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Respirology (Carlton, Vic.) Nov 2023Long COVID, or post-acute COVID-19 sequelae, is experienced by an estimated one in eight adults following acute COVID-19. Long COVID is a new and complex chronic health... (Review)
Review
Long COVID, or post-acute COVID-19 sequelae, is experienced by an estimated one in eight adults following acute COVID-19. Long COVID is a new and complex chronic health condition that typically includes multiple symptoms that cross organ systems and fluctuate over time; a one-size-fits-all approach is, therefore, not likely to be appropriate nor relevant for long COVID treatment. 'Treatable Traits' is a personalized medicine approach, purpose-built to address the complexity and heterogeneity of complex chronic conditions. This comprehensive review aimed to understand how a treatable traits approach could be applied to long COVID, by first identifying the most prevalent long COVID treatable traits and then the available evidence for strategies to target these traits. An umbrella review of 22 systematic reviews identified 34 symptoms and complications common with long COVID, grouped into eight long COVID treatable trait clusters: neurological, chest, psychological, pain, fatigue, sleep impairment, functional impairment and other. A systematic review of randomized control trials identified 18 studies that explored different intervention approaches for long COVID prevention (k = 4) or management (k = 14). While a single study reported metformin as effective for long COVID prevention, the findings need to be replicated and consensus is required around how to define long COVID as a clinical trial endpoint. For long COVID management, current evidence supports exercise training or respiratory muscle training for long COVID treatable traits in the chest and functional limitation clusters. While there are studies exploring interventions targeting other long COVID treatable traits, further high-quality RCTs are needed, particularly targeting treatable traits in the clusters of fatigue, psychological, pain and sleep impairment.
Topics: Adult; Humans; Post-Acute COVID-19 Syndrome; COVID-19; Chronic Disease; Fatigue; Pain
PubMed: 37715729
DOI: 10.1111/resp.14596 -
Movement Disorders Clinical Practice Dec 2023Individuals with multiple system atrophy (MSA) often complain about pain, nonetheless this remains a poorly investigated non-motor feature of MSA. (Review)
Review
BACKGROUND
Individuals with multiple system atrophy (MSA) often complain about pain, nonetheless this remains a poorly investigated non-motor feature of MSA.
OBJECTIVES
Here, we aimed at assessing the prevalence, characteristics, and risk factors for pain in individuals with MSA.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines, we systematically screened the PubMED, Cochrane, and Web of Science databases for papers published in English until September 30, 2022, combining the following keywords: "pain," "multiple system atrophy," "MSA," "olivopontocerebellar atrophy," "OPCA," "striatonigral degeneration," "SND," "Shy Drager," and "atypical parkinsonism."
RESULTS
The search identified 700 records. Sixteen studies provided information on pain prevalence in cohorts of MSA individuals and were included in a qualitative assessment based on the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Thirteen studies (11 cross-sectional, two longitudinal) scored ≥14 points on QUADAS assessment and were included in a quantitative analysis, pooling data from 1236 MSA individuals. The resulting pooled prevalence of pain in MSA was 67% (95% confidence intervals [CI] = 57%-75%), and significantly higher in individuals with MSA of parkinsonian rather than cerebellar type (76% [95% CI = 63%-87%] vs. 45% [95% CI = 33%-57%], = 0.001). Pain assessment tools and collected information were highly heterogeneous across studies. Two studies reported pain treatment strategies and found that only every second person with MSA complaining about pain had received targeted treatment.
CONCLUSIONS
We found that pain is a frequent, but still under-recognized and undertreated feature of MSA. Further research is needed to improve pain detection and treatment in MSA.
PubMed: 38094640
DOI: 10.1002/mdc3.13897 -
Frontiers in Immunology 2023Sepsis is a systemic inflammation caused by a maladjusted host response to infection. In severe cases, it can cause multiple organ dysfunction syndrome (MODS) and even... (Review)
Review
Sepsis is a systemic inflammation caused by a maladjusted host response to infection. In severe cases, it can cause multiple organ dysfunction syndrome (MODS) and even endanger life. Acupuncture is widely accepted and applied in the treatment of sepsis, and breakthroughs have been made regarding its mechanism of action in recent years. In this review, we systematically discuss the current clinical applications of acupuncture in the treatment of sepsis and focus on the mechanisms of acupuncture in animal models of systemic inflammation. In clinical research, acupuncture can not only effectively inhibit excessive inflammatory reactions but also improve the immunosuppressive state of patients with sepsis, thus maintaining immune homeostasis. Mechanistically, a change in the acupoint microenvironment is the initial response link for acupuncture to take effect, whereas PROKR2 neurons, high-threshold thin nerve fibres, cannabinoid CB2 receptor (CB2R) activation, and Ca influx are the key material bases. The cholinergic anti-inflammatory pathway of the vagus nervous system, the adrenal dopamine anti-inflammatory pathway, and the sympathetic nervous system are key to the transmission of acupuncture information and the inhibition of systemic inflammation. In MODS, acupuncture protects against septic organ damage by inhibiting excessive inflammatory reactions, resisting oxidative stress, protecting mitochondrial function, and reducing apoptosis and tissue or organ damage.
Topics: Animals; Humans; Sepsis; Acupuncture Therapy; Inflammation; Vagus Nerve
PubMed: 37753078
DOI: 10.3389/fimmu.2023.1242640 -
Frontiers in Immunology 2023Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ transplant outcomes. However, a critical appraisal of these studies and a demonstration of the prognostic value of complement-activating status over anti-HLA DSA mean fluorescence intensity (MFI) level are lacking.
METHODS
We conducted a systematic review, meta-analysis and critical appraisal evaluating the role of complement-activating anti-HLA DSAs on allograft outcomes in different solid organ transplants. We included studies through Medline, Cochrane, Scopus, and Embase since inception of databases till May 05, 2023. We evaluated allograft loss as the primary outcome, and allograft rejection as the secondary outcome. We used the Newcastle-Ottawa Scale and funnel plots to assess risk of bias and used bias adjustment methods when appropriate. We performed multiple subgroup analyses to account for sources of heterogeneity and studied the added value of complement assays over anti-HLA DSA MFI level.
RESULTS
In total, 52 studies were included in the final meta-analysis (11,035 patients). Complement-activating anti-HLA DSAs were associated with an increased risk of allograft loss (HR 2.77; 95% CI 2.33-3.29, p<0.001; I²=46.2%), and allograft rejection (HR 4.98; 95% CI 2.96-8.36, p<0.01; I²=70.9%). These results remained significant after adjustment for potential sources of bias and across multiple subgroup analyses. After adjusting on pan-IgG anti-HLA DSA defined by the MFI levels, complement-activating anti-HLA DSAs were significantly and independently associated with an increased risk of allograft loss.
DISCUSSION
We demonstrated in this systematic review, meta-analysis and critical appraisal the significant deleterious impact and the independent prognostic value of circulating complement-activating anti-HLA DSAs on solid organ transplant risk of allograft loss and rejection.
Topics: Humans; Graft Rejection; Organ Transplantation; Complement System Proteins; Transplantation, Homologous; HLA Antigens
PubMed: 37849755
DOI: 10.3389/fimmu.2023.1265796 -
International Journal of Molecular... Jul 2023Maresins are lipid mediators derived from omega-3 fatty acids with anti-inflammatory and pro-resolving properties, capable of promoting tissue regeneration and... (Review)
Review
Maresins are lipid mediators derived from omega-3 fatty acids with anti-inflammatory and pro-resolving properties, capable of promoting tissue regeneration and potentially serving as a therapeutic agent for chronic inflammatory diseases. The aim of this review was to systematically investigate preclinical and clinical studies on maresin to inform translational research. Two independent reviewers performed comprehensive searches with the term "Maresin (NOT) Review" on PubMed. A total of 137 studies were included and categorized into 11 human organ systems. Data pertinent to clinical translation were specifically extracted, including delivery methods, optimal dose response, and specific functional efficacy. Maresins generally exhibit efficacy in treating inflammatory diseases, attenuating inflammation, protecting organs, and promoting tissue regeneration, mostly in rodent preclinical models. The nervous system has the highest number of original studies ( = 25), followed by the cardiovascular system, digestive system, and respiratory system, each having the second highest number of studies ( = 18) in the field. Most studies considered systemic delivery with an optimal dose response for mouse animal models ranging from 4 to 25 μg/kg or 2 to 200 ng via intraperitoneal or intravenous injection respectively, whereas human in vitro studies ranged between 1 and 10 nM. Although there has been no human interventional clinical trial yet, the levels of MaR1 in human tissue fluid can potentially serve as biomarkers, including salivary samples for predicting the occurrence of cardiovascular diseases and periodontal diseases; plasma and synovial fluid levels of MaR1 can be associated with treatment response and defining pathotypes of rheumatoid arthritis. Maresins exhibit great potency in resolving disease inflammation and bridging tissue regeneration in preclinical models, and future translational development is warranted.
Topics: Animals; Humans; Mice; Anti-Inflammatory Agents; Chronic Disease; Docosahexaenoic Acids; Inflammation; Macrophages
PubMed: 37446190
DOI: 10.3390/ijms241311012 -
Scientific Reports Aug 2023Cancer-related fatigue (CRF) affects therapeutic compliance and clinical outcomes including recurrence and mortality. This study aimed to comprehensively and... (Meta-Analysis)
Meta-Analysis
Cancer-related fatigue (CRF) affects therapeutic compliance and clinical outcomes including recurrence and mortality. This study aimed to comprehensively and comparatively assess the severity-based prevalence of CRF. From two public databases (PubMed and Cochrane Library), we extracted data containing information on both prevalence and severity of fatigue in cancer patients through December 2021. We conducted a meta-analysis to produce point estimates using random effects models. Subgroup analyses were used to assess the prevalence and severity by the organ/system tumor development, treatment phase, therapeutic type, sex and assessment method. A total of 151 data (57 studies, 34,310 participants, 11,805 males and 22,505 females) were selected, which indicated 43.0% (95% CI 39.2-47.2) of fatigue prevalence. The total CRF prevalence including 'mild' level of fatigue was 70.7% (95% CI 60.6-83.3 from 37 data). The prevalence of 'severe' fatigue significantly varied by organ/system types of cancer origin (highest in brain tumors 39.7% vs. lowest in gynecologic tumors 3.9%) and treatment phase likely 15.9% (95% CI 8.1-31.3) before treatment, 33.8% (95% CI 27.7-41.2) ongoing treatment, and 24.1% (95% CI 18.6-31.2) after treatment. Chemotherapy (33.1%) induced approximately 1.5-fold higher prevalence for 'severe' CRF than surgery (22.0%) and radiotherapy (24.2%). The self-reported data for 'severe' CRF was 20-fold higher than those assessed by physicians (23.6% vs. 1.6%). Female patients exhibited a 1.4-fold higher prevalence of 'severe' fatigue compared to males. The present data showed quantitative feature of the prevalence and severity of CRF based on the cancer- or treatment-related factors, sex, and perspective of patient versus physician. In the context of the medical impact of CRF, our results provide a comparative reference to oncologists or health care providers making patient-specific decision.
Topics: Male; Humans; Female; Prevalence; Neoplasms; Fatigue; Genital Neoplasms, Female; Self Report; Quality of Life
PubMed: 37550326
DOI: 10.1038/s41598-023-39046-0 -
Diagnostic and Prognostic Research Aug 2023Numerous biomarkers have been proposed for diagnosis, therapeutic, and prognosis in sepsis. Previous evaluations of the value of biomarkers for predicting mortality due... (Review)
Review
Basal procalcitonin, C-reactive protein, interleukin-6, and presepsin for prediction of mortality in critically ill septic patients: a systematic review and meta-analysis.
BACKGROUND
Numerous biomarkers have been proposed for diagnosis, therapeutic, and prognosis in sepsis. Previous evaluations of the value of biomarkers for predicting mortality due to this life-threatening condition fail to address the complexity of this condition and the risk of bias associated with prognostic studies. We evaluate the predictive performance of four of these biomarkers in the prognosis of mortality through a methodologically sound evaluation.
METHODS
We conducted a systematic review a systematic review and meta-analysis to determine, in critically ill adults with sepsis, whether procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), and presepsin (sCD14) are independent prognostic factors for mortality. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials up to March 2023. Only Phase-2 confirmatory prognostic factor studies among critically ill septic adults were included. Random effects meta-analyses pooled the prognostic association estimates.
RESULTS
We included 60 studies (15,681 patients) with 99 biomarker assessments. Quality of the statistical analysis and reporting domains using the QUIPS tool showed high risk of bias in > 60% assessments. The biomarker measurement as a continuous variable in models adjusted by key covariates (age and severity score) for predicting mortality at 28-30 days showed a null or near to null association for basal PCT (pooled OR = 0.99, 95% CI = 0.99-1.003), CRP (OR = 1.01, 95% CI = 0.87 to 1.17), and IL-6 (OR = 1.02, 95% CI = 1.01-1.03) and sCD14 (pooled HR = 1.003, 95% CI = 1.000 to 1.006). Additional meta-analyses accounting for other prognostic covariates had similarly null findings.
CONCLUSION
Baseline, isolated measurement of PCT, CRP, IL-6, and sCD14 has not been shown to help predict mortality in critically ill patients with sepsis. The role of these biomarkers should be evaluated in new studies where the patient selection would be standardized and the measurement of biomarker results.
TRIAL REGISTRATION
PROSPERO (CRD42019128790).
PubMed: 37537680
DOI: 10.1186/s41512-023-00152-2 -
Biotechnology Advances Oct 2023Temperature affects cellular processes at different spatiotemporal scales, and identifying the genetic and molecular mechanisms underlying temperature responses paves... (Review)
Review
Temperature affects cellular processes at different spatiotemporal scales, and identifying the genetic and molecular mechanisms underlying temperature responses paves the way to develop approaches for mitigating the effects of future climate scenarios. A systems view of the effects of temperature on cellular physiology can be obtained by focusing on metabolism since: (i) its functions depend on transcription and translation and (ii) its outcomes support organisms' development, growth, and reproduction. Here we provide a systematic review of modelling efforts directed at investigating temperature effects on properties of single biochemical reactions, system-level traits, metabolic subsystems, and whole-cell metabolism across different prokaryotes and eukaryotes. We compare and contrast computational approaches and theories that facilitate modelling of temperature effects on key properties of enzymes and their consideration in constraint-based as well as kinetic models of metabolism. In addition, we provide a summary of insights from computational approaches, facilitating integration of omics data from temperature-modulated experiments with models of metabolic networks, and review the resulting biotechnological applications. Lastly, we provide a perspective on how different types of metabolic modelling can profit from developments in machine learning and models of different cellular layers to improve model-driven insights into the effects of temperature relevant for biotechnological applications.
Topics: Temperature; Metabolic Networks and Pathways; Phenotype; Models, Biological
PubMed: 37348662
DOI: 10.1016/j.biotechadv.2023.108203 -
Clinical and Translational Medicine Jan 2024The impact of fibroblasts on the immune system provides insight into the function of fibroblasts. In various tissue microenvironments, multiple fibroblast subtypes... (Review)
Review
BACKGROUND
The impact of fibroblasts on the immune system provides insight into the function of fibroblasts. In various tissue microenvironments, multiple fibroblast subtypes interact with immunocytes by secreting growth factors, cytokines, and chemokines, leading to wound healing, fibrosis, and escape of cancer immune surveillance. However, the specific mechanisms involved in the fibroblast-immunocyte interaction network have not yet been fully elucidated.
MAIN BODY AND CONCLUSION
Therefore, we systematically reviewed the molecular mechanisms of fibroblast-immunocyte interactions in fibrosis, from the history of cellular evolution and cell subtype divisions to the regulatory networks between fibroblasts and immunocytes. We also discuss how these communications function in different tissue and organ statuses, as well as potential therapies targeting the reciprocal fibroblast-immunocyte interplay in fibrosis. A comprehensive understanding of these functional cells under pathophysiological conditions and the mechanisms by which they communicate may lead to the development of effective and specific therapies targeting fibrosis.
Topics: Humans; Fibroblasts; Cross Reactions; Cell Division; Cytokines; Fibrosis
PubMed: 38264932
DOI: 10.1002/ctm2.1545 -
Cureus Sep 2023is traditionally used to prevent and treat some diseases such as liver disorders, hypertension, insomnia, diabetes, and cancer. spore extracts are also reported to... (Review)
Review
is traditionally used to prevent and treat some diseases such as liver disorders, hypertension, insomnia, diabetes, and cancer. spore extracts are also reported to share similar bioactivities as extracts from its other parts. However, there is no systematic review that elucidates its pharmacological effect. Our aim is to comprehensively summarise current evidence of spore extracts to clarify its benefits to be applied in further studies. We searched five primary databases: PubMed, Virtual Health Library (VHL), Global Health Library (GHL), System for Information on Grey Literature in Europe (SIGLE), and Google Scholar on September 13, 2021. Articles were selected according to inclusion and exclusion criteria. A manual search was applied to find more relevant articles. Ninety studies that reported the pharmacological effects and/or safety of spores were included in this review. The review found that spore extracts showed quite similar effects as other parts of this medicinal plant including anti-tumor, anti-inflammatory, antioxidant effects, and immunomodulation. sporoderm-broken extract demonstrated higher efficiency than unbroken spore extract. extracts also showed their effects on some genes responsible for the body's metabolism, which implied the benefits in metabolic diseases. The safety of should be investigated in depth as high doses of the extract could increase levels of cancer antigen (CA)72-4, despite no harmful effect shown on body organs. Generally, there is a lot of potential in the studies of compounds with pharmacological effects and new treatments. Sporoderm breaking technique could contribute to the production of extracts with more effective prevention and treatment of diseases. High doses of spore extract should be used with caution as there was a concern about the increase in CA.
PubMed: 37790044
DOI: 10.7759/cureus.44574