Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report.

Schwann cells are essential for the maintenance and function of motor neurons, axonal networks, and the neuromuscular junction. In amyotrophic lateral sclerosis, where motor neuron function is progressively lost, Schwann cell function may also be impaired. Recently, important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported. This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles, marking, to our knowledge, the first instance of such treatment. An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis. After initial diagnosis, the patient underwent a combination of generic riluzole, sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis, and taurursodiol. The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function. We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired (senescent) and that exposure of the patient's Schwann cells to allogeneic Schwann cell-derived exosomal vesicles, cultured expanded from a cadaver donor improved their growth capacity in vitro. After a period of observation lasting 10 weeks, during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored, the patient received weekly consecutive infusions of 1.54 × 10 12 (×2), and then consecutive infusions of 7.5 × 10 12 (×6) allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco's phosphate-buffered saline. None of the infusions were associated with adverse events such as infusion reactions (allergic or otherwise) or changes in vital signs. Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend. A more sensitive in-house assay suggested possible inflammasome activation during the disease course. A trend for clinical stabilization was observed during the infusion period. Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles. Initial findings suggest that this approach is safe.

The role of emboli detection studies in acute inpatient vertebral artery dissection.

BACKGROUND: Prompt diagnosis and treatment of vertebral artery dissection (VAD) is critical for preventing stroke. The use of emboli detection studies (EDS) using Doppler ultrasonography is an emerging method that has been proposed to predict stroke risk and guide subsequent treatment. Limited data exists on the predictive value of this emerging modality in the posterior circulation. This study aims to assess the predictive value of emboli detection studies (EDS) in forecasting inpatient stroke in VAD patients and identify associated risk factors. Patients were recruited between January 2009 and January 2018. METHODS: We performed a retrospective analysis of 104 consecutive patients with VAD who underwent EDS at our institution. Patients underwent transcranial ultrasonography for detection of microemboli and were followed clinically and radiographically thereafter for evidence of stroke. RESULTS: A total of 104 patients with spontaneous (58 %), traumatic (39 %) or iatrogenic (4 %) VAD were included in our analysis. Stroke occurred more frequently in patients with spontaneous VAD compared to traumatic VAD (p < 0.001). Microemboli were detected in 17 patients (16 %), including 18.3 % of spontaneous VAD, 12.5 % of traumatic VAD, and 25 % of iatrogenic VAD. 61 patients (59 %) suffered a posterior circulation stroke, however there was no significant association between detection of microemboli and stroke events (60 % of patients without microemboli vs. 53 % of patients with ≥ 1 HITS during EDS; p = 0.6). Similarly, no microemboli were detected in any of the patients who went on to develop a delayed stroke. CONCLUSIONS: In our single-institution retrospective analysis of patients with VAD, the detection of microemboli on EDS was not associated with stroke nor was it predictive of delayed stroke. Additionally, patients with spontaneous VAD may be at higher risk for stroke compared to traumatic VAD.

Association of bradykinin receptor 2 (BDKRB2) variants with physical performance and muscle mass: Findings from the LACE sarcopenia trial.

INTRODUCTION: Understanding genetic contributors to sarcopenia (age-related loss of muscle strength and mass) is key to finding effective therapies. Variants of the bradykinin receptor 2 (BDKRB2) have been linked to athletic and muscle performance. The rs1799722-9 and rs5810761 T alleles have been shown to be overrepresented in endurance athletes, possibly due to increased transcriptional rates of the receptor. These variants have been rarely studied in older people or people with sarcopenia. METHODS: We performed a post hoc sub-study of the Leucine and ACE (LACE) inhibitor trial, which enrolled 145 participants aged ≥70 years with low grip strength and low gait speed. Participants' blood samples were genotyped for rs179972 using TaqMan and rs5810761 by amplification through Hotstar Taq. Genotypes were compared with outcomes of physical performance and body composition measures. RESULTS: Data from 136 individuals were included in the analysis. For rs1799722 the genotype frequency (TT: 17, CC: 48, CT: 71) remained in Hardy-Weinberg Equilibrium (HWE p = 0.248). There was no difference between the genotypes for six-Minute Walk Distance (6MWD) or Short Physical Performance Battery (SPPB). Men with the TT genotype had a significantly greater 6MWD than other genotypes (TT 400m vs CT 310m vs CC 314m, p = 0.027), and greater leg muscle mass (TT 17.59kg vs CT 15.04kg vs CC 15.65kg, p = 0.007). For rs5810761, the genotype frequency (-9-9: 31, +9+9: 43, -9+9: 60) remained in HWE (p = 0.269). The +9+9 genotype was associated with a significant change in SPPB score at 12 months (-9-9 0 vs -9+9 0 vs +9+9-1, p<0.001), suggesting an improvement. In men, the -9-9 genotype was associated with lower arm fat (-9-9 2.39kg vs -9+9 2.72kg vs +9+9 2.76kg, p = 0.019). CONCLUSION: In men, the rs1799722 TT genotype was associated with longer 6MWD and greater leg muscle mass, while the rs5810761 -9-9 genotype was associated with lower arm fat mass.

Acute Surgical Site Complications in Direct Anterior Total Hip Arthroplasty: Impact of Local Subcutaneous Tissue Depth and Body Mass Index.

Background: Body mass index (BMI) is an imperfect measure of patients' adiposity and operative risk. Radiographic and direct subcutaneous measurements have been utilized in attempts to more accurately characterize the risk of postoperative complications, including surgical site infection. This study aims to evaluate whether direct tissue depth measurement is a more accurate predictor of skin complication following direct anterior total hip arthroplasty (THA). Methods: A retrospective chart review of patients who underwent elective THA between April 30, 2020, and January 31, 2023, was performed. Baseline demographics, antibiotics, anticoagulation, and intraoperatively measured tissue depths at proximal, middle, and distal portions of the incision were recorded. Patient follow-up was reviewed to assess the development of skin complication in the acute postoperative period. Results: Data were collected from 280 patients who underwent THA via direct anterior approach by a single surgeon. The mean age was 66.0 years, and 52.1% were female. A total of 18/280 (6.4%) patients developed an abrasion (5/18) or superficial surgical site infection (13/18) within the first 60 days postoperatively. Patients who developed skin complications had a significantly higher BMI (33.7 kg/m2 vs 29.9 kg/m2; P = .0021). Patients with a BMI >30 kg/m2 had more than 5 times increased odds of developing a superficial skin complication in the acute 60-day postoperative period compared to those with a BMI <30 kg/m2 (Odds ratio = 5.318, P = .0059). None of the measured tissue depths, nor their average together, were shown to be significant predictors of skin complications. Conclusions: This study showed that BMI is a significant predictor of acute skin complications in direct anterior THA patients. No other significant predictors were found to be associated with increased risk, including proximal, middle, and distal tissue depths.

Functional diversity of bacterial microbiota associated with the toxigenic benthic dinoflagellate Prorocentrum.

Interactions between bacterial microbiota and epibenthic species of the dinoflagellate Prorocentrum may define the onset and persistence of benthic harmful algal blooms (bHABs). Chemical ecological interactions within the dinoflagellate phycosphere potentially involve a complex variety of organic molecules, metabolites, and toxins, including undefined bioactive compounds. In this study, the bacterial diversity and core members of the dinoflagellate-associated microbiota were defined from 11 strains of three epibenthic Prorocentrum species, representing three geographically disjunct locations within Mexican coastal waters. Microbiota profiles in stable monoclonal Prorocentrum cultures were obtained by sequencing amplicons of the V3-V4 region of the 16S rRNA gene. Thirteen classes of bacteria were identified among dinoflagellate clones, where Alphaproteobacteria, Gammaproteobacteria, and Bacteroidia were consistently dominant. The bacterial community structure exhibited significantly different grouping by the location of origin of dinoflagellate clones. No significant diversity difference was found among free-living or unattached bacteria in the dinoflagellate culture medium (M) compared with those in closer association with the dinoflagellate host cells (H). Twelve taxa were defined as core members of the bacterial assemblage, representing the genera Algiphilus, Cohaesibacter, Labrenzia, Mameliella, Marinobacter, Marivita, Massilia, Muricauda, Roseitalea, and an unclassified member of the Rhodobacteraceae. The core members are inferred to significantly contribute to primary and secondary metabolic functions, but no direct correlation with dinoflagellate toxigenicity was apparent. Overall the bacterial profile and implied gene functionality indicated a suite of positive interactions, suggesting either mutualism or commensalism with the dinoflagellate. The further characterization and interpretation of specific gene functions and interactions between bacteria and dinoflagellates, such as epibenthic members of genus Prorocentrum, are key to understanding their role in toxigenesis and bHAB development.

Associations Between Neighborhood Racialized Economic Segregation with Cardiometabolic Health and Cortisol in a Racially/Ethnically Diverse Sample of Children from Minneapolis-St. Paul.

Introduction: Past research shows that structural racism contributes to disparities in cardiometabolic health among racially/ethnically minoritized populations. Methods: This cross-sectional study examined the correlation between census tract-level racialized economic segregation and child health metrics among a racially and ethnically diverse cohort of 350 children (ages 6.5-13.8) from Minneapolis-St. Paul, MN. Results: A consistent cardiometabolic and cortisol outcome gradient was observed across the index of concentration at the extremes tertiles, such that health risk factors increased as tract privilege decreased. Conclusion: Racialized economic segregation was associated with less favorable child health outcomes, underscoring the potential importance of place-based interventions for promoting children's health.

Individual Variation in the Distribution of Apolipoprotein B Levels Across the Spectrum of LDL-C or Non-HDL-C Levels.

Importance: Although apolipoprotein B (apoB) is a superior marker of lipid-related risk compared with low-density lipoprotein cholesterol (LDL-C), few data exist to translate the goals and thresholds from LDL-C to their apoB equivalent. In addition, although current American College of Cardiology/American Heart Association guidelines provide a relative indication for apoB measurement among individuals with hypertriglyceridemia, whether discordance is limited to those subgroups is unknown. Objectives: To assess the variability in apoB level across the spectrum of LDL-C or non-high-density lipoprotein cholesterol (non-HDL-C) levels and evaluate whether discordance between apoB and LDL-C or non-HDL-C is limited to specifiable subgroups. Design, Setting, and Participants: This cross-sectional study used data from a nationally representative sample of 12 688 adult participants not using statins in the National Health and Nutrition Examination Survey between 2005 and 2016. Statistical analysis was performed from April 2023 to February 2024. Main Outcomes and Measures: Quantile regression was used to assess the population distribution of apoB across LDL-C or non-HDL-C levels. Discordance between apoB and LDL-C was the difference between measured apoB and median apoB levels for an individual's LDL-C level. Discordance was evaluated by age, sex, race and ethnicity, obesity, diabetes, triglyceride level, hemoglobin A1c level, body mass index (BMI), statin use, and metabolic health (defined as a BMI between 18.5 and 24.9, triglyceride level <150 mg/dL, and no diabetes). Results: Among the sample of 12 688 participants (median age, 41.0 years [IQR, 29.0-54.0 years]; 52.9% women) for LDL-C values of 55, 70, 100, and 190 mg/dL, the corresponding population median apoB levels were 49, 60, 80, and 140 mg/dL, respectively. For given levels of LDL-C, a range of apoB values was observed. At an LDL-C level of 100 mg/dL, the 95% population distribution of apoB ranged from 66 mg/dL to 99 mg/dL. ApoB variability was highest for LDL-C values estimated using the Friedewald equation, lower when using Sampson or Martin-Hopkins equations, and lowest for non-HDL-C. Although individuals with metabolic risk factors were more likely to have discordantly high apoB levels (ie, had higher median observed apoB levels relative to what was estimated based on LDL-C), significant variability in apoB levels was observed even among metabolically healthy individuals. Conclusions and Relevance: This study suggests that even metabolically healthy individuals may have discordantly high apoB levels relative to LDL-C or non-HDL-C levels. The current guideline approach for apoB testing only for those with hypertriglyceridemia appears too narrow. Population percentile data can be used to translate LDL-C goals and thresholds to their apoB equivalent to facilitate clinical adoption.

The Causal-Benefit Model to Prevent Cardiovascular Events.

Selecting individuals for preventive lipid-lowering therapy is presently governed by the 10-year risk model. Once a prespecified level of cardiovascular disease risk is equaled or exceeded, individuals become eligible for preventive lipid-lowering therapy. A key limitation of this model is that only a small minority of individuals below the age of 65 years are eligible for therapy. However, just under one-half of all cardiovascular disease events occur below this age. Additionally, in many, the disease that caused their events after 65 years of age developed and progressed before 65 years of age. The causal-benefit model of prevention identifies individuals based both on their risk and the estimated benefit from lowering atherogenic apoB lipoprotein levels. Adopting the causal-benefit model would increase the number of younger subjects eligible for preventive treatment, would increase the total number of cardiovascular disease events prevented at virtually the same number to treat, and would be cost-effective.

Virtual fitness buddy ecosystem: a mixed reality precision health physical activity intervention for children.

6-11-year-old children provide a critical window for physical activity (PA) interventions. The Virtual Fitness Buddy ecosystem is a precision health PA intervention for children integrating mixed reality technology to connect people and devices. A cluster randomized, controlled trial was conducted across 19 afterschool sites over two 6-month cohorts to test its efficacy in increasing PA and decreasing sedentary behavior. In the treatment group, a custom virtual dog via a mixed reality kiosk helped children set PA goals while sharing progress with parents to receive feedback and support. Children in the control group set PA goals using a computer without support from the virtual dog or parents. 303 children had 8+ hours of PA data on at least one day of each of the 3 intervention time intervals. Conversion of sedentary time was primarily to light-intensity PA and was strongest for children with low baseline moderate-to-vigorous PA than children above 45 min of baseline moderate-to-vigorous PA. Findings suggest that the VFB ecosystem can promote sustainable PA in children and may be rapidly diffused for widespread public health impact.

Structure-sparing resection for the management of cervical chordomas: a retrospective institutional series.

OBJECTIVE: Chordomas are a rare and relatively slow-growing malignancy of notochordal origin with a nearly 50% recurrence rate. Chordomas of the cervical spine are particularly challenging tumors given surrounding vital anatomical structures. Although standard in other areas of the spine, en bloc resection of cervical chordomas is exceedingly difficult and carries the risk of significant postoperative morbidity. Here, the authors present their institutional experience with 13 patients treated with a structure-sparing radical resection and adjuvant radiation for cervical chordomas. METHODS: Records of the standing senior author and institutional database of spinal surgeries were retrospectively reviewed for surgically managed cervical and high thoracic chordomas between 1997 and 2022. Chordomas whose epicenter was cervical but touched the clivus or had extension to the thoracic spine were included in this series. Clinical and operative data were gathered and analyzed for the index surgery and any revisions needed. Outcome metrics such as recurrence rates, complication rates, functional status, progression-free interval (PFI) and overall survival (OS) were evaluated. RESULTS: The median patient age at diagnosis was 57 (range 32-80) years. The median modified Rankin Scale (mRS) score at the time of presentation was 1 (range 0-4). Approximately 40% of tumors were located in the upper cervical spine (occiput-C2). The median time from diagnosis to surgery was 74.5 (range 10-483) days. Gross-total resection was achieved in just under 40% of patients. All patients received adjuvant radiotherapy. The mean duration of follow-up was 4.09 years, with a mean PFI of 3.80 (range 1.16-13.1) years. Five patients experienced recurrence (38.5%). The mean OS was 3.44 years. Three patients died during the follow-up period; 2 due to disease progression and 1 died in the immediate postoperative period. One patient was lost to follow-up. A significant positive relationship was identified between high cervical tumor location and disease recurrence (p = 0.021). CONCLUSIONS: While en bloc resection is appropriate and feasible for tumors in the sacral spine, the cervical region poses a significant technical challenge and is associated with increased postoperative morbidity. Radical resection may allow for achievement of negative operative margins and, along with sparing postoperative morbidity following resection of cervical chordomas, maintaining a similar rate of recurrence when compared with en bloc resection while preserving quality of life.

Discordance among apoB, non-high-density lipoprotein cholesterol, and triglycerides: implications for cardiovascular prevention.

BACKGROUND AND AIMS: Despite growing evidence that apolipoprotein B (apoB) is the most accurate marker of atherosclerotic cardiovascular disease (ASCVD) risk, its adoption in clinical practice has been low. This investigation sought to determine whether low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (HDL-C), and triglycerides are sufficient for routine cardiovascular care. METHODS: A sample of 293 876 UK Biobank adults (age: 40-73 years, 42% men), free of cardiovascular disease, with a median follow-up for new-onset ASCVD of 11 years was included. Distribution of apoB at pre-specified levels of LDL-C, non-HDL-C, and triglycerides was examined graphically, and 10-year ASCVD event rates were compared for high vs. low apoB. Residuals of apoB were constructed after regressing apoB on LDL-C, non-HDL-C, and log-transformed triglycerides and used as predictors in a proportional hazards regression model for new-onset ASCVD adjusted for standard risk factors, including HDL-C. RESULTS: ApoB was highly correlated with LDL-C and non-HDL-C (Pearson's r = .96, P < .001 for both) but less so with log triglycerides (r = .42, P < .001). However, apoB ranges necessary to capture 95% of all observations at pre-specified levels of LDL-C, non-HDL-C, or triglycerides were wide, spanning 85.8-108.8 md/dL when LDL-C 130 mg/dL, 88.3-112.4 mg/dL when non-HDL-C 160 mg/dL, and 67.8-147.4 md/dL when triglycerides 115 mg/dL. At these levels (±10 mg/dL), 10-year ASCVD rates for apoB above mean + 1 SD vs. below mean - 1 SD were 7.3 vs. 4.0 for LDL-C, 6.4 vs. 4.6 for non-HDL-C, and 7.0 vs. 4.6 for triglycerides (all P < .001). With 19 982 new-onset ASCVD events on follow-up, in the adjusted model, residual apoB remained statistically significant after accounting for LDL-C and HDL-C (hazard ratio 1.06, 95% confidence interval 1.0-1.07), after accounting for non-HDL-C and HDL-C (hazard ratio 1.04, 95% confidence interval 1.03-1.06), and after accounting for triglycerides and HDL-C (hazard ratio 1.13, 95% confidence interval 1.12-1.15). None of the residuals of LDL-C, non-HDL-C, or of log triglycerides remained significant when apoB was included in the model. CONCLUSIONS: High variability of apoB at individual levels of LDL-C, non-HDL-C, and triglycerides coupled with meaningful differences in 10-year ASCVD rates and significant residual information contained in apoB for prediction of new-onset ASCVD events demonstrate that LDL-C, non-HDL-C, and triglycerides are not adequate proxies for apoB in clinical care.

Obturator to Femoral Nerve Transfer: 2-Dimensional Operative Video.

Injury to the femoral nerve can cause femoral nerve palsy,1 resulting in severe ambulation difficulties and loss of sensory function in the anteromedial thigh and medial calf.2,3 Treatment options focus on nerve repair by direct coaptation, nerve grafting, or nerve transfer.3 If the proximal nerve stump is inaccessible, the location of nerve injury is at a distance from the site of muscle innervation, and/or there is a large nerve gap, nerve transfer may be a promising alternative treatment option.4-6 Nerve transfer uses only one coaptation site and allows for a faster recovery time due to a shorter nerve regeneration distance.2,3 A 32-year-old woman presented with persistent and severe proximal right lower extremity weakness after a right retroperitoneal femoral nerve schwannoma resection at an outside institution. After surgery, she reported that she could not flex her right hip or extend her right knee. MRI demonstrated a right femoral nerve gap defect (7.5 cm) at the schwannoma resection site. A right obturator to femoral nerve transfer was performed (see Video). 1.5-year follow-up visit showed that she had begun to have evidence of active recruitment of the right quadriceps muscle and started walking without a knee brace. 2.5-year follow-up visit showed improving strength (4-) in her right quadriceps muscle, independent walking for longer distances, and participation in sporting activities. The patient consented to the procedure, and the patients and any identifiable individuals consented to publication of his/her image. Institutional Review Board approval was not required for this single case observational surgical video.

Loss of tumor-derived SMAD4 enhances primary tumor growth but not metastasis following BMP4 signalling.

BACKGROUND: Bone morphogenetic protein 4 (BMP4) is a potent inhibitor of breast cancer metastasis. However, a tumor-promoting effect of BMP4 is reported in other tumor types, especially when SMAD4 is inactive. METHODS: To assess the requirement for SMAD4 in BMP4-mediated suppression of metastasis, we knocked down SMAD4 in two different breast tumors and enforced SMAD4 expression in a third line with endogenous SMAD4 deletion. In addition, we assessed the requirement for SMAD4 in tumor cell-specific BMP signalling by expression of a constitutively active BMP receptor. Delineation of genes regulated by BMP4 in the presence or absence of SMAD4 was assessed by RNA sequencing and a BMP4-induced gene, MYO1F was assessed for its role in metastasis. Genes regulated by BMP4 and/or SMAD4 were assessed in a publicly available database of gene expression profiles of breast cancer patients. RESULTS: In the absence of SMAD4, BMP4 promotes primary tumor growth that is accompanied by increased expression of genes associated with DNA replication, cell cycle, and MYC signalling pathways. Despite increased primary tumor growth, BMP4 suppresses metastasis in the absence of tumor cell expression of SMAD4. Consistent with the anti-metastatic activity of BMP4, enforced signalling through the constitutively active receptor in SMAD4 positive tumors that lacked BMP4 expression still suppressed metastasis, but in the absence of SMAD4, the suppression of metastasis was largely prevented. Thus BMP4 is required for suppression of metastasis regardless of tumor SMAD4 status. The BMP4 upregulated gene, MYO1F, was shown to be a potent suppressor of breast cancer metastasis. Gene signature upregulated by BMP4 in the absence of SMAD4 was associated with poor prognosis in breast cancer patients, whereas gene signature upregulated by BMP4 in the presence of SMAD4 was associated with improved prognosis. CONCLUSIONS: BMP4 expression is required for suppression of metastasis regardless of the SMAD4 status of the tumor cells. Since BMP4 is a secreted protein, we conclude that it can act both in an autocrine manner in SMAD4-expressing tumor cells and in a paracrine manner on stromal cells to suppress metastasis. Deletion of SMAD4 from tumor cells does not prevent BMP4 from suppressing metastasis via a paracrine mechanism.

Risk factors for vascular injuries in anterior lumbar interbody fusion: a single-institution retrospective study.

OBJECTIVE: Vascular injuries in anterior lumbar interbody fusion (ALIF) occur due to the vascular manipulation needed to achieve optimal disc space exposure. In this study, the authors aimed to evaluate intraoperative vascular injuries in patients undergoing single- and multilevel ALIF at a large tertiary academic center. METHODS: Prospectively collected data specifically addressing postoperative complications in patients who underwent ALIF by neurosurgery spine faculty working with a specialized vascular surgeon were retrospectively reviewed. Demographic characteristics and intraoperative data were collected. Patients were split into vascular injury and non-vascular injury groups. Outcome comparisons were conducted using the chi-square exact and Wilcoxon rank-sum tests for categorical and continuous data, respectively. Logistic regression was used to investigate associations with vascular injury, with univariate analysis first conducted to identify candidate associations. Based on these results, variables demonstrating a between-groups test statistic of p < 0.10 were included in the multivariate analysis to determine the independent predictors of vascular injuries. RESULTS: In total, 323 patients who underwent ALIF procedures were identified: 51% were male (n = 166) and 49% were female (n = 157). The mean age was 57.1 years, with 56% (n = 182) having undergone prior lumbar surgery. Vascular injuries were encountered intraoperatively in 7.1% (n = 23) of patients, and the majority (91% [n = 21]) involved the left common iliac vein. Patients with vascular injuries were statistically older (mean 63.6 vs 56.6 years), had greater incidence rates of coronary artery disease, opioid use, multilevel ALIF surgery involving the L2-3 level, and surgery involving multiple disc spaces, had more multilevel anterior instrumentation, and experienced greater blood loss during surgery and longer length of stay (all p < 0.05). Overall, there was 1 death (0.3%) secondary to aortic artery injury. Multivariate analysis identified opioid use, multilevel ALIF involving L2-3, and multiple interbodies as statistically independent predictors of vascular injury (all p < 0.05). CONCLUSIONS: Identifying patient risk factors can reduce the risk of vascular injuries in ALIF. Opioid use, multilevel ALIF involving L2-3, and multiple interbodies were independent predictors of vascular injuries in ALIF.

Characteristics and Outcomes of Patients Treated with Cervical Spine Fusion at High Volume Hospitals.

BACKGROUND: High volume (HV) has been associated with improved outcomes in various neurosurgical procedures. The objective of this study was to explore the regional distribution of HV spine centers for cervical spine fusion and compare characteristics and outcomes for patients treated at HV centers versus lower volume centers. METHODS: The National Inpatient Sample database 2016-2020 was queried for patients undergoing cervical spine fusion for degenerative pathology. HV was defined as case-loads greater than 2 standard deviations above the mean. Patient characteristics, procedures, and outcomes were compared. RESULTS: Of 3895 hospitals performing cervical spine fusion for degenerative pathology, 28 (0.76%) were HV. The Mid-Atlantic and West South Central regions had the highest number of HV hospitals. HV hospitals were more likely to perform open anterior fusion surgeries (P < 0.01). Patients treated at HV hospitals were less likely to have severe symptomatology or comorbidities (P < 0.01 for all). When controlling for severity and demographics on multivariate analysis, HV centers had higher odds of length of stay ≤1 day, favorable discharge, and decreased total charges. CONCLUSIONS: Patients who underwent cervical spine fusion surgery at HV hospitals were less complex and had increased odds of length of stay ≤1, favorable discharge, and total charges in the lower 25th percentile than patients treated at non-HV hospitals. Physician comfort, patient selection, institutional infrastructure, and geographic characteristics likely play a role.

Momentary Factors and Study Characteristics Associated With Participant Burden and Protocol Adherence: Ecological Momentary Assessment.

BACKGROUND: Ecological momentary assessment (EMA) has become a popular mobile health study design to understand the lived experiences of dynamic environments. The numerous study design choices available to EMA researchers, however, may quickly increase participant burden and could affect overall adherence, which could limit the usability of the collected data. OBJECTIVE: This study quantifies what study design, participant attributes, and momentary factors may affect self-reported burden and adherence. METHODS: The EMA from the Phase 1 Family Matters Study (n=150 adult Black, Hmong, Latino or Latina, Native American, Somali, and White caregivers; n=1392 observation days) was examined to understand how participant self-reported survey burden was related to both design and momentary antecedents of adherence. The daily burden was measured by the question "Overall, how difficult was it for you to fill out the surveys today?" on a 5-item Likert scale (0=not at all and 4=extremely). Daily protocol adherence was defined as completing at least 2 signal-contingent surveys, 1 event-contingent survey, and 1 end-of-day survey each. Stress and mood were measured earlier in the day, sociodemographic and psychosocial characteristics were reported using a comprehensive cross-sectional survey, and EMA timestamps for weekends and weekdays were used to parameterize time-series models to evaluate prospective correlates of end-of-day study burden. RESULTS: The burden was low at 1.2 (SD 1.14) indicating "a little" burden on average. Participants with elevated previous 30-day chronic stress levels (mean burden difference: 0.8; P=.04), 1 in 5 more immigrant households (P=.02), and the language primarily spoken in the home (P=.04; 3 in 20 more non-English-speaking households) were found to be population attributes of elevated moderate-high burden. Current and 1-day lagged nonadherence were correlated with elevated 0.39 and 0.36 burdens, respectively (P=.001), and the association decayed by the second day (ß=0.08; P=.47). Unit increases in momentary antecedents, including daily depressed mood (P=.002) and across-day change in stress (P=.008), were positively associated with 0.15 and 0.07 higher end-of-day burdens after controlling for current-day adherence. CONCLUSIONS: The 8-day EMA implementation appeared to capture momentary sources of stress and depressed mood without substantial burden to a racially or ethnically diverse and immigrant or refugee sample of parents. Attention to sociodemographic attributes (eg, EMA in the primary language of the caregiver) was important for minimizing participant burden and improving data quality. Momentary stress and depressed mood were strong determinants of participant-experienced EMA burden and may affect adherence to mobile health study protocols. There were no strong indicators of EMA design attributes that created a persistent burden for caregivers. EMA stands to be an important observational design to address dynamic public health challenges related to human-environment interactions when the design is carefully tailored to the study population and to study research objectives.