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Background Most previous studies compared the risk for non-melanoma skin cancer (NMSC) in biologic-treated common inflammatory diseases with the general population. Whether the increased NMSC risk is caused by the disease itself, the biologics, or both remains unknown. Methods We systematically searched PubMed, Embase, Medline, Web of Science, and Cochrane Library from inception to May 2021. Studies were included if they assessed the risk of NMSC for rheumatoid arthritis (RA), inflammatory bowel disease (IBD), or psoriasis patients treated with biologics compared with patients not receiving biologics. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using the fixed- or random-effects model. Results The current meta-analysis included 12 studies. Compared with patients with the inflammatory disease without biologics, patients receiving biological therapy were associated with an increased risk for NMSC (RR 1.25, 95% CI 1.14 to 1.37), especially in patients with RA (RR 1.24, 95% CI 1.13 to 1.36) and psoriasis (RR 1.28, 95% CI 1.07 to 1.52), but not in patients with IBD (RR 1.49, 95% CI 0.46 to 4.91). The risks for squamous cell skin cancer and basal cell skin cancer were both increased for patients receiving biologics. However, the risk of NMSC did not increase in patients treated with biologics less than 2 years. Conclusions Current evidence suggests that increased risk of NMSC was identified in RA and psoriasis treated with biologics compared with patients not receiving biologics, but not in patients with IBD. The inner cause for the increased risk of NMSC in IBD patients should be further discussed.

Background and Aim Accumulating evidence indicates a plausible association between inflammatory bowel diseases and the risk of adverse health outcomes. However, the conclusions are inconsistent. We aimed to perform an umbrella review of meta-analyses to appraise and grade the evidence of the association between inflammatory bowel diseases and the risk of adverse health outcomes. Methods Meta-analyses of observational studies that examined the associations between inflammatory bowel disease and the risk of adverse health outcomes in PubMed, EMBASE, and Web of Science were screened. Results This umbrella review identified 25 meta-analyses, which yielded 123 effect estimates for 60 unique putative health outcomes. Patients with inflammatory bowel diseases had a higher risk of adverse health outcomes, including multiple cancers, cardiovascular disease, adverse pregnancy outcomes, adverse oral outcomes, and other adverse events. Moreover, inflammatory bowel diseases caused greater harm to health based on the presented evidence. However, none of the evidence was classified as “high” quality, only 15% was classified as “moderate,” and 65% of outcomes were rated as “very low.” Conclusion Patients with inflammatory bowel diseases had a higher risk of adverse health outcomes and further studies should be conducted to draw firmer conclusions.

The purpose of this meta-analysis was to assess the associations between inflammatory bowel disease (IBD) and risk of the gastric, small bowel and colorectal cancer. We searched the PubMed and Web of Science for observational studies published before June 2020, and the quality of each included study was evaluated according to the Newcastle–Ottawa–Scale. Twenty-six studies comprising 531 449 IBD patients and more than 65 million reference individuals were included. Although IBD was significantly associated with 67% increased risk of the total gastric, small bowel and colorectal cancer. After stratifying by cancer location, IBD mainly increased the risk of intestinal cancer instead of gastric cancer. Furthermore, Crohn’s disease (CD) significantly increased the risk of both small bowel cancer and colorectal cancer, while ulcerative colitis (UC) only increased the risk of colorectal cancer. In subgroup analysis, associations between IBD and risk of total gastric, small bowel and colorectal cancer were similar between male and female, except for that male IBD patients but not female had a significantly higher risk of small bowel cancer. Additionally, IBD patients in different geographical areas had different associations with risk of various gastrointestinal tract cancers. IBD is mainly associated with increased risk of cancers in the lower gastrointestinal tract, including small bowel cancer and colorectal cancer. Because studies about the association between IBD and risk of gastric cancer and the populations in Asia are limited, more observational studies are required in the future.

Objective The purpose of this umbrella review was to assess the associations between sarcopenia and adverse health‐related outcomes. Design An umbrella review of meta‐analyses of observational studies. Setting and Participants Patients with sarcopenia and controls without sarcopenia were included. Measures The PubMed, Web of Science and Embase were searched for relevant systematic review and meta‐analysis. AMSTAR and GRADE system were used for methodological quality and evidence quality assessments, respectively. Results Totally 54 outcomes extracted from 30 meta‐analyses were analyzed. Twenty out of 21 prognostic outcomes indicated that sarcopenia was significantly associated with poorer prognosis of gastric cancer, hepatocellular cancer, urothelial cancer, head and neck cancer, hematological malignancy, pancreatic cancer, breast cancer, colorectal cancer, lung cancer, esophageal cancer, and ovarian cancer. Besides, 10 out of 16 postoperative outcomes suggested that sarcopenia significantly increased the risk of multiple postoperative complications and prolonged the length of hospitalization of patients with digestive cancer. In age‐related outcomes, sarcopenia significantly increased the risk of dysphagia, cognitive impairment, fractures, falls, hospitalization, and all‐cause mortality of elderly populations. Moreover, sarcopenia was also associated with higher level of albuminuria, risk of depression, and several metabolic diseases. Conclusions and Implications Sarcopenia significantly affected a wide range of adverse health‐related outcomes, particularly in patients of tumor and elderly populations. Because evidences of most outcomes were rated as “low” and “very low,” more prospective cohort studies are required in the future., Sarcopenia significantly affected a wide range of adverse health‐related outcomes, particularly in patients of tumor and elderly populations. Besides, associations between sarcopenia and risk of metabolic diseases, depression and albuminuria were also noticeable.

Background Fish contains a variety of essential nutrients, which may contribute to multiple health benefits in humans. Conversely, it also may contain contaminants, resulting in confusion over the health impact of fish consumption. Scope and approach To assess the strength and validity of associations between fish intake and multiple health outcomes. We performed an umbrella review of systematic reviews and meta-analyses in humans. Key findings and conclusions: Of the 55 unique outcomes in the identified 89 systematic reviews and meta-analyses, fish consumption did more benefit than harm for a variety of health outcomes with largest risk reduction at 2 to 4 servings per week. Dose-response analyses revealed that every 20 g/d (approximately one serving/week) increment could decrease 2%–7% risk of coronary heart disease mortality, cardiovascular disease mortality, all-cause mortality, stroke, myocardial infarction, acute coronary syndrome, heart failure, gastrointestinal cancer, metabolic syndrome, dementia and Alzheimer's disease. Beneficial associations were also found for cancers, atopic, musculoskeletal, gastrointestinal and ophthalmologic outcomes. Caution is warranted for potential allergy or contamination when advising during pregnancy and young children. Fish intake appears generally safe in this umbrella review with largest risk reduction for a range of health outcomes at two to four servings per week, and seems more beneficial than harmful. High-quality prospective studies are needed.

Observational studies have reported an association between metabolic syndrome (MetS) and colorectal cancer risk with inconsistent risk estimates. We conducted this meta-analysis to evaluate the risk of colorectal cancer in individuals with MetS. PubMed, Embase, and Web of Science were searched for related studies from database inception to 21 January 2021. Risk estimates for colorectal cancer were extracted from individual articles and pooled using a fixed-effect or random-effect model according to the heterogeneity. MetS was significantly associated with a higher risk of colorectal cancer in both sexes (relative risk [RR] 1.36, 95% confidence interval [CI] 1.26–1.47, P

Previously, our meta‐analysis and other studies have suggested that allium vegetable consumption is beneficial for health, but no umbrella review has been conducted to assess the evidence of the various health benefits of allium vegetable consumption. Therefore, we conducted this umbrella review on this topic. This umbrella review included a total of 16 meta‐analyses with 50 unique outcomes. The most beneficial cancer‐related outcome was shown for gastric cancer (risk ratio 0.78; 95% confidence interval [CI] 0.67–0.91). In addition, only 8 weeks of garlic consumption significantly decreased serum total cholesterol (weighted mean differences −17.20 mg/dl; 95% CI −23.10 to −11.30), and patients with dyslipidemia who consumed garlic experienced more benefits than the whole population. Diabetic patients with longer durations of garlic intake experienced more benefits in terms of fasting blood glucose (FBG), HbA1c, and serum fructosamine than healthy participants, and garlic intake was associated with blood pressure reduction in hypertensive patients but not in normotensive participants. Limited side effects of garlic, such as garlic odor and gastrointestinal complaints, were reported among the included meta‐analyses. Our results suggested that allium vegetables might be beneficial for cancer prevention. In particular, garlic was comparatively safe and is recommended as a long‐term dietary component for patients with dyslipidemia, diabetes, and hypertension.

Green leafy vegetables (GLVs) are a key element of healthy eating patterns and are an important source of lutein. To clarify the evidence for associations between GLVs and lutein intake and multiple health outcomes, we performed a review. A total of 24 meta-analyses with 29 health outcomes were identified by eligibility criteria. Dose-response analyses revealed that, per 100 g/d GLV intake was associated with a decreased risk (ca. 25%) of all-cause mortality, coronary heart disease and stroke. Beneficial effects of GLV intake were found for cardiovascular disease and bladder and oral cancer. Dietary lutein intake was inversely associated with age-related macular degeneration, age-related cataracts, coronary heart disease, stroke, oesophageal cancer, non-Hodgkin lymphoma, metabolic syndrome, and amyotrophic lateral sclerosis. Caution was warranted for contamination with potentially pathogenic organisms, specifically Escherichia coli. GLV consumption and lutein intake therein are generally safe and beneficial for multiple health outcomes in humans.

The efficacy of PD-1/PD-L1 blockades is heterogeneous in different molecular subtypes of gastric cancer (GC). In this study, we analyzed relevant clinical trials to identify the molecular subtypes associated with the efficacy of PD-1/PD-L1 blockades, and public datasets, patient samples, and GC cell lines were used for investigating potential mechanisms. We found that GC with EBV-positive, MSI-H/dMMR, TMB-H or PIK3CA mutant subtype had enhanced efficacy of PD-L1/PD-1 blockades. Also, differentially expressed genes of these molecular subtypes shared the same gene signature and functional annotations related to immunity. Meanwhile, CIBERSORT identified that the overlapping landscapes of tumor-infiltrating immune cells in the four molecular subtypes were mainly M1-like macrophages (M1). The relationships between M1 and clinical characteristics, M1, and gene signatures associated with PD-1/PD-L1 blockades also revealed that M1 was associated with improved prognosis and required for the efficacy of PD-L1/PD-1 blockades in GC. We identified that tumor-infiltrating CD68+CD163− macrophages could represent M1 calculated by CIBERSORT in clinical application, and CXCL9, 10, 11/CXCR3 axis was involved in the mechanism of CD68+CD163− macrophages in the enhanced efficacy of PD-L1/PD-1 blockades. In conclusion, CD68+CD163− macrophages are required for the efficacy of PD-L1/PD-1 blockades and expand the applicable candidates in GC patients without the molecular subtypes.

Background: Cancer-associated cachexia is characterized by ongoing loss of skeletal muscle and has a high incidence in gastric cancer. Although studies have focused on the effect of inflammatory cytokines on skeletal muscle loss, it is not clear whether inflammatory cytokines affect other physiological functions, particularly immunity in gastric cancer. Thus, we aim to investigate the relationships between circulating TNF-α, skeletal muscle and peripheral immune status in gastric cancer.Methods: Totally 392 gastric cancer patients in cohort A and 60 gastric cancer patients in cohort B were selected from the prospective cohort study NCT03115931 and ChiCTR1900026578 in West China Hospital, Sichuan University, respectively. Besides, human skeletal muscle myoblasts (HSMMs) and peripheral CD8+ T cells completed about 7 to 9 days successive TNF-α intervention with different concentrations. Results: From data in cohort A, multivariate analysis showed that preoperative weight loss ≥5% was associated with circulating TNF-α (P =0.001) and TNM stage (P =0.002). ROC curve indicated that cut-off point of 9.96 pg/ml for circulating TNF-α was an important warning of weight loss ≥5% in patient with gastric cancer. Before surgery, high circulating TNF-α (≥ 9.96 pg/ml) was associated with significantly lower body weight, skeletal muscle mass and handgrip strength but not fat mass. After radical surgery, high circulating TNF-α was also associated with significantly more loss of body weight and skeletal muscle mass instead of fat mass. In cohort B and vitro experiments, immunohistochemistry, western blot and flow cytometry identified that high TNF-α led to myofiber change, decreased expression of AMP-dependent protein kinase (AMPK) and phosphate-AMPK in skeletal muscle and increased myoblast apoptosis. Flow cytometry found that circulating TNF-α was not correlated with PD-1, LAG-3, TIM-3 and TIGIT expressed on peripheral CD8+ T cells, and TNF-α not only promoted the proliferation of CD8+ T cells but also increased their apoptosis ratio at higher concentration.Conclusions: In our study, we found that TNF-α could result in myofiber change, interfered glycometabolism of skeletal muscle, whereas promoted the proliferation of CD8+ T cells in gastric cancer during cachexia, and preoperative circulating TNF-α of more than 9.96 pg/ml could indicate a high risk of weight loss.

Lycopene is a potent lipophilic antioxidant in tomato. We aim to clarify the evidence for associations between tomato and lycopene and multiple health outcomes. Umbrella review of meta-analyses and systematic reviews was performed in humans. A total of 174 articles were searched, 17 articles with 20 health outcomes were identified by eligibility criteria. Tomato intake was inversely associated with all-cause mortality, coronary heart disease mortality, cerebrovascular disease mortality, prostate cancer, and gastric cancer. Dietary lycopene intake or serum lycopene was inversely associated with all-cause mortality, prostate cancer, stroke, cardiovascular disease, metabolic syndrome, and male infertility. Caution was warranted for potential allergy and pollution. The quality of the vast majority of evidence by GRADE was low or very low with the remaining six as moderate. The intake of tomato or lycopene was generally safe and beneficial for multiple health outcomes in humans. But the quality of the evidence was not high.

We read with interest the study by Axelrad et al 1 which reported that Crohn’s disease (CD) and UC were associated with nearly ninefold and twofold increased risk of small bowel cancer (SBC), respectively. However, there were also two observational studies2 3 suggesting that UC was not associated with risk of SBC. Because epidemiological studies about IBD and risk of SBC were controversial, to better understand this issue, we conducted this meta-analysis. We searched the PubMed and Web of Science for relevant studies published before 1 June 2020. We included observational studies investigating the associations between IBD and risk of SBC (including adenocarcinoma, neuroendocrine tumour and sarcoma) and reporting the HR, OR or other measures of association. The pooled OR and 95% CIs were estimated with random-effect model when the significant …

We read with interest the study by Zhang et al 1 which investigated the associations between oral antibiotic use and risk of colorectal cancer (CRC). The study included 166 057 participants and found that antibiotic use was associated with an increased risk of colon cancer but a reduced risk of rectal cancer. We also noticed another study by Armstrong et al 2 reporting that patients prescribed antibiotics in up to 15 years preceding diagnosis were associated with a higher risk of CRC. However, the study by Armstrong et al did not analyse the risk of colon cancer and rectal cancer, respectively. Considering current studies about antibiotic use and risk of CRC were inconsistent, we conducted this meta-analysis. The PubMed and Web of Science were …

We read with interest the study by Cheung et al 1 reporting that long-term use of proton pump inhibitors (PPIs) was associated with an increased risk of gastric cancer (GC) in participants after Helicobacter pylori eradication. Considering PPIs were widely used for the treatment of acid-related disorders, and previous studies about PPIs use and risk of GC did not have a consistent result. To better understand this issue, we conducted this meta-analysis that investigated the associations between long-term PPIs use and risk of GC. We searched the PubMed, Embase and Web of Science for potential studies published before March 2018. …

Scope The aim of this article is to conduct an umbrella review to study the strength and validity of associations between tea consumption and diverse health outcomes. Methods and results Meta-analyses of observational studies examining associations between tea consumption and health outcomes in all human populations and settings are screened. The umbrella review identifies 96 meta-analyses with 40 unique health outcomes. Tea consumption shows greater benefits than harm to health in this review. Dose-response analyses of tea consumption indicates reduced risks of total mortality, cardiac death, coronary artery disease, stroke, and type 2 diabetes mellitus with increment of two to three cups per day. Beneficial associations are also found for several cancers, skeletal, cognitive, and maternal outcomes. Harmful associations are found for esophageal and gastric cancer when the temperature of intake is more than 55-60 °C. Conclusion Tea consumption, except for very hot tea, seems generally safe at usual levels of intake, with summary estimates indicating the largest reduction for diverse health outcomes at two to three cups per day. Generally, tea consumption seems more beneficial than harmful in this umbrella review. Randomized controlled trials are further needed to understand whether the observed associations are causal.

Background: Aspirin has been widely used as treatment for inflammation, pain and cardiovascular events, and recently some studies found that patients of cancer with aspirin use seemed to have longer survival. However, the supporting data varied, and the arguments existed among studies. To better understand this issue, we conducted this systematic review and meta-analysis to investigate whether patients of cancer with aspirin use had longer survival. Methods: This study has been registered in PROSPERO (No· CRD42018102280). We searched the PubMed, Web of Science and Embase for studies about aspirin use and survival of cancer published before May 2018, and the references of related studies were also reviewed. The primary outcomes were cancer-specific survival and overall survival for patients of cancer. In meta-analysis, pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated with random-effects or fixed-effects model according to the heterogeneity which was estimated by Q statistic. Subgroup analysis was performed to identify the associations between aspirin use and survival of different kinds of cancers, and the influences of prediagnosis or postdiagnosis aspirin use and duration of aspirin use were also assessed. For colorectal cancer, we specially assessed the influence of PIK3CA mutation status and prostaglandin-endoperoxide synthase 2 (PTGS2) expression in this study. Findings: Totally 57 observational studies with 17 kinds of cancers and 1274 933 participants were included. Compared with aspirin nonusers, patients of cancer with postdiagnosis aspirin use had both prolonged cancer-specific survival (OR 0·86; 95% CI 0·72-0·99; P heterogeneity

We read with interest the study by Villumsen et al 1 which reported that patients with IBD had a 22% increased risk of Parkinson’s disease (PD) compared with non-IBD individuals. The study supported the theory that intestinal environment could influence the function of central nervous system which was also called the gut–brain axis. Recently, a meta-analysis by Zhu et al 2 suggested that the overall risk of PD in patients with IBD was significantly higher than controls (OR 1.41; 95% CI 1.19 to 1.66). However, only four studies were included in the meta-analysis. We also noticed a case–control study by Camacho-Soto et al 3 reporting that the risk of PD was inversely associated with IBD (OR 0.85; 95% CI 0.80 to 0.91), which was not …