Quantifying Gut Microbial Short-Chain Fatty Acids and Their Isotopomers in Mechanistic Studies Using a Rapid, Readily Expandable LC-MS Platform.

Short-chain fatty acids (SCFAs) comprise the largest group of gut microbial fermentation products. While absorption of most nutrients occurs in the small intestine, indigestible dietary components, such as fiber, reach the colon and are processed by the gut microbiome to produce a wide array of metabolites that influence host physiology. Numerous studies have implicated SCFAs as key modulators of host health, such as in regulating irritable bowel syndrome (IBS). However, robust methods are still required for their detection and quantitation to meet the demands of biological studies probing the complex interplay of the gut-host-health paradigm. In this study, a sensitive, rapid-throughput, and readily expandible UHPLC-QqQ-MS platform using 2-PA derivatization was developed for the quantitation of gut-microbially derived SCFAs, related metabolites, and isotopically labeled homologues. The utility of this platform was then demonstrated by investigating the production of SCFAs in cecal contents from mice feeding studies, human fecal bioreactors, and fecal/bacterial fermentations of isotopically labeled dietary carbohydrates. Overall, the workflow proposed in this study serves as an invaluable tool for the rapidly expanding gut-microbiome and precision nutrition research field.

A Neptune-mass exoplanet in close orbit around a very low-mass star challenges formation models.

Theories of planet formation predict that low-mass stars should rarely host exoplanets with masses exceeding that of Neptune. We used radial velocity observations to detect a Neptune-mass exoplanet orbiting LHS 3154, a star that is nine times less massive than the Sun. The exoplanet's orbital period is 3.7 days, and its minimum mass is 13.2 Earth masses. We used simulations to show that the high planet-to-star mass ratio (>3.5 × 10-4) is not an expected outcome of either the core accretion or gravitational instability theories of planet formation. In the core-accretion simulations, we show that close-in Neptune-mass planets are only formed if the dust mass of the protoplanetary disk is an order of magnitude greater than typically observed around very low-mass stars.

Safety and functional outcomes of early antiplatelet therapy within 24 hours following mechanical thrombectomy for secondary prevention in emergent large-vessel occlusion strokes: a registry study.

OBJECTIVE: The aim of this study was to demonstrate the safety and functional outcomes of antiplatelet use within 24 hours following mechanical thrombectomy (MT). METHODS: A retrospective review of prospectively collected data for consecutive patients who underwent MT for acute ischemic stroke (AIS) between 2016 and 2020 was performed. Patient demographics, comorbidities, Alberta Stroke Program Early CT Score (ASPECTS), antiplatelet use, neurological status, and tissue plasminogen activator use were collected. Patients were stratified into two groups, early (< 24 hours) or late (> 24 hours), based on when antiplatelet therapy was initiated post-MT. The primary outcome was safety, determined based on the rate of symptomatic intracranial hemorrhage (sICH) and inpatient mortality. The secondary outcome was functional independence (defined as modified Rankin Scale [mRS] score ≤ 2) at discharge and 30 days and 90 days postoperatively. The two cohorts were compared using univariate analysis. Multiple imputations were used to create complete data sets for missing data. Multivariable analysis was used to identify predictors for sICH and functional outcomes. RESULTS: A total of 190 patients met inclusion criteria (95 per group). Significant differences between the early and late groups included sex, preoperative intravenous thrombolysis, angioplasty, stent placement, and thrombectomy site. ICH (symptomatic and asymptomatic) and inpatient mortality were not significantly different between the groups. The mRS score was significantly lower at discharge (p < 0.001), 30 days (p = 0.011), and 90 days (p = 0.024) following MT in the early group. Functional independence was significantly higher in the early antiplatelet group at discharge (p = 0.015) and at 30 days (p = 0.006). Early antiplatelet use was independently associated with significantly increased odds of achieving functional independence at discharge (OR 3.07, p = 0.007) and 30 days (OR 5.78, p = 0.004). Early antiplatelet therapy was not independently associated with increased odds of sICH. CONCLUSIONS: Early antiplatelet initiation after MT in patients with AIS was independently associated with significantly increased odds of improved postoperative functional outcomes without increased odds of developing sICH.

Effect of Respiratory Viral Panel Adoption on Antibiotic Use in Ventilated Patients.

Rationale: Rapid respiratory viral panel (RVP) testing has become widely used to aid in the diagnosis and treatment of acute respiratory failure. However, the impact of RVP on antibiotic stewardship in critically ill patients is unclear. Objectives: To assess if adoption of RVP testing at hospitals was associated with changes in antibiotic duration in intensive care unit patients receiving invasive mechanical ventilation. Methods: With data from the Premier Inc. database from 2016 to 2019, we used interrupted time series with multivariable hierarchical linear regression models to quantify trends in outcomes for 31,644 patients in the 12 months before RVP adoption, the level change in outcomes at the time of RVP adoption (estimand of interest), and changes in outcome trends in the 12 months after RVP adoption. Results: Hospital adoption of RVP testing (n = 62,603) was associated with a decrease in days of antibiotics by 0.5 days (95% confidence interval, -0.8, -0.1) in the first month after adoption. There was also a significant decrease in the risk of Clostridioides difficile infection by 0.9% (95% confidence interval, -1.6, -0.3). There were no significant changes in other outcomes, including hospitalization costs, hospital length of stay, or rates of ventilator-associated pneumonia. Conclusions: Hospital adoption of RVP testing was associated with modest reductions in both antibiotic duration and risk of C. difficile infection among intensive care unit patients with acute respiratory failure and suspected infection.

The Effect of Preoperative Symptom Duration on Patient-Reported Outcomes After Anterior Cervical Discectomy and Fusion in Nonmyelopathic Patients: Analyses From the Michigan Spine Surgery Improvement Collaborative (MSSIC).

BACKGROUND: The effect of preoperative symptom duration (PSD) on patient-reported outcomes (PROs) in anterior cervical discectomy and fusion (ACDF) for radiculopathy is unclear. OBJECTIVE: To determine whether PSD is a predictor for PRO after ACDF for radiculopathy. METHODS: The Michigan Spine Surgery Improvement Collaborative registry was queried between March, 2014, and July, 2019, for patients who underwent ACDF without myelopathy and PROs (baseline, 90 days, 1 year, 2 years). PROs were measured by numerical rating scales for neck/arm pain, Patient-Reported Outcomes Measurement Information System Short Form-Physical Function (PROMIS-PF), EuroQol-5D (EQ5D), and North American Spine Society satisfaction. Univariate analyses were used to evaluate the proportion of patients reaching minimal clinically important differences (MCID). PSD was <3 months, 3 month-1 year, or >1 years. Multiple logistic regression models were used to estimate the association between PSD and PRO reaching MCID. The discriminative ability of the model was evaluated by receiver operating characteristic curve. RESULTS: We included 2233 patients who underwent ACDF with PSD <3 months (278, 12.4%), 3 month-1 year (669, 30%), and >1 years (1286, 57.6%). Univariate analyses demonstrated a greater proportion of patients achieving MCID in <3-month cohort for arm numerical rating scales, PROMIS-PF, EQ5D, and North American Spine Society Satisfaction. Multivariable analyses demonstrated using <3 months PSD as a reference, PSD >1 years was associated with decreased odds of achieving MCID for EQ5D (odds ratio 0.5, CI 0.32-0.80, P = .004). Private insurance and increased baseline PRO were associated with significantly higher odds for achieving PROMIS-PF MCID and EQ5D-MCID. CONCLUSION: Preoperative symptom duration greater than 1 year in patients who underwent ACDF for radiculopathy was associated with worse odds of achieving MCID for multiple PROs.

Radiographic and Patient-Reported Outcomes of Lordotic Versus Non-lordotic Static Interbody Devices in Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Longitudinal Comparative Cohort Study.

Introduction Minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) is increasingly used to treat lumbar degenerative pathology. Its effect on sagittal parameters remains controversial. Static and expandable lordotic interbody devices (cages) were developed to improve segmental and overall lumbar lordosis. This study aimed to compare the radiographic and patient-reported outcomes (PROs) between static lordotic and non-lordotic titanium cages in patients undergoing 1-2 level MI-TLIF for degenerative conditions.  Methods We reviewed consecutive eligible patients who underwent 1-2 level MI-TLIF (7/2017-11/2019) at a single institution by multiple surgeons. Standing X-rays and PROs were collected at preoperative, 1-month, and 6-month postoperative intervals. Using univariate analyses, we compared the two cohorts regarding confounders, radiographic parameters, and proportions of patients reaching minimal clinically important difference (MCID) for PROs. Results One-hundred-twenty-five patients were reviewed. Forty-seven had lordotic and seventy-eight non-lordotic cages. The lordotic cohort was significantly younger than the non-lordotic (55.9 years vs. 60.7 years, p= 0.042). The baseline radiographic parameters were not significantly different between cohorts. At the preoperative-6-month interval, the lordotic cohort had significant improvement in lumbar lordosis versus non-lordotic cohort (2.95° ± 7.2° vs. -0.3° ± 7.1°, p=0.024). Both cohorts showed improvement in segmental lordosis, anterior and posterior interspace height, and low subsidence grade with no significant difference between cohorts at all intervals. Overall, 69.1-83.8% of patients achieved MCID in all PROs with no significant difference between cohorts. Conclusions The use of a static lordotic titanium cage in 1-2 level MI-TLIF did not result in significantly different radiographic improvements or PROs compared with a non-lordotic cage.

Ocular manifestations of disseminated Mycobacterium chimaera infection after cardiothoracic surgery.

OBJECTIVE: To describe the ocular manifestations of disseminated Mycobacterium chimaera infection after cardiothoracic surgery. DESIGN: Retrospective, observational case series. PARTICIPANTS: Patients with disseminated M. chimaera infection treated at the University of Alberta Hospital and Royal Alexandra Hospital in Edmonton, Alberta, Canada. METHODS: Seven patients (14 eyes) with systemic M. chimaera infection after aortic graft and/or valvular surgeries were reviewed for ocular involvement. Cases were identified based on histopathologic analysis of cardiac tissue, repeat positive mycobacterial blood cultures, and cerebrospinal fluid analysis. Clinical ocular findings, fundus autofluorescence, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), and autopsy results are described. RESULTS: The mean age of our patients was 63 years (range, 22-76 years). Aortic graft and/or valvular surgeries were performed between June 2015 and April 2016. The mean duration from surgery to diagnosis of infection was 27 months (range, 19-36 months). All patients exhibited white-yellowish choroidal lesions. Bilateral, multifocal choroiditis was observed in 6 patients (12 eyes), who died of disseminated M. chimaera infection despite aggressive, multiagent antimicrobial therapy. One patient had a solitary, white-yellow choroidal lesion in the left eye only. Choroidal lesions were hyperfluorescent on late-phase fluorescein angiography and corresponded to localized choroidal thickening and retinal elevation on SD-OCT. CONCLUSIONS: M. chimaera infection after cardiothoracic surgery can cause life-threatening disease involving multiple organ systems. Ocular involvement is an important and possibly early clinical finding, with good correlation to systemic disease severity. Ophthalmological assessment and multimodal imaging may aid in early diagnosis and can be used to monitor disease progression.

Influence of high-protein and high-carbohydrate diets on serum lipid and fructosamine concentrations in healthy cats.

OBJECTIVES: The aim of this study was to determine whether high-protein and high-carbohydrate diets exert differential effects on serum cholesterol, triglyceride and fructosamine concentrations in healthy cats. METHODS: A randomised, crossover diet trial was performed in 35 healthy shelter cats. Following baseline health assessments, cats were randomised into groups receiving either a high-protein or high-carbohydrate diet for 4 weeks. The cats were then fed a washout diet for 4 weeks before being transitioned to whichever of the two studied diets they had not yet received. Fasting serum cholesterol, triglyceride and fructosamine concentrations were determined at the end of each 4-week diet period. RESULTS: Cats on the high-carbohydrate diet had significantly lower serum cholesterol (P <0.001) concentrations compared with baseline measurements. Cats on the high-protein diet had significantly higher serum cholesterol (P <0.001) and triglyceride (P <0.001) concentrations, yet lower fructosamine (P <0.001) concentrations compared with baseline measurements. In contrast, overweight cats (body condition score [BCS] >5) had lower cholesterol (P = 0.007) and triglyceride (P = 0.032) concentrations on the high-protein diet than cats within other BCS groups. CONCLUSIONS AND RELEVANCE: Diets higher in protein and lower in carbohydrates appear beneficial for short-term glucose control in healthy cats. A high-protein diet was associated with significantly elevated cholesterol and triglyceride concentrations in healthy cats, even though the increase was significantly less pronounced in cats with a BCS >5. This finding suggests that overweight cats process high-protein diets, cholesterol and triglycerides differently than leaner cats.

The effect of ketorolac on posterior minimally invasive transforaminal lumbar interbody fusion: an interim analysis from a randomized, double-blinded, placebo-controlled trial.

BACKGROUND CONTEXT: Postoperative pain control following posterior lumbar fusion continues to be challenging and often requires high doses of opioids for pain relief. The use of ketorolac in spinal fusion is limited due to the risk of pseudarthrosis. However, recent literature suggests it may not affect fusion rates with short-term use and low doses. PURPOSE: We sought to demonstrate noninferiority regarding fusion rates in patients who received ketorolac after undergoing minimally invasive (MIS) posterior lumbar interbody fusion. Additionally, we sought to demonstrate ketorolac's opioid-sparing effect on analgesia in the immediate postoperative period. STUDY DESIGN/SETTING: This is a prospective, randomized, double-blinded, placebo-controlled trial. We are reporting our interim analysis. PATIENT SAMPLE: Adults with degenerative spinal conditions eligible to undergo a one to three-level MIS transforaminal lumbar interbody fusion (TLIF). OUTCOME MEASURES: Six-month and 1-year radiographic fusion as determined by Suk criteria, postoperative opioid consumption as measured by intravenous milligram morphine equivalent, length of stay, and drug-related complications. Self-reported and functional measures include validated visual analog scale, short-form 12, and Oswestry Disability Index. METHODS: A double-blinded, randomized placebo-controlled, noninferiority trial of patients undergoing 1- to 3-level MIS TLIF was performed with bone morphogenetic protein (BMP). Patients were randomized to receive a 48-hour scheduled treatment of either intravenous ketorolac (15 mg every 6 hours) or saline in addition to a standardized pain regimen. The primary outcome was fusion. Secondary outcomes included 48-hour and total postoperative opioid use demonstrated as milligram morphine equivalence, pain scores, length of stay (LOS), and quality-of-life outcomes. Univariate analyses were performed. The present study provides results from a planned interim analysis. RESULTS: Two hundred and forty-six patients were analyzed per protocol. Patient characteristics were comparable between the groups. There was no significant difference in 1-year fusion rates between the two treatments (p=.53). The difference in proportion of solid fusion between the ketorolac and placebo groups did not reach inferiority (p=.072, 95% confidence interval, -.07 to .21). There was a significant reduction in total/48-hour mean opioid consumption (p<.001) and LOS (p=.001) for the ketorolac group while demonstrating equivalent mean pain scores in 48 hours postoperative (p=.20). There was no significant difference in rates of perioperative complications. CONCLUSIONS: Short-term use of low-dose ketorolac in patients who have undergone MIS TLIF with BMP demonstrated noninferior fusion rates. Ketorolac safely demonstrated a significant reduction in postoperative opioid use and LOS while maintaining equivalent postoperative pain control.

Age as a Risk Factor for Complications Following Anterior Cervical Discectomy and Fusion: Analysis From the Michigan Spine Surgery Improvement Collaborative (MSSIC).

STUDY DESIGN: Retrospective analysis of prospectively collected registry data using multivariable analyses of imputed data. OBJECTIVE: We sought to demonstrate that age would not be associated with complications in patients undergoing anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: Elderly patients (≥70 yrs) undergoing ACDF are considered a higher risk for complications. However, conclusive evidence is lacking. The Michigan Spine Surgery Improvement Collaborative (MSSIC) is a quality improvement collaborative with 30 hospitals across Michigan. METHODS: The study included all patients who had 1 to 4 level ACDF (September 2015-August 2019) for 90-day complications. Major and minor complications were defined using a validated classification. Multiple imputations were used to generate complete covariate datasets. Generalized estimating equation model was used to identify associations with complications using the whole cohort and elderly subgroup analyses. Bonferroni correction was used. RESULTS: Nine thousand one hundred thirty five patients (11.1% ≥ 70 yrs and 88.9% <70 yrs) with 2266 complications were analyzed. Comparing elderly versus non-elderly, the elderly had a significantly higher rate of any complications (31.5% vs. 24.0%, P < 0.001) and major complications (14.1% vs. 7.0%, P < 0.001). On multivariable analysis, age was not independently associated with any complication. POD#0 ambulation and preop independent ambulation were independently associated with significantly decreased odds of any complication. In the elderly, independent preoperative ambulation was protective for any complication (odds ratio [OR] 0.53, 0.39-0.73 95% confidence interval [CI]), especially major complications (OR 0.41, 0.27-0.61 95% CI). CONCLUSION: Age was not an independent risk factor for complications in patients that underwent ACDF. In the elderly, independent preoperative ambulation was especially protective for major complications.Level of Evidence: 3.

Fucosylated Human Milk Oligosaccharide Foraging within the Species Bifidobacterium pseudocatenulatum Is Driven by Glycosyl Hydrolase Content and Specificity.

Human milk enriches members of the genus Bifidobacterium in the infant gut. One species, Bifidobacterium pseudocatenulatum, is found in the gastrointestinal tracts of adults and breastfed infants. In this study, B. pseudocatenulatum strains were isolated and characterized to identify genetic adaptations to the breastfed infant gut. During growth on pooled human milk oligosaccharides (HMOs), we observed two distinct groups of B. pseudocatenulatum, isolates that readily consumed HMOs and those that did not, a difference driven by variable catabolism of fucosylated HMOs. A conserved gene cluster for fucosylated HMO utilization was identified in several sequenced B. pseudocatenulatum strains. One isolate, B. pseudocatenulatum MP80, which uniquely possessed GH95 and GH29 α-fucosidases, consumed the majority of fucosylated HMOs tested. Furthermore, B. pseudocatenulatum SC585, which possesses only a single GH95 α-fucosidase, lacked the ability to consume the complete repertoire of linkages within the fucosylated HMO pool. Analysis of the purified GH29 and GH95 fucosidase activities directly on HMOs revealed complementing enzyme specificities with the GH95 enzyme preferring 1-2 fucosyl linkages and the GH29 enzyme favoring 1-3 and 1-4 linkages. The HMO-binding specificities of the family 1 solute-binding protein component linked to the fucosylated HMO gene cluster in both SC585 and MP80 are similar, suggesting differential transport of fucosylated HMO is not a driving factor in each strain's distinct HMO consumption pattern. Taken together, these data indicate the presence or absence of specific α-fucosidases directs the strain-specific fucosylated HMO utilization pattern among bifidobacteria and likely influences competitive behavior for HMO foraging in situ. IMPORTANCE Often isolated from the human gut, microbes from the bacterial family Bifidobacteriaceae commonly possess genes enabling carbohydrate utilization. Isolates from breastfed infants often grow on and possess genes for the catabolism of human milk oligosaccharides (HMOs), glycans found in human breast milk. However, catabolism of structurally diverse HMOs differs between bifidobacterial strains. This study identifies key gene differences between Bifidobacterium pseudocatenulatum isolates that may impact whether a microbe successfully colonizes an infant gut. In this case, the presence of complementary α-fucosidases may provide an advantage to microbes seeking residence in the infant gut. Such knowledge furthers our understanding of how diet drives bacterial colonization of the infant gut.

The Effect of Morbid Obesity on Complications, Readmission, and Patient-Reported Outcomes Following Minimally Invasive Transforaminal Lumbar Interbody Fusion: An Inverse Propensity Score Weighted Analysis.

STUDY DESIGN: Retrospective review of prospectively collected data at a single institution. OBJECTIVE: To compare perioperative and clinical outcomes in morbidly obese patients who underwent minimally invasive transforaminal lumbar interbody fusion (MiTLIF). SUMMARY OF BACKGROUND DATA: Obesity remains a serious public health concern. Obese patients who undergo lumbar fusion have historically thought to be at higher risk for complications and fare worse regarding quality-of-life outcomes. However, recent literature may demonstrate comparable risk and outcomes in obese patients. An increasing number of patients are categorized as morbidly obese (body mass index [BMI] ≥ 40 kg/m2). Perioperative and patient-reported outcomes (PROs) are lacking in this patient population. METHODS: The authors retrospectively reviewed a prospectively collected database of all morbidly obese and non-obese patients that underwent MiTLIF between 2015 and 2018 for degenerative conditions who had minimum 1-year follow-up for outcome assessment. An inverse propensity/probability of treatment weighting was utilized to create a synthetic weighted sample in which covariates were independent of obesity designation to adjust for imbalance between groups. Generalized estimating equations (GEE) was used to estimate the association of morbid obesity and complications and 1-year PROs. RESULTS: A total of 292 patients were analyzed with 234 non-obese patients and 58 morbidly obese patients. Multivariate analysis failed to demonstrate any association between morbid obesity and achieving minimal clinically important difference (MCID) for Oswestry disability index (ODI), visual analog scale (VAS), or short form-12 (SF-12) physical component score. However, morbid obesity was associated with significant decrease in odds of achieving MCID for SF-12 mental component score (P = 0.001). Increased surgery duration was significantly associated with morbid obesity (P = 0.001). Morbid obesity exhibited no statistically significant association with postoperative complications, readmission, pseudarthrosis, or adjacent segment disease (ASD). CONCLUSION: Morbidly obese patients who undergo MiTLIF can achieve meaningful clinical improvement comparable to nonobese patients. Morbid obesity was associated with longer surgical times but was not associated with postoperative complications, readmission, or ASD.Level of Evidence: 3.

A comparative study between high-definition volumetric imaging computed tomography and multi-slice computed tomography in the detection of acute thoraco-lumbar disc extrusions in dogs.

Computed tomography (CT) is commonly used to image intervertebral disc extrusion (IVDE) in dogs. The current gold standard for CT imaging is the use of multi-slice CT (MS CT) units. Smaller high-definition volumetric imaging (HDVI) mobile CT has been marketed for veterinary practice. This unit is described as an advanced flat panel. The goal of this manuscript was to evaluate the ability of the HDVI CT in detecting IVDE without the need for CT myelography, compared with the detection of acute disc extrusions with a MS CT without the need for MS CT myelogram. Retrospective blinded analyses of 219 dogs presented for thoraco-lumbar IVDE that had a HDVI CT (n = 123) or MS CT (n = 96) were performed at a single referral hospital. A total of 123 cases had HDVI CT scans with surgically confirmed IVDE. The IVDE was identified in 88/123 (72%) dogs on pre-contrast HDVI CT. The remaining 35/128 (28%) cases required a HDVI CT myelogram to identify the IVDE. Ninety-six cases had MS CT scans with surgically confirmed IVDE. The IVDE was identified in 78/96 (81%) dogs on the pre-contrast MS CT. The remaining 18/96 (19%) cases had a MS CT myelogram to identify the IVDE. Multi-slice CT detected IVDE significantly more than HDVI CT (p = 0.032). This study showed that the ability of HDVI CT for detecting IVDE is lower than that of MS CT. The HDVI CT system may be useful in smaller referral practices, with a lower case load where space is limited.

Age as a Predictor for Complications and Patient-reported Outcomes in Multilevel Transforaminal Lumbar Interbody Fusions: Analyses From the Michigan Spine Surgery Improvement Collaborative (MSSIC).

STUDY DESIGN: Retrospective review of a multi-institutional data registry. OBJECTIVE: The authors sought to determine the association between age and complications & patient-reported outcomes (PRO) in patients undergoing multilevel transforaminal interbody lumbar fusion (MTLIF). SUMMARY OF BACKGROUND DATA: Elderly patients undergoing MTLIF are considered high risk. However, data on complications and PRO are lacking. Additionally, safety of multilevel lumbar fusion in the elderly remains uncertain. METHODS: Patients ≥50-year-old who underwent MTLIF for degenerative lumbar spine conditions were analyzed. Ninety-day complications and PROs (baseline, 90-d, 1-y, 2-y) were queried using the MSSIC database. PROs were measured by back & leg visual analog scale (VAS), Patient-reported Outcomes Measurement Information System (PROMIS), EuroQol-5D (EQ-5D), and North American Spine Society (NASS) Patient Satisfaction Index. Univariate analyses were used to compare among elderly and complication cohorts. Generalized estimating equation (GEE) was used to identify predictors of complications and PROs. RESULTS: A total of 3120 patients analyzed with 961 (31%) ≥ 70-y-o and 2159 (69%) between 50-69. A higher proportion of elderly experienced postoperative complications (P = .003) including urinary retention (P = <.001) and urinary tract infection (P = .002). Multivariate analysis demonstrated that age was not independently associated with complications. Number of operative levels was associated with any (P = .001) and minor (P = .002) complication. Incurring a complication was independently associated with worse leg VAS and PROMIS scores (P = <.001). Preoperative independent ambulation was independently associated with improved PROMIS, and EQ5D (P = <.001). Within the elderly, preoperative independent ambulation and lower BMI were associated with improved PROMIS (P = <.001). Complications had no significant effect on PROs in the elderly. CONCLUSIONS: Age was not associated with complications nor predictive of functional outcomes in patients who underwent MTLIF. Age alone, therefore, may not be an appropriate surrogate for risk. Furthermore, baseline preoperative independent ambulation was associated with better clinical outcomes and should be considered during preoperative surgical counseling.Level of Evidence: 3.

Emerging functions of branched ubiquitin chains.

Ubiquitylation is a critical post-translational modification that controls a wide variety of processes in eukaryotes. Ubiquitin chains of different topologies are specialized for different cellular functions and control the stability, activity, interaction properties, and localization of many different proteins. Recent work has highlighted a role for branched ubiquitin chains in the regulation of cell signaling and protein degradation pathways. Similar to their unbranched counterparts, branched ubiquitin chains are remarkably diverse in terms of their chemical linkages, structures, and the biological information they transmit. In this review, we discuss emerging themes related to the architecture, synthesis, and functions of branched ubiquitin chains. We also describe methodologies that have recently been developed to identify and decode the functions of these branched polymers.

Big data registries in spine surgery research: the lurking dangers.

Spine surgery research has improved considerably over the last few decades. Its' most recent growth is in large part due to the mounting increase in studies conducted using national databases and registries. With easy access to a large number of patients, the benefit of these registries has become evident. However, as with any research, this type of data must be used responsibly with the appropriate strengths and limitations kept in mind. Inappropriate use of these registries continues to be a growing concern as potentially false or inaccurate conclusions can adversely impact clinical practice. It is, therefore, the author and the readers' responsibility to acknowledge and understand the limitations of this type of data. Knowledge of methodological requirements in the use and analyses of registry data is essential to ensuring quality evidence with proper interpretation.

Patient Satisfaction with Neurosurgery Telemedicine Visits During the Coronavirus Disease 2019 Pandemic: A Prospective Cohort Study.

BACKGROUND: Telemedicine refers to various modalities for remote care, including telephone calls, imaging review, and real-time video teleconferencing visits. Although it has not been widely used in outpatient neurosurgery settings, the COVID-19 (coronavirus disease 2019) pandemic has necessitated a broader adoption. Our goal is to show the level of patient satisfaction with their telemedicine care. METHODS: We prospectively studied consecutive telemedicine patients who scheduled outpatient neurosurgery visits from May 15 to June 8, 2020. Patients were seen by the surgeon via real-time video conferencing using Google Meet, and then completed a telemedicine satisfaction survey. Our primary outcome was telemedicine satisfaction scores. We compared satisfaction scores between new and established patients and between patients within and outside of a 15-mile radius of the nearest clinic location. Sensitivity analyses were performed to account for the nonrespondents. Descriptive and univariate analyses were performed. A P value of <0.05 was considered significant. RESULTS: Five-hundred and ninety patients completed a telemedicine visit during the study period. One patient from out of state was excluded. Three-hundred and ten patients (52.6%) responded. The average age was 60.9 ± 13.60 years; 59% were female, 20.6% were new patients; the average distance to the clinic was 28.03 ± 36.09 km (17.42 ± 22.43 miles). The mean overall satisfaction score was 6.32 ± 1.27. Subgroup analyses by new/established patient status and distance from their home to the clinic showed no significant difference in mean satisfaction scores between groups. CONCLUSIONS: Telemedicine provided a viable and satisfactory option for neurosurgical patients in the outpatient setting during the COVID-19 pandemic.

Efficacy and safety of cilostazol-nimodipine combined therapy on delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage: a prospective, randomised, double-blinded, placebo-controlled trial protocol.

INTRODUCTION: Delayed cerebral ischaemia (DCI) due to cerebral vasospasm (cVS) remains the foremost contributor to morbidity and mortality following aneurysmal subarachnoid haemorrhage (aSAH). Past efforts in preventing and treating DCI have failed to make any significant progress. To date, our most effective treatment involves the use of nimodipine, a calcium channel blocker. Recent studies have suggested that cilostazol, a platelet aggregation inhibitor, may prevent cVS. Thus far, no study has evaluated the effect of cilostazol plus nimodipine on the rate of DCI following aSAH. METHODS AND ANALYSIS: This is a multicentre, double-blinded, randomised, placebo-controlled superiority trial investigating the effect of cilostazol on DCI. Data concerning rates of DCI, symptomatic and radiographic vasospasm, length of intensive care unit stay, and long-term functional and quality-of-life (QoL) outcomes will be recorded. All data will be collected with the aim of demonstrating that the use of cilostazol plus nimodipine will safely decrease the incidence of DCI, and decrease the rates of both radiographic and symptomatic vasospasm with subsequent improvement in long-term functional and QoL outcomes when compared with nimodipine alone. ETHICS AND DISSEMINATION: Ethical approval was obtained from all participating hospitals by the Ascension Providence Hospital Institutional Review Board. The results of this study will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04148105.