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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 -
Tidsskrift For Den Norske Laegeforening... Nov 2017Population groups of different ancestry appear to have varying prevalence of diabetes, different risks of developing cardiovascular disease and different responses to... (Review)
Review
BACKGROUND
Population groups of different ancestry appear to have varying prevalence of diabetes, different risks of developing cardiovascular disease and different responses to certain drugs that are used for these conditions. We wished to review the literature in this field.
MATERIAL AND METHOD
We have performed searches in several databases for systematic review articles published from the year 2000 onwards, and supplemented these with articles from reference lists, our own literature archives and a pyramid search in the Norwegian Electronic Health Library database. Altogether 37 articles were included.
RESULTS
With regard to diagnosed diabetes, the prevalence of coronary heart disease and stroke varies among groups of South Asian, East Asian, African and European ancestry. In patients of South Asian ancestry, the risk of coronary heart disease appears to be twice that of Europeans, and the disease occurs 5–10 years earlier. The prevalence of stroke is especially high in persons of African ancestry. Risk factors such as dyslipidemia and hypertension are distributed differently among these groups. The therapeutic response to drugs such as beta blockers, ACE inhibitors and various statins differs; for example, statin doses in Asians may often be halved in relation to those used for Caucasians, and ACE inhibitors are not recommended as monotherapy for hypertension in persons of African ancestry. These differences are partly attributable to variations in genetic disposition.
INTERPRETATION
The findings are clinically significant – better insight in this field enables optimal tailoring of treatment for each patient, with more rapid achievement of goals and reduced risk of adverse effects. The recommendations given in this article are consistent with and complement the Directorate of Health’s revised guidelines for the treatment of diabetes.
Topics: Antihypertensive Agents; Asian People; Black People; Cardiovascular Diseases; Diabetes Mellitus; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pharmacogenetics; Stroke; White People
PubMed: 29181932
DOI: 10.4045/tidsskr.16.0680 -
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 -
Vaccines Jul 2021Understanding the risks of COVID-19 in patients with Multiple Sclerosis (MS) receiving disease-modifying therapies (DMTs) and their immune reactions is vital to analyze... (Review)
Review
Understanding the risks of COVID-19 in patients with Multiple Sclerosis (MS) receiving disease-modifying therapies (DMTs) and their immune reactions is vital to analyze vaccine response dynamics. A systematic review on COVID-19 course and outcomes in patients receiving different DMTs was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Emerging data on SARS-CoV-2 vaccines was used to elaborate recommendations. Data from 4417 patients suggest that MS per se do not portend a higher risk of severe COVID-19. As for the general population, advanced age, comorbidities, and higher disability significantly impact COVID-19 outcomes. Most DMTs have a negligible influence on COVID-19 incidence and outcome, while for those causing severe lymphopenia and hypogammaglobulinemia, such as anti-CD20 therapies, there might be a tendency of increased hospitalization, worse outcomes and a higher risk of re-infection. Blunted immune responses have been reported for many DMTs, with vaccination implications. Clinical evidence does not support an increased risk of MS relapse or vaccination failure, but vaccination timing needs to be individually tailored. For cladribine and alemtuzumab, it is recommended to wait 3-6 months after the last cycle until vaccination. For the general anti-CD20 therapies, vaccination must be deferred toward the end of the cycle and the next dose administered at least 4-6 weeks after completing vaccination. Serological status after vaccination is highly encouraged. Growing clinical evidence and continuous surveillance are extremely important to continue guiding future treatment strategies and vaccination protocols.
PubMed: 34358189
DOI: 10.3390/vaccines9070773 -
Brazilian Oral Research Dec 2017The process involved in periapical lesions, which occur as an outcome of pulpal necrosis, is regulated by the immune system including regulatory T cells (Treg) and T... (Review)
Review
The process involved in periapical lesions, which occur as an outcome of pulpal necrosis, is regulated by the immune system including regulatory T cells (Treg) and T helper 17 cell (Th17) responses. The objective of this study was to conduct a frequency systematic review to determine the presence of Treg/Th17 responses and the influence of these cells in the progression of chronic inflammatory periapical lesions in humans. A systematic computerized search was carried out in Pubmed, Medline, Web of Science and Scopus electronic databases from their date of inception through the first week of May 2017. In addition, the reference lists of the included articles and the grey literature were hand-searched. Articles that evaluated the presence and influence of Treg/Th17 in the progression of human periapical lesions were included. Study selection and the quality assessment of the included articles (using the Newcastle-Ottawa scale) were carried out by two authors. Fifty-seven titles/abstracts were screened and eight studies met the eligibility criteria and were included in this systematic review. The included studies showed large variation in the type of periapical lesion assessed, mean age, age range, type of experiment and findings regarding the participation of Th17 and Treg in the status of inflammatory periapical lesions. The studies showed the involvement of Treg in the modulation of the inflammatory response in radicular cysts and periapical granulomas. This systematic review highlights the relationship between Treg and Th17 acting in a subtle balance inhibiting or promoting the progression of human periapical lesions.
Topics: Chronic Disease; Cytokines; Disease Progression; Forkhead Transcription Factors; Humans; Periapical Periodontitis; Publication Bias; T-Lymphocytes, Regulatory; Th17 Cells
PubMed: 29267664
DOI: 10.1590/1807-3107bor-2017.vol31.0103 -
Seminars in Arthritis and Rheumatism Apr 2020ImmunoglobulinG4-related disease (IgG4-RD) is a recently recognized disease and, as such, there is a pressing need to identify biomarkers for diagnosis, monitoring...
OBJECTIVE
ImmunoglobulinG4-related disease (IgG4-RD) is a recently recognized disease and, as such, there is a pressing need to identify biomarkers for diagnosis, monitoring disease activity, and predicting prognosis and response to therapy. Here, we review the recent development and identification of biomarkers for IgG4-RD.
METHODS
Through extensive literature review and analysis, we updated the biomarkers for IgG4-RD and further put forward our own viewpoints.
RESULTS
In addition to traditional biomarkers, such as serum IgG4 concentration and typical histological characteristics, several novel indicators, including IgG2, serum soluble IL-2 receptor (sIL2R), and cc-chemokine ligand 18 (CCL18), indicate inflammation and fibrosis and can be used to accurately diagnose and predict treatment response. Studies to identify target autoantigens in IgG4-RD have shed light on the unmet need for biomarkers that can identify this disorder. Additionally, both serological and histopathologic immune cells involved in antigen-induced responses, innate immune cells (macrophages, mast cells, and the I-IFN/ IL-33 pathway), as well as subsequent acquired immune cells (T and B cell subsets), may also serve as new biomarkers for IgG4-RD. Since IgG4-RD often clinically manifests with multiple organs involvement, non-invasive PET-CT can improve diagnosis and antidiastole levels.
CONCLUSION
These novel biomarkers provide information to help diagnose IgG4-RD, monitor disease activity, as well as predict prognosis and response to therapy.
Topics: Biomarkers; Chemokines, CC; Humans; Immunoglobulin G; Immunoglobulin G4-Related Disease; Receptors, Interleukin-2
PubMed: 31280934
DOI: 10.1016/j.semarthrit.2019.06.018 -
Arthritis Research & Therapy Nov 2016Tendon disease is characterized by the development of fibrosis. Transforming growth factor beta (TGF-β), bone morphogenic proteins (BMPs) and connective tissue growth... (Review)
Review
BACKGROUND
Tendon disease is characterized by the development of fibrosis. Transforming growth factor beta (TGF-β), bone morphogenic proteins (BMPs) and connective tissue growth factor (CTGF) are key mediators in the pathogenesis of fibrotic disorders. The aim of this systematic review was to investigate the evidence for the expression of TGF-β, BMPs and CTGF along tendon disease progression and the response of tendon cells to these growth factors accordingly.
METHOD
We conducted a systematic screen of the scientific literature using the Medline database. The search terms used were "tendon AND TGF-β," "tendon AND BMP" or "tendon AND CTGF." Studies of human samples, animal tendon injury and overuse models were included.
RESULTS
Thirty-three studies were included. In eight studies the expression of TGF-β, BMPs or CTGF was dysregulated in chronic tendinopathy and tendon tear patient tissues in comparison with healthy control tissues. The expression of TGF-β, BMPs and CTGF was increased and showed temporal changes in expression in tendon tissues from animal injury or overuse models compared with the healthy control (23 studies), but the pattern of upregulation was inconsistent between growth factors and also the type of animal model. No study investigated the differences in the effect of TGF-β, BMPs or CTGF treatment between patient-derived cells from healthy and diseased tendon tissues. Tendon cells derived from animal models of tendon injury showed increased expression of extracellular matrix protein genes and increased cell signaling response to TGF-β and BMP treatments compared with the control cells (two studies).
CONCLUSION
The expression of TGF-β, BMPs and CTGF in tendon tissues is altered temporally during healing in animal models of tendon injury or overuse, but the transition during the development of human tendon disease is currently unknown. Findings from this systematic review suggest a potential and compelling role for TGF-β, BMPs and CTGF in tendon disease; however, there is a paucity of studies analyzing their expression and stimulated cellular response in well-phenotyped human samples. Future work should investigate the dynamic expression of these fibrotic growth factors and their interaction with tendon cells using patient samples at different stages of human tendon disease.
Topics: Animals; Bone Morphogenetic Proteins; Connective Tissue Growth Factor; Fibrosis; Humans; Tendinopathy; Transforming Growth Factor beta
PubMed: 27863509
DOI: 10.1186/s13075-016-1165-0 -
Journal of Alzheimer's Disease : JAD 2023Perfusion imaging has the potential to identify neurodegenerative disorders in a preclinical stage. However, to correctly interpret perfusion-derived parameters, the...
BACKGROUND
Perfusion imaging has the potential to identify neurodegenerative disorders in a preclinical stage. However, to correctly interpret perfusion-derived parameters, the impact of perfusion modifiers should be evaluated.
OBJECTIVE
In this systematic review, the impact of acute and chronic intake of four acetylcholinesterase inhibitors (AChEIs) on cerebral perfusion in adults was investigated: physostigmine, donepezil, galantamine, and rivastigmine.
RESULTS
Chronic AChEI treatment results in an increase of cerebral perfusion in treatment-responsive patients with Alzheimer's disease, dementia with Lewy bodies, and Parkinson's disease dementia in the frontal, parietal, temporal, and occipital lobes, as well as the cingulate gyrus. These effects appear to be temporary, dose-related, and consistent across populations and different AChEI types. On the contrary, further perfusion decline was reported in patients not receiving AChEIs or not responding to the treatment.
CONCLUSION
AChEIs appear to be a potential perfusion modifier in neurodegenerative patients. More research focused on quantitative perfusion in both patients with and without a cholinergic deficit is needed to draw conclusions on whether AChEI intake should be considered when analyzing perfusion data.
Topics: Humans; Cholinesterase Inhibitors; Acetylcholinesterase; Dementia; Piperidines; Indans; Phenylcarbamates; Parkinson Disease; Rivastigmine; Alzheimer Disease; Galantamine; Cognition; Perfusion; Cerebrovascular Circulation
PubMed: 37182871
DOI: 10.3233/JAD-221125