P =0.015). CONCLUSION: Here, we present a novel ERAS prospective RCT in the elective spine surgery population. Although we do not detect a difference in the primary outcome of short-term opioid use, we observe significantly reduced opioid use at 6-month follow-up as well as an increased likelihood of home disposition after surgery in the ERAS group.
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Recuperación Mejorada Después de la Cirugía , Trastornos Relacionados con Opioides , Adulto , Humanos , Analgésicos Opioides/uso terapéutico , Columna Vertebral , Satisfacción del Paciente , Tiempo de Internación , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/epidemiología , Estudios RetrospectivosRESUMEN
PURPOSE: Gender is a known social determinant of health which has been linked disparities in medical care. This study intends to assess the impact of gender on 90-day and long-term morbidity and mortality outcomes following supratentorial brain tumor resection in a coarsened-exact matched population. MATERIALS AND METHODS: A total of 1970 consecutive patients at a single, university-wide health system undergoing supratentorial brain tumor resection over a six-year period (09 June 2013 to 26 April 2019) were analyzed retrospectively. Coarsened Exact Matching was employed to match patients on key demographic factors including history of prior surgery, smoking status, median household income, American Society of Anesthesiologists (ASA) grade, and Charlson Comorbidity Index (CCI), amongst others. Primary outcomes assessed included readmission, ED visit, unplanned reoperation, and mortality within 90 days of surgery. Long-term outcomes such as mortality and unplanned return to surgery during the entire follow-up period were also recorded. RESULTS: Whole-population regression demonstrated significantly increased mortality throughout the entire follow-up period for the male cohort (p = 0.004, OR = 1.32, 95% CI = 1.09 - 1.59); however, no significant difference was found after coarsened exact matching was performed (p = 0.08). In both the whole-population regression and matched-cohort analysis, no significant difference was observed between gender and readmission, ED visit, unplanned reoperation, or mortality in the 90-day post-operative window, in addition to return to surgery after throughout the entire follow-up period. CONCLUSION: After controlling for confounding variables, female birth gender did not significantly predict any difference in morbidity and mortality outcomes following supratentorial brain tumor resection. Difference between mortality outcomes in the pre-matched population versus the matched cohort suggests the need to better manage the underlying health conditions of male patients in order to prevent future disparities.
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Readmisión del Paciente , Neoplasias Supratentoriales , Femenino , Predicción , Humanos , Masculino , Complicaciones Posoperatorias/epidemiología , Reoperación , Estudios Retrospectivos , Neoplasias Supratentoriales/cirugíaRESUMEN
PURPOSE: It is well documented that the interaction between many social factors can affect clinical outcomes. However, the independent effects of economics on outcomes following surgery are not well understood. The goal of this study is to investigate the role socioeconomic status has on postoperative outcomes in a cerebellopontine angle (CPA) tumor resection population. MATERIALS AND METHODS: Over 6 years (07 June 2013 to 24 April 2019), 277 consecutive CPA tumor cases were reviewed at a single, multihospital academic medical center. Patient characteristics obtained included median household income, Charlson Comorbidity Index (CCI), race, BMI, tobacco use, amongst 23 others. Outcomes studied included readmission, ED evaluation, unplanned return to surgery (during and after index admission), return to surgery after index admission, and mortality within 90 days, in addition to reoperation and mortality throughout the entire follow-up period. Univariate analysis was conducted amongst the entire population with significance set at a p value <0.05. The population was divided into quartiles based on median household income and univariate analysis conducted between the lowest (Q1) and highest (Q4) socioeconomic quartiles, with significance set at a p value <0.05. Stepwise regression was conducted to determine the correlations amongst study variables and identify confounding factors. RESULTS: Regression analysis of 273 patients did not find household income to be associated with any of the long-term outcomes assessed. Similarly, a Q1 vs Q4 comparison did not yield significantly different odds of outcomes assessed. CONCLUSION: Although not statistically significant, the odds ratios suggest socioeconomic status may have a clinically significant effect on postsurgical outcomes. Further studies in larger, matched populations are necessary to validate these findings.
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Neuroma Acústico , Hospitalización , Humanos , Neuroma Acústico/cirugía , Procedimientos Neuroquirúrgicos , Readmisión del Paciente , Reoperación , Estudios Retrospectivos , Clase SocialRESUMEN
PURPOSE: Gender is a known social determinant of health (SDOH) that has been linked to neurosurgical outcome disparities. To improve quality of care, there exists a need to investigate the impact of gender on procedure-specific outcomes. The objective of this study was to assess the role of gender on short- and long-term outcomes following resection of meningiomas - the most common benign brain neoplasm of adulthood - between exact matched patient cohorts. MATERIAL AND METHODS: All consecutive patients undergoing supratentorial meningioma resection (n = 349) at a single, university-wide health system over a 6-year period were analyzed retrospectively. Coarsened exact matching was employed to match patients on numerous key characteristics related to outcomes. Primary outcomes included readmission, ED visit, reoperation, and mortality within 30 and 90 days of surgery. Mortality and reoperation were also assessed during the entire follow-up period. Outcomes were compared between matched female and male cohorts. RESULTS: Between matched cohorts, no significant difference was observed in morbidity or mortality at 30 days (p = 0.42-0.75), 90-days (p = 0.23-0.69), or throughout the follow-up period (p = 0.22-0.45). Differences in short-term mortality could not be assessed due to the low number of mortality events. CONCLUSIONS: After matching on characteristics known to impact outcomes and when isolated from other SDOHs, gender does not independently affect morbidity and mortality following meningioma resection. Further research on the role of other SDOHs in this population is merited to better understand underlying drivers of disparity.
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Neoplasias Meníngeas , Meningioma , Neoplasias Supratentoriales , Humanos , Masculino , Femenino , Adulto , Meningioma/cirugía , Meningioma/epidemiología , Estudios Retrospectivos , Reoperación , Neoplasias Supratentoriales/cirugía , Neoplasias Meníngeas/cirugía , Neoplasias Meníngeas/epidemiología , Readmisión del PacienteRESUMEN
OBJECTIVE: Our objective was to determine the impact of total preincision infusion time on surgical site infections (SSIs) and establish an optimal time threshold for subsequent prospective study. BACKGROUND: SSIs remain a major cause of morbidity. Although regulated, the total time of infusion of preincision antibiotics varies widely. Impact of infusion time on SSI risk is poorly understood. METHODS: All consecutive patients (n = 46,791) undergoing inpatient surgical intervention were retrospectively enrolled (2014-2015) and monitored for 1 year. Primary outcomes: the presence of SSI infection as predicted by reduced preoperative antibiotic infusion time. SECONDARY OUTCOMES: preintervention compliance, the impact of a quality improvement algorithm to optimize infusion time compliance. Multivariate logistic regression of the retrospective cohort demonstrated predictors of infection. Receiver-operating characteristic analysis demonstrated the timing threshold predictive of infection. Cost impact of avoidable infections was analyzed. RESULTS: Only 36.1% of patients received preincision infusion of vancomycin in compliance with national and institutional standards (60-120âmin). Cephalosporin infusion times were 53 times more likely to be compliant [odds ratio (OR) 53.33, P < 0.001]. Vancomycin infusion times that were not compliant with national standards (less than standard 60-120âmin) did not predict infection. However, significantly noncompliant, reduced preincision infusion time, significantly predicted SSI (<24.6âmin infusion, AUC = 0.762). Vancomycin infusion, initiated too close to surgical incision, predicted increased SSI (OR = 4.281, P < 0.001). Implementation of an algorithm to improve infusion time, but not powered to demonstrate infection /reduction, improved vancomycin infusion start time (257% improvement, P < 0.001) and eliminated high-risk infusions (sub-24.6âmin). CONCLUSIONS: Initially, vancomycin infusion rarely met national guidelines; however, minimal compliance breach was not associated with SSI implications. The retrospective data here suggest a critical infusion time for infection reduction (24.6 min before incision). Prospective implementation of an algorithm led to 100% compliance. These data suggest that vancomycin administration timing should be studied prospectively.
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Antibacterianos/administración & dosificación , Profilaxis Antibiótica , Infección de la Herida Quirúrgica/prevención & control , Adulto , Algoritmos , Cefazolina/administración & dosificación , Femenino , Humanos , Infusiones Intravenosas , Masculino , Pennsylvania , Mejoramiento de la Calidad , Estudios Retrospectivos , Factores de Tiempo , Vancomicina/administración & dosificaciónRESUMEN
PURPOSE: This study assessed the ability of the LACE + [Length of stay, Acuity of admission, Charlson Comorbidity Index (CCI) score, and Emergency department visits in the past 6 months] index to predict adverse outcomes after urologic surgery. METHODS: LACE + scores were retrospectively calculated for all consecutive patients (n = 9824) who received urologic surgery at one multi-center health system over 2 years (2016-2018). Coarsened exact matching was employed to sort patient data before analysis; matching criteria included duration of surgery, BMI, and race among others. Outcomes including unplanned hospital readmission, emergency room visits, and reoperation were compared for patients with different LACE + quartiles. RESULTS: 722 patients were matched between Q1 and Q4; 1120 patients were matched between Q2 and Q4; 2550 patients were matched between Q3 and Q4. Higher LACE + score significantly predicted readmission within 90 days (90D) of discharge for Q1 vs Q4 and Q2 vs Q4. Increased LACE + score also significantly predicted 90D emergency room visits for Q1 vs Q4, Q2 vs Q4, and Q3 vs Q4. LACE + score was also significantly predictive of 90D reoperation for Q1 vs Q4. LACE + score did not predict 90D reoperation for Q2 vs Q4 or Q3 vs Q4 or 90D readmission for Q3 vs. Q4. CONCLUSION: These results suggest that LACE + may be a suitable prediction model for important patient outcomes after urologic surgery.
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Tiempo de Internación/estadística & datos numéricos , Readmisión del Paciente/estadística & datos numéricos , Enfermedades Urológicas/cirugía , Procedimientos Quirúrgicos Urológicos , Servicio de Urgencia en Hospital , Predicción , Hospitalización , Humanos , Complicaciones Posoperatorias/epidemiología , Reoperación , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Enfermedades Urológicas/complicacionesRESUMEN
OBJECTIVE: Enhanced recovery after surgery (ERAS) pathways have previously been shown to be feasible and safe in elective spinal procedures. As publications on ERAS pathways have recently emerged in elective neurosurgery, long-term outcomes are limited. We report on our 18-month experience with an ERAS pathway in elective spinal surgery. METHODS: A historical cohort of 149 consecutive patients was identified as the control group, and 1,141 patients were prospectively enrolled in an ERAS protocol. The primary outcome was the need for opioid use one month postoperation. Secondary outcomes were opioid and nonopioid consumption on postoperative day (POD) 1, opioid use at three and six months postoperation, inpatient pain scores, patient satisfaction scores, postoperative Foley catheter use, mobilization/ambulation on POD0-1, length of stay, complications, and intensive care unit admissions. RESULTS: There was significant reduction in use of opioids at one, three, and six months postoperation (38.6% vs 70.5%, P < 0.001, 36.5% vs 70.9%, P < 0.001, and 23.6% vs 51.9%, P = 0.008) respectively. Both groups had similar surgical procedures and demographics. PCA use was nearly eliminated in the ERAS group (1.4% vs 61.6%, P < 0.001). ERAS patients mobilized faster on POD0 compared with control (63.5% vs 20.7%, P < 0.001). Fewer patients in the ERAS group required postoperative catheterization (40.7% vs 32.7%, P < 0.001). The ERAS group also had decreased length of stay (3.4 vs 3.9 days, P = 0.020). CONCLUSIONS: ERAS protocols for all elective spine and peripheral nerve procedures are both possible and effective. This standardized approach to patient care decreases opioid usage, eliminates the use of PCAs, mobilizes patients faster, and reduces length of stay.
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Analgésicos Opioides , Recuperación Mejorada Después de la Cirugía , Analgésicos Opioides/uso terapéutico , Humanos , Tiempo de Internación , Dolor Postoperatorio/tratamiento farmacológico , Nervios Periféricos , Complicaciones Posoperatorias , Estudios RetrospectivosRESUMEN
OBJECTIVE: Assess the safety of overlapping surgery before implementation of new recommendations and regulations. BACKGROUND: Overlapping surgery is a longstanding practice that has not been well studied. There remains a need to analyze data across institutions and specialties to draw well-informed conclusions regarding appropriate application of this practice. METHODS: Coarsened exact matching was used to assess the impact of overlap on outcomes amongst all surgical interventions (n = 61,524) over 1 year (2014) at 1 health system. Overlap was categorized as: any, beginning, or end overlap. Study subjects were matched 1:1 on 11 variables. Serious unanticipated events were studied including unplanned return to operating room, readmission, and mortality. RESULTS: In all, 8391 patients (13.6%) had any overlap and underwent coarsened exact matching. For beginning/end overlap, matched groups were created (total matched population N = 4534/3616 patients, respectively). Any overlap did not predict unanticipated return to surgery (9.8% any overlap vs 10.1% no overlap; P = 0.45). Further, any overlap did not predict an increase in reoperation, readmission, or emergency room (ER) visits at 30 or 90 days (30D reoperation 3.6% vs 3.7%; P = 0.83, 90D reoperation 3.8% vs 3.9%; P = 0.84) (30D readmission 9.9% vs 10.2%; P = 0.45, 90D readmissions 6.9% vs 7.0%; P = 0.90) (30D ER 5.4% vs 5.6%; P = 0.60, 90D ER 4.8% vs 4.7%; P = 0.71). In addition, any overlap was not associated with mortality over the surgical follow-up period (90D mortality 1.7% vs 2.1%; P = 0.06). Beginning/end overlap had results similar to any overlap. CONCLUSION: Overlapping, nonconcurrent surgery is not associated with an increase in reoperation, readmission, ER visits, or unanticipated return to surgery.
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Readmisión del Paciente/estadística & datos numéricos , Seguridad del Paciente/estadística & datos numéricos , Reoperación/estadística & datos numéricos , Procedimientos Quirúrgicos Operativos/métodos , Centros Médicos Académicos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Estudios Retrospectivos , Procedimientos Quirúrgicos Operativos/mortalidad , Procedimientos Quirúrgicos Operativos/normas , Adulto JovenRESUMEN
Nucleotomy is a common surgical procedure and is also performed in ex vivo mechanical testing to model decreased nucleus pulposus (NP) pressurization that occurs with degeneration. Here, we implement novel and noninvasive methods using magnetic resonance imaging (MRI) to study internal 3D annulus fibrosus (AF) deformations after partial nucleotomy and during axial compression by evaluating changes in internal AF deformation at reference loads (50 N) and physiological compressive loads (â¼10% strain). One particular advantage of this methodology is that the full 3D disc deformation state, inclusive of both in-plane and out-of-plane deformations, can be quantified through the use of a high-resolution volumetric MR scan sequence and advanced image registration. Intact grade II L3-L4 cadaveric human discs before and after nucleotomy were subjected to identical mechanical testing and imaging protocols. Internal disc deformation fields were calculated by registering MR images captured in each loading state (reference and compressed) and each condition (intact and nucleotomy). Comparisons were drawn between the resulting three deformation states (intact at compressed load, nucleotomy at reference load, nucleotomy at compressed load) with regard to the magnitude of internal strain and direction of internal displacements. Under compressed load, internal AF axial strains averaged -18.5% when intact and -22.5% after nucleotomy. Deformation orientations were significantly altered by nucleotomy and load magnitude. For example, deformations of intact discs oriented in-plane, whereas deformations after nucleotomy oriented axially. For intact discs, in-plane components of displacements under compressive loads oriented radially outward and circumferentially. After nucleotomy, in-plane displacements were oriented radially inward under reference load and were not significantly different from the intact state at compressed loads. Re-establishment of outward displacements after nucleotomy indicates increased axial loading restores the characteristics of internal pressurization. Results may have implications for the recurrence of pain, design of novel therapeutics, or progression of disc degeneration.
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OBJECTIVE: The objective of this study is to investigate the prevalence and disparity of chronic opioid usage in surgical patients and the potential risk factors associated with chronic opioid usage. BACKGROUND: Chronic opioid usage is common in surgical patients; however, the characteristics of opioid usage in surgical patients is unclear. In this study, we hypothesize that the prevalence of chronic opioid usage in surgical patients is high, and that significant disparities may exist among different surgical populations. METHODS: Data of opioid usage in outpatients among different surgical services were extracted from the electronic medical record database. Patient demographics, clinical characteristics of sex, age, race, body mass index (BMI), specialty visited, duration of opioid use, and opioid type were collected. Chronic opioid users were defined as patients who had been recorded as taking opioids for at least 90 days determined by the first and last visit dates under opioid usage during the investigation. RESULTS: There were 79,123 patients included in this study. The average prevalence is 9.2%, ranging from 4.4% to 23.8% among various specialties. The prevalence in orthopedics (23.8%), neurosurgery (18.7%), and gastrointestinal surgery (14.4%) ranked in the top three subspecialties. Major factors influencing chronic opioid use include age, Ethnicitiy, Subspecialtiy, and multiple specialty visits. Approximately 75% of chronic users took opioids that belong to the category II Drug Enforcement Administration classification. CONCLUSIONS: Overall prevalence of chronic opioid usage in surgical patients is high with widespread disparity among different sex, age, ethnicity, BMI, and subspecialty groups. Information obtained from this study provides clues to reduce chronic opioid usage in surgical patients.
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Analgésicos Opioides/uso terapéutico , Dolor Crónico/tratamiento farmacológico , Dolor Postoperatorio/tratamiento farmacológico , Procedimientos Quirúrgicos Operativos/métodos , Centros Médicos Académicos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Analgésicos Opioides/efectos adversos , Dolor Crónico/fisiopatología , Intervalos de Confianza , Estudios Transversales , Bases de Datos Factuales , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Evaluación de Resultado en la Atención de Salud , Dimensión del Dolor/efectos de los fármacos , Dolor Postoperatorio/diagnóstico , Valor Predictivo de las Pruebas , Prevalencia , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Procedimientos Quirúrgicos Operativos/estadística & datos numéricos , Estados UnidosRESUMEN
The mucopolysaccharidoses (MPS) are a family of lysosomal storage disorders characterized by deficient activity of enzymes that degrade glycosaminoglycans (GAGs). Skeletal disease is common in MPS patients, with the severity varying both within and between subtypes. Within the spectrum of skeletal disease, spinal manifestations are particularly prevalent. Developmental and degenerative abnormalities affecting the substructures of the spine can result in compression of the spinal cord and associated neural elements. Resulting neurological complications, including pain and paralysis, significantly reduce patient quality of life and life expectancy. Systemic therapies for MPS, such as hematopoietic stem cell transplantation and enzyme replacement therapy, have shown limited efficacy for improving spinal manifestations in patients and animal models. Therefore, there is a pressing need for new therapeutic approaches that specifically target this debilitating aspect of the disease. In this review, we examine how pathological abnormalities affecting the key substructures of the spine - the discs, vertebrae, odontoid process and dura - contribute to the progression of spinal deformity and symptomatic compression of neural elements. Specifically, we review current understanding of the underlying pathophysiology of spine disease in MPS, how the tissues of the spine respond to current clinical and experimental treatments, and discuss future strategies for improving the efficacy of these treatments.
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Glicosaminoglicanos/metabolismo , Mucopolisacaridosis/fisiopatología , Enfermedades de la Columna Vertebral/fisiopatología , Terapia de Reemplazo Enzimático , Humanos , Mucopolisacaridosis/terapia , Calidad de Vida , Enfermedades de la Columna Vertebral/terapia , Columna Vertebral/fisiopatologíaRESUMEN
Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder characterized by deficient ß-glucuronidase activity, which leads to the accumulation of incompletely degraded glycosaminoglycans (GAGs). MPS VII patients present with severe skeletal abnormalities, which are particularly prevalent in the spine. Incomplete cartilage-to-bone conversion in MPS VII vertebrae during postnatal development is associated with progressive spinal deformity and spinal cord compression. The objectives of this study were to determine the earliest postnatal developmental stage at which vertebral bone disease manifests in MPS VII and to identify the underlying cellular basis of impaired cartilage-to-bone conversion, using the naturally-occurring canine model. Control and MPS VII dogs were euthanized at 9 and 14 days-of-age, and vertebral secondary ossification centers analyzed using micro-computed tomography, histology, qPCR, and protein immunoblotting. Imaging studies and mRNA analysis of bone formation markers established that secondary ossification commences between 9 and 14 days in control animals, but not in MPS VII animals. mRNA analysis of differentiation markers revealed that MPS VII epiphyseal chondrocytes are unable to successfully transition from proliferation to hypertrophy during this critical developmental window. Immunoblotting demonstrated abnormal persistence of Sox9 protein in MPS VII cells between 9 and 14 days-of-age, and biochemical assays revealed abnormally high intra and extracellular GAG content in MPS VII epiphyseal cartilage at as early as 9 days-of-age. In contrast, assessment of vertebral growth plates and primary ossification centers revealed no significant abnormalities at either age. The results of this study establish that failed vertebral bone formation in MPS VII can be traced to the failure of epiphyseal chondrocytes to undergo hypertrophic differentiation at the appropriate developmental stage, and suggest that aberrant processing of Sox9 protein may contribute to this cellular dysfunction. These results also highlight the importance of early diagnosis and therapeutic intervention to prevent the progression of debilitating skeletal disease in MPS patients.
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Condrocitos/citología , Epífisis/citología , Mucopolisacaridosis VII/complicaciones , Mucopolisacaridosis VII/fisiopatología , Osteogénesis , Animales , Enfermedades Óseas/etiología , Enfermedades Óseas/fisiopatología , Diferenciación Celular , Perros , Glicosaminoglicanos/metabolismo , Humanos , Hipertrofia , Columna Vertebral/fisiología , Microtomografía por Rayos XRESUMEN
Despite the prevalence of disc degeneration and its contributions to low back problems, many current treatments are palliative only and ultimately fail. To address this, nucleus pulposus replacements are under development. Previous work on an injectable hydrogel nucleus pulposus replacement composed of n-carboxyethyl chitosan, oxidized dextran, and teleostean has shown that it has properties similar to native nucleus pulposus, can restore compressive range of motion in ovine discs, is biocompatible, and promotes cell proliferation. The objective of this study was to determine if the hydrogel implant will be contained and if it will restore mechanics in human discs undergoing physiologic cyclic compressive loading. Fourteen human lumbar spine segments were tested using physiologic cyclic compressive loading while intact, following nucleotomy, and again following treatment of injecting either phosphate buffered saline (PBS) (sham, n = 7) or hydrogel (implant, n = 7). In each compressive test, mechanical parameters were measured immediately before and after 10,000 cycles of compressive loading and following a period of hydrated recovery. The hydrogel implant was not ejected from the disc during 10,000 cycles of physiological compression testing and appeared undamaged when discs were bisected following all mechanical tests. For sham samples, creep during cyclic loading increased (+15%) from creep during nucleotomy testing, while for implant samples creep strain decreased (-3%) toward normal. There was no difference in compressive modulus or compressive strains between implant and sham samples. These findings demonstrate that the implant interdigitates with the nucleus pulposus, preventing its expulsion during 10,000 cycles of compressive loading and preserves disc creep within human L5-S1 discs. This and previous studies provide a solid foundation for continuing to evaluate the efficacy of the hydrogel implant.
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Hidrogel de Polietilenoglicol-Dimetacrilato/farmacología , Vértebras Lumbares/efectos de los fármacos , Vértebras Lumbares/fisiología , Agua/metabolismo , Adulto , Anciano , Humanos , Inyecciones , Degeneración del Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/fisiopatología , Vértebras Lumbares/metabolismo , Vértebras Lumbares/fisiopatología , Ensayo de Materiales , Persona de Mediana Edad , Prótesis e Implantes , Soporte de Peso , Adulto JovenRESUMEN
BACKGROUND: Circumferential decompression has been demonstrated to be the first-line therapy for patients with metastatic tumors in the thoracic spine requiring surgical intervention. However, there is significant debate regarding whether these tumors are best accessed anteriorly utilizing a thoracotomy or posteriorly. We used decision analysis to determine which approach yields greater health-related quality of life (QOL). METHODS: We searched Medline, Embase, and the Cochrane Library for relevant articles published between 1990 and 2011 on anterior and posterior approaches to metastatic disease in the thoracic spine. QOL values for major treatment outcomes were determined using the existing literature. Separate models were created for ambulatory and nonambulatory patients. A Monte Carlo simulation and sensitivity analyses were used to determine which treatment strategy resulted in the highest QOL. RESULTS: For ambulatory patients, an anterior approach resulted in a slightly higher QOL, and for nonambulatory patients, a posterior approach was favored, but these differences were not statistically significant. CONCLUSIONS: Using a decision-analytic model, we found no significant difference in QOL resulting from anterior versus posterior approaches to metastatic lesions in the thoracic spine. Decisions should instead be based on surgeon comfort, tumor characteristics, anatomy of the lesion, patient-related factors, and goals of the operation.
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Descompresión Quirúrgica/métodos , Procedimientos de Cirugía Plástica/métodos , Neoplasias de la Columna Vertebral/secundario , Neoplasias de la Columna Vertebral/cirugía , Vértebras Torácicas/cirugía , Toracotomía/métodos , Técnicas de Apoyo para la Decisión , Humanos , Metaanálisis como Asunto , PronósticoRESUMEN
OBJECT: There is significant practice variation and uncertainty as to the value of surgical treatments for lumbar spine disorders. The authors' aim was to establish a multicenter registry to assess the efficacy and costs of common lumbar spinal procedures by using prospectively collected outcomes. METHODS: An observational prospective cohort study was completed at 13 academic and community sites. Patients undergoing single-level fusion for spondylolisthesis or single-level lumbar discectomy were included. The 36-Item Short Form Health Survey (SF-36) and Oswestry Disability Index (ODI) data were obtained preoperatively and at 1, 3, 6, and 12 months postoperatively. Power analysis estimated a sample size of 160 patients: lumbar disc (125 patients) and lumbar listhesis (35 patients). The quality-adjusted life year (QALY) data were calculated using 6-dimension utility index scores. Direct costs and complication costs were estimated using Medicare reimbursement values from 2011, and indirect costs were estimated using the human capital approach with the 2011 US national wage index. Total costs equaled $14,980 for lumbar discectomy and $43,852 for surgery for lumbar spondylolisthesis. RESULTS: There were 198 patients enrolled over 1 year. The mean age was 46 years (49% female) for lumbar discectomy (n = 148) and 58.1 years (60% female) for lumbar spondylolisthesis (n = 50). Ten patients with disc herniation (6.8%) and 1 with listhesis (2%) required repeat operation at 1 year. The overall 1-year follow-up rate was 88%. At 30 days, both lumbar discectomy and single-level fusion procedures were associated with significant improvements in ODI, visual analog scale, and SF-36 scores (p = 0.0002), which persisted at the 1-year evaluation (p < 0.0001). By 1 year, more than 80% of patients in each cohort who were working preoperatively had returned to work. Lumbar discectomy was associated with a gain of 0.225 QALYs over the 1-year study period ($66,578/QALY gained). Lumbar spinal fusion for Grade I listhesis was associated with a gain of 0.195 QALYs over the 1-year study period ($224,420/QALY gained). CONCLUSIONS: This national spine registry demonstrated successful collection of high-quality outcomes data for spinal procedures in actual practice. These data are useful for demonstrating return to work and cost-effectiveness following surgical treatment of single-level lumbar disc herniation or spondylolisthesis. One-year cost per QALY was obtained, and this cost per QALY is expected to improve further by 2 years. This work sets the stage for real-world analysis of the value of health interventions.
Asunto(s)
Análisis Costo-Beneficio/economía , Discectomía/economía , Vértebras Lumbares/cirugía , Sistema de Registros , Fusión Vertebral/economía , Espondilolistesis/economía , Espondilolistesis/cirugía , Adulto , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Espondilolistesis/epidemiologíaRESUMEN
BACKGROUND: Scoliosis causes abnormal spinal curvature and torsional rotation of the vertebrae and has implications for human suffering and societal cost. In differential geometry, Writhe describes three-dimensional curvature. Differential geometric quantities can inform better diagnostic metrics of scoliotic deformity. This evaluation could help physicians and researchers study scoliosis and determine treatments. METHODS: Eight adult lumbar spine CT scans were analyzed in custom MATLAB programs to estimate Writhe and Cobb angle. Five patients exhibited scoliotic curvature, and three controls were asymptomatic. Vertebral centroids in three-dimensional space were determined, and Writhe was approximated. A T-test determined whether the affected spines had greater Writhe than the controls. Cohen's D test was used to determine effect size. RESULTS: Writhe of scoliotic spines (5.4E-4 ± 2.7E-4) was significantly higher than non-scoliotic spines (8.2E-5 ± 1.1E-4; p = 0.008). CONCLUSION: Writhe, a measure of curvature derived from 3D imaging, is significantly greater in scoliotic than in non-scoliotic spines. Future directions must include more subjects and examine writhe as a marker of scoliosis severity, progression, and response to treatment.
Asunto(s)
Escoliosis , Adulto , Humanos , Escoliosis/diagnóstico por imagen , Columna Vertebral , Imagenología Tridimensional/métodos , PredicciónRESUMEN
STUDY DESIGN: Retrospective Matched Cohort Study. OBJECTIVES: Low median household income (MHI) has been correlated with worsened surgical outcomes, but few studies have rigorously controlled for demographic and medical factors at the patient level. This study isolates the relationship between MHI and surgical outcomes in a lumbar fusion cohort using coarsened exact matching. METHODS: Patients undergoing single-level, posterior lumbar fusion at a single institution were consecutively enrolled and retrospectively analyzed (n = 4263). Zip code was cross-referenced to census data to derive MHI. Univariate regression correlated MHI to outcomes. Patients with low MHI were matched to those with high MHI based on demographic and medical factors. Outcomes evaluated included complications, length of stay, discharge disposition, 30- and 90 day readmissions, emergency department (ED) visits, reoperations, and mortality. RESULTS: By univariate analysis, MHI was significantly associated with 30- and 90 day readmission, ED visits, reoperation, and non-home discharge, but not mortality. After exact matching (n = 270), low-income patients had higher odds of non-home discharge (OR = 2.5, P = .016) and higher length of stay (mean 100.2 vs 92.6, P = .02). There were no differences in surgical complications, ED visits, readmissions, or reoperations between matched groups. CONCLUSIONS: Low MHI was significantly associated with adverse short-term outcomes from lumbar fusion. A matched analysis controlling for confounding variables uncovered longer lengths of stay and higher rates of discharge to post-acute care (vs home) in lower MHI patients. Socioeconomic disparities affect health beyond access to care, worsen surgical outcomes, and impose costs on healthcare systems. Targeted interventions must be implemented to mitigate these disparities.
RESUMEN
OBJECTIVE: Race plays a salient role in access to surgical care. However, few investigations have assessed the impact of race within surgical populations after care has been delivered. The objective of this study was to employ an exact matching protocol to a homogenous population of spine surgery patients in order to isolate the relationships between race and short-term postoperative outcomes. METHODS: In total, 4263 consecutive patients who underwent single-level, posterior-only lumbar fusion at a single multihospital academic medical center were retrospectively enrolled. Of these patients, 3406 patients self-identified as White and 857 patients self-identified as non-White. Outcomes were initially compared across all patients via logistic regression. Subsequently, White patients and non-White patients were exactly matched on the basis of key demographic and health characteristics (1520 matched patients). Outcome disparities were evaluated between the exact-matched cohorts. Primary outcomes were readmissions, emergency department (ED) visits, reoperations, mortality, intraoperative complications, and discharge disposition. RESULTS: Before matching, non-White patients were less likely to be discharged home and more likely to be readmitted, evaluated in the ED, and undergo reoperation. After matching, non-White patients experienced higher rates of nonhome discharge, readmissions, and ED visits. Non-White patients did not have more surgical complications either before or after matching. CONCLUSIONS: Between otherwise similar cohorts of spinal fusion cases, non-White patients experienced unfavorable discharge disposition and higher risk of multiple adverse postoperative outcomes. However, these findings were not accounted for by differences in surgical complications, suggesting that structural factors underlie the observed disparities.