Endoscopic Versus Open Carpal Tunnel Release: An Umbrella Review and a Meta-analysis.

INTRODUCTION: Whether endoscopic carpal tunnel release (ECTR) versus open carpal tunnel release (OCTR) has superior outcomes remains a controversial topic. Therefore, we sought to perform an umbrella review and meta-analysis to compare ECTR and OCTR with regards to (1) postoperative functional ability, (2) operative outcomes, and (3) time to return to work. METHODS: A PubMed, Scopus, and Cochrane database search was conducted for all meta-analyses comparing ECTR and OCTR performed between 2000 and 2022 in accordance to PRISMA and Joanna Briggs Institute guidance for umbrella reviews. The primary outcomes were as follows: (1) functional ability-symptoms severity, postoperative grip strength, postoperative pinch strength, 2-point discrimination, and pain; (2) operative outcomes-operation time, total complications, nerve injury, and scar-related complication; and (3) time to return to work. Quality was assessed using the Assessment of Multiple Systematic Reviews. Pooled analysis was performed to compare several clinical outcome measures between groups, depending on the availability of data using Review Manager Version 5.2.11. RESULTS: A total of 9 meta-analyses were included, 5 were of high quality and 4 were moderate quality. For functional ability, ECTR was associated with better pinch strength after 3 months (0.70, 95% confidence interval [CI] = 0.00, 1.40, P = 0.05) and 6 months (0.77, 95% CI = 0.14, 1.40, P = 0.02, I2 = 84%). For return to work, OCTR was associated with longer return to work compared with ECTR (-10.89, 95% CI = -15.14, -6.64, P < 0.00001, I2= 83%). There were no significant differences between OCTR and ECTR in the hand function, symptom severity, grip strength, pain, operation time, and total complications. CONCLUSIONS: In an umbrella review and meta-analysis of ECTR versus OCTR, ECTR was associated with a higher pinch strength, and a shorter time to return to work. Differences in major complications, such as nerve injury, were unclear due to statistical inconsistency and bias.

Resident Salary Compared to Living Wages at United States Training Institutions.

OBJECTIVE: To compare living wages and salaries at US residency programs. SUMMARY BACKGROUND DATA: It is unknown how resident salary compares to living wages across the United States (US). METHODS: Cross-sectional analysis of publicly available resident salary affordability from training centers with post-graduate-year (PGY)-1 through PGY-7 resident compensation for 2022-2023 was compared with the Massachusetts Institute of Technology (MIT) Living-Wage Calculator. Resident salary to living wage ratios were calculated using PGY-4 salary for each family composition. Univariate and multivariable analysis of PGY-4 salary affordability was performed, accounting for proportion of expected living wages to taxes, transportation, housing, healthcare, childcare, and food, as well as unionization and state income-tax. RESULTS: 118 residency programs, representing over 60% of US trainees, were included, 20 (17%) of which were unionized. Single-parent families were unable to earn a living wage until PGY-7. Residents with 1 child in 2-adult (single-income) and 2-adult (dual-income) families earn below living wages until PGY-5 and PGY-3, respectively. Residents with more than 1 child never earn a living wage. Multivariable regression analysis using PGY-4 salary: living wage ratios in single-child, 2-parent homes showed food expense and unionization status were consistent predictors of affordability. Unionization was associated with lower affordability pre-stipend, almost equivalent affordability post-stipend, and lower affordability post-stipend and union dues. CONCLUSIONS: Resident salaries often preclude residents with children from earning a living wage. Unionization is not associated with increased resident affordability in this cross-sectional analysis. All annual reimbursement data should be centrally compiled, and additional stipends should be considered for residents with children.

Who Can Be Discharged Home after Adult Spinal Deformity Surgery?

Introduction: After adult spinal deformity (ASD) surgery, patients often require postoperative rehabilitation at an inpatient rehabilitation (IPR) center or a skilled nursing facility (SNF). However, home discharge is often preferred by patients and hsas been shown to decrease costs. In a cohort of patients undergoing ASD surgery, we sought to (1) report the incidence of discharge to home, (2) determine the factors significantly associated with discharge to home in the form of a simple scoring system, and (3) evaluate the impact of discharge disposition on patient-reported outcome measures (PROMs). Methods: A single-institution, retrospective cohort study was undertaken for patients undergoing ASD surgery from 2009 to 2021. Inclusion criteria were ≥ 5-level fusion, sagittal/coronal deformity, and at least 2-year follow-up. Exposure variables included preoperative, perioperative, and radiographic data. The primary outcome was discharge status (dichotomized as home vs. IPR/SNF). Secondary outcomes included PROMs, such as the numeric rating scales (NRSs) for back and leg pain, the Oswestry Disability Index (ODI), and EQ-5D. A subanalysis comparing IPR to SNF discharge was conducted. Univariate analysis was performed. Results: Of 221 patients undergoing ASD surgery with a mean age of 63.6 ± 17.6, 112 (50.6%) were discharged home, 71 (32.2%) were discharged to an IPR center, and 38 (17.2%) were discharged to an SNF. Patients discharged home were significantly younger (55.7 ± 20.1 vs. 71.8 ± 9.1, p < 0.001), had lower rate of 2+ comorbidities (38.4% vs. 45.0%, p = 0.001), and had less hypertension (57.1% vs. 75.2%, p = 0.005). Perioperatively, patients who were discharged home had significantly fewer levels instrumented (10.0 ± 3.0 vs. 11.0 ± 3.4 levels, p = 0.030), shorter operative times (381.4 ± 139.9 vs. 461.6 ± 149.8 mins, p < 0.001), less blood loss (1101.0 ± 977.8 vs. 1739.7 ± 1332.9 mL, p < 0.001), and shorter length of stay (5.4 ± 2.8 vs. 9.3 ± 13.9 days, p < 0.001). Radiographically, preoperative SVA (9.1 ± 6.5 vs. 5.2 ± 6.8 cm, p < 0.001), PT (27.5 ± 11.1° vs. 23.4 ± 10.8°, p = 0.031), and T1PA (28.9 ± 12.7° vs. 21.6 ± 13.6°, p < 0.001) were significantly higher in patients who were discharged to an IPR center/SNF. Additionally, the operating surgeon also significantly influenced the disposition status (p < 0.001). A scoring system of the listed factors was proposed and was validated using univariate logistic regression (OR = 1.55, 95%CI = 1.34-1.78, p < 0.001) and ROC analysis, which revealed a cutoff value of > 6 points as a predictor of non-home discharge (AUC = 0.75, 95%CI = 0.68-0.80, p < 0.001, sensitivity = 63.3%, specificity = 74.1%). The factors in the scoring system were age > 56, comorbidities ≥ 2, hypertension, TIL ≥ 10, operative time > 357 mins, EBL > 1200 mL, preop SVA > 6.6 cm, preop PT > 33.6°, and preop T1PA > 15°. When comparing IPR (n = 71) vs. SNF (n = 38), patients discharged to an SNF were significantly older (74.4 ± 8.6 vs. 70.4 ± 9.1, p = 0.029) and were more likely to be female (89.5% vs. 70.4%, p = 0.024). Conclusions: Approximately 50% of patients were discharged home after ASD surgery. A simple scoring system based on age > 56, comorbidities ≥ 2, hypertension, total instrumented levels ≥ 10, operative time > 357 mins, EBL > 1200 mL, preop SVA > 6.6 cm, preop PT > 33.6°, and preop T1PA > 15° was proposed to predict non-home discharge. These findings may help guide postoperative expectations and resource allocation after ASD surgery.

Global Economic Evaluation of the Reported Costs of Deep Brain Stimulation.

INTRODUCTION: Despite the known benefits of deep brain stimulation (DBS), the cost of the procedure can limit access and can vary widely. Our aim was to conduct a systematic review of the reported costs associated with DBS, as well as the variability in reporting cost-associated factors to ultimately increase patient access to this therapy. METHODS: A systematic review of the literature for cost of DBS treatment was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed and Embase databases were queried. Olsen & Associates (OANDA) was used to convert all reported rates to USD. Cost was corrected for inflation using the US Bureau of Labor Statistics Inflation Calculator, correcting to April 2022. RESULTS: Twenty-six articles on the cost of DBS surgery from 2001 to 2021 were included. The median number of patients across studies was 193, the mean reported age was 60.5 ± 5.6 years, and median female prevalence was 38.9%. The inflation- and currency-adjusted mean cost of the DBS device was USD 21,496.07 ± USD 8,944.16, the cost of surgery alone was USD 14,685.22 ± USD 8,479.66, the total cost of surgery was USD 40,942.85 ± USD 17,987.43, and the total cost of treatment until 1 year of follow-up was USD 47,632.27 ± USD 23,067.08. There were no differences in costs observed across surgical indication or country. CONCLUSION: Our report describes the large variation in DBS costs and the manner of reporting costs. The current lack of standardization impedes productive discourse as comparisons are hindered by both geographic and chronological variations. Emphasis should be put on standardized reporting and analysis of reimbursement costs to better assess the variability of DBS-associated costs in order to make this procedure more cost-effective and address areas for improvement to increase patient access to DBS.

Combined Anterior-Posterior vs. Posterior-Only Approach in Adult Spinal Deformity Surgery: Which Strategy Is Superior?

Introduction: Whether a combined anterior-posterior (AP) approach offers additional benefits over the posterior-only (P) approach in adult spinal deformity (ASD) surgery remains unknown. In a cohort of patients undergoing ASD surgery, we compared the combined AP vs. the P-only approach in: (1) preoperative/perioperative variables, (2) radiographic measurements, and (3) postoperative outcomes. Methods: A single-institution, retrospective cohort study was performed for patients undergoing ASD surgery from 2009 to 2021. Inclusion criteria were ≥5-level fusion, sagittal/coronal deformity, and 2-year follow-up. The primary exposure was the operative approach: a combined AP approach or P alone. Postoperative outcomes included mechanical complications, reoperation, and minimal clinically important difference (MCID), defined as 30% of patient-reported outcome measures (PROMs). Multivariable linear regression was controlled for age, BMI, and previous fusion. Results: Among 238 patients undergoing ASD surgery, 34 (14.3%) patients underwent the AP approach and 204 (85.7%) underwent the P-only approach. The AP group consisted mostly of anterior lumbar interbody fusion (ALIF) at L5/S1 (73.5%) and/or L4/L5 (38.0%). Preoperatively, the AP group had more previous fusions (64.7% vs. 28.9%, p < 0.001), higher pelvic tilt (PT) (29.6 ± 11.6° vs. 24.6 ± 11.4°, p = 0.037), higher T1 pelvic angle (T1PA) (31.8 ± 12.7° vs. 24.0 ± 13.9°, p = 0.003), less L1-S1 lordosis (-14.7 ± 28.4° vs. -24.3 ± 33.4°, p < 0.039), less L4-S1 lordosis (-25.4 ± 14.7° vs. 31.6 ± 15.5°, p = 0.042), and higher sagittal vertical axis (SVA) (102.6 ± 51.9 vs. 66.4 ± 71.2 mm, p = 0.005). Perioperatively, the AP approach had longer operative time (553.9 ± 177.4 vs. 397.4 ± 129.0 min, p < 0.001), more interbodies placed (100% vs. 17.6%, p < 0.001), and longer length of stay (8.4 ± 10.7 vs. 7.0 ± 9.6 days, p = 0.026). Radiographically, the AP group had more improvement in T1PA (13.4 ± 8.7° vs. 9.5 ± 8.6°, p = 0.005), L1-S1 lordosis (-14.3 ± 25.6° vs. -3.2 ± 20.2°, p < 0.001), L4-S1 lordosis (-4.7 ± 16.4° vs. 3.2 ± 13.7°, p = 0.008), and SVA (65.3 ± 44.8 vs. 44.8 ± 47.7 mm, p = 0.007). These outcomes remained statistically significant in the multivariable analysis controlling for age, BMI, and previous fusion. Postoperatively, no significant differences were found in mechanical complications, reoperations, or MCID of PROMs. Conclusions: Preoperatively, patients undergoing the combined anterior-posterior approach had higher PT, T1PA, and SVA and lower L1-S1 and L4-S1 lordosis than the posterior-only approach. Despite increased operative time and length of stay, the anterior-posterior approach provided greater sagittal correction without any difference in mechanical complications or PROMs.

Cost considerations for vestibular schwannoma screening and imaging: a systematic review.

Vestibular schwannomas (VS) account for approximately 8% of all intracranial neoplasms. Importantly, the cost of the diagnostic workup for VS, including the screening modalities most commonly used, has not been thoroughly investigated. Our aim is to conduct a systematic review of the published literature on costs associated with VS screening. A systematic review of the literature for cost of VS treatment was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The terms "vestibular schwannoma," "acoustic neuroma," and "cost" were queried using the PubMed and Embase databases. Studies from all countries were considered. Cost was then corrected for inflation using the US Bureau of Labor Statistics Inflation Calculator, correcting to April 2022. The search resulted in an initial review of 483 articles, of which 12 articles were included in the final analysis. Screening criteria were used for non-neurofibromatosis type I and II patients who complained of asymmetric hearing loss, tinnitus, or vertigo. Patients included in the studies ranged from 72 to 1249. The currency and inflation-adjusted mean cost was $418.40 (range, $21.81 to $487.03, n = 5) for auditory brainstem reflex and $1433.87 (range, $511.64 to $1762.15, n = 3) for non-contrasted computed tomography. A contrasted magnetic resonance imaging (MRI) scan was found to have a median cost of $913.27 (range, $172.25-$2733.99; n = 8) whereas a non-contrasted MRI was found to have a median cost of $478.62 (range, $116.61-$3256.38, n = 4). In terms of cost reporting, of the 12 articles, 1 (8.3%) of them separated out the cost elements, and 10 (83%) of them used local prices, which include institutional costs and/or average costs of multiple institutions. Our findings describe the limited data on published costs for screening and imaging of VS. The paucity of data and significant variability of costs between studies indicates that this endpoint is relatively unexplored, and the cost of screening is poorly understood.

Impact of neurovascular comorbidities and complications on outcomes after procedural management of arteriovenous malformations.

OBJECTIVE: Cerebral arteriovenous malformations (AVMs) are complex vascular lesions at perpetual risk for rupture, which can lead to significant morbidity and mortality. This study sought to evaluate the dynamic relationship between comorbidities and post-procedure complications to quantify the risk of poor discharge outcomes to create a predictive outcomes model. METHODS: The National Inpatient Sample (NIS) data from 2012 to 2015 was queried for AVM treatment using International Classification of Diseases, Ninth Revision codes. The Neurovascular Comorbidities Index (NCI) quantified patient comorbidity burden. In-hospital complications included surgical and medical complications or seizures. The primary outcome was the NIS Subarachnoid Hemorrhage Outcome Measure (NIS-SOM). RESULTS: A total of 1363 patients were included. A total of 1330 patients (98%) underwent embolization, 28 (2%) underwent resection, and 9 (0.7%) underwent radiosurgery. A higher NCI was associated with the occurrence of any complication (odds ratio [OR], 1.30 if NCI = 2; P < 0.001). Higher NCI was also significantly associated with a poor NIS-SOM outcome (OR, 2.45 if NCI = 2 and no complications; P < 0.001). A ruptured AVM with intracranial hemorrhage (ICH) increased the risk of in-hospital complications (OR, 2.16; P = 0.007) and a poor NIS-SOM outcome (OR, 3.18; P < 0.001). Various hypothetical patient scenarios and the predicted outcomes are also presented. CONCLUSION: Neurovascular comorbidities have a significant impact on poor functional outcomes at discharge in patients with and without complications following procedural management of AVMs. At the time of initial patient assessment, risk stratification strategies should take into account neurovascular comorbidities and potential complications. Such an approach would ultimately optimize patient outcomes and increase the value of care provided.

Creation and Validation of a Stroke Scale to Increase Utility of National Inpatient Sample Administrative Data for Clinical Stroke Research.

INTRODUCTION: The National Inpatient Sample (NIS) has led to several breakthroughs via large sample size. However, utility of NIS is limited by the lack of admission NIHSS and 90-day modified Rankin score (mRS). This study creates estimates for stroke severity at admission and 90-day mRS using NIS data for acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT). METHODS: Three patient cohorts undergoing MT for AIS were utilized: Cohort 1 (N = 3729) and Cohort 3 (N = 1642) were derived from NIS data. Cohort 2 (N=293) was derived from a prospectively-maintained clinical registry. Using Cohort 1, Administrative Stroke Outcome Variable (ASOV) was created using disposition and mortality. Factors reflective of stroke severity were entered into a stepwise logistic regression predicting poor ASOV. Odds ratios were used to create the Administrative Data Stroke Scale (ADSS). Performances of ADSS and ASOV were tested using Cohort 2 and compared with admission NIHSS and 90-day mRS, respectively. ADSS performance was compared with All Patient Refined-Diagnosis Related Group (APR-DRG) severity score using Cohort 3. RESULTS: Agreement of ASOV with 90-day mRS > 2 was fair (κ = 0.473). Agreement with 90-day mRS > 3 was substantial (κ = 0.687). ADSS significantly correlated (p < 0.001) with clinically-significant admission NIHSS > 15. ADSS performed comparably (AUC = 0.749) to admission NIHSS (AUC = 0.697) in predicting 90-day mRS > 2 and mRS > 3 (AUC = 0.767, 0.685, respectively). ADSS outperformed APR-DRG severity score in predicting poor ASOV (AUC = 0.698, 0.682, respectively). CONCLUSION: We developed and validated measures of stroke severity at admission (ADSS) and outcome (ASOV, estimate for 90-day mRS > 3) to increase utility of NIS data in stroke research.

Impact of Neurovascular Comorbidities and Complications on Outcomes After Procedural Management of Intracranial Aneurysm: Part 2, Ruptured Intracranial Aneurysm.

OBJECTIVE: We aim to define the dynamic interplay between neurovascular-specific comorbidities and in-hospital complications on outcomes (functional outcome and mortality), length of stay (LOS), and cost of hospital stay. METHODS: The 2012-2015 National Inpatient Sample (NIS) was queried for intracranial aneurysm treatment after subarachnoid hemorrhage using International Classification of Diseases, Ninth Revision codes. Neurovascular comorbidity index (NCI) was aggregated. NIS-Subarachnoid Hemorrhage Severity Score (NIS-SSS) was used as a Hunt-Hess grade proxy. In-hospital complications were medical complications, surgical complications, seizures, and cerebral vasospasm. Outcomes were functional outcome (modified Rankin Scale [mRS]-equivalent measure), in-hospital mortality, LOS, and cost. Multivariable logistic regression models were built for mRS equivalent and in-hospital mortality. Multivariable linear regression models in log scale were built for LOS and cost. RESULTS: A total of 5353 patients were included. The median NCI was 4.00 (interquartile range [IQR], 0.00-7.00) and 2882 patients (54%) had in-hospital complication. Higher NCI (odds ratio [OR], 1.13 if NCI = 1; OR, 2.05 if NCI = 7; P < 0.001) was associated with any complication, seizure (OR, 1.11, NCI = 1; OR, 1.60, NCI = 7; P < 0.001), medical complication (OR, 1.18, NCI = 1; OR, 2.50, NCI = 7; P < 0.001), surgical complication (OR, 1.13, NCI = 1; OR, 1.91, NCI = 7; P < 0.001), and cerebral vasospasm (OR, 1.09, NCI = 1; OR, 1.49, NCI = 7; P < 0.001). Patients with higher NCI (OR, 1.06, NCI = 1; OR, 1.95, NCI = 7; P < 0.001) or with in-hospital complication (P < 0.001) had poorer mRS equivalent outcome. Similar trends were observed for other outcomes including in-hospital mortality, LOS, and cost. CONCLUSIONS: Neurovascular comorbidities are the primary driver of poor mRS equivalent outcome, in-hospital mortality, higher LOS, and higher cost after ruptured intracranial aneurysm procedural treatment. The conditional event of complication influences patients with moderate comorbidities more so than those with low or high comorbidities.

Impact of insurance type on national variation in cost of endovascular treatment for unruptured cerebral aneurysms.

BACKGROUND: Identifying drivers of nationwide variation in healthcare costs could help reduce overall cost. Endovascular treatment for unruptured cerebral aneurysms (ETUCR) is an elective neurointerventional procedure that allows for detailed analysis of cost variation. This study aimed to investigate the role of insurance type in cost variation of ETUCR. METHODS: A retrospective analysis of patients undergoing ETUCR was done. Demographic and hospital data were obtained from the National Inpatient Sample 2012-2015. Multivariate analysis was done using a generalized linear model. Oaxaca-Blinder decomposition was performed to identify factors driving cost variation. RESULTS: There was a significant difference in median cost ($25 331.82 vs $25 825.25, respectively, P<0.001) as well as length of stay (P<0.001) and complications (P<0.001) between patients with private insurance and Medicare. In multivariate analysis, insurance type was not predictive of increased cost. Among patients aged 65-75 years there was a higher median cost with private insurance compared to Medicare ($28 373.85 vs $25 558.25, respectively, P<0.001) but no difference in complications or length of stay. Oaxaca-Blinder decomposition showed higher marginal costs associated with private insurance patients at hospitals with greater endovascular operative volume (P=0.015). CONCLUSIONS: In patients aged 65-75 years, private insurance is associated with higher costs compared to Medicare; however, insurance type is not predictive of increased cost in multivariate analysis. Differential treatment of private insurance and Medicare patients at hospitals with greater operative volume seems to influence this difference, likely due to differential reimbursement schemes that lead to weaker cost controls.

Impact of Neurovascular Comorbidities and Complications on Outcomes After Procedural Management of Intracranial Aneurysm: Part 1, Unruptured Intracranial Aneurysm.

OBJECTIVE: This study investigates the relationship between neurovascular comorbidities and in-hospital complications in determining functional outcome, mortality, length of stay (LOS), and cost of stay. METHODS: Patients were identified from the 2012-2015 National Inpatient Sample (NIS) using International Classification of Diseases, Ninth Revision codes for unruptured intracranial aneurysm (UIA) treatment in patients without subarachnoid hemorrhage. In-hospital complications were divided into medical complications, surgical complications, and seizures. Primary outcomes were functional outcome measured by modified Rankin Scale (mRS)-equivalent measure, in-hospital mortality, LOS, and cost. Multivariable logistic regression models were built for mRS-equivalent and in-hospital mortality. Multivariable linear regression models in log scale were built for LOS and cost. RESULTS: A total of 7398 procedurally managed patients with UIA were included (median age, 58 years; 75% female; 66% white; 43% private insurance). Higher Neurovascular Comorbidities Index (NCI) was associated with seizure (odds ratio [OR], 1.11 if NCI = 1; OR, 2.49 if NCI = 7; P < 0.001), medical complication (OR, 1.21, NCI = 1; OR, 3.46, NCI = 7; P < 0.001), and surgical complication (OR, 1.25, NCI = 1; OR, 3.47, NCI = 7; P < 0.001). NCI remained significantly predictive of poor mRS-equivalent outcome (OR, 1.20, NCI = 1; OR, 5.79, NCI = 7; P < 0.001), in-hospital mortality (OR, 1.98, NCI = 1; OR, 10.9, NCI = 7; P < 0.001), LOS (coefficient dependent on multiple variables, P < 0.001), and cost (coefficient dependent on multiple variables, P < 0.001) after adjustment. CONCLUSIONS: Neurovascular comorbidities are the primary driver of poor mRS-equivalent outcome, in-hospital mortality, higher LOS, and higher cost after procedural treatment of UIA. The conditional event of complication influences patients with fewer comorbidities more so than those with no comorbidities or high comorbidities. It is imperative to precisely account for these factors to optimize targeted resource allocation and increase the value of care for patients with UIA.

The economic impact of open versus endoscope-assisted craniosynostosis surgery.

OBJECTIVE: Open and endoscope-assisted repair are surgical options for sagittal craniosynostosis, with limited research evaluating each technique's immediate and long-term costs. This study investigates the cost-effectiveness of open and endoscope-assisted repair for single, sagittal suture craniosynostosis. METHODS: The authors performed a retrospective cohort study of patients undergoing single, sagittal suture craniosynostosis repair (open in 17 cases, endoscope-assisted in 16) at less than 1 year of age at Monroe Carell Jr. Children's Hospital at Vanderbilt (MCJCHV) between August 2015 and August 2017. Follow-up data were collected/analyzed for 1 year after discharge. Surgical and follow-up costs were derived by merging MCJCHV financial data with each patient's electronic medical record (EMR) and were adjusted for inflation using the healthcare Producer Price Index. Proxy helmet costs were derived from third-party out-of-pocket helmet prices. To account for variable costs and probabilities, overall costs were calculated using TreeAge tree diagram software. RESULTS: Open repair occurred in older patients (mean age 5.69 vs 2.96 months, p < 0.001) and required more operating room time (median 203 vs 145 minutes, p < 0.001), more ICU days (median 3 vs 1 day, p < 0.001), more hospital days (median 4 vs 1 day, p < 0.001), and more frequently required transfusion (88% vs 6% of cases). Compared to patients who underwent open surgery, patients who underwent endoscopically assisted surgery more often required postoperative orthotic helmets (100% vs 6%), had a similar number of follow-up clinic visits (median 3 vs 3 visits, p = 0.487) and CT scans (median 3 vs 2 scans), and fewer emergency department visits (median 1 vs 3 visits). The TreeAge diagram showed that, overall, open repair was 73% more expensive than endoscope-assisted repair ($31,314.10 vs $18,081.47). Sensitivity analysis identified surgical/hospital costs for open repair (mean $30,475, SEM $547) versus endoscope-assisted repair (mean $13,746, SEM $833) (p < 0.001) as the most important determinants of overall cost. Two-way sensitivity analysis comparing initial surgical/hospital costs confirmed that open repair remains significantly more expensive under even worst-case initial repair scenarios ($3254.81 minimum difference). No major surgical complications or surgical revisions occurred in either cohort. CONCLUSIONS: The results of this study suggest that endoscope-assisted craniosynostosis repair is significantly more cost-effective than open repair, based on markedly lower costs and similar outcomes, and that the difference in initial surgical/hospital costs far outweighs the difference in subsequent costs associated with helmet therapy and outpatient management, although independent replication in a multicenter study is needed for confirmation due to practice and cost variation across institutions. Longer-term results will also be needed to examine whether cost differences are maintained.

The cost of hydrocephalus: a cost-effectiveness model for evaluating surgical techniques.

In BriefThe authors analyzed the costs associated with the three different procedures used to treat hydrocephalus in the pediatric population. They believe this study highlights the importance of patient-specific treatment decisions that are based on etiology and previous intervention. The patient-specific medical characteristics are a driving force in the cost of care.

Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome.

BACKGROUND: Both the adrenergic and renin-angiotensin systems contribute to orthostatic circulatory homeostasis, which is impaired in postural orthostatic tachycardia syndrome (POTS). Activating autoantibodies to the α1-adrenergic and ß1/2-adrenergic receptors have previously been found in sera from patients with POTS. We hypothesized that patients with POTS might also harbor activating autoantibodies to the angiotensin II type 1 receptor (AT1R) independently of antiadrenergic autoimmunity. This study examines a possible pathophysiological role for AT1R autoantibodies in POTS. METHODS AND RESULTS: Serum immunoglobulin G from 17 patients with POTS, 6 patients with recurrent vasovagal syncope, and 10 normal controls was analyzed for the ability to activate AT1R and alter AT1R ligand responsiveness in transfected cells in vitro. Of 17 subjects with POTS, 12 demonstrated significant AT1R antibody activity in immunoglobulin G purified from their serum. No significant AT1R antibody activity was found in the subjects with vasovagal syncope or healthy subjects. AT1R activation by POTS immunoglobulin G was specifically blocked by the AT1R blocker losartan. Moreover, POTS immunoglobulin G significantly shifted the angiotensin II dosage response curve to the right, consistent with an inhibitory effect. All subjects with POTS were positive for one or both autoantibodies to the AT1R and α1-adrenergic receptor. CONCLUSIONS: Most patients with POTS harbor AT1R antibody activity. This supports the concept that AT1R autoantibodies and antiadrenergic autoantibodies, acting separately or together, may exert a significant impact on the cardiovascular pathophysiological characteristics in POTS.

Antiadrenergic autoimmunity in postural tachycardia syndrome.

AIMS: Postural tachycardia syndrome (POTS), a common and debilitating cardiovascular disorder, is characterized by an exaggerated heart rate increase during orthostasis and a wide spectrum of adrenergic-related symptoms. To determine the aetiology of POTS, we examined a possible pathophysiological role for autoantibodies against α1-adrenergic (α1AR) and ß1/2-adrenergic receptors (ß1/2AR). METHODS AND RESULTS: Immunoglobulin G (IgG) derived from 17 POTS patients, 7 with recurrent vasovagal syncope (VVS), and 11 normal controls was analysed for its ability to modulate activity and ligand responsiveness of α1AR and ß1/2AR in transfected cells and to alter contractility of isolated rat cremaster arterioles in vitro. Immunoglobulin G activation of α1AR and ß1/2AR was significantly higher in POTS compared with VVS and controls in cell-based assays. Eight, 11, and 12 of the 17 POTS patients possessed autoantibodies that activated α1AR, ß1AR and ß2AR, respectively. Pharmacological blockade suppressed IgG-induced activation of α1AR and ß1/2AR. Eight of 17 POTS IgG decreased the α1AR responsiveness to phenylephrine and 13 of 17 POTS IgG increased the ß1AR responsiveness to isoproterenol irrespective of their ability to directly activate their receptors. Postural tachycardia syndrome IgG contracted rat cremaster arterioles, which was reversed by α1AR blockade. The upright heart rate correlated with IgG-mediated ß1AR and α1AR activity but not with ß2AR activity. CONCLUSION: These data confirm a strong relationship between adrenergic autoantibodies and POTS. They support the concept that allosteric-mediated shifts in the α1AR and ß1AR responsiveness are important in the pathophysiology of postural tachycardia.

AT2R autoantibodies block angiotensin II and AT1R autoantibody-induced vasoconstriction.

Activating autoantibodies to the angiotensin type 1 receptor (AT1R) are associated with hypertensive disorders. The angiotensin type 2 receptor (AT2R) is known to counter-regulate the actions of AT1R. We investigated whether AT2R autoantibodies produced in immunized rabbits will activate AT2R and suppress the vasopressor responses to angiotensin II and AT1R-activating autoantibodies. Five rabbits immunized with a peptide corresponding to the second extracellular loop of AT2R developed high AT2R antibody titers. Rabbit anti-AT2R sera failed to directly dilate isolated rat cremaster arterioles; however, when co-perfused with angiotensin II or AT1R-activating autoantibodies, the anti-AT2R sera significantly inhibited their contractile effects. Rabbit anti-AT2R sera recognized a predominant sequence near the N-terminus of the AT2R second extracellular loop. A decoy peptide based on this sequence effectively reversed the opposing effect of the anti-AT2R sera on angiotensin II-induced contraction of rat cremaster arterioles. A similar blockade of the anti-AT2R sera effect was observed with the AT2R antagonist PD 123319 and the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. Rabbit anti-AT2R sera reacted specifically with AT2R. No cross-reactivity with AT1R was observed. Blood pressure did not change in immunized animals. However, the pressor responses to incremental angiotensin II infusions were blunted in immunized animals. Thirteen subjects with primary aldosteronism demonstrated increased AT2R autoantibody levels compared with normal controls. In conclusion, AT2R autoantibodies produced in immunized rabbits have the ability to activate AT2R and counteract the AT1R-mediated vasoconstriction. These autoantibodies provide useful and selective tools for the study of their roles in blood pressure regulation and possible therapeutic intervention.

Novel retro-inverso peptide inhibitor reverses angiotensin receptor autoantibody-induced hypertension in the rabbit.

Activating autoantibodies to the angiotensin II type 1 receptor (AT1R) have been implicated in hypertensive disorders. We investigated whether AT1R antibodies produced in immunized rabbits will activate AT1R and contribute to hypertension by a direct contractile effect on the vasculature and whether they can be blocked by a novel decoy peptide. A multiple antigenic peptide containing the AT1R epitope AFHYESQ, which is the receptor-binding epitope of AT1R-activating autoantibodies, was used to immunize 6 rabbits. AT1R antibody activity was analyzed in AT1R-transfected cells, and their contractile effects were assayed using isolated perfused rat cremaster resistance arterioles. A retro-inverso D-amino acid epitope-mimetic peptide was tested for AT1R antibody inhibition in vitro and in vivo. All immunized animals produced high AT1R antibody titers and developed elevated blood pressure. No changes in measured blood chemistry values were observed after immunization. Rabbit anti-AT1R sera induced significant AT1R activation in transfected cells and vasoconstriction in the arteriole assay, both of which were blocked by losartan and the retro-inverso D-amino acid peptide. A single intravenous bolus injection of the retro-inverso d-amino acid peptide (1 mg/kg) into immunized rabbits dropped the mean arterial pressure from 122±11 to 82±6 mm Hg. Rabbit anti-AT1R sera partially suppressed angiotensin II-induced contraction of isolated rat cremaster arterioles, and the pressor response to angiotensin II infusion was attenuated in immunized animals. In conclusion, AT1R-activating autoantibodies and the retro-inverso d-amino acid peptide, respectively, have important etiologic and therapeutic implications in hypertensive subjects who harbor these autoantibodies.

Activating autoantibodies to the ß1/2-adrenergic and M2 muscarinic receptors associate with atrial tachyarrhythmias in patients with hyperthyroidism.

We have previously demonstrated that activating autoantibodies to ß1-adrenergic receptor (ß1AR) and M2 muscarinic receptor (M2R) facilitate atrial fibrillation (AF) in patients with Graves' disease (GD). The objectives of this expanded study were to examine the prevalence of ß1AR, ß2AR, and M2R autoantibodies in hyperthyroidism subjects. Sera from 81 patients including 31 with GD and AF, 36 with GD and sinus rhythm, 9 with toxic multinodular goiter, 5 with subacute thyroiditis, and 10 control subjects were examined for these autoantibodies by ELISA. Sera from 20 ELISA-positive GD subjects, 10 with AF and 10 with sinus rhythm, were assayed for autoantibody bioactivity using cell-based bioassays. In patients with GD and AF, 45, 65, and 77 % were ELISA positive for ß1AR, M2R, and ß2AR autoantibodies, respectively. In patients with GD and sinus rhythm, 17, 39, and 75 % were ELISA positive for ß1AR, M2R, and ß2AR autoantibodies, respectively. ß1AR and M2R autoantibodies were co-present in 39 % of patients with GD and AF compared to 14 % in GD with sinus rhythm (p = 0.026). Patients with toxic multinodular goiter or subacute thyroiditis had a low prevalence of autoantibodies. The mean ß1AR and M2R autoantibody activity was elevated in both GD groups but higher in those with AF than those with sinus rhythm. ß2AR autoantibody activity was also increased in both groups. In conclusion, ß1AR, ß2AR, and M2R autoantibodies were elevated in GD. ß1AR and M2R autoantibodies appear to be related to concurrent AF, while ß2AR autoantibodies were equally prevalent in those with a sinus tachycardia and those with AF.