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.

Meta-Analytical Accuracy of ANCA Renal Risk Score for Prediction of Renal Outcome in Patients With ANCA-Associated Glomerulonephritis

Background: To evaluate the diagnostic accuracy of antineutrophil cytoplasmic antibody (ANCA) renal risk score (ARRS) for prediction of renal outcome in patients with ANCA-associated glomerulonephritis (ANCA-GN).Methods: We searched PubMed, EMBASE, Ovid, Web of Science, the Cochrane Library, and ClinicalTrials.gov for studies, which used ARRS to predict end-stage renal disease (ESRD) in patients with ANCA-GN. Two reviewers independently screened articles for inclusion, assessed the quality of studies with both an adapted Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. We calculated the combined patients with ESRD in the ARRS categories and presented the summary and individual estimates based on the ARRS categories. Then, the sensitivity, specificity, diagnostic odds ratio (DOR), positive/negative likelihood ratio, and the area under the receiver operating characteristic (AUROC) curves of the pooled data for ARRS were used to assess the accuracy of the “above the low-risk threshold” (ARRS ≥ 2) and “high-risk grade” (ARRS ≥ 8) for renal outcome of patients with ANCA-GN. The hierarchical summary ROC (HSROC) was used to verify the accuracy value. The clinical utility of ARRS was evaluated by the Fagan plot. Heterogeneity was explored using meta-regression and subgroup analysis.Results: A total of 12 distinct cohorts from 11 articles involving 1,568 patients with ANCA-GN were analyzed. The cumulative patients with ESRD at the maximum follow-up of 60 months was 5% (95% CI: 0.02–0.07; p < 0.001) for ANCA-GN with low ARRS (0–1 points) and significantly increased to 22% (95% CI: 0.15–0.29; p < 0.001) medium ARRS (2–7 points). The combined cumulative patients with ESRD was 59% (95% CI: 0.49–0.69; p < 0.001) high ARRS (8–11 points). The pooled sensitivity of ARRS ≥ 2 in predicting ESRD was 98% with a specificity of 30% and a DOR of 15.08 and the mean AUROC value was 0.82. The pooled sensitivity of ARRS ≥ 8 in predicting ESRD was 58% with a specificity of 86% and a DOR of 7.59. The meta-regression and subgroup analysis indicated that variation in the geographic regions, study design, index risk, follow-up time, age of patient, publication year, and number of patient could be the potential sources of heterogeneity in the diagnosis of ARRS ≥ 8.Conclusion: This meta-analysis emphasized the good performance of the ARRS score in predicting the renal outcome in patients with ANCA-GN. However, these findings should be verified by future large-scale prospective studies.

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.

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.

Accuracy of ultrasound in distinguishing pathology of malignant thyroid diseases: A protocol for systematic review and meta-analysis

Review question / Objective: This meta-analysis aimed to determine the accuracy of ultrasound in distinguishing pathology of malignant thyroid diseases. Eligibility criteria: Type of study. This study will only include high quality clinical cohort or case control studies. Type of patients. The patients should be those who had undergone breast diseases. Intervention and comparison. This study compares AI with pathology for diagnosing breast diseases. Type of outcomes. The primary outcomes include sensitivity, specificity, positive and negative likelihood ratio, diagnostic odds ratio, and the area under the curve of the summary receiver operating characteristic.

Mid-Regional Pro-Adrenomedullin, Methemoglobin and Carboxyhemoglobin as Prognosis Biomarkers in Critically Ill Patients with COVID-19: An Observational Prospective Study

Mid-regional pro-adrenomedullin (MR-proADM), methemoglobin (MetHb), and carboxyhemoglobin (COHb) levels have been associated with sepsis. In this study, we assessed the role of this potential biomarkers in critically ill COVID-19 patients. Outcomes were mortality and a combined event (mortality, venous or arterial thrombosis, and orotracheal intubation (OTI)) during a 30-day follow-up. A total of 95 consecutive patients were included, 51.6% required OTI, 12.6% patients died, 8.4% developed VTE, and 3.1% developed arterial thrombosis. MetHb and COHb levels were not associated with mortality nor combined event. Higher MR-proADM levels were found in patients with mortality (median of 1.21 [interquartile range-IQR-0.84;2.33] nmol/L vs. 0.76 [IQR 0.60;1.03] nmol/L, p = 0.011) and combined event (median of 0.91 [IQR 0.66;1.39] nmol/L vs. 0.70 [IQR 0.51;0.82] nmol/L, p < 0.001); the positive likelihood ratio (LR+) and negative likelihood ratio (LR−) for mortality were 2.40 and 0.46, respectively. The LR+ and LR− for combined event were 3.16 and 0.63, respectively. MR-proADM ≥1 nmol/L was the optimal cut-off for mortality and combined event prediction. The predictive capacity of MR-proADM showed an area under the ROC curve of 0.73 (95% CI, 0.62–0.81) and 0.72 (95% CI, 0.62–0.81) for mortality and combined event, respectively. In conclusion, elevated on-admission MR-proADM levels were associated with higher risk of 30-day mortality and 30-day poor outcomes in a cohort of critically ill patients with COVID-19.

Diagnostic accuracy of computed tomography angiography (CTA) for diagnosing blunt cerebrovascular injury in trauma patients: a systematic review and meta-analysis

Objectives Previous literature showed that the diagnostic accuracy of computed tomographic angiography (CTA) is not equally comparable with that of the rarely used golden standard of digital subtraction angiography (DSA) for detecting blunt cerebrovascular injuries (BCVI) in trauma patients. However, advances in CTA technology may prove CTA to become equally accurate. This study investigated the diagnostic accuracy of CTA in detecting BCVI in comparison with DSA in trauma patients. Methods An electronic database search was performed in PubMed, EMBASE, and Cochrane Library. Summary estimates of sensitivity, specificity, positive and negative likelihood, diagnostic odds ratio, and 95% confidence intervals were determined using a bivariate random-effects model. Results Of the 3293 studies identified, 9 met the inclusion criteria. Pooled sensitivity was 64% (95% CI, 53–74%) and specificity 95% (95% CI, 87–99%) The estimated positive likelihood ratio was 11.8 (95%, 5.6–24.9), with a negative likelihood ratio of 0.38 (95%, 0.30–0.49) and a diagnostic odds ratio of 31 (95%, 17–56). Conclusion CTA has reasonable specificity but low sensitivity when compared to DSA in diagnosing any BCVI. An increase in channels to 64 slices did not yield better sensitivity. There is a risk for underdiagnosis of BCVI when only using DSA to confirm CTA-positive cases, especially in those patients with low-grade injuries. Key Points • Low sensitivity and high specificity were seen in identifying BCVI with CTA as compared to DSA. • Increased CTA detector channels (≤ 64) did not lead to higher sensitivity when detecting BCVI. • The use of CTA instead of DSA may lead to underdiagnosis and, consequently, undertreatment of BCVI.

Diagnostic value of endobronchial ultrasound elastography combined with rapid onsite cytological evaluation in endobronchial ultrasound-guided transbronchial needle aspiration

Background Endobronchial ultrasound (EBUS) elastography has been used in EBUS-guided transbronchial needle aspiration (EBUS-TBNA) to identify malignant lymph nodes based on tissue stiffness. Rapid onsite cytological evaluation (ROSE) has been widely utilized for onsite evaluation of sample adequacy and for guiding sampling during EBUS-TBNA. The aim of this study was to investigate the diagnostic value of combined EBUS elastography and ROSE in evaluating mediastinal and hilar lymph node status. Methods Retrospective chart review was performed from December 2018 to September 2020. Patient demographics, EBUS elastography scores, and ROSE, pathologic, and clinical outcome data were collected. The EBUS elastography scores were classified as follows: Type 1, predominantly nonblue; Type 2, partially blue and partially nonblue; and Type 3, predominantly blue. A receiver operating characteristic curve was used to compare the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio for evaluation of malignant lymph nodes among the EBUS elastography, ROSE, and EBUS combined with ROSE groups. Results A total of 245 patients (345 lymph nodes) were included. The sensitivity and specificity of the EBUS elastography group for the diagnosis of malignant lymph nodes were 90.51% and 57.26%, respectively. The sensitivity and specificity in the ROSE group were 96.32% and 79.05%, respectively. The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of EBUS elastography combined with ROSE were 86.61%, 92.65%, 11.78, and 0.14, respectively, and the area under the curve was 0.942. Conclusions Combining EBUS elastography and ROSE significantly increased the diagnostic value of EBUS-TBNA in evaluating mediastinal and hilar lymph node status compared to each method alone.