Vitamin D and SARS-CoV-2 Infection: SERVE Study (SARS-CoV-2 Exposure and the Role of Vitamin D among Hospital Employees).

BACKGROUND: Recognition of the role of vitamin D in immune function has led to interest in its relationship with SARS-CoV-2 infection. Although clinical studies to date have had conflicting results, many individuals currently take high doses of vitamin D to prevent infection. OBJECTIVE: The goal of this study was to investigate the relationship between serum 25-hydroxyvitamin D (25OHD) and vitamin D supplement use with incident SARS-CoV-2 infection. METHODS: In this prospective cohort study, 250 health care workers were enrolled at a single institution and observed for 15 mo. Participants completed questionnaires every 3 mo regarding new SARS-CoV-2 infection, vaccination, and supplement use. Serum was drawn at baseline, 6, and 12 mo for 25OHD and SARS-CoV-2 nucleocapsid antibodies. RESULTS: The mean age of the participants was 40 y, BMI 26 kg/m2, 71% were Caucasian, and 78% female. Over 15 mo, 56 participants (22%) developed incident SARS-CoV-2 infections. At baseline, ∼50% reported using vitamin D supplements (mean daily dose 2250 units). Mean serum 25OHD was 38 ng/mL. Baseline 25OHD did not predict incident SARS-CoV-2 infection (OR: 0.98; 95% CI: 0.80, 1.20). Neither the use of vitamin D supplements (OR: 1.18; 95% CI: 0.65, 2.14) or supplement dose was associated with incident infection (OR: 1.01 per 100-units increase; 95% CI: 0.99, 1.02). CONCLUSION: In this prospective study of health care workers, neither serum 25OHD nor the use of vitamin D supplements was associated with the incident SARS-CoV-2 infection. Our findings argue against the common practice of consuming high-dose vitamin D supplements for the presumed prevention of COVID-19.

Opportunistic Evaluation of Trabecular Bone Texture by MRI Reflects Bone Mineral Density and Microarchitecture.

CONTEXT: Many individuals at high risk for fracture are never evaluated for osteoporosis and subsequently do not receive necessary treatment. Utilization of magnetic resonance imaging (MRI) is burgeoning, providing an ideal opportunity to use MRI to identify individuals with skeletal deficits. We previously reported that MRI-based bone texture was more heterogeneous in postmenopausal women with a history of fracture compared to controls. OBJECTIVE: The present study aimed to identify the microstructural characteristics that underlie trabecular texture features. METHODS: In a prospective cohort, we measured spine volumetric bone mineral density (vBMD) by quantitative computed tomography (QCT), peripheral vBMD and microarchitecture by high-resolution peripheral QCT (HRpQCT), and areal BMD (aBMD) by dual-energy x-ray absorptiometry. Vertebral trabecular bone texture was analyzed using T1-weighted MRIs. A gray level co-occurrence matrix was used to characterize the distribution and spatial organization of voxelar intensities and derive the following texture features: contrast (variability), entropy (disorder), angular second moment (ASM; uniformity), and inverse difference moment (IDM; local homogeneity). RESULTS: Among 46 patients (mean age 64, 54% women), lower peripheral vBMD and worse trabecular microarchitecture by HRpQCT were associated with greater texture heterogeneity by MRI-higher contrast and entropy (r ∼ -0.3 to 0.4, P < .05), lower ASM and IDM (r ∼ +0.3 to 0.4, P < .05). Lower spine vBMD by QCT was associated with higher contrast and entropy (r ∼ -0.5, P < .001), lower ASM and IDM (r ∼ +0.5, P < .001). Relationships with aBMD were less pronounced. CONCLUSION: MRI-based measurements of trabecular bone texture relate to vBMD and microarchitecture, suggesting that this method reflects underlying microstructural properties of trabecular bone. Further investigation is required to validate this methodology, which could greatly improve identification of patients with skeletal fragility.

Utility of Seated Lateral Radiographs in the Diagnosis and Classification of Lumbar Degenerative Spondylolisthesis.

STUDY DESIGN: Retrospective cohort study. PURPOSE: Our goal was to determine which radiographic images are most essential for degenerative spondylolisthesis (DS) classification and instability detection. OVERVIEW OF LITERATURE: The heterogeneity in DS requires multiple imaging views to evaluate vertebral translation, disc space, slip angle, and instability. However, there are several restrictions on frequently used imaging perspectives such as flexion-extension and upright radiography. METHODS: We assessed baseline neutral upright, standing flexion, seated lateral radiographs, and magnetic resonance imaging (MRI) for patients identified with spondylolisthesis from January 2021 to May 2022 by a single spine surgeon. DS was classified by Meyerding and Clinical and Radiographic Degenerative Spondylolisthesis classifications. A difference of >10° or >8% between views, respectively, was used to characterize angular and translational instability. Analysis of variance and paired chi-square tests were utilized to compare modalities. RESULTS: A total of 136 patients were included. Seated lateral and standing flexion radiographs showed the greatest slip percentage (16.0% and 16.7%), while MRI revealed the lowest (12.2%, p <0.001). Standing flexion and lateral radiographs when seated produced more kyphosis (4.66° and 4.97°, respectively) than neutral upright and MRI (7.19° and 7.20°, p <0.001). Seated lateral performed similarly to standing flexion in detecting all measurement parameters and categorizing DS (all p >0.05). Translational instability was shown to be more prevalent when associated with seated lateral or standing flexion than when combined with neutral upright (31.5% vs. 20.2%, p =0.041; and 28.1% vs. 14.6%, p =0.014, respectively). There were no differences between seated lateral or standing flexion in the detection of instability (all p >0.20). CONCLUSIONS: Seated lateral radiographs are appropriate alternatives for standing flexion radiographs. Films taken when standing up straight do not offer any more information for DS detection. Rather than standing flexion-extension radiographs, instability can be detected using an MRI, which is often performed preoperatively, paired with a single seated lateral radiograph.

Creation of a Risk Calculator for Predicting New-Onset Cardiac Arrhythmias in Patients Undergoing Lumbar Fusion.

INTRODUCTION: As an increasing number of lumbar fusion procedures are being conducted at specialty hospitals and surgery centers, appropriate patient selection and risk stratification is critical to minimizing patient transfers. Postoperative cardiac arrhythmia has been linked to worse patient outcomes and is a common cause of patient transfer. Therefore, we created a risk calculator to predict a patient's likelihood of developing a new-onset postoperative cardiac arrhythmia after lumbar spinal fusion, which may improve preoperative facility selection. METHODS: A retrospective review was conducted of patients who undergoing lumbar fusion from 2017 to 2021 at a single academic center. Patients were excluded if they had any medical history of a cardiac arrhythmia. Multivariable regression was conducted to determine independent predictors of inpatient arrhythmias. The final regression was applied to a bootstrap to validate an arrhythmia prediction model. A risk calculator was created to determine a patient's risk of new-onset cardiac arrhythmia. RESULTS: A total of 1,622 patients were included, with 45 patients developing a new-onset postoperative arrhythmia. Age (OR = 1.05; 95% CI, 1.02 to 1.09; P = 0.003), history of beta-blocker use (OR = 2.01; 95% CI, 1.08 to 3.72; P = 0.027), and levels fused (OR = 1.59; 95% CI, 1.20 to 2.00; P = 0.001) were all independent predictors of having a new-onset inpatient arrhythmia. This multivariable regression produced an area under the curve of 0.742. The final regression was applied to a bootstrap prediction modeling technique to create a risk calculator including the male sex, age, body mass index, beta-blocker use, and levels fused (OR = 1.04, [CI = 1.03 to 1.06]) that produced an area under the curve of 0.733. CONCLUSION: A patient's likelihood of developing postoperative cardiac arrhythmias may be predicted by comorbid conditions and demographic factors including age, sex, body mass index, and beta-blocker use. Knowledge of these risk factors may improve appropriate selection of an outpatient surgical center or orthopaedic specialty hospital versus an inpatient hospital for lumbar fusions.

Reasons for transfer and subsequent outcomes among patients undergoing elective spine surgery at an orthopedic specialty hospital.

Objective: To evaluate the reasons for transfer as well as the 90-day outcomes of patients who were transferred from a high-volume orthopedic specialty hospital (OSH) following elective spine surgery. Materials and Methods: All patients admitted to a single OSH for elective spine surgery from 2014 to 2021 were retrospectively identified. Ninety-day complications, readmissions, revisions, and mortality events were collected and a 3:1 propensity match was conducted. Results: Thirty-five (1.5%) of 2351 spine patients were transferred, most commonly for arrhythmia (n = 7; 20%). Thirty-three transferred patients were matched to 99 who were not transferred, and groups had similar rates of complications (18.2% vs. 10.1%; P = 0.228), readmissions (3.0% vs. 4.0%; P = 1.000), and mortality (6.1% vs. 0%; P = 0.061). Conclusion: Overall, this study demonstrates a low transfer rate following spine surgery. Risk factors should continue to be optimized in order to decrease patient risks in the postoperative period at an OSH.

Colonic Epithelial Angiotensin-Converting Enzyme 2 (ACE2) Expression in Blacks and Whites: Potential Implications for Pathogenesis Covid-19 Racial Disparities.

BACKGROUND: Covid-19 toll is disproportionate in Blacks although the mechanisms remain incompletely understood. From a biological perspective, several host proteins have received most attention as logical susceptibility targets. Specifically, angiotensin-converting enzyme 2 (ACE2) serves as the epithelial cell receptor and acts in concert with transmembrane protease serine 2 (TMPRSS2). Intriguingly, ACE2 can also suppress the inflammatory response and therefore may impact the severity of Covid-19 infections (from the exuberant immune response a.k.a. "cytokine storm"). We, therefore, assessed expression of ACE2 and TMPRSS2 in Blacks versus Whites. METHODS: Archived mucosal biopsies from colonoscopic biopsies of visually normal rectal mucosa without concurrent neoplasia or inflammation were used for this study. Total mRNA was isolated and subjected to real-time polymerase chain reaction for ACE2, and TMPRSS2 was assessed from non-Hispanic Blacks (n = 45) and non-Hispanic Whites (n = 38). GAPDH and beta-actin were used for normalization. Multivariable analysis was performed using Analyse-IT software. RESULTS: ACE2 and TMPRSS2 levels were not altered by gender, BMI, or age. ACE2 levels were lower in Blacks than Whites achieving statistical significance in multivariable (0.51-fold, p = 0.03) but not quite in univariable (p = 0.07) analysis. This downregulation was mirrored in TMRPSS2 in both univariable (p = 0.03) and multivariable analyses (0.41-fold, p = 0.02). Moreover, there was a strong correlation between ACE2 and TMPRSS2 levels (r-squared = 0.78). CONCLUSIONS: To our knowledge, this is the first report on racial differences inACE2 and TMPRSS2 mucosal expression. This may provide potential biological underpinnings for the disproportionately higher mortality of Covid-19 in Blacks and should spur future studies.

Impact of Heart Disease History on Safety of Telemedicine Cardiac Clearance Appointments.

PURPOSE: The objective of this study was to compare complication, readmission, mortality, and cancellation rates between patients who had either an in-person or telemedicine preoperative cardiac clearance visit before spine surgery. METHODS: A retrospective review was conducted on patients who underwent a spine procedure at a single tertiary academic center from February 1, 2020, to June 30, 2021. Cancellations, inpatient complications, 90-day readmissions, and inpatient and 90-day mortality rates were compared between in-person and telemedicine cardiac clearance visits. Secondary analysis included multiple logistic regression to determine independent predictors of case cancellations and complications. Alpha was set at P < 0.05. RESULTS: A total of 1,331 consecutive patients were included, with 775 patients (58.2%) having an in-person cardiac clearance visit and 556 (41.8%) having telemedicine clearance. Overall, the telemedicine cohort did not have more cancellations, complications, or readmissions. Regardless of the type of clearance, patients with a history of cardiac disease had more inpatient complications (15.8% versus 6.9%, P < 0.001) and higher 90-day mortality rates (2.3% versus 0.4%, P = 0.005). Subgroup analysis of patients with a history of cardiac disease showed that patients who had telemedicine visits had more cancellations (4.6% versus 10.9%, P = 0.036) and higher 90-day mortality rates (1.4% versus 4.4%, P = 0.045). On regression analysis, telemedicine visits were not independent predictors of preoperative cancellation rates (P = 0.173) but did predict greater preoperative cancellations among patients with cardiac history (odds ratio 2.73, P = 0.036). DISCUSSION: Patients with cardiac disease who undergo preoperative telemedicine visits have greater preoperative surgical cancellation rates and postoperative 90-day mortality rates. Although preoperative telemedicine visits may be appropriate for most patients, a history of cardiac disease should be a contraindication.

MRI-based Texture Analysis of Trabecular Bone for Opportunistic Screening of Skeletal Fragility.

CONTEXT: Many individuals at high risk for osteoporosis and fragility fracture are never screened by traditional methods. Opportunistic use of imaging obtained for other clinical purposes is required to foster identification of these patients. OBJECTIVE: The aim of this pilot study was to evaluate texture features as a measure of bone fragility, by comparing clinically acquired magnetic resonance imaging (MRI) scans from individuals with and without a history of fragility fracture. METHODS: This study retrospectively investigated 100 subjects who had lumbar spine MRI performed at our institution. Cases (n = 50) were postmenopausal women with osteoporosis and a confirmed history of fragility fracture. Controls (n = 50) were age- and race-matched postmenopausal women with no known fracture history. Trabecular bone from the lumbar vertebrae was segmented to create regions of interest within which a gray level co-occurrence matrix was used to quantify the distribution and spatial organization of voxel intensity. Heterogeneity in the trabecular bone texture was assessed by several features, including contrast (variability), entropy (disorder), and angular second moment (homogeneity). RESULTS: Texture analysis revealed that trabecular bone was more heterogeneous in fracture patients. Specifically, fracture patients had greater texture variability (+76% contrast; P = 0.005), greater disorder (+10% entropy; P = 0.005), and less homogeneity (-50% angular second moment; P = 0.005) compared with controls. CONCLUSIONS: MRI-based textural analysis of trabecular bone discriminated between patients with known osteoporotic fractures and controls. Further investigation is required to validate this promising methodology, which could greatly expand the number of patients screened for skeletal fragility.

Patients with abnormal microarchitecture have an increased risk of early complications after spinal fusion surgery.

Spine fusion is one of the most common orthopedic surgeries, with more than 400,000 cases performed annually. While these procedures correct debilitating pain and deformities, complications occur in up to 45%. As successful fusion rests upon early stability of hardware in bone, patients with structural skeletal deficits may be at particular risk for complications. Few studies have investigated this relationship, and none have used higher order imaging to evaluate microstructural mechanisms for complications. Standard DXA measurements are subject to artifact in patients with spinal disease and therefore provide limited information. The goal of this prospective study was to investigate pre-operative bone quality as a risk factor for early post-operative complications using high resolution peripheral QCT (HR-pQCT) measurements of volumetric BMD (vBMD) and microarchitecture. We hypothesized that patients with low vBMD and abnormal microarchitecture at baseline would have more skeletal complications post-operatively. Conversely, we hypothesized that pre-operative DXA measurements would not be predictive of complications. Fifty-four subjects (mean age 63 years, BMI 27 kg/m2) were enrolled pre-operatively and followed for 6 months after multi-level lumbar spine fusion. Skeletal complications occurred in 14 patients. Patients who developed complications were of similar age and BMI to those who did not. Baseline areal BMD and Trabecular Bone Score by DXA did not differ. In contrast, HR-pQCT revealed that patients who developed complications had lower trabecular vBMD, fewer and thinner trabeculae at both the radius and tibia, and thinner tibial cortices. In summary, abnormalities of both trabecular and cortical microarchitecture were associated the development of complications within the first six months following spine fusion surgery. Our results suggest a mechanism for early skeletal complications after fusion. Given the burgeoning number of fusion surgeries, further studies are necessary to investigate strategies that may improve bone quality and lower the risk of post-operative complications.