Combined Odds Ratio Research Articles

Has the degree of outcome reporting bias in surgical randomized trials changed? A meta-regression analysis.

Outcome reporting bias in individual trials can compromise the validity of pooled estimates within systematic reviews. Recent strategies have attempted to address outcome reporting bias, which favours the full reporting of statistically significant outcomes over non-significant outcomes. We examined whether the association between full outcome reporting and statistical significance in surgical trials has changed from 2009 to 2019. We systematically searched for 350 surgical randomized controlled trials (RCTs) from 2009 and 350 surgical RCTs from 2019. Outcomes were classified as fully reported, partially reported, qualitatively reported or unreported. For each outcome, a contingency table was populated with full outcome reporting (yes/no) and statistical significance (yes/no). We combined odds ratios in random effects meta-analysis to estimate the association between full outcome reporting and statistical significance in 2009 compared with 2019. Twenty-eight percent of outcomes in 2009 were incompletely reported, compared with 30% in 2019. In 2009, significant outcomes were more likely to be fully reported than non-significant outcomes (OR=2.4, 95% CI 1.7-3.4, I2 = 35%), but the opposite association was seen in 2019 (OR=0.51, 95% CI 0.34-0.77, I2 = 43%). RCTs from 2019 were less likely to demonstrate outcome reporting bias favouring significant outcomes (OR=0.21, 95% CI 0.12-0.35, P < 0.001). Outcome reporting bias favouring the full reporting of significant over non-significant outcomes was demonstrated in 2009, but the opposite association was seen in 2019. There remains a high prevalence of incomplete outcome reporting. We recommend ongoing adherence to trial protocol guidelines to improve outcome reporting transparency and completeness.

Risk of Schizophrenia in Patients with Psoriasis: A Systematic Review and Meta‐Analysis

Background. Several studies have shown that psoriasis patients have a higher prevalence rate of schizophrenia, but none has thoroughly examined this association across different ages and genders. Thus, our systematic review and meta‐analysis aims to combine all available evidence and evaluate the risk of schizophrenia in psoriasis patients. Methods. Two independent investigators extracted published studies from PubMed, Embase, Medline, and Web of Science databases from inception until May 2023 and screened 160 articles for eligibility. We included 8 studies in this meta‐analysis. A random‐effects model was employed to estimate the pooled odds ratio (OR) and 95% confidence interval (CI) for schizophrenia in patients with psoriasis. The study protocol is registered with PROSPERO, number CRD42023428576. Results. A total of eight studies with 889,747,79 participants met the eligibility criteria. The pooled OR of psoriasis in patients with schizophrenia versus subjects without schizophrenia was 1.66 (95% CI: [1.20, 2.29]) with a significant level of heterogeneity (I2 = 97%). Specifically, the OR for psoriasis in children with schizophrenia was 12.90 (95% CI: [1.97, 84.64]), with an I2 combined value of 98% and psoriasis in adults with schizophrenia 2.57 (95% CI: [1.44, 4.58]), with an I2 combined value of 61.3%. The combined OR for all age groups was 5.27 (95% CI: [3.02, 9.19]). Additionally, we found that the OR value for psoriasis in females with schizophrenia was 1.74 (95% CI: [1.74, 2.11]), with an I2 combined value of 59%. For male patients, the OR value was 1.58 (95% CI: [1.25, 2.01]), with an I2 combined value of 77%. Conclusions. Our study shows an increased risk of schizophrenia in people with psoriasis. We demonstrated a significantly increased risk of schizophrenia among children with psoriasis and found that females with psoriasis were more likely to have schizophrenia than men with psoriasis under the same conditions.

Metformin use and Occurrence of Hepatocellular Carcinoma in Patients with Type II Diabetes Mellitus: A Systematic Review

Objectives: There is not much clarity on the metformin's preventive effect in hepatocellular carcinoma (HCC). The aim of this study was to determine the association between metformin use and HCC. Materials and Methods: An electronic search was carried on Web of Science, Scopus, and PubMed/MEDLINE, from January 2010 to January 2022, for 12 years. Case–control and cohort studies were part of the eligible studies. Data were extracted by two independent reviewers. The Newcastle–Ottawa scale was used to check the quality of studies. Results: A total of 928 (872 + 56) studies were identified in our search, among which a total of 623 articles were analyzed after removing the duplicates. After the retrieved papers were analyzed for their titles and abstracts, a total of 575 articles were excluded on the basis of inclusion criteria, respectively. Forty-eight full-text articles were assessed for final data extraction, of which 11 articles were selected. The pooled analysis of included studies showed a combined odds ratio of 0.87; 95% confidence interval 0.86–0.89 for the association between HCC and the use of metformin. It was noticed that all the studies found nonmetformin therapy to entail a higher risk of HCC in comparison to therapy with metformin with the funnel plot showing asymmetric distribution, with Egger's test showing P < 0001. Conclusions: Metformin use reduces the HCC development risk, and therefore, it may be used in diabetics for the prevention of HCC.

Appraisal of the causal effect of plasma caffeine on adiposity, type 2 diabetes, and cardiovascular disease: two sample mendelian randomisation study

ObjectiveTo investigate the potential causal effects of long term plasma caffeine concentrations on adiposity, type 2 diabetes, and major cardiovascular diseases.DesignTwo sample mendelian randomisation study.SettingGenome-wide association study summary data for...

Parameters influencing pedestrian injury and severity – A systematic review and meta-analysis

Pedestrians account for 26% of all traffic fatalities worldwide. According to in-depth collision databases, around 3500 variables can affect the outcome of a collision, making it crucial to establish the relationship between each variable and the outcome. To date, there is no method defined to assess these variables' relevance other than a statistical correlation, which can sometimes lead to reasonable conclusions, but only under specific circumstances. This article addresses this issue by first conducting a literature review to determine all relevant variables, followed by developing a variable selection criterion to select crucial variables, and then conducting a meta-analysis to quantify these relationships. Epidemiological studies published between 1990 and 2022 were examined, including 93 papers from 19 different nations that considered 904,655 pedestrian collisions. Of the 204 variables that were extracted from these studies, 152 were examined using the variable selection criterion, and 68 were found to be significant. Of these, 20 were included in the meta-analysis, which combined odds ratios to aggregate the effect of a variable across various studies, thus removing study-specific conclusions. This study makes a compelling argument that using statistical correlation by itself is insufficient to determine a variable's significance. The proposed method is an objective way to distinguish the variables for stakeholders and identify their relevance. This study offers a definitive list of the 15 characteristics that must be present in any pedestrian-to-vehicle collision databases, as well as a list of 53 variables that require additional investigation, allowing for appropriate actions for safer roads.

890: THERAPEUTIC USE OF INHALED CORTICOSTEROIDS IN COVID-19: A SYSTEMATIC REVIEW AND META-ANALYSIS

Introduction: Previous randomized trials suggest the benefit of inhaled budesonide for COVID-19 patients in outpatient settings. We evaluated available studies on the effect of the therapeutic use of inhaled corticosteroids (ICS) on mortality and pertinent clinical outcomes. Methods: A comprehensive literature search was conducted across the WHO, LitCOVID, and EMBASE databases from inception until June 30th, 2022. The primary outcome was overall mortality and secondary outcomes included symptom-based clinical improvement rates at day 14, ER visits or hospitalization, and adverse events. Data analysis was performed using Review Manager Software, version 5.2, to evaluate the combined odds ratio (OR) with 95% confidence intervals (CI) using a random-effects model. Results: Nine studies (7 RCTs (3 budesonide, 3 ciclesonide, 1 fluticasone RCTs), & 2 observational studies) were included in the mortality meta-analysis. Of the 3,934 patients included, 103 patients died (44 out of 1925 in the ICS group and 59 out of 2009 in the non-ICS group). The odds of mortality in the therapeutic ICS use group were lower compared to the non-ICS therapy group (OR 0.78, 95% CI 0.48-1.28, p-value=0.33, I2=0%). The result was statistically insignificant, possibly due to the low mortality rate. But therapeutic ICS showed statistically significant clinical improvement rates at day 14 (5 RCTs; 3 Ciclesonide, 2 Budesonide) (OR 1.56, 95% CI 1.31-1.86, p < 0.0001, I2=0%). The number of ED visits/Hospitalization rate, and adverse events were not statistically significant between the groups (OR 0.73, 95% CI 0.32-1.70, p= 0.47 I2=75% and OR 1.10 95% CI 0.67-1.82, p=0.70, I2=28%). Conclusions: This meta-analysis shows that the therapeutic use of ICS in COVID-19 is associated with higher symptom-based clinical improvement rates. Although the reduction in mortality odds remained insignificant, as the overall mortality rates were low which increased the confidence interval overall. Early administration of ICS showed a trend towards the reduced likelihood of urgent care needs. Well-designed trials are needed to explore ICS efficacy in patients with a high risk of disease progression and in reducing the incidence of long-term COVID-19 symptoms or post-acute sequelae of SARS-CoV-2.

Rheumatoid arthritis and risk of site-specific cancers: Mendelian randomization study in European and East Asian populations

BackgroundThe associations of rheumatoid arthritis (RA) with risk of site-specific cancers beyond lymphohematopoietic cancer have been scarcely explored. We conducted a Mendelian randomization investigation of the associations of RA with site-specific cancers in European and East Asian populations.MethodsIndependent genetic variants strongly associated with RA in European and East Asian populations were selected as instrumental variables from genome-wide association studies of 58,284 European individuals (14,361 cases and 43,923 controls) and 22,515 East Asian individuals (4873 cases and 17,642 controls), respectively. The associations of genetic variants with overall and 22 site-specific cancers were extracted from the UK Biobank study (n = 367,561), the FinnGen study (n = 260,405), Biobank Japan (n = 212,453), and international consortia. The associations for one outcome from different data sources were combined by meta-analysis.ResultsIn the European population, the combined odds ratios per 1-unit increase in log odds of genetic liability to RA were 1.06 (95% confidence interval [CI] 1.03–1.10) for head and neck cancer, 1.06 (95% CI 1.02–1.10) for cervical cancer, 0.92 (95% CI 0.87–0.96) for testicular cancer, and 0.94 (95% CI 0.90–0.98) for multiple myeloma. In the East Asian population, the corresponding odds ratios were 1.17 (95% CI 1.06–1.29) for pancreatic cancer, 0.91 (95% CI 0.88–0.94) for breast cancer, and 0.90 (95% CI 0.84–0.96) for ovarian cancer. There were suggestive associations for breast and ovarian cancer and overall cancer in the European population. No other associations were observed.ConclusionThis study suggests that RA may play a role in the development of several site-specific cancers.

The association between bisphenol a exposure and attention deficit hyperactivity disorder in children: a meta-analysis of observational studies.

The association between Bisphenol A (BPA) exposure and attention deficit hyperactivity disorder (ADHD) has been a controversial topic. Objective: To evaluate the connection between BPA exposure and ADHD. We search Scopus, Web of Science, and Medline databases until August 2022. The meta-analysis was performed by using the software Stata 12.0 to calculate thecombined effect value Odds ratios (OR) and 95% confidence interval (95%CI). A total of 8 studies were included in this meta-analysis, including 5,710 children. Using the random effect model, it was found that compared with the lowest level of BPA exposure, the OR (95%CI) value of urine BPA exposure and ADHD in the highest level of BPA exposure was 1.76 (1.13-2.74). Based on the current meta-analysis results, BPA exposure may be a significant contributing factor to the development of ADHD in children.

TNF-α promoter variant (G-308A) is associated with susceptibility to P. falciparum infection and severe malaria: a meta-analysis and trial sequential analysis

Tumor necrosis factor-alpha (TNF-α) plays an essential role in Plasmodium falciparum infection, with lower levels associated with susceptibility to infection and higher levels linked with organ failure in severe malaria. Genetic polymorphisms in the promoter region of the TNF-α gene (G-308A and G-238A) affect plasma TNF-α levels. Numerous case-control studies have been conducted to determine the possible association between TNF-α polymorphisms and susceptibility to malaria infection and clinical severity; however, the results are inconsistent. Various databases such as Google Scholar, Science Direct, PubMed, and Scopus were searched for relevant articles for the present meta-analysis. Data were extracted from the eligible studies based on inclusion and exclusion criteria. Meta-analysis was carried out with CMA v.3.3.070 software, and combined odds ratio, 95% confidence interval, and p values were calculated. Further, a trial sequential analysis was also performed to test whether enough number of case and controls have been enrolled to date to draw a valid conclusion. Allele (OR = 9.757, p value=.049) and heterozygous (OR = 8.98, p value=.016) comparison model revealed the TNF-α G-308A variant as a susceptible genetic factor for P. falciparum infection. Similarly, a significant association of TNF-α G-308A polymorphism with P. falciparum malarial severity was also observed (A versus G: OR = 1.761, p value = .000; and GG + GA versus GG: OR = 1.769, p value = .000). However, no association of TNF-α (G-238A) polymorphism was observed with infection and severity of P. falciparum or Plasmodium vivax malaria. TNF-α G-308A variant is associated with susceptibility to P. falciparum infection and clinical severity. However, further studies on different populations are required.

The role of FTO variant rs1421085 in the relationship with obesity: a systematic review and meta-analysis.

Fat mass and obesity-associated (FTO) is considered the first locus associated with adiposity, a concerning health problem worldwide. Many studies have evaluated the relationship between the FTO variants and obesity susceptibility. While the strong association of FTO rs1421085 with the risk of obesity across populations was reported in different studies, some researchers found a lack of association of this variant with adiposity. This systematic review and meta-analysis aimed to assess the association between obesity and rs1421085 polymorphism. We systematically searched PubMed, Scopus, and Google Scholar up to June 2022 to find pertinent studies. To further assess this issue, we surveyed the probable association of rs1421085 with obesity development among Iranian adults using the logistic regression analysis, and the obtained results were used for doing meta-analysis. After selection, nine eligible studies were included in the meta-analysis through the random- and fixed-effect models to determine the combined odds ratios (OR) and 95% confidence intervals (CI). According to our meta-analysis conducted on 5169 obese and 7772 non-obese individuals using different genetic models, including recessive, dominant, over-dominant, and additive, rs1421085 could positively increase the risk of obesity under all tested genetic models. Also, we detected a high to moderate level of heterogeneity among different studies under various genetic models. This meta-analysis further verified the positive association of FTO rs1421085 with the risk of developing obesity. This study is registered as PROSPERO CRD42021220092. Level I, systematic reviews and meta-analyses.

Complex impacts of gallstone disease on metabolic syndrome and nonalcoholic fatty liver disease.

Patients with gallstone disease (GSD) often have highly co-occurrence with metabolic syndrome (MetS) and Nonalcoholic fatty liver disease (NAFLD) both associated with insulin resistance (IR). Meanwhile, highly prevalence of NAFLD was found in patients who received cholecystectomy. However, the associations of GSD with MetS, NAFLD is inconsistent in the published literature. And risk of cholecystectomy on NAFLD is unclear. We searched the Medline EMBASE and WOS databases for literature that met our study topic. To be specific, studies with focus on associations between GSD and MetS/NAFLD, and risk evaluation on cholecystectomy and NAFLD incidence were enrolled for further analysis. The random effect model was used to calculate the combined relative ratio (RR) and odds ratio (OR)and 95% confidence interval (CI). Seven and six papers with focus on connections between GSD and NAFLD/MetS prevalence. Correspondingly, seven papers with focus on risk of cholecystectomy on NAFLD occurrence were also enrolled into meta-analysis. After pooling the results from individual study, patients with GSD had higher risk of MetS (OR:1.45, 95%CI: 1.23-1.67, I2 = 41.1%, P=0.165). Risk of GSD was increased by 52% in NAFLD patients (pooled OR:1.52, 95%CI:1.24-1.80). And about 32% of increment on NAFLD prevalence was observed in patients with GSD (pooled OR: 1.32, 95%CI:1.14-1.50). With regard to individual MetS components, patients with higher systolic blood pressure were more prone to develop GSD, with combined SMD of 0.29 (96%CI: 0.24-0.34, P<0.05). Dose-response analysis found the GSD incidence was significantly associated with increased body mass index (BMI) (pooled OR: 1.02, 95%CI:1.01-1.03) in linear trends. Patients who received cholecystectomy had a higher risk of post-operative NAFLD (OR:2.14, 95%CI: 1.43-2.85), P<0.05). And this impact was amplified in obese patients (OR: 2.51, 95%CI: 1.95-3.06, P<0.05). Our results confirmed that controls on weight and blood pressure might be candidate therapeutic strategy for GSD prevention. And concerns should be raised on de-novo NAFLD after cholecystectomy.

Do General Pathologists Assess Gastric and Duodenal Eosinophilia?

Eosinophilic diseases of the gastrointestinal tract (EGIDs), eosinophilic gastritis (EoG), and eosinophilic duodenitis (EoD) are rarely suspected clinically and infrequently detected by pathologists. To determine whether histories of allergic or eosinophilic disorders and requests to rule out EoG and EoD affect pathologists' awareness of eosinophils in gastrointestinal biopsies. Thirty-one community-based pathologists were given 16 sets of biopsies from gastric and duodenal mucosa with elevated eosinophils, Helicobacter pylori gastritis, atrophic gastritis, normal stomach and duodenum, lymphocytosis, and celiac disease. Participants were assigned to 3 groups: group A did not receive histories of allergic or eosinophilic conditions; group B received similar histories plus a clue of possible allergic or eosinophilic conditions; and group C received the same histories as B and was asked to rule out EoG/EoD. A list of gastric and duodenal diagnoses and a space for comments were provided. Results were analyzed descriptively. Pathologists correctly diagnosed most noneosinophilic gastrointestinal disorders, indicating competence in gastrointestinal pathology. With respect to EoG and EoD, pathologists in group C performed significantly better that those in groups A and B. The combined odds ratio with 95% CI was 12.34 (2.87-53.04), P < .001, for A versus C and 4.02 (1.60-10.09), P < .02, for B versus C. Most pathologists neither reported gastric/duodenal eosinophilia nor diagnosed EoG/EoD, even when provided histories of eosinophilic disorders. Requests to rule out EoG/EoD resulted in only 4 of 11 participants evaluating and counting eosinophils in some cases. Simple evidence-based histopathologic criteria are needed before pathologists can be expected to consider and diagnose EGIDs.

The presence of diabetic retinopathy closely associated with the progression of non-alcoholic fatty liver disease: A meta-analysis of observational studies.

Background and Objective: Although growing evidence indicates that non-alcoholic fatty liver disease is related to diabetic retinopathy (DR), research results significantly vary. Therefore, we conducted a meta-analysis to assess the association between the progression of non-alcoholic fatty liver disease and the onset of DR. Methods: PubMed, Embase, and Cochrane databases were searched until 7 November 2021. Combined odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association. Results: We identified 18 studies involving 12,757 patients. The pooled effect assessment showed that liver fibrosis was positively correlated with DR (OR = 1.69, 95%CI 1.30-2.20; p < 0.0001); non-alcoholic fatty liver disease was not associated with the risk of DR (OR = 1.15, 95%CI 0.75-1.76; p = 0.51); non-alcoholic fatty liver disease was positively correlated with DR in patients with type 1 diabetes (OR = 2.96, 95%CI 1.48-5.94; p = 0.002). In patients with type 2 diabetes, there was no association between non-alcoholic fatty liver disease and DR (OR = 0.92, 95%CI 0.59-1.43; p = 0.70). Subgroup analysis showed no correlation in both Asian and Caucasian races. Conclusion: There is a significant correlation between liver fibrosis and DR. This suggests that the ocular examination of DR could be helpful in predicting whether patients with non-alcoholic fatty liver disease would progress to liver fibrosis.

Autologous Transplantation for Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis

Background: The relevance of autologous hematopoietic cell transplantation (ASCT), a crucial part of multiple myeloma (MM) therapy for eligible patients, has been questioned in light of improvements in induction therapy that result in excellent responses. To increase progression free and overall survival, it is crucial to continue developing first-line treatments using non-ASCT and ASCT-based methods. In addition, it is important to determine if a specific patient population might benefit from a given strategy to develop personalized cancer care based on risk stratification. In our meta-analysis, we assessed the efficacy outcomes of HDT/ASCT in combination with standard induction treatment as compared to standard-dose therapy alone for newly diagnosed MM. Materials & Methods: A comprehensive literature search was carried out on PubMed (Medline), EMBASE, CENTRAL (Cochrane Library), and Google Scholar from inception till 20th July 2022. HDT/ASCT versus standard-dose therapy (SDT) employing novel therapies was evaluated in phase 3 RCTs. The inclusion criteria were randomized controlled trials (RCTs) that directly compared combination chemotherapy followed by consolidation with HDT/ASCT(high-dose therapy with melphalan followed by autologous stem cell transplant) to SDT(Standard Dose therapy) alone without ASCT in patients with newly diagnosed MM(Multiple Myeloma). We included papers which reported PFS and OS as their endpoints using intention-to-treat analysis and had a minimum of 2 years of follow-up. All the original studies, review articles, and clinical trials with a sample size of <100 were excluded from the review. Review Manager Software (RevMan, version 5.3) was employed for statistical analyses, and forest plots were created to analyze the results visually. The Mantel-Haenszel random effect model was applied. Higgins's I2 test was used to evaluate heterogeneity across the studies. Results: A total of five Randomized Controlled Trials consisting of 3,294 participants were included in the meta-analysis. Only four studies included in the analysis reported OS. The pooled analysis reported no significant benefit for overall survival in the HDT/ASCT group compared to SDT (OR: 0.77, 95% CI; 0.49, 1.23, I2= 76%, P=0.28); however, the results were limited by significant heterogeneity. (Forest Plot 1). The combined odds ratio(OR) for complete response(CR) was 1.18 (OR: 1.18, 95%CI; 0.96-1.44, I2=21%, P= 0.11) with SDT compared with HDT/ASCT, although it is not statistically significant. (Forest Plot 3). Similarly, the combined odds ratio for a complete response did not favor any treatment group (OR: 1.18, 95%CI; 0.96-1.44, I2=21%, P= 0.11). All five studies reported PFS. Our results indicated statistically significant PFS in HDT/ASCT group as compared to the SDT alone group (OR: 0.57, 95% CI; 0.46-0.70, I2= 66%, P <0.00001). (Forest Plot 2) Conclusion: HDT/ASCT was linked with a better PFS as compared to SDT without ASCT in newly diagnosed multiple myeloma. The OS was comparable for both HDT/ASCT and SDT without ASCT in all RCTs. Overall survival for multiple myeloma patients has gradually improved over the last two decade. Overall survival benefit will be difficult to demonstrate between the two approaches as new and better treatments are getting available for salvage and bridging multiple myeloma patients to receive ASCT. ASCT in any line of treatment results in deeper remission and better outcomes, as well as equalizes the PFS benefit seen in using ASCT in first line treatment. Based on data from our meta-analysis, use of HDT/ASCT should be individualized based on disease risk group and patient's preference. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

MicroRNA in the diagnosis of lung cancer: An overview of ten systematic reviews.

To provide theoretical support for clinical diagnosis of lung cancer through an overview of systematic reviews (SRs) of the diagnostic value of miRNA. We searched PubMed, Embase, and the Cochrane Library to collect SRs of the diagnostic value of microRNA for lung cancer until April 2021. A comprehensive database search was carried out, screened, and extracted information independently by two researchers, to compare and analyze the sensitivity and specificity of relevant literatures. The ROBIS tool was applied to assess the risk of bias of included SRs and meta-analysis. A total of 10 SRs were included the results of risk of bias assessment by ROBIS tool showed: 10 SRs completely matched the four questions of phase one. In phase two, nine SRs were low risk of bias in the including criteria field; one study was uncertain; nine SRs were low risk of bias, one study was uncertain in the literature search and screening field; nine SRs were low risk of bias in the data abstraction and quality assessment field, one SR was high; and 10 SRs were low risk of bias in the data synthesis field. In the phase three of comprehensive risk of bias results, 8 studies were low risk, one was high risk, and one study was uncertain. MiRNA had a pooled sensitivity of 0.77 (95% CI: 0.73-0.81) and specificity of 0.81 (95% CI: 0.79-0.84). The summarized area under the SROC curve was 0.86 (95% CI: 0.83-0.89), and combined diagnostic odds ratio was 14.68 (10.87-19.81). The sensitivity and specificity of multiple MicroRNA was 0.80 (0.73-0.85) and 0.80 (0.76-0.83); the sensitivity and specificity of single MicroRNA was 0.74 (0.69-0.79) and 0.83 (0.80-0.88). MiRNA is a promising biomarker for the diagnosis of lung cancer in Chinese population, with advanced sensitivity and specificity. It provides a faster and less invasive assessment of lung cancer than other markers that require histopathological analysis. We should improve the reliability of the conclusion. The construction of diagnosis for lung cancer provides reliable evidence support.

Diagnostic Reliability of CRTC1/3::MAML2 Gene Fusion Transcripts in Discriminating Histologically Similar Intraosseous Mucoepidermoid Carcinoma from Glandular Odontogenic Cyst: A Systematic Review and Meta-analysis.

Intraosseous mucoepidermoid carcinoma (IMEC) and Glandular odontogenic cyst (GOC) are those two pathological entities causing diagnostic dilemma due to the histopathological similarity. An accurate distinction between the two entities is difficult as both presents with a common radiological and histological similarities. The aim of our systematic review was to establish the diagnostic reliability of CRTC1/3::MAML2 gene fusion for the distinction between IMEC and GOC. A complete electronic literature search was made in MEDLINE by PubMed, Google Scholar, and EMBASE databases. Articles with keywords using molecular genetic findings of CRTC1/3::MAML2 gene fusion transcripts, IMEC and GOC were assessed and included for the systematic review. Twelve subgroups having both qualitative and quantitative analysis revealed CRTC1/3::MAML2 sensitivity of 100% and specificity of 70.59% in differentiating GOC and IMEC. Fixed-effects model confirmed translocation-negative cases to have a decreased risk of association with IMEC (combined odds ratio 8.770, 95% confidence interval -2.45 to 31.45, p < 0.002). The current evidence supports that in all cases with positive gene fusion transcript of the CRTC1/3::MAML2 was specific for IMEC and was significantly differentiating it from GOC. Whereas cases of IMEC with negative gene fusion transcript pose diagnostic difficulty in differentiating from a GOC which is negative for CRTC1/3::MAML2 expression.

Effect of pharmacological treatment on outcomes of heart failure with preserved ejection fraction: an updated systematic review and network meta-analysis of randomized controlled trials

BackgroundOptimal treatment strategies for patients with heart failure with preserved ejection fraction (HFpEF) remain uncertain. The goal of this study was to compare the treatment effects of different therapeutic agents for patients with HFpEF.MethodsRandomized controlled trials (RCTs) published before June 2022 were searched from PubMed, Clinical Trials gov, and the Cochrane Central Register databases. Combined odds ratios (ORs) with 95% confidence intervals (CI) were calculated for the primary and secondary outcomes. All-cause death was the primary endpoint and cardiac death, hospitalization for HF, and worsening HF (WHF) events were secondary endpoints in this meta-analysis.ResultsFifteen RCTs including 31,608 patients were included in this meta-analysis. All-cause and cardiac death were not significantly correlated between drug treatments and placebo. Compared with placebo, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor neprilysin inhibitors (ARNIs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors significantly reduced HF hospitalizations [odds ratio (OR) = 0.64, (95% confidence interval (95%CI 0.43 − 0.96), OR = 0.73, (95%CI 0.61 − 0.86), and OR = 0.74, (95%CI 0.66 − 0.83), respectively] without heterogeneity among studies. Only SGLT2 inhibitors significantly reduced WHF events [OR = 0.75, (95%CI 0.67 − 0.83)].ConclusionsNo treatments were effective in reducing mortality, but ARNIs, ACEIs or SGLT2 inhibitors reduced HF hospitalizations and only SGLT2 inhibitors reduced WHF events for patients with HFpEF.

Association between homocysteine and nonalcoholic fatty liver disease: Mendelian randomisation study.

Many observational studies explore the relationship between homocysteine (Hcy) and nonalcoholic fatty liver disease (NAFLD), whereas the causality of this association remains uncertain, especially in European populations. We performed a bidirectional Mendelian randomisation study to elucidate the causal association between Hcy and NAFLD. Furthermore, we explored the relationship of Hcy with liver enzymes, including alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Two-sample Mendelian randomisation study was conducted. Summary statistics for Hcy were obtained from a genome-wide association studies (GWAS) meta-analysis comprising 44,147 subjects. Summary-level data for NAFLD were acquired from a GWAS meta-analysis of 8434 cases and 770,180 noncases and another GWAS meta-analysis of 1483 cases and 17,781 noncases. Summary-level data for three liver enzymes were available from the UK Biobank. Genetic associations of Hcy concentrations with NAFLD and liver enzymes were observed. Genetically predicted higher Hcy concentrations were consistently associated with an increased NAFLD risk in two data sources. The combined odds ratio of NAFLD was 1.25 (95% confidence interval [CI], 1.05-1.45) per SD increase in Hcy concentrations. Genetically predicted higher Hcy concentrations showed significant association with ALP (Beta .69; 95% CI, 0.04-1.34), ALT (Beta 0.56; 95% CI, 0.15-0.97) and AST levels (Beta .57; 95% CI, 0.10-1.04). Genetic liability to NAFLD was not associated with Hcy concentrations. This study has clinical implications as it indicates that increased Hcy concentrations increase the relevant liver enzymes and may play a role in NAFLD risk in European populations.

Plasma phospholipid arachidonic acid in relation to non-alcoholic fatty liver disease: Mendelian randomization study

ObjectivesThe role of plasma phospholipid arachidonic acid (AA) in the development of non-alcoholic fatty liver disease (NALFD), cirrhosis, and liver cancer remains unclear. This study aimed to determine the causality of the associations of plasma phospholipid AA with NALFD, cirrhosis, and liver cancer using Mendelian randomization analysis. MethodsNine independent single-nucleotide polymorphisms associated with plasma phospholipid AA at the genome-wide significance were used as instrumental variables. Summary-level data for three outcomes were obtained from 1) a genome-wide association study for NAFLD, 2) the UK Biobank study, and 3) the FinnGen study. The sensitivity analysis excluding the pleiotropic variant rs174547 in the FADS1 gene was performed. Estimates from different sources were combined using the fixed-effects meta-analysis method. ResultsPer standard deviation increase in AA levels, the combined odds ratio was 1.06 (95% confidence interval, 1.02–1.11; P = 0.008) for NAFLD, 1.05 (95% confidence interval, 1.01–1.09; P = 0.009) for cirrhosis, and 0.99 (95% confidence interval, 0.94–1.05; P = 0.765) for liver cancer. The associations remained stable in the sensitivity analysis excluding rs174547. ConclusionsThis study suggests potential causal associations of high levels of plasma phospholipid AA with the risk of NAFLD and cirrhosis.

The Anticancer Effect of Metformin Combined with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-small Cell Lung Cancer Patients with or Without Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.

Despite the growing evidence for the anticancer effect of metformin or its combination with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), the efficacies and side effects of such strategies in non-small cell lung cancer (NSCLC) patients with or without type 2 diabetes mellitus (T2DM) are not well understood. This meta-analysis was performed to determine the efficacy and side effects of metformin combined with EGFR-TKIs (MET-EGFR-TKIs) for the treatment of NSCLC with or without T2DM. PubMed and Cochrane Library databases were used to retrieve relevant studies through August 2020 using the keywords "metformin", "EGFR-TKIs" ("gefitinib" or "erlotinib" or "afatinib" or "icotinib" or "dacomitinib") and "lung cancer". The patients in the experimental group received MET-EGFR-TKIs, while those in the control group received only EGFR-TKIs. The outcome analysis reported overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Random-effect models and fixed-effect models were used to estimate the combined hazard ratio (HR) and odds ratio (OR) depending on the data heterogeneity. Three studies (including 1996 patients) were included in the current meta-analysis. There were significant differences in PFS (HR 0.84; 95% confidence interval (CI) 0.75-0.95; P = 0.004) and OS (HR 0.77; 95% CI, 0.50-1.04; P < 0.001) between the MET-EGFR-TKI and EGFR-TKI groups. Although the ORR (OR 1.38; 95% CI 0.66-2.88; P = 0.105) and DCR (OR 2.61, 95% CI 0.68-9.95, P = 0.160) were improved, there was no statistical significance. OS subgroup analysis showed that the combination was more effective in NSCLC with T2DM than in NSCLC without T2DM (HR 0.84; 95% CI 0.74-0.95; P < 0.005). MET-EGFR-TKIs provided benefits for PFS and OS, and OS subgroup analysis showed that patients with NSCLC with T2DM received greater benefit than NSCLC patients without T2DM. However, further large-scale, well-designed randomized controlled trials (RCTs) are warranted to confirm the findings in the present investigation.