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RMD Open Mar 2023Type I interferons (IFN-I) contribute to a broad range of rheumatic and musculoskeletal diseases (RMDs). Compelling evidence suggests that the measurement of IFN-I...
Association between type I interferon pathway activation and clinical outcomes in rheumatic and musculoskeletal diseases: a systematic literature review informing EULAR points to consider.
BACKGROUND
Type I interferons (IFN-I) contribute to a broad range of rheumatic and musculoskeletal diseases (RMDs). Compelling evidence suggests that the measurement of IFN-I pathway activation may have clinical value. Although several IFN-I pathway assays have been proposed, the exact clinical applications are unclear. We summarise the evidence on the potential clinical utility of assays measuring IFN-I pathway activation.
METHODS
A systematic literature review was conducted across three databases to evaluate the use of IFN-I assays in diagnosis and monitor disease activity, prognosis, response to treatment and responsiveness to change in several RMDs.
RESULTS
Of 366 screened, 276 studies were selected that reported the use of assays reflecting IFN-I pathway activation for disease diagnosis (n=188), assessment of disease activity (n=122), prognosis (n=20), response to treatment (n=23) and assay responsiveness (n=59). Immunoassays, quantitative PCR (qPCR) and microarrays were reported most frequently, while systemic lupus erythematosus (SLE), rheumatoid arthritis, myositis, systemic sclerosis and primary Sjögren's syndrome were the most studied RMDs. The literature demonstrated significant heterogeneity in techniques, analytical conditions, risk of bias and application in diseases. Inadequate study designs and technical heterogeneity were the main limitations. IFN-I pathway activation was associated with disease activity and flare occurrence in SLE, but their incremental value was uncertain. IFN-I pathway activation may predict response to IFN-I targeting therapies and may predict response to different treatments.
CONCLUSIONS
Evidence indicates potential clinical value of assays measuring IFN-I pathway activation in several RMDs, but assay harmonisation and clinical validation are urged. This review informs the EULAR points to consider for the measurement and reporting of IFN-I pathway assays.
Topics: Humans; Interferon Type I; Musculoskeletal Diseases; Myositis; Lupus Erythematosus, Systemic
PubMed: 36882218
DOI: 10.1136/rmdopen-2022-002864 -
Transplantation Reviews (Orlando, Fla.) Jul 2022The COVID-19 pandemic has a great impact on solid organ transplant (SOT) recipients due to their comorbidities and their maintenance immunosuppression. So far, studies... (Review)
Review
BACKGROUND
The COVID-19 pandemic has a great impact on solid organ transplant (SOT) recipients due to their comorbidities and their maintenance immunosuppression. So far, studies about the different aspects of the impact of the pandemic on SOT recipients are limited.
OBJECTIVES
This systematic review summarizes the risk factors that make SOT patients more vulnerable for severe COVID-19 disease or mortality and the impact of immunosuppressive therapy. Furthermore, their clinical outcomes, mortality risk, immunosuppression, immunity and COVID-19 vaccination efficacy are discussed.
METHODS
A systematic search on PubMed was performed to select original articles on SOT recipients concerning the following four topics: (1) mortality and clinical course; (2) risk factors for mortality and composite outcomes; (3) maintenance immunosuppression; (4) immunity to COVID-19 infection and (5) vaccine immunogenicity. Relevant data were extracted, analyzed and summarized in tables.
RESULTS
This systematic review includes 77 articles. Mortality was associated with advanced age. Post-transplantation time or comorbidities were variably identified as independent risk factors for mortality or severe disease. However, generally, no comorbidity was reported as a major risk factor. SOT recipients have a higher risk of acute kidney injury, but no higher rate of mortality compared to non-transplanted patients was found. Immunosuppression was individually adjusted, without leading to high rates of graft dysfunction. Generally, no association between type of immunosuppression and mortality was found. SOT patients established humoral and cellular immune responses after COVID-19 disease comparable to immunocompetent people. At last, SOT patients experience a diminished immune response after two-dose vaccination with SARS-COV-2-mRNA-vaccines.
CONCLUSION
More research is needed to address the direct effect of COVID-19 disease on the graft in lung transplant recipients, as well as the factors ameliorating the immune response in SOT recipients.
Topics: COVID-19; COVID-19 Vaccines; Humans; Organ Transplantation; Pandemics; SARS-CoV-2; Transplant Recipients
PubMed: 35809422
DOI: 10.1016/j.trre.2022.100710 -
MedRxiv : the Preprint Server For... Apr 2023Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing beta cells. Efforts to prevent T1D have focused on modulating immune responses and...
BACKGROUND
Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing beta cells. Efforts to prevent T1D have focused on modulating immune responses and supporting beta cell health; however, heterogeneity in disease progression and responses to therapies have made these efforts difficult to translate to clinical practice, highlighting the need for precision medicine approaches to T1D prevention.
METHODS
To understand the current state of knowledge regarding precision approaches to T1D prevention, we performed a systematic review of randomized-controlled trials from the past 25 years testing disease-modifying therapies in T1D and/or identifying features linked to treatment response, analyzing bias using a Cochrane-risk-of-bias instrument.
RESULTS
We identified 75 manuscripts, 15 describing 11 prevention trials for individuals with increased risk for T1D, and 60 describing treatments aimed at preventing beta cell loss in individuals at disease onset. Seventeen agents tested, mostly immunotherapies, showed benefit compared to placebo (only two prior to T1D onset). Fifty-seven studies employed precision analyses to assess features linked to treatment response. Age, measures of beta cell function and immune phenotypes were most frequently tested. However, analyses were typically not prespecified, with inconsistent methods reporting, and tended to report positive findings.
CONCLUSIONS
While the quality of prevention and intervention trials was overall high, low quality of precision analyses made it difficult to draw meaningful conclusions that inform clinical practice. Thus, prespecified precision analyses should be incorporated into the design of future studies and reported in full to facilitate precision medicine approaches to T1D prevention.
PLAIN LANGUAGE SUMMARY
Type 1 diabetes (T1D) results from the destruction of insulin-producing cells in the pancreas, necessitating lifelong insulin dependence. T1D prevention remains an elusive goal, largely due to immense variability in disease progression. Agents tested to date in clinical trials work in a subset of individuals, highlighting the need for precision medicine approaches to prevention. We systematically reviewed clinical trials of disease-modifying therapy in T1D. While age, measures of beta cell function, and immune phenotypes were most commonly identified as factors that influenced treatment response, the overall quality of these studies was low. This review reveals an important need to proactively design clinical trials with well-defined analyses to ensure that results can be interpreted and applied to clinical practice.
PubMed: 37131690
DOI: 10.1101/2023.04.12.23288421 -
Frontiers in Bioscience (Landmark... Dec 2021Both stress and hypertension (HTN) are considered major health problems that negatively impact the cerebral vasculature. In this article we summarize the possible... (Review)
Review
OBJECTIVES
Both stress and hypertension (HTN) are considered major health problems that negatively impact the cerebral vasculature. In this article we summarize the possible relationship between stress and HTN.
METHODS
We conducted a systematic review of the literature using a database search of MEDLINE, PubMed, Scopus, and Web of Science.
RESULTS
Psychological stress is known to be an important risk factor for essential hypertension. Acute stress can induce transient elevations of blood pressure in the context of the fight-or-flight response. With increased intensity and duration of a perceived harmful event, the normal physiological response is altered, resulting in a failure to return to the resting levels. These changes are responsible for the development of HTN. Genetic and behavioral factors are also very important for the pathogenesis of hypertension under chronic stress situation. In addition, HTN and chronic stress may lead to impaired auto-regulation, regional vascular remodeling, and breakdown of the blood brain barrier (BBB). The effects of both HTN and chronic stress on the cerebral blood vessels shows that both have common structural and functional effects including endothelial damage with subsequent increased wall thickness, vessel resistance, stiffness, arterial atherosclerosis, and altered hemodynamics.
CONCLUSION
Most of the above mentioned vascular effects of stress were primarily reported in animal models. Further in-vivo standardization of pathological vascular indices and imaging modalities is warranted. Radiological quantification of these cerebrovascular changes is therefore essential for in depth understanding of the healthy and diseased cerebral arteries functions, identification and stratification of patients at risk of cardiovascular and neurological adverse events, enactment of preventive measures prior to the onset of systemic HTN, and the initiation of personalized medical management.
Topics: Animals; Blood Pressure; Humans; Hypertension; Vascular Remodeling
PubMed: 34994178
DOI: 10.52586/5057 -
Cureus May 2023CANOMAD, characterized by chronic ataxic neuropathy, ophthalmoplegia, immunoglobulin M (IgM) paraprotein, cold agglutinins, and disialosyl antibodies, encompasses a... (Review)
Review
CANOMAD, characterized by chronic ataxic neuropathy, ophthalmoplegia, immunoglobulin M (IgM) paraprotein, cold agglutinins, and disialosyl antibodies, encompasses a clinical, radiological, and laboratory diagnosis. CANOMAD is a rare condition, with fewer than 100 cases reported in the literature. The understanding and diagnosis of the disease have improved in the last few years, but the treatment of CANOMAD is mainly unknown, and there is not a clear consensus about it. We conducted a systematic review regarding the efficacy of rituximab in CANOMAD's treatment to investigate the clinical and biological response of CANOMAD in patients treated with rituximab. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-Analyses of Observational Studies in Epidemiology (MOOSE) reporting guidelines for this systematic review. To analyze the bias of the study, we used the Joanna Briggs Institute's (JBI) Critical Appraisal Checklist to analyze the bias of the case reports, and we used the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool for the observational studies. We only included case reports, case series, and observational studies written in English with patients formally diagnosed with CANOMAD and treated with rituximab. We excluded systematic reviews, literature reviews, and meta-analyses. We investigated the clinical and biological responses of the patients to rituximab. The clinical response was classified as complete recovery (CR), partial response (PR), stable disease (SD), and non-response (NR). We gathered 34 patients. The literature uses a modified Rankin score to define complete improvement (CR), partial response (PR), stable disease (SD), and progression. Clinically, there were three patients with CR, five with PR, 15 with SD, and 11 with progression. The biological response was assessed by measuring the decrease in antibody titers in 27 patients. Among those, six patients had CR, 12 had PR, eight had SD, and one had progression. Among 15 patients with neurological evaluation, 10 had ocular symptoms, and two presented with bulbar symptoms. Seven of the ten patients with ocular symptoms had SD, two had PR, and one had progression. Only 14 patients had a report of demyelinating features. Three had an axonal pattern, six had a demyelinating pattern, and five had a mixed pattern. Among patients with an axonal pattern, three had an SD. Among patients with a demyelinating pattern, three had a PR, two had an SD, and one had progression. Among patients with a mixed pattern, four had SD, and one had progression. We concluded that patients with CR have a shorter disease duration than patients with PR, SD, or progression. In addition, patients with CR had longer follow-ups than the other groups, suggesting that being treated early with rituximab improves the clinical outcome and has a sustained effect. There were no differences in the frequency of ocular and bulbar symptoms among patients with CANOMAD. The axonal pattern is more common in patients with SD, suggesting that axonal and mixed patterns could be markers of a bad prognosis.
PubMed: 37337500
DOI: 10.7759/cureus.39237 -
Gut Microbes Dec 2023Loss of response to therapy in inflammatory bowel disease (IBD) has led to a surge in research focusing on precision medicine. Three systematic reviews have been... (Review)
Review
Loss of response to therapy in inflammatory bowel disease (IBD) has led to a surge in research focusing on precision medicine. Three systematic reviews have been published investigating the associations between gut microbiota and disease activity or IBD therapy. We performed a systematic review to investigate the microbiome predictors of response to advanced therapy in IBD. Unlike previous studies, our review focused on predictors of response to therapy; so the included studies assessed microbiome predictors before the proposed time of response or remission. We also provide an update of the available data on mycobiomes and viromes. We highlight key themes in the literature that may serve as future biomarkers of treatment response: the abundance of fecal SCFA-producing bacteria and opportunistic bacteria, metabolic pathways related to butyrate synthesis, and non-butyrate metabolomic predictors, including bile acids (BAs), amino acids, and lipids, as well as mycobiome predictors of response.
Topics: Humans; Gastrointestinal Microbiome; Inflammatory Bowel Diseases; Feces; Fecal Microbiota Transplantation; Biomarkers
PubMed: 38044504
DOI: 10.1080/19490976.2023.2287073 -
Quality of Life Research : An... Dec 2021Diabetic foot disease is one of the most serious and expensive complications of diabetes. Patient-reported outcome measures (PROMs) analyse patients' perception of their... (Review)
Review
PURPOSE
Diabetic foot disease is one of the most serious and expensive complications of diabetes. Patient-reported outcome measures (PROMs) analyse patients' perception of their disability, functionality and health. The goal of this work was to conduct a systematic review regarding the specific PROMs related to the evaluation of diabetic foot disease and to extract and analyse the values of their measurement properties.
METHODS
Electronic databases included were PubMed, CINAHL, Scopus, PEDro, Cochrane, SciELO and EMBASE. The search terms used were foot, diabet*, diabetic foot, questionnaire, patient-reported outcome, self-care, valid*, reliabil*. Studies whose did not satisfy the Critical Appraisals Skills Programme (CASP) Diagnostic Study Checklist were excluded. The measurement properties extracted were: Internal Consistency, Test-retest, Inter-rater and Intra-rater, Standard Error of Measurement, Minimum Detectable Measurement Difference, Content Validity, Construct Validity, Criterion Validity and Responsiveness.
RESULTS
The PROMs selected for this review were 12 questionnaires. The Diabetic foot self-care questionnaire (DFSQ-UMA) and the Questionnaire for Diabetes Related Foot Disease (Q-DFD) were the PROMs that showed the highest number of completed measurement properties.
CONCLUSION
According to the results, it is relevant to create specific questionnaires for the evaluation of diabetic foot disease. It seems appropriate to use both DFSQ-UMA and Q-DFD when assessing patients with diabetic foot disease.
Topics: Diabetes Mellitus; Diabetic Foot; Foot Diseases; Humans; Patient Reported Outcome Measures; Quality of Life; Surveys and Questionnaires
PubMed: 34109501
DOI: 10.1007/s11136-021-02892-4 -
Microbial Pathogenesis Feb 2020Mycoplasma pneumoniae (M. pneumoniae) is a small bacterium characterized by the absence of cell wall. It is a human pathogen causing upper and lower respiratory...
Mycoplasma pneumoniae (M. pneumoniae) is a small bacterium characterized by the absence of cell wall. It is a human pathogen causing upper and lower respiratory infections, both in adults and children. However, it is also considered to be implicated in the pathogenesis of several types of extra-respiratory diseases, including some gastrointestinal disorders. The liver involvement in children during or after M. pneumoniae infections is analyzed and discussed in this review. Through a systematic literature search, it is evidenced that M. pneumoniae is not infrequently associated with alteration of liver function, but rarely causes acute and severe hepatitis in children. M. pneumoniae should be considered as an unusual cause of acute hepatitis in children, whenever the most common hepatotropic viruses have been excluded. The pathogenesis of M. pneumoniae-related hepatitis is likely to be immune-mediated: both the innate and adaptive immune responses may play a fundamental role. However, the exact pathological mechanisms have to be elucidated yet. Further clinical studies are needed in order to understand the actual relevance of this microorganism in liver disease and its pathogenesis.
Topics: Acute Disease; Child; Databases, Factual; Gastrointestinal Diseases; Hepatitis; Humans; Liver; Mycoplasma pneumoniae; Pneumonia, Mycoplasma
PubMed: 31712120
DOI: 10.1016/j.micpath.2019.103863 -
Vaccine Apr 2022Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics.... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics. Response to immunizations in this group is not well known.
OBJECTIVE
A systematic review was performed to evaluate three primary outcomes: efficacy; immunogenicity; and safety of vaccines in children with chronic conditions treated with biologics.
METHODS
The protocol for our systematic review and meta-analysis was registered and published with PROSPERO. We searched electronic bibliographic databases for studies published from 2009 to 2019, focusing on vaccinations in children with chronic conditions treated with biologics.
RESULTS
We retrieved 532 records. Thirty-one full-text articles were selected, and 14 were included in the meta-analysis. No significant publication bias was found.
EFFICACY
limited data are available regarding the efficacy of vaccination, as most studies have focused on immunogenicity as surrogate outcome for efficacy. Immunogenicity: patients receiving anti-TNF-alpha therapy had a statistically significant risk of poor seroconversion (p = 0.028) and seroprotection by the serotype B influenza vaccine [inflammatory bowel disease (IBD) p = 0.013; juvenile idiopathic arthritis (JIA) p = 0.004]. We found adequate responses with H1N1 and H3N2 serotypes. Few studies existed for pneumococcal, hepatitis A virus, hepatitis B virus, varicella-zoster virus, Measles Mumps Rubella virus, and multiple vaccine administration.
SAFETY
vaccine administration was not associated with serious side effects, but JIA patients on anti-TNF alpha therapy had a statistically significant risk of presenting with myalgia or arthralgia postinfluenza vaccine (p = 0.014).
CONCLUSIONS
More evidence concerning efficacy, immunogenicity, and safety of vaccinations is needed to guide physicians in the vaccine decision process for this pediatric population.
Topics: Biological Products; Child; Humans; Immunogenicity, Vaccine; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Measles-Mumps-Rubella Vaccine; Pneumococcal Vaccines; Tumor Necrosis Factor Inhibitors
PubMed: 35370019
DOI: 10.1016/j.vaccine.2022.03.041 -
Alimentary Pharmacology & Therapeutics Apr 2024Stricturing Crohn's disease (CD) occurs most commonly in the terminal ileum and poses a clinical problem. Cross-sectional imaging modalities such as intestinal... (Review)
Review
BACKGROUND
Stricturing Crohn's disease (CD) occurs most commonly in the terminal ileum and poses a clinical problem. Cross-sectional imaging modalities such as intestinal ultrasound (IUS), computed tomography enterography (CTE), and magnetic resonance enterography (MRE) allow for assessment of the entire bowel wall and associated peri-enteric findings. Radiologic definitions of strictures have been developed for CTE and MRE; their reliability and responsiveness are being evaluated in index development programs. A comprehensive assessment strategy for strictures using IUS is needed.
AIMS
To provide a detailed summary of definitions, diagnosis and monitoring of strictures on IUS as well as technical aspects of image acquisition.
METHODS
We searched four databases up to 6 January 2024. Two-stage screening was done in duplicate. We assessed risk of bias using QUADAS-2.
RESULTS
There were 56 studies eligible for inclusion. Definitions for strictures on IUS are heterogeneous, but the overall accuracy for diagnosis of strictures is high. The capability of IUS for characterising inflammation versus fibrosis in strictures is not accurate enough to be used in clinical practice or trials. We summarise definitions for improvement of strictures on IUS, and discuss parameters for image acquisition and standardisation.
CONCLUSIONS
This systematic review is the first step for a structured program to develop a stricture IUS index for CD.
Topics: Humans; Crohn Disease; Constriction, Pathologic; Reproducibility of Results; Intestines; Intestinal Obstruction; Magnetic Resonance Imaging
PubMed: 38436124
DOI: 10.1111/apt.17918