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ESMO Open Apr 2023Programmed death-ligand 1[PD-(L)1], cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and lymphocyte-activation gene 3 (LAG-3) inhibitors are recent breakthroughs in... (Review)
Review
Programmed death-ligand 1[PD-(L)1], cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and lymphocyte-activation gene 3 (LAG-3) inhibitors are recent breakthroughs in cancer treatment, however not all patients benefit from it. Thus new therapies are under investigation, such as anti-TIGIT [anti-T-cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif domains] antibodies. TIGIT is an immune checkpoint inhibiting lymphocyte T cells by several mechanisms. In vitro models showed its inhibition could restore antitumor response. Furthermore, its association with anti-PD-(L)1 therapies could synergistically improve survival. We carried out a review of the clinical trial about TIGIT referenced in the PubMed database, finding three published clinical trials on anti-TIGIT therapies. Vibostolimab was evaluated in a phase I alone or in combination with pembrolizumab. The combination had an objective response rate of 26% in patients with a non-small-cell lung cancer (NSCLC) naïve of anti-programmed cell death protein 1 (anti-PD-1). Etigilimab was tested in a phase I alone or in combination with nivolumab, but the study was stopped due to business reasons. In the phase II CITYSCAPE trial, tiragolumab demonstrated higher objective response rate and progression-free survival in combination with atezolizumab than atezolizumab alone in advanced PD-L1-high NSCLC. The ClinicalTrials.gov database references 70 trials of anti-TIGIT in patients with cancer, 47 of them with ongoing recruitment. Only seven were phase III, including five about patients with NSCLC, mostly with combination therapy. Data from phase I-II trials highlighted that targeting TIGIT represents a safe therapeutic approach, with an acceptable toxicity profile maintained when adding anti-PD-(L)1 antibodies. Frequent adverse events were pruritus, rash, and fatigue. Grade 3-4 adverse events were reported in nearly one in three patients. Anti-TIGIT antibodies are under development as a novel immunotherapy approach. A promising research area includes the combination with anti-PD-1 therapies in advanced NSCLCs.
Topics: Humans; Antibodies, Monoclonal; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Nivolumab
PubMed: 36933320
DOI: 10.1016/j.esmoop.2023.101184 -
Human Reproduction Update Jun 2022Uterine natural killer cells (uNK) are the most abundant lymphocytes found in the decidua during implantation and in first trimester pregnancy. They are important for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Uterine natural killer cells (uNK) are the most abundant lymphocytes found in the decidua during implantation and in first trimester pregnancy. They are important for early placental development, especially trophoblast invasion and transformation of the spiral arteries. However, inappropriate uNK function has been implicated in reproductive failure, such as recurrent miscarriage (RM) or recurrent implantation failure (RIF). Previous studies have mainly focussed on peripheral NK cells (pNK), despite the well-documented differences in pNK and uNK phenotype and function. In recent years, there has been an explosion of studies conducted on uNK, providing a more suitable representation of the immune environment at the maternal-foetal interface. Here, we summarize the evidence from studies published on uNK in women with RM/RIF compared with controls.
OBJECTIVE AND RATIONALE
The objectives of this systematic review and meta-analysis are to evaluate: differences in uNK level in women with RM/RIF compared with controls; pregnancy outcome in women with RM/RIF stratified by high and normal uNK levels; correlation between uNK and pNK in women with RM/RIF; and differences in uNK activity in women with RM/RIF compared with controls.
SEARCH METHODS
MEDLINE, EMBASE, Web of Science and Cochrane Trials Registry were searched from inception up to December 2020 and studies were selected in accordance with PRISMA guidelines. Meta-analyses were performed for uNK level, pregnancy outcome and uNK/pNK correlation. Narrative synthesis was conducted for uNK activity. Risk of bias was assessed by ROBINS-I and publication bias by Egger's test.
OUTCOMES
Our initial search yielded 4636 articles, of which 60 articles were included in our systematic review. Meta-analysis of CD56+ uNK level in women with RM compared with controls showed significantly higher levels in women with RM in subgroup analysis of endometrial samples (standardized mean difference (SMD) 0.49, CI 0.08, 0.90; P = 0.02; I2 88%; 1100 women). Meta-analysis of CD56+ uNK level in endometrium of women with RIF compared with controls showed significantly higher levels in women with RIF (SMD 0.49, CI 0.01, 0.98; P = 0.046; I2 84%; 604 women). There was no difference in pregnancy outcome in women with RM/RIF stratified by uNK level, and no significant correlation between pNK and uNK levels in women with RM/RIF. There was wide variation in studies conducted on uNK activity, which can be broadly divided into regulation and receptors, uNK cytotoxicity, cytokine secretion and effect of uNK on angiogenesis. These studies were largely equivocal in their results on cytokine secretion, but most studies found lower expression of inhibitory receptors and increased expression of angiogenic factors in women with RM.
WIDER IMPLICATIONS
The observation of significantly increased uNK level in endometrium of women with RM and RIF may point to an underlying disturbance of the immune milieu culminating in implantation and/or placentation failure. Further research is warranted to elucidate the underlying pathophysiology. The evidence for measuring pNK as an indicator of uNK behaviour is sparse, and of limited clinical use. Measurement of uNK level/activity may be more useful as a diagnostic tool, however, a standardized reference range must be established before this can be of clinical use.
Topics: Abortion, Habitual; Cytokines; Embryo Implantation; Endometrium; Female; Humans; Killer Cells, Natural; Placenta; Pregnancy; Uterus
PubMed: 35265977
DOI: 10.1093/humupd/dmac006 -
The Cochrane Database of Systematic... Apr 2016Ganoderma lucidum is a natural medicine that is widely used and recommended by Asian physicians and naturopaths for its supporting effects on immune system. Laboratory... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ganoderma lucidum is a natural medicine that is widely used and recommended by Asian physicians and naturopaths for its supporting effects on immune system. Laboratory research and a handful of preclinical trials have suggested that G. lucidum carries promising anticancer and immunomodulatory properties. The popularity of taking G. lucidum as an alternative medicine has been increasing in cancer patients. However, there is no systematic review that has been conducted to evaluate the actual benefits of G. lucidum in cancer treatment.
OBJECTIVES
To evaluate the clinical effects of G. lucidum on long-term survival, tumour response, host immune functions and quality of life in cancer patients, as well as adverse events associated with its use.
SEARCH METHODS
We searched an extensive set of databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, NIH, AMED, CBM, CNKI, CMCC and VIP Information/Chinese Scientific Journals Database was searched for randomised controlled trials (RCTs) in October 2011. Other strategies used were scanning the references of articles retrieved, handsearching of the International Journal of Medicinal Mushrooms and contact with herbal medicine experts and manufacturers of G. lucidum. For this update we updated the searches in February 2016.
SELECTION CRITERIA
To be eligible for being included in this review, studies had to be RCTs comparing the efficacy of G. lucidum medications to active or placebo control in patients with cancer that had been diagnosed by pathology. All types and stages of cancer were eligible for inclusion. Trials were not restricted on the basis of language.
DATA COLLECTION AND ANALYSIS
Five RCTs met the inclusion criteria and were included in this review. Two independent review authors assessed the methodological quality of individual trials. Common primary outcomes were tumour response evaluated according to the World Health Organization (WHO) criteria, immune function parameters such as natural killer (NK)-cell activity and T-lymphocyte co-receptor subsets, and quality of life measured by the Karnofsky scale score. No trial had recorded long-term survival rates. Associated adverse events were reported in one study. A meta-analysis was performed to pool available data from the primary trials. Results were gauged using relative risks (RR) and standard mean differences (SMD) for dichotomous and continuous data respectively, with a 95% confidence interval (CI).
MAIN RESULTS
The methodological quality of primary studies was generally unsatisfying and the results were reported inadequately in many aspects. Additional information was not available from primary trialists. The meta-analysis results showed that patients who had been given G. lucidum alongside with chemo/radiotherapy were more likely to respond positively compared to chemo/radiotherapy alone (RR 1.50; 95% CI 0.90 to 2.51, P = 0.02). G. lucidum treatment alone did not demonstrate the same regression rate as that seen in combined therapy. The results for host immune function indicators suggested that G. lucidum simultaneously increases the percentage of CD3, CD4 and CD8 by 3.91% (95% CI 1.92% to 5.90%, P < 0.01), 3.05% (95% CI 1.00% to 5.11%, P < 0.01) and 2.02% (95% CI 0.21% to 3.84%, P = 0.03), respectively. In addition, leukocyte, NK-cell activity and CD4/CD8 ratio were marginally elevated. Four studies showed that patients in the G. lucidum group had relatively improved quality of life in comparison to controls. One study recorded minimal side effects, including nausea and insomnia. No significant haematological or hepatological toxicity was reported.
AUTHORS' CONCLUSIONS
Our review did not find sufficient evidence to justify the use of G. lucidum as a first-line treatment for cancer. It remains uncertain whether G. lucidum helps prolong long-term cancer survival. However, G. lucidum could be administered as an alternative adjunct to conventional treatment in consideration of its potential of enhancing tumour response and stimulating host immunity. G. lucidum was generally well tolerated by most participants with only a scattered number of minor adverse events. No major toxicity was observed across the studies. Although there were few reports of harmful effect of G. lucidum, the use of its extract should be judicious, especially after thorough consideration of cost-benefit and patient preference. Future studies should put emphasis on the improvement in methodological quality and further clinical research on the effect of G. lucidum on cancer long-term survival are needed. An update to this review will be performed every two years.
Topics: Antineoplastic Agents; Humans; Immunity, Cellular; Neoplasms; Randomized Controlled Trials as Topic; Reishi
PubMed: 27045603
DOI: 10.1002/14651858.CD007731.pub3 -
The Cochrane Database of Systematic... Sep 2018This review is an update of a previously published review, "Vitamin D for the management of multiple sclerosis" (published in the Cochrane Library; 2010, Issue 12).... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review is an update of a previously published review, "Vitamin D for the management of multiple sclerosis" (published in the Cochrane Library; 2010, Issue 12). Multiple sclerosis (MS) is characterised by inflammation, demyelination, axonal or neuronal loss, and astrocytic gliosis in the central nervous system (CNS), which can result in varying levels of disability. Some studies have provided evidence showing an association of MS with low levels of vitamin D and benefit derived from its supplementation.
OBJECTIVES
To evaluate the benefit and safety of vitamin D supplementation for reducing disease activity in people with MS.
SEARCH METHODS
We searched the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Specialized Register up to 2 October 2017 through contact with the Information Specialist with search terms relevant to this review. We included references identified from comprehensive electronic database searches and from handsearches of relevant journals and abstract books from conferences.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs that compared vitamin D versus placebo, routine care, or low doses of vitamin D in patients with MS. Vitamin D was administered as monotherapy or in combination with calcium. Concomitant interventions were allowed if they were used equally in all trial intervention groups.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the methodological quality of studies, while another review author sorted any disagreements. We expressed treatment effects as mean differences (MDs) for continuous outcomes (Expanded Disability Status Scale and number of magnetic resonance imaging (MRI) gadolinium-enhancing T1 lesions), as standardised MDs for health-related quality of life, as rate differences for annualised relapse rates, and as risk differences (RDs) for serious adverse events and minor adverse events, together with 95% confidence intervals (CIs).
MAIN RESULTS
We identified 12 RCTs enrolling 933 participants with MS; 464 were randomised to the vitamin D group, and 469 to the comparator group. Eleven trials tested vitamin D₃, and one trial tested vitamin D₂. Vitamin D₃ had no effect on the annualised relapse rate at 52 weeks' follow-up (rate difference -0.05, 95% CI -0.17 to 0.07; I² = 38%; five trials; 417 participants; very low-quality evidence according to the GRADE instrument); on the Expanded Disability Status Scale at 52 weeks' follow-up (MD -0.25, 95% CI -0.61 to 0.10; I² = 35%; five trials; 221 participants; very low-quality evidence according to GRADE); and on MRI gadolinium-enhancing T1 lesions at 52 weeks' follow-up (MD 0.02, 95% CI -0.45 to 0.48; I² = 12%; two trials; 256 participants; very low-quality evidence according to GRADE). Vitamin D₃ did not increase the risk of serious adverse effects within a range of 26 to 52 weeks' follow-up (RD 0.01, 95% CI -0.03 to 0.04; I² = 35%; eight trials; 621 participants; low-quality evidence according to GRADE) or minor adverse effects within a range of 26 to 96 weeks' follow-up (RD 0.02, 95% CI -0.02 to 0.06; I² = 20%; eight trials; 701 participants; low-quality evidence according to GRADE). Three studies reported health-related quality of life (HRQOL) using different HRQOL scales. One study reported that vitamin D improved ratings on the psychological and social components of the HRQOL scale but had no effects on the physical components. The other two studies found no effect of vitamin D on HRQOL. Two studies reported fatigue using different scales. One study (158 participants) reported that vitamin D₃ reduced fatigue compared with placebo at 26 weeks' follow-up. The other study (71 participants) found no effect on fatigue at 96 weeks' follow-up. Seven studies reported on cytokine levels, four on T-lymphocyte proliferation, and one on matrix metalloproteinase levels, with no consistent pattern of change in these immunological outcomes. The randomised trials included in this review provided no data on time to first treated relapse, number of participants requiring hospitalisation owing to progression of the disease, proportion of participants who remained relapse-free, cognitive function, or psychological symptoms.
AUTHORS' CONCLUSIONS
To date, very low-quality evidence suggests no benefit of vitamin D for patient-important outcomes among people with MS. Vitamin D appears to have no effect on recurrence of relapse, worsening of disability measured by the Expanded Disability Status Scale (EDSS), and MRI lesions. Effects on health-related quality of life and fatigue are unclear. Vitamin D₃ at the doses and treatment durations used in the included trials appears to be safe, although available data are limited. Seven ongoing studies will likely provide further evidence that can be included in a future update of this review.
Topics: Cholecalciferol; Ergocalciferols; Fatigue; Humans; Multiple Sclerosis; Quality of Life; Randomized Controlled Trials as Topic; Vitamins
PubMed: 30246874
DOI: 10.1002/14651858.CD008422.pub3 -
Frontiers in Immunology 2022Cerebral infarction/ischemia-reperfusion injury is currently the disease with the highest mortality and disability rate of cardiovascular disease. Current studies have... (Review)
Review
Cerebral infarction/ischemia-reperfusion injury is currently the disease with the highest mortality and disability rate of cardiovascular disease. Current studies have shown that nerve cells die of ischemia several hours after ischemic stroke, which activates the innate immune response in the brain, promotes the production of neurotoxic substances such as inflammatory cytokines, chemokines, reactive oxygen species and - nitrogen oxide, and mediates the destruction of blood-brain barrier and the occurrence of a series of inflammatory cascade reactions. Meanwhile, the expression of adhesion molecules in cerebral vascular endothelial cells increased, and immune inflammatory cells such as polymorphonuclear neutrophils, lymphocytes and mononuclear macrophages passed through vascular endothelial cells and entered the brain tissue. These cells recognize antigens exposed by the central nervous system in the brain, activate adaptive immune responses, and further mediate secondary neuronal damage, aggravating neurological deficits. In order to reduce the above-mentioned damage, the body induces peripheral immunosuppressive responses through negative feedback, which increases the incidence of post-stroke infection. This process is accompanied by changes in the immune status of the ischemic brain tissue in local and systemic systems. A growing number of studies implicate noncoding RNAs (ncRNAs) as novel epigenetic regulatory elements in the dysfunction of various cell subsets in the neurovascular unit after cerebral infarction/ischemia-reperfusion injury. In particular, recent studies have revealed advances in ncRNA biology that greatly expand the understanding of epigenetic regulation of immune responses and inflammation after cerebral infarction/ischemia-reperfusion injury. Identification of aberrant expression patterns and associated biological effects of ncRNAs in patients revealed their potential as novel biomarkers and therapeutic targets for cerebral infarction/ischemia-reperfusion injury. Therefore, this review systematically presents recent studies on the involvement of ncRNAs in cerebral infarction/ischemia-reperfusion injury and neuroimmune inflammatory cascades, and elucidates the functions and mechanisms of cerebral infarction/ischemia-reperfusion-related ncRNAs, providing new opportunities for the discovery of disease biomarkers and targeted therapy. Furthermore, this review introduces clustered regularly interspaced short palindromic repeats (CRISPR)-Display as a possible transformative tool for studying lncRNAs. In the future, ncRNA is expected to be used as a target for diagnosing cerebral infarction/ischemia-reperfusion injury, judging its prognosis and treatment, thereby significantly improving the prognosis of patients.
Topics: Mice; Animals; Humans; RNA, Long Noncoding; Endothelial Cells; Reactive Oxygen Species; Neuroinflammatory Diseases; Epigenesis, Genetic; Mice, Inbred C57BL; Reperfusion Injury; Brain Ischemia; RNA, Untranslated; Cerebral Infarction; Inflammation; Cytokines
PubMed: 36275741
DOI: 10.3389/fimmu.2022.930171 -
Journal of Clinical Medicine Sep 2021Neutrophil-lymphocyte ratio (NLR) is a biomarker of the systemic inflammatory response. The objective of this systematic scoping review was to examine the literature on... (Review)
Review
Neutrophil-lymphocyte ratio (NLR) is a biomarker of the systemic inflammatory response. The objective of this systematic scoping review was to examine the literature on NLR and inflammatory bowel disease (IBD). PubMed, Embase, Cochrane CENTRAL, CINAHL, ClinicalTrials.gov, Cochrane Specialized Register, DOAJ, PDQT, Biosis Citation Index, Scopus, and Web of Science were systematically searched. A total of 2621 citations yielding 62 primary studies were synthesized under four categories: distinguishing patients with IBD from controls, disease activity differentiation, clinical outcome prediction, and association of NLR with other IBD biomarkers. Thirty-eight studies employed receiver operating characteristic (ROC) curve analysis to generate optimal NLR cutpoints for applications including disease activity differentiation and prediction of response to treatment. Among the most promising findings, NLR may have utility for clinical and endoscopic disease activity differentiation and prediction of loss of response to infliximab (IFX). Overall findings suggest NLR may be a promising IBD biomarker. Assessment of NLR is non-invasive, low cost, and widely accessible given NLR is easily calculated from blood count data routinely and serially monitored in patients with IBD. Further research is justified to elucidate how evaluation of NLR in research and clinical practice would directly impact the quality and cost of care for patients living with IBD.
PubMed: 34575330
DOI: 10.3390/jcm10184219 -
The Cochrane Database of Systematic... Jun 2022Thyroid-associated ophthalmopathy (TAO) is the most frequent extrathyroidal manifestation of Graves' disease, affecting up to 50% of patients. It has a great impact on... (Review)
Review
BACKGROUND
Thyroid-associated ophthalmopathy (TAO) is the most frequent extrathyroidal manifestation of Graves' disease, affecting up to 50% of patients. It has a great impact on quality of life. Rituximab (RTX) is a human/murine chimeric monoclonal antibody that targets the CD20 receptor on B-lymphocytes. Preliminary work has shown that blocking this CD20 receptor with RTX may affect the clinical course of TAO by reducing inflammation and the degree of proptosis. OBJECTIVES: This review update, originally published in 2013, assesses the efficacy and safety of using RTX for the treatment of TAO.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2022, Issue 2), which contains the Cochrane Eyes and Vision Trials Register, Ovid MEDLINE, Ovid Embase, Latin American and Caribbean Health Science Information database (LILACS), the ISRCTN registry, clinicaltrials.gov and the WHO International Clinical Trials Registry Platform (WHO ICTRP). There were no language restrictions in the electronic search for trials. We last searched the electronic databases on 22 February 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of RTX administered by intravenous infusion using any dosage regimen for the treatment of active TAO in adults, compared to placebo or glucocorticoids treatment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently scanned titles and abstracts, and screened full-text reports of potentially relevant studies. The outcomes of interest in this review were: clinical activity score (CAS), NOSPECS severity scale, proptosis (mm), palpebral aperture (mm), extraocular motility (degrees or diplopia rating scale), quality of life and adverse effects.
MAIN RESULTS
We identified two studies that met the inclusion criteria in this updated review. Across both studies, the mean age of participants was 55 years and 77% were women. RTX compared to intravenous methylprednisolone (IVMP) One study, conducted in Italy, compared RTX (n = 15 after one participant withdrew) with IVMP (n = 16) for active TAO (CAS ≥ 3 out of 7 or 4 out of 10). We judged this study to be at low risk of bias in most domains, but it was stopped early because of disease reactivation in the comparator group (5/16 participants). This study provided low-certainty evidence that RTX may result in CAS improvement at 24 weeks compared to IVMP (15/15 versus 12/16 improved by ≥ 2 points; risk ratio (RR) 1.32, 95% confidence interval (CI) 0.98 to 1.78). Only very low-certainty evidence was available for the other outcomes: NOSPECS improvement by 2 or more classes (3/15 versus 3/16; RR 1.07, 95% CI 0.25 to 4.49); proptosis improvement by 2 mm or more (0/15 versus 1/16; RR 0.35, 95% CI 0.02 to 8.08); palpebral aperture improvement by 3 mm or more (2/15 versus 0/16; RR 5.31, 95% CI 0.28 to 102.38); motility improvement by 1 class or more (3/15 versus 3/16; RR 1.07, 95% CI 0.25 to 4.49); and improvement on the Graves' ophthalmopathy QoL scale by at least 6 points for "functioning" (5/14 versus 8/13; RR 0.58, 95% CI 0.25 to 1.32), and "appearance" (9/14 versus 6/13; RR 1.39, 95% CI 0.69 to 2.82). Adverse events were more common in the RTX group (RR 1.39, 95% CI 0.90 to 2.13; low-certainty evidence). Minor adverse effects (mild infusion reactions) were observed in most people receiving RTX at first infusion. Two participants experienced a major infusion reaction, likely cytokine release syndrome. RTX compared to placebo One study, conducted in the USA, enrolled 25 participants with active TAO (CAS ≥ 4 out of 7), comparing RTX (13 participants) to placebo. We judged this study to be at low risk of bias in most domains, but it was stopped early due to recruitment issues. It provided very low-certainty evidence on the following outcomes at 24 weeks: CAS improvement by 2 or more points (4/13 RTX versus 3/12 placebo; RR 1.23, 95% CI 0.34 to 4.40); NOSPECS improvement by 2 or more classes (2/13 versus 2/12; RR 0.92, 95% CI 0.15 to 5.56); proptosis improvement by 2 mm or more (2/13 versus 4/12; RR 0.46, 95% CI 0.10 to 2.08); palpebral aperture median change (0 mm in RTX group, in both eyes separately, versus -0.5 mm and 0.5 mm in placebo group right and left eye, respectively); motility median diplopia score (3 versus 2.5); SF-12 physical component median score (45.9 versus 40.3) and mental component median score (52.8 versus 46.1). More participants in the RTX group experienced adverse effects (8/13 versus 3/12; RR 2.46, 95% CI 0.84 to 7.18). AUTHORS' CONCLUSIONS: There is currently insufficient evidence to support the use of RTX in people with TAO. Future studies investigating RTX in people with active TAO may need to be multi-centre in order to recruit enough participants to make an adequate judgement on the efficacy and safety of this novel therapy.
Topics: Adult; Animals; Antibodies, Monoclonal; Diplopia; Female; Graves Ophthalmopathy; Humans; Male; Mice; Middle Aged; Rituximab
PubMed: 35709102
DOI: 10.1002/14651858.CD009226.pub3 -
Thrombosis Journal Jul 2023Venous thromboembolism (VTE) is a common thrombotic vascular disease that has a significant impact on people's well-being and quality of life. A plethora of clinical... (Review)
Review
BACKGROUND
Venous thromboembolism (VTE) is a common thrombotic vascular disease that has a significant impact on people's well-being and quality of life. A plethora of clinical studies explore the relationship between inflammatory biomarkers and VTE but yield conflicting results. This article proposed to pool these studies to draw a more convincing conclusion.
METHODS
We searched several databases for studies before April 2023. Available data was processed using Stata software (version 15.0 SE) and R (version 4.1.2). This meta-analysis has been registered in PROSPERO (CRD42022321815). The VTE in this review encompassed pulmonary embolism, deep vein thrombosis, and cerebral venous thrombosis.
RESULTS
A total of 25 articles were finally involved in this study. Our results revealed that higher levels of high-sensitivity C-reactive protein (hs-CRP, MD, 0.63, 95%CI, 0.21-1.05) and C-reactive protein (CRP)> 3ug/ml (OR, 1.52, 95%CI, 1.18-1.96) might be regarded as risk factors for future VTE occurrence. The elevated levels of monocyte (MD, 0.03, 95%CI, 0.00-0.05), hs-CRP (0.85, 0.61-1.08), CRP (0.66, 0.20-1.13) and IL-6 (0.47, 0.25-0.70) might represent the previous VTE; a series of markers such as white blood cell (1.43, 0.88-1.98), neutrophil (1.79, 1.02-2.56), monocyte (0.17, 0.14-0.21), hs-CRP (3.72, 1.45-5.99), IL-6 (5.99, 4.52-7.46), platelet-lymphocyte ratio (33.1, 24.45-41.78) and neutrophil-lymphocyte ratio (1.34, 0.95-1.73) increased during the acute phase of VTE.
CONCLUSIONS
In general, activated inflammatory biomarkers might not only be correlated with an increased risk of VTE, but may also give a hint of the occurrence of VTE in clinical settings.
PubMed: 37525162
DOI: 10.1186/s12959-023-00526-y -
International Journal of Molecular... Dec 2022Endometriosis is a chronic inflammatory disorder, characterized by the presence of endometrial cells outside the uterine cavity. An increasing number of studies... (Review)
Review
Endometriosis is a chronic inflammatory disorder, characterized by the presence of endometrial cells outside the uterine cavity. An increasing number of studies correlate the immune system with endometriosis, particularly NK receptors (NKR), which have been suggested to play an essential role in the pathogenesis of the disease. This systematic review aims to enlighten the role of NKR in endometriosis. A literature search was performed independently by two reviewers, to identify studies assessing the role of NKR in endometriosis. In total, 18 studies were included. Endometriosis pathogenesis seems to be marked by the overexpression of NK inhibitor receptors (KIRS), namely, CD158a+, KIR2DL1, CD94/NKG2A, PD-1, NKB1, and EB6, and inhibiting ligands such as PD-L1, HLA-E, HLA-G, and HLA-I. Concurrently, there is a decrease in NK-activating receptors and natural cytotoxicity receptors (NCRs), such as NKp46, NKp30, and NKG2D. The immune shift from NK surveillance to NK suppression is also apparent in the greater relative number of ITIM domains compared with ITAM domains in NKRs. In conclusion, NK receptor activity seems to dictate the immunocompetency of women to clear endometriotic cells from the peritoneal cavity. Future research could explore NKRs as therapeutic targets, such as that which is now well established in cancer therapy through immunotherapy.
Topics: Humans; Female; Receptors, Natural Killer Cell; Killer Cells, Natural; Endometriosis; Endometrium
PubMed: 36613776
DOI: 10.3390/ijms24010331 -
Health Science Reports May 2022Older people have higher rates of comorbidities and may experience more severe inflammatory responses; therefore, are at higher risk of death. Herein, we aimed to... (Review)
Review
BACKGROUND AND AIMS
Older people have higher rates of comorbidities and may experience more severe inflammatory responses; therefore, are at higher risk of death. Herein, we aimed to systematically review the mortality in coronavirus disease 2019 (COVID-19) patients and its predictors in this age group.
METHODS
We searched PubMed, Web of Science, and Science Direct using relevant keywords. Retrieved records underwent a two-step screening process consisting of title/abstract and full-text screenings to identify the eligible studies.
RESULTS
Summarizing findings of 35 studies demonstrated that older patients have higher mortality rates compared to the younger population. A review of articles revealed that increasing age, body mass index, a male gender, dementia, impairment or dependency in daily activities, presence of consolidations on chest X-ray, hypoxemic respiratory failure, and lower oxygen saturation at admission were risk factors for death. High d-dimer levels, 25-hydroxy vitamin D serum deficiencies, high C-reactive protein (≥5 mg/L) levels plus any other abnormalities of lymphocyte, higher blood urea nitrogen or lactate dehydrogenase, and higher platelet count were predictors of poor prognosis and mortality in the elderly. Studies have also shown that previous treatment with renin-angiotensin-aldosterone system inhibitors, pharmacological treatments of respiratory disorders, antibiotics, corticosteroids, vitamin K antagonist, antihistamines, azithromycin, Itolizumab (an anti-CD6 monoclonal antibody) in combination with other antivirals reduces COVID-19 worsening and mortality. Vaccination against seasonal influenza might also reduce COVID-19 mortality.
CONCLUSION
Overall, a critical consideration is necessary for the care and management of COVID-19 in the aged population considering the drastic contrasts in manifestation and prognosis compared to other age groups. Mortality from COVID-19 is independently associated with the patient's age. Elderly patients with COVID-19 are more vulnerable to poor outcomes. Thus, strict preventive measures, timely diagnosis, and aggressive therapeutic/nontherapeutic care are of great importance to reduce acute respiratory distress syndrome and severe complications in older people.
PubMed: 35620541
DOI: 10.1002/hsr2.657