The relationship between psychological aspects and trajectories of symptoms in total knee arthroplasty and total hip arthroplasty

Background This study aimed to examine different trajectories of physical symptoms in hip and knee arthroplasty patients from presurgery to 1 year postsurgery and relate this to preoperative anxiety and depressive symptoms. Methods Patients (N = 345) completed the Hip injury and Osteoarthritis Outcome Score or the Knee injury and Osteoarthritis Outcome Score to examine their preoperative and postoperative pain, stiffness, and function, presurgery, and 3, 6, and 12 months postsurgery. Presurgery anxiety and depressive symptoms were assessed using the 7-item Generalized Anxiety Disorder Scale and the 9-item Patient Health Questionnaire. Latent trajectory analysis was used to identify different subgroups in trajectories. The step-3 method was used to assess subgroup characteristics. Results The effect of time on pain, function, and stiffness was different between subgroups of patients. Knee patients belonged mainly to classes with least improvement. Least improvement in pain was characterized by a combination of high levels of both anxiety and depressive symptoms. Anxiety and depressive symptoms were independently related to less reduction in stiffness while little improvement in function was characterized by higher depressive symptoms. Conclusion The results of this study indicate that anxiety and depressive symptoms were significantly, but differently, related to the distinct physical symptoms examined

Do dissatisfied patients have unrealistic expectations?: A systematic review and best-evidence synthesis in knee and hip arthroplasty patients

End-stage osteoarthritis is commonly treated with joint replacement. Despite high clinical success rates, up to 28% of patients are dissatisfied with the outcome.This best-evidence synthesis aimed to review studies with different forms of study design and methodology that examined the relationship between (fulfilment of) outcome expectations of hip and knee patients and satisfaction with outcome.A literature search was performed in PubMed, Web of Science, PsycInfo, Cochrane, and Google Scholar to identify studies conducted up to November 2017. The methodological quality of studies was assessed using the Newcastle-Ottawa Scale.In this best-evidence synthesis systematic review, the following main results could be seen. In only half of all studies were preoperative expectations associated with level of satisfaction, while in almost all studies (93%), fulfilment of expectations was related to satisfaction. The effect of met expectations did not differ between hip and knee patients or study design.Fulfilment of expectations seems to be consistently associated with patient satisfaction with outcome. Emphasis in future research must be placed on the operationalization and measurement of expectations and satisfaction to determine the (strength of the) influence of these different forms of assessment on the (existence of the) relationship. Cite this article: EFORT Open Rev 2020;5:226-240. DOI: 10.1302/2058-5241.5.190015

High pre-operative expectations precede both unfulfilled expectations and clinical improvement after total hip and total knee replacement

Background This prospective study aimed to examine whether patients’ and physicians’ outcome expectations were related to subjective (ie, fulfillment of expectations) and objective outcomes (ie, change in pain and function) in hip and knee arthroplasty patients up to 6 months post-surgery. Methods Patients’ (N = 395) and physicians’ outcome expectations were examined 1 week post-consultation. Patients’ post-operative functional status and the extent of fulfillment of expectations were examined 5 weeks, 3 months, and 6 months post-surgery. Patients and physicians completed the Hospital for Special Surgery Hip/Knee Replacement (Fulfillment) Expectations Survey. Patients completed the Hip/Knee injury and Osteoarthritis Outcome Score. Linear regression analyses were performed to examine the relationship between physicians’ expectations and patients’ change in pain and function and extent of fulfillment of expectations, and a possible mediated effect of patients’ pre-operative expectations. Results Patients’ high expectations were consistently associated with better objective outcomes (ie, change in pain and function). Yet, high expectations in patients were also negatively related to subjective outcomes (ie, the extent of fulfillment of expectations). Physicians’ expectations were only positively associated with objective improvement in knee patients, and not in hip patients. Additionally, knee patients’ expectations partly mediated the relationship between physicians’ expectations and change in pain and function, 6 months post-surgery. Conclusion Although patients’ high expectations were associated with better objective outcomes, improvement was still less than patients expected. Thus, patients often have too high expectations of outcomes of surgery. In addition, physicians were able to influence patients’ expectations and to change experienced knee patients’ outcomes

The relationship between psychological aspects and trajectories of symptoms in total knee arthroplasty and total hip arthroplasty

Background This study aimed to examine different trajectories of physical symptoms in hip and knee arthroplasty patients from presurgery to 1 year postsurgery and relate this to preoperative anxiety and depressive symptoms. Methods Patients (N = 345) completed the Hip injury and Osteoarthritis Outcome Score or the Knee injury and Osteoarthritis Outcome Score to examine their preoperative and postoperative pain, stiffness, and function, presurgery, and 3, 6, and 12 months postsurgery. Presurgery anxiety and depressive symptoms were assessed using the 7-item Generalized Anxiety Disorder Scale and the 9-item Patient Health Questionnaire. Latent trajectory analysis was used to identify different subgroups in trajectories. The step-3 method was used to assess subgroup characteristics. Results The effect of time on pain, function, and stiffness was different between subgroups of patients. Knee patients belonged mainly to classes with least improvement. Least improvement in pain was characterized by a combination of high levels of both anxiety and depressive symptoms. Anxiety and depressive symptoms were independently related to less reduction in stiffness while little improvement in function was characterized by higher depressive symptoms. Conclusion The results of this study indicate that anxiety and depressive symptoms were significantly, but differently, related to the distinct physical symptoms examined

Indoleamine 2,3-dioxygenase (IDO)-1 and IDO-2 activity and severe course of COVID-19

COVID-19 is a pandemic with high morbidity and mortality. In an autopsy cohort of COVID-19 patients, we found extensive accumulation of the tryptophan degradation products 3-hydroxy-anthranilic acid and quinolinic acid in the lungs, heart, and brain. This was not related to the expression of the tryptophan-catabolizing indoleamine 2,3-dioxygenase (IDO)-1, but rather to that of its isoform IDO-2, which otherwise is expressed rarely. Bioavailability of tryptophan is an absolute requirement for proper cell functioning and synthesis of hormones, whereas its degradation products can cause cell death. Markers of apoptosis and severe cellular stress were associated with IDO-2 expression in large areas of lung and heart tissue, whereas affected areas in brain were more restricted. Analyses of tissue, cerebrospinal fluid, and sequential plasma samples indicate early initiation of the kynurenine/aryl-hydrocarbon receptor/IDO-2 axis as a positive feedback loop, potentially leading to severe COVID-19 pathology

Neurofilament light increases over time in severe COVID-19 and is associated with delirium

Neurological monitoring in sedated Intensive Care Unit patients is constrained by the lack of reliable blood-based biomarkers. Neurofilament light is a cross-disease biomarker for neuronal damage with potential clinical applicability for monitoring Intensive Care Unit patients. We studied the trajectory of neurofilament light over a month in Intensive Care Unit patients diagnosed with severe COVID-19 and explored its relation to clinical outcomes and pathophysiological predictors. Data were collected over a month in 31 Intensive Care Unit patients (166 plasma samples) diagnosed with severe COVID-19 at Amsterdam University Medical Centre, and in the first week after emergency department admission in 297 patients with COVID-19 (635 plasma samples) admitted to Massachusetts General hospital. We observed that Neurofilament light increased in a non-linear fashion in the first month of Intensive Care Unit admission and increases faster in the first week of Intensive Care Unit admission when compared with mild-moderate COVID-19 cases. We observed that baseline Neurofilament light did not predict mortality when corrected for age and renal function. Peak neurofilament light levels were associated with a longer duration of delirium after extubation in Intensive Care Unit patients. Disease severity, as measured by the sequential organ failure score, was associated to higher neurofilament light values, and tumour necrosis factor alpha levels at baseline were associated with higher levels of neurofilament light at baseline and a faster increase during admission. These data illustrate the dynamics of Neurofilament light in a critical care setting and show associations to delirium, disease severity and markers for inflammation. Our study contributes to determine the clinical utility and interpretation of neurofilament light levels in Intensive Care Unit patients

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population