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.

How to Distinguish Marfan Syndrome from Marfanoid Habitus in a Physical Examination—Comparison of External Features in Patients with Marfan Syndrome and Marfanoid Habitus

Marfan Syndrome (MFS) is a systemic disorder caused by mutations in fibrillin-1. The most common cause of mortality in MFS is dissection and rupture of the aorta. Due to a highly variable and age-dependent clinical spectrum, the diagnosis of MFS still remains sophisticated. The aim of the study was to determine if there exist phenotypic features that can play the role of “red flags” in cases of MFS suspicion. The study population included 306 patients (199 children and 107 adults) who were referred to the Department of Pediatric Cardiology due to suspicion of MFS. All patients underwent complete clinical evaluation in order to confirm the diagnosis of MFS according to the modified Ghent criteria. MFS was diagnosed in 109 patients and marfanoid habitus in 168 patients. The study excluded 29 patients with other hereditary thoracic aneurysm syndromes. Comparative analysis between patients with Marfan syndrome and marfanoid habitus was performed. Symptoms with high prevalence and high positive likelihood ratio were identified (pectus carinatum, reduced elbow extension, hindfoot deformity, gothic palate, downslanting palpebral fissures, lens subluxation, myopia ≥ 3 dioptres remarkably high stature). The differentiation between patients with MFS and marfanoid body habitus is not possible by only assessing external body features; however, “red flags” could be helpful in the screening phase.

MRI and CT imaging biomarkers of cerebral amyloid angiopathy in lobar intracerebral hemorrhage

Background: Cerebral amyloid angiopathy (CAA), a common cause of intracerebral hemorrhage (ICH), is diagnosed using the Boston criteria including magnetic resonance imaging (MRI) biomarkers (cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS). The simplified Edinburgh criteria include computed tomography (CT) biomarkers (subarachnoid extension (SAE) and finger-like projections (FLPs)). The underlying mechanisms and diagnostic accuracy of CT compared to MRI biomarkers of CAA are unknown. Methods: We included 140 survivors of spontaneous lobar supratentorial ICH with both acute CT and MRI. We assessed associations between MRI and CT biomarkers and the diagnostic accuracy of CT- compared to MRI-based criteria. Results: FLPs were more common in patients with strictly lobar CMB (44.7% vs 23.5%; p = 0.014) and SAE was more common in patients with cSS (61.3% vs 31.2%; p = 0.002). The high probability of the CAA category of the simplified Edinburgh criteria showed 87.2% (95% confidence interval (CI): 78.3–93.4) specificity, 29.6% (95% CI: 18.0–43.6) sensitivity, 59.3% (95% CI: 38.8–77.6) positive predictive value, and 66.4% (95%: CI 56.9–75.0) negative predictive value, 2.3 (95% CI: 1.2–4.6) positive likelihood ratio and 0.8 (95% CI 0.7–1.0) negative likelihood ratio for probable CAA (vs non-probable CAA), defined by the modified Boston criteria; the area under the receiver operating characteristic curve (AUROC) was 0.62 (95% CI: 0.54–0.71). Conclusion: In lobar ICH survivors, we found associations between putative biomarkers of parenchymal CAA (FLP and strictly lobar CMBs) and putative biomarkers of leptomeningeal CAA (SAE and cSS). In a hospital population, CT biomarkers might help rule-in probable CAA (diagnosed using the Boston criteria), but their absence is probably not as useful to rule it out, suggesting an important continued role for MRI in ICH survivors with suspected CAA.

Diagnostic accuracy of calprotectin in periprosthetic joint infection: a diagnostic meta-analysis

Background Periprosthetic joint infection (PJI) is considered to be one of the most challenging complications of joint replacement, which remains unpredictable. As a simple and emerging biomarker, calprotectin (CLP) has been considered to be useful in ruling out PJI in recent years. The purpose of this study was to investigate the accuracy and sensitivity of CLP in the diagnosis of PJI. Methods We searched and screened the publications from PubMed, Web of Science, EMBASE, and Cochrane Library from database establishment to June 2021. Subsequently, Stata version 16.0 software was used to combine the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), operating characteristic curve, and area under the curve (AUC). Heterogeneity across articles was evaluated by the I2 statistics. Finally, sources of heterogeneity were detected by subgroup analysis based on study design, detection method, sample size, and cutoff values. Results A total of 7 studies were included in our study, comprising 525 patients. The pooled sensitivity, specificity, PLR, and NLR of CLP for PJI diagnosis were 0.94(95% CI 0.87–0.98), 0.93(95% CI 0.87–0.96), 13.65(95% CI 6.89–27.08), and 0.06(95% CI 0.02–0.15), respectively, while the DOR and AUC were 222.33(95% CI 52.52–941.11) and 0.98 (95% CI 0.96–0.99), respectively. Conclusion Synovial CLP is a reliable biomarker and can be used as a diagnostic criterion for PJI in the future. However, the uncertainty resulting from the poor study numbers and sample sizes limit our ability to definitely draw conclusions on the basis of our study.

Synovial calprotectin for the diagnosis of periprosthetic joint infection: a diagnostic meta-analysis

Background Periprosthetic joint infections (PJI) are a rare but severe complication of total joint arthroplasty (TJA). However, the diagnosis of PJI remains difficult. It is one of the research that focuses about diagnosis for PJI for majority researchers to discover a novel biomarker. This meta-analysis tried to evaluate diagnostic value of synovial calprotectin for PJI. Methods This meta-analysis search of the literature was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library. Literature quality was appraised using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) based on RevMan (version 5.3). The diagnostic value of calprotectin for PJI was evaluated by calculating sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), diagnostic score and area under SROC (AUC) based on the Stata version 14.0 software. We conduct subgroup analysis according to the study design, cutoff values, the country of study, and gold standard. Results Seven studies were included in this meta-analysis. The pooled sensitivity of synovial calprotectin for the diagnosis of PJI was 0.94 (95% CI, 0.87–0.98), and the specificity was 0.93 (95% CI, 0.87–0.96). The pooled AUC, PLR, and NLR for synovial calprotectin were 0.98 (95% CI, 0.96–0.99), 13.65 (95% CI, 6.89–27.07), and 0.06 (95% CI, 0.02–0.15), respectively. The pooled diagnostic score and DOR were 5.4 (95% CI, 3.96–6.85) and 222.32 (95% CI, 52.52–941.12), respectively. Conclusion In summary, this meta-analysis indicates that synovial calprotectin is a promising biomarker of assistant diagnosis for PJI, as well as recommended test for excluding diagnostic tool.

Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid for the Diagnosis of Cerebral Aspergillosis

Purpose: Cerebral aspergillosis (CA) is a rare but often fatal, difficult-to-diagnose, opportunistic infection. The utility of metagenomic next-generation sequencing (mNGS) for diagnosis of CA is unclear. We evaluated the usefulness of mNGS of the cerebrospinal fluid (CSF) for the diagnosis of CA.Methods: This prospective study involved seven consecutive patients with confirmed CA in whom CSF mNGS was performed. Serum (1→3)-β-D-glucan and galactomannan levels were determined, and histopathological examination and mNGS of the CSF were conducted. CSF specimens from three non-infected patients were used as positive controls.Results: mNGS of the CSF was positive in six of the seven confirmed CA cases (85.71% sensitivity). In the cryptococcal meningitis group (control), mNGS of the CSF was positive for Aspergillus in two patients (84.62% specificity). The positive likelihood ratio, negative likelihood ratio, and Youden’s index of mNGS for CA in the CSF were 5.565, 0.169, and 0.7, respectively. Among the six mNGS-positive cases, more than two Aspergillus species were found in four (4/6, 66.67%). In the positive controls, the addition of one A. fumigatus spore yielded a standardised species-specific read number (SDSSRN) of 25.45 by mNGS; the detection rate would be 0.98 if SDSSRN was 2.Conclusion: mNGS facilitates the diagnosis of CA and may reduce the need for cerebral biopsy in patients with suspected CA.Trial Registration Number: Chinese Clinical Trial Registry, ChiCTR1800020442.

Specimen Mammography for Intraoperative Margin Assessment in Breast Conserving Surgery: A Meta-Analysis

Specimen mammography is one of the widely used intraoperative methods assessing margin status in breast conserving surgery. We performed a meta-analysis to evaluate the diagnostic accuracy of specimen mammography. Literature databases including Pubmed, Cochrane Library, Web of Science and EMBASE were searched prior to May 2020. 18 studies with a total of 1142 patients were included. Data was extracted to perform pooled analysis, heterogeneity testing, threshold effect testing, sensitivity analysis, publication bias analysis and subgroup analyses. The pooled weighted values were a sensitivity of 0.55 (95% CI, 0.45–0.64), a specificity of 0.85 (95% CI, 0.77–0.90), a DOR of 7 (95% CI, 4–11) and a pooled positive likelihood ratio of 3.6 (95% CI 2.4-5.3). The area under the receiver operator characteristic curve was 0.75 (95% CI 0.71-0.78). In the subgroup analysis, the pooled specificity in the positive margin defined as tumor at margin subgroup was lower than the other positive margin definition subgroup (0.79 [95% CI: 0.66, 0.91] vs. 0.88 [95% CI: 0.81, 0.95], p = 0.01). Our findings indicated specimen mammography to be an accurate and intraoperative imaging technique for margin assessment in breast conserving surgery.

Clinical Performance of BAL Metagenomic Next-Generation Sequence and Serum (1,3)-β-D-Glucan for Differential Diagnosis of Pneumocystis jirovecii Pneumonia and Pneumocystis jirovecii Colonisation

BackgroundDifferentiating Pneumocystis jirovecii infection from colonisation is crucial for appropriate therapy administration. In this study, we evaluated the performance of bronchoalveolar lavage fluid (BAL) metagenomic next-generation sequencing (mNGS) and serum 1,3-β-D-glucan (BDG) tests in differentiating colonisation and infection with P. jirovecii.MethodsFrom January 2018 to March 2021, 47 patients were enrolled in this study at the Hunan Provincial People’s Hospital. The final diagnosis was used as a reference, and cases were classified into the P. jirovecii pneumonia (PJP) group or the P. jirovecii colonisation (PJC) group. Clinical data were recorded. The performances of mNGS and BDG were compared.ResultThe fungal load significantly differed between patients with PJP and PJC, with median reads of 3,215.79 ± 1,797 vs. 5.61 ± 0.88 in the PJP and PJC groups, respectively (P < 0.0001). BDG also significantly differed between the two groups, with a median titre of 233.60 ± 39.65 pg/ml in the PJP group and 68.48 ± 19.21 pg/ml in the PJC group (P = 0.0006). The area under the curve was 0.973 (95%CI: 0.868–1.007) for mNGS of the BAL and 0.879 (95%CI: 0.769–0.989) for the serum BDG. The optimal threshold value for discriminating P. jirovecii infection from colonisation appeared to be 14 reads (sensitivity, 83.3%; specificity, 95.7%; positive likelihood ratio, 19.2) and BDG = 88.6 pg/ml (sensitivity, 79.2%; specificity, 92.9%; positive likelihood ratio, 18.2). No correlation between mNGS reads and the BDG titre was found in mNGS-positive patients (r2 = 0.0076, P = 0.583). The levels of lactate dehydrogenase and C-reactive protein were significantly higher in the PJP group than in the PJC group.ConclusionBAL mNGS and serum BDG are useful adjunct tests that can assist with differentiating between colonisation and infection of P. jirovecii.

Elevated De Ritis Ratio Is Associated With Poor Prognosis in COVID-19: A Systematic Review and Meta-Analysis

Objective: This meta-analysis aims to assess whether elevated De Ritis ratio is associated with poor prognosis in patients with coronavirus 2019 (COVID-19).Methods: A systematic literature search was performed using PubMed, Embase, and EuropePMC databases up until September 17, 2021. De Ritis ratio is also known as Aspartate aminotransferase/alanine transaminase (AST/ALT) ratio. The main outcome was poor prognosis, a composite of mortality, severity, the need for ICU care, and intubation. The effect measure was odds ratios (ORs) and mean differences. We generated sensitivity and specificity, negative and positive likelihood ratio (NLR and PLR), diagnostic odds ratio (DOR), and area under curve (AUC).Results: There were eight studies with 4,606 patients. De Ritis ratio was elevated in 44% of the patients. Patients with poor prognosis have higher De Ritis ratio [mean difference 0.41 (0.31, 0.50), p < 0.001; I2: 81.0%] and subgroup analysis showed that non-survivors also have higher De Ritis Ratio [mean difference 0.47 (0.46, 0.48), p < 0.001; I2: 0%]. Elevated De Ritis ratio was associated with poor prognosis [OR 3.28 (2.39, 4.52), p < 0.001; I2: 35.8%]. It has a sensitivity of 55% (36–73), specificity of 71% (52–85), PLR 1.9, NLR.63, DOR of 3 (2–4), and AUC of.67 (0.63–0.71). The posterior probability of poor prognosis was 38% if De Ritis is elevated, while 17% if De Ritis is not elevated.Conclusion: Elevated De Ritis ratio is associated with poor prognosis in patients with COVID-19.Systematic Review Registration: PROSPERO ID: CRD42020216634.

Prevalence and Prognosis of Fever Symptoms, Hypo-, and Hyperthermia in Unselected Emergency Patients

Assessments of history and body temperature are cornerstones of the diagnostic workup in all patients presenting to emergency departments (ED). Yet, the objective measurement of temperature and the subjective perception of fever can differ. This is a secondary exploratory analysis of a consecutive all-comer study, performed at an adult ED in Switzerland. Trained medical students interviewed all patients if fever was present. Altered temperature (>38.0 °C/<36.0 °C) measured at triage using an ear thermometer was used as the reference standard for diagnostic performance. In case of a disagreement between fever symptoms and altered temperature, discordance was noted. Outcome measures for case severity (acute morbidity, hospitalization, intensive care, and in-hospital mortality) were extracted from the electronic health records. Odds ratios (OR) for discordance between signs and symptoms and outcomes were calculated. Among 2183 patients, 325 patients reported fever symptoms. The sensitivity of fever symptoms as a test for altered temperature was 36.3%. Specificity was 91.5%. The negative predictive value was 84.1%, positive likelihood ratio was 4.2 and negative likelihood ratio was 0.7. The adjusted OR for discordance between fever symptoms and altered temperature was 1.71 (95% CI: 1.2–2.44) for acute morbidity, 1.56 (95% CI: 1.13–2.15) for hospitalization, and 1.12 (95% CI: 0.64–1.59) for intensive care. Unadjusted OR for mortality was 1.5 (95% CI: 0.69–3.25). Fever symptoms and altered temperature broadly overlap, but presentations can be stratified according to concordance between signs and symptoms. In case of discordance, the odds for acute morbidity and hospitalization are increased. Discordance may therefore be further investigated as a red flag for a serious outcome.