Mental health after lumbar spine surgery: cognitive appraisal processes and outcome in a longitudinal cohort study.

BACKGROUND CONTEXT: A not uncommon finding following spine surgery is that many patients do not achieve mental health improvement up to population norms for their age cohort, despite improvement in pain and functioning. PURPOSE: This study examined how patients who were categorized as depressed versus not depressed think about health-related quality of life as assessed by cognitive-appraisal processes. It examined cross-sectional and longitudinal differences over 12 months postsurgery. DESIGN: Prospective longitudinal cohort study with data collected at presurgery and at ∼3- and ∼12-months postsurgery from August 2013 to August 2023. PATIENT SAMPLE: We included 173 adults undergoing lumbar spine surgery for degenerative spinal conditions at an academic medical center. The study sample was 47% female, with a mean age of 61 (SD=15.0), and a median level of education of college graduate. OUTCOME MEASURES: Depression was defined as a Mental Component Score (MCS)≤38 on the Rand-36, building on studies that equated MCS scores with significant depression as assessed by clinically validated depression scales. The Quality-of-Life Appraisal Profile assessed the cognitive-appraisal domains of Experience Sampling and Standards of Comparison. METHODS: The analysis focused on two comparisons: cross-sectionally comparing those who were not depressed (n=82) to those who were depressed (n=77) at baseline; and comparing longitudinal trajectories among those depressed before surgery and improved (n=54) versus did not improve (n=23). T-tests characterized group differences in appraisal endorsement; analysis of variance evaluated appraisal items in terms of explained variance; and Pearson correlation coefficients assessed direction of association in predicting mental health. RESULTS: There were presurgical and longitudinal differences in both cognitive appraisal domains. Before surgery, depressed patients were less likely than nondepressed patients to endorse emphasizing the positive; more likely to focus on worst moments, recent flare-ups, their spinal condition, and the future; and more likely to compare themselves to high aspirations (eg, perfect health). Over time, among those who were depressed before surgery, those who improved focused decreasingly on worst moments and on the time before their spinal condition, and increasingly on emphasizing the positive and balancing the positives/negatives. Appraisal explained more variance in mental health among those who did not improve as compared to those who did, at all timepoints. All appraisal items were more highly correlated with mental health among those who remained depressed as compared to those who improved, particularly over time. CONCLUSIONS: Endorsement of cognitive appraisal processes was different for depressed versus nondepressed spine-surgery patients before surgery and distinguished those who were depressed before surgery and improved versus those who did not improve. These findings suggest that targeted interventions could be beneficial for addressing mental health concerns during the spine surgery recovery trajectory. These interventions might use appraisal measures to identify patients likely to remain depressed after surgery, and then focus on helping these patients shift their focus and standards of comparison.

Genomic analysis across 53 canine cancer types reveals novel mutations and high clinical actionability potential.

A genomic understanding of the oncogenic processes and individual variability of human cancer has steadily fueled improvement in patient outcomes over the past 20 years. Mutations within tumour tissues are routinely assessed through clinical genomic diagnostic assays by academic and commercial laboratories to facilitate diagnosis, prognosis and effective treatment stratification. The application of genomics has unveiled a wealth of mutation-based biomarkers in canine cancers, suggesting that the transformative principles that have revolutionized human cancer medicine can be brought to bear in veterinary oncology. To advance clinical genomics and genomics-guided medicine in canine oncology, we have developed and validated a canine cancer next-generation sequencing gene panel for the identification of multiple mutation types in clinical specimens. With this panel, we examined the genomic landscapes of 828 tumours from 813 dogs, spanning 53 cancer types. We identified 7856 alterations, encompassing copy number variants, single nucleotide variants, indels and internal tandem duplications. Additionally, we evaluated the clinical utility of these alterations by incorporating a biomarker framework from comprehensive curation of primary canine literature and inferences from human cancer genomic biomarker literature and clinical diagnostics. Remarkably, nearly 90% of the cases exhibited mutations with diagnostic, prognostic or therapeutic implications. Our work represents a thorough assessment of genomic landscapes in a large cohort of canine cancers, the first of its kind for its comprehensive inclusion of multiple mutation types and structured annotation of biomarkers, demonstrating the clinical potential of leveraging mutation-based biomarkers in veterinary oncology.

A self-binding immune complex vaccine elicits strong neutralizing responses against herpes simplex virus in mice.

Introduction: It has been known for over half a century that mixing an antigen with its cognate antibody in an immune complex (IC) can enhance antigen immunogenicity. However, many ICs produce inconsistent immune responses, and the use of ICs in the development new vaccines has been limited despite the otherwise widespread success of antibody-based therapeutics. To address this problem, we designed a self-binding recombinant immune complex (RIC) vaccine which mimics the larger ICs generated during natural infection. Materials and methods: In this study, we created two novel vaccine candidates: 1) a traditional IC targeting herpes simplex virus 2 (HSV-2) by mixing glycoprotein D (gD) with a neutralizing antibody (gD-IC); and 2) an RIC consisting of gD fused to an immunoglobulin heavy chain and then tagged with its own binding site, allowing self-binding (gD-RIC). We characterized the complex size and immune receptor binding characteristics in vitro for each preparation. Then, the in vivo immunogenicity and virus neutralization of each vaccine were compared in mice. Results: gD-RIC formed larger complexes which enhanced C1q receptor binding 25-fold compared to gD-IC. After immunization of mice, gD-RIC elicited up to 1,000-fold higher gD-specific antibody titers compared to traditional IC, reaching endpoint titers of 1:500,000 after two doses without adjuvant. The RIC construct also elicited stronger virus-specific neutralization against HSV-2, as well as stronger cross-neutralization against HSV-1, although the proportion of neutralizing antibodies to total antibodies was somewhat reduced in the RIC group. Discussion: This work demonstrates that the RIC system overcomes many of the pitfalls of traditional IC, providing potent immune responses against HSV-2 gD. Based on these findings, further improvements to the RIC system are discussed. RIC have now been shown to be capable of inducing potent immune responses to a variety of viral antigens, underscoring their broad potential as a vaccine platform.