BACKGROUND: Recent studies have suggested the role of primary laboratory tests in addition to clinical symptoms for patients suspected to have coronavirus disease 2019 (COVID-19), which play a significant role in the diagnosis of COVID-19. However, the results of these studies are contradictory. The present study was conducted to evaluate biochemical, serological, and immunological tests for the diagnosis of COVID-19 patients.
METHODS: This study was presented in accordance with the PRISMA protocol. This protocol is registered with the code CRD42019145410 in PROSPERO. We conducted a comprehensive literature search in databases, including Web of Science, PubMed/Medline, CINAHL Scopus, Cochrane Library, EMBASE, Science Direct, and EBSCO to find citations from the beginning of January 2019 until the beginning of April 2020 without any restrictions.
RESULTS: Finally, 51 studies, including 5,490 COVID-19 patients, were included in the present metaanalysis. The prevalence of different factors observed in laboratory findings was as follows: the prevalence of lymphopenia in patients with COVID-19 accounted for 51.6% (95% CI: 44.0-59.1), elevated C-reactive protein (CRP) was 63.6% (95% CI: 57.0-69.8), elevated erythrocyte sedimentation rate (ESR) was 62.5% (95% CI: 50.1-73.5), elevated tumor necrosis factor alpha (TNFα) was 28.7% (95% CI: 9.0-62.1), elevated serum amyloid-A level was 74.7% (95% CI: 50.0-89.7), elevated procalcitonin level was 72.6% (95% CI: 58.1-83.5), elevated interleukin-6 level was 59.9% (95% CI: 48.2-70.5), reduced CD3 level was 68.3% (95% CI: 50.1-82.2), reduced CD4 level was 62.0% (95% CI: 51.1- 71.6), elevated lactate dehydrogenase (LDH) level accounted for 53.1% (95% CI: 43.6-62.4), elevated brain natriuretic peptide (BNP) accounted for 48.9% (95% CI: 30.4-67.7), reduced albumin and reduced pre-albumin levels in patients with COVID-19 were estimated to be 54.7% (95% CI: 38.1-70.2) and 49.0% (95% CI: 26.6-71.8), and D-dimer level was 44.9% (95% CI: 31.0-59.6).
CONCLUSIONS: The results show lymphopenia, elevated ESR level, elevated CRP level, elevated serum amyloid-A, elevated TNFα, elevated procalcitonin level, elevated interleukin-6 level, reduced CD3, reduced CD4, elevated BNP, elevated LDH, reduced albumin, reduced pre-albumin, and elevated Ddimer levels as the most common findings at the time of admission.

BACKGROUND: We report a case of a patient with immunoglobulin A multiple myeloma associated with a masked kappa light chain. Serum immunofixation showed a monoclonal band in the IgA heavy chain lane without corre-spondence with the light chain and a monoclonal band in total kappa light chain lane without correspondence with the heavy chain.
METHODS: To distinguish between heavy chain disease and immunoglobulin with \"masked\" light chains, two tubes containing the patient\'s serum were incubated with a very high concentration of anti-total kappa and anti-total lambda antisera for 48 hours at 4°C in order to facilitate immunoprecipitation of the involved light chain. After centrifugation, the supernatant was analyzed by using the IFs method on the Hydrasys 2 Scan Focusing Sebia® without dilution. Then we applied the anti-IgA, anti-total kappa and anti-total lambda antisera.
RESULTS: The serum immunofixation test of the sample treated with a high concentration of anti-total kappa showed the disappearance of the monoclonal bands corresponding to IgA heavy chain lane and kappa light chain lane, indicating that precipitation had occurred and that the IgA did have kappa light chains that could not be detected by the standard immunofixation protocol. The serum immunofixation test of the sample treated with anti-total lambda showed the disappearance of the polyclonal background in lambda light chain lane, confirming that the precipitation with lambda light chains according to the previously mentioned protocol has done well.
CONCLUSIONS: This case illustrates some of the difficulties encountered and the corrective actions that can be taken for the detection of immunoglobulins with masked light chains.

BACKGROUND: The incidence of cryptococcosis amongst HIV-negative persons is increasing. Whilst the excellent performance of the CrAg testing in people living with HIV is well described, the diagnostic performance of the CrAg LFA has not been systematically evaluated in HIV-negative cohorts on serum or cerebrospinal fluid.
METHODS: We performed a systematic review to characterise the diagnostic performance of IMMY CrAg® LFA in HIV-negative populations on serum and cerebrospinal fluid. A systematic electronic search was performed using Medline, Embase, Global Health, CENTRAL, WoS Science Citation Index, SCOPUS, Africa-Wide Information, LILACS and WHO Global Health Library. Studies were screened and data extracted from eligible studies by two independent reviewers. A fixed effect meta-analysis was used to estimate the diagnostic sensitivity and specificity.
RESULTS: Of 447 records assessed for eligibility, nine studies met our inclusion criteria, including 528 participants overall. Amongst eight studies that evaluated the diagnostic performance of the IMMY CrAg® LFA on serum, the pooled median sensitivity was 96% (95% Credible Interval (CrI) 68-100%) with a pooled specificity estimate of 96% (95%CrI 84-100%). Amongst six studies which evaluated the diagnostic performance of IMMY CrAg® LFA on CSF, the pooled median sensitivity was 99% (95%CrI 95-100%) with a pooled specificity median of 99% (95%CrI 95-100%).
CONCLUSIONS: This review demonstrates a high pooled sensitivity and specificity for the IMMY CrAg® LFA in HIV-negative populations, in keeping with findings in HIV-positive individuals. The review was limited by the small number of studies. Further studies using IMMY CrAg® LFA in HIV-negative populations would help to better determine the diagnostic value of this test.

BACKGROUND: Cryptococcosis is an increasingly common infection given the growing immunocompromised population worldwide. Cryptococcal antigen (CrAg) testing demonstrates excellent sensitivity and specificity and is the mainstay of diagnosis. However, there may be rare instances in which false-negative CrAg results can delay diagnosis and early treatment, which are critical to ensure positive outcomes.
METHODS: A 31-year-old man living with HIV/AIDS who was not taking antiretroviral therapy was hospitalized with fever, diarrhea, and headaches. CD4 count on presentation was 71 cells/uL, and HIV viral load was 3,194,949 copies/mL. Serum CrAg testing was initially negative, however CSF CrAg performed several days later was positive at 1:40 and blood and CSF cultures grew Cryptococcus neoformans. Colonoscopy revealed mucosal papules throughout the sigmoid colon, and tissue biopsy showed yeast within the lamina propria consistent with GI cryptococcosis. Given the high burden of disease, the original serum CrAg specimen was serially diluted and subsequently found to be positive at 1:2,560, confirming the postzone phenomenon.
CONCLUSIONS: Cryptococcosis has a wide array of presentations including intraluminal GI disease, as seen in this patient. While serum CrAg testing displays excellent test characteristics, it is important for clinicians to be aware of the rare instances in which false-negative results may occur in the presence of excess antigen, as in this case.

BACKGROUND: Streptococcus pneumoniae is a leading cause of bacterial meningitis worldwide. Conventional microbiological assays take several days and require the use of various drugs for empirical treatment. Rapid antigen tests in cerebrospinal fluid (CSF) may be useful to triage pneumococcal meningitis immediately.
OBJECTIVE: To elucidate whether rapid antigen tests in CSF are useful in the triage of pneumococcal meningitis.
METHODS: Data sourcesCochrane CENTRAL, MEDLINE, EMBASE, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov databases were searched. Study eligibility criteriaAll types of cohort studies except multiple-group studies, where the sensitivity and specificity of rapid antigen tests in CSF compared with CSF culture can be extracted. ParticipantsPatients with suspected meningitis. TestsRapid antigen tests in CSF. Reference standardsOne or more of the following: blood culture, CSF culture, and polymerase chain reaction in CSF. Assessment of risk of biasThe methodological quality of the included studies was assessed using QUADAS-2. Methods of data synthesisWe used a random-effects bivariate model for the meta-analysis. We conducted a subgroup analysis by dividing studies into types of antigen tests, adults and children, low-income and high-income countries, and with or without exposure to antibiotics before lumbar puncture.
RESULTS: Forty-four studies involving 14 791 participants were included. Most studies had a moderate-to-low methodological quality. Summary sensitivity and specificity were 99.5% (95% confidence interval (CI), 92.4-100%) and 98.2% (95% CI, 96.9-98.9%), respectively. Positive predictive values and negative predictive values at the median prevalence (4.2%) in the included studies were 70.8% (95% CI, 56.6-79.9%) and 100% (95% CI, 99.7-100%), respectively. The diagnostic accuracy was consistent across the various subgroups, except for slightly reduced sensitivity in high-income countries.
CONCLUSIONS: Rapid antigen tests in CSF would be useful in triaging pneumococcal meningitis. Further studies are warranted to investigate the clinical benefit of ruling out pneumococcal meningitis based on the results of rapid antigen tests.

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Discoid lupus erythematosus and oral lichen planus are chronic systemic immune system-mediated diseases with unclear etiology and pathogenesis. The oral mucosa is the common primary site of pathogenesis in both, whereby innate and adaptive immunity and inflammation play crucial roles. The clinical manifestations of discoid lupus erythematosus on the oral mucosa are very similar to those of oral lichen planus; therefore, its oral lesion is classified under oral lichenoid lesions. In practice, the differential diagnosis of discoid lupus erythematosus and oral lichen planus has always relied on the clinical manifestations, with histopathological examination as an auxiliary diagnostic tool. However, the close resemblance of the clinical manifestations and histopathology proves challenging for accurate differential diagnosis and further treatment. In most cases, dentists and pathologists fail to distinguish between the conditions during the early stages of the lesions. It should be noted that both are considered to be precancerous conditions, highlighting the significance of early diagnosis and treatment. In the context of unknown etiology and pathogenesis, we suggest a serological and genetic diagnostic method based on TNF-α and IL-10. These are the two most common cytokines produced by the innate and adaptive immune systems and they play a fundamental role in maintaining immune homeostasis and modulating inflammation. The prominent variability in their expression levels and gene polymorphism typing in different lesions compensates for the low specificity of current conventional diagnostic protocols. This new diagnostic scheme, starting from the immunity and inflammation of the oral mucosa, enables simultaneous comparison of discoid lupus erythematosus and oral lichen planus. With relevant supportive evidence, this information can enhance physicians\' understanding of the two diseases, contribute to precision medicine, and aid in prevention of precancerous conditions.

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BACKGROUND: Urinary antigen tests (UATs) have been used for the early detection of legionellosis and have demonstrated moderate sensitivity and high specificity. However, the most recent systematic review and meta-analysis published in 2009 evaluated the accuracy of UATs; since then, UAT accuracy may have changed owing to advances and developments in UAT technology and epidemiological changes in the frequency of Legionella species that cause legionellosis. Therefore, this systematic review and meta-analysis aimed to update the accuracy of UATs for legionellosis among patients with suspected pneumonia.
METHODS: Overall, 1326 studies were screened, 21 of which fulfilled the eligibility criteria for quality assessment and meta-analysis. Data from 5772 patients, including 1368 (23.7%) with the target condition (i.e., suspected legionellosis), were included in the analysis. The overall quality of the included studies, which was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, was unclear.
RESULTS: The calculated pooled sensitivity and specificity were 0.79 (95% confidence interval [CI], 0.71-0.85) and 1.00 (95% CI, 0.99-1.00), respectively. Subpopulation analysis revealed that the accuracy of UATs for sensitivity and specificity for Legionella pneumophilia serogroup 1 was 0.86 (95% CI, 0.78-0.91) and 1.00 (95% CI, 0.99-1.00), respectively.
CONCLUSIONS: This study demonstrated that the sensitivity and specificity of UATs were moderate and high, respectively, which is comparable to the results reported in 2009. Therefore, UATs may be a useful method for the early detection of legionellosis caused by Legionella pneumophila serogroup 1.
BACKGROUND: The review protocol was prospectively registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000041080).

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune multisystemic diseases characterized by necrotizing inflammation of small vessels and the presence of circulating ANCA. The prevalence of overlap AAV with other autoimmune diseases was low.
METHODS: We report a case of a 54-year-old woman who presented with a 20-year-history of sicca symptoms, the presence of anti-Ro/SS-A, anti-La/SS-B antibodies, myeloperoxidase -ANCA (MPO-ANCA), significant increase of serum IgG4 level, microscopic hematuria, non-nephrotic proteinuria, and progressive renal dysfunction. A renal biopsy showed pauci-immune necrotizing glomerulonephritis with crescents with severe tubulointerstitial nephritis (TIN) which shows extensive infiltration of IgG4-positive plasma cells. Considering these findings and the clinical course, the disease was considered more likely to be MPO-ANCA-associated vasculitis accompanied by IgG4-TIN with underlying primary Sjögren syndrome (pSS).
CONCLUSIONS: This report shows a possible unusual disease overlap of MPO-ANCA-associated vasculitis and IgG4-TIN with underlying pSS.