Excitatory and Inhibitory Descending Commissural Interneurons Differentially Integrate Supraspinal and Segmental Sensory Signals.

The limited information about how descending inputs from the brain and sensory inputs from the periphery use spinal cord interneurons (INs) is a major barrier to understanding how these inputs may contribute to motor functions under normal and pathologic conditions. Commissural interneurons (CINs) are a heterogeneous population of spinal INs that has been implicated in crossed motor responses and bilateral motor coordination (ability to use the right and left side of the body in a coordinated manner) and, therefore, are likely involved in many types of movement (e.g., dynamic posture stabilization, jumping, kicking, walking). In this study, we incorporate mouse genetics, anatomy, electrophysiology, and single-cell calcium imaging to investigate how a subset of CINs, those with descending axons called dCINs, are recruited by descending reticulospinal and segmental sensory signals independently and in combination. We focus on two groups of dCINs set apart by their principal neurotransmitter (glutamate and GABA) and identified as VGluT2+ dCINs and GAD2+ dCINs. We show that VGluT2+ and GAD2+ dCINs are both extensively recruited by reticulospinal and sensory input alone but that VGluT2+ and GAD2+ dCINs integrate these inputs differently. Critically, we find that when recruitment depends on the combined action of reticulospinal and sensory inputs (subthreshold inputs), VGluT2+ dCINs, but not GAD2+ dCINs, are recruited. This difference in the integrative capacity of VGluT2+ and GAD2+ dCINs represents a circuit mechanism that the reticulospinal and segmental sensory systems may avail themselves of to regulate motor behaviors both normally and after injury.SIGNIFICANCE STATEMENT The way supraspinal and peripheral sensory inputs use spinal cord interneurons is fundamental to defining how motor functions are supported both in health and disease. This study, which focuses on dCINs, a heterogeneous population of spinal interneurons critical for crossed motor responses and bilateral motor coordination, shows that both glutamatergic (excitatory) and GABAergic (inhibitory) dCINs can be recruited by supraspinal (reticulospinal) or peripheral sensory inputs. Additionally, the study demonstrates that in conditions where the recruitment of dCINs depends on the combined action of reticulospinal and sensory inputs, only excitatory dCINs are recruited. The study uncovers a circuit mechanism that the reticulospinal and segmental sensory systems may avail themselves of to regulate motor behaviors both normally and after injury.

Evaluating the strength of evidence for genes implicated in peroxisomal disorders using the ClinGen clinical validity framework and providing updates to the peroxisomal disease nomenclature.

Peroxisomal disorders are heterogeneous in nature, with phenotypic overlap that is indistinguishable without molecular testing. Newborn screening and gene sequencing for a panel of genes implicated in peroxisomal diseases are critical tools for the early and accurate detection of these disorders. It is therefore essential to evaluate the clinical validity of the genes included in sequencing panels for peroxisomal disorders. The Peroxisomal Gene Curation Expert Panel (GCEP) assessed genes frequently included on clinical peroxisomal testing panels using the Clinical Genome Resource (ClinGen) gene-disease validity curation framework and classified gene-disease relationships as Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Known Disease Relationship. Subsequent to gene curation, the GCEP made recommendations to update the disease nomenclature and ontology in the Monarch Disease Ontology (Mondo) database. Thirty-six genes were assessed for the strength of evidence supporting their role in peroxisomal disease, leading to 36 gene-disease relationships, after two genes were removed for their lack of a role in peroxisomal disease and two genes were curated for two different disease entities each. Of these, 23 were classified as Definitive (64%), one as Strong (3%), eight as Moderate (23%), two as Limited (5%), and two as No known disease relationship (5%). No contradictory evidence was found to classify any relationships as Disputed or Refuted. The gene-disease relationship curations are publicly available on the ClinGen website (https://clinicalgenome.org/affiliation/40049/). The changes to peroxisomal disease nomenclature are displayed on the Mondo website (http://purl.obolibrary.org/obo/MONDO_0019053). The Peroxisomal GCEP-curated gene-disease relationships will inform clinical and laboratory diagnostics and enhance molecular testing and reporting. As new data will emerge, the gene-disease classifications asserted by the Peroxisomal GCEP will be re-evaluated periodically.

Acute kidney injury and early fluid load in a retrospective cohort of neonatal sepsis.

BACKGROUND: Sepsis and acute kidney injury (AKI) are associated with mortality in the newborn intensive care unit (NICU). There is a paucity of studies that describe AKI and fluid overload in neonatal sepsis and their association with mortality. METHODS: Retrospective study of neonates with culture positive sepsis admitted to the NICU between June 2020 and June 2021 was conducted. Primary outcome was in-hospital mortality according to AKI as defined by the neonatal modified Kidney Diseases Improving Outcomes criteria. Secondary outcomes were early fluid overload and vasopressor use. RESULTS: Thirty-three percent of neonates had AKI with sepsis, and 57% of cases were severe AKI. AKI was associated with mortality after adjusting for variables that were different between survivors and non-survivors (aOR 5.7 [95% CI 1.1-36], p = 0.04). Early fluid overload occurred in 27% of neonates who were at higher risk of having AKI with sepsis (OR 7.4 [95% CI 1.6-26.0], p = 0.01) and higher risk of mortality (aOR 17.8 [95% CI 2-7545], p = 0.02). CONCLUSIONS: AKI and early fluid overload are associated with mortality in sepsis in our retrospective cohort. Mitigating AKI and early fluid overload in sepsis might be a fruitful strategy in reducing mortality with sepsis. A higher resolution version of the Graphical abstract is available as Supplementary information.

Clinical validity assessment of genes frequently tested on intellectual disability/autism sequencing panels.

PURPOSE: Neurodevelopmental disorders (NDDs), such as intellectual disability (ID) and autism spectrum disorder (ASD), exhibit genetic and phenotypic heterogeneity, making them difficult to differentiate without a molecular diagnosis. The Clinical Genome Resource Intellectual Disability/Autism Gene Curation Expert Panel (GCEP) uses systematic curation to distinguish ID/ASD genes that are appropriate for clinical testing (ie, with substantial evidence supporting their relationship to disease) from those that are not. METHODS: Using the Clinical Genome Resource gene-disease validity curation framework, the ID/Autism GCEP classified genes frequently included on clinical ID/ASD testing panels as Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Known Disease Relationship. RESULTS: As of September 2021, 156 gene-disease pairs have been evaluated. Although most (75%) were determined to have definitive roles in NDDs, 22 (14%) genes evaluated had either Limited or Disputed evidence. Such genes are currently not recommended for use in clinical testing owing to the limited ability to assess the effect of identified variants. CONCLUSION: Our understanding of gene-disease relationships evolves over time; new relationships are discovered and previously-held conclusions may be questioned. Without periodic re-examination, inaccurate gene-disease claims may be perpetuated. The ID/Autism GCEP will continue to evaluate these claims to improve diagnosis and clinical care for NDDs.

The influence of cognitive behavioral therapy on lumbar spine surgery outcomes: a systematic review and meta-analysis.

PURPOSE: As more patients undergo lumbar spine surgery, novel interventions may improve physical and mental health outcomes. Few studies summarize the benefit of cognitive behavioral therapy (CBT) among lumbar spine surgery patients. This study collects randomized control trial data to investigate the influence of CBT on patient reported outcomes among lumbar spine surgery patients. METHODS: Our study used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and a medical library expert assisted in searching PubMed/MEDLINE, Scopus, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PsycINFO, and Google Scholar. We calculated standardized mean differences (SMD) to evaluate the effect size of CBT versus control groups with a sensitivity analysis. RESULTS: Our meta-analysis included seven studies with a total of 531 patients. The majority of included studies evaluated lumbar fusion, with preoperative CBT performed by physiotherapists. The largest effects were observed for overall quality of life (SMD = 0.55 [95% CI 0.05, 1.05], p < 0.001, I2 = 86.7%) and psychological outcomes (SMD = 0.61 [95% CI 0.28, 0.94], p < 0.001, I2 = 89.7%) though disability and pain outcomes also favored CBT intervention. Included studies demonstrated low overall bias but large heterogeneity. Sensitivity analysis demonstrated negligible study design differences and revealed moderators including CBT session frequency and final follow-up duration (p < 0.001). CONCLUSION: Compared to usual care or alternative therapy control arms, CBT delivered the most improvement with overall quality of life and psychological outcomes. Among appropriately selected patients, CBT could improve perioperative disability, pain, quality of life, and psychological health following lumbar spine surgery.

How I curate: applying American Society of Hematology-Clinical Genome Resource Myeloid Malignancy Variant Curation Expert Panel rules for RUNX1 variant curation for germline predisposition to myeloid malignancies.

The broad use of next-generation sequencing and microarray platforms in research and clinical laboratories has led to an increasing appreciation of the role of germline mutations in genes involved in hematopoiesis and lineage differentiation that contribute to myeloid neoplasms. Despite implementation of the American College of Medical Genetics and Genomics and Association for Molecular Pathology 2015 guidelines for sequence variant interpretation, the number of variants deposited in ClinVar, a genomic repository of genotype and phenotype data, and classified as having uncertain significance or being discordantly classified among clinical laboratories remains elevated and contributes to indeterminate or inconsistent patient care. In 2018, the American Society of Hematology and the Clinical Genome Resource co-sponsored the Myeloid Malignancy Variant Curation Expert Panel to develop rules for classifying gene variants associated with germline predisposition to myeloid neoplasia. Herein, we demonstrate application of our rules developed for the RUNX1 gene to variants in six examples to show how we would classify them within the proposed framework.

Glanzmann thrombasthenia: genetic basis and clinical correlates.

Glanzmann thrombasthenia (GT) is an autosomal recessive disorder of platelet aggregation caused by quantitative or qualitative defects in integrins αIIb and ß3. These integrins are encoded by the ITGA2B and ITGB3 genes and form platelet glycoprotein (GP)IIb/IIIa, which acts as the principal platelet receptor for fibrinogen. Although there is variability in the clinical phenotype, most patients present with severe mucocutaneous bleeding at an early age. A classic pattern of abnormal platelet aggregation, platelet glycoprotein expression and molecular studies confirm the diagnosis. Management of bleeding is based on a combination of hemostatic agents including recombinant activated factor VII with or without platelet transfusions and antifibrinolytic agents. Refractory bleeding and platelet alloimmunization are common complications. In addition, pregnant patients pose unique management challenges. This review highlights clinical and molecular aspects in the approach to patients with GT, with particular emphasis on the significance of multidisciplinary care.

Preoperative patient activation is predictive of improvements in patient-reported outcomes following minimally invasive lumbar decompression.

PURPOSE: To determine whether there is an association between preoperative 10-Item Patient Activation Measure (PAM-10) scores and clinical outcomes following MIS LD. METHODS: Patients undergoing a primary MIS LD were retrospectively reviewed and stratified according to their preoperative PAM-10 scores: "low PAM," "moderate PAM," and "high PAM." Preoperative PAM score cohorts were tested for improvements in Oswestry Disability Index (ODI), 12-Item Short-Form Physical Component Score (SF-12 PCS), and Visual Analog Scale (VAS) back and leg pain using multivariate linear regression. RESULTS: Eighty-nine patients were included: 29 had a low PAM score, 32 had a moderate PAM score, and 28 had a high PAM score. Cohorts experienced similar preoperative VAS back pain, VAS leg pain, ODI, and SF-12 PCS. Patients with low PAM scores experienced a trend of higher pain scores throughout 6 months with VAS back pain being significant at 3 months and VAS leg pain being significant at 6-week and 3-month follow-up. Patients with lower PAM scores experienced a worse improvement in ODI at 6-week, 3-month, and 6-month timepoints. Lastly, patients with lower PAM scores demonstrated less improvement in SF-12 PCS at 3-month and 6-month follow-up. CONCLUSIONS: Lower preoperative PAM scores were associated with worse improvement in clinical outcomes following MIS LD. Patients with lower PAM scores had diminished improvement in long-term patient-reported outcomes including ODI, SF-12, and VAS back and leg pain. Our investigation suggests that preoperative PAM assessments may be an effective tool to predict postoperative outcomes following MIS LD.

Subtelomeric rearrangements in Indian children with idiopathic intellectual disability/developmental delay: Frequency estimation & clinical correlation using fluorescence in situ hybridization (FISH).

BACKGROUND & OBJECTIVES: Subtelomeres are prone to deleterious rearrangements owing to their proximity to unique sequences on the one end and telomeric repetitive sequences, which increase their tendency to recombine, on the other end. These subtelomeric rearrangements resulting in segmental aneusomy are reported to contribute to the aetiology of idiopathic intellectual disability/developmental delay (ID/DD). We undertook this study to estimate the frequency of subtelomeric rearrangements in children with ID/DD. METHODS: One hundred and twenty seven children with idiopathic ID/DD were tested for subtelomeric rearrangements using karyotyping and FISH. Blood samples were cultured, harvested, fixed and GTG-banded using the standard protocols. RESULTS: Rearrangements involving the subtelomeres were observed in 7.8 per cent of the tested samples. Detection of rearrangements visible at the resolution of the karyotype constituted 2.3 per cent, while those rearrangements detected only with FISH constituted 5.5 per cent. Five deletions and five unbalanced translocations were detected. Analysis of parental samples wherever possible was informative regarding the inheritance of the rearrangement. INTERPRETATION & CONCLUSIONS: The frequency of subtelomeric rearrangements observed in this study was within the reported range of 0-35 per cent. All abnormal genotypes were clinically correlated. Further analysis with array technologies presents a future prospect. Our results suggest the need to test individuals with ID/DD for subtelomeric rearrangements using sensitive methods such as FISH.

Neighborhood Deprivation and Treatment Challenges in Pediatric Musculoskeletal Infections: A Socioeconomic Analysis.

Introduction Musculoskeletal (MSK) infections are prevalent in the pediatric population, with previous research highlighting the significant impact of socioeconomic status (SES) on treatment outcomes. However, the specific link in pediatric cohorts remains poorly understood. The Area Deprivation Index (ADI), a measure of neighborhood-level disadvantage, serves as a crucial marker for SES. This study aims to investigate how ADI influences disease characteristics, treatment delays, and outcomes in pediatric patients with MSK infections. Methods A single-center retrospective cohort analysis was conducted using patient charts from a large urban pediatric hospital over six years from 2017 to 2022. Patients aged 0-18 years with diagnoses of osteomyelitis, septic arthritis, cellulitis, or pyomyositis were identified using the International Classification of Diseases - 10th Revision (ICD-10) codes. Data collection included demographics, disease characteristics, treatment delay intervals, and complications. Patient zip codes were obtained and entered into the Neighborhood Atlas® mapping website to determine their ADI. Patients were then stratified into four groups based on ADI scores: 1-10, 11-20, 21-40, and 41-100. Statistical analysis included the use of the Mann-Whitney U test for continuous data and the Chi-square/Fisher's exact test for binary and categorical data comparisons among the ADI groups. Results A total of 121 patients were included. Categorization based on ADI revealed 25 (20.7%) patients in the 1-10 ADI percentile group, 36 (29.8%) in the 11-20 group, 38 (31.4%) in the 21-40 group, and 22 (18.2%) in the 41-100 group. There were no significant differences between ADI and patient demographics, disease characteristics, presentation delay interval, treatment received, and complications. Conclusion The study demonstrates that there was no significant difference between ADI groups regarding demographics, disease characteristics, presentation delay interval, treatment received, and complications in pediatric populations. Despite the lack of evidence for differences in MSK infections attributable to ADI, this does not negate the potential existence of such a relationship.

Evaluating the clinical validity of genes related to hemostasis and thrombosis using the Clinical Genome Resource gene curation framework.

BACKGROUND: Inherited bleeding, thrombotic, and platelet disorders (BTPDs) are a heterogeneous set of diseases, many of which are very rare globally. Over the past 5 decades, the genetic basis of some of these disorders has been identified, and recently, high-throughput sequencing has become the primary means of identifying disease-causing genetic variants. OBJECTIVES: Knowledge of the clinical validity of a gene-disease relationship is essential to provide an accurate diagnosis based on results of diagnostic gene panel tests and inform the construction of such panels. The Scientific and Standardization Committee for Genetics in Thrombosis and Hemostasis undertook a curation process for selecting 96 TIER1 genes for BTPDs. The purpose of the process was to evaluate the evidence supporting each gene-disease relationship and provide an expert-reviewed classification for the clinical validity of genes associated with BTPDs. METHODS: The Clinical Genome Resource (ClinGen) Hemostasis/Thrombosis Gene Curation Expert Panel assessed the strength of evidence for TIER1 genes using the semiquantitative ClinGen gene-disease clinical validity framework. ClinGen Lumping and Splitting guidelines were used to determine the appropriate disease entity or entities for each gene, and 101 gene-disease relationships were identified for curation. RESULTS: The final outcome included 68 Definitive (67%), 26 Moderate (26%), and 7 Limited (7%) classifications. The summary of each curation is available on the ClinGen website. CONCLUSION: Expert-reviewed assignment of gene-disease relationships by the ClinGen Hemostasis/Thrombosis Gene Curation Expert Panel facilitates accurate molecular diagnoses of BTPDs by clinicians and diagnostic laboratories. These curation efforts can allow genetic testing to focus on genes with a validated role in disease.

Expert Panel Curation of 31 Genes in Relation to Limb Girdle Muscular Dystrophy.

Introduction: Limb girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous autosomal conditions with some degree of phenotypic homogeneity. LGMD is defined as having onset >2 years of age with progressive proximal weakness, elevated serum creatine kinase levels and dystrophic features on muscle biopsy. Advances in massively parallel sequencing have led to a surge in genes linked to LGMD. Methods: The ClinGen Muscular Dystrophies and Myopathies gene curation expert panel (MDM GCEP, formerly Limb Girdle Muscular Dystrophy GCEP) convened to evaluate the strength of evidence supporting gene-disease relationships (GDR) using the ClinGen gene-disease clinical validity framework to evaluate 31 genes implicated in LGMD. Results: The GDR was exclusively LGMD for 17 genes, whereas an additional 14 genes were related to a broader phenotype encompassing congenital weakness. Four genes (CAPN3, COL6A1, COL6A2, COL6A3) were split into two separate disease entities, based on each displaying both dominant and recessive inheritance patterns, resulting in curation of 35 GDRs. Of these, 30 (86%) were classified as Definitive, 4 (11%) as Moderate and 1 (3%) as Limited. Two genes, POMGNT1 and DAG1, though definitively related to myopathy, currently have insufficient evidence to support a relationship specifically with LGMD. Conclusions: The expert-reviewed assertions on the clinical validity of genes implicated in LGMDs form an invaluable resource for clinicians and molecular geneticists. We encourage the global neuromuscular community to publish case-level data that help clarify disputed or novel LGMD associations.

A prospective cohort study of assisted bladder emptying following primary cloacal repair: The Children's National experience.

INTRODUCTION/BACKGROUND: Although the combination of bladder dysfunction and upper tract anomalies puts patient with cloaca at risk for renal disease, the rarity of this condition makes it difficult to study empirically. As a high-volume center, we uniquely capture bladder function outcomes following our growing number of cloacal repairs. OBJECTIVE: 1) Describe the rates of incomplete bladder emptying following primary cloacal repair (at 2-3 months after repair and last follow up), and 2) identify clinical factors associated with assisted bladder emptying. STUDY DESIGN: We performed a prospective cohort study of patients undergoing primary cloaca repair by our Children's National Colorectal Center team between 2020 and 2021. The primary outcome was assisted bladder emptying at 2-3 months postoperatively and last visit. Covariables included preoperative characteristics (cloacagram measurements), ARM complexity (moderate = common channel [CC] <3-cm, severe = CC ≥ 3-cm), vesicoureteral reflux (VUR) status, sacral ratio (good ≥0.7, intermediate 0.7-0.4, poor ≤0.4), spinal cord status, means of preoperative bladder emptying, and operative details (age at repair, repair type, & concomitant laparotomy). RESULTS: Eighteen participants were eligible. A majority had moderate cloaca (78%), VUR (67%), spinal cord abnormalities (89%), and good sacral ratios (56%). Preoperatively, 10 patients were diapered for urine and 8 had assisted bladder emptying. Surgical repairs were performed at a median age of 8 months (range 4-46). Nine (50%) patients underwent urogenital separation (UGS), eight (44%) total urogenital mobilization, and 1 (6%) perineal sparing posterior sagittal anorectoplasty with introitoplasty. Exploratory laparotomy was performed in 7 (39%) patients. At 2-3 months, 7 patients were voiding and 11 required assisted bladder emptying. Median length of long-term follow up was 12 months (range 5-25), and 8 patients were voiding and 10 required assisted bladder emptying. Postoperative need for assisted bladder emptying was significantly associated with assisted bladder emptying preoperatively, a shorter urethra and increasing common channel length, UGS and exploratory laparotomy. Spinal cord imaging findings were not associated. DISCUSSION: Bladder emptying following cloaca repair is likely a result of congenital function and surgical effects. Indeed, increasingly cloaca complexity requiring UGS and laparotomy was associated with both pre- and post-operative assisted bladder emptying. The lack of association with spinal cord imaging may reflect a divergence between anatomy and function. CONCLUSION: Approximately half of patients required assisted bladder emptying in this study. Associated factors included urethral and common channel length, the need for assisted bladder emptying preoperatively, the type of surgical approach and additional laparotomy. Being diapered with seemingly normal voiding prior to surgery did not guarantee normal bladder function postoperatively.

Validation of Neck Disability Index Severity among Patients Receiving One or Two-Level Anterior Cervical Surgery.

STUDY DESIGN: Retrospective cohort. PURPOSE: To evaluate the validity of established severity thresholds for Neck Disability Index (NDI) among patients undergoing anterior cervical discectomy and fusion (ACDF) or cervical disc arthroplasty (CDA). OVERVIEW OF LITERATURE: Few studies have examined the validity of established NDI threshold values among patients undergoing ACDF or CDA. METHODS: A surgical database was reviewed to identify patients undergoing cervical spine procedures. Demographics, operative characteristics, comorbidities, NDI, Visual Analog Scale (VAS), and 12-item Short Form (SF-12) physical and mental composite scores (PCS and MCS) were recorded. NDI severity was categorized using previously established threshold values. Improvement from preoperative scores at each postoperative timepoint and convergent validity of NDI was evaluated. Discriminant validity of NDI was evaluated against VAS neck and arm and SF-12 PCS and MCS. RESULTS: All 290 patients included in the study demonstrated significant improvements from baseline values for all patient-reported outcome measures (PROMs) at all postoperative timepoints (p<0.001) except SF-12 MCS at 2 years (p =0.393). NDI showed a moderate- to-strong correlation (r≥0.419) at most timepoints for VAS neck, VAS arm, SF-12 PCS, and SF-12 MCS (p<0.001, all). NDI severity categories demonstrated significant differences in mean VAS neck, VAS arm, SF-12 PCS, and SF-12 MCS at all timepoints (p<0.001, all). Differences between NDI severity groups were not uniform for all PROMs. VAS neck values demonstrated significant intergroup differences at most timepoints, whereas SF-12 MCS showed significantly different values between most severity groups. CONCLUSIONS: Neck disability is strongly correlated with neck and arm pain, physical function, and mental health and demonstrates worse outcomes with increasing severity. Previously established severity categories may be more applicable to pain than physical function or mental health and may be more uniformly applied preoperatively for cervical spine patients.

History of Prior Lumbar Surgery Does Not Impact Mental Health Outcomes Following Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: The objective of this study was to evaluate the impact of undergoing a prior lumbar procedure on mental health outcomes following anterior cervical discectomy and fusion. SUMMARY OF BACKGROUND DATA: Revision and reoperations are perceived as risk factors for worse mental health outcomes. METHODS: A retrospective review of a surgical database was performed for cervical and lumbar procedures. The mental health measures used were: Short Form 12-Item Mental Composite Score (SF-12 MCS) and Patient Health Questionnaire 9 (PHQ-9). Secondary outcomes of interest were Visual Analogue Scale for neck and arm pain, Neck Disability Index, and Short Form 12-Item Physical Composite Score (SF-12 PCS). All outcomes were collected preoperatively and at 6 weeks, 12 weeks, 6 months, and 1 year postoperatively. Minimum clinically important difference (MCID) was calculated using established values. Patients were grouped based on the surgical history of an elective lumbar spine procedure and propensity-matched. Differences in postoperative outcome scores and MCID achievement were evaluated using linear and logistic regression respectively. RESULTS: A total of 74 patients were included in this study. Mental health outcomes did not demonstrate significant differences between groups for SF-12 MCS and PHQ-9 for all time points except at 6 weeks for PHQ-9 ( P =0.038). MCID achievement was not significantly impacted by surgical history for all outcome measures at all postoperative time points (all P >0.050). The majority of patients achieved an MCID by the 1-year time point for all outcomes for patients without a prior lumbar surgery except for Visual Analogue Scale arm and SF-12 PCS, while those with a surgical history achieved an MCID for all outcomes except SF-12 PCS and PHQ-9. CONCLUSIONS: Anterior cervical discectomy and fusion patients with a past history of lumbar surgery demonstrated significant improvements in depression, neck and arm pain, disability, and physical function as those without a past lumbar surgical history. Prior surgery also did not impact MCID achievement for all outcomes.

Preoperative Duration of Symptoms Does Not Affect Outcomes of Anterior Lumbar Interbody Fusion.

BACKGROUND: Previous studies have examined the impact of preoperative duration of symptoms (DOS) on lumbar spinal surgery outcomes although this has not been explored for anterior lumbar interbody fusion (ALIF). OBJECTIVE: To assess the impact of preoperative DOS on patient-reported outcome measures (PROMs) of ALIF with posterior instrumentation. METHODS: A database was retrospectively reviewed for ALIFs with posterior instrumentation. PROMs recorded at preoperative, 6-wk, 12-wk, 6-mo, and 1-yr postoperative timepoints included Visual Analog Scale back and leg, Oswestry Disability Index, 12-Item Short-Form Physical Component Score (SF-12 PCS), and PROM Information System physical function. Achievement of minimum clinically important difference (MCID) was determined by comparing differences in postoperative PROMs from baseline to established values. Patients were grouped based on preoperative DOS into <1-yr and ≥1-yr groups. Differences in PROMs were compared using a t-test, whereas MCID achievement used a χ2 test. RESULTS: Fifty-three patients were included, with 20 in the <1-yr group and 33 in the ≥1-yr group. The most common diagnosis was isthmic spondylolisthesis. No significant preoperative differences were observed in any PROM. DOS groups demonstrated significantly different scores for SF-12 PCS at 6 wk (P = .049). No significant differences in MCID achievement were observed between groups for any PROM. CONCLUSION: ALIF patients demonstrated similar levels of pain, disability, and physical function regardless of preoperative DOS, except for back pain and physical function at intermittent timepoints. MCID achievement did not differ based on DOS for all outcome measures.

Risk Factors for Failing to Reach a Minimal Clinically Important Difference Following Minimally Invasive Lumbar Decompression.

BACKGROUND: Clinically important postoperative changes can be best evaluated through the minimal clinically important difference (MCID). Our study aims to evaluate risk factors associated with failure to achieve MCID following lumbar decompression (LD). METHODS: Demographics, perioperative characteristics, and patient-reported outcome measures (PROM) for pain, disability, and physical function were retrospectively reviewed and collected for patients undergoing LD. MCID achievement was calculated using established values. Relative risk of demographic and perioperative characteristics with failure to meet MCID for all PROMs was calculated. Least absolute shrinkage and selection operator (LASSO) was used to estimate individual risk factors, and postestimation logistic regression was performed. RESULTS: The study cohort included 811 patients. Comorbidity burden was associated with failed MCID for visual analog scale (VAS) back and leg pain and Oswestry Disability Index (ODI). Operative levels or duration was associated with failed MCID for VAS leg pain, 12-item short form physical component summary (SF-12 PCS), and the patient-reported outcomes measurement information system physical function (PROMIS PF). Preoperative spinal pathology was associated with failed MCID for VAS leg pain, ODI, SF-12 PCS, and PROMIS PF. Additional risk factors included the type of operation, insurance, age, and body mass index. LASSO selected insurance, age, comorbidity burden, blood loss, operative duration, and type of spinal pathology as significant risk factors for failure to reach MCID. CONCLUSION: Failure to reach MCID was greatest for VAS back. Age, comorbidity burden, and prolonged procedures were significantly associated with risk for failure to reach MCID for a majority of PROMs. Comorbidity burden combined with operative outcomes may place patients at increased risk for failure to reach MCID for pain, disability, and physical function following LD. CLINICAL RELEVANCE: Establishes risk factors for failing to reach the threshold of meaningful difference in symptoms after LD surgery.

Differences in Clinically Important Physical Function Improvement in Workers' Compensation Population.

BACKGROUND: Patients receiving workers' compensation demonstrate a propensity for poorer postoperative outcomes. This study aims to determine rates of minimum clinically important difference (MCID) achievement in patients receiving workers' compensation following transforaminal lumbar interbody fusion (TLIF). METHODS: We retrospectively reviewed a prospective surgical database from 2015 to 2020 for primary, single-level TLIFs with posterior instrumentation for degenerative spinal pathologies. Visual analog scale (VAS) for back and leg, Oswestry Disability Index (ODI), 12-Item Short Form Physical Component Summary (SF-12 PCS), and Patient-Reported Outcome Measurement Information System physical function (PROMIS-PF) were collected pre- and postoperatively. Patients were separated by workers' compensation (WC) status. Propensity score matching was performed to account for differences in demographic characteristics. Postoperative improvements in patient-reported outcome measures (PROMs) were calculated using paired Student's t test, and intergroup differences were determined by Mann-Whitney U test. Achievement of MCID was determined using established values, and intergroup differences were assessed using χ 2 analysis. RESULTS: A total of 121 patients were included in this study with 29 WC and 92 non-WC patients. The mean age was 53.5 years with the majority being men (63.6%) and nonobese (54.5%). WC patients demonstrated significantly poorer PROM values at all timepoints except for preoperative VAS back (P = 0.297) and leg (P = 0.475). Overall achievement of MCID was significantly lower for WC patients for VAS back (P = 0.040), ODI (P = 0.001), SF-12 PCS (P = 0.010), and PROMIS-PF (P = 0.039). CONCLUSION: WC patients demonstrated poorer postoperative outcomes at multiple timepoints. Additionally, a significantly lower rate of MCID achievement for back pain, disability, and physical function was observed for WC patients. CLINICAL RELEVANCE: These results suggest that WC patients may require alternative preoperative counseling about realistic expectations for improvement following lumbar fusion.

Impact of Depression Severity on Patient-Reported Outcome Measures Following Multilevel Anterior Cervical Discectomy and Fusion.

BACKGROUND: Few studies have investigated the effects of preoperative depression and multilevel procedures on patient-reported outcomes (PROs) following anterior cervical discectomy and fusion (ACDF). This study aims to determine the impact of preoperative depression on PROs in single vs multilevel ACDF procedures. METHODS: Eligible primary single or multilevel ACDF procedures were retrospectively reviewed from 2015 to 2020 using a surgical database. PROs included visual analog scale (VAS), Neck Disability Index (NDI), 12-Item Short Form Physical Composite Summary and Mental Composite Summary (SF-12 PCS and MCS), and Patient-Reported Outcomes Measurement Information System physical function (PROMIS PF). PROs were collected preoperatively and at 6 weeks, 12 weeks, 6 months, and 1 year postoperatively. Patients were stratified into 3 groups based on Patient Health Questionnaire-9 (PHQ-9) score. Differences in PROs were assessed based on preoperative depression severity or both preoperative depression severity and number of operative levels. RESULTS: Our patient cohort included 42 individuals with minimal preoperative depressive symptoms, 32 having mild and 27 having moderate to severe. Baseline PRO values were significantly different between groups (all P < 0.01). Improvement significantly differed between groups at 6 weeks for VAS arm, NDI, and SF-12 MCS (all P < 0.05), and at 12 wweeks for VAS neck, NDI, SF-12 PCS and MCS, and PROMIS PF (all P < 0.05). SF-12 PCS and MCS at 6 months and VAS arm and SF-12 MCS at 1 year demonstrated significant intergroup differences (all P < 0.05). VAS arm at 1 year (P = 0.029), NDI at 12 weeks (P = 0.034), PROMIS PF at 6 weeks (P = 0.038), and SF-MCS at all postoperative time points were impacted by both preoperative depression severity and number of levels fused. CONCLUSION: Depression severity impacted recovery of pain, disability, and physical function preoperatively and at intermittent postoperative time points. Both severity and multilevel procedures impacted pain and mental health at intermittent postoperative time points. In addition to depression, multilevel ACDF procedures are an additional factor that must be considered in expected improvement of postoperative outcomes. CLINICAL RELEVANCE: Multilevel ACDF procedures and preoperative depression severity both impact postoperative pain, disability, and physical function.

Dual Role of Neck Disability Index in the Assessment of Quality of Life in Cervical Spine Patients.

INTRODUCTION: The Neck Disability Index (NDI) is a well-established measure for patients with cervical myelopathy, radiculopathy, or myeloradiculopathy. Few studies have examined the relationship between NDI and mental health outcomes after anterior cervical diskectomy and fusion (ACDF). Our study sets out to determine the possible correlations between NDI and mental health outcome measures after ACDF. METHODS: A prospectively maintained surgical registry was retrospectively reviewed for elective ACDF procedures from December 2013 to December 2019. Demographic and perioperative characteristics were collected. Primary outcomes of interest were NDI, 12-Item Short Form Mental Component Summary (SF-12 MCS), and Patient Health Questionnaire-9 (PHQ-9). Outcomes were collected preoperatively and postoperatively (6 weeks, 12 weeks, 6 months, 1 year, and 2 years). Postoperative improvement for all outcomes was evaluated using a paired Student t-test. Correlations between NDI and mental health outcomes were evaluated using the Pearson correlation coefficient. Strength of association was determined using the following criteria: weak (0.1 ≤ |r| < 0.3), moderate (0.3 ≤ |r| < 0.5), and strong (|r| ≥ 0.5). RESULTS: A total of 225 patients were included in this study. Most of the patients underwent a single-level procedure and had a spinal pathology of herniated nucleus pulposus. NDI demonstrated significant improvements through 2 years compared with preoperative values (all P < 0.001). Similarly, SF-12 MCS and PHQ-9 significantly improved through 1-year postoperatively (all P ≤ 0.010) but was not maintained at 2 years (P = 0.835; P = 0.128). NDI demonstrated a significant but moderate correlation with SF-12 MCS at the preoperative time point, but a strong correlation was observed at all postoperative time points (all P ≤ 0.001). A significant and strong correlation between NDI and PHQ-9 was demonstrated at all time points (all P ≤ 0.002). DISCUSSION: NDI demonstrated notable and strong correlations with mental health outcome measures at all postoperative time points. NDI is an effective measure to assess neck disability but may also help capture changes to mental health symptoms after ACDF.