Publications by authors named "Kevin Foley"

183 Publications

Does reduction of the Meyerding grade correlate with outcomes in patients undergoing decompression and fusion for grade I degenerative lumbar spondylolisthesis?

J Neurosurg Spine 2021 Sep 17:1-8. Epub 2021 Sep 17.

1Department of Neurological Surgery, University of California, San Francisco, San Francisco, California.

Objective: Reduction of Meyerding grade is often performed during fusion for spondylolisthesis. Although radiographic appearance may improve, correlation with patient-reported outcomes (PROs) is rarely reported. In this study, the authors' aim was to assess the impact of spondylolisthesis reduction on 24-month PRO measures after decompression and fusion surgery for Meyerding grade I degenerative lumbar spondylolisthesis.

Methods: The Quality Outcomes Database (QOD) was queried for patients undergoing posterior lumbar fusion for spondylolisthesis with a minimum 24-month follow-up, and quantitative correlation between Meyerding slippage reduction and PROs was performed. Baseline and 24-month PROs, including the Oswestry Disability Index (ODI), EQ-5D, Numeric Rating Scale (NRS)-back pain (NRS-BP), NRS-leg pain (NRS-LP), and satisfaction (North American Spine Society patient satisfaction questionnaire) scores were noted. Multivariable regression models were fitted for 24-month PROs and complications after adjusting for an array of preoperative and surgical variables. Data were analyzed for magnitude of slippage reduction and correlated with PROs. Patients were divided into two groups: < 3 mm reduction and ≥ 3 mm reduction.

Results: Of 608 patients from 12 participating sites, 206 patients with complete data were identified in the QOD and included in this study. Baseline patient demographics, comorbidities, and clinical characteristics were similarly distributed between the cohorts except for depression, listhesis magnitude, and the proportion with dynamic listhesis (which were accounted for in the multivariable analysis). One hundred four (50.5%) patients underwent lumbar decompression and fusion with slippage reduction ≥ 3 mm (mean 5.19, range 3 to 11), and 102 (49.5%) patients underwent lumbar decompression and fusion with slippage reduction < 3 mm (mean 0.41, range 2 to -2). Patients in both groups (slippage reduction ≥ 3 mm, and slippage reduction < 3 mm) reported significant improvement in all primary patient reported outcomes (all p < 0.001). There was no significant difference with regard to the PROs between patients with or without intraoperative reduction of listhesis on univariate and multivariable analyses (ODI, EQ-5D, NRS-BP, NRS-LP, or satisfaction). There was no significant difference in complications between cohorts.

Conclusions: Significant improvement was found in terms of all PROs in patients undergoing decompression and fusion for lumbar spondylolisthesis. There was no correlation with clinical outcomes and magnitude of Meyerding slippage reduction.
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http://dx.doi.org/10.3171/2021.3.SPINE202059DOI Listing
September 2021

Transition from static culture to stirred tank bioreactor for the allogeneic production of therapeutic discogenic cell spheres.

Stem Cell Res Ther 2021 08 12;12(1):455. Epub 2021 Aug 12.

DiscGenics Inc, 5940 Harold Gatty Dr, Salt Lake City, UT, 84116, USA.

Background: Culturing cells as cell spheres results in a tissue-like environment that drives unique cell phenotypes, making it useful for generating cell populations intended for therapeutic use. Unfortunately, common methods that utilize static suspension culture have limited scalability, making commercialization of such cell therapies challenging. Our team is developing an allogeneic cell therapy for the treatment of lumbar disc degeneration comprised of discogenic cells, which are progenitor cells expanded from human nucleus pulposus cells that are grown in a sphere configuration.

Methods: We evaluate sphere production in Erlenmeyer, horizontal axis wheel, stirred tank bioreactor, and rocking bag format. We then explore the use of ramped agitation profiles and computational fluid dynamics to overcome obstacles related to cell settling and the undesired impact of mechanical forces on cell characteristics. Finally, we grow discogenic cells in stirred tank reactors (STRs) and test outcomes in vitro (potency via aggrecan production and identity) and in vivo (rabbit model of disc degeneration).

Results: Computation fluid dynamics were used to model hydrodynamic conditions in STR systems and develop statistically significant correlations to cell attributes including potency (measured by aggrecan production), cell doublings, cell settling, and sphere size. Subsequent model-based optimization and testing resulted in growth of cells with comparable attributes to the original static process, as measured using both in vitro and in vivo models. Maximum shear rate (1/s) was maintained between scales to demonstrate feasibility in a 50 L STR (200-fold scale-up).

Conclusions: Transition of discogenic cell production from static culture to a stirred-tank bioreactor enables cell sphere production in a scalable format. This work shows significant progress towards establishing a large-scale bioprocess methodology for this novel cell therapy that can be used for other, similar cell therapies.
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http://dx.doi.org/10.1186/s13287-021-02525-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359559PMC
August 2021

Adipose Tissue Inflammation Is Directly Linked to Obesity-Induced Insulin Resistance, while Gut Dysbiosis and Mitochondrial Dysfunction Are Not Required.

Function (Oxf) 2020 25;1(2):zqaa013. Epub 2020 Aug 25.

Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada.

Obesity is associated with adipose tissue hypertrophy, systemic inflammation, mitochondrial dysfunction, and intestinal dysbiosis. Rodent models of high-fat diet (HFD)-feeding or genetic deletion of multifunctional proteins involved in immunity and metabolism are often used to probe the etiology of obesity; however, these models make it difficult to divorce the effects of obesity, diet composition, or immunity on endocrine regulation of blood glucose. We, therefore, investigated the importance of adipose inflammation, mitochondrial dysfunction, and gut dysbiosis for obesity-induced insulin resistance using a spontaneously obese mouse model. We examined metabolic changes in skeletal muscle, adipose tissue, liver, the intestinal microbiome, and whole-body glucose control in spontaneously hyperphagic C57Bl/6J mice compared to lean littermates. A separate subset of lean and obese mice was subject to 8 weeks of obesogenic HFD feeding, or to pair feeding of a standard rodent diet. Hyperphagia, obesity, adipose inflammation, and insulin resistance were present in obese mice despite consuming a standard rodent diet, and these effects were blunted with caloric restriction. However, hyperphagic obese mice had normal mitochondrial respiratory function in all tissues tested and no discernable intestinal dysbiosis relative to lean littermates. In contrast, feeding mice an obesogenic HFD altered the composition of the gut microbiome, impaired skeletal muscle mitochondrial bioenergetics, and promoted poor glucose control. These data show that adipose inflammation and redox stress occurred in all models of obesity, but gut dysbiosis and mitochondrial respiratory dysfunction are not always required for obesity-induced insulin resistance. Rather, changes in the intestinal microbiome and mitochondrial bioenergetics may reflect physiological consequences of HFD feeding.
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http://dx.doi.org/10.1093/function/zqaa013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276887PMC
August 2020

Reflections from a "geriatric" patient.

Authors:
Kevin T Foley

J Am Geriatr Soc 2021 Jul 14. Epub 2021 Jul 14.

Department of Family and Community Medicine, Michigan State University, College of Osteopathic Medicine, East Lansing, Michigan, USA.

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http://dx.doi.org/10.1111/jgs.17353DOI Listing
July 2021

Impact of predominant symptom location among patients undergoing cervical spine surgery on 12-month outcomes: an analysis from the Quality Outcomes Database.

J Neurosurg Spine 2021 Jul 9:1-11. Epub 2021 Jul 9.

4Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota.

Objective: The impact of the type of pain presentation on outcomes of spine surgery remains elusive. The aim of this study was to assess the impact of predominant symptom location (predominant arm pain vs predominant neck pain vs equal neck and arm pain) on postoperative improvement in patient-reported outcomes.

Methods: The Quality Outcomes Database cervical spine module was queried for patients undergoing 1- or 2-level anterior cervical discectomy and fusion (ACDF) for degenerative spine disease.

Results: A total of 9277 patients were included in the final analysis. Of these patients, 18.4% presented with predominant arm pain, 32.3% presented with predominant neck pain, and 49.3% presented with equal neck and arm pain. Patients with predominant neck pain were found to have higher (worse) 12-month Neck Disability Index (NDI) scores (coefficient 0.24, 95% CI 0.15-0.33; p < 0.0001). The three groups did not differ significantly in odds of return to work and achieving minimal clinically important difference in NDI score at the 12-month follow-up.

Conclusions: Analysis from a national spine registry showed significantly lower odds of patient satisfaction and worse NDI score at 1 year after surgery for patients with predominant neck pain when compared with patients with predominant arm pain and those with equal neck and arm pain after 1- or 2-level ACDF. With regard to return to work, all three groups (arm pain, neck pain, and equal arm and neck pain) were found to be similar after multivariable analysis. The authors' results suggest that predominant pain location, especially predominant neck pain, might be a significant determinant of improvement in functional outcomes and patient satisfaction after ACDF for degenerative spine disease. In addition to confirmation of the common experience that patients with predominant neck pain have worse outcomes, the authors' findings provide potential targets for improvement in patient management for these specific populations.
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http://dx.doi.org/10.3171/2020.12.SPINE202002DOI Listing
July 2021

Accuracy and Efficiency of Fusion Robotics™ Versus Mazor-X™ in Single-Level Lumbar Pedicle Screw Placement.

Cureus 2021 Jun 26;13(6):e15939. Epub 2021 Jun 26.

Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences at University at Buffalo, Buffalo, USA.

Introduction There has been a surge in robot utilization in spine surgery over the past five years with the rapid development of new spine robotic platforms. This study aimed to compare a new robotic spine platform from Fusion Robotics(Fusion Robotics, Helena, MT) with the widely used Mazor-X Stealth Edition robotic platform (Medtronic, Dublin, Ireland) in terms of workflow and lumbar pedicle screw placement accuracy. Methods A cadaver lab was conducted, which included four procedures with single-level lumbar pedicle screw placement using the Fusion Robotics system. These four procedures were compared to four propensity-score matched cases with single-level lumbar pedicle screw placement using the Mazor-X Stealth Edition. A single surgeon performed all surgeries. The cases were matched in terms of demographics (age, sex, race, BMI) and comorbidities (Charlson Comorbidity Index score). The primary outcome measure was the operative workflow efficiency (duration as measured with a stopwatch by an independent observer). The secondary outcome measures were pedicle screw accuracy and accuracy to plan. Results After propensity-score matching, there were four cases in each group with no significant between-group differences in terms of sex, race, BMI, or surgical levels; however, there were significant differences in terms of age (p=0.01) and comorbidities (p<0.001). The workflow efficiency measurement showed that the Fusion Robotics platform had a significantly shorter duration in terms of the system set-up time, planning to in-position time, and total procedure time (p<0.05). However, there was no significant difference between the robotic platforms in terms of creating a sterile barrier, scanning and importing images, creating a plan, screw placement, screw accuracy, and screw accuracy to plan. Conclusion Based on our findings, the Fusion Robotics platform had a significantly shorter procedure workflow duration while maintaining the same accuracy as the most commonly used robotic platform (Mazor-X). This is the first study to directly compare different spine surgery robotic systems.
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http://dx.doi.org/10.7759/cureus.15939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236238PMC
June 2021

A CRISPR-based assay for the study of eukaryotic DNA repair onboard the International Space Station.

PLoS One 2021 30;16(6):e0253403. Epub 2021 Jun 30.

MiniPCR Bio, Cambridge, Massachusetts, United States of America.

As we explore beyond Earth, astronauts may be at risk for harmful DNA damage caused by ionizing radiation. Double-strand breaks are a type of DNA damage that can be repaired by two major cellular pathways: non-homologous end joining, during which insertions or deletions may be added at the break site, and homologous recombination, in which the DNA sequence often remains unchanged. Previous work suggests that space conditions may impact the choice of DNA repair pathway, potentially compounding the risks of increased radiation exposure during space travel. However, our understanding of this problem has been limited by technical and safety concerns, which have prevented integral study of the DNA repair process in space. The CRISPR/Cas9 gene editing system offers a model for the safe and targeted generation of double-strand breaks in eukaryotes. Here we describe a CRISPR-based assay for DNA break induction and assessment of double-strand break repair pathway choice entirely in space. As necessary steps in this process, we describe the first successful genetic transformation and CRISPR/Cas9 genome editing in space. These milestones represent a significant expansion of the molecular biology toolkit onboard the International Space Station.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253403PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244870PMC
June 2021

Oxygen toxicity seizures during United States Navy Treatment Table 6: An acceptable risk in monoplace chambers?

Diving Hyperb Med 2021 Jun;51(2):167-172

Department of Hyperbaric Medicine, Fiona Stanley Hospital, Murdoch, Western Australia.

Introduction: Hyperbaric oxygen treatment (HBOT) may be complicated by oxygen toxicity seizures, which typically occur with hyperbaric partial pressures of oxygen exceeding 203 kPa (2 atmospheres absolute). All other hyperbaric units in Australia exclusively use a multiplace chamber when treating with United States Navy Treatment Table 6 (USN TT6) due to this perceived risk. The purpose of this study was to determine the safety of a monoplace chamber when treating decompression illness (DCI) with USN TT6.

Methods: A retrospective review of the medical records of all patients treated at Fiona Stanley Hospital Hyperbaric Medicine Unit with USN TT6 between November 2014 and June 2020 was undertaken. These data were combined with previous results from studies performed at our hyperbaric unit at Fremantle Hospital from 1989 to 2014, creating a data set covering a 30-year period.

Results: One thousand treatments with USN TT6 were performed between 1989 and 2020; 331 in a monoplace chamber and 669 in a multiplace chamber. Four seizures occurred: a rate of 0.59% (1/167) in a multiplace chamber; and none in a monoplace chamber, indicating no statistically significant difference between seizures in a monoplace versus multiplace chamber (P = 0.31).

Conclusions: The rate of oxygen toxicity seizures in a monoplace chamber is not significantly higher than for treatment in the multiplace chamber. We conclude that using the monoplace chamber for USN TT6 in selected patients poses an acceptably low seizure risk.
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http://dx.doi.org/10.28920/dhm51.2.167-172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426124PMC
June 2021

Oxygen toxicity seizure mimics.

Diving Hyperb Med 2021 Jun;51(2):161-166

Department of Hyperbaric Medicine, Fiona Stanley Hospital, Perth, Australia.

Introduction: Oxygen toxicity seizures (OTS) are a well-recognised complication of hyperbaric oxygen treatment (HBOT). As such, seizure-like activity during HBOT is usually presumed to be a result of central nervous system oxygen toxicity (CNS-OT). Four cases are reported here where causes other than CNS-OT were determined as being the likely cause of the seizure; causes we have labelled 'OTS mimics'. Through review of the current literature, and our hyperbaric medicine unit's experience to date, we aimed to highlight the relevance of these OTS mimics, as the potential for significant morbidity and mortality exists with incorrect diagnoses.

Methods: A retrospective review of the medical records of all patients treated at the Fiona Stanley Hospital and Fremantle Hospital hyperbaric medicine units who had a seizure during HBOT between November 1989 and June 2020. These events were reviewed to determine whether causes for seizures other than oxygen toxicity were evident.

Results: Four OTS mimics were identified: posterior reversible encephalopathy syndrome, pethidine toxicity, previous subarachnoid haemorrhage with resultant epilepsy, and severe hypoglycaemia.

Conclusions: This case series highlights the need for caution when diagnosing an apparent OTS. Multiple conditions may mimic the signs and symptoms of oxygen toxicity. This creates scope for misdiagnosis, with potential for consequent morbidity and mortality. A pragmatic approach is necessary to any patient exhibiting seizure-like activity during HBOT, with suspicion for other underlying pathologies.
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http://dx.doi.org/10.28920/dhm51.2.161-166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426116PMC
June 2021

Effects of Obesity-Associated Chronic Inflammation on Peripheral Blood Immunophenotype Are Not Mediated by TNF in Female C57BL/6J Mice.

Immunohorizons 2021 Jun 4;5(6):370-383. Epub 2021 Jun 4.

McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada;

Chronic low-grade systemic inflammation in obesity contributes to the development and progression of aspects of metabolic syndrome. In obese male mice, expanded adipose tissue releases proinflammatory cytokines, including TNF, which promotes an increase in immature, proinflammatory, peripheral blood Ly-6C monocytes. The aim of this study was to characterize how TNF alters circulating cellular immunity in female mice with diet-induced obesity. We initially quantified peripheral blood immune cells by flow cytometry in female wild-type C57BL/6J mice after 3-30 wk of allocation to a high-fat (HF) or standard chow diet. We assessed effects of diet and time on neutrophil, monocyte, B cell, NK cell, CD4 T cell, and CD8 T cell populations. There was a significant interaction of the effects of diet type and time on the numbers and prevalence of circulating total monocytes and Ly-6C, Ly-6C, and Ly-6C subsets. Circulating monocytes, in particular Ly-6C monocytes, were increased in HF-fed mice compared with chow-fed mice. Ly-6C monocytes from HF-fed mice also had a more immature phenotype yet were highly responsive to the chemotactic ligand CCL2 and had greater intracellular production of TNF. Comparisons of the effects of HF diet feeding in littermate wild-type (TNF) and TNF female mice showed that genetic ablation of TNF did not protect from higher adiposity or an increase in circulating, immature, proinflammatory Ly-6C monocytes during HF diet-induced obesity. These data emphasize the importance of considering biological sex when determining the mechanisms of TNF action in obesity-induced cellular inflammation and in other chronic inflammatory conditions.
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http://dx.doi.org/10.4049/immunohorizons.2100038DOI Listing
June 2021

Identifying patients at risk for nonroutine discharge after surgery for cervical myelopathy: an analysis from the Quality Outcomes Database.

J Neurosurg Spine 2021 May 7:1-9. Epub 2021 May 7.

15Department of Neurological Surgery, University of Utah, Salt Lake City, Utah.

Objective: Optimizing patient discharge after surgery has been shown to impact patient recovery and hospital/physician workflow and to reduce healthcare costs. In the current study, the authors sought to identify risk factors for nonroutine discharge after surgery for cervical myelopathy by using a national spine registry.

Methods: The Quality Outcomes Database cervical module was queried for patients who had undergone surgery for cervical myelopathy between 2016 and 2018. Nonroutine discharge was defined as discharge to postacute care (rehabilitation), nonacute care, or another acute care hospital. A multivariable logistic regression predictive model was created using an array of demographic, clinical, operative, and patient-reported outcome characteristics.

Results: Of the 1114 patients identified, 11.2% (n = 125) had a nonroutine discharge. On univariate analysis, patients with a nonroutine discharge were more likely to be older (age ≥ 65 years, 70.4% vs 35.8%, p < 0.001), African American (24.8% vs 13.9%, p = 0.007), and on Medicare (75.2% vs 35.1%, p < 0.001). Among the patients younger than 65 years of age, those who had a nonroutine discharge were more likely to be unemployed (70.3% vs 36.9%, p < 0.001). Overall, patients with a nonroutine discharge were more likely to present with a motor deficit (73.6% vs 58.7%, p = 0.001) and more likely to have nonindependent ambulation (50.4% vs 14.0%, p < 0.001) at presentation. On multivariable logistic regression, factors associated with higher odds of a nonroutine discharge included African American race (vs White, OR 2.76, 95% CI 1.38-5.51, p = 0.004), Medicare coverage (vs private insurance, OR 2.14, 95% CI 1.00-4.65, p = 0.04), nonindependent ambulation at presentation (OR 2.17, 95% CI 1.17-4.02, p = 0.01), baseline modified Japanese Orthopaedic Association severe myelopathy score (0-11 vs moderate 12-14, OR 2, 95% CI 1.07-3.73, p = 0.01), and posterior surgical approach (OR 11.6, 95% CI 2.12-48, p = 0.004). Factors associated with lower odds of a nonroutine discharge included fewer operated levels (1 vs 2-3 levels, OR 0.3, 95% CI 0.1-0.96, p = 0.009) and a higher quality of life at baseline (EQ-5D score, OR 0.43, 95% CI 0.25-0.73, p = 0.001). On predictor importance analysis, baseline quality of life (EQ-5D score) was identified as the most important predictor (Wald χ2 = 9.8, p = 0.001) of a nonroutine discharge; however, after grouping variables into distinct categories, socioeconomic and demographic characteristics (age, race, gender, insurance status, employment status) were identified as the most significant drivers of nonroutine discharge (28.4% of total predictor importance).

Conclusions: The study results indicate that socioeconomic and demographic characteristics including age, race, gender, insurance, and employment may be the most significant drivers of a nonroutine discharge after surgery for cervical myelopathy.
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http://dx.doi.org/10.3171/2020.11.SPINE201442DOI Listing
May 2021

Patient-reported outcome improvements at 24-month follow-up after fusion added to decompression for grade I degenerative lumbar spondylolisthesis: a multicenter study using the Quality Outcomes Database.

J Neurosurg Spine 2021 Apr 16:1-10. Epub 2021 Apr 16.

16Department of Neurological Surgery, University of California, San Francisco, California.

Objective: The ideal surgical management of grade I lumbar spondylolisthesis has not been determined despite extensive prior investigations. In this cohort study, the authors used data from the large, multicenter, prospectively collected Quality Outcomes Database to bridge the gap between the findings in previous randomized trials and those in a more heterogeneous population treated in a typical practice. The objective was to assess the difference in patient-reported outcomes among patients undergoing decompression alone or decompression plus fusion.

Methods: The primary outcome measure was change in 24-month Oswestry Disability Index (ODI) scores. The minimal clinically important difference (MCID) in ODI score change and 30% change in ODI score at 24 months were also evaluated. After adjusting for patient-specific and clinical factors, multivariable linear and logistic regressions were employed to evaluate the impact of fusion on outcomes. To account for differences in age, sex, body mass index, and baseline listhesis, a sensitivity analysis was performed using propensity score analysis to match patients undergoing decompression only with those undergoing decompression and fusion.

Results: In total, 608 patients who had grade I lumbar spondylolisthesis were identified (85.5% with at least 24 months of follow-up); 140 (23.0%) underwent decompression alone and 468 (77.0%) underwent decompression and fusion. The 24-month change in ODI score was significantly greater in the fusion plus decompression group than in the decompression-only group (-25.8 ± 20.0 vs -15.2 ± 19.8, p < 0.001). Fusion remained independently associated with 24-month ODI score change (B = -7.05, 95% CI -10.70 to -3.39, p ≤ 0.001) in multivariable regression analysis, as well as with achieving the MCID for the ODI score (OR 1.767, 95% CI 1.058-2.944, p = 0.029) and 30% change in ODI score (OR 2.371, 95% CI 1.286-4.371, p = 0.005). Propensity score analysis resulted in 94 patients in the decompression-only group matched 1 to 1 with 94 patients in the fusion group. The addition of fusion to decompression remained a significant predictor of 24-month change in the ODI score (B = 2.796, 95% CI 2.228-13.275, p = 0.006) and of achieving the 24-month MCID ODI score (OR 2.898, 95% CI 1.214-6.914, p = 0.016) and 24-month 30% change in ODI score (OR 2.300, 95% CI 1.014-5.216, p = 0.046).

Conclusions: These results suggest that decompression plus fusion in patients with grade I lumbar spondylolisthesis may be associated with superior outcomes at 24 months compared with decompression alone, both in reduction of disability and in achieving clinically meaningful improvement. Longer-term follow-up is warranted to assess whether this effect is sustained.
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http://dx.doi.org/10.3171/2020.9.SPINE201082DOI Listing
April 2021

Design of experiment (DOE) applied to artificial neural network architecture enables rapid bioprocess improvement.

Bioprocess Biosyst Eng 2021 Jun 27;44(6):1301-1308. Epub 2021 Feb 27.

DiscGenics Inc, Salt Lake City, Utah, USA.

Modern bioprocess development employs statistically optimized design of experiments (DOE) and regression modeling to find optimal bioprocess set points. Using modeling software, such as JMP Pro, it is possible to leverage artificial neural networks (ANNs) to improve model accuracy beyond the capabilities of regression models. Herein, we bridge the gap between a DOE skill set and a machine learning skill set by demonstrating a novel use of DOE to systematically create and evaluate ANN architecture using JMP Pro software. Additionally, we run a mammalian cell culture process at historical, one factor at a time, standard least squares regression, and ANN-derived set points. This case study demonstrates the significant differences between one factor at a time bioprocess development, DOE bioprocess development and the relative power of linear regression versus an ANN-DOE hybrid modeling approach.
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http://dx.doi.org/10.1007/s00449-021-02529-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144078PMC
June 2021

Inflammation promotes adipocyte lipolysis via IRE1 kinase.

J Biol Chem 2021 Jan-Jun;296:100440. Epub 2021 Feb 19.

Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute and Centre for Metabolism, Obesity, and Diabetes Research McMaster University, Hamilton, Ontario, Canada. Electronic address:

Obesity associates with inflammation, insulin resistance, and higher blood lipids. It is unclear if immune responses facilitate lipid breakdown and release from adipocytes via lipolysis in a separate way from hormones or adrenergic signals. We found that an ancient component of ER stress, inositol-requiring protein 1 (IRE1), discriminates inflammation-induced adipocyte lipolysis versus lipolysis from adrenergic or hormonal stimuli. Our data show that inhibiting IRE1 kinase activity was sufficient to block adipocyte-autonomous lipolysis from multiple inflammatory ligands, including bacterial components, certain cytokines, and thapsigargin-induced ER stress. IRE1-mediated lipolysis was specific for inflammatory triggers since IRE1 kinase activity was dispensable for isoproterenol and cAMP-induced lipolysis in adipocytes and mouse adipose tissue. IRE1 RNase activity was not associated with inflammation-induced adipocyte lipolysis. Inhibiting IRE1 kinase activity blocked NF-κB activation, interleukin-6 secretion, and adipocyte-autonomous lipolysis from inflammatory ligands. Inflammation-induced lipolysis mediated by IRE1 occurred independently from changes in insulin signaling in adipocytes, suggesting that inflammation can promote IRE1-mediated lipolysis independent of adipocyte insulin resistance. We found no role for canonical unfolded protein responses or ABL kinases in linking ER stress to IRE1-mediated lipolysis. Adiponectin-Cre-mediated IRE1 knockout in mice showed that adipocyte IRE1 was required for inflammatory ligand-induced lipolysis in adipose tissue explants and that adipocyte IRE1 was required for approximately half of the increase in blood triglycerides after a bacterial endotoxin-mediated inflammatory stimulus in vivo. Together, our results show that IRE1 propagates an inflammation-specific lipolytic program independent from hormonal or adrenergic regulation. Targeting IRE1 kinase activity may benefit metabolic syndrome and inflammatory lipid disorders.
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http://dx.doi.org/10.1016/j.jbc.2021.100440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010698PMC
August 2021

Impact of surgeon and hospital factors on surgical decision-making for grade 1 degenerative lumbar spondylolisthesis: a Quality Outcomes Database analysis.

J Neurosurg Spine 2021 Feb 19:1-11. Epub 2021 Feb 19.

1Department of Neurological Surgery, University of Miami, Florida.

Objective: Surgical treatment for degenerative spondylolisthesis has been proven to be clinically challenging and cost-effective. However, there is a range of thresholds that surgeons utilize for incorporating fusion in addition to decompressive laminectomy in these cases. This study investigates these surgeon- and site-specific factors by using the Quality Outcomes Database (QOD).

Methods: The QOD was queried for all cases that had undergone surgery for grade 1 spondylolisthesis from database inception to February 2019. In addition to patient-specific covariates, surgeon-specific covariates included age, sex, race, years in practice (0-10, 11-20, 21-30, > 30 years), and fellowship training. Site-specific variables included hospital location (rural, suburban, urban), teaching versus nonteaching status, and hospital type (government, nonfederal; private, nonprofit; private, investor owned). Multivariable regression and predictor importance analyses were performed to identify predictors of the treatment performed (decompression alone vs decompression and fusion). The model was clustered by site to account for site-specific heterogeneity in treatment selection.

Results: A total of 12,322 cases were included with 1988 (16.1%) that had undergone decompression alone. On multivariable regression analysis clustered by site, adjusting for patient-level clinical covariates, no surgeon-specific factors were found to be significantly associated with the odds of selecting decompression alone as the surgery performed. However, sites located in suburban areas (OR 2.32, 95% CI 1.09-4.84, p = 0.03) were more likely to perform decompression alone (reference = urban). Sites located in rural areas had higher odds of performing decompression alone than hospitals located in urban areas, although the results were not statistically significant (OR 1.33, 95% CI 0.59-2.61, p = 0.49). Nonteaching status was independently associated with lower odds of performing decompression alone (OR 0.40, 95% CI 0.19-0.97, p = 0.04). Predictor importance analysis revealed that the most important determinants of treatment selection were dominant symptom (Wald χ2 = 34.7, accounting for 13.6% of total χ2) and concurrent diagnosis of disc herniation (Wald χ2 = 31.7, accounting for 12.4% of total χ2). Hospital teaching status was also found to be relatively important (Wald χ2 = 4.2, accounting for 1.6% of total χ2) but less important than other patient-level predictors.

Conclusions: Nonteaching centers were more likely to perform decompressive laminectomy with supplemental fusion for spondylolisthesis. Suburban hospitals were more likely to perform decompression only. Surgeon characteristics were not found to influence treatment selection after adjustment for clinical covariates. Further large database registry experience from surgeons at high-volume academic centers at which surgically and medically complex patients are treated may provide additional insight into factors associated with treatment preference for degenerative spondylolisthesis.
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http://dx.doi.org/10.3171/2020.8.SPINE201015DOI Listing
February 2021

Artificial Intelligence-enabled, Real-time Intraoperative Ultrasound Imaging of Neural Structures Within the Psoas: Validation in a Porcine Spine Model.

Spine (Phila Pa 1976) 2021 Feb;46(3):E146-E152

Semmes-Murphey Clinic & Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, TN.

Study Design: Experimental in-vivo animal study.

Objective: The aim of this study was to evaluate an Artificial Intelligence (AI)-enabled ultrasound imaging system's ability to detect, segment, classify, and display neural and other structures during trans-psoas spine surgery.

Summary Of Background Data: Current methodologies for intraoperatively localizing and visualizing neural structures within the psoas are limited and can impact the safety of lateral lumbar interbody fusion (LLIF). Ultrasound technology, enhanced with AI-derived neural detection algorithms, could prove useful for this task.

Methods: The study was conducted using an in vivo porcine model (50 subjects). Image processing and machine learning algorithms were developed to detect neural and other anatomic structures within and adjacent to the psoas muscle while using an ultrasound imaging system during lateral lumbar spine surgery (SonoVision,™ Tissue Differentiation Intelligence, USA). The imaging system's ability to detect and classify the anatomic structures was assessed with subsequent tissue dissection. Dice coefficients were calculated to quantify the performance of the image segmentation.

Results: The AI-trained ultrasound system detected, segmented, classified, and displayed nerve, psoas muscle, and vertebral body surface with high sensitivity and specificity. The mean Dice coefficient score for each tissue type was >80%, indicating that the detected region and ground truth were >80% similar to each other. The mean specificity of nerve detection was 92%; for bone and muscle, it was >95%. The accuracy of nerve detection was >95%.

Conclusion: This study demonstrates that a combination of AI-derived image processing and machine learning algorithms can be developed to enable real-time ultrasonic detection, segmentation, classification, and display of critical anatomic structures, including neural tissue, during spine surgery. AI-enhanced ultrasound imaging can provide a visual map of important anatomy in and adjacent to the psoas, thereby providing the surgeon with critical information intended to increase the safety of LLIF surgery.Level of Evidence: N/A.
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http://dx.doi.org/10.1097/BRS.0000000000003704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787186PMC
February 2021

"July Effect" Revisited: July Surgeries at Residency Training Programs are Associated with Equivalent Long-term Clinical Outcomes Following Lumbar Spondylolisthesis Surgery.

Spine (Phila Pa 1976) 2021 Jun;46(12):836-843

Department of Neurological Surgery, University of California, San Francisco, Ca.

Study Design: Retrospective analysis of a prospective registry.

Objective: We utilized the Quality Outcomes Database (QOD) registry to investigate the "July Effect" at QOD spondylolisthesis module sites with residency trainees.

Summary Of Background Data: There is a paucity of investigation on the long-term outcomes following surgeries involving new trainees utilizing high-quality, prospectively collected data.

Methods: This was an analysis of 608 patients who underwent single-segment surgery for grade 1 degenerative lumbar spondylolisthesis at 12 high-enrolling sites. Surgeries were classified as occurring in July or not in July (non-July). Outcomes collected included estimated blood loss, length of stay, operative time, discharge disposition, complications, reoperation and readmission rates, and patient-reported outcomes (Oswestry Disability Index [ODI], Numeric Rating Scale [NRS] Back Pain, NRS Leg Pain, EuroQol-5D [EQ-5D] and the North American Spine Society [NASS] Satisfaction Questionnaire). Propensity score-matched analyses were utilized to compare postoperative outcomes and complication rates between the July and non-July groups.

Results: Three hundred seventy-one surgeries occurred at centers with a residency training program with 21 (5.7%) taking place in July. In propensity score-matched analyses, July surgeries were associated with longer operative times ( average treatment effect = 22.4 minutes longer, 95% confidence interval 0.9-449.0, P = 0.041). Otherwise, July surgeries were not associated with significantly different outcomes for the remaining perioperative parameters (estimated blood loss, length of stay, discharge disposition, postoperative complications), overall reoperation rates, 3-month readmission rates, and 24-month ODI, NRS back pain, NRS leg pain, EQ-5D, and NASS satisfaction score (P > 0.05, all comparisons).

Conclusion: Although July surgeries were associated with longer operative times, there were no associations with other clinical outcomes compared to non-July surgeries following lumbar spondylolisthesis surgery. These findings may be due to the increased attending supervision and intraoperative education during the beginning of the academic year. There is no evidence that the influx of new trainees in July significantly affects long-term patient-centered outcomes.Level of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003903DOI Listing
June 2021

Perspectives on the Treatment of Lumbar Disc Degeneration: The Value Proposition for a Cell-Based Therapy, Immunomodulatory Properties of Discogenic Cells and the Associated Clinical Evaluation Strategy.

Front Surg 2020 16;7:554382. Epub 2020 Dec 16.

DiscGenics Inc., Salt Lake City, UT, United States.

Low back pain (LBP) is a serious medical condition that affects a large percentage of the population worldwide. One cause of LBP is disc degeneration (DD), which is characterized by progressive breakdown of the disc and an inflamed disc environment. Current treatment options for patients with symptomatic DD are limited and are often unsuccessful, so many patients turn to prescription opioids for pain management in a time when opioid usage, addiction, and drug-related deaths are at an all-time high. In this paper, we discuss the etiology of lumbar DD and currently available treatments, as well as the potential for cell therapy to offer a biologic, non-opioid alternative to patients suffering from the condition. Finally, we present an overview of an investigational cell therapy called IDCT (Injectable Discogenic Cell Therapy), which is currently under evaluation in multiple double-blind clinical trials overseen by major regulatory agencies. The active ingredient in IDCT is a novel allogeneic cell population known as Discogenic Cells. These cells, which are derived from intervertebral disc tissue, have been shown to possess both regenerative and immunomodulatory properties. Cell therapies have unique properties that may ultimately lead to decreased pain and improved function, as well as curb the numbers of patients pursuing opioids. Their efficacy is best assessed in rigorous double-blinded and placebo-controlled clinical studies.
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http://dx.doi.org/10.3389/fsurg.2020.554382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772215PMC
December 2020

Retooling the Health Care Workforce for an Aging America: A Current Perspective.

Gerontologist 2021 06;61(4):487-496

Department of Family and Community Medicine, College of Osteopathic Medicine, Michigan State University, East Lansing.

A 2008 Institute of Medicine (IoM) report outlined a vision for health care and a workforce capable of addressing health and extended care needs of our aging population. It highlighted dramatic shortages necessitating bold action and outlined recommendations aimed at building a sizable and qualified workforce. This study updates report findings and progress made on its recommendations. Through review of publicly accessible, internet-based literature and government and professional organization websites, current workforce data and recent policy changes are compared to the report's statistics and recommendations. Direct comparisons are limited by changing definitions, context, and data collection and analyses methods. Future workforce-need projections are estimated using reports from various sources. Inability to forecast medical advances, socioeconomic changes, and world events affects the accuracy of these projections. Nonetheless, clear conclusions emerge despite such limitations. Progress toward fulfilling the IoM goals is variable and insufficient. The current and projected numbers for all geriatric health providers remain inadequate compared to estimated 2030 demand. Challenges in meeting estimated needs persist essentially unchanged. The 2008 IoM framework and recommendations remain relevant and constitute an important roadmap to complete unfinished goals. Initial findings from this update provide a platform for developing practice and policy reforms.
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http://dx.doi.org/10.1093/geront/gnaa163DOI Listing
June 2021

The Part-Time Geriatrics Fellowship: Five Easy Steps for Creating an Alternative Training Option.

J Am Geriatr Soc 2020 12 5;68(12):E69-E71. Epub 2020 Oct 5.

Department of Family and Community Medicine, College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan.

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http://dx.doi.org/10.1111/jgs.16849DOI Listing
December 2020

Gut microbiota impairs insulin clearance in obese mice.

Mol Metab 2020 12 26;42:101067. Epub 2020 Aug 26.

Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute McMaster University, Hamilton, Ontario, L8N 3Z5, Canada. Electronic address:

Objective: Hyperinsulinemia can be both a cause and consequence of obesity and insulin resistance. Hyperinsulinemia can result from increased insulin secretion and/or reduced insulin clearance. While many studies have focused on mechanisms triggering insulin secretion during obesity, the triggers for changes in insulin clearance during obesity are less defined. In this study, we investigated the role of the microbiota in regulating insulin clearance during diet-induced obesity.

Methods: Blood glucose and insulin clearance were tested in conventional male mice treated with antibiotics and germ-free mice colonized with microbes from mice that were fed a control (chow) diet or an obesogenic high-fat diet (HFD). The composition of the fecal microbiota was analyzed using 16S rRNA sequencing.

Results: Short-term HFD feeding and aging did not alter insulin clearance in the mice. Oral antibiotics mitigated impaired blood insulin clearance in the mice fed an HFD for 12 weeks or longer. Germ-free mice colonized with microbes from HFD-fed donor mice had impaired insulin but not C-peptide clearance. Microbe-transmissible insulin clearance impairment was only observed in germ-free mice after more than 6 weeks post-colonization upon HFD feeding. Five bacterial taxa predicted >90% of the variance in insulin clearance. Mechanistically, impaired insulin clearance was associated with lower levels of hepatic Ceacam-1 but increased liver and skeletal muscle insulin-degrading enzyme (IDE) activity.

Conclusions: Gut microbes regulate insulin clearance during diet-induced obesity. A small cluster of microbes or their metabolites may be targeted for mitigating defects in insulin clearance and hyperinsulinemia during the progression of obesity and type 2 diabetes.
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http://dx.doi.org/10.1016/j.molmet.2020.101067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522491PMC
December 2020

The Institute for Healthcare Improvement-NeuroPoint Alliance collaboration to decrease length of stay and readmission after lumbar spine fusion: using national registries to design quality improvement protocols.

J Neurosurg Spine 2020 Aug 21:1-10. Epub 2020 Aug 21.

4Carolina Neurosurgery & Spine Associates, Neuroscience and Musculoskeletal Institutes, Atrium Health Charlotte, North Carolina.

Objective: National databases collect large amounts of clinical information, yet application of these data can be challenging. The authors present the NeuroPoint Alliance and Institute for Healthcare Improvement (NPA-IHI) program as a novel attempt to create a quality improvement (QI) tool informed through registry data to improve the quality of care delivered. Reducing the length of stay (LOS) and readmission after elective lumbar fusion was chosen as the pilot module.

Methods: The NPA-IHI program prospectively enrolled patients undergoing elective 1- to 3-level lumbar fusions across 8 institutions. A three-pronged approach was taken that included the following phases: 1) Research Phase, 2) Development Phase, and 3) Implementation Phase. Primary outcomes were LOS and readmission. From January to June 2017, a learning system was created utilizing monthly conference calls, weekly data submission, and continuous refinement of the proposed QI tool. Nonparametric tests were used to assess the impact of the QI intervention.

Results: The novel QI tool included the following three areas of intervention: 1) preoperative discharge assessment (location, date, and instructions), 2) inpatient changes (LOS rounding checklist, daily huddle, and pain assessments), and 3) postdischarge calls (pain, primary care follow-up, and satisfaction). A total of 209 patients were enrolled, and the most common procedure was a posterior laminectomy/fusion (60.2%). Seven patients (3.3%) were readmitted during the study period. Preoperative discharge planning was completed for 129 patients (61.7%). A shorter median LOS was seen in those with a known preoperative discharge date (67 vs 80 hours, p = 0.018) and clear discharge instructions (71 vs 81 hours, p = 0.030). Patients with a known preoperative discharge plan also reported significantly increased satisfaction (8.0 vs 7.0, p = 0.028), and patients with increased discharge readiness (scale 0-10) also reported higher satisfaction (r = 0.474, p < 0.001). Those receiving postdischarge calls (76%) had a significantly shorter LOS than those without postdischarge calls (75 vs 99 hours, p = 0.020), although no significant relationship was seen between postdischarge calls and readmission (p = 0.342).

Conclusions: The NPA-IHI program showed that preoperative discharge planning and postdischarge calls have the potential to reduce LOS and improve satisfaction after elective lumbar fusion. It is our hope that neurosurgical providers can recognize how registries can be used to both develop and implement a QI tool and appreciate the importance of QI implementation as a separate process from data collection/analysis.
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http://dx.doi.org/10.3171/2020.5.SPINE20457DOI Listing
August 2020

Development and Validation of Cervical Prediction Models for Patient-Reported Outcomes at 1 Year After Cervical Spine Surgery for Radiculopathy and Myelopathy.

Spine (Phila Pa 1976) 2020 Nov;45(22):1541-1552

Department of Orthopaedic Surgery, Center for Musculoskeletal Research, Vanderbilt University School of Medicine, Nashville, Tennessee.

Study Design: Retrospective analysis of prospectively collected registry data.

Objective: To develop and validate prediction models for 12-month patient-reported outcomes of disability, pain, and myelopathy in patients undergoing elective cervical spine surgery.

Summary Of Background Data: Predictive models have the potential to be utilized preoperatively to set expectations, adjust modifiable characteristics, and provide a patient-centered model of care.

Methods: This study was conducted using data from the cervical module of the Quality Outcomes Database. The outcomes of interest were disability (Neck Disability Index:), pain (Numeric Rating Scale), and modified Japanese Orthopaedic Association score for myelopathy. Multivariable proportional odds ordinal regression models were developed for patients with cervical radiculopathy and myelopathy. Patient demographic, clinical, and surgical covariates as well as baseline patient-reported outcomes scores were included in all models. The models were internally validated using bootstrap resampling to estimate the likely performance on a new sample of patients.

Results: Four thousand nine hundred eighty-eight patients underwent surgery for radiculopathy and 2641 patients for myelopathy. The most important predictor of poor postoperative outcomes at 12-months was the baseline Neck Disability Index score for patients with radiculopathy and modified Japanese Orthopaedic Association score for patients with myelopathy. In addition, symptom duration, workers' compensation, age, employment, and ambulatory and smoking status had a statistically significant impact on all outcomes (P < 0.001). Clinical and surgical variables contributed very little to predictive models, with posterior approach being associated with higher odds of having worse 12-month outcome scores in both the radiculopathy and myelopathy cohorts (P < 0.001). The full models overall discriminative performance ranged from 0.654 to 0.725.

Conclusions: These predictive models provide individualized risk-adjusted estimates of 12-month disability, pain, and myelopathy outcomes for patients undergoing spine surgery for degenerative cervical disease. Predictive models have the potential to be used as a shared decision-making tool for evidence-based preoperative counselling.

Level Of Evidence: 2.
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http://dx.doi.org/10.1097/BRS.0000000000003610DOI Listing
November 2020

Patients with a depressive and/or anxiety disorder can achieve optimum Long term outcomes after surgery for grade 1 spondylolisthesis: Analysis from the quality outcomes database (QOD).

Clin Neurol Neurosurg 2020 10 17;197:106098. Epub 2020 Jul 17.

Department of Neurologic Surgery, University of Michigan, Ann Arbor, Michigan, United States.

Introduction: In the current study, we sought to compare baseline demographic, clinical, and operative characteristics, as well as baseline and follow-up patient reported outcomes (PROs) of patients with any depressive and/or anxiety disorder undergoing surgery for low-grade spondylolisthesis using a national spine registry.

Patients And Methods: The Quality Outcomes Database (QOD) was queried for patients undergoing surgery for Meyerding grade 1 lumbar spondylolisthesis undergoing 1-2 level decompression or 1 level fusion at 12 sites with the highest number of patients enrolled in QOD with 2-year follow-up data.

Results: Of the 608 patients identified, 25.6 % (n = 156) had any depressive and/or anxiety disorder. Patients with a depressive/anxiety disorder were less likely to be discharged home (p < 0.001). At 3=months, patients with a depressive/anxiety disorder had higher back pain (p < 0.001), lower quality of life (p < 0.001) and higher disability (p = 0.013); at 2 year patients with depression and/or anxiety had lower quality of life compared to those without (p < 0.001). On multivariable regression, depression was associated with significantly lower odds of achieving 20 % or less ODI (OR 0.44, 95 % CI 0.21-0.94,p = 0.03). Presence of an anxiety disorder was not associated with decreased odds of achieving that milestone at 3 months. The presence of depressive-disorder, anxiety-disorder or both did not have an impact on ODI at 2 years. Finally, patient satisfaction at 2-years did not differ between the two groups (79.8 % vs 82.7 %,p = 0.503).

Conclusion: We found that presence of a depressive-disorder may impact short-term outcomes among patients undergoing surgery for low grade spondylolisthesis but longer term outcomes are not affected by either a depressive or anxiety disorder.
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http://dx.doi.org/10.1016/j.clineuro.2020.106098DOI Listing
October 2020

A Dozen Testosterone Samples From One Patient, on One Day?

Authors:
Kevin F Foley

Lab Med 2021 Jan;52(1):e5-e7

Department of Pathology, Kaiser Permanente Northwest, Portland, Oregon.

The differential diagnosis of female virilization and infertility can be significantly narrowed using routine laboratory testing. The case presented herein is an example of a 28 year old Caucasian female patient with amenorrhea, hirsutism, and infertility in the context of markedly elevated serum testosterone levels. This case highlights the use of bilateral ovarian vein sampling for testosterone as a means to localize the ectopic testosterone production and to guide future surgical procedures. Adrenal vein sampling procedures are relatively more common than other methods. Ovarian vein sampling is less common, yet in this case, it proved diagnostic. This case demonstrates the needed cooperation of the clinical laboratory and the patient care team performing the catheterization, for this type of testing to be useful. In this unique case, we discovered bilateral production of androgens.
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http://dx.doi.org/10.1093/labmed/lmaa032DOI Listing
January 2021

Metrics Development for Minimal Invasive Unilateral Laminotomy for Bilateral Decompression of Lumbar Spinal Stenosis With and Without Spondylolisthesis by an International Expert Panel.

Global Spine J 2020 Apr 28;10(2 Suppl):168S-175S. Epub 2020 May 28.

Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY, USA.

Study Design: Prospective study.

Objectives: To develop, operationally define, and seek consensus from procedure experts on the metrics that best characterize a reference approach to the performance of a minimally invasive unilateral laminotomy for bilateral decompression (ULBD) for lumbar spinal stenosis.

Methods: A Metrics Group consisting of 3 experienced spine surgeons (2 neurosurgeons, 1 orthopedic surgeon), each with over 25 years of clinical practice, and an educational expert formed the Metrics Group that characterized a lumbar decompression surgery for spinal stenosis as a "reference" procedure. In a modified Delphi panel, 26 spine surgeons from 14 countries critiqued these metrics and their operational definitions before reaching consensus.

Results: Performance metrics consisting of 6 phases with 42 steps, 21 errors, and 17 sentinel errors were identified that characterize the procedure. During the peer review, these were evaluated, modified, and agreed.

Conclusions: Surgical procedures can be broken down into elemental tasks necessary for the safe and effective completion of a reference approach to a specified surgical procedure. Spinal experts from 16 countries reached consensus on performance metrics for the procedure. This metric-based characterization can be used in a training curriculum and also for assessment of training and performance in clinical practice.
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http://dx.doi.org/10.1177/2192568219893675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263325PMC
April 2020

Impact of Dominant Symptom on 12-Month Patient-Reported Outcomes for Patients Undergoing Lumbar Spine Surgery.

Neurosurgery 2020 10;87(5):1037-1045

Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota.

Background: The impact of symptom characteristics on outcomes of spine surgery remains elusive.

Objective: To determine the impact of symptom location, severity, and duration on outcomes following lumbar spine surgery.

Methods: We queried the Quality Outcomes Database (QOD) for patients undergoing elective lumbar spine surgery for lumbar degenerative spine disease. Multivariable regression was utilized to determine the impact of preoperative symptom characteristics (location, severity, and duration) on improvement in disability, quality of life, return to work, and patient satisfaction at 1 yr. Relative predictor importance was determined using an importance metric defined as Wald χ2 penalized by degrees of freedom.

Results: A total of 22 022 subjects were analyzed. On adjusted analysis, we found patients with predominant leg pain were more likely to be satisfied (P < .0001), achieve minimum clinically important difference (MCID) in Oswestry Disability Index (ODI) (P = .002), and return to work (P = .03) at 1 yr following surgery without significant difference in Euro-QoL-5D (EQ-5D) (P = .09) [ref = predominant back pain]. Patients with equal leg and back pain were more likely to be satisfied (P < .0001), but showed no significant difference in achieving MCID (P = .22) or return to work (P = .07). Baseline numeric rating scale-leg pain and symptom duration were most important predictors of achieving MCID and change in EQ-5D. Predominant symptom was not found to be an important determinant of return to work. Worker's compensation was found to be most important determinant of satisfaction and return to work.

Conclusion: Predominant symptom location is a significant determinant of functional outcomes following spine surgery. However, pain severity and duration have higher predictive importance. Return to work is more dependent on sociodemographic features as compared to symptom characteristics.
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http://dx.doi.org/10.1093/neuros/nyaa240DOI Listing
October 2020

NOD2 in hepatocytes engages a liver-gut axis to protect against steatosis, fibrosis, and gut dysbiosis during fatty liver disease in mice.

Am J Physiol Endocrinol Metab 2020 08 9;319(2):E305-E314. Epub 2020 Jun 9.

Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.

Obesity promotes nonalcoholic fatty liver disease (NAFLD). The intestinal microbiota contributes to NAFLD progression through a gut-to-liver pathway that promotes inflammation and fibrosis. Gut microbiota-derived factors can travel to the liver and activate immune responses in liver resident cells to promote inflammation and NAFLD. Little is known about bacterial sensors or immune responses that can protect against NAFLD. We tested whether the bacterial cell wall sensor nucleotide-binding oligomerization domain-containing (NOD)2 protects against diet-induced NAFLD in mice. Whole body deletion of NOD2 exacerbated liver steatosis and fibrosis in mice fed a NAFLD-promoting diet. Mice with a hepatocyte-specific deletion of NOD2 () also had higher liver steatosis and fibrosis compared with littermate wild-type mice (WT) fed a NAFLD-promoting diet. Hepatocyte-specific NOD2 deletion altered the composition of the gut microbiome. mice had increased relative abundance of Clostridiales and lower Erysipelotrichaceae among other changes in cecal bacteria compared with littermate WT mice. Hepatocyte-specific NOD2 deletion altered a transcriptional program of liver inflammation, metabolism, and fibrosis. mice had higher levels of transcripts involved in lipid and cholesterol metabolism. mice had higher transcript levels of transforming growth factor-β and collagen isoforms, which coincided with higher levels of liver collagen compared with WT mice. These data show that bacterial cell wall sensing within hepatocytes can engage retrograde cross-talk from the liver to the gut, where liver immunity communicates with the gut to influence the intestinal host-microbe relationship during diet-induced NAFLD, and NOD2 within the hepatocyte confers protection from liver steatosis and fibrosis.
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http://dx.doi.org/10.1152/ajpendo.00181.2020DOI Listing
August 2020

Predictors of the Best Outcomes Following Minimally Invasive Surgery for Grade 1 Degenerative Lumbar Spondylolisthesis.

Neurosurgery 2020 Jun 4. Epub 2020 Jun 4.

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California.

Background: The factors driving the best outcomes following minimally invasive surgery (MIS) for grade 1 degenerative lumbar spondylolisthesis are not clearly elucidated.

Objective: To investigate the factors that drive the best 24-mo patient-reported outcomes (PRO) following MIS surgery for grade 1 degenerative lumbar spondylolisthesis.

Methods: A total of 259 patients from the Quality Outcomes Database lumbar spondylolisthesis module underwent single-level surgery for degenerative grade 1 lumbar spondylolisthesis with MIS techniques (188 fusions, 72.6%). Twenty-four-month follow-up PROs were collected and included the Oswestry disability index (ODI) change (ie, 24-mo minus baseline value), numeric rating scale (NRS) back pain change, NRS leg pain change, EuroQoL-5D (EQ-5D) questionnaire change, and North American Spine Society (NASS) satisfaction questionnaire. Multivariable models were constructed to identify predictors of PRO change.

Results: The mean age was 64.2 ± 11.5 yr and consisted of 148 (57.1%) women and 111 (42.9%) men. In multivariable analyses, employment was associated with superior postoperative ODI change (β-7.8; 95% CI [-12.9 to -2.6]; P = .003), NRS back pain change (β -1.2; 95% CI [-2.1 to -0.4]; P = .004), EQ-5D change (β 0.1; 95% CI [0.01-0.1]; P = .03), and NASS satisfaction (OR = 3.7; 95% CI [1.7-8.3]; P < .001). Increasing age was associated with superior NRS leg pain change (β -0.1; 95% CI [-0.1 to -0.01]; P = .03) and NASS satisfaction (OR = 1.05; 95% CI [1.01-1.09]; P = .02). Fusion surgeries were associated with superior ODI change (β -6.7; 95% CI [-12.7 to -0.7]; P = .03), NRS back pain change (β -1.1; 95% CI [-2.1 to -0.2]; P = .02), and NASS satisfaction (OR = 3.6; 95% CI [1.6-8.3]; P = .002).

Conclusion: Preoperative employment and surgeries, including a fusion, were predictors of superior outcomes across the domains of disease-specific disability, back pain, leg pain, quality of life, and patient satisfaction. Increasing age was predictive of superior outcomes for leg pain improvement and satisfaction.
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http://dx.doi.org/10.1093/neuros/nyaa206DOI Listing
June 2020

RIPK2 Dictates Insulin Responses to Tyrosine Kinase Inhibitors in Obese Male Mice.

Endocrinology 2020 08;161(8)

Department of Biochemistry and Biomedical Sciences and Farncombe Family Digestive Health Research Institute, Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada.

Tyrosine kinase inhibitors (TKIs) used in cancer are also being investigated in diabetes. TKIs can improve blood glucose control in diabetic cancer patients, but the specific kinases that alter blood glucose or insulin are not clear. We sought to define the role of Receptor Interacting Serine/Threonine Kinase 2 (RIPK2) in mouse models of insulin resistance. We tested the TKI gefitinib, which inhibits RIPK2 activity, in wild-type (WT), Nod1-/-, Nod2-/-, and Ripk2-/- mice fed an obesogenic high-fat diet. Gefitinib lowered blood glucose during a glucose tolerance test (GTT) in a nucleotide-binding oligomerization domain (NOD)-RIPK2-independent manner in all obese mice. However, gefitinib lowered glucose-stimulated insulin secretion only in obese Ripk2-/- mice. Gefitinib had no effect on insulin secretion in obese WT, Nod1-/-, or Nod2-/- mice. Hence, genetic deletion of Ripk2 promoted the insulin-sensitizing potential of gefitinib, since this TKI lowered both blood glucose and insulin only in Ripk2-/- mice. Gefitinib did not alter the inflammatory profile of pancreas, adipose, liver, or muscle tissues in obese Ripk2-/- mice compared with obese WT mice. We also tested imatinib, a TKI that does not inhibit RIPK2 activity, in obese WT mice. Imatinib lowered blood glucose during a GTT, consistent with TKIs lowering blood glucose independently of RIPK2. However, imatinib increased glucose-stimulated insulin secretion during the glucose challenge. These data show that multiple TKIs lower blood glucose, where actions of TKIs on RIPK2 dictate divergent insulin responses, independent of tissue inflammation. Our data show that RIPK2 limits the insulin sensitizing effect of gefitinib, whereas imatinib increased insulin secretion.
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http://dx.doi.org/10.1210/endocr/bqaa086DOI Listing
August 2020
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