Should pelvic incidence influence realignment strategy? A detailed analysis in adult spinal deformity.

OBJECTIVE: The purpose of this study was to assess how various realignment strategies affect mechanical failure and clinical outcomes in pelvic incidence (PI)-stratified cohorts following adult spinal deformity (ASD) surgery. METHODS: Median and interquartile range statistics were calculated for demographics and surgical details. Further statistical analysis was used to define subsets within PI generating significantly different rates of mechanical failure. These subsets of PI were further analyzed as subcohorts for the outcomes and effects of realignment within each subcohort. Multivariate logistic regression analysis controlling for baseline frailty and lumbar lordosis (LL; L1-S1) analyzed the association of age-adjusted realignment and Global Alignment and Proportion (GAP) strategies with the incidence of mechanical failure and clinical improvement within PI-stratified groups. RESULTS: A parabolic relationship between PI and mechanical failure was noted, whereas patients with either < 51° (n = 174, 39.1% of cohort) or > 63° (n = 114, 25.6% of cohort) of PI generated higher rates of mechanical failure (18.0% and 20.0%, respectively) and lower rates of good outcome (80.3% and 77.6%, respectively) than those with moderate PI (51°-63°). Patients with lower PI more often met good outcome criteria when undercorrected in age-adjusted PI-LL mismatch and sagittal age-adjusted score, and those not meeting good outcome criteria were more likely to deteriorate in GAP relative LL from first to final follow-up (OR 13.4, 95% CI 1.3-139.2). In those with moderate PI, patients were more likely to meet good outcome when aligned on the GAP lordosis distribution index (LDI; OR 1.7, 95% CI 0.9-3.3). Patients with higher PI meeting good outcome were more likely to be overcorrected in sagittal vertical axis (OR 2.4, 95% CI 1.1-5.2) at first follow-up and less likely to be undercorrected in T1 pelvic angle (OR 0.4, 95% CI 0.2-0.9) by final follow-up. When assessing GAP alignment, patients were more likely to meet good outcome when aligned on GAP LDI (OR 3.5, 95% CI 1.4-8.9). CONCLUSIONS: There was a parabolic relationship between PI and both mechanical failure and clinical improvement following deformity correction in this study. Understanding the associations between this fixed parameter and poor outcomes can aid the surgeon in strategical planning when seeking to realign ASD.

Musical training does not enhance neural sound encoding at early stages of the auditory system: A large-scale multisite investigation.

Musical training has been associated with enhanced neural processing of sounds, as measured via the frequency following response (FFR), implying the potential for human subcortical neural plasticity. We conducted a large-scale multi-site preregistered study (n > 260) to replicate and extend the findings underpinning this important relationship. We failed to replicate any of the major findings published previously in smaller studies. Musical training was related neither to enhanced spectral encoding strength of a speech stimulus (/da/) in babble nor to a stronger neural-stimulus correlation. Similarly, the strength of neural tracking of a speech sound with a time-varying pitch was not related to either years of musical training or age of onset of musical training. Our findings provide no evidence for plasticity of early auditory responses based on musical training and exposure.

Gut Microbiome Compositional and Functional Features Associate with Alzheimer's Disease Pathology.

BACKGROUND: The gut microbiome is a potentially modifiable factor in Alzheimer's disease (AD); however, understanding of its composition and function regarding AD pathology is limited. METHODS: Shallow-shotgun metagenomic data was used to analyze fecal microbiome from participants enrolled in the Wisconsin Microbiome in Alzheimer's Risk Study, leveraging clinical data and cerebrospinal fluid (CSF) biomarkers. Differential abundance and ordinary least squares regression analyses were performed to find differentially abundant gut microbiome features and their associations with CSF biomarkers of AD and related pathologies. RESULTS: Gut microbiome composition and function differed between people with AD and cognitively unimpaired individuals. The compositional difference was replicated in an independent cohort. Differentially abundant gut microbiome features were associated with CSF biomarkers of AD and related pathologies. DISCUSSION: These findings enhance our understanding of alterations in gut microbial composition and function in AD, and suggest that gut microbes and their pathways are linked to AD pathology.

Developing a risk score to inform the use of rhBMP-2 in adult spinal deformity surgery.

BACKGROUND: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has not shown superior benefit overall in cost-effectiveness during adult spinal deformity (ASD) surgery. STUDY DESIGN/SETTING: Retrospective PURPOSE: Generate a risk score for pseudarthrosis to inform the utilization of rhBMP-2, balancing costs against quality of life and complications. METHODS: ASD patients with 3-year data were included. Quality of life gained was calculated from ODI to SF-6D and translated to quality-adjusted life years (QALYs). Cost was calculated using the PearlDiver database and CMS definitions for complications and comorbidities. Established weights were generated for predictive variables via logistic regression to yield a predictive risk score for pseudarthrosis that accounted for frailty, diabetes, depression, ASA grade, thoracolumbar kyphosis and three-column osteotomy use. Risk score categories, established via conditional inference tree (CIT)-derived thresholds were tested for cost-utility of rhBMP-2 usage, controlling for age, prior fusion, and baseline deformity and disability. RESULTS: 64% of ASD patients received rhBMP-2 (308/481). There were 17 (3.5%) patients that developed pseudarthrosis. rhBMP-2 use overall did not lower pseudarthrosis rates (OR: 0.5, [0.2-1.3]). Pseudarthrosis rates for each risk category were: No Risk (NoR) 0%; Low-Risk (LowR) 1.6%; Moderate Risk (ModR) 9.3%; High-Risk (HighR) 24.3%. Patients receiving rhBMP-2 had similar QALYs overall to those that did not (0.163 vs. 0.171, p = .65). rhBMP-2 usage had worse cost-utility in the LowR cohort (p < .001). In ModR patients, rhBMP-2 usage had equivocal cost-utility ($53,398 vs. $61,581, p = .232). In the HighR cohort, the cost-utility was reduced via rhBMP-2 usage ($98,328 vs. $211,091, p < .001). CONCLUSION: Our study shows rhBMP-2 demonstrates effective cost-utility for individuals at high risk for developing pseudarthrosis. The generated score can aid spine surgeons in the assessment of risk and enhance justification for the strategic use of rhBMP-2 in the appropriate clinical contexts. LEVEL OF EVIDENCE: III.

Ketone body metabolism and the NLRP3 inflammasome in Alzheimer's disease.

Alzheimer's disease (AD) is a degenerative brain disorder and the most common form of dementia. AD pathology is characterized by senile plaques and neurofibrillary tangles (NFTs) composed of amyloid-ß (Aß) and hyperphosphorylated tau, respectively. Neuroinflammation has been shown to drive Aß and tau pathology, with evidence suggesting the nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome as a key pathway in AD pathogenesis. NLRP3 inflammasome activation in microglia, the primary immune effector cells of the brain, results in caspase-1 activation and secretion of IL-1ß and IL-18. Recent studies have demonstrated a dramatic interplay between the metabolic state and effector functions of immune cells. Microglial metabolism in AD is of particular interest, as ketone bodies (acetone, acetoacetate (AcAc), and ß-hydroxybutyrate (BHB)) serve as an alternative energy source when glucose utilization is compromised in the brain of patients with AD. Furthermore, reduced cerebral glucose metabolism concomitant with increased BHB levels has been demonstrated to inhibit NLRP3 inflammasome activation. Here, we review the role of the NLRP3 inflammasome and microglial ketone body metabolism in AD pathogenesis. We also highlight NLRP3 inflammasome inhibition by several ketone body therapies as a promising new treatment strategy for AD.

Glyphosate effects on growth and biofilm formation in bee gut symbionts and diverse associated bacteria.

Biofilm formation is a common adaptation enabling bacteria to thrive in various environments and withstand external pressures. In the context of host-microbe interactions, biofilms play vital roles in establishing microbiomes associated with animals and plants and are used by opportunistic microbes to facilitate survival within hosts. Investigating biofilm dynamics, composition, and responses to environmental stressors is crucial for understanding microbial community assembly and biofilm regulation in health and disease. In this study, we explore in vivo colonization and in vitro biofilm formation abilities of core members of the honey bee (Apis mellifera) gut microbiota. Additionally, we assess the impact of glyphosate, a widely used herbicide with antimicrobial properties, and a glyphosate-based herbicide formulation on growth and biofilm formation in bee gut symbionts as well as in other biofilm-forming bacteria associated with diverse animals and plants. Our results demonstrate that several strains of core bee gut bacterial species can colonize the bee gut, which probably depends on their ability to form biofilms. Furthermore, glyphosate exposure elicits variable effects on bacterial growth and biofilm formation. In some instances, the effects correlate with the bacteria's ability to encode a susceptible or tolerant version of the enzyme inhibited by glyphosate in the shikimate pathway. However, in other instances, no such correlation is observed. Testing the herbicide formulation further complicates comparisons, as results often diverge from glyphosate exposure alone, suggesting that co-formulants influence bacterial growth and biofilm formation. These findings highlight the nuanced impacts of environmental stressors on microbial biofilms, with both ecological and host health-related implications. IMPORTANCE: Biofilms are essential for microbial communities to establish and thrive in diverse environments. In the honey bee gut, the core microbiota member Snodgrassella alvi forms biofilms, potentially aiding the establishment of other members and promoting interactions with the host. In this study, we show that specific strains of other core members, including Bifidobacterium, Bombilactobacillus, Gilliamella, and Lactobacillus, also form biofilms in vitro. We then examine the impact of glyphosate, a widely used herbicide that can disrupt the bee microbiota, on bacterial growth and biofilm formation. Our findings demonstrate the diverse effects of glyphosate on biofilm formation, ranging from inhibition to enhancement, reflecting observations in other beneficial or pathogenic bacteria associated with animals and plants. Thus, glyphosate exposure may influence bacterial growth and biofilm formation, potentially shaping microbial establishment on host surfaces and impacting health outcomes.

Aspirin in prevention of venous thromboembolism following hip fracture surgery: A systematic review and meta-analysis.

Background: Many orthopaedic surgeons routinely prescribe aspirin (ASA) as prophylaxis for venous thromboembolism (VTE) following hip fracture surgery (HFS). The purpose of this study is to assess the effectiveness of aspirin to other agents in preventing VTE and mortality following hip fracture surgery. Methods: Following PRISMA guidelines, we performed a search for HFS studies from 1998 to 2023 reporting comparisons between aspirin and other chemoprophylaxis methods for VTE (DVT - deep vein thrombosis; PE - pulmonary embolism). SPSS Meta-analysis function was used to calculate Mean Effect Size Estimate (MESE) and 95 % Confidence Intervals for each outcome. Reverse Fragility Index (RFI) and Fragility Quotient (FQ) were calculated for each study. Results: Of the 847 articles screened, 4 studies with 5 comparisons met the search criteria to be included for analysis. A total of 1194 participants were included in these studies. There was a decreased risk of mortality seen with use of aspirin compared to other agents (MESE = 0.86, 95 % CI: [0.07-1.66]; p=.03). There was no increased risk of DVT or PE with use of aspirin (both p>.4). The overall RFI and FQ for all 19 outcomes were 12 (IQR: 6.5-15) and 0.080 (IQR: 0.027-0.110), respectively. Ten studies (52.6 %) reported a loss-to-follow-up (LTF) greater than the overall RFI. Conclusions: Aspirin demonstrates similar protective effects on prevention of VTE compared to other agents and may have significant protective effects on overall mortality following surgical intervention for hip fractures. However, the current evidence concerning its use in this arena is less than robust, with more than half of the studied outcomes considered statistically fragile.

Contemporary utilization of three-column osteotomy techniques in a prospective complex spinal deformity multicenter database: implications on full-body alignment and perioperative course.

BACKGROUND: Research has focused on the increased correction from a three-column osteotomy (3CO) during adult spinal deformity (ASD) surgery. However, an in-depth analysis on the performance of a 3CO in a cohort of complex spinal deformity cases has not been described. STUDY DESIGN/SETTING: This is a retrospective study on a prospectively enrolled, complex ASD database. PURPOSE: This study aimed to determine if three-column osteotomies demonstrate superior benefit in correction of complex sagittal deformity at the cost of increased perioperative complications. METHODS: Surgical complex adult spinal deformity patients were included and grouped into thoracolumbar 3COs compared to those who did not have a 3CO (No 3CO) (remaining cohort). Rigid deformity was defined as ΔLL less than 33% from standing to supine. Severe deformity was defined as global (SVA > 70 mm) or C7-PL > 70 mm, or lumbopelvic (PI-LL > 30°). Means comparison tests assessed correction by 3CO grade/location. Multivariate analysis controlling for baseline deformity evaluated outcomes up to six weeks compared to No 3CO. RESULTS: 648 patients were included (Mean age 61 ± 14.6 years, BMI 27.55 ± 5.8 kg/m2, levels fused: 12.6 ± 3.8). 126 underwent 3CO, a 20% higher usage than historical cohorts. 3COs were older, frail, and more likely to undergo revision (OR 5.2, 95% CI [2.6-10.6]; p < .001). 3COs were more likely to present with both severe global/lumbopelvic deformity (OR 4), 62.4% being rigid. 3COs had greater use of secondary rods (OR 4st) and incurred 4 times greater risk for: massive blood loss (> 3500 mL), longer LOS, SICU admission, perioperative wound and spine-related complications, and neurologic complications when performed below L3. 3COs had similar HRQL benefit, but higher perioperative opioid use. Mean segmental correction increased by grade (G3-21; G4-24; G5-27) and was 4 × greater than low-grade osteotomies, especially below L3 (OR 12). 3COs achieved 2 × greater spinopelvic correction. Higher grades properly distributed lordosis 50% of the time except L5. Pelvic compensation and non-response were relieved more often with increasing grade, with greater correction in all lower extremity parameters (p < .01). Due to the increased rate of complications, 3COs trended toward higher perioperative cost ($42,806 vs. $40,046, p = .086). CONCLUSION: Three-column osteotomy usage in contemporary complex spinal deformities is generally limited to more disabled individuals undergoing the most severe sagittal and coronal realignment procedures. While there is an increased perioperative cost and prolongation of length of stay with usage, these techniques represent the most powerful realignment techniques available with a dramatic impact on normalization at operative levels and reciprocal changes.

AMPK-mediated regulation of endogenous cholesterol synthesis does not affect atherosclerosis in a murine Pcsk9-AAV model.

BACKGROUND AND AIMS: Dysregulated cholesterol metabolism is a hallmark of atherosclerotic cardiovascular diseases, yet our understanding of how endogenous cholesterol synthesis affects atherosclerosis is not clear. The energy sensor AMP-activated protein kinase (AMPK) phosphorylates and inhibits the rate-limiting enzyme in the mevalonate pathway HMG-CoA reductase (HMGCR). Recent work demonstrated that when AMPK-HMGCR signaling was compromised in an Apoe-/- model of hypercholesterolemia, atherosclerosis was exacerbated due to elevated hematopoietic stem and progenitor cell mobilization and myelopoiesis. We sought to validate the significance of the AMPK-HMGCR signaling axis in atherosclerosis using a non-germline hypercholesterolemia model with functional ApoE. METHODS: Male and female HMGCR S871A knock-in (KI) mice and wild-type (WT) littermate controls were made atherosclerotic by intravenous injection of a gain-of-function Pcsk9D374Y-adeno-associated virus followed by high-fat and high-cholesterol atherogenic western diet feeding for 16 weeks. RESULTS: AMPK activation suppressed endogenous cholesterol synthesis in primary bone marrow-derived macrophages from WT but not HMGCR KI mice, without changing other parameters of cholesterol regulation. Atherosclerotic plaque area was unchanged between WT and HMGCR KI mice, independent of sex. Correspondingly, there were no phenotypic differences observed in hematopoietic progenitors or differentiated immune cells in the bone marrow, blood, or spleen, and no significant changes in systemic markers of inflammation. When lethally irradiated female mice were transplanted with KI bone marrow, there was similar plaque content relative to WT. CONCLUSIONS: Given previous work, our study demonstrates the importance of preclinical atherosclerosis model comparison and brings into question the importance of AMPK-mediated control of cholesterol synthesis in atherosclerosis.

The Infected Polypropylene Mesh: When Does Biofilm Form and Which Antiseptic Solution Most Effectively Removes It?

BACKGROUND: Polypropylene (PPE) mesh is commonly utilized to reconstruct catastrophic extensor mechanism disruptions in revision total knee arthroplasty. Unfortunately, these procedures are associated with a high rate of periprosthetic joint infection. The purpose of the current study was to: 1) visualize and quantify the progression of bacterial biofilm growth on PPE-mesh; and 2) determine which antiseptic solutions effectively remove viable bacteria. METHODS: Knitted PPE mesh samples were cultured with either methicillin-sensitive Staphylococcus aureus (MSSA) or Escherichia coli (E. coli) for 7 days, with regular quantification of colony forming units (CFUs) and visualization using scanning electron microscopy to identify maturity. Immature (24 hour) and mature (72 hour) biofilm was treated with one of 5 commercial antiseptics for 3 minutes. A 0.05% chlorhexidine gluconate, a surfactant-based formulation of ethanol, acetic acid, sodium acetate, benzalkonium chloride, diluted povidone-iodine (0.35%), undiluted (10%) povidone-iodine, and 1:1 combination of 10% povidone-iodine and 3% hydrogen peroxide. A 3-log reduction in CFUs compared to saline was considered clinically meaningful. RESULTS: The CFU counts plateaued, indicating maturity, at 72 hours for both MSSA and E. coli. The scanning electron microscopy confirmed confluent biofilm formation after 72 hours. The 10% povidone-iodine was clinically effective against all MSSA biofilms and immature E. coli biofilms. The 10% povidone-iodine with hydrogen peroxide was effective in all conditions. Only 10% povidone iodine formulations produced significantly (P < .0083) reduced CFU counts against mature biofilms. CONCLUSIONS: Bacteria rapidly form biofilm on PPE mesh. Mesh contamination can be catastrophic, and clinicians should consider utilizing an antiseptic solution at the conclusion of mesh implantation. Undiluted povidone-iodine with hydrogen peroxide should be considered when attempting to salvage infected PPE mesh.

Mitigation of CXCL10 secretion by metabolic disorder drugs in microglial-mediated neuroinflammation.

Metabolic disorders are associated with several neurodegenerative diseases. We previously identified C-X-C motif chemokine ligand 10 (CXCL10), also known as interferon gamma-induced protein 10 (IP-10), as a major contributor to the type I interferon response in microglial-mediated neuroinflammation. Therefore, we hypothesized FDA-approved metabolic disorder drugs that attenuate CXCL10 secretion may be repurposed as a treatment for neurodegenerative diseases. Screening, dose curves, and cytotoxicity assays in LPS-stimulated microglia yielded treprostinil (hypertension), pitavastatin (hyperlipidemia), and eplerenone (hypertension) as candidates that significantly reduced CXCL10 secretion (in addition to other pro-inflammatory mediators) without impacting cell viability. Altogether, these data suggest metabolic disorder drugs that attenuate CXCL10 as potential treatments for neurodegenerative disease through mitigating microglial-mediated neuroinflammation.

Myeloid AMPK signaling restricts fibrosis but is not required for metformin improvements during CDAHFD-induced NASH in mice.

Metabolic programming underpins inflammation and liver macrophage activation in the setting of chronic liver disease. Here, we sought to identify the role of an important metabolic regulator, AMP-activated protein kinase (AMPK), specifically within myeloid cells during the progression of non-alcoholic steatohepatitis (NASH) and whether treatment with metformin, a firstline therapy for diabetes and activator of AMPK could stem disease progression. Male and female Prkaa1fl/fl/Prkaa2fl/fl (Flox) control and Flox-LysM-Cre+ (MacKO) mice were fed a low-fat control or a choline-deficient, amino acid defined 45% Kcal high-fat diet (CDAHFD) for 8 weeks, where metformin was introduced in the drinking water (50 or 250 mg/kg/day) for the last 4 weeks. Hepatic steatosis and fibrosis were dramatically increased in response to CDAHFD-feeding compared to low-fat control. While myeloid AMPK signaling had no effect on markers of hepatic steatosis or circulating markers, fibrosis as measured by total liver collagen was significantly elevated in livers from MacKO mice, independent of sex. Although treatment with 50 mg/kg/day metformin had no effect on any parameter, intervention with 250 mg/kg/day metformin completely ameliorated hepatic steatosis and fibrosis in both male and female mice. While the protective effect of metformin was associated with lower final body weight, and decreased expression of lipogenic and Col1a1 transcripts, it was independent of myeloid AMPK signaling. These results suggest that endogenous AMPK signaling in myeloid cells, both liver-resident and infiltrating, acts to restrict fibrogenesis during CDAHFD-induced NASH progression but is not the mechanism by which metformin improves markers of NASH.

Lower Hounsfield Units at the Planned Lowest Instrumented Vertebra is an Independent Risk Factor for Complications Following Adult Cervical Deformity Surgery.

BACKGROUND: The association of Hounsfield units (HU) and junctional pathologies in adult cervical deformity (ACD) surgery has not been elucidated. OBJECTIVE: Assess if the bone mineral density of the LIV, as assessed by HUs, is prognostic for the risk of complications after ACD surgery. STUDY DESIGN/SETTING: Retrospective cohort study. METHODS: HUs were measured on preoperative CT scans. Means comparison test assessed differences in HUs based on the occurrence of complications, linear regression assessed the correlation of HUs with risk factors, and multivariable logistic regression followed by a conditional inference tree derived a threshold for HUs based on the increased likelihood of developing a complication. RESULTS: In all, 107 ACD patients were included. Thirty-one patients (29.0%) developed a complication (18.7% perioperative), with 20.6% developing DJK and 11.2% developing DJF. There was a significant correlation between lower LIVs and lower HUs (r=0.351, P=0.01), as well as age and HUs at the LIV. Age did not correlate with change in the DJK angle (P>0.2). HUs were lower at the LIV for patients who developed a complication and an LIV threshold of 190 HUs was predictive of complications (OR: 4.2, [1.2-7.6]; P=0.009). CONCLUSIONS: Low bone mineral density at the lowest instrumented vertebra, as assessed by a threshold lower than 190 Hounsfield units, may be a crucial risk factor for the development of complications after cervical deformity surgery. Preoperative CT scans should be routinely considered in at-risk patients to mitigate this modifiable risk factor during surgical planning. LEVEL OF EVIDENCE: Level-III.

Scalp Reconstruction With Free Tissue Transfer as a Palliative Surgical Intervention in a High-Risk Population.

Microvascular reconstruction of the scalp is frequently indicated in patients with locally advanced tumors, among other etiologies, in a relatively high-risk, older patient population that often has multiple medical comorbidities. A retrospective analysis was performed on patients undergoing microvascular scalp reconstruction at Emory University Hospital and Grady Memorial Hospital between 2011 and 2021. Patient demographics, wound characteristics, operative details, and complications were recorded. Statistical analysis using univariate and multivariate models was performed. Forty-two patients underwent 45 microvascular scalp reconstructive procedures during the study period. The median age was 63 years. Wounds were predominantly oncologic (n=38, 84.4%) and frequently involved deeper structures [calvarium (n=38, 84.4%), dura (n=17, 37.8%)]. At a median follow-up of 350 days, 33 patients (73.3%) had healed flaps, 9 (20.0%) had wound healing issues but ultimately successful reconstruction, and 3 (6.7%) experienced flap failure. Most patients (n=33, 80.9%) were discharged home or to a rehabilitation facility, while the remaining 8 patients (19.1%) were discharged to hospice or died. The 30-day mortality was 4 patients (8.9%) and the 6-month mortality was 8 patients (20.5%). There was a statistically significant difference in 30-day mortality (P=0.0001) on univariate analysis and 6-month mortality (P=0.003) on both univariate and multivariate analysis for patients >70 years. While age >70 years is a risk factor for mortality in patients undergoing microvascular scalp reconstruction, mortality was commonly related to underlying disease processes rather than complication of surgery. Microvascular reconstruction for scalp defects has a high success rate and can be offered as a palliative procedure for patients with locally advanced cancers, advanced age, and multiple comorbidities.

Impact of congestive heart failure on patients undergoing lumbar spine fusion for adult spine deformity.

Background: With the increasing amount of elective spine fusion patients presenting with cardiac disease and congestive heart failure, it is becoming difficult to assess when it is safe to proceed with surgery. Assessing the severity of heart failure (HF) through ejection fraction may provide insight into patients' short- and long-term risks. Purpose: The purpose of this study was to assess the severity of HF on perioperative outcomes of spine fusion surgery patients. Study Design/Setting: This was a retrospective cohort study of the PearlDiver database. Patient Sample: We enrolled 670,526 patients undergoing spine fusion surgery. Outcome Measures: Thirty-day and 90-day complication rates, discharge destination, length of stay (LOS), physician reimbursement, and hospital costs. Methods: Patients undergoing elective spine fusion surgery were isolated and stratified by preoperative HF with preserved ejection fraction (P-EF) or reduced ejection fraction (R-EF) (International Classification of Diseases-9: 428.32 [chronic diastolic HF] and 428.22 [chronic systolic HF]). Means comparison tests (Chi-squared and independent samples t-tests, as appropriate) compared differences in demographics, diagnoses, comorbidities, procedural characteristics, LOS, 30-day and 90-day complication outcomes, and total hospital charges between those diagnosed with P-EF and those not R-EF. Binary logistic regression assessed the odds of complication associated with HF, controlling for levels fused (odds ratio [OR] [95% confidence interval]). Statistical significance was set at P < 0.05. Results: Totally 670,526 elective spine fusion patients were included. Four thousand and seventy-seven were diagnosed with P-EF and 2758 R-EF. Overall, P-EF patients presented with higher rates of morbid obesity, chronic kidney disease, chronic obstructive pulmonary disease, diabetes mellitus, and hypertension (all P < 0.001). In relation to No-HF, P-EF patients had higher rates of 30-day major complications including pulmonary embolism, pneumonia, cerebrovascular accident (CVA), myocardial infarctions (MI), sepsis, and death (all P < 0.001). Furthermore, P-EF was associated significantly with increased odds of pneumonia (OR: 2.07 [1.64-2.56], P < 0.001) and sepsis (OR: 2.09 [1.62-2.66], P < 0.001). Relative to No-HF, R-EF was associated with significantly higher odds of MI (OR: 3.66 [2.34-5.47]), CVA (OR: 2.70 [1.67-4.15]), and pneumonia (OR: 1.85 [1.40-2.40]) (all P < 0.001) postoperative within 30 days. Adjusting for prior history of MI, CAD, and the presence of a pacemaker R-EF was a significant predictor of an MI 30 days postoperatively (OR: 2.2 [1.14-4.32], P = 0.021). Further adjusting for history of CABG or stent placement, R-EF was associated with higher odds of CVA (OR: 2.11 [1.09-4.19], P = 0.028) and MI (OR: 2.27 [1.20-4.43], P = 0.013). Conclusions: When evaluating the severity of HF before spine surgery, R-EF was associated with a higher risk of major complications, especially the occurrence of a myocardial infarction 30 days postoperatively. During preoperative risk assessment, congestive HF should be considered thoroughly when thinking of postoperative outcomes with emphasis on R-EF.

Zinc utilization by microglia in Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia defined by two key pathological characteristics in the brain, amyloid-ß (Aß) plaques and neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau. Microglia, the primary innate immune cells of the central nervous system (CNS), provide neuroprotection through Aß and tau clearance but may also be neurotoxic by promoting neuroinflammation to exacerbate Aß and tau pathogenesis in AD. Recent studies have demonstrated the importance of microglial utilization of nutrients and trace metals in controlling their activation and effector functions. Trace metals, such as zinc, have essential roles in brain health and immunity, and zinc dyshomeostasis has been implicated in AD pathogenesis. As a result of these advances, the mechanisms by which zinc homeostasis influences microglial-mediated neuroinflammation in AD is a topic of continuing interest since new strategies to treat AD are needed. Here, we review the roles of zinc in AD, including zinc activation of microglia, the associated neuroinflammatory response, and the application of these findings in new therapeutic strategies.

Talker change detection by listeners varying in age and hearing loss.

Despite a vast literature on how speech intelligibility is affected by hearing loss and advanced age, remarkably little is known about the perception of talker-related information in these populations. Here, we assessed the ability of listeners to detect whether a change in talker occurred while listening to and identifying sentence-length sequences of words. Participants were recruited in four groups that differed in their age (younger/older) and hearing status (normal/impaired). The task was conducted in quiet or in a background of same-sex two-talker speech babble. We found that age and hearing loss had detrimental effects on talker change detection, in addition to their expected effects on word recognition. We also found subtle differences in the effects of age and hearing loss for trials in which the talker changed vs trials in which the talker did not change. These findings suggest that part of the difficulty encountered by older listeners, and by listeners with hearing loss, when communicating in group situations, may be due to a reduced ability to identify and discriminate between the participants in the conversation.

Comparison of multilevel low-grade techniques versus three-column osteotomies in adult spinal deformity surgery: does harmonious correction matter?

OBJECTIVE: Recent debate has arisen between whether to use a three-column osteotomy (3CO) or multilevel low-grade (MLG) techniques to treat severe sagittal malalignment in adult spinal deformity (ASD) surgery. The goal of this study was to compare the outcomes of 3CO and MLG techniques performed in corrective surgeries for ASD. METHODS: ASD patients who had a baseline PI-LL > 30° and 2-year follow-up data were included. Patients underwent either 3CO or MLG (thoracolumbar posterior column osteotomies at ≥ 3 levels or anterior lumbar interbody fusion at ≥ 3 levels with no 3CO). The segmental utility ratio was used to assess relative segmental correction (segmental correction divided by overall correction in lordosis divided by the number of thoracolumbar interventions [interbody fusion, thoracolumbar posterior column osteotomies, and 3CO]). The paired t-test was used to assess lordotic distribution by differences in lordosis between adjacent lumbar disc spaces (e.g., L1-2 to L2-3). Multivariate analysis, controlling for age, sex, BMI, osteoporosis, baseline pelvic incidence, and T1 pelvic angle, was used to evaluate the complication rates and radiographic and patient-reported outcomes between the groups. RESULTS: A total of 93 patients were included, 53% of whom underwent MLG and 47% of whom underwent 3CO. The MLG group had a lower BMI (p < 0.05). MLG patients received fewer previous fusions than 3CO patients (31% vs 80%, p < 0.001). MLG patients had 24% less blood loss but a 22% longer operative time (565 vs 419 minutes, p = 0.008). Using adjusted analysis, the 3CO group had greater segmental and relative correction at each level (segmental utility ratio mean 69% for 3CO vs 23% for MLG, p < 0.001). However, the 3CO group had lordotic differences between two adjacent lumbar disc pairs (range -0.5° to 9.0°, p = 0.009), while MLG was more harmonious (range 2.2°-6.5°, p > 0.4). MLG patients were more likely to undergo realignment to age-adjusted standards (OR 5.6, 95% CI 1.2-46.4; p = 0.033). MLG patients were less likely to develop neurological complications or undergo reoperation (OR 0.4, 95% CI 0.1-0.9; p = 0.041). Adjusted analysis revealed that MLG patients more often met a substantial clinical benefit in the Oswestry Disability Index score (OR 5.3, 95% CI 1.1-26.8; p = 0.043). CONCLUSIONS: MLG techniques showed better utility in lumbar distribution and age-adjusted global correction while minimizing neurological complications and reoperation rates by 2 years postoperatively. In selected instances, these techniques may offer the spine deformity surgeon a safer alternative when correcting severe adult spinal deformity.

Comparison of evaluation methods for improving the usability of a Spanish mHealth tool.

OBJECTIVE: Mobile health (mHealth) technology is now widely used across health conditions and populations. The rigorous development of these tools has yielded improved health outcomes, yet the ideal approach for developing mHealth tools continues to evolve, indicating the need for rigorous usability evaluation methods. This study compares two usability evaluation methods - cognitive interviews and usability assessments employing a think-aloud approach - for adapting an evidence-based mHealth tool from English into Spanish. METHODS: We conducted cognitive interviews and usability assessments using a think-aloud protocol to evaluate the usability of an HIV mHealth application among 40 Spanish-speaking adults with HIV in New York City, NY, and La Romana, Dominican Republic. The Health IT Usability Evaluation Model (Health-ITUEM) was used to guide the analysis of qualitative data collected from each method. RESULTS: Participants (N = 40) averaged 43 years old (SD = 12.26; range 20-79), identified primarily Hispanic/Latino (92.5 %), and resided in La Romana (50 %) or New York City (50 %). Both usability evaluation methods yielded similar findings, highlighting learnability and information needs as crucial components of participant feedback for the mHealth application. Cognitive interviews captured participants' perspectives on the app's interface and design. On the other hand, results from usability assessments offered insights into participants' competency while interacting with the mHealth tool. CONCLUSION: Findings from this study highlight the contributions and limitations of including cognitive interviews and task-based usability assessments using a think-aloud approach in mHealth usability testing. Future research should employ a multi-method approach, incorporating complementary usability evaluation methods and engaging participants in multiple assessments. Using complementary usability evaluation methods may provide a more comprehensive understanding of the usability and participant experience aspects of a mHealth tool compared to using a single usability evaluation method.

Top 50 most impactful publications on massive rotator cuff tears.

Background: Bibliometric analysis is a useful tool for measuring the scholarly impact of a topic and its more and less heavily studied aspects. The purpose of this study is to use bibliometric analysis to comprehensively analyze the 50 articles with the highest citation indices in studies evaluating the treatment and outcomes of massive rotator cuff tears (mRCTs). Methods: This cross-sectional study identified articles within the Scopus database published through December 2022. Keywords used were "massive rotator cuff tear." Articles were sorted in chronological order. The year published and number of citations were recorded. A citation index (CI) was calculated for each article by dividing the number of citations by number of years published [1 citation/1 year published (2021) = CI of 1]. Of these, the 50 articles with the highest CIs were carried forward for evaluation. Frequencies and distributions were assessed for data of each variable collected. Results: These search methods produced 625 articles regarding mRCT research (ranging from January 1986 to December 2022). Four of the top 10 most impactful articles were published in the 2010s. The level of evidence (LOE) published with the greatest frequency was level of evidence 4 (41%). The journal Arthroscopy published the highest number within the top 50 (26%) followed by the Journal of Bone and Joint Surgery and the American Journal of Sports Medicine (20% each). Clinical studies composed 88% of the top 50. Case series (38%) predominated, while systematic reviews (20%) and randomized control trials (8%) were less prevalent. The majority of studies concentrated on the clinical outcomes of certain interventions (62%), mainly comparing multiple interventions. Conclusion: Despite the relatively high prevalence of mRCTs (40% of all tears), this topic comprises only a small proportion of all rotator cuff research. This analysis has identified gaps within and limitations of the findings concerning mRCTs for researchers to propose research questions targeting understudied topics and influence the future treatment and outcomes of this clinically difficult diagnosis.