Accuracy of Non-Contrast MRI for the Detection of Hepatocellular Carcinoma: A systematic review and meta-analysis

Non-contrast MRI is used for identifying patients with hepatocellular carcinoma (HCC), especially among high-risk patients with cirrhosis or chronic viral hepatitis. The accuracy of non-contrast MRI has been investigated with varying results. We performed this meta-analysis to consolidate the evidence on the accuracy of non-contrast MRI for the detection of HCC. We conducted a systematic search in the databases of PubMed Central, SCOPUS, MEDLINE, EMBASE and Cochrane from inception till November 2020. We used the STATA software “Midas” package for meta-analysis. We included 15 studies with 3,756 patients. The pooled sensitivity and specificity of non-contrast MRI for HCC detection were 84% (95%CI, 78%-88%) and 94% (95%CI, 91%-97%). The positive likelihood ratio was 14.9 (95% CI, 9.0-24.7) and the negative one 0.17 (0.12-0.23). The overall quality of the studies was high. We found significant heterogeneity based on chi-square test results and I2 statistic > 75%. Deek’s test showed the absence of publication bias. We found that non-contrast MRI has high sensitivity and specificity as a tool for detecting HCC. Studies exploring its accuracy in different ethnic populations are required to strengthen the evidence. doi: https://doi.org/10.12669/pjms.38.3.5142 How to cite this:Lu L, Pan X. Accuracy of Non-Contrast MRI for the Detection of Hepatocellular Carcinoma: A systematic review and meta-analysis. Pak J Med Sci. 2022;38(3):---------. doi: https://doi.org/10.12669/pjms.38.3.5142 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Trajectories of frailty with aging: Coordinated analysis of five longitudinal studies

Background and Objectives There is an urgent need to better understand frailty and it’s predisposing factors. Although numerous cross-sectional studies have identified various risk and protective factors of frailty, there is a limited understanding of longitudinal frailty progression. Furthermore, discrepancies in the methodologies of these studies hamper comparability of results. Here, we use a coordinated analytical approach in five independent cohorts to evaluate longitudinal trajectories of frailty and the effect of three previously identified critical risk factors: sex, age, and education. Research Design and Methods We derived a frailty index (FI) for five cohorts based on the accumulation of deficits approach. Four linear and quadratic growth curve models were fit in each cohort independently. Models were adjusted for sex/gender, age, years of education, and a sex/gender-by-age interaction term. Results Models describing linear progression of frailty best fit the data. Annual increases in FI ranged from 0.002 in the InCHIANTI cohort to 0.009 in the LASA. Women had consistently higher levels of frailty than men in all cohorts, ranging from an increase in the mean FI in women from 0.014 in the HRS cohort to 0.046 in the LASA cohort. However, the associations between sex/gender and rate of frailty progression were mixed. There was significant heterogeneity in within-person trajectories of frailty about the mean curves. Discussion and Implications Our findings of linear longitudinal increases in frailty highlight important avenues for future research. Specifically, we encourage further research to identify potential effect modifiers or groups that would benefit from targeted or personalized interventions.

Application of the Controlled Source Radiomagnetotellurics (CSRMT) in the Study of Rocks Overlying Kimberlite Pipes in Yakutia/Siberia

Тhe task of searching for kimberlite pipes in covered areas of the Yakutia kimberlite province is very difficult due to the significant heterogeneity of the rocks overlying kimberlite pipes. The overlying strata of terrigenous sediments contain rocks of the trap complex (dolerite sills, tuff bodies). We consider the results of the controlled source radiomagnetotelluric (CSRMT) soundings in Yakutia/Siberia. Due to the great thickness of the overlying rocks (near 100 m) and the relatively small horizontal sizes of kimberlite pipes (80–200 m), they cannot confidently be detected directly. An additional difficulty in identifying pipe anomalies is the presence of a layer of conductive carbonaceous siltstones in the overlying strata. Therefore, the main aim of the CSRMT surveys was the study of overlying rocks and the search for indirect indications of the presence of pipes. Possibilities to study the structure of dolerite sills located within overlying sediments and to map the top edge of hosting carbonate rocks are demonstrated using the CSRMT data. The pinching out of dolerite sills above pipes («windows in traps») and the lowering of the top edge of hosting rocks at pipes can be considered as indirect indications of the presence of pipes.

Chikungunya outbreak in Bangladesh (2017): sociodemographic and clinical characteristics of patients from three hotspots

Background Chikungunya is a severely debilitating disease. Bangladesh witnessed one of the largest outbreaks in 2017. Here, we described the clinical profile of the chikungunya outbreak in Bangladesh and its heterogeneity across three hotspots. Methods This was a descriptive cross-sectional study of 432 individuals interviewed from the outpatient department of three study sites (Dhaka, Chittagong, and Sitakundu Upazilla of Bangladesh) after confirmation by the study physicians. Both laboratory-confirmed cases and probable cases were recruited between July and October 2017. Results Of all, 18% (79) were laboratory confirmed, and 353 82% (335) were probable cases. The male:female ratio was almost equal (1.09:1), and the predominant age group was 18–59 years. The mean age of the presentation was 36.07 ± 13.62 (SD) years. Fever and arthralgia were the most common presentations and were present in > 95% of cases. Other frequent symptoms were fatigue, myalgia, headache, nausea, and vomiting. Approximately half of the patients had arthritis and erythematous rash. Arthritis was predominant in Chittagong city, while maculopapular rash was not observed in Sitakunda city. However, fatigue, nausea, and vomiting are more common among patients in Dhaka city. Significant heterogeneity of clinical manifestations was present across the three hotspots (p < 0.05 for all). Both confirmed and probable cases shared similar characteristics except muscle ache (p = 0.22) and rash (p = 0.37). Conclusion The clinical profile of chikungunya virus-induced disease displays significant location-related heterogeneity in Bangladesh during a large outbreak. Although the causes of such differences are unclear, improved public and medical personnel education on this condition may lead to earlier diagnosis and treatment.

Diagnostic Accuracy of Contemporary Selection Criteria in Prostate Cancer Patients Eligible for Active Surveillance: A Bayesian Network Meta-Analysis

BackgroundSeveral active surveillance (AS) criteria have been established to screen insignificant prostate cancer (insigPCa, defined as organ confined, low grade and small volume tumors confirmed by postoperative pathology). However, their comparative diagnostic performance varies. The aim of this study was to compare the diagnostic accuracy of contemporary AS criteria and validate the absolute diagnostic odds ratio (DOR) of optimal AS criteria.MethodsFirst, we searched Pubmed and performed a Bayesian network meta-analysis (NMA) to compare the diagnostic accuracy of contemporary AS criteria and obtained a relative ranking. Then, we searched Pubmed again to perform another meta-analysis to validate the absolute DOR of the top-ranked AS criteria derived from the NMA with two endpoints: insigPCa and favorable disease (defined as organ confined, low grade tumors). Subgroup and meta-regression analyses were conducted to identify any potential heterogeneity in the results. Publication bias was evaluated.ResultsSeven eligible retrospective studies with 3,336 participants were identified for the NMA. The diagnostic accuracy of AS criteria ranked from best to worst, was as follows: Epstein Criteria (EC), Yonsei criteria, Prostate Cancer Research International: Active Surveillance (PRIAS), University of Miami (UM), University of California-San Francisco (UCSF), Memorial Sloan-Kettering Cancer Center (MSKCC), and University of Toronto (UT). I2 = 50.5%, and sensitivity analysis with different insigPCa definitions supported the robustness of the results. In the subsequent meta-analysis of DOR of EC, insigPCa and favorable disease were identified as endpoints in ten and twenty-two studies, respectively. The pooled DOR for insigPCa and favorable disease were 0.44 (95%CI, 0.31–0.58) and 0.66 (95%CI, 0.61–0.71), respectively. According to a subgroup analysis, the DOR for favorable disease was significantly higher in US institutions than that in other regions. No significant heterogeneity or evidence of publication bias was identified.ConclusionsAmong the seven AS criteria evaluated in this study, EC was optimal for positively identifying insigPCa patients. The pooled diagnostic accuracy of EC was 0.44 for insigPCa and 0.66 when a more liberal endpoint, favorable disease, was used.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/], PROSPERO [CRD42020157048].

Liver Stiffness, Albuminuria and Chronic Kidney Disease in Patients with NAFLD: A Systematic Review and Meta-Analysis

An association between liver stiffness, a surrogate measure of liver fibrosis, and chronic kidney disease (CKD) in patients with nonalcoholic fatty liver disease (NAFLD) has been proposed. However, most studies were small and had low statistical power. We systematically searched PubMed-MEDLINE and Scopus from inception to August 2021 for cross-sectional or cohort studies reporting the association between liver stiffness diagnosed by vibration controlled transient elastography (VCTE) and renal dysfunction. The primary outcome was CKD, defined as a composite of urinary albumin to creatinine ratio (UACR) ≥ 30 mg/g and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Measures of association from individual studies were meta-analyzed using random effects models. Of the 526 titles initially scrutinized, 7 cross-sectional studies fulfilled the criteria and were included. For CKD, risk was higher in patients with liver fibrosis assessed by VCTE, compared with patients without (n = 5 studies: OR 2.49, 95% CI 1.89–3.29; test for overall effect z = 6.475, p < 0.001). When increased UACR was considered as an outcome, elevated liver stiffness was associated with a significantly increased risk as well (n = 3 studies: OR 1. 98 95% CI 1.29–3.05; test for overall effect z = 3.113, p = 0.002). Neither analysis showed significant heterogeneity (I2 = 0% and I2 = 46.5%, respectively for the two outcomes). This meta-analysis indicates that elevated liver stiffness is associated with increased odds of kidney outcomes among patients with NAFLD. Wider use of VCTE to screen for advanced fibrosis might help identify patients at risk of end-stage renal disease.

Exposure to silicates and systemic autoimmune-related outcomes in rodents: a systematic review

Background Autoimmunity can result from the interplay between genetic background and effects of environmental and/or occupational exposure to hazardous materials. Several compounds, including silica dust, have been linked with systemic autoimmunity and systemic autoimmune diseases, based on epidemiological evidence. For asbestos, a strong link with systemic autoimmune diseases does not yet exist, however, several studies have documented features of autoimmunity following asbestos exposure. Even so, human studies are limited in their ability to identify and examine isolated exposures, making it difficult to demonstrate causation or to assess pathogenic mechanisms. Therefore, this systematic review examines the existing animal evidence regarding autoimmunity and exposure to silicates (silica and asbestos). Methods PubMed and EMBASE were systematically searched for peer-reviewed studies examining systemic autoimmune disease-related outcomes after silicate exposure in rodents. Literature databases were searched up to September 2021 for studies written in English and where the full text was available. Search strings were established based on a PECO (Population, Exposure, Comparator, Outcome) format. After title, abstract, and full-text screening, thirty-four studies were identified for further analysis. Quality assessment through ToxR tool and qualitative analysis of the results was performed. Results Although there was significant heterogeneity in the included studies in terms of exposure protocol and genetic background of the rodent models used, it was noted that both genetic background and exposure to silicates [(crystalline) silica and asbestos] are highly relevant to the development of (sub-) clinical systemic autoimmune disease. Conclusion Parallels were observed between the findings from the animal (this review) and human (epidemiological) studies, arguing that experimental animal models are valuable tools for examining exacerbation or development of autoimmune disease after silicate exposure. However, genetic background and synergism between exposures should be considered in future studies.

Association Between Vitamin D and Influenza: Meta-Analysis and Systematic Review of Randomized Controlled Trials

Background: Vitamin D supplementation improves the immune function of human body and can be a convenient way to prevent influenza. However, evidence on the protective effect of vitamin D supplementation on influenza from Randomized Controlled Trials (RCTs) is inconclusive.Methods: RCTs regarding the association between vitamin D supplementation and influenza were identified by searching PubMed, Cochrane library, Embase and Chinese Biomedical Database (CBM) from inception until present (last updated on 10 November 2021). Studies that reported dosages and durations of vitamin D supplementation and number of influenza infections could be included. Heterogeneity was assessed using Cochran's Q test and I2 statistics, the meta-analysis was conducted by using a random-effects model, the pooled effects were expressed with risk ratio (RR) with 95% confidence interval (95% CI).Results: 10 trials including 4859 individuals were ultimately eligible after scanning. There was no evidence of a significant heterogeneity among studies (I2 = 27%, P = 0.150). Meta-regression analysis finding indicated that country, latitude, average age, economic level, follow-up period and average daily vitamin D intake did not cause the statistical heterogeneity. The study finding indicates that substitution with vitamin D significantly reduces the risk of influenza infections (RR = 0.78, 95% CI:0.64–0.95). No evidence of publication bias was observed. Omission of any single trial had little impact on the pooled risk estimates.Conclusions: The meta-analysis produced a corroboration that vitamin D supplement has a preventive effect on influenza. Strategies for preventing influenza can be optimized by vitamin D supplementation.

Coverage and Determinants of Infant Postnatal Care in Nigeria: a Population-based Cross-sectional Study

Background: In 2019, Nigeria had the most under-5 child deaths globally, many of which occurred within the neonatal period, especially in the first week after birth. Despite the effectiveness of infant postnatal care (PNC) attendance recommended by the World Health Organization (WHO), this problem persists. Therefore, the study examined coverage and determinants of infant PNC attendance in Nigeria. Methods: Nigeria Demographic Health Survey (NDHS) 2018 data were used to evaluate infant PNC coverage and determinants. Infant PNC was defined as receipt of care within two days of birth. Children delivered up to two years before the 2018 NDHS were included. We examined predictors of infant PNC with Poisson regression models to estimate relative risks (RR).Results: The national coverage of infant PNC was 37.3% (95% CI: 35.8%–38.7%). Significant heterogeneity in PNC attendance exists at state and regional levels. Facility delivery was strongly associated with uptake of PNC (RR: 6.07; 95% CI: 5.60–6.58). Greater maternal education, maternal employment, urban residence, female head of household, and greater wealth were also associated with increased likelihood of PNC visits. Conclusions: Uptake of infant PNC in Nigeria is low. Interventions are urgently needed to promote equity in access and increase demand.

Genome-wide Discovery for Diabetes-Dependent Triglycerides-Associated Loci

Objective: Discover loci associated with triglyceride (TG) levels in the context of type 2 diabetes (T2D). Research Design and Methods: Genome-wide association study (GWAS) was performed in 424,120 genotyped participants of the UK Biobank (UKB) with T2D status and TG levels. Association analyses of TG levels were performed stratified by T2D status for genetic variants with minor allele count (MAC) at least 20 in each stratum. Effect differences of genetic variants by T2D status were determined by Cochrans Q-test implemented in METAL (p-value<5x10-8). Validation of significant variants was pursued in 25,137 participants of the Mass General Brigham Biobank (MGBB). Results: Among 21,176 T2D and 402,944 non-T2D samples, stratified GWAS identified 19 and 315 genomic risk loci significantly associated with TG levels, respectively. Only chr6p21.32 exhibited genome-wide significant heterogeneity (I2=98.4%; pheterogeneity=2.1x10-15), with log(TG) effect estimates of -0.066 (95%CI: -0.082, -0.050) and 0.002 (95%CI: -0.002, 0.006) for T2D and non-T2D, respectively. The lead variant rs9274619:A (allele frequency 0.095) is located 2Kb upstream of the HLA-DQB1 gene. We replicated this finding among 25,137 participants (6,951 T2D cases) of MGBB (pheterogeneity=9.5x10-3). Phenome-wide interaction association analyses showed that the lead variant was strongly associated with a concomitant diagnosis of type 1 diabetes (T1D) as well as diabetes-associated complications. Conclusion: An intergenic variant near HLA-DQB1 significantly associates with decreased triglycerides only among those with T2D and highlights an immune overlap with T1D.