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Frontiers in Neurology 2023Guillain-Barre syndrome (GBS) is an immune-mediated neuropathy. This has raised the possibility that the neutrophil-lymphocyte ratio (NLR) may be a biomarker of its...
BACKGROUND AND OBJECTIVES
Guillain-Barre syndrome (GBS) is an immune-mediated neuropathy. This has raised the possibility that the neutrophil-lymphocyte ratio (NLR) may be a biomarker of its activity. We conducted a systematic review and meta-analysis to summarize the evidence of NLR as a potential biomarker for GBS.
METHODS
We systematically searched databases (PubMed, Ovid-Medline, Embase, Scopus, Web of Science, SciELO Citation Index, LILACS, and Google Scholar) until October 2021 for studies evaluating pre-treatment NLR values in GBS patients. A meta-analysis using a random-effects model to estimate pooled effects was realized for each outcome and a narrative synthesis when this was not possible. Subgroup and sensitivity analysis were realized. GRADE criteria were used to identify the certainty of evidence for each result.
RESULTS
Ten studies from 745 originally included were selected. Regarding GBS patients versus healthy controls, a meta-analysis of six studies (968 patients) demonstrated a significant increase in NLR values in GBS patients (MD: 1.76; 95% CI: 1.29, 2.24; I2 = 86%) with moderate certainty due to heterogeneity of GBS diagnosis criteria used. Regarding GBS prognosis, assessed by Hughes Score ≥ 3, NLR had a sensitivity between 67.3 and 81.5 and a specificity between 67.3 and 87.5 with low certainty due to imprecision, and heterogeneity. In relation to respiratory failure, NLR had a sensitivity of 86.5 and specificity of 68.2 with high and moderate certainty, respectively.
DISCUSSION
With moderate certainty, mean NLR is higher in GBS patients compared to healthy controls. Furthermore, we found that NLR could be a prognostic factor for disability and respiratory failure with low and moderate certainty, respectively. These results may prove useful for NLR in GBS patients; however, further research is needed.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021285212.
PubMed: 37333004
DOI: 10.3389/fneur.2023.1153690 -
Cancer Sep 2023The World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations are lifestyle-based guidelines that aim to reduce cancer risk. A... (Meta-Analysis)
Meta-Analysis
Adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations and cancer risk: A systematic review and meta-analysis.
BACKGROUND
The World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations are lifestyle-based guidelines that aim to reduce cancer risk. A systematic review and meta-analysis of studies investigating associations between a score for adherence to the 2018 Cancer Prevention Recommendations and cancer risk was conducted.
METHODS
MEDLINE, Embase, Web of Science, and Scopus were searched for studies published to November 28, 2022. In meta-analysis, the estimated risk ratios and 95% CIs for adherence score as a continuous (per 1-point increment) and categorical (highest vs. lowest score category) variable using random-effects models were estimated.
RESULTS
Eighteen studies (11 cohort; seven case-control) were included investigating incidence of breast (n = 7), colorectal (n = 5), prostate (n = 2), lung (n = 2), pancreatic (n = 1), endometrial (n = 1), unknown primary cancer (n = 1), chronic lymphocytic leukemia (n = 1), and overall (any) cancer (n = 1). The summary risk ratio per 1-point increment in adherence score was 0.89 (95% CI, 0.85-0.93; I = 76.5%; n = 7) for breast cancer, 0.88 (95% CI, 0.84-0.91; I = 26.2%; n = 4) for colorectal cancer, and 0.92 (95% CI, 0.86-0.98, I = 66.0%; n = 2) for lung cancer. There were no significant associations with prostate or other cancers. Meta-analysis results using categorical adherence score variables were consistent with these findings.
CONCLUSIONS
Greater adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations was associated with lower risk of breast, colorectal, and lung cancers. Future studies investigating associations with risk of other forms of cancer are warranted.
PROSPERO REGISTRATION NUMBER
CRD42022313327.
Topics: Male; Humans; United States; Risk; Life Style; Breast Neoplasms; Incidence; Colorectal Neoplasms; Risk Factors; Diet
PubMed: 37309215
DOI: 10.1002/cncr.34842 -
International Journal of Environmental... Apr 2023The rate of new human immunodeficiency virus (HIV) infections globally is alarming. Although antiretroviral therapy (ART) improves the quality of life among this group... (Meta-Analysis)
Meta-Analysis Review
The rate of new human immunodeficiency virus (HIV) infections globally is alarming. Although antiretroviral therapy (ART) improves the quality of life among this group of patients, ARTs are associated with risk of cardiovascular diseases (CVD). Moreover, virally suppressed patients still experience immune activation associated with HIV migration from reservoir sites. Statins are widely recommended as therapeutic agents to control ART-related CVD; however, their impacts on the cluster of differentiation (CD)4 count and viral load are inconsistent. To assess the effect of statins on markers of HIV infections, immune activation and cholesterol, we thoroughly reviewed evidence from randomised controlled trials. We found 20 relevant trials from three databases with 1802 people living with HIV (PLHIV) on statin-placebo treatment. Our evidence showed no significant effect on CD4 T-cell count standardised mean difference (SMD): (-0.59, 95% confidence intervals (CI): (-1.38, 0.19), = 0.14) following statin intervention in PLHIV on ART. We also found no significant difference in baseline CD4 T-cell count (SD: (-0.01, 95%CI: (-0.25, 0.23), = 0.95). Our findings revealed no significant association between statins and risk of viral rebound in PLHIV with undetectable viral load risk ratio (RR): (1.01, 95% CI: (0.98, 1.04), = 0.65). Additionally, we found a significant increase in CD8CD38HLA-DR T-cells (SMD (1.10, 95% CI: (0.93, 1.28), < 0.00001) and CD4CD38HLA-DR T-cells (SMD (0.92, 95% CI: (0.32, 1.52), = 0.003). Finally, compared to placebo, statins significantly reduced total cholesterol (SMD: (-2.87, 95% CI: (-4.08, -1.65), < 0.0001)). Our results suggest that the statin lipid-lowering effect in PLHIV on ART may elevate immune activation without influencing the viral load and CD4 count. However, due to the limited evidence synthesised in this meta-analysis, we recommend that future powered trials with sufficient sample sizes evaluate statins' effect on CD4 count and viral load, especially in virally suppressed patients.
Topics: Humans; HIV Infections; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Quality of Life; HIV-1; HLA-DR Antigens; CD4 Lymphocyte Count; Cardiovascular Diseases; Cholesterol; Viral Load
PubMed: 37174188
DOI: 10.3390/ijerph20095668 -
BMC Infectious Diseases May 2023Numerous vaccination research experiments have been conducted on non-primate hosts to prevent or control HTLV-1 infection. Therefore, reviewing recent advancements for...
BACKGROUND
Numerous vaccination research experiments have been conducted on non-primate hosts to prevent or control HTLV-1 infection. Therefore, reviewing recent advancements for status assessment and strategic planning of future preventative actions to reduce HTLV-1 infection and its consequences would be essential.
METHODS
MEDLINE, Scopus, Web of Science, and Clinicaltrials.gov were searched from each database's inception through March 27, 2022. All original articles focusing on developing an HTLV-1 vaccine candidate were included.
RESULTS
A total of 47 studies were included. They used a variety of approaches to develop the HTLV-1 vaccine, including DNA-based, dendritic-cell-based, peptide/protein-based, and recombinant vaccinia virus approaches. The majority of the research that was included utilized Tax, Glycoprotein (GP), GAG, POL, REX, and HBZ as their main peptides in order to develop the vaccine. The immunization used in dendritic cell-based investigations, which were more recently published, was accomplished by an activated CD-8 T-cell response. Although there hasn't been much attention lately on this form of the vaccine, the initial attempts to develop an HTLV-1 immunization depended on recombinant vaccinia virus, and the majority of results seem positive and effective for this type of vaccine. Few studies were conducted on humans. Most of the studies were experimental studies using animal models. Adenovirus, Cytomegalovirus (CMV), vaccinia, baculovirus, hepatitis B, measles, and pox were the most commonly used vectors.
CONCLUSIONS
This systematic review reported recent progression in the development of HTLV-1 vaccines to identify candidates with the most promising preventive and therapeutic effects.
Topics: Animals; Humans; Human T-lymphotropic virus 1; HTLV-I Infections; T-Lymphocytes; Vaccinia virus; Viral Vaccines; Peptides
PubMed: 37170214
DOI: 10.1186/s12879-023-08289-7 -
Experimental Gerontology Jun 2023Ageing is associated with several physiological changes, including changes in the immune system. Age-related changes in the innate and adaptive immune system are thought... (Review)
Review
INTRODUCTION
Ageing is associated with several physiological changes, including changes in the immune system. Age-related changes in the innate and adaptive immune system are thought to contribute to frailty. Understanding the immunological determinants of frailty could help to develop and deliver more effective care to older people. This systematic review aims to study the association between biomarkers of the ageing immune system and frailty.
METHODS
The search strategy was performed in PubMed and Embase, using the keywords "immunosenescence", "inflammation", "inflammaging" and "frailty". We included studies that investigated the association of biomarkers of the ageing immune system and frailty cross-sectionally in older adults, without an active disease that affects immune parameters. Three independent researchers selected the studies and performed data extraction. Study quality was assessed using the Newcastle-Ottawa scale adapted for cross-sectional studies.
RESULTS
A total of 44 studies, with a median number of 184 participants, was included. Study quality was good in 16 (36 %), moderate in 25 (57 %) and poor in 3 (7 %) of studies. The most frequently studied inflammaging biomarkers were IL-6, CRP and TNF-α. Associations with frailty were observed for increased levels of (i) IL-6 in 12 of 24 studies, (ii) CRP in 7 of 19 studies, and (ii) TNF-α in 4 of 13 studies. In none of the other studies were associations observed of frailty with these biomarkers. Different types of T-lymphocyte subpopulations were studied but each subset was studied only once, and the study sample sizes were low.
CONCLUSION
Our review of 44 studies on the relation between immune biomarkers and frailty identified IL-6 and CRP as the biomarkers that were most consistently associated with frailty. T-lymphocyte subpopulations were investigated but too infrequently to draw strong conclusions yet, although initial results are promising. Additional studies are required in order to further validate these immune biomarkers in larger cohorts. Furthermore, prospective studies in more uniform settings and larger cohorts are needed to further investigate the association with immune candidate biomarkers for which potential associations with ageing and frailty were previously observed, before these can be used in clinical practice to help assess frailty and improve the care treatments of older patients.
Topics: Humans; Aged; Prospective Studies; Tumor Necrosis Factor-alpha; Cross-Sectional Studies; Interleukin-6; Aging; Frailty; Biomarkers; Immune System; Frail Elderly
PubMed: 37028607
DOI: 10.1016/j.exger.2023.112163 -
Medicine Apr 2023The occurrence and development of non-small cell lung cancer (NSCLC) are closely related to the immune status of the tumor-host. The immunosuppression caused by tumor... (Meta-Analysis)
Meta-Analysis
The effect of ginsenoside Rg3 combined with chemotherapy on immune function in non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
The occurrence and development of non-small cell lung cancer (NSCLC) are closely related to the immune status of the tumor-host. The immunosuppression caused by tumor cells and toxic side effects produced by chemotherapeutic drugs results in a decrease in immune function, ultimately leading to the failure of clinical chemotherapy treatment. Ginsenoside Rg3 has been clinically reported to have positive effects in enhancing immune function in patients. Thus, we screened and evaluated the quality of the evidence regarding the benefits of ginsenoside Rg3 and conducted a meta-analysis to assess the impact on improving immune function in NSCLC.
METHODS
The PubMed, EMBASE, Cochrane Library, CNKI, Weipu (VIP), and Wanfang databases were searched in this study, all from the time of library construction to January 2023.
RESULTS
In total,12 trials with a sample size of 1008 cases were included based on the eligible criteria. The results showed that compared with first-line chemotherapy alone, the combination of ginsenoside Rg3 and first-line chemotherapy could better improve level of the CD3+ T lymphocytes [mean difference (MD) = 4.72; 95% confidence intervals (CI): 3.92, 5.53; P < .00001], CD4+ T lymphocytes (MD = 4.93; 95% CI: 4.61, 5.26; P < .00001), CD8+ T lymphocytes (MD = 2.67; 95% CI: 0.93, 4.37; P = .003), CD4+/CD8+ T lymphocytes (MD = 0.20; 95% CI: 0.09, 0.32; P = .0006), increase the activity of nature killer cells (MD = 2.11; 95% CI: 0.58, 3.63; P = .007), recover the decline of the white blood cell count induced by chemotherapy, and improve the clinical efficacy for patients.
CONCLUSION
This study confirmed that ginsenoside Rg3 has some efficacy advantages for improving immune function in patients with NSCLC.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Randomized Controlled Trials as Topic; Immunity
PubMed: 37026927
DOI: 10.1097/MD.0000000000033463 -
International Journal of Environmental... Mar 2023Stimulating protective immunity with vaccines appears to be the most promising option for providing widespread moderate to high protection against COVID-19 in people... (Review)
Review
BACKGROUND
Stimulating protective immunity with vaccines appears to be the most promising option for providing widespread moderate to high protection against COVID-19 in people over the age of 18. Regular exercise improves the immune response, transmitting possible benefits against virus infections. The aim of this review is to study the effects of physical activity on vaccine injections, helping to develop new recommendations for COVID-19 vaccination campaigns.
METHODS
A comprehensive review of the existing literature was undertaken using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The internal quality of the studies was assessed according to the Physiotherapy Evidence Database (PEDro) scale. The outcomes analyzed were antibody titer, the level of lymphocytes CD4, CD8, InterLeukin 6 (IL6), leukocytes level, the visual analogue scale (VAS) for overall pain rating, arm and forearm circumferences and volume of oxygen (VO2) peak.
RESULTS
Fourteen articles were selected for the analysis. The majority of studies were randomized controlled trials (RCT) ( = 8) and controlled trials (CT) ( = 6). According to PEDro, the 'fair' category ( = 7) was the most represented, followed by 'good' ( = 6) and 'excellent' ( = 1). Physical training showed a positive effect on antibody titers of the vaccine; yet, different variables seem to influence antibody titers: higher new vs. old antigen in the vaccine, higher in younger vs. older individuals, and higher in females vs. males. After exercise, when analyzing variables of direct response to the vaccine, such as the amount of CD4, IL-6 and leukocytes, higher levels were observed in the patients who performed physical exercise compared to the control group. In the same way, better results were observed in physiological variables such as VO2 and limb circumferences, or subjective variables such as pain, which showed better results than the control group.
CONCLUSIONS
The immune response (antibody titers) depends on age, gender and the intensity of physical activity: long-term protocols at moderate intensity are the most recommended. All of these aspects also have to be carefully considered for the COVID-19 vaccination.
Topics: Male; Female; Humans; Adult; Middle Aged; COVID-19 Vaccines; COVID-19; Exercise; Vaccination; Pain; Immunity
PubMed: 36982095
DOI: 10.3390/ijerph20065183 -
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 -
International Journal of Molecular... Feb 2023Cancer is the second leading contributor to global deaths caused by non-communicable diseases. The cancer cells are known to interact with the surrounding non-cancerous... (Review)
Review
Cancer is the second leading contributor to global deaths caused by non-communicable diseases. The cancer cells are known to interact with the surrounding non-cancerous cells, including the immune cells and stromal cells, within the tumor microenvironment (TME) to modulate the tumor progression, metastasis and resistance. Currently, chemotherapy and radiotherapy are the standard treatments for cancers. However, these treatments cause a significant number of side effects, as they damage both the cancer cells and the actively dividing normal cells indiscriminately. Hence, a new generation of immunotherapy using natural killer (NK) cells, cytotoxic CD8 T-lymphocytes or macrophages was developed to achieve tumor-specific targeting and circumvent the adverse effects. However, the progression of cell-based immunotherapy is hindered by the combined action of TME and TD-EVs, which render the cancer cells less immunogenic. Recently, there has been an increase in interest in using immune cell derivatives to treat cancers. One of the highly potential immune cell derivatives is the NK cell-derived EVs (NK-EVs). As an acellular product, NK-EVs are resistant to the influence of TME and TD-EVs, and can be designed for "off-the-shelf" use. In this systematic review, we examine the safety and efficacy of NK-EVs to treat various cancers in vitro and in vivo.
Topics: Humans; Neoplasms; Extracellular Vesicles; Killer Cells, Natural; T-Lymphocytes; Immunotherapy; Tumor Microenvironment
PubMed: 36835438
DOI: 10.3390/ijms24044026 -
Frontiers in Immunology 2023Glutamate, as one of the most important carbon sources in the TCA cycle, is central in metabolic processes that will subsequently influence tumor progression. Several... (Review)
Review
Glutamate, as one of the most important carbon sources in the TCA cycle, is central in metabolic processes that will subsequently influence tumor progression. Several factors can affect the expression of glutamate receptors, playing either a tumor-promoting or tumor-suppressor role in cancer. Thus, the activation of glutamate receptors by the ligand could play a role in tumor development as ample studies have demonstrated the expression of glutamate receptors in a broad range of tumor cells. Glutamate and its receptors are involved in the regulation of different immune cells' development and function, as suggested by the receptor expression in immune cells. The activation of glutamate receptors can enhance the effectiveness of the effector's T cells, or decrease the cytokine production in immunosuppressive myeloid-derived suppressor cells, increasing the antitumor immune response. These receptors are essential for the interaction between tumor and immune cells within the tumor microenvironment (TME) and the regulation of antitumor immune responses. Although the role of glutamate in the TCA cycle has been well studied, few studies have deeply investigated the role of glutamate receptors in the regulation of cancer and immune cells within the TME. Here, by a systematic review of the available data, we will critically assess the physiopathological relevance of glutamate receptors in the regulation of cancer and immune cells in the TME and provide some unifying hypotheses for futures research on the role of glutamate receptors in the immune modulation of the tumor.
Topics: Humans; Tumor Microenvironment; Neoplasms; T-Lymphocytes; Glutamic Acid; Receptors, Glutamate
PubMed: 36817470
DOI: 10.3389/fimmu.2023.1123841