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Journal of the European Academy of... Jun 2024Rosacea is a chronic and psychologically ladened disease affecting 1%-3% of people worldwide. The identification and validation of biomarkers in rosacea patients has the... (Review)
Review
Rosacea is a chronic and psychologically ladened disease affecting 1%-3% of people worldwide. The identification and validation of biomarkers in rosacea patients has the potential to improve disease progression, support diagnosis, provide objective measures for clinical trials and aid in management. The objective of this review is to systematically identify all rosacea biomarkers, categorize them by type and identify trends to improve disease expression. Eligibility criteria for this review (PROSPERO CRD42023397510) include randomized controlled trials, case-control studies, cohort studies and other observational studies. No restrictions were placed on patient demographics (age, sex, ethnicity) or language of publication until February 2023. Quality of studies was assessed using the National Institute of Health quality assessment tool. The literature search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A total of 805 unique articles were screened based on the applied inclusion and exclusion criteria. After the articles were screened based on title/abstract and full-text, a total of 38 studies were included, reporting on a total of 119 unique biomarkers. The results of this review and current rosacea pathogenic mechanisms provide the greatest support for the innate cathelicidin and inflammasome, T1 and T17 pathways. The most commonly reported biomarkers include IL-1β, TNF-α, IL-37, IFN-γ and MMP-9. Biomarkers identified in this study support current theories of rosacea pathogenesis and provide direction for research to further our knowledge. However, more research is needed to identify biomarkers panels that can provide diagnostic utility. This may be difficult due to the heterogeneity of the disease and potential differences between rosacea subtypes.
Topics: Rosacea; Humans; Biomarkers; Cathelicidins; Antimicrobial Cationic Peptides
PubMed: 38078369
DOI: 10.1111/jdv.19732 -
Clinica Chimica Acta; International... Jun 2024High serum galectin-3 has been associated with adverse outcomes among dialysis patients, although its prognostic role remains unclear among individuals with... (Review)
Review
BACKGROUND AND AIMS
High serum galectin-3 has been associated with adverse outcomes among dialysis patients, although its prognostic role remains unclear among individuals with earlier-stage chronic kidney disease. The present systematic review aims to evaluate the association of serum galectin-3 with survival, cardiovascular disease and kidney disease progression among non-dialysis chronic kidney disease patients.
METHODS
PubMed, Scopus, Web of Science, CENTRAL and Google Scholar were systematically searched till November 10, 2023. All observational studies assessing the prognostic role of serum galectin-3 in patients with non-dialysis chronic kidney disease were included.
RESULTS
Overall, 12 studies (10 cohort, 2 cross-sectional) were included, comprising 9,349 patients. The endpoint of survival was assessed in 5 studies, indicating a significant association between increasing serum galectin-3 levels and higher all-cause mortality risk (Hazard ratio per unit: 1.22, 95 % confidence intervals-CI: 1.05-1.41, ≥6 ng/mL: 2.66, 95 % CI: 1.68-4.23). Current evidence coming from 4 studies was inconclusive regarding the potential link of galectin-3 and kidney function decline, yielding conflicting results. No significant associations between serum galectin-3 and heart failure, cardiovascular events or death were consistently reported.
CONCLUSIONS
This systematic review supports the prognostic role of galectin-3 in chronic kidney disease, as its increased serum values may be associated with higher all-cause mortality risk. No clear role could be supported for serum galectin-3 regarding the prediction of cardiovascular disease or kidney disease progression.
Topics: Humans; Renal Insufficiency, Chronic; Galectin 3; Cardiovascular Diseases; Galectins; Blood Proteins; Disease Progression; Prognosis
PubMed: 38750780
DOI: 10.1016/j.cca.2024.119727 -
Frontiers in Immunology 2023Inflammatory processes are involved in the pathophysiology of both Alzheimer's disease (AD) and multiple sclerosis (MS) but their exact contribution to disease... (Review)
Review
UNLABELLED
Inflammatory processes are involved in the pathophysiology of both Alzheimer's disease (AD) and multiple sclerosis (MS) but their exact contribution to disease progression remains to be deciphered. Biomarkers are needed to define pathophysiological processes of these disorders, who may increasingly co-exist in the elderly generations of the future, due to the rising prevalence in both and ameliorated treatment options with improved life expectancy in MS. The purpose of this review was to provide a systematic overview of inflammatory biomarkers, as measured in the cerebrospinal fluid (CSF), that are associated with clinical disease progression. International peer-reviewed literature was screened using the PubMed and Web of Science databases. Disease progression had to be measured using clinically validated tests representing baseline functional and/or cognitive status, the evolution of such clinical scores over time and/or the transitioning from one disease stage to a more severe stage. The quality of included studies was systematically evaluated using a set of questions for clinical, neurochemical and statistical characteristics of the study. A total of 84 papers were included (twenty-five for AD and 59 for MS). Elevated CSF levels of chitinase-3-like protein 1 (YKL-40) were associated with disease progression in both AD and MS. Osteopontin and monocyte chemoattractant protein-1 were more specifically related to disease progression in AD, whereas the same was true for interleukin-1 beta, tumor necrosis factor alpha, C-X-C motif ligand 13, glial fibrillary acidic protein and IgG oligoclonal bands in MS. We observed a broad heterogeneity of studies with varying cohort characterization, non-disclosure of quality measures for neurochemical analyses and a lack of adequate longitudinal designs. Most of the retrieved biomarkers are related to innate immune system activity, which seems to be an important mediator of clinical disease progression in AD and MS. Overall study quality was limited and we have framed some recommendations for future biomarker research in this field.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42021264741.
Topics: Humans; Aged; Alzheimer Disease; Biomarkers; Disease Progression; Multiple Sclerosis
PubMed: 37520580
DOI: 10.3389/fimmu.2023.1162340 -
Journal of Alzheimer's Disease Reports 2024Alzheimer's disease (AD) causes progressive decline of cognition and function. There is a lack of systematic literature reviews on prognostic and predictive factors in...
BACKGROUND
Alzheimer's disease (AD) causes progressive decline of cognition and function. There is a lack of systematic literature reviews on prognostic and predictive factors in its early clinical stages (eAD), i.e., mild cognitive impairment due to AD and mild AD dementia.
OBJECTIVE
To identify prognostic factors affecting eAD progression and predictive factors for treatment efficacy and safety of approved and/or under late-stage development disease-modifying treatments.
METHODS
Databases were searched (August 2022) for studies reporting prognostic factors associated with eAD progression and predictive factors for treatment response. The Quality in Prognostic Factor Studies tool or the Cochrane risk of bias tool were used to assess risk of bias. Two reviewers independently screened the records. A single reviewer performed data extraction and quality assessment. A second performed a 20% check. Content experts reviewed and interpreted the data collected.
RESULTS
Sixty-one studies were included. Self-reporting, diagnosis definition, and missing data led to high risk of bias. Population size ranged from 110 to 11,451. Analyses found data indicating that older age was and depression may be associated with progression. Greater baseline cognitive impairment was associated with progression. may be a prognostic factor, a predictive factor for treatment efficacy and predicts an adverse response (ARIA). Elevated biomarkers (CSF/plasma p-tau, CSF t-tau, and plasma neurofilament light) were associated with disease progression.
CONCLUSIONS
Age was the strongest risk factor for progression. Biomarkers were associated with progression, supporting their use in trial selection and aiding diagnosis. Baseline cognitive impairment was a prognostic factor. predicted ARIA, aligning with emerging evidence and relevant to treatment initiation/monitoring.
PubMed: 38405341
DOI: 10.3233/ADR-230045 -
The Cochrane Database of Systematic... Sep 2023Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that affects millions of people worldwide. The disease course varies greatly... (Review)
Review
BACKGROUND
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that affects millions of people worldwide. The disease course varies greatly across individuals and many disease-modifying treatments with different safety and efficacy profiles have been developed recently. Prognostic models evaluated and shown to be valid in different settings have the potential to support people with MS and their physicians during the decision-making process for treatment or disease/life management, allow stratified and more precise interpretation of interventional trials, and provide insights into disease mechanisms. Many researchers have turned to prognostic models to help predict clinical outcomes in people with MS; however, to our knowledge, no widely accepted prognostic model for MS is being used in clinical practice yet.
OBJECTIVES
To identify and summarise multivariable prognostic models, and their validation studies for quantifying the risk of clinical disease progression, worsening, and activity in adults with MS.
SEARCH METHODS
We searched MEDLINE, Embase, and the Cochrane Database of Systematic Reviews from January 1996 until July 2021. We also screened the reference lists of included studies and relevant reviews, and references citing the included studies.
SELECTION CRITERIA
We included all statistically developed multivariable prognostic models aiming to predict clinical disease progression, worsening, and activity, as measured by disability, relapse, conversion to definite MS, conversion to progressive MS, or a composite of these in adult individuals with MS. We also included any studies evaluating the performance of (i.e. validating) these models. There were no restrictions based on language, data source, timing of prognostication, or timing of outcome.
DATA COLLECTION AND ANALYSIS
Pairs of review authors independently screened titles/abstracts and full texts, extracted data using a piloted form based on the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS), assessed risk of bias using the Prediction Model Risk Of Bias Assessment Tool (PROBAST), and assessed reporting deficiencies based on the checklist items in Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD). The characteristics of the included models and their validations are described narratively. We planned to meta-analyse the discrimination and calibration of models with at least three external validations outside the model development study but no model met this criterion. We summarised between-study heterogeneity narratively but again could not perform the planned meta-regression.
MAIN RESULTS
We included 57 studies, from which we identified 75 model developments, 15 external validations corresponding to only 12 (16%) of the models, and six author-reported validations. Only two models were externally validated multiple times. None of the identified external validations were performed by researchers independent of those that developed the model. The outcome was related to disease progression in 39 (41%), relapses in 8 (8%), conversion to definite MS in 17 (18%), and conversion to progressive MS in 27 (28%) of the 96 models or validations. The disease and treatment-related characteristics of included participants, and definitions of considered predictors and outcome, were highly heterogeneous amongst the studies. Based on the publication year, we observed an increase in the percent of participants on treatment, diversification of the diagnostic criteria used, an increase in consideration of biomarkers or treatment as predictors, and increased use of machine learning methods over time. Usability and reproducibility All identified models contained at least one predictor requiring the skills of a medical specialist for measurement or assessment. Most of the models (44; 59%) contained predictors that require specialist equipment likely to be absent from primary care or standard hospital settings. Over half (52%) of the developed models were not accompanied by model coefficients, tools, or instructions, which hinders their application, independent validation or reproduction. The data used in model developments were made publicly available or reported to be available on request only in a few studies (two and six, respectively). Risk of bias We rated all but one of the model developments or validations as having high overall risk of bias. The main reason for this was the statistical methods used for the development or evaluation of prognostic models; we rated all but two of the included model developments or validations as having high risk of bias in the analysis domain. None of the model developments that were externally validated or these models' external validations had low risk of bias. There were concerns related to applicability of the models to our research question in over one-third (38%) of the models or their validations. Reporting deficiencies Reporting was poor overall and there was no observable increase in the quality of reporting over time. The items that were unclearly reported or not reported at all for most of the included models or validations were related to sample size justification, blinding of outcome assessors, details of the full model or how to obtain predictions from it, amount of missing data, and treatments received by the participants. Reporting of preferred model performance measures of discrimination and calibration was suboptimal.
AUTHORS' CONCLUSIONS
The current evidence is not sufficient for recommending the use of any of the published prognostic prediction models for people with MS in clinical routine today due to lack of independent external validations. The MS prognostic research community should adhere to the current reporting and methodological guidelines and conduct many more state-of-the-art external validation studies for the existing or newly developed models.
Topics: Adult; Humans; Prognosis; Multiple Sclerosis; Reproducibility of Results; Systematic Reviews as Topic; Disease Progression
PubMed: 37681561
DOI: 10.1002/14651858.CD013606.pub2 -
Critical Care Medicine Feb 2024Clinical deterioration of patients hospitalized outside the ICU is a source of potentially reversible morbidity and mortality. To address this, some acute care hospitals...
RATIONALE
Clinical deterioration of patients hospitalized outside the ICU is a source of potentially reversible morbidity and mortality. To address this, some acute care hospitals have implemented systems aimed at detecting and responding to such patients.
OBJECTIVES
To provide evidence-based recommendations for hospital clinicians and administrators to optimize recognition and response to clinical deterioration in non-ICU patients.
PANEL DESIGN
The 25-member panel included representatives from medicine, nursing, respiratory therapy, pharmacy, patient/family partners, and clinician-methodologists with expertise in developing evidence-based Clinical Practice Guidelines.
METHODS
We generated actionable questions using the Population, Intervention, Control, and Outcomes (PICO) format and performed a systematic review of the literature to identify and synthesize the best available evidence. We used the Grading of Recommendations Assessment, Development, and Evaluation Approach to determine certainty in the evidence and to formulate recommendations and good practice statements (GPSs).
RESULTS
The panel issued 10 statements on recognizing and responding to non-ICU patients with critical illness. Healthcare personnel and institutions should ensure that all vital sign acquisition is timely and accurate (GPS). We make no recommendation on the use of continuous vital sign monitoring among unselected patients. We suggest focused education for bedside clinicians in signs of clinical deterioration, and we also suggest that patient/family/care partners' concerns be included in decisions to obtain additional opinions and help (both conditional recommendations). We recommend hospital-wide deployment of a rapid response team or medical emergency team (RRT/MET) with explicit activation criteria (strong recommendation). We make no recommendation about RRT/MET professional composition or inclusion of palliative care members on the responding team but suggest that the skill set of responders should include eliciting patients' goals of care (conditional recommendation). Finally, quality improvement processes should be part of a rapid response system.
CONCLUSIONS
The panel provided guidance to inform clinicians and administrators on effective processes to improve the care of patients at-risk for developing critical illness outside the ICU.
Topics: Humans; Clinical Deterioration; Critical Care; Critical Illness; Evidence-Based Practice; Intensive Care Units
PubMed: 38240510
DOI: 10.1097/CCM.0000000000006072 -
Biomolecules Nov 2023Peripheral artery disease (PAD) involves atherosclerosis of the lower extremity arteries and is a major contributor to limb loss and death worldwide. Several studies... (Review)
Review
Peripheral artery disease (PAD) involves atherosclerosis of the lower extremity arteries and is a major contributor to limb loss and death worldwide. Several studies have demonstrated that interleukins (ILs) play an important role in the development and progression of PAD; however, a comprehensive literature review has not been performed. A systematic review was conducted and reported according to PRISMA guidelines. MEDLINE was searched from inception to 5 December 2022, and all studies assessing the association between ILs and PAD were included. We included 17 studies from a pool of 771 unique articles. Five pro-inflammatory ILs (IL-1β, IL-2, IL-5, IL-6, and IL-8) and one pro-atherogenic IL (IL-12) were positively correlated with PAD diagnosis and progression. In contrast, two anti-inflammatory ILs (IL-4 and IL-10) were protective against PAD diagnosis and adverse limb events. Specifically, IL-6 and IL-8 were the most strongly associated with PAD and can act as potential disease biomarkers to support the identification and treatment of PAD. Ongoing work to identify and validate diagnostic/prognostic inflammatory biomarkers for PAD has the potential to assist clinicians in identifying high-risk patients for further evaluation and management which could reduce the risk of adverse cardiovascular and limb events.
Topics: Humans; Interleukin-6; Prognosis; Interleukin-8; Peripheral Arterial Disease; Atherosclerosis; Biomarkers; Risk Factors
PubMed: 38002322
DOI: 10.3390/biom13111640 -
Nutrients Aug 2023During the disease course, most Inflammatory Bowel Disease patients present a condition of malnutrition, undernutrition, or even overnutrition. These conditions are... (Review)
Review
During the disease course, most Inflammatory Bowel Disease patients present a condition of malnutrition, undernutrition, or even overnutrition. These conditions are mainly due to suboptimal nutritional intake, alterations in nutrient requirements and metabolism, malabsorption, and excessive gastrointestinal losses. A suboptimal nutritional status and low micronutrient serum levels can have a negative impact on both induction and maintenance of remission and on the quality of life of Inflammatory Bowel Disease patients. We performed a systematic review including all the studies evaluating the connection between nutrition, nutrition status (including undernutrition and overnutrition), micronutrient deficiency, and both disease course and therapeutic response in Inflammatory Bowel Disease patients. This systematic review was performed using PubMed/MEDLINE and Scopus. Four main clinical settings concerning the effect of nutrition on disease course in adult Inflammatory Bowel Disease patients were analyzed (induction of remission, maintenance of remission, risk of surgery, post-operative recurrence, and surgery-related complications). Four authors independently reviewed abstracts and manuscripts for eligibility. 6077 articles were found; 762 duplicated studies were removed. Out of 412 full texts analyzed, 227 were included in the review. The evidence summarized in this review showed that many nutritional aspects could be potential targets to induce a better control of symptoms, a deeper remission, and overall improve the quality of life of Inflammatory Bowel Disease patients.
Topics: Adult; Humans; Nutritional Status; Quality of Life; Malnutrition; Inflammatory Bowel Diseases; Disease Progression; Micronutrients; Overnutrition
PubMed: 37686856
DOI: 10.3390/nu15173824 -
Journal of the American Heart... Dec 2023Cardiovascular calcification, characterized by deposition of calcium phosphate in the arterial wall and heart valves, is associated with cardiovascular morbidity and...
BACKGROUND
Cardiovascular calcification, characterized by deposition of calcium phosphate in the arterial wall and heart valves, is associated with cardiovascular morbidity and mortality and is commonly seen in aging, diabetes, and chronic kidney disease. Whether evidence-based interventions could significantly attenuate cardiovascular calcification progression remains uncertain.
METHODS AND RESULTS
We conducted a systematic review of randomized controlled trials involving interventions, compared with placebo, another comparator, or standard of care, to attenuate cardiovascular calcification. Included clinical trials involved participants without chronic kidney disease, and the outcome was cardiovascular calcification measured using radiological methods. Quality of evidence was determined by the Cochrane risk of bias and Grading of Recommendations, Assessment, Development, and Evaluations assessment. Forty-nine randomized controlled trials involving 9901 participants (median participants 104, median duration 12 months) were eligible for inclusion. Trials involving aged garlic extract (n=6 studies) consistently showed attenuation of cardiovascular calcification. Trials involving 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (n=14), other lipid-lowering agents (n=2), hormone replacement therapies (n=3), vitamin K (n=5), lifestyle measures (n=4), and omega-3 fatty acids (n=2) consistently showed no attenuation of cardiovascular calcification with these therapies. Trials involving antiresorptive (n=2), antihypertensive (n=2), antithrombotic (n=4), and hypoglycemic agents (n=3) showed mixed results. Singleton studies involving salsalate, folate with vitamin B6 and 12, and dalcetrapib showed no attenuation of cardiovascular calcification. Overall, Cochrane risk of bias was moderate, and the Grading of Recommendations, Assessment, Development, and Evaluations assessment for a majority of analyses was moderate certainty of evidence.
CONCLUSIONS
Currently, there are insufficient or conflicting data for interventions evaluated in clinical trials for mitigation of cardiovascular calcification. Therapy involving aged garlic extract appears most promising, but evaluable studies were small and of short duration.
Topics: Humans; Antioxidants; Diabetes Mellitus; Disease Progression; Hypoglycemic Agents; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Vascular Calcification; Garlic; Phytotherapy; Plant Extracts
PubMed: 38014685
DOI: 10.1161/JAHA.123.031676 -
Orphanet Journal of Rare Diseases Aug 2023To understand the benefit-risk profile for historical and current treatments for MLD. (Review)
Review
A systematic review of clinical effectiveness and safety for historical and current treatment options for metachromatic leukodystrophy in children, including atidarsagene autotemcel.
OBJECTIVE
To understand the benefit-risk profile for historical and current treatments for MLD.
METHODS
A systematic review was conducted on the effectiveness, safety, and costs of MLD treatments: allogeneic haematopoietic stem cell transplantation (HSCT) and atidarsagene autotemcel (arsa-cel) according to best practice.
RESULTS
A total of 6940 titles and abstracts were retrieved from the literature searches and 26 from other sources. From these, 35 manuscripts reporting on a total of 12 studies were selected for inclusion in the review. There were no controlled multi-armed trials. However, we provide observations comparing two interventional therapies (alloHSCT and arsa-cel) and each of these to standard/supportive care (natural history). There were no benefits for survival, gross motor function and cognitive function for LI patients receiving alloHSCT, as patients experienced disease progression similar to LI natural history. For juvenile patients receiving alloHSCT, no differences in survival were observed versus natural history, however stabilisation of cognitive and motor function were reported for some patients (particularly for pre- or minimally-symptomatic LJ patients), while others experienced disease progression. Furthermore, alloHSCT was associated with severe complications such as treatment-related mortality, graft versus host disease, and re-transplantation in both LI and EJ treated patients. Most LI and EJ patients treated with arsa-cel appeared to have normal development, preservation, or slower progression of gross motor function and cognitive function, in contrast to the rapid decline observed in natural history patients. A survival benefit for arsa-cel versus natural history and versus alloHSCT was observed in LI patients.LI and EJ patients treated with arsa-cel had better gross motor function and cognitive function compared to alloHSCT, which had limited effect on motor and cognitive decline. No data has been reported for arsa-cel treatment of LJ patients.
CONCLUSIONS
Overall, this systematic review indicates that compared to NHx and HSCT, treatment with arsa-cel results in clinically relevant benefits in LI and EJ MLD patients by preserving cognitive function and motor development in most patients, and increased survival for LI patients. Nevertheless, further research is required to confirm these findings, given they are based on results from non-RCT studies.
Topics: Humans; Child; Leukodystrophy, Metachromatic; Treatment Outcome; Cognition; Cognitive Dysfunction; Disease Progression
PubMed: 37644601
DOI: 10.1186/s13023-023-02814-2