scholarly journals Diagnostic and Prognostic Performance of Liquid Biopsy-Derived Exosomal MicroRNAs in Thyroid Cancer Patients: A Systematic Review and Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4295 ◽  
Author(s):  
Eman A. Toraih ◽  
Rami M. Elshazli ◽  
Lily N. Trinh ◽  
Mohammad H. Hussein ◽  
Abdallah A. Attia ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Meta Analysis ◽  
False Negative ◽  
Area Under The Curve ◽  
High Sensitivity ◽  
High Specificity ◽  
Likelihood Ratios ◽  
Discriminative Ability ◽  
Exosomal Mirnas ◽  
True False

Circulatory tumor-derived exosomal microRNAs (miRNAs) play key roles in cancer development/progression. We aimed to assess the diagnostic/prognostic value of circulating exosomal miRNA in thyroid cancer (TC). A search in PubMed, Scopus, Web of Science, and Science Direct up to 22 May 2021 was performed. The true/false positive (TP/FP) and true/false negative (TN/FN) rates were extracted from each eligible study to obtain the pooled sensitivity, specificity, positive/negative likelihood ratios (PLR/NLR), diagnostic odds ratio (DOR), and their 95% confidence intervals (95%CIs). The meta-analysis included 12 articles consisting of 1164 Asian patients and 540 controls. All miRNAs were quantified using qRT-PCR assays. The pooled sensitivity was 82% (95%CI = 77–86%), pooled specificity was 76% (95%CI = 71–80%), and pooled DOR was 13.6 (95%CI = 8.8–21.8). The best biomarkers with high sensitivity were miR-16-2-3p (94%), miR-223-5p (91%), miR-130a-3p (90%), and miR182-5p (94%). Similarly, they showed high specificity, in addition to miR-34c-5p. Six panels of two to four exosomal miRNAs showed higher diagnostic values with an area under the curve (AUC) ranging from 0.906 to 0.981. The best discriminative ability to differentiate between cancer and non-cancer individuals was observed for miR-146b-5p + miR-223-5p + miR-182-5p (AUC = 0.981, sensitivity = 93.8% (84.9–98.3), specificity = 92.9% (76.5–99.1)). In conclusion, the expression levels of exosomal miRNAs could predict TC.

scholarly journals Utility of recombinant human TSH stimulation test in the follow-up of patients with differentiated thyroid cancer depending on basal thyroglobulin results

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Amaia Sandúa ◽  
Monica Macias ◽  
Carolina Perdomo ◽  
Juan Carlos Galofre ◽  
Roser Ferrer ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
High Sensitivity ◽  
Thyroid Stimulating Hormone ◽  
Stimulation Test ◽  
Human Thyroid ◽  
Antithyroglobulin Antibodies ◽  
Structural Disease

AbstractBackgroundThyroglobulin (Tg) is fundamental for differentiated thyroid cancer (DTC) monitoring. Tg detection can be enhanced using recombinant human thyroid-stimulating hormone (TSH) (rhTSH). This study is aimed to evaluate the use of the rhTSH stimulation test when using a high-sensitivity Tg assay.MethodsWe retrospectively studied 181 rhTSH tests from 114 patients with DTC and negative for antithyroglobulin antibodies (anti-TgAb). Image studies were performed in all cases. Serum Tg and anti-TgAb were measured using specific immunoassays.ResultsrhTSH stimulation in patients with basal serum Tg (b-Tg) concentrations lower than 0.2 ng/mL always resulted in rhTSH-stimulated serum Tg (s-Tg) concentrations lower than 1.0 ng/mL and negative structural disease. In patients with b-Tg concentration between 0.2 and 1.0 ng/mL, s-Tg detected one patient (1/30) who showed biochemical incomplete response. Patients with negative images had lower s-Tg than those with nonspecific or abnormal findings (p<0.05). Receiver operating characteristic curve analysis of the s-Tg to detect altered images showed an area under the curve of 0.763 (p<0.05). With an s-Tg cutoff of 0.85 ng/mL, the sensitivity was 100%, decreasing to 96.15% with an s-Tg cutoff of 2 ng/mL.ConclusionsPatients with DTC with b-Tg concentrations equal or higher than 0.2 ng/mL can benefit from the rhTSH stimulation test.

scholarly journals Value of Xpert MTB/RIF Using Bronchoalveolar Lavage Fluid for the Diagnosis of Pulmonary Tuberculosis: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Hong-Chao Liu ◽  
Yu-Lu Gao ◽  
Dan-Feng Li ◽  
Xi-Yi Zhao ◽  
Yuan-Qing Pan ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pulmonary Tuberculosis ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Meta Analysis ◽  
Area Under The Curve ◽  
Culture Method ◽  
Lavage Fluid ◽  
Likelihood Ratios ◽  
Sensitivity Specificity

Background: The performance of Xpert MTB/RIF using bronchoalveolar lavage fluid (BAL) for the diagnosis of pulmonary tuberculosis (PTB) remains unclear. Therefore, a systematic review/meta-analysis was conducted. Methods: Studies published before December 31, 2019, were retrieved from the PubMed, Embase, and Web of Science databases using the keywords “pulmonary tuberculosis,” “Xpert MTB/RIF,” and “BAL.” Two independent evaluators extracted the data and assessed the bias risk of the included studies. A random-effects model was used to calculate the overall sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR, respectively), diagnostic odds ratio (DOR), and the area under the curve (AUC), as well as the respective 95% confidence intervals (CIs). Results: Nineteen trials involving 3019 participants met the inclusion criteria. Compared to the culture method, the pooled sensitivity, specificity, PLR, NLR, DOR, and the AUC with 95% CIs of Xpert MTB/RIF were 0.87 (0.84–0.90), 0.92 (0.91–0.93), 10.21 (5.78–18.02), 0.16 (0.12–0.22), 78.95 (38.59–161.53), and 0.9467 (0.9462-0.9472), respectively. Relative to the composite reference standard, the observed values were 0.69 (0.65–0.72), 0.98 (0.98–0.99), 37.50 (18.59–75.62), 0.30 (0.21–0.43), 171.98 (80.82–365.96), and 0.9691 (0.9683–0.9699), respectively. All subgroups, except children, showed high sensitivity and specificity. Conclusions: The use of Xpert MTB/RIF in the context of BAL samples has a high diagnostic performance for PTB (except for children) and may serve as an alternative rapid diagnostic tool.

scholarly journals Diagnostic and prognostic value of miRNAs in hepatoblastoma: A systematic review with meta-analysis

2021 ◽  
Author(s):  
Bin Wu ◽  
◽  
Lixia Guo ◽  
Kaikai Zhen ◽  
Chao Sun
Keyword(s):  
Systematic Review ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Area Under The Curve ◽  
Prognostic Indicator ◽  
Diagnostic Odds Ratio ◽  
Diagnostic Value ◽  
Likelihood Ratios ◽  
Clinical Value ◽  
Diagnostic And Prognostic Value

Review question / Objective: Background and aim: Increasing evidence has revealed the valuable diagnostic and prognostic applications of dysregulated microRNAs (miRNAs) in hepatoblastoma (HB), the most common hepatic malignancy during childhood. However, these results are inconsistent and remain to be elucidated. In the present study, we aimed to systematically compile up-to-date information regarding the clinical value of miRNAs in HB. Methods: Articles concerning the diagnostic and prognostic value of single miRNAs for HB were searched from databases. The sensitivity (SEN), specificity (SPE), positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and hazard ratios (HRs) were separately pooled to explore the diagnostic and prognostic performance of miRNA. Subgroup and meta-regression analyses were further carried out only in the event of heterogeneity. Results: In all, 20 studies, involving 264 HB patients and 206 healthy individuals, met the inclusion criteria in the six included literature articles. For the diagnostic analysis of miRNAs in HB, the pooled SEN and SPE were 0.76 (95% CI: 0.72–0.80) and 0.75 (95% CI: 0.70–0.80), respectively. Moreover, the pooled PLR was 2.79 (95% CI: 2.12–3.66), NLR was 0.34 (95% CI: 0.26–0.45), DOR was 10.24 (95% CI: 6.55–16.00), and AUC was 0.83, indicating that miRNAs had moderate diagnostic value in HB. For the prognostic analysis of miRNAs in HB, the abnormal expressions of miR-21, miR-34a, miR-34b, miR-34c, miR-492, miR-193, miR-222, and miR-224 in patients were confirmed to be associated with a worse prognosis. The pooled HR was 1.74 (95% CI: 1.20–2.29) for overall survival (OS) and 1.74 (95% CI: 1.31–2.18) for event-free survival (EFS), suggesting its potential as a prognostic indicator for HB. Conclusion: To the best of our knowledge, this is the first comprehensive systematic review and meta-analysis that examines the diagnostic and prognostic role of dysregulated miRNAs in HB patients. The combined meta-analysis results supported the previous individual finds that miRNAs might provide a new, noninvasive method for the diagnostic and prognostic analyses ofHB.

scholarly journals Correlation of Immunohistochemistry and Fluorescence in Situ Hybridization for HER-2 Assessment in Breast Cancer Patients: Single Centre Experience

2018 ◽  
Vol 6 (4) ◽  
pp. 593-599 ◽  
Author(s):  
Magdalena Bogdanovska-Todorovska ◽  
Slavica Kostadinova-Kunovska ◽  
Rubens Jovanovik ◽  
Blagica Krsteska ◽  
Goran Kondov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
In Situ Hybridisation ◽  
False Negative ◽  
High Sensitivity ◽  
High Specificity ◽  
Fluorescence In Situ Hybridisation ◽  
Breast Cancer Patients ◽  
Her 2

BACKGROUND: Accurate assessment of HER-2 is imperative in selecting patients for targeted therapy. Most commonly used test methods for HER-2 are immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). We evaluated the concordance between FISH and IHC for HER-2 in breast cancer samples using Food and Drug Administration approved tests.MATERIAL AND METHODS: Archived paraffin tissue blocks from 73 breast cancer patients were used. HER-2 immunostaining was performed using Ventana anti–HER-2 monoclonal antibody. The FISH assay was performed using PathVysion™ HER-2 DNA Probe Kit.RESULTS: Of the 73 cases 68.5% were IHC 0/1+, 15.07% were IHC 2+ and 16.44% were IHC 3+. Successful hybridisation was achieved in 72 cases. HER-2 FISH amplification was determined in 16.67% cases. Ten IHC 3+ and two IHC 2+ cases were FISH positive. Two of the IHC 3+ cases were FISH negative. Concordance rate was 100%, 18.18% and 83.33% for IHC 0/1+, 2+ and 3+ group, respectively. Total concordance was 84.72%, kappa 0.598 (p < 0.0001). The sensitivity of IHC in detecting IHC 2+ and IHC 3+ cases was 16.7% and 83.3%, and the specificity was 85% and 96.67%, respectively.CONCLUSION: The consistency between the methods was highest for IHC negative and lowest for IHC equivocal cases. The immunohistochemistry showed high sensitivity for IHC 2+/3+ cases and high specificity for IHC 3+ cases. Our results support the view that false-positive rather than false-negative IHC results are a problem with HER-2/IHC testing, and that IHC should be used as an initial screening test, but IHC 2+/ 3+ results should be confirmed by FISH.

1267 Utility of Artificial Intelligence in the Cystoscopic Detection of Bladder Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  
S Ganesananthan ◽  
S Ganesananthan ◽  
B S Simpson ◽  
J M Norris
Keyword(s):  
Artificial Intelligence ◽  
Bladder Cancer ◽  
Sensitivity And Specificity ◽  
Meta Analysis ◽  
External Validation ◽  
High Sensitivity ◽  
Diagnostic Odds Ratio ◽  
Pooled Analysis ◽  
Likelihood Ratios ◽  
Novel Technology

Abstract Aim Detection of suspected bladder cancer at diagnostic cystoscopy is challenging and is dependent on clinician skill. Artificial Intelligence (AI) algorithms, specifically, machine learning and deep learning, have shown promise in accurate classification of pathological images in various specialties. However, utility of AI for urothelial cancer diagnosis is unknown. Here, we aimed to systematically review the extant literature in this field and quantitively summarise the role of these algorithms in bladder cancer detection. Method The EMBASE, PubMed and CENTRAL databases were searched up to December 22nd 2020 , in accordance with the PRISMA guidelines, for studies that evaluated AI algorithms for cystoscopic diagnosis of bladder cancer. Random-effects meta-analysis was performed to summarise eligible studies. Risk of Bias was assessed using the QUADAS-2 tool. Results Five from 6715 studies met criteria for inclusion. Pooled sensitivity and specificity values were 0.93 (95% CI 0.89–0.95) and 0.93 (95% CI 0.80–0.89) respectively. Pooled positive likelihood and negative likelihood ratios were 14 (95% CI 4.3–44) and 0.08 (95% CI: 0.05–0.11), respectively. Pooled diagnostic odds ratio was 182 (95% CI 61–546). Summary AUC curve value was 0.95 (95% CI 0.93–0.97). No significant publication bias was noted. Conclusions In summary, AI algorithms performed very well in detection of bladder cancer in this pooled analysis, with high sensitivity and specificity values. However, as with other clinical AI usage, further external validation through deployment in real clinical situations is essential to assess true applicability of this novel technology.

scholarly journals Automated detection of cribriform growth patterns in prostate histology images

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Pierre Ambrosini ◽  
Eva Hollemans ◽  
Charlotte F. Kweldam ◽  
Geert J. L. H. van Leenders ◽  
Sjoerd Stallinga ◽  
...  
Keyword(s):  
Deep Learning ◽  
False Positive ◽  
Clinical Decision Making ◽  
False Negative ◽  
Area Under The Curve ◽  
High Sensitivity ◽  
False Positives ◽  
Growth Patterns ◽  
Learning Method ◽  
Method Performance

Abstract Cribriform growth patterns in prostate carcinoma are associated with poor prognosis. We aimed to introduce a deep learning method to detect such patterns automatically. To do so, convolutional neural network was trained to detect cribriform growth patterns on 128 prostate needle biopsies. Ensemble learning taking into account other tumor growth patterns during training was used to cope with heterogeneous and limited tumor tissue occurrences. ROC and FROC analyses were applied to assess network performance regarding detection of biopsies harboring cribriform growth pattern. The ROC analysis yielded a mean area under the curve up to 0.81. FROC analysis demonstrated a sensitivity of 0.9 for regions larger than $${0.0150}\,\hbox {mm}^{2}$$ 0.0150 mm 2 with on average 7.5 false positives. To benchmark method performance for intra-observer annotation variability, false positive and negative detections were re-evaluated by the pathologists. Pathologists considered 9% of the false positive regions as cribriform, and 11% as possibly cribriform; 44% of the false negative regions were not annotated as cribriform. As a final experiment, the network was also applied on a dataset of 60 biopsy regions annotated by 23 pathologists. With the cut-off reaching highest sensitivity, all images annotated as cribriform by at least 7/23 of the pathologists, were all detected as cribriform by the network and 9/60 of the images were detected as cribriform whereas no pathologist labelled them as such. In conclusion, the proposed deep learning method has high sensitivity for detecting cribriform growth patterns at the expense of a limited number of false positives. It can detect cribriform regions that are labelled as such by at least a minority of pathologists. Therefore, it could assist clinical decision making by suggesting suspicious regions.

Diagnostic and prognostic values of circular RNAs for lung cancer: a meta-analysis

2020 ◽  
pp. postgradmedj-2019-137178
Author(s):  
Qian Yang ◽  
Lizhen Chen ◽  
Li Yang ◽  
Yuanshuai Huang
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Area Under The Curve ◽  
High Sensitivity ◽  
Cochrane Library ◽  
Clinicopathological Parameters ◽  
Circular Rnas ◽  
Lung Cancer Patients ◽  
Diagnostic Values

Circular RNAs (circRNAs) may serve as potential biomarkers for patients with lung cancer. The aim of this meta-analysis was to analyse the diagnostic, prognostic and clinicopathological values of circRNAs in lung cancer patients. A systematic search of PubMed, Embase, Web of Science, Scopus and the Cochrane Library databases was performed for relevant articles from inception to 29 January 2020. Pooled parameters including sensitivity, specificity and area under the curve (AUC) were used to assess the diagnostic performance, HRs and 95% CIs were used to evaluate overall survival (OS) and ORs were used to estimate clinicopathological parameters. 52 studies from 45 articles were enrolled in this study, including 17 on diagnosis and 35 on prognosis. For diagnostic values, circRNAs could discriminate lung cancer patients from the controls, with AUC of 0.83 (95% CI: 0.79 to 0.86), a relatively high sensitivity of 0.77 (95% CI: 0.73 to 0.81) and specificity of 0.75 (95% CI: 0.71 to 0.79). For prognostic significances, overexpression of 23 upregulated circRNAs was relevant to a poor prognosis (OS: HR=2.21, 95% CI: 1.96 to 2.49, p<0.001), and overexpression of 9 downregulated circRNAs was correlated with a favourable prognosis (OS: HR=0.62, 95% CI: 0.53 to 0.73, p<0.001). As for clinicopathological parameters, high expression of 23 upregulated circRNAs was associated with unfavourable clinicopathological features while 9 downregulated circRNAs proved the contrary. In conclusion, this study confirmed that circRNAs might serve as important biomarkers for diagnostic and prognostic values of lung cancer.

scholarly journals Accuracy of proton magnetic resonance for diagnosing non-alcoholic steatohepatitis: a meta-analysis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tae-Hoon Kim ◽  
Chang-Won Jeong ◽  
Hong Young Jun ◽  
ChungSub Lee ◽  
SiHyeong Noh ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Imaging Modality ◽  
Meta Analysis ◽  
Area Under The Curve ◽  
Diagnostic Odds Ratio ◽  
Diagnostic Methods ◽  
Likelihood Ratios ◽  
Alcoholic Fatty Liver ◽  
Noninvasive Diagnostics ◽  
Alcoholic Steatohepatitis

Abstract Liver biopsy is the reference standard test to differentiate between non-alcoholic steatohepatitis (NASH) and simple steatosis (SS) in non-alcoholic fatty liver disease (NAFLD), but noninvasive diagnostics are warranted. The diagnostic accuracy in NASH using MR imaging modality have not yet been clearly identified. This study was assessed the accuracy of magnetic resonance imaging (MRI) method for diagnosing NASH. Data were extracted from research articles obtained after a literature search from multiple electronic databases. Random-effects meta-analyses were performed to obtain overall effect size of the area under the receiver operating characteristic(ROC) curve, sensitivity, specificity, likelihood ratios(LR), diagnostic odds ratio(DOR) of MRI method in detecting histopathologically-proven SS(or non-NASH) and NASH. Seven studies were analyzed 485 patients, which included 207 SS and 278 NASH. The pooled sensitivity was 87.4% (95% CI, 76.4–95.3) and specificity was 74.3% (95% CI, 62.4–84.6). Pooled positive LR was 2.59 (95% CI, 1.96–3.42) and negative LR was 0.17 (95% CI, 0.07–0.38). DOR was 21.57 (95% CI, 7.27–63.99). The area under the curve of summary ROC was 0.89. Our meta-analysis shows that the MRI-based diagnostic methods are valuable additions in detecting NASH.

scholarly journals Relationship between nerve conduction studies and the Functional Dexterity Test in workers with carpal tunnel syndrome

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Francesco Sartorio ◽  
Francesca Dal Negro ◽  
Elisabetta Bravini ◽  
Giorgio Ferriero ◽  
Stefano Corna ◽  
...  
Keyword(s):  
Carpal Tunnel Syndrome ◽  
Diagnostic Accuracy ◽  
Carpal Tunnel ◽  
Nerve Conduction ◽  
High Specificity ◽  
Nerve Conduction Studies ◽  
Likelihood Ratios ◽  
Discriminative Ability ◽  
Convenience Sample ◽  
Tunnel Syndrome

Abstract Background Dexterity impairments caused by carpal tunnel syndrome (CTS) make working and daily activities challenging. We aimed to investigate: i) the relationship between dexterity and nerve conduction studies (NCS) in workers with classic symptoms presentation; ii) the ability of the Functional Dexterity Test (FDT) to discriminate different levels of CTS severity as classified by NCS; iii) the diagnostic accuracy of a clinical battery composed of the FDT, Phalen’s test and Tinel’s sign. Methods In a convenience sample of individuals diagnosed with CTS, we correlated FDT net scores with the NCS-based classification by means of Spearman’s (rho) test. Discriminative ability of the FDT was assessed by ANOVA, and a ROC curve determined cutoff thresholds. Sensitivity, specificity, and likelihood ratios (LRs) were used to investigate the diagnostic accuracy of the clinical battery. Results Data from 180 hands were collected. The FDT was significantly correlated (rho = 0.25, p <  0.001) with NCS. The FDT was able to discriminate subjects with severe/extreme NCS findings, and two thresholds (0.29–0.36) were identified. Adding the FDT to the provocative tests improved the overall diagnostic accuracy (specificity: 0.97, CI95% 0.83–0.99; LR+: 14.49, CI95% 2.09–100.53). Conclusions Sensorimotor impairments related to CTS can affect hand dexterity. The FDT discriminated patients with severe NCS involvement. Positive results on the clinical battery (Phalen, Tinel, and FDT) could help to confirm the CTS diagnosis, showing a very high specificity and LR+. On the contrary, the low sensitivity is not able to rule out CTS in individuals with negative results.

scholarly journals Associations and prognostic accuracy of electrolyte imbalances in predicting poor COVID-19 outcome: a systematic review and meta-analysis of 28 observational studies

2021 ◽  
Author(s):  
Harris Jun Jie Muhammad Danial Song ◽  
Alys Zhi Qin Chia ◽  
Benjamin Kye Jyn Tan ◽  
Chong Boon Teo ◽  
Horng Ruey Chua ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Observational Studies ◽  
Inflammatory Marker ◽  
Meta Analysis ◽  
Area Under The Curve ◽  
Cochrane Library ◽  
Likelihood Ratios ◽  
Predictive Values ◽  
Poor Outcome ◽  
Prognostic Accuracy

BACKGROUND: Serum electrolyte imbalances are highly prevalent in COVID-19 patients. However, their associations with COVID-19 outcomes are inconsistent, and of unknown prognostic value. OBJECTIVES: To systematically clarify the associations and prognostic accuracy of electrolyte imbalances (sodium, calcium, potassium, magnesium, chloride and phosphate) in predicting poor COVID-19 clinical outcome. METHODS: PubMed, Embase and Cochrane Library were searched. Odds of poor clinical outcome (a composite of mortality, intensive-care unit (ICU) admission, need for respiratory support and acute respiratory distress syndrome) were pooled using mixed-effects models. The associated prognostic sensitivity, positive and negative likelihood ratios (LR+, LR-) and predictive values (PPV, NPV; assuming 25% pre-test probability), and area under the curve (AUC) were computed. RESULTS: We included 28 observational studies from 953 records with low to moderate risk-of-bias. Hyponatremia (OR=2.08, 95%CI=1.48-2.94, I2=93%, N=8), hypernatremia (OR=4.32, 95%CI=3.17-5.88, I2=45%, N=7) and hypocalcemia (OR=3.31, 95%CI=2.24-4.88, I2=25%, N=6) were associated with poor COVID-19 outcome. These associations remained significant on adjustment for covariates such as demographics and comorbidities. Hypernatremia was 97% specific in predicting poor outcome (LR+ 4.0, PPV=55%, AUC=0.80) despite no differences in CRP and IL-6 levels between hypernatremic and normonatremic patients. Hypocalcemia was 76% sensitive in predicting poor outcome (LR- 0.44, NPV=87%, AUC=0.71). Overall quality of evidence ranged from very low to moderate. CONCLUSION: Hyponatremia, hypernatremia and hypocalcemia are associated with poor COVID-19 clinical outcome. Hypernatremia is 97% specific for a poor outcome and the association is independent of inflammatory marker levels. Further studies should evaluate if correcting these imbalances help improve clinical outcome.

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