Biochemical testing for the diagnosis of Wilson's disease: A systematic review

BackgroundWilson''s disease (WD) is a rare inherited disorder that leads to copper accumulation in the liver, brain, and other organs. WD is prevalent worldwide, with an occurrence of 1 per 30,000 live births. Currently, there is no gold standard diagnostic test for WD. The objective of this systematic review is to determine the diagnostic accuracy for WD of three biochemical tests, namely hepatic copper, 24‐hour urinary copper, and ceruloplasmin using the Leipzig criteria.MethodsAdhering to PRISMA guidelines, databases including PubMed/MEDLINE, CINAHL Plus, Web of Science, and Cochrane were searched. Studies that comprised of confirmed or suspected WD along with normal populations were included with adult and pediatric group. The sensitivity, specificity, negative predictive value and positive predictive value were computed using RevMan 5.4.ResultsNine studies were included. The best practice evidence for 24‐hour urinary copper test ranged from a cutoff value of 0.64–1.6 μmol/24 h (N = 268; sensitivity = 75.6%, specificity = 98.3%). Hepatic copper test was optimally cutoff based on the ROC curve analysis at 1.2 μmol/g yielding a power of 96.4% sensitivity and 95.4% specificity (N = 1,150); however, the tried and tested 4 μmol/g cutoff, with 99.4% sensitivity and 96.1% specificity, is more widely accepted. The ceruloplasmin test cutoff value was found to be ranging from 0.14 to 0.2 g/L (N = 4,281; sensitivity = 77.1%–99%, specificity = 55.9%–82.8%).ConclusionThis paper provides a large‐scale analysis of current evidence pertaining to the biochemical diagnosis of WD employing the Leipzig criteria. The laboratory values are typically based on specific subgroups based on age, ethnicity, and clinical subgroups. The findings of this systematic review must be used with caution, given the over‐ or under‐estimation of the index tests.     

Two-Dimensional Echocardiographic Detection of Asymptomatic Pulmonary Thromboembolism

Asymptomatic pulmonary thromboembolism is a well-known clinical entity. In this case, a routine two-dimensional echocardiogram detected a thrombus in the right atrium. During the examination, it was seen to move into the right ventricle and across the pulmonic valve into the pulmonary artery. The patient remained completely asymptomatic. To my knowledge, this is the first case describing two-dimensional echocardiographic demonstration of asymptomatic pulmonary thromboembolism.     

Hemimegalencephaly: A rare congenital malformation of cortical development

Hemimegalencephaly is a rare congenital malformation of cortical development usually associated with developmental delay and refractory epilepsy that sooner or later require hemispherectomy.     

Colchicine,COVID‐19 and hematological parameters: A meta‐analysis

IntroductionColchicine has the potential in reducing patient morbidity and mortality in COVID‐19 infection owing to its anti‐inflammatory properties. This study aims to determine the efficacy of colchicine in optimizing inflammatory hematological biomarker levels among COVID‐19 patients.MethodsIn accordance to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) 2020 statement guidelines, a systematic search was conducted using the following keywords: Colchicine, covid*, SARS‐CoV‐2, anti‐inflammatory, trials, clinical, hematological, laboratory. Databases were searched from December 2019 until August 26, 2021: MEDLINE/PubMed, Web of Science, Cochrane, Scopus, and EMBASE. Other sources were located through ClinicalTrials.Gov, manually searching SAGE, Science Direct, Elsevier, and Google Scholar. The meta‐analysis was conducted using Review Manager 5.4.ResultsIn total, six studies were included, of which four reported c‐reactive protein (CRP) standardized mean reductions in the colchicine group (N = 165) as opposed to the control (N = 252; SMD = −0.49, p < 0.001). On noting lactate dehydrogenase (LDH) values post treatment, the colchicine group (N = 204) showed significant reductions at the end of treatment compared to control (N = 290; SMD = −0.85, p < 0.001). Finally, the D‐dimer values in colchicine groups (N = 129) compared to control (N = 216) also documented a negative effect size (SMD = −0.9, p < 0.001).ConclusionColchicine has efficacy in reducing inflammatory biomarkers observed in moderate‐to‐severe COVID‐19 patients. It may be worthwhile to consider monitoring the clinical and laboratory parameters of patients in further trials to consider colchicine as a strong candidate for an adjunct to COVID‐19 treatment.     

The radiological presentation of Rasmussen aneurysm secondary to pulmonary tuberculosis and COVID-19: A case report

Rasmussen aneurysm is rare diagnosis occurring in patients with long-standing tuberculosis. TB-COVID-19 co-infection in the context of Rasmussen aneurysm is a rare occurrence, yet new cases are emerging. An elderly male was recently diagnosed with TB-COVID-19 co-infection and presented with sudden onset massive hemoptysis. The patient was diagnosed with Rasmussen aneurysm after being evaluated by computed tomography pulmonary angiogram due to a suggestive clinical presentation. Interventional radiologists planned for embolization of pulmonary artery, with an unidentifiable source. It was suspected that the patient''s source of bleeding was hampered due to local tamponade effect or thrombosis of the aneurysm. The patient remained stable after 24 hours on computed tomography pulmonary angiogram. Our case emphasizes the importance of Rasmussen aneurysm as a differential diagnosis when presented with a TB-COVID-19 co-infection and sudden onset of hemoptysis symptomatically and radiologically. The timely diagnosis and management are key to improve mortality.     

The correlation of D‐dimer to stroke diagnosis within 24 hours: A meta‐analysis

BackgroundDiagnosing D‐Dimer early is essential to optimize clinical treatment and quality of life and reduce mortality. This study aims to identify the difference of D‐Dimer levels (ng/ml) in patients with stroke within the 6‐ and 24‐h period compared to patients that mimic stroke.MethodsAn electronic database search across PubMed/MEDLINE, Cochrane, Web of Science, CINAHL, EMBASE, and Scopus was conducted until December 10, 2021. Studies were eligible if they included adult patients with stroke compared to stroke mimics or controls reporting D‐Dimer values. Quality assessment was conducted using GRADE. The standardized mean difference and 95% confidence intervals were calculated in addition to the difference of means in the crude form. Heterogeneity was assessed using Cochran''s Q statistic and the I ² index. A random‐effects model was used. The statistical analysis was conducted using RevMan 5.4.ResultsOut of 2901, there were 318 (11%) participants from upper‐middle‐income countries, whereas the others were from high‐income countries. Large positive effect size was found for D‐Dimer in the stroke group (Cohen''s d = 2.82 [1.73–3.9]; p < 0.00001), meaning that those with stroke had higher D‐Dimer values on presentation compared to the stroke mimics/controls. A large difference in means was found in the two groups (MD = 685.1 [324.2, 1045.99]; p < 0.00001), suggesting that there was a significantly higher laboratory value in the stroke group.ConclusionOur findings must be used in caution as the most reliable diagnostic tests for stroke are CT and MRI. Laboratory testing such as D‐Dimer values is a valuable clinical adjuvant in diagnosing total stroke.     

Anakinra treatment efficacy in reduction of inflammatory biomarkers in COVID‐19 patients: A meta‐analysis

IntroductionAnakinra is being empirically considered for the treatment of COVID‐19 patients. The aim is to assess the efficacy of anakinra treatment on inflammatory marker reduction, including c‐reactive protein (CRP) concentrations, serum ferritin, and serum d‐dimer levels.MethodsAdhering to PRISMA 2020 statement guidelines, a systematic search was conducted across the following databases from December 2019 until January 10, 2022: PubMed/MEDLINE, Cochrane Central, Web of Science, Scopus, and EMBASE. The following keywords were employed: Anakinra, COVID*, SARS‐CoV‐2, inflammatory, CRP, D‐dimer, Ferritin, hematological, laboratory, clinical, trials. The findings were collated and presented in a tabulated manner, and statistically analyzed using Review Manger 5.4 (Cochrane).ResultsIn total, 2032 patients were included (881 in the anakinra and 1151 in the control/standard care group); 69.1% of them were males. Overall, the mean difference from admission until last follow‐up in CRP values was −9.66, where notable reductions were seen in the anakinra group (SMD = −0.46, p < 0.00001, N = 655). Serum ferritin mean values were reduced by 1467.16 in the anakinra group (SMD = −0.31, p = 0.004, N = 537). D‐dimer mean values were largely reduced by 4.04 in the anakinra group (SMD = −0.38, p = 0.0004, N = 375).ConclusionThis study finds that anakinra is potentially a strong candidate as an anti‐inflammatory agent to reduce mortality in COVID‐19 patients, specifically in patients with elevated inflammatory biomarkers.