Clinical Implications of Co-administering Apixaban with Key Interacting Medications.

With many available data sources, clinicians need to consider the benefit-risk profile of individual anticoagulants when balancing the need for anticoagulation, including evaluating the risks in patients with comorbidities and potential drug-drug interactions. This narrative review presents clinical data across multiple phases of drug development for the use of apixaban, a selective factor Xa inhibitor, when taken concomitantly with other agents, and evaluates the benefit-risk profile of apixaban with these interacting medications. Key subgroup analyses from the phase 3 ARISTOTLE trial (NCT00412984) are presented using data from patients who received either concomitant inhibitors or inducers of cytochrome P450 3A4 and/or P­glycoprotein. We also review the available evidence for the use of apixaban in patients with cancer-associated thromboembolism, as well as the use of apixaban in patients with COVID-19.

Importance of the lumbar paraspinal muscles on the maintenance of global sagittal alignment after lumbar pedicle subtraction osteotomy.

OBJECTIVE: There are limited data about the influence of the lumbar paraspinal muscles on the maintenance of sagittal alignment after pedicle subtraction osteotomy (PSO) and the risk factors for sagittal realignment failure. The authors aimed to investigate the influence of preoperative lumbar paraspinal muscle quality on the postoperative maintenance of sagittal alignment after lumbar PSO. METHODS: Patients who underwent lumbar PSO with preoperative lumbar MRI and pre- and postoperative whole-spine radiography in the standing position were included. Spinopelvic measurements included pelvic incidence, sacral slope, pelvic tilt, L1-S1 lordosis, T4-12 thoracic kyphosis, spinosacral angle, C7-S1 sagittal vertical axis (SVA), T1 pelvic angle, and mismatch between pelvic incidence and L1-S1 lordosis. Validated custom software was used to calculate the percent fat infiltration (FI) of the psoas major, as well as the erector spinae and multifidus (MF). A multivariable linear mixed model was applied to further examine the association between MF FI and the postoperative progression of SVA over time, accounting for repeated measures over time that were adjusted for age, sex, BMI, and length of follow-up. RESULTS: Seventy-seven patients were recruited. The authors' results demonstrated significant correlations between MF FI and the maintenance of corrected sagittal alignment after PSO. After adjustment for the aforementioned parameters, the model showed that the MF FI was significantly associated with the postoperative progression of positive SVA over time. A 1% increase from the preoperatively assessed total MF FI was correlated with an increase of 0.92 mm in SVA postoperatively (95% CI 0.42-1.41, p < 0.0001). CONCLUSIONS: This study included a large patient cohort with midterm follow-up after PSO and emphasized the importance of the lumbar paraspinal muscles in the maintenance of sagittal alignment correction. Surgeons should assess the quality of the MF preoperatively in patients undergoing PSO to identify patients with severe FI, as they may be at higher risk for sagittal decompensation.

Importance of the cervical paraspinal muscles in postoperative patient-reported outcomes and maintenance of sagittal alignment after anterior cervical discectomy and fusion.

OBJECTIVE: The aim of this study was to investigate the influence of preoperatively assessed paraspinal muscle parameters on postoperative patient-reported outcomes and maintenance of cervical sagittal alignment after anterior cervical discectomy and fusion (ACDF). METHODS: Patients with preoperative and postoperative standing cervical spine lateral radiographs and preoperative cervical MRI who underwent an ACDF between 2015 and 2018 were reviewed. Muscles from C3 to C7 were segmented into 4 functional groups: anterior, posteromedial, posterolateral, and sternocleidomastoid. The functional cross-sectional area and also the percent fat infiltration (FI) were calculated for all groups. Radiographic alignment parameters collected preoperatively and postoperatively included C2-7 lordosis and C2-7 sagittal vertical axis (SVA). Neck Disability Index (NDI) scores were recorded preoperatively and at 2 and 4-6 months postoperatively. To investigate the relationship between muscle parameters and postoperative changes in sagittal alignment, multivariable linear mixed models were used. Multivariable linear regression models were used to analyze the correlations between the changes in NDI scores and the muscles' FI. RESULTS: A total of 168 patients with NDI and 157 patients with sagittal alignment measurements with a median follow-up of 364 days were reviewed. The mixed models showed that a greater functional cross-sectional area of the posterolateral muscle group at each subaxial level and less FI at C4-6 were significantly associated with less progression of C2-7 SVA over time. Moreover, there was a significant correlation between greater FI of the posteromedial muscle group measured at the C7 level and less NDI improvement at 4-6 months after ACDF. CONCLUSIONS: The findings highlight the importance of preoperative assessment of the cervical paraspinal muscle morphology as a predictor for patient-reported outcomes and maintenance of C2-7 SVA after ACDF.

Association Between Severity of Cervical Central Spinal Stenosis and Paraspinal Muscle Parameters in Patients Undergoing Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: Retrospective study. OBJECTIVE: The aim of this study was to evaluate the association between severity and level of cervical central stenosis (CCS) and the fat infiltration (FI) of the cervical multifidus/rotatores (MR) at each subaxial levels. SUMMARY OF BACKGROUND DATA: The relationship between cervical musculature morphology and the severity of CCS is poorly understood. METHODS: Patients with preoperative cervical magnetic resonance imaging (MRI) who underwent anterior cervical discectomy and fusion (ACDF) were reviewed. The cervical MR were segmented from C3 to C7 and the percent FI was measured using a custom-written Matlab software. The severity of the CCS at each subaxial level was assessed using a previously published classification. Grade 3, representing a loss of cerebrospinal fluid space and deformation of the spinal cord > 25%, was set as the reference and compared to the other gradings. Multivariable linear regression analyses were conducted and adjusted for age, sex, and body mass index. RESULTS: 156 consecutive patients were recruited. A spinal cord compression at a certain level was significantly associated with a greater FI of the MR below that level. After adjustment for the above-mentioned confounders, our results showed that spinal cord compression at C3/4 and C4/5 was significantly associated with greater FI of the MR from C3 to C6 and C5 to C7, respectively. A spinal cord compression at C5/6 or C6/7 was significantly associated with greater FI of the MR at C7. CONCLUSION: Our results demonstrated significant correlations between the severity of CCS and a greater FI of the MR. Moreover, significant level-specific correlations were found. A significant increase in FI of the MR at the levels below the stenosis was observed in patients presenting with spinal cord compression. Given the segmental innervation of the MR, the increased FI might be attributed to neurogenic atrophy. LEVEL OF EVIDENCE: 3.

Discrepancies in recommendations for return to regular activities after cervical spine surgery: A survey study.

Background: The recommended timing for returning to common activities after cervical spine surgery varies widely among physicians based on training background and personal opinion, without clear guidelines or consensus. The purpose of this study was to analyze spine surgeons' responses about the recommended timing for returning to common activities after different cervical spine procedures. Methods: This was a survey study including 91 spine surgeons. The participants were asked to complete an anonymous online survey. Questions regarding their recommended time for returning to regular activities (showering, driving, biking, running, swimming, sedentary work, and nonsedentary work) after anterior cervical decompression and fusion (ACDF), cervical disc replacement (CDR), posterior cervical decompression and fusion (PCDF), and laminoplasty were included. Comparisons of recommended times for return to activities after each surgical procedure were made based on surgeons' years in practice. Results: For ACDF and PCDF, there were no statistically significant differences in recommended times for return to any activity when stratified by years in practice. When considering CDR, return to non-sedentary work differed between surgeons in practice for 10 to 15 years, who recommended return at 3 months, and all other groups of surgeons, who recommended 6 weeks. Laminoplasty surgery yielded the most variability in activity recommendations, with earlier recommended return (6 weeks) to biking, non-sedentary work, and sedentary work in the most experienced surgeon group (>15 years in practice) than in all other surgeon experience groups (3 months). Conclusions: We observed significant variability in surgeon recommendations for return to regular activities after cervical spine surgery.

Deep-learning reconstructed lumbar spine 3D MRI for surgical planning: pedicle screw placement and geometric measurements compared to CT.

PURPOSE: To test equivalency of deep-learning 3D lumbar spine MRI with "CT-like" contrast to CT for virtual pedicle screw planning and geometric measurements in robotic-navigated spinal surgery. METHODS: Between December 2021 and June 2022, 16 patients referred for spinal fusion and decompression surgery with pre-operative CT and 3D MRI were retrospectively assessed. Pedicle screws were virtually placed on lumbar (L1-L5) and sacral (S1) vertebrae by three spine surgeons, and metrics (lateral deviation, axial/sagittal angles) were collected. Vertebral body length/width (VL/VW) and pedicle height/width (PH/PW) were measured at L1-L5 by three radiologists. Analysis included equivalency testing using the 95% confidence interval (CI), a margin of ± 1 mm (± 2.08° for angles), and intra-class correlation coefficients (ICCs). RESULTS: Across all vertebral levels, both combined and separately, equivalency between CT and MRI was proven for all pedicle screw metrics and geometric measurements, except for VL at L1 (mean difference: - 0.64 mm; [95%CI - 1.05, - 0.24]), L2 (- 0.65 mm; [95%CI - 1.11, - 0.20]), and L4 (- 0.78 mm; [95%CI - 1.11, - 0.46]). Inter- and intra-rater ICC for screw metrics across all vertebral levels combined ranged from 0.68 to 0.91 and 0.89-0.98 for CT, and from 0.62 to 0.92 and 0.81-0.97 for MRI, respectively. Inter- and intra-rater ICC for geometric measurements ranged from 0.60 to 0.95 and 0.84-0.97 for CT, and 0.61-0.95 and 0.93-0.98 for MRI, respectively. CONCLUSION: Deep-learning 3D MRI facilitates equivalent virtual pedicle screw placements and geometric assessments for most lumbar vertebrae, with the exception of vertebral body length at L1, L2, and L4, compared to CT for pre-operative planning in patients considered for robotic-navigated spine surgery.

Association patterns between lumbar paraspinal muscles and sagittal malalignment in preoperative patients undergoing lumbar three-column osteotomy.

PURPOSE: We aim to investigate the associations between lumbar paraspinal muscles and sagittal malalignment in patients undergoing lumbar three-column osteotomy. METHODS: Patients undergoing three-column osteotomy between 2016 and 2021 with preoperative lumbar magnetic resonance imaging (MRI) and whole spine radiographs in the standing position were included. Muscle measurements were obtained using a validated custom software for segmentation and muscle evaluation to calculate the functional cross-sectional area (fCSA) and percent fat infiltration (FI) of the m. psoas major (PM) as well as the m. erector spinae (ES) and m. multifidus (MM). Spinopelvic measurements included pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), L1-S1 lordosis (LL), T4-12 thoracic kyphosis (TK), spino-sacral angle (SSA), C7-S1 sagittal vertical axis (SVA), T1 pelvic angle (TPA) and PI-LL mismatch (PI - LL). Statistics were performed using multivariable linear regressions adjusted for age, sex, and body mass index (BMI). RESULTS: A total of 77 patients (n = 40 female, median age 64 years, median BMI 27.9 kg/m2) were analyzed. After adjusting for age, sex and BMI, regression analyses demonstrated that a greater fCSA of the ES was significantly associated with greater SS and SSA. Moreover, our results showed a significant correlation between a greater FI of the ES and a greater kyphosis of TK. CONCLUSION: This study included a large patient cohort with sagittal alignment undergoing three-column osteotomy and is the first to demonstrate significant associations between the lumbar paraspinal muscle parameters and global sagittal alignment. Our findings emphasize the importance of the lumbar paraspinal muscles in sagittal malalignment.

Laser Technology Advancements in the Treatment of Benign Prostatic Hypertrophy.

PURPOSE OF REVIEW: Lasers have had a significant impact on the treatment of benign prostatic hypertrophy. This article attempts to distill the advancements in laser technology for the treatment of benign prostatic hypertrophy (BPH) into key and understandable points to help make this topic more accessible to urologists. RECENT FINDINGS: The holmium:yttrium-aluminum-garnet (YAG) laser, one of the most significant lasers in the field of urology, has recently been improved with pulse modulating technology (Moses™ technology). New thulium:YAG technology allows both pulsed and continuous wave modes. The thulium fiber laser is one of the newer lasers to come to market and has been shown to have effective and safe outcomes. GreenLight™ lasers are predominantly used in photovaporization procedures and have also been studied extensively, although less in recent years. The modern urologist is fortunate to have many high-quality lasers and a wide variety of surgical techniques to choose from when treating BPH. Understanding the basic laser principles and applications will help urologists to select the best treatment options for their patients with BPH.

Health Care Resource Utilization and Total Costs of Care for Adult Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia in the United States: A Retrospective Claims Analysis.

PURPOSE: Although immunotherapies such as blinatumomab and inotuzumab have led to improved outcomes, financial burden and health resource utilization (HRU) have increased for adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). This study assessed real-world HRU and costs of care among adult patients with R/R B-ALL by line of therapy (LoT) in the United States. METHODS: We selected patients from the MarketScanⓇ Database (January 1, 2016 through December 31, 2020) as follows: ≥1 claims of ALL-indicated first-line (1L) therapies, ≥1 diagnosis of ALL before the index date (1L initiation date), 6-month continuous enrollment before the index date, second-line (2L) therapy initiation, ≥18 years old at 2L, no clinical trial enrollment, no diagnosis of other forms of non-Hodgkin's lymphoma, and no claim for daratumumab or nelarabine during the study period. Outcome measures included claim-based time to next treatment (TTNT), all-cause and adverse event (AE)-related HRU, and all-cause and AE-related costs. FINDINGS: The R/R B-ALL cohort (N = 203) was 60% male, median age of 41 years, and median Charlson Comorbidity Index score of 3.0. Mean (SD) follow-up was 17.8 (11.8) months. Of those who received 2L, 55.7% (113/203) required 3L, and 15% (30/203) initiated 4L+. Patients relapsed quickly, with a median TTNT of 170 days, 169 days, and 205 days for 2L, 3L, and 4L+, respectively. Hospitalization rates were high across each LoT (2L, 88%; 3L, 73%; 4L+, 73%), and the mean (SD) inpatient length of stay increased by LoT as follows: 8.6 (6.8) days for 2L, 10.6 (13.3) for 3L, and 11.6 (13.6) for 4L+. Mean (SD) overall costs were substantial within each LoT at $513,279 ($599,209), $340,419 ($333,555), and $390,327 ($332,068) for 2L, 3L, and 4L+, respectively. The mean (SD) overall/per-patient-per-month AE-related costs were $358,676 ($497,998) for 2L, $202,621 ($272,788) for 3L, and $210,539 ($267,814) for 4L+. Among those receiving blinatumomab or inotuzumab within each LoT, the mean (SD) total costs were $566,373 ($621,179), $498,070 ($376,260), and $512,908 ($159,525) for 2L, 3L, and 4L+, respectively. IMPLICATIONS: These findings suggest that adult patients with R/R B-ALL relapse frequently with standard of care and incur a substantial HRU and cost burden with each LoT. Those treated with blinatumomab or inotuzumab incurred higher total costs within each LoT compared with the overall R/R B-ALL cohort. Alternative therapies with longer duration of remission are urgently needed, and HRU should be considered for future studies examining the optimal sequencing of therapy.

Association Between Cervical Sagittal Alignment and Subaxial Paraspinal Muscle Parameters.

STUDY DESIGN: Retrospective review of prospectively collected data. OBJECTIVE: The authors aim to investigate the association between muscle functional group characteristics and sagittal alignment parameters in patients undergoing anterior cervical discectomy and fusion. SUMMARY OF BACKGROUND DATA: The relationship between the morphology of cervical paraspinal muscles and sagittal alignment is not well understood. MATERIALS AND METHODS: Patients with preoperative cervical magnetic resonance imaging and cervical spine lateral radiographs in standing position who underwent anterior cervical discectomy and fusion between 2015 and 2018 were reviewed. Radiographic alignment parameters included C2 to 7 lordosis, C2 to 7 sagittal vertical axis (SVA), C2 slope, neck tilt, T1 slope, and thoracic inlet angle. Muscles from C3 to C7 were categorized into four functional groups: sternocleidomastoid group, anterior group, posteromedial group, and posterolateral group (PL). A custom-written Matlab software was used to assess the functional cross-sectional area (fCSA) and percent fat infiltration (FI) for all groups. Multivariable linear regression analyses were conducted and adjusted for age, sex, and body mass index. RESULTS: A total of 172 patients were included. Regression analyses demonstrated that a greater C2 to 7 SVA was significantly associated with a greater FI of the anterior group from C3 to C5 and with a higher fCSA of the PL group at C3 to C4, and C6 to 7. A larger C2 slope was significantly correlated with a greater FI of the anterior group at C3 to C4 and a higher fCSA of the PL group from C3 to C5. CONCLUSION: This work proposes new insights into the complex interaction between sagittal alignment and cervical paraspinal muscles by emphasizing the importance of these muscles in sagittal alignment. The authors hypothesize that with cervical degeneration, the stabilizing function of the anterior muscles decreases, which may result in an increase in the compensatory mechanism of the PL muscles. Consequently, there may be a corresponding increase in the C2 to C7 SVA and a larger C2 slope.

Association between severity of the cervical foraminal stenosis and paraspinal muscle parameters in patients undergoing anterior cervical discectomy and fusion.

OBJECTIVE: The cervical multifidus and rotatores muscles are innervated by the posterior rami of the spinal nerves of the corresponding level, and it has been hypothesized that cervical foraminal stenosis (CFS) affecting the spinal nerves results in changes in these muscles. The purpose of this study was to evaluate the relationship between the severity of CFS and fat infiltration (FI) of the multifidus and rotatores muscles. METHODS: Patients who received preoperative cervical MRI, underwent anterior cervical decompression and fusion between 2015 and 2018, and met inclusion and exclusion criteria were included. Multifidus and rotatores muscles were segmented bilaterally from C3 to C7, and the percent FI was measured using custom-written MATLAB software. The severity of the CFS was assessed by the Kim classification. Multivariable linear mixed models were conducted and adjusted for age, sex, BMI, and repeated measures. RESULTS: In total, 149 patients were included. Linear mixed modeling results showed that a more severe CFS at C3-4 was correlated with a greater FI of the multifidus and rotatores muscles at C4 (estimate 0.034, 95% CI 0.003-0.064; p = 0.031), a more severe CFS at C4-5 was correlated with a greater FI of the multifidus and rotatores muscles at C5 (estimate 0.037, 95% CI 0.015-0.057; p < 0.001), a more severe CFS at C5-6 was correlated with a greater FI of the multifidus and rotatores muscles at C6 (estimate 0.041, 95% CI 0.019-0.062; p < 0.001) and C7 (estimate 0.035, 95% CI 0.012-0.058; p = 0.003), and a more severe CFS at C6-7 was correlated with a greater FI of the multifidus and rotatores muscles at C7 (estimate 0.049, 95% CI 0.027-0.071; p < 0.001). CONCLUSIONS: These results demonstrated level- and side-specific correlations between the FI of the multifidus and rotatores muscles and severity of CFS. Given the segmental innervation of the multifidus and rotatores muscles, the authors hypothesize that the observed increased FI could be reflective of changes due to muscle denervation from CFS.

Image-based estimation of the left ventricular cavity volume using deep learning and Gaussian process with cardio-mechanical applications.

In this investigation, an image-based method has been developed to estimate the volume of the left ventricular cavity using cardiac magnetic resonance (CMR) imaging data. Deep learning and Gaussian processes have been applied to bring the estimations closer to the cavity volumes manually extracted. CMR data from 339 patients and healthy volunteers have been used to train a stepwise regression model that can estimate the volume of the left ventricular cavity at the beginning and end of diastole. We have decreased the root mean square error (RMSE) of cavity volume estimation approximately from 13 to 8 ml compared to the common practice in the literature. Considering the RMSE of manual measurements is approximately 4 ml on the same dataset, 8 ml of error is notable for a fully automated estimation method, which needs no supervision or user-hours once it has been trained. Additionally, to demonstrate a clinically relevant application of automatically estimated volumes, we inferred the passive material properties of the myocardium given the volume estimates using a well-validated cardiac model. These material properties can be further used for patient treatment planning and diagnosis.

Sensitivity analysis and inverse uncertainty quantification for the left ventricular passive mechanics.

Personalized computational cardiac models are considered to be a unique and powerful tool in modern cardiology, integrating the knowledge of physiology, pathology and fundamental laws of mechanics in one framework. They have the potential to improve risk prediction in cardiac patients and assist in the development of new treatments. However, in order to use these models for clinical decision support, it is important that both the impact of model parameter perturbations on the predicted quantities of interest as well as the uncertainty of parameter estimation are properly quantified, where the first task is a priori in nature (meaning independent of any specific clinical data), while the second task is carried out a posteriori (meaning after specific clinical data have been obtained). The present study addresses these challenges for a widely used constitutive law of passive myocardium (the Holzapfel-Ogden model), using global sensitivity analysis (SA) to address the first challenge, and inverse-uncertainty quantification (I-UQ) for the second challenge. The SA is carried out on a range of different input parameters to a left ventricle (LV) model, making use of computationally efficient Gaussian process (GP) surrogate models in place of the numerical forward simulator. The results of the SA are then used to inform a low-order reparametrization of the constitutive law for passive myocardium under consideration. The quality of this parameterization in the context of an inverse problem having observed noisy experimental data is then quantified with an I-UQ study, which again makes use of GP surrogate models. The I-UQ is carried out in a Bayesian manner using Markov Chain Monte Carlo, which allows for full uncertainty quantification of the material parameter estimates. Our study reveals insights into the relation between SA and I-UQ, elucidates the dependence of parameter sensitivity and estimation uncertainty on external factors, like LV cavity pressure, and sheds new light on cardio-mechanic model formulation, with particular focus on the Holzapfel-Ogden myocardial model.

Neural network-based left ventricle geometry prediction from CMR images with application in biomechanics.

Combining biomechanical modelling of left ventricular (LV) function and dysfunction with cardiac magnetic resonance (CMR) imaging has the potential to improve the prognosis of patient-specific cardiovascular disease risks. Biomechanical studies of LV function in three dimensions usually rely on a computerized representation of the LV geometry based on finite element discretization, which is essential for numerically simulating in vivo cardiac dynamics. Detailed knowledge of the LV geometry is also relevant for various other clinical applications, such as assessing the LV cavity volume and wall thickness. Accurately and automatically reconstructing personalized LV geometries from conventional CMR images with minimal manual intervention is still a challenging task, which is a pre-requisite for any subsequent automated biomechanical analysis. We propose a deep learning-based automatic pipeline for predicting the three-dimensional LV geometry directly from routinely-available CMR cine images, without the need to manually annotate the ventricular wall. Our framework takes advantage of a low-dimensional representation of the high-dimensional LV geometry based on principal component analysis. We analyze how the inference of myocardial passive stiffness is affected by using our automatically generated LV geometries instead of manually generated ones. These insights will inform the development of statistical emulators of LV dynamics to avoid computationally expensive biomechanical simulations. Our proposed framework enables accurate LV geometry reconstruction, outperforming previous approaches by delivering a reconstruction error 50% lower than reported in the literature. We further demonstrate that for a nonlinear cardiac mechanics model, using our reconstructed LV geometries instead of manually extracted ones only moderately affects the inference of passive myocardial stiffness described by an anisotropic hyperelastic constitutive law. The developed methodological framework has the potential to make an important step towards personalized medicine by eliminating the need for time consuming and costly manual operations. In addition, our method automatically maps the CMR scan into a low-dimensional representation of the LV geometry, which constitutes an important stepping stone towards the development of an LV geometry-heterogeneous emulator.

Increased Ascorbate Biosynthesis Does Not Improve Nitrogen Fixation Nor Alleviate the Effect of Drought Stress in Nodulated Medicago truncatula Plants.

Legume plants are able to establish nitrogen-fixing symbiotic relations with Rhizobium bacteria. This symbiosis is, however, affected by a number of abiotic constraints, particularly drought. One of the consequences of drought stress is the overproduction of reactive oxygen (ROS) and nitrogen species (RNS), leading to cellular damage and, ultimately, cell death. Ascorbic acid (AsA), also known as vitamin C, is one of the antioxidant compounds that plants synthesize to counteract this oxidative damage. One promising strategy for the improvement of plant growth and symbiotic performance under drought stress is the overproduction of AsA via the overexpression of enzymes in the Smirnoff-Wheeler biosynthesis pathway. In the current work, we generated Medicago truncatula plants with increased AsA biosynthesis by overexpressing MtVTC2, a gene coding for GDP-L-galactose phosphorylase. We characterized the growth and physiological responses of symbiotic plants both under well-watered conditions and during a progressive water deficit. Results show that increased AsA availability did not provide an advantage in terms of plant growth or symbiotic performance either under well-watered conditions or in response to drought.

Does country of origin influence research outcomes in operative interventions for lumbar spinal stenosis?

INTRODUCTION: Bias undermines evidence-based decision making. To counter this, surgeons must be aware of biases that may influence studies' reported outcomes. Lumbar spinal stenosis often requires operative intervention, with multiple available surgical strategies. Our aim was to assess the role that country of origin plays in published surgical outcomes for lumbar spinal stenosis. METHODS: We performed a search strategy of MEDLINE and EMBASE for all English language primary research papers evaluating operative interventions for lumbar spinal stenosis during the years 2010-2019 inclusive. Small case series and meta-analyses were excluded. Papers were assessed for outcome positivity and country of origin. Data analysis was conducted using GraphPad Prism statistical software. RESULTS: A total of 487 papers met the inclusion criteria. Of these, 419 (86%) reported positive outcomes. Asian studies were the most likely to report positive outcomes, at 93% (220 of 236), followed by US studies at 89% (98 of 110). European studies had the lowest positive publication rate at 69% (84 of 121). Region of origin was an independent predictor of positive study outcome on multivariable analysis when controlling for different study designs and healthcare systems. CONCLUSION: There is an association between country of origin and positive reported outcome in studies evaluating interventions for lumbar spinal stenosis. Clinicians should consider this when making management decisions based on published evidence. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.

Methods to Mitigate Industry Influence in Industry Sponsored Research.

Medical and surgical research has always had a long-standing relationship with industry-based funding from sources, such as drug and device companies. Concerns exist surrounding the association between funding sources, outcome from studies and publication bias. Studies demonstrating increased odds ratios associated with positive results in industry sponsored studies across medicine have stimulated Cochrane reviews, literature reviews and other articles to examine this relationship further. In spine surgery in particular, studies with positive results have an odds ratio of 3.3 of being published. This article discusses the biases associated with industry sponsorship, possible ways to reduce such biases and ways to improve transparency in research relationships. This article explores the types of bias that can be encountered at different stages of research including previous trials in spine surgery. The means of improving transparency including the Physician Payment Sunshine Act of 2010 and International Committee of Medical Journal Editors (ICJME) accreditation are discussed. We recognize that physicians undertaking industry sponsored research should be protected and not be liable to perverse incentives. We conclude that mitigating bias in industry sponsored research is a multistep process and needs a multifaceted approach. The main beneficiary of research should be patients and as such a collective effort from medical professionals, health care institutions, journals and industry should approach research, and publications with that in mind.

A systematic review of the presentation of scan-negative suspected cauda equina syndrome.

BACKGROUND: A significant proportion of patients presenting with suspected cauda equina syndrome (CES) do not have associated radiological evidence to support the diagnosis, often termed 'scan-negative'. Due to the limited number of studies regarding the matter, there is no clear understanding for this presentation. As a result, no treatment protocol exists for the scan-negative group. The purpose of this review is to assess the potential contributing factors leading to the presentation of suspected CES with normal imaging. METHODS: A systematic review was conducted on PubMed and Cochrane databases. Bibliographies of key articles and Google Scholar were searched for additional results. The search strategy provided 204 results. Of those, 8 had no identifiable causation for suspected CES and were included for systematic review. RESULTS: 6 of 8 studies investigated for a difference in clinical presentation between cohorts that may indicate a normal scan. Studies were either inconclusive and contradictory. Two studies suggest a functional somatic disorder as reasoning for negative MRI, with positive provisional findings. CONCLUSION: A psychogenic hypothesis is plausible and warrants further investigation. The need for additional studies is essential to scheming a potential treatment protocol for the scan-negative population, which currently does not exist.