Lumbar spine intervertebral disc desiccation is associated with medical comorbidities linked to systemic inflammation.

INTRODUCTION: Symptomatic disc degeneration is a common cause of low back pain. Recently, the prevalence of low back pain has swiftly risen leading to increased patient disability and loss of work. The increase in back pain also coincides with a rapid rise in patient medical comorbidities. However, a comprehensive study evaluating a link between patient's medical comorbidities and their influence on lumbar intervertebral disc morphology is lacking in the literature. METHODS: Electronic medical records (EMR) were retrospectively reviewed to determine patient-specific medical characteristics. Magnetic resonance imaging (MRI) was evaluated for lumbar spine intervertebral disc desiccation and height loss according to the Griffith-modified Pfirrmann grading system. Bivariate and multivariable linear regression analyses assessed strength of associations between patient characteristics and lumbar spine Pfirrmann grade severity (Pfirrmann grade of the most affected lumbar spine intervertebral disc) and cumulative grades (summed Pfirrmann grades for all lumbar spine intervertebral discs). RESULTS: In total, 605 patients (304 diabetics and 301 non-diabetics) met inclusion criteria. Bivariate analysis identified older age, diabetes, American Society of Anesthesiologists (ASA) class, hypertension, chronic obstructive pulmonary disease (COPD), peripheral vascular disease, and hypothyroidism as being strongly associated with an increasing cumulative Pfirrmann grades. Multivariable models similarly found an association linking increased cumulative Pfirrmann grades with diabetes, hypothyroidism, and hypertension, while additionally identifying non-white race, heart disease, and previous lumbar surgery. Chronic pain, depression, and obstructive sleep apnea (OSA) were associated with increased Pfirrmann grades at the most affected level without an increase in cumulative Pfirrmann scores. Glucose control was not associated with increasing severity or cumulative Pfirrmann scores. CONCLUSION: These findings provide specific targets for future studies to elucidate key mechanisms by which patient-specific medical characteristics contribute to the development and progression of lumbar spine disc desiccation and height loss. LEVEL OF EVIDENCE: III (retrospective cohort).

DXA2: An Automated Program for Extraction of Dual-Energy X-Ray Absorptiometry Data.

INTRODUCTION/BACKGROUND: Since the 1970s imaging devices have been rapidly advancing to provide researchers, clinicians, radiologists, and practitioners greater capabilities to image bone. Today, dual-energy X-ray absorptiometry (DXA) has emerged as the gold standard for the assessment of bone and body composition. Despite recent improvements in DXA image quality and reduced radiation dosages and scan times, the data extraction process has yet to be streamlined. The objective of this study was to design an application to allow DXA users to quickly and accurately transfer DXA report data directly into a user-friendly format. METHODOLOGY: Initial development of the DXA Data Xtraction Assistant (DXA2) included processing 485 DXA reports from a previous study. Using Python script, numeric data from these DXA reports were converted to .csv files and then merged into one file, effectively compiling and organizing all table data from each report, by participant and visit number. A graphical user interface was then developed and beta tested using multiple DXA manufacturers, models, and software versions. To compare the effectiveness of the DXA2 to the current standard of manual extraction, all 485 reports were manually transcribed into Microsoft Excel. The time required per report and the error rates were compared. RESULTS: Manual transcription, by an experienced researcher, took over 10 h with an error rate of 0.6% and average error magnitude of 51%. Data extraction from DXA2 took less than 25 min to retrospectively reformat all DXA reports for the DXA2 and transcribe all 485 reports with 100% accuracy. CONCLUSION: The DXA2 application automates DXA report data extraction and aggregation for clinical, research, and applied settings and drastically reduces manual data entry time and eliminates transcription errors.

Automated extraction of biplanar stereo-radiographic image measurements: Mizzou 3D SPinE.

PURPOSE: Although several studies have reported on the application of biplanar stereo-radiographic technology in pediatric clinical practice, few have performed large-scale analyses. The manual extraction of these types of data is time-consuming, which often precludes physicians and scientists from effectively utilizing these valuable measurements. To fill the critical gap between clinical assessments and large-scale evidence-based research, we have addressed one of the primary hurdles in using data derived from these types of imaging modalities in pediatric clinical practice by developing an application to automatically transcribe and aggregate three-dimensional measurements in a manner that facilitates statistical analyses. METHODS: Mizzou 3D SPinE was developed using R software; the application, instructions, and process were beta tested with four separate testers. We compared 1309 manually compiled three-dimensional deformity measurements derived from thirty-five biplanar three-dimensional reconstructions (image sets) from ten pediatric patients to those derived from Mizzou 3D SPinE. We assessed the difference between manually entered values and extracted values using a Fisher's exact test. RESULTS: Mizzou 3D SPinE significantly reduced the duration of data entry (95.8%) while retaining 100% accuracy. Manually compiled data resulted in an error rate of 1.58%, however, the magnitude of errors ranged from 5.97 to 2681.82% significantly increased the transcription accuracy (p value < 0.0001) while also significantly reducing transcription time (0.33 vs. 8.08 min). CONCLUSION: Mizzou 3D SPinE is an essential component in improving evidence-based patient care by allowing clinicians and scientists to quickly compile three-dimensional data at regular intervals in an automated, efficient manner without transcription errors.

scBSP: A fast and accurate tool for identifying spatially variable genes from spatial transcriptomic data.

Spatially resolved transcriptomics have enabled the inference of gene expression patterns within two and three-dimensional space, while introducing computational challenges due to growing spatial resolutions and sparse expressions. Here, we introduce scBSP, an open-source, versatile, and user-friendly package designed for identifying spatially variable genes in large-scale spatial transcriptomics. scBSP implements sparse matrix operation to significantly increase the computational efficiency in both computational time and memory usage, processing the high-definition spatial transcriptomics data for 19,950 genes on 181,367 spots within 10 seconds. Applied to diverse sequencing data and simulations, scBSP efficiently identifies spatially variable genes, demonstrating fast computational speed and consistency across various sequencing techniques and spatial resolutions for both two and three-dimensional data with up to millions of cells. On a sample with hundreds of thousands of sports, scBSP identifies SVGs accurately in seconds to on a typical desktop computer.

Midterm Outcomes After Osteochondral Allograft Transplantation in the Knee Using High-Chondrocyte Viability Grafts.

BACKGROUND: Osteochondral allograft transplantation (OCAT) has become a standard-of-care treatment option for patients with large symptomatic articular defects. Recent advances in allograft science and OCAT protocols have been reported to result in consistently robust outcomes after OCAT in the knee. However, only short-term comparisons have been reported, and analyses are lacking for treatment failure risk factors that account for confounding variables. HYPOTHESIS: Midterm functional graft survival rate would exceed 80% for all OCATs combined, with consideration of risk factors for lower survivorship including older patient age, higher body mass index (BMI), tibiofemoral bipolar OCAT, and nonadherence to prescribed postoperative rehabilitation protocols. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients with outcome data available at ≥5 years after primary OCAT using high chondrocyte-viability (HCV) osteochondral allografts were analyzed according to 2 clinically relevant definitions: (1) initial treatment failure, defined by revision or arthroplasty surgery performed for the primary OCAT at any time point during the study period; and (2) functional graft failure, defined by documented conversion to arthroplasty after primary or revision OCAT at any time point during the study period. Analyses were used to assess outcomes for each definition, separately for age group, sex, obesity status, tobacco use, type of OCAT surgery, osteotomy status, concurrent ligament surgery status, and adherence to postoperative protocols. Kaplan-Meier analyses were used to assess differences in survival rates, and Cox proportional hazards models were used to assess risk factors and multivariable relationships with survival. Patient-reported outcome measures for pain, function, mobility, and satisfaction were also analyzed. RESULTS: Analysis included 137 primary knee OCATs performed in 134 patients with a mean follow-up of 66 months (59 female, 75 male; mean age, 37.8 years; mean BMI, 28.5). The midterm (5- to 8-year) functional graft survival rate for patients undergoing primary OCAT in the knee using HCV grafts was 82% for all cases combined, ranging from 69% for tibiofemoral bipolar HCV OCATs to 89% for patellofemoral bipolar, 94% for multisurface unipolar, and 97% for single-surface unipolar. Initial treatment failure rates (revision or arthroplasty after primary OCAT) and OCAT nonsurvival rates (arthroplasty after primary or revision OCAT) were greater for older patient age, concurrent ligament reconstruction, tibiofemoral bipolar OCAT, and nonadherence to the prescribed postoperative rehabilitation protocols. When adjusted for patients' age, BMI, and tobacco use status, different surgery types did not demonstrate an increased risk for failure, while concurrent ligament reconstruction and nonadherence did. Patients who experienced functional graft survival after primary OCAT reported significantly greater improvements in PROMIS Physical Function and Mobility (Patient-Reported Outcomes Measurement Information System), International Knee Documentation Committee questionnaire, and Single Assessment Numeric Evaluation scores such that they were significantly higher at final follow-up as compared with patients who required arthroplasty. Patient-reported improvements in pain, function, and mobility exceeded minimal clinically important differences for ≥5 years after primary OCAT. When asked if they were satisfied with primary OCAT surgery, 76.2% of patients were very satisfied or satisfied with their results, while 8.5% were neutral and 15.4% were unsatisfied or very unsatisfied. CONCLUSION: With use of HCV osteochondral allografts, midterm (5- to 8-year) functional graft survival rates for patients undergoing primary OCAT in the knee were notably higher than previously reported midterm rates for traditional OCATs. When adjusted for patient characteristics, risk factors for nonsurvival included concurrent ligament reconstruction for knee instability and nonadherence to the prescribed postoperative rehabilitation protocols. Patients who experienced functional graft survival for ≥5 years after primary OCAT reported statistically significant and clinically meaningful improvements in pain, function, and mobility.

IgA Nephropathy: Current Understanding and Perspectives on Pathogenesis and Targeted Treatment.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, with varied clinical and histopathological features between individuals, particularly across races. As an autoimmune disease, IgAN arises from consequences of increased circulating levels of galactose-deficient IgA1 and mesangial deposition of IgA-containing immune complexes, which are recognized as key events in the widely accepted "multi-hit" pathogenesis of IgAN. The emerging evidence further provides insights into the role of genes, environment, mucosal immunity and complement system. These developments are paralleled by the increasing availability of diagnostic tools, potential biomarkers and therapeutic agents. In this review, we summarize current evidence and outline novel findings in the prognosis, clinical trials and translational research from the updated perspectives of IgAN pathogenesis.

Dimension-agnostic and granularity-based spatially variable gene identification.

Identifying spatially variable genes (SVGs) is critical in linking molecular cell functions with tissue phenotypes. Spatially resolved transcriptomics captures cellular-level gene expression with corresponding spatial coordinates in two or three dimensions and can be used to infer SVGs effectively. However, current computational methods may not achieve reliable results and often cannot handle three-dimensional spatial transcriptomic data. Here we introduce BSP (big-small patch), a spatial granularity-guided and non-parametric model to identify SVGs from two or three-dimensional spatial transcriptomics data in a fast and robust manner. This new method has been extensively tested in simulations, demonstrating superior accuracy, robustness, and high efficiency. BSP is further validated by substantiated biological discoveries in cancer, neural science, rheumatoid arthritis, and kidney studies with various types of spatial transcriptomics technologies.

IgA nephropathy to proliferative glomerulonephritis with monoclonal IgAκ deposits: a pattern switch.

We report the case of a 31-year-old male who presented with repeated episodes of nephritic-nephrotic syndrome in concomitance with infection. IgA was diagnosed and was initially responsive to treatment with immunosuppressors but further disease flare did not respond to treatment. Based on three consecutive renal biopsies over 8 years, a pattern switch from endocapillary proliferative IgA nephropathy to membranous proliferative glomerulonephritis with monoclonal IgAκ deposits was observed. Bortezomib-dexamethasone combination therapy finally led to a favorable renal response. This case provides new insights into the pathophysiological mechanisms of proliferative glomerulonephritis with monoclonal immunoglobin deposits (PGNMID), highlighting the importance of repeat renal biopsies and routine evaluation of monoclonal immunoglobin deposits in proliferative glomerulonephritis with refractory nephrotic syndrome.

Dimension-agnostic and granularity-based spatially variable gene identification.

Identifying spatially variable genes (SVGs) is critical in linking molecular cell functions with tissue phenotypes. Spatially resolved transcriptomics captures cellular-level gene expression with corresponding spatial coordinates in two or three dimensions and can be used to infer SVGs effectively. However, current computational methods may not achieve reliable results and often cannot handle three-dimensional spatial transcriptomic data. Here we introduce BSP (big-small patch), a spatial granularity-guided and non-parametric model to identify SVGs from two or three-dimensional spatial transcriptomics data in a fast and robust manner. This new method has been extensively tested in simulations, demonstrating superior accuracy, robustness, and high efficiency. BSP is further validated by substantiated biological discoveries in cancer, neural science, rheumatoid arthritis, and kidney studies with various types of spatial transcriptomics technologies.

Dimension-agnostic and granularity-based spatially variable gene identification using BSP.

Identifying spatially variable genes (SVGs) is critical in linking molecular cell functions with tissue phenotypes. Spatially resolved transcriptomics captures cellular-level gene expression with corresponding spatial coordinates in two or three dimensions and can be used to infer SVGs effectively. However, current computational methods may not achieve reliable results and often cannot handle three-dimensional spatial transcriptomic data. Here we introduce BSP (big-small patch), a non-parametric model by comparing gene expression pattens at two spatial granularities to identify SVGs from two or three-dimensional spatial transcriptomics data in a fast and robust manner. This method has been extensively tested in simulations, demonstrating superior accuracy, robustness, and high efficiency. BSP is further validated by substantiated biological discoveries in cancer, neural science, rheumatoid arthritis, and kidney studies with various types of spatial transcriptomics technologies.

Single-cell biological network inference using a heterogeneous graph transformer.

Single-cell multi-omics (scMulti-omics) allows the quantification of multiple modalities simultaneously to capture the intricacy of complex molecular mechanisms and cellular heterogeneity. Existing tools cannot effectively infer the active biological networks in diverse cell types and the response of these networks to external stimuli. Here we present DeepMAPS for biological network inference from scMulti-omics. It models scMulti-omics in a heterogeneous graph and learns relations among cells and genes within both local and global contexts in a robust manner using a multi-head graph transformer. Benchmarking results indicate DeepMAPS performs better than existing tools in cell clustering and biological network construction. It also showcases competitive capability in deriving cell-type-specific biological networks in lung tumor leukocyte CITE-seq data and matched diffuse small lymphocytic lymphoma scRNA-seq and scATAC-seq data. In addition, we deploy a DeepMAPS webserver equipped with multiple functionalities and visualizations to improve the usability and reproducibility of scMulti-omics data analysis.

Is It Cost Effective to Obtain Fungal and Acid-Fast Bacillus Cultures during Spine Debridement?

STUDY DESIGN: Retrospective study. PURPOSE: To identify the rate of positive acid-fast bacillus (AFB) and fungal cultures during spine debridement, determine whether these infections are more common in certain spine segments, identify comorbidities associated with these infections, and determine whether the universal performance of fungal and AFB cultures during spine debridement is cost effective. OVERVIEW OF LITERATURE: Spine infections are associated with significant morbidity and costs. Spine fungal and AFB infections are rare, but their incidence has not been well documented. As such, guidance regarding sample procurement for AFB and fungal cultures is lacking. METHODS: A retrospective review of medical record data from patients undergoing spine irrigation and debridement (I&D) at the University of Missouri over a 10-year period was performed. RESULTS: For patients undergoing spine I&D, there was a 4% incidence of fungal infection and 0.49% rate of AFB infection. Steroid use was associated with a higher likelihood (odds ratio, 5.62; 95% confidence interval, 1.33-23.75) of positive fungal or AFB cultures. Although not significant, patients undergoing multiple I&D procedures had higher rates of positive fungal cultures during each subsequent I&D. Over a 10-year period, if fungal cultures are obtained for each patient, it would cost our healthcare system $12,151.58. This is compared to an average cost of $177,297.64 per missed fungal infection requiring subsequent treatment. CONCLUSIONS: Spine fungal infections occur infrequently at a rate of 4%. Physicians should strongly consider obtaining samples for fungal cultures in patients undergoing spine I&D, especially those using steroids and those undergoing multiple I&Ds. Our AFB culture rates mirror the false positive rates seen in previous orthopedic literature. It is unlikely to be cost effective to send for AFB cultures in areas with low endemic rates of AFB.

Surgical Reduction of Spondylolisthesis During Lumbar Fusion: Are Complications Associated With Slip Correction?

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: The objective of this study was to quantify the rates of complication following surgical treatment for symptomatic degenerative and isthmic spondylolisthesis and to examine the association between slip reduction and complication rates. SUMMARY OF BACKGROUND DATA: It is unclear if the degree of spondylolisthesis reduction during lumbar spine fusion in adults influences the rate of surgical complications. METHODS: This is a retrospective cohort study of 1-level and 2-level adult fusion patients with degenerative or isthmic spondylolisthesis. The degree of reduction and complications were calculated, and complication rates between those with and without reduction were compared. RESULTS: The surgical reduction was improved by 1 Meyerding grade in 56.5% of the 140 patients included in this analysis. Of those patients, 60% had a grade 1 spondylolisthesis. In addition, 62.5% of grade 2 slips had an improvement by 1 grade. Surgical reduction during lumbar fusion did not result in a higher rate of complications compared with in situ fusion. CONCLUSIONS: During 1-level or 2-level lumbar fusion for degenerative or isthmic spondylolisthesis, a 1-grade reduction of the slip was achieved in 56% of patients in this retrospective case series. Reduction of the spondylolisthesis was not associated with a higher rate of complication when compared with in situ fusion. LEVEL OF EVIDENCE: Level IV.

Ultrasound-Guided Nerve Blocks in the Head and Neck for Chronic Pain Management: The Anatomy, Sonoanatomy, and Procedure.

BACKGROUND: Ultrasound guided nerve blocks have become a popular tool in the armamentarium for pain physicians because of its advantages over fluoroscopy by offering portable, radiation-free and real-time imaging. But ultrasound guided procedures require training and practice to gain the expertise. There is a scarcity of review articles describing ultrasound guided injections techniques for nerve blocks of the head and neck. OBJECTIVE: To elucidate the anatomy, sonoanatomy, indications, techniques, side effects and complications for the most frequently utilized nerve blocks of the head and neck in chronic pain management. STUDY DESIGN: Narrative review. SETTING: Academic medical center. METHODS: Literature review of publications in English language of the related topics using Medline (Ovid) search engine. RESULTS: Deep cervical plexus block, cervical sympathetic ganglion block, trigeminal nerve and pterygopalatine ganglion block at the pterygopalatine fossa, greater occipital nerve block, third occipital nerve and medial branch block, and cervical selective nerve root block are discussed in this paper. The review begins with in depth discussion about the anatomy of the target nerve, followed by reviewing the available literature on the indications for the procedures. Detailed description of the procedure techniques is also presented. The volume and selection of medications is also discussed if there is available research. The review will conclude with summary of side effects, complications and precautions. LIMITATION: We only review those nerve blocks of the head and neck that would benefit from ultrasound guided injections in chronic pain management. Other nerve blocks such as transnasal sphenopalatine ganglion block, the interscalene brachial plexus block, superficial and intermediate cervical plexus block, anterior suprascapular nerve block, superficial trigeminal nerve block are not discussed due to either that ultrasound guidance is not warranted or they are rarely utilized in chronic pain management. This paper is not a systematic review, thus it might not include all the available evidence. Many of the available evidence is case series and case reports. More randomized control studies are warranted in the future to validate these techniques. CONCLUSION: Ultrasound guided nerve blocks of the head and neck are useful techniques for pain physicians to learn.

Monoclonal Gammopathy of Renal Significance (MGRS): Prospects for Treatment in Integrated Chinese and Western Medicine.

Monoclonal gammopathy of renal significance (MGRS) is a pathological state which presents with a spectrum of renal lesions. MGRS is characterized by pathogenic monoclonal immunoglobulins or light chains produced by a premalignant plasma cell or B cell clone. In view of inadequate understanding in the past, the low detection rate of MGRS often results in poor outcomes and reduces quality of life of patients. Thus, MGRS stands for a group of clinical refractory renal diseases. To date, no standard treatment strategy for MGRS is available. Current consensus suggests a clone-directed approach that aims to eradicate the offending clone, but its long-term prognosis is not clear. In this article, we discuss the diagnostic methods, highlight treatment advances, and introduce integrated Chinese and Western medicine in the management of MGRS.

Telemedicine in the Coronavirus Disease 2019 Pandemic: A Pediatric Rehabilitation Perspective.

ABSTRACT: In the spring of 2020, coronavirus disease 2019 evolved into a worldwide pandemic, forcing traditional face-to-face healthcare to a standstill. Telemedicine was quickly adopted as a major tool for pediatric rehabilitation services. This article describes the national legislative response of the United States to the coronavirus disease 2019 pandemic and the opportunities and challenges of implementing telemedicine in pediatric rehabilitation outpatient settings, consultations, as well as physician and patient education. The feasibility of performing a remote pediatric musculoskeletal and neurological tele-evaluation is also discussed. Although challenges exist, telemedicine has demonstrated its potential and has proven to be a practical system. Future developments in technology and accessibility, in addition to support from government and third-party payers, have the potential to make telemedicine an effective and vital platform in a coordinated healthcare system.

Comorbidities associated with cervical spine degenerative disc disease.

Determining important links between medical comorbidities and cervical spine degenerative disc disease (DDD) will help elucidate pathomechanisms of disc degeneration. Electronic medical records and magnetic resonance imaging were retrospectively reviewed to evaluate 799 patients assessed for cervical spine pathology. Bivariate analysis identified older age, diabetes, ASA class, cancer, COPD, depression, hypertension, hypothyroidism, Medicare status, peripheral vascular disease, history of previous cervical spine surgery, smoking, and lower median household income as having strong associations with increased cumulative grade of cervical spine DDD. This study provides evidence suggesting aging and accumulation of medical comorbidities influence severity of cervical spine DDD.

Treatment effects of Chinese medicine (Yi-Qi-Qing-Jie herbal compound) combined with immunosuppression therapies in IgA nephropathy patients with high-risk of end-stage renal disease (TCM-WINE): study protocol for a randomized controlled trial.

BACKGROUND: IgA nephropathy (IgAN) is the most common glomerular disease worldwide. It has a high incidence in Asians and is more likely to progress to end-stage renal disease (ESRD). For high-risk IgAN, which is clinically characterized by massive proteinuria and renal dysfunction, however, there has been no international consensus on treatment options. Compared with other developed countries, IgAN patients in China are often found to have severe kidney function loss at initial diagnosis. Yi-Qi-Qing-Jie formula (YQF; a compound recipe of Chinese medicinal herbs) has shown potential renal protection in our previous clinical studies. To further confirm the efficacy and safety of YQF in the treatment of high-risk IgAN, we have designed a prospective double-blind randomized placebo-controlled trial. METHODS/DESIGN: The TCM-WINE study is a single-center, prospective, double-blind randomized placebo-controlled trial. We plan to randomize 60 participants with biopsy-proven IgAN to a YQF combined group (YQF compound combined with prednisolone, and cyclophosphamide if necessary) or an immunosuppression group (placebo-YQF combined with prednisolone, and cyclophosphamide if necessary). The two groups will enter a 48-week in-trial treatment phase and receive post-trial follow-up until study completion (3 years). All patients will receive optimal supportive care. The primary composite outcome is defined as the first occurrence of a 40% decrease in estimated glomerular filtration rate (eGFR) from the baseline lasting for 3 months, initiating continuous renal replacement treatment, or death due to chronic kidney disease (CKD) during the 3-year study phase. The secondary endpoint events are defined as the mean annual eGFR decline rate (eGFR slope, ml/min per 1.73 m2 per year), which is calculated by the eGFR regression curve for each eligible patient, and proteinuria remission (prescribed as proteinuria < 0.5 g/day) at weeks 24, 36, and 48 during the in-trial phase. The remission rate of symptoms and inflammation status will be evaluated at week 48. Safety monitoring and assessment will be undertaken during the study. DISCUSSION: The TCM-WINE study will evaluate the effects and safety of YQF combined therapy compared with immunosuppression monotherapy on the basis of the optimal supportive treatment in high-risk IgAN. The evidence from this study will provide a novel, effective, and safe Chinese characteristic therapy for high-risk IgAN patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03418779. Registered on 18 June 2018.