-
Endokrynologia Polska Jun 2024Iron is one of the essential microelements necessary for maintaining the body's homeostasis. It serves various roles, including being a crucial component in the proper...
Iron is one of the essential microelements necessary for maintaining the body's homeostasis. It serves various roles, including being a crucial component in the proper structure of many enzymes and supporting the transport of oxygen and electrons. Its deficiency can lead to anaemia, which is a common clinical condition often associated with thyroid diseases. Iron deficiency is one of the most common nutritional deficiencies, and its prevalence is strongly associated with socioeconomic status. It is the primary cause of anaemia in 42% of children and 50% of women. Importantly, iron deficiency is placed among the top 5 causes of disability in women. Thyroid peroxidase (TPO) is an enzyme essential for the production of thyroid hormones, and iron is a key factor in its proper functioning. Therefore, in the case of iron deficiency, the activity of this enzyme is also reduced. Iron is also a factor that is important in epigenetic modification processes, and its deficiency may contribute to genomic changes potentially promoting the development of autoimmune thyroid diseases. Adequate supplementation in patients with Hashimoto's disease is one of the crucial elements of effective therapy. In addition to iodine, selenium, and magnesium supplementation, attention should be paid to proper iron intake. Iron is an element that is a component of the heme enzyme- thyroid peroxidase, which owes its activity to the binding of haem, and its function is the production of thyroid hormones. Iron can be delivered to the body in haem and non-haem forms. The haem form is found particularly in haemoglobin-rich red meat, but also in eggs, fish, and poultry. On the other hand, non-haem iron can be found in legumes, grains, fruits, and vegetables. Our study aimed to gather and summarise knowledge from scientific literature regarding iron deficiency anaemia and its association with hypothyroidism in women, as well as the possible mechanisms and pathogenesis of these conditions. The paper also aims to highlight that considering the high risk of iron deficiency, assessing iron status along with ferritin should be an integral part of additional diagnostic measures in cases of hypothyroidism, particularly Hashimoto's disease.
PubMed: 38923898
DOI: 10.5603/ep.97860 -
Medicine Jun 2024Moderate red wine (RW) consumption is associated with a low risk of cardiovascular disease (CVD). However, few studies have evaluated the effects of RW and white wine... (Meta-Analysis)
Meta-Analysis
Red wine alleviates atherosclerosis-related inflammatory markers in healthy subjects rather than in high cardiovascular risk subjects: A systematic review and meta-analysis.
BACKGROUND
Moderate red wine (RW) consumption is associated with a low risk of cardiovascular disease (CVD). However, few studies have evaluated the effects of RW and white wine (WW) on inflammatory markers related to atherosclerosis in healthy individuals and high-risk subjects for CVD. This study aimed to assess the effect of RW on inflammatory markers in healthy individuals and high-risk subjects for CVD compared with moderate alcohol consumption.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA) was followed in this study. The PubMed, Embase, Cochrane, Web of Science, SinoMed, EbscoHost, and ScienceDirect databases were searched. The risk of bias and quality of the included trials were assessed using the Cochrane Handbook. The main results are summarized in Stata 12.
RESULTS
Twelve studies were included in the meta-analysis. The results demonstrated that RW significantly decreased circulating intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor-alpha (TNF-α), lymphocyte function-associated antigen-1, and Sialyl-Lewis X expression on the surface of monocytes in healthy subjects, but not in patients with CVD. Additionally, RW significantly decreased Sialyl-Lewis X but increased clusters of differentiation 40 (CD40) expressed on the surface of T lymphocytes and significantly decreased C-C chemokine receptor type 2 (CCR2) and very late activation antigen 4 (VLA-4) expressed on the surface of monocytes. Interestingly, subgroup analysis also found that RW significantly decreased circulating interleukin-6 (IL-6) in Spain but not in other countries, and significantly increased αMβ2 (Mac-1) in the group that had an intervention duration of less than 3 weeks.
CONCLUSIONS
Moderate consumption of RW is more effective than WW in alleviating atherosclerosis-related inflammatory markers in healthy people rather than high-risk subjects for CVD, but this needs to be further confirmed by studies with larger sample sizes.
Topics: Humans; Wine; Atherosclerosis; Biomarkers; Inflammation; Cardiovascular Diseases; Healthy Volunteers; Heart Disease Risk Factors
PubMed: 38847707
DOI: 10.1097/MD.0000000000038229 -
European Journal of Cancer (Oxford,... May 2024Cancer patients with autoimmune disease have been excluded from randomized trials of immune checkpoint blockers (ICBs). We conducted a systematic review of observational... (Review)
Review
A systematic review and meta-analysis of observational studies and uncontrolled trials reporting on the use of checkpoint blockers in patients with cancer and pre-existing autoimmune disease.
BACKGROUND
Cancer patients with autoimmune disease have been excluded from randomized trials of immune checkpoint blockers (ICBs). We conducted a systematic review of observational studies and uncontrolled trials including cancer patients with pre-existing autoimmune disease who received ICBs.
METHODS
We searched 5 electronic databases through November 2023. Study selection, data collection, and quality assessment were performed independently by 2 investigators. We performed a meta-analysis to pool incidence of immune-related adverse events (irAEs), including de novo events and flares of existing autoimmune disease, hospitalizations due to irAEs, as well as deaths.
RESULTS
A total of 95 studies were included (23,897 patients with cancer and preexisting autoimmune disease). The most common cancer evaluated was lung cancer (30.7 %) followed by skin cancer (15.7 %). Patients with autoimmune disease were more likely to report irAEs compared to patients without autoimmune disease (relative risk 1.3, 95 % CI 1.0 to 1.6). The pooled occurrence rate of any irAEs (flares or de novo) was 61 % (95 % CI 54 % to 68 %); that of flares was 36 % (95 % CI 30 % to 43 %), and that of de novo irAEs was 23 % (95 % CI 16 % to 30 %). Flares were mild (grade <3) in half of cases and more commonly reported in patients with psoriasis/psoriatic arthritis (39 %), inflammatory bowel disease (37 %), and rheumatoid arthritis (36 %). 32 % of the patients with irAEs required hospitalization and treatment of irAEs included corticosteroids in 72 % of the cases. The irAEs mortality rate was 0.07 %. There were no statistically significant differences in cancer response to ICBs between patients with and without autoimmune disease.
CONCLUSIONS
Although more patients with pre-existing autoimmune disease had irAEs, these were mild and managed with corticosteroids in most cases, with no impact on cancer response. These results suggest that ICBs can be used in these patients, but careful monitoring is required, as over a third of the patients will experience a flare of their autoimmune disease and/or require hospitalization. These findings provide a crucial foundation for oncologists to refine their monitoring and management strategies, ensuring that the benefits of ICB therapy are maximized while minimizing its risks.
PubMed: 38834015
DOI: 10.1016/j.ejca.2024.114148 -
Molecular Psychiatry May 2024Previous meta-analyses have documented the association of immune-inflammatory pathways with the pathophysiology of Major Depressive Episode (MDE), as reflected by...
Previous meta-analyses have documented the association of immune-inflammatory pathways with the pathophysiology of Major Depressive Episode (MDE), as reflected by alterations in peripheral blood immune cell counts. However, it remains unclear whether these immunological changes are distinct in individuals experiencing suicidal ideation (SI) or suicidal behavior (SB), beyond the context of an MDE. This systematic review and meta-analysis aimed to examine peripheral immune cell profiles across samples with SI/SB and compare them to healthy controls or patients with MDE. A systematic literature search was conducted in MEDLINE, Embase, and PsycINFO for articles published from inception until June 12, 2023. Two independent reviewers screened the articles for inclusion, extracted data, and assessed the risk of bias using the Newcastle-Ottawa scale. Meta-analyses were performed using a random-effects model to calculate standardized mean differences (SMDs) and 95% confidence intervals (CIs) for immune cell counts or ratios between groups with and without SI/SB. Heterogeneity across studies was assessed using the restricted maximum-likelihood estimator for tau statistic and I-statistic and tested by the Q test. Publication bias was evaluated using the Egger´s test and funnel plots. Meta-regression analyses were conducted to explore the potential moderating effects of age, gender, current or lifetime SI/SB, and the type of self-harming behavior (SI or SB). The study was registered with PROSPERO (CRD42023433089). The systematic review included 30 studies, with data from 19 studies included in the meta-analyses comprising 139 unique comparisons. Eleven different cell populations or ratios were included, comprising 1973 individuals with SI/SB and 5537 comparison subjects. White blood cell (WBC) and neutrophil counts were higher in individuals with SI/SB than in controls (WBC: SMD = 0.458; 95% CI = 0.367-0.548; p value ≤ 0.001; I = 0.002% and; Neutrophils: SMD = 0.581; 95% CI = 0.408-0.753; p < 0.001), indicating an inflammatory process. The neutrophil-to-lymphocyte ratio (NLR) emerged as a potential marker, demonstrating a notable elevation in individuals with SI/SB (SMD = 0.695; 95% CI = 0.054-1.335; p value = 0.033; I = 94.281%; Q test p value ≤ 0.001). The elevated NLR appears to be primarily driven by the increase in neutrophil counts, as no significant differences were found in lymphocyte counts between groups. Comparisons among participants with and without SI/SB and depression revealed similar trends with increased NLR, monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) observed in depressed individuals with SI/SB compared to those without SI/SB. Broad alteration in the peripheral immune cell populations and their ratios were observed in individuals with SI/SB, indicating an immune activation or dysfunction. Notably, these immunological changes were also evident when comparing MDE individuals with and without SI/SB, suggesting that such immune dysfunction associated with suicidality cannot be solely attributed to or explained by depressive symptoms. The NLR, MLR, and PLR ratios, in combination with novel immune cellular and protein biomarkers, open new avenues in understanding the immunological underpinnings of SI/SB. These findings highlight the potential utility of immune markers as part of a multi-modal approach for risk stratification and therapeutic monitoring in SI/SB.
PubMed: 38802507
DOI: 10.1038/s41380-024-02587-5 -
Frontiers in Immunology 2024Currently, therapies such as chimeric antigen receptor-T Cell (CAR-T) and immune checkpoint inhibitors like programmed cell death protein-1 (PD-1) blockers are showing...
Currently, therapies such as chimeric antigen receptor-T Cell (CAR-T) and immune checkpoint inhibitors like programmed cell death protein-1 (PD-1) blockers are showing promising results for numerous cancer patients. However, significant advancements are required before CAR-T therapies become readily available as off-the-shelf treatments, particularly for solid tumors and lymphomas. In this review, we have systematically analyzed the combination therapy involving engineered CAR-T cells and anti PD-1 agents. This approach aims at overcoming the limitations of current treatments and offers potential advantages such as enhanced tumor inhibition, alleviated T-cell exhaustion, heightened T-cell activation, and minimized toxicity. The integration of CAR-T therapy, which targets tumor-associated antigens, with PD-1 blockade augments T-cell function and mitigates immune suppression within the tumor microenvironment. To assess the impact of combination therapy on various tumors and lymphomas, we categorized them based on six major tumor-associated antigens: mesothelin, disialoganglioside GD-2, CD-19, CD-22, CD-133, and CD-30, which are present in different tumor types. We evaluated the efficacy, complete and partial responses, and progression-free survival in both pre-clinical and clinical models. Additionally, we discussed potential implications, including the feasibility of combination immunotherapies, emphasizing the importance of ongoing research to optimize treatment strategies and improve outcomes for cancer patients. Overall, we believe combining CAR-T therapy with PD-1 blockade holds promise for the next generation of cancer immunotherapy.
Topics: Humans; Programmed Cell Death 1 Receptor; Immunotherapy, Adoptive; Lymphoma; Immune Checkpoint Inhibitors; Receptors, Chimeric Antigen; Animals; Neoplasms; Combined Modality Therapy; Tumor Microenvironment; Antigens, Neoplasm; T-Lymphocytes
PubMed: 38799440
DOI: 10.3389/fimmu.2024.1389971 -
Journal of Gastrointestinal Cancer May 2024Pembrolizumab is associated with the development of gastritis, but its clinical features have not been characterized. To explore the clinical features of pembrolizumab...
BACKGROUND
Pembrolizumab is associated with the development of gastritis, but its clinical features have not been characterized. To explore the clinical features of pembrolizumab induced gastritis and provide reference for the prevention and treatment of gastritis.
METHODS
Case reports and case series related to pembrolizumab induced gastritis were retrospectively analyzed by searching the database from inception to September 30, 2023.
RESULTS
Thirty-nine patients with gastritis entered the study with a median age of 63 years (range 34, 81). The median time to gastritis was 11.1 months (range 0.3, 60) and 7 cycles (range 1, 27) after administration. Epigastric pain (24 cases, 61.5%), nausea (17 cases, 43.6%), and vomiting (16 cases, 41.0%) were the most frequently complained symptoms. Esophagogastroduodenoscopy mainly showed erythematous (16 cases, 41.0%), hemorrhage (14 cases, 35.9%) and erosions (11 cases, 28.2%). Gastric mucosal biopsy shows chronic active gastritis with lymphocytic infiltration. These patients' symptoms and gastric mucosa improved or recovered after receiving systemic steroid and proton pump inhibitor therapy regardless of whether pembrolizumab was discontinued. These patients' symptoms and gastric mucosa improved or recovered after treatment with systemic steroids, proton pump inhibitors, and biological agents.
CONCLUSIONS
Gastritis is an extremely rare adverse effect of pembrolizumab. When patients receiving pembrolizumab complain of abdominal symptoms, endoscopy, tissue biopsy, and immunohistochemical staining should be actively performed for early identification and diagnosis of gastritis.
PubMed: 38787493
DOI: 10.1007/s12029-024-01067-x -
PloS One 2024The objective of this study was to evaluate the relationship between the platelet-to-lymphocyte ratio (PLR) and systemic lupus erythematosus (SLE). Additionally, the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The objective of this study was to evaluate the relationship between the platelet-to-lymphocyte ratio (PLR) and systemic lupus erythematosus (SLE). Additionally, the study aimed to establish an association between PLR and SLE disease activity, specifically lupus nephritis (LN).
METHODS
We conducted a comprehensive search across Medline, Embase, and Cochrane databases to identify relevant articles. Subsequently, we performed meta-analyses to compare PLR between SLE patients and controls, as well as active and inactive SLE cases, along with LN and non-LN groups. Furthermore, a meta-analysis was conducted on correlation coefficients between PLR and various parameters in SLE patients, including the SLE Disease Activity Index (SLEDAI), C3, C4, anti-dsDNA, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP).
RESULTS
In total, fifteen studies comprising 1,522 SLE patients and 1,424 controls were eligible for inclusion. The meta-analysis demonstrated a significant elevation of PLR in the SLE group compared to the control group (Standardized Mean Difference [SMD] = 0.604, 95% Confidence Interval [CI] = 0.299-0.909, p < 0.001). Upon stratification by ethnicity, an elevated PLR was observed in the SLE group among both Asian and Arab populations. Subgroup analysis based on sample size revealed consistently higher PLR in both small (n < 200) and large sample (n ≥ 200) SLE groups. Moreover, when considering disease activity, there was a noteworthy trend of increased PLR in the active disease group compared to the inactive group (SMD = 0.553, 95% CI = 0.000-1.106, p = 0.050). However, the meta-analysis did not demonstrate a significant distinction in PLR between the LN and non-LN groups. Notably, a positive association was established between PLR and SLEDAI (correlation coefficient = 0.325, 95% CI = 0.176-0.459, p < 0.001). Furthermore, PLR exhibited positive correlations with ESR, CRP, proteinuria, C3, and anti-dsDNA antibody levels.
CONCLUSIONS
The outcomes of this meta-analysis underscored the elevated PLR in SLE patients, suggesting its potential as a biomarker for gauging systemic inflammation in SLE. Additionally, PLR exhibited correlations with SLEDAI, as well as with key indicators such as ESR, CRP, proteinuria, C3, and anti-dsDNA antibody levels.
Topics: Humans; Lupus Erythematosus, Systemic; Biomarkers; Lymphocytes; Blood Platelets; Inflammation; Blood Sedimentation; Platelet Count; C-Reactive Protein; Lupus Nephritis; Lymphocyte Count
PubMed: 38753735
DOI: 10.1371/journal.pone.0303665 -
BioMed Research International 2024Many COVID-19 patients display adverse symptoms, such as reduced physical ability, poor quality of life, and impaired pulmonary function. Therefore, this systematic...
INTRODUCTION
Many COVID-19 patients display adverse symptoms, such as reduced physical ability, poor quality of life, and impaired pulmonary function. Therefore, this systematic review is aimed at evaluating the effectiveness of physical exercise on various psychophysiological indicators among COVID-19 patients who may be at any stage of their illness (i.e., critically ill, hospitalized, postdischarge, and recovering).
METHODS
A systematic search was conducted in PubMed, Scopus, ScienceDirect, Web of Science, and Google Scholar from 2019 to 2021. Twenty-seven studies, which assessed a total of 1525 patients, were included and analysed.
RESULTS
Overall, data revealed significant improvements in the following parameters: physical function, dyspnoea, pulmonary function, quality of life (QOL), lower limb endurance and strength, anxiety, depression, physical activity level, muscle strength, oxygen saturation, fatigue, C-reactive protein (CRP), interleukin 6 (IL-6), tumour necrosis factor-alpha (TNF-), lymphocyte, leukocytes, and a fibrin degradation product (D-dimer).
CONCLUSIONS
Physical training turns out to be an effective therapy that minimises the severity of COVID-19 in the intervention group compared to the standard treatment. Therefore, physical training could be incorporated into conventional treatment of COVID-19 patients. More randomized controlled studies with follow-up evaluations are required to evaluate the long-term advantages of physical training. Future research is essential to establish the optimal exercise intensity level and assess the musculoskeletal fitness of recovered COVID-19 patients. This trial is registered with CRD42021283087.
Topics: Humans; Adaptation, Physiological; Anxiety; COVID-19; Exercise; Exercise Therapy; Muscle Strength; Quality of Life; SARS-CoV-2
PubMed: 38726292
DOI: 10.1155/2024/3325321 -
Cureus Mar 2024Advanced pancreatic cancer is one of the prominent contributors to cancer-related mortality globally. Chemotherapy, especially gemcitabine, is generally used for the... (Review)
Review
Advanced pancreatic cancer is one of the prominent contributors to cancer-related mortality globally. Chemotherapy, especially gemcitabine, is generally used for the treatment of advanced pancreatic cancer. Despite the treatment, the fatality rate for advanced pancreatic cancer is alarmingly high. Thus, the dire need for better treatment alternatives has drawn focus to cancer vaccinations. The Wilms tumor gene (WT1), typically associated with Wilms tumor, is found to be excessively expressed in some cancers, such as pancreatic cancer. This characteristic feature is harvested to develop cancer vaccines against WT1. This review aims to systematically summarize the clinical trials investigating the efficacy and safety of WT1 vaccines in patients with advanced pancreatic cancer. An extensive literature search was conducted on databases Medline, Web of Science, ScienceDirect, and Google Scholar using the keywords "Advanced pancreatic cancer," "Cancer vaccines," "WT1 vaccines," and "Pulsed DC vaccines," and the results were exclusively studied to construct this review. WT1 vaccines work by introducing peptides from the WT1 protein to trigger an immune response involving cytotoxic T lymphocytes via antigen-presenting cells. Upon activation, these lymphocytes induce apoptosis in cancer cells by specifically targeting those with increased WT1 levels. WT1 vaccinations, which are usually given in addition to chemotherapy, have demonstrated clinically positive results and minimal side effects. However, there are several challenges to their widespread use, such as the immunosuppressive nature of tumors and heterogeneity in expression. Despite these limitations, the risk-benefit profile of cancer vaccines is encouraging, especially for the WT1 vaccine in the treatment of advanced pancreatic cancer. Considering the fledgling status of their development, large multicentric, variables-matched, extensive analysis across diverse demographics is considered essential.
PubMed: 38665761
DOI: 10.7759/cureus.56934 -
Clinical Nutrition (Edinburgh, Scotland) Jun 2024Dysbiosis is emerging as a potential trigger of systemic lupus erythematosus (SLE). Group 3 innate lymphoid cells (ILC3s) are recognised as key regulators of intestinal... (Review)
Review
BACKGROUND AND AIMS
Dysbiosis is emerging as a potential trigger of systemic lupus erythematosus (SLE). Group 3 innate lymphoid cells (ILC3s) are recognised as key regulators of intestinal homeostasis. The aryl hydrocarbon receptor (AhR) is critical to intestinal ILC3 development and function. This mechanistic review aimed to investigate whether AhR activation of gut ILC3s facilitates IL-22-mediated antimicrobial peptide (AMP) production to enhance colonisation resistance and ameliorate SLE pathology associated with intestinal dysbiosis. Furthermore, nutritional AhR ligand potential to enhance pathogen resistance was explored.
METHODOLOGY
This mechanistic review involved a three-tranche systematic literature search (review, mechanism, intervention) using PubMed with critical appraisal. Data was synthesised into themes and summarised in a narrative analysis.
RESULTS
Preclinical mechanistic data indicate that AhR modulation of intestinal ILC3s optimises pathogen resistance via IL-22-derived AMPs. Pre-clinical research is required to validate this mechanism in SLE. Data on systemic immune consequences of AhR modulation in lupus suggest UVB-activated ligands induce aberrant AhR signalling while many dietary ligands exert beneficial effects. Data on xenobiotic-origin ligands is varied, although considerable evidence has demonstrated negative effects on Th17 to Treg balance. Limited human evidence supports the role of nutritional AhR ligands in modulating SLE pathology. Preclinical and clinical data support anti-inflammatory effects of dietary AhR ligands.
CONCLUSION
Current evidence is insufficient to fully validate the hypothesis that AhR modulation of intestinal ILC3s can enhance pathogen resistance to ameliorate lupus pathology driven by dysbiosis. However, anti-inflammatory effects of dietary AhR ligands suggest a promising role as a therapeutic intervention for SLE.
Topics: Receptors, Aryl Hydrocarbon; Humans; Lupus Erythematosus, Systemic; Dysbiosis; Lymphocytes; Gastrointestinal Microbiome; Ligands; Animals; Immunity, Innate; Interleukin-22; Interleukins; Intestines; Antimicrobial Peptides
PubMed: 38631087
DOI: 10.1016/j.clnu.2024.04.008