No evidence of association between either Modic change or disc degeneration and five circulating inflammatory proteins.

Introduction: Intervertebral disc degeneration and Modic change are the main spinal structural changes associated with chronic low back pain (LBP). Both conditions are thought to manifest local inflammation and if inflammatory proteins translocate to the blood circulation could be detected systemically. The work here assesses whether the presence of disc degeneration is associated with detectable blood level changes of five inflammatory markers and whether chronic LBP is associated with these changes. Materials and Methods: Two hundred and forty TwinsUK cohort participants with both MRI disc degeneration grade and Modic change extent, and IL-6, IL-8, IL-8 TNF, and CX3CL1 protein blood concentration measurements were included in this work. Linear mixed effects models were used to test the association of blood cytokine concentration with disc degeneration score and Modic change volumetric score. Association of chronic LBP status from questionnaires with disc degeneration, Modic change, and cytokine blood concentration was also tested. Results: No statistically significant association between disc degeneration or Modic change with cytokine blood concentration was found. Instead, regression analysis pointed strong association between cytokine blood concentration with body mass index for IL-6 and with age for IL-6 and TNF. Mild association was found between IL-8 blood concentration and body mass index. Additionally, LBP status was associated with Modic change volumetric score but not associated with any cytokine concentration. Conclusions: We found no evidence that Modic change and disc degeneration are able to produce changes in tested blood cytokine concentration. However, age and body mass index have strong influence on cytokine concentration and both are associated with the conditions studied which may confound associations found in the literature. It is then unlikely that cytokines produced in the disc or vertebral bone marrow induce chronic LBP.

Are current machine learning applications comparable to radiologist classification of degenerate and herniated discs and Modic change? A systematic review and meta-analysis.

INTRODUCTION: Low back pain is the leading contributor to disability burden globally. It is commonly due to degeneration of the lumbar intervertebral discs (LDD). Magnetic resonance imaging (MRI) is the current best tool to visualize and diagnose LDD, but places high time demands on clinical radiologists. Automated reading of spine MRIs could improve speed, accuracy, reliability and cost effectiveness in radiology departments. The aim of this review and meta-analysis was to determine if current machine learning algorithms perform well identifying disc degeneration, herniation, bulge and Modic change compared to radiologists. METHODS: A PRISMA systematic review protocol was developed and four electronic databases and reference lists were searched. Strict inclusion and exclusion criteria were defined. A PROBAST risk of bias and applicability analysis was performed. RESULTS: 1350 articles were extracted. Duplicates were removed and title and abstract searching identified original research articles that used machine learning (ML) algorithms to identify disc degeneration, herniation, bulge and Modic change from MRIs. 27 studies were included in the review; 25 and 14 studies were included multi-variate and bivariate meta-analysis, respectively. Studies used machine learning algorithms to assess LDD, disc herniation, bulge and Modic change. Models using deep learning, support vector machine, k-nearest neighbors, random forest and naïve Bayes algorithms were included. Meta-analyses found no differences in algorithm or classification performance. When algorithms were tested in replication or external validation studies, they did not perform as well as when assessed in developmental studies. Data augmentation improved algorithm performance when compared to models used with smaller datasets, there were no performance differences between augmented data and large datasets. DISCUSSION: This review highlights several shortcomings of current approaches, including few validation attempts or use of large sample sizes. To the best of the authors' knowledge, this is the first systematic review to explore this topic. We suggest the utilization of deep learning coupled with semi- or unsupervised learning approaches. Use of all information contained in MRI data will improve accuracy. Clear and complete reporting of study design, statistics and results will improve the reliability and quality of published literature.

Long-COVID fatigue is not predicted by pre-pandemic plasma IL-6 levels in mild COVID-19.

OBJECTIVE AND DESIGN: Fatigue is a prominent symptom in the general population and may follow viral infection, including SARS-CoV2 infection which causes COVID-19. Chronic fatigue lasting more than three months is the major symptom of the post-COVID syndrome (known colloquially as long-COVID). The mechanisms underlying long-COVID fatigue are unknown. We hypothesized that the development of long-COVID chronic fatigue is driven by the pro-inflammatory immune status of an individual prior to COVID-19. SUBJECTS AND METHODS: We analyzed pre-pandemic plasma levels of IL-6, which plays a key role in persistent fatigue, in N = 1274 community dwelling adults from TwinsUK. Subsequent COVID-19-positive and -negative participants were categorized based on SARS-CoV-2 antigen and antibody testing. Chronic fatigue was assessed using the Chalder Fatigue Scale. RESULTS: COVID-19-positive participants exhibited mild disease. Chronic fatigue was a prevalent symptom among this population and significantly higher in positive vs. negative participants (17% vs 11%, respectively; p = 0.001). The qualitative nature of chronic fatigue as determined by individual questionnaire responses was similar in positive and negative participants. Pre-pandemic plasma IL-6 levels were positively associated with chronic fatigue in negative, but not positive individuals. Raised BMI was associated with chronic fatigue in positive participants. CONCLUSIONS: Pre-existing increased IL-6 levels may contribute to chronic fatigue symptoms, but there was no increased risk in individuals with mild COVID-19 compared with uninfected individuals. Elevated BMI also increased the risk of chronic fatigue in mild COVID-19, consistent with previous reports.

Evidence for infection in intervertebral disc degeneration: a systematic review.

PURPOSE: Back pain is a major problem worldwide and is linked to intervertebral disc degeneration and Modic change. Several studies report growth of bacteria following extraction of degenerate discs at spine surgery. A pathophysiological role for infection in back pain has been proposed. METHOD: We conducted a PRISMA systematic review. MEDLINE, PubMed, Scopus and Web of Science were searched with the terms Modic change, intervertebral dis*, bacteria, microb*, and infect*. Date limits of 2001-2021 were set. Human studies investigating the role of bacteria in disc degeneration or Modic change in vertebrae were included. RESULTS: Thirty-six articles from 34 research investigations relating to bacteria in human degenerate discs were found. Cutibacterium acnes was identified in pathological disc material. A 'candidate bacterium' approach has been repeatedly adopted which may have biased results to find species a priori, with disc microbial evidence heavily weighted to find C. acnes. CONCLUSION: Evidence to date implicates C. acnes identified through culture, microscopy and sequencing, with some suggestion of diverse bacterial colonisation in the disc. This review found studies which used culture methods and conventional PCR for bacterial detection. Further agnostic investigation using newer methods should be undertaken.

Depression and poor outcome after an acute coronary event: Clarification of risk periods and mechanisms.

OBJECTIVE: Lifetime depression and depression around the time of an acute coronary syndrome event have been associated with poor cardiac outcomes. Our study sought to examine the persistence of this association, especially given modern cardiac medicine's successes. METHODS: For 332 patients admitted for an acute coronary syndrome, a baseline interview assessed major depression status, and psychological measures were administered. At 1 and 12 months post-acute coronary syndrome event, telephone interviews collected rates of hospital readmission and/or death and major depression status, while biomarker information was examined using medical records. RESULTS: The 12-month mortality rate was 2.3% and cardiac readmission rate 21.0%. Depression subsequent to an acute coronary syndrome event resulted in a threefold and 2.5-fold increase in 1-month and 12-month odds of cardiac readmission or death, respectively. No relationship with past depressive episodes was found. Poor sleep was associated with higher trait anxiety and neuroticism scores and with more severe depression. CONCLUSION: Lifetime depression may increase the risk of depression around the time of an acute coronary syndrome but not influence cardiac outcomes. We suggest that poor sleep quality may be causal or indicate high anxiety/neuroticism, which increases risk to depression and contributes to poor cardiac outcomes rather than depression being the primary causal factor.

Suprasensory phenomena in those with a bipolar disorder.

OBJECTIVES: To increase awareness of the sensory changes experienced during hypo/manic and depressive states by those with a bipolar disorder and determine if the prevalence of such features is similar across differing bipolar sub-types. METHODS: We interviewed 66 patients who acknowledged sensory changes during hypo/manic states. They were allocated to bipolar I, bipolar II and soft bipolar diagnostic categories and the prevalence of 10 differing sensory changes was quantified during hypo/manic and depressive phases. RESULTS: Bipolar I patients were just as likely, if not more likely, to report suprasensory changes which typically involved enhancement of senses during hypo/manic phases and muting or blunting during depressive phases. The high prevalence of changes in intuition, empathy, appreciation of danger and predictive capacities suggests that these are more part of the intrinsic bipolar mood domain states and not necessarily suprasensory, while changes in primary senses of smell, taste, vision, touch and hearing appear to more commonly define the suprasensory domain. CONCLUSIONS: It is important for clinicians and patients with a bipolar disorder to be aware of non-psychotic, suprasensory phenomena. Identification of such features may aid diagnosis and also explain the recognised increased creativity in those with a bipolar condition.

Acute coronary syndrome and depression: A review of shared pathophysiological pathways.

OBJECTIVE: To examine the evidence for shared pathophysiological pathways in acute coronary syndrome and major depression and to conceptualise the dynamic interplay of biological systems and signalling pathways that link acute coronary syndrome and depression within a framework of neuro-visceral integration. METHODS: Relevant articles were sourced via a search of published literature from MEDLINE, EMBASE and PubMed using a variety of search terms relating to biological connections between acute coronary syndrome and depression. Additional articles from bibliographies of retrieved papers were assessed and included where relevant. RESULTS: Despite considerable research efforts, a clear understanding of the biological processes connecting acute coronary syndrome and depression has not been achieved. Shared abnormalities are evident across the immune, platelet/endothelial and autonomic/stress-response systems. From the available evidence, it seems unlikely that a single explanatory model could account for the complex interactions of biological pathways driving the pathophysiology of these disorders and their comorbidity. CONCLUSION: A broader conceptual framework of mind-body or neuro-visceral integration that can incorporate the existence of several causative scenarios may be more useful in directing future research and treatment approaches for acute coronary syndrome-associated depression.

Acute coronary syndrome-associated depression: the salience of a sickness response analogy?

Depression emerging in conjunction with acute coronary syndrome (ACS) is thought to constitute a distinct high-risk phenotype with inflammatory determinants. This review critically examines the notion put forward in the literature that ACS-associated depression constitutes a meaningful subtype that is qualitatively different from depressive syndromes observed in psychiatric patients; and evaluates the salience of an analogy to the acute sickness response to infection or injury as an explanatory model. Specific features differentiating ACS-associated depression from other phenotypes are discussed, including differences in depression symptom profiles, timing of the depressive episode in relation to ACS, severity of the cardiac event, and associated immune activation. While an acute sickness response analogy offers a plausible conceptual framework, concrete evidence is lacking for inflammatory activity as the triggering mechanism. It is likely that ACS-associated depression encompasses several causative scenarios.

Characterising acute coronary syndrome-associated depression: Let the data speak.

Depression in the context of acute coronary syndrome (ACS) is understood to confer increased morbidity and mortality risk. The pathophysiological mechanisms underlying this association remain poorly understood, although several candidates including inflammation, cardiac autonomic dysregulation, and behavioural factors are viewed as of key importance. No single bio-behavioural explanatory model of ACS-associated depression has emerged, likely due the substantial heterogeneity across both conditions. We studied 344 patients with ACS; 45 fulfilled diagnostic (DSM-IV) criteria for a major depressive episode occurring within 1-month of ACS, and 13 had ongoing major depression that pre-dated ACS and continued through to 1 month post-ACS. We employed two statistical methods (multinomial logistic regression; and latent class analysis) and a range of immunological, autonomic and nutritional markers in an attempt to characterise a biological basis for ACS-associated depression. Regression modelling failed to accurately predict categorical group membership of ACS-associated depression. An alternative data-driven approach produced a three-class solution, with the derived classes differing on measure of C-reactive protein, vitamin D, omega-6:omega-3 ratio, heart rate variability, and age (all p⩽0.004). The majority of participants with ACS-associated and ongoing depression were members of the class characterised by the greatest biological disturbance. Patients with depression differed from those without depression on a range of psychological trait and state variables; additionally reporting poorer sleep quality, higher levels of social isolation, and functional impairment, but had similar biological profiles. Patients with ongoing depression generally had higher scores on these psychological/behavioural measures. Our novel analytic approach identified a combination of biomarkers suggestive of a role for immune, autonomic, and nutritional pathways in the manifestation of depression during ACS, in the context of additional psychosocial and behavioural vulnerabilities. Further studies are required to confirm the causal role of these factors in perpetuating depression and increasing risk of poor-health outcomes.

Predictors of post-natal depression are shaped distinctly by the measure of 'depression'.

BACKGROUND: Many variables have been proposed as predictive of post-natal depression (PND). AIMS: To investigate and refine PND risk variables. METHOD: We recruited a large sample and employed two measures of PND (the dimensional Edinburgh Postnatal Depression Scale or EPDS, and DSM-defined major depression). RESULTS: High levels of stress in the post-natal period, previous depression and higher depression scores during pregnancy were the only consistent predictors across measures. Those exceeding the EPDS cut-off had additional psychosocial risk factors while those meeting criteria for major depression were strongly predicted by a past history of depression as well as higher pre-natal state depression scores. LIMITATIONS: The EPDS has been used with variable cut off scores across multiple studies. We used only nine of the 10 EPDS items, electing to exclude the self-harm related question, but preserving the recommended EPDS cut-off score, and which might have impacted on predictions. CONCLUSIONS: Study results generated a refined set of predictors of PND but, more importantly, identified that predictors of PND status are distinctly influenced by the measure of PND. Such inconsistencies are intrinsically noteworthy and of potential key importance in shaping intervention strategies.

Self-focus and social evaluative threat increase salivary cortisol responses to acute stress in men.

This experiment tested the hypothesis that self-focused attention might increase cortisol release. Social self-preservation theory suggests that social evaluation and associated feelings of shame are associated with cortisol reactivity, whereas one implication of objective self-awareness theory is that self-critical awareness and associated feelings of anxiety might be associated with increases in cortisol. 120 participants completed a public speech task either in front of an evaluative panel (social threat), in a non-evaluative setting while watching themselves in real-time on a television (self-focus), or in the mere presence of a non-evaluative person (control). Cortisol increased comparably among men in the social threat and self-focus conditions, but not among men in the control condition. There were no effects for women. Shame was correlated with increased cortisol in the social threat condition, whereas anxiety was correlated with increased cortisol in the self-focus condition. One broad implication of this work is that negative evaluation may increase cortisol regardless of whether this source comes from oneself or others.