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Ante-mortem diagnosis of bovine tuberculosis (bTB) is based mainly on the tuberculin skin test (TST) and the ...-IFN release assay (IGRA). Some infected animals escape screening tests, thus, limit herd sanitation. Previous reports have suggested a predominant pattern of multi-organ lesions attributable to Mycobacterium bovis (the causative agent of bTB) bacteraemia. A case--control study was conducted to investigate blood PCR as an alternative tool for improving ante-mortem detection of TST false-negative bovines. Cases comprised 70 TST false-negative bovines (cases), which were serology positive, and controls included 81 TST positive bovines; all of them confirmed as infected with M. bovis. Detection of the IS6110 target through touchdown blood-PCR (IS6110 TD-PCR) was performed. The positivity of the blood-PCR was 27.2% in the control group. This performance was similar to the 15% obtained among cases (p = 0.134). Most cases identified by the IS6110 TD-PCR exhibited focalized lesions (p = 0.002). Results demonstrated that blood-PCR could detect TST false-negative cattle, even if they are negative for IGRA. Considering that cases exhibited humoral response to M. bovis, further studies conducted in a pre-serological stage could provide evidence about the real contribution of the technique in herds. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance diffusion-weighted imaging (DWI) is the most sensitive modality for ischemic stroke diagnosis. However, DWI may fail to detect ischemic lesions in a proportion of patients. Methods: Following PRISMA statement, a systematic search of Medline, Embase, and Web of Science was conducted until January 3, 2024. The inclusion was confined to English literature with sufficient reporting. Proportions of DWInegative ischemic stroke were pooled. For binary variables, odds ratios (ORs) were computed using the random-effects model. Results: Fourteen studies constituting 16,268 patients with a clinical diagnosis of ischemic stroke and available DWI findings were included. Intravenous thrombolysis (IVT) was administered to 19.6% of the DWI-negative group and 15.3% of the DWI-positive group. DWI-negative ischemic stroke was reported in 16% (95% CI: 10-24%; after sensitivity analysis: 11% [95% CI: 8-15%]) of stroke patients. Among minor stroke patients (National Institutes of Health Stroke scale [NIHSS] of 5 or less), 24% (95% CI 12-42%) had negative DWI findings. Predictors of DWI-negative scans included posterior circulation stroke, history of ischemic heart disease, prior stroke, or prior transient ischemic attack. Cardioembolic stroke (OR, 0.62, 95% CI: 0.41-0.93) and history of atrial fibrillation increased the likelihood of positive DWI findings (OR, 0.56, 95% CI: 0.45-0.71). Patients with DWI-negative ischemic stroke had higher odds of good functional outcomes (modified Rankin scale [mRS] of 0-1) (OR, 2.26; 95% CI: 1.03-4.92), lower odds of stroke recurrence (OR, 0.68; 95% CI: 0.48-0.96), and lower odds of severe disability or mortality (mRS of 3-6) (OR, 0.44; 95% CI: 0.34-0.57) compared to patients with positive DWI. Rates of symptomatic intracerebral hemorrhage after IVT were comparable between groups. Conclusion: DWI-negative findings were present in a significant proportion of ischemic stroke patients and may be utilized as a marker for favorable prognosis. [ABSTRACT FROM AUTHOR]

Progressive Multifocal Leukoencephalopathy (PML) is a possibly fatal demyelinating disease and John Cunningham Polyomavirus (JCPyV) is believed to cause this condition. The so-called JCPyV was initially reported in lymphoma and Human Immunodeficiency Virus (HIV) cases, whereas nowadays, its incidence is increasing in Multiple Sclerosis (MS) cases treated with natalizumab (Tysabri). However, there are conflicting literature data on its pathology and diagnosis, whereas some misdiagnosed reports exist, giving rise to further questions towards the topic. In reality, the so-called PML and the supposed JCPyV are not what they seem to be. In addition, novel and more frequent PML-like conditions may be reported, especially after the Coronavirus Disease 2019 (COVID-19) pandemic. [ABSTRACT FROM AUTHOR]

This document discusses a case study of a false-negative result in the anti-HCV antibody test, which is used to diagnose hepatitis C virus (HCV) infection. The patient in question had a positive HCV-RNA test but a negative anti-HCV result. The study found that the false-negative result was likely due to defects in the testing reagent used. The authors recommend using a combination of different detection methods and establishing appropriate retesting rules to improve the recognition of false-negative results. They also suggest using the fourth-generation HCV test, which detects both anti-HCV and the core antigen simultaneously, for improved clinical sensitivity. [Extracted from the article]

Autonomous Recording Units (ARUs) are widely used to survey for a variety of taxa. This survey method allows for high spatial and temporal coverage but will typically include identification errors that can bias estimates of occupancy. In some instances, verifying all individual detections is prohibitive. To direct verification effort, we developed a model to estimate the probability that transcribers would agree on an identification. Agreement probability was positively influenced by transcriber skill, identification confidence, species commonness and some song types. In contrast, agreement probability was lower when an acoustic signal was classified as a trill. We evaluated our model on independent data where all species detections were verified, and verification effort (time) was quantified. Our model performed well at predicting transcriber agreement on independent data (AUC = 0.71). We applied the model to randomised subsets of the independent data to compare the cost benefit of three approaches to verification under varying effort. We show how modelling probability of transcriber agreement can be used to more efficiently direct verification of species acoustic tags. Our approach could be adapted elsewhere to quantify and reduce species misidentifications in unverified passive acoustic monitoring data for either manual processing or detections from automated classifiers. [ABSTRACT FROM AUTHOR]

Ante-mortem diagnosis of bovine tuberculosis (bTB) is based mainly on the tuberculin skin test (TST) and the ɣ-IFN release assay (IGRA). Some infected animals escape screening tests, thus, limit herd sanitation. Previous reports have suggested a predominant pattern of multi-organ lesions attributable to Mycobacterium bovis (the causative agent of bTB) bacteraemia. A case–control study was conducted to investigate blood PCR as an alternative tool for improving ante-mortem detection of TST false-negative bovines. Cases comprised 70 TST false-negative bovines (cases), which were serology positive, and controls included 81 TST positive bovines; all of them confirmed as infected with M. bovis. Detection of the IS6110 target through touchdown blood-PCR (IS6110 TD-PCR) was performed. The positivity of the blood-PCR was 27.2% in the control group. This performance was similar to the 15% obtained among cases (p = 0.134). Most cases identified by the IS6110 TD-PCR exhibited focalized lesions (p = 0.002). Results demonstrated that blood-PCR could detect TST false-negative cattle, even if they are negative for IGRA. Considering that cases exhibited humoral response to M. bovis, further studies conducted in a pre-serological stage could provide evidence about the real contribution of the technique in herds.

Optical genome mapping (OGM) has been known as an all-in-one technology for chromosomal aberration detection. However, there are also aberrations beyond the detection range of OGM. This study aimed to report the aberrations missed by OGM and analyze the contributing factors. OGM was performed by taking both GRCh37 and GRCh38 as reference genomes. The OGM results were analyzed in blinded fashion and compared to standard assays. Quality control (QC) metrics, sample types, reference genome, effective coverage and classes and locations of aberrations were then analyzed. In total, 154 clinically reported variations from 123 samples were investigated. OGM failed to detect 10 (6.5%, 10/154) aberrations with GRCh37 assembly, including five copy number variations (CNVs), two submicroscopic balanced translocations, two pericentric inversion and one isochromosome (mosaicism). All the samples passed pre-analytical and analytical QC. With GRCh38 assembly, the false-negative rate of OGM fell to 4.5% (7/154). The breakpoints of the CNVs, balanced translocations and inversions undetected by OGM were located in segmental duplication (SD) regions or regions with no DLE-1 label. In conclusion, besides variations with centromeric breakpoints, structural variations (SVs) with breakpoints located in large repetitive sequences may also be missed by OGM. GRCh38 is recommended as the reference genome when OGM is performed. Our results highlight the necessity of fully understanding the detection range and limitation of OGM in clinical practice. [ABSTRACT FROM AUTHOR]

BackgroundMagnetic resonance diffusion-weighted imaging (DWI) is the most sensitive modality for ischemic stroke diagnosis. However, DWI may fail to detect ischemic lesions in a proportion of patients.MethodsFollowing PRISMA statement, a systematic search of Medline, Embase, and Web of Science was conducted until January 3, 2024. The inclusion was confined to English literature with sufficient reporting. Proportions of DWI-negative ischemic stroke were pooled. For binary variables, odds ratios (ORs) were computed using the random-effects model.ResultsFourteen studies constituting 16,268 patients with a clinical diagnosis of ischemic stroke and available DWI findings were included. Intravenous thrombolysis (IVT) was administered to 19.6% of the DWI-negative group and 15.3% of the DWI-positive group. DWI-negative ischemic stroke was reported in 16% (95% CI: 10–24%; after sensitivity analysis: 11% [95% CI: 8–15%]) of stroke patients. Among minor stroke patients (National Institutes of Health Stroke scale [NIHSS] of 5 or less), 24% (95% CI 12–42%) had negative DWI findings. Predictors of DWI-negative scans included posterior circulation stroke, history of ischemic heart disease, prior stroke, or prior transient ischemic attack. Cardioembolic stroke (OR, 0.62, 95% CI: 0.41–0.93) and history of atrial fibrillation increased the likelihood of positive DWI findings (OR, 0.56, 95% CI: 0.45–0.71). Patients with DWI-negative ischemic stroke had higher odds of good functional outcomes (modified Rankin scale [mRS] of 0–1) (OR, 2.26; 95% CI: 1.03–4.92), lower odds of stroke recurrence (OR, 0.68; 95% CI: 0.48–0.96), and lower odds of severe disability or mortality (mRS of 3–6) (OR, 0.44; 95% CI: 0.34–0.57) compared to patients with positive DWI. Rates of symptomatic intracerebral hemorrhage after IVT were comparable between groups.ConclusionDWI-negative findings were present in a significant proportion of ischemic stroke patients and may be utilized as a marker for favorable prognosis.

Breast MRI is a highly sensitive imaging modality that often detects findings that are occult on mammography and US. Given the overlap in appearance of benign and malignant lesions, an accurate method of tissue sampling for MRI-detected findings is essential. Although MRI-directed US and correlation with mammography can be helpful for some lesions, a correlate is not always found. MRI-guided biopsy is a safe and effective method of tissue sampling for findings seen only on MRI. The unique limitations of this technique, however, contribute to false negatives, which can result in delays in diagnosis and adverse patient outcomes; this is of particular importance as most MRI examinations are performed in the high-risk or preoperative setting. Here, we review strategies to minimize false negatives in biopsy of suspicious MRI findings, including appropriate selection of biopsy modality, use of meticulous MRI-guided biopsy technique, management after target nonvisualization, assessment of adequate lesion sampling, and determination of radiologypathology concordance. A proposed management algorithm for MRI-guided biopsy results will also be discussed. [ABSTRACT FROM AUTHOR]

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Polymerase chain reaction (PCR) is commonly used to detect Listeria monocytogenes , foodborne pathogen. This study conducted in silico genomic analysis to investigate the specificity and binding efficacy of four published pairs of PCR primers targeting Listeria prfA -virulence gene cluster (pVGC) based on Listeria sequences available. We first performed comprehensive genomic analyses of the pVGC, the main pathogenicity island in Listeria spp. In total, 2961 prfA , 642 plcB , 629 mpl , and 1181 hlyA gene sequences were retrieved from the NCBI database. Multiple sequence alignments and phylogenetic trees were generated using unique (non-identical or not-shared) sequences of each represented genes, targeting four pairs of PCR primers published previously, namely 202 prfA , 82 plcB , 150 mpl , and 176 hlyA unique gene sequences. Only the hlyA gene showed strong (over 94%) primer mapping results, while prfA, plcB , and mpl genes showed weak (<50%) matching results. In addition, nucleotide variations were observed at the 3′ end of the primers, indicating non-binding to the targets could potentially cause false-negative results. Thus, we propose designing degenerate primers or multiple PCR primers based on as many isolates as possible to minimize the false-negative risk and reach the aim of low tolerable limits of detection. [ABSTRACT FROM AUTHOR]

BACKGROUND: The MAVARIC study supported the use of the FocalPoint GS (FPGS) imaging system "No Further Review" (NFR) technology for cervical screening and recommended further investigation. A validation study (Nuttall et al.) was performed by Cervical Screening Wales before implementing the NFR slide reporting technology within the cervical screening program in Wales, United Kingdom. METHOD: A total of 45,317 SurePath liquid‐based cytology cervical screening samples were submitted for FPGS scanning within four Welsh cytology laboratories between 2006 and 2011. The study, Computer Assisted Evaluation, Screening and Reporting, involved scanning the slides using the FPGS and comparing the results with manual screening performed under established Cervical Screening Wales protocols. RESULTS: An increased number of abnormal cases presented in the NFR reporting category, significantly greater than that previously encountered. This anomaly resulted in higher false‐negative rates with potentially life‐changing consequences for the screening participant. Subsequent investigation determined that this increase in cases created an algorithm cascade or "sump" effect, which resulted in an unprecedented increased number of samples categorized as NFR. This exceeded the calibration parameters set for the FPGS and was thought to be caused by an increase in the number of younger women attending for screening following the death of a young reality television celebrity from cervical cancer. CONCLUSION: Adequate and timely calibration of FPGS technology is vital for quality assurance of the results produced, particularly following events that may impact on cervical precancer incidence rates. Failure to do so can result in potentially catastrophic screening incidents that are avoidable. Adequate and timely calibration of FocalPoint GS technology is necessary for quality assurance of the results produced, particularly following events that may impact on cervical precancer incidence rates. Failure to do so can result in potentially catastrophic screening incidents that are avoidable. [ABSTRACT FROM AUTHOR]

Objectives: The primary goal of this study was to examine the ultrasound and cytological characteristics of inconsistent cases (false negatives and false positives)of ultrasound-guided fine-needle aspiration cytology (US-FNAC) of cervical lymph nodes, to investigate factors influencing the diagnostic accuracy of fine-needle aspiration, and to improve diagnostic efficiency. Methods: The results of US and FNAC of cervical lymph nodes in 562 cases treated at our institution from February 2019 to June 2021 were retrospectively analyzed. FNAC cytology results were compared with the final diagnostic results (242 surgical resections/core-needle biopsy, 320 cases followed up for more than 1 year), and the final diagnostic results were taken as the gold standard, and the ultrasound features and clinicopathology-related features were systematically retrospectively analyzed in cases of inconsistency. Results: The overall diagnostic accuracy of US-FNAC for cervical lymph nodes was 94.9%, with a false-negative rate of 6.7% and a false-positive rate of 3.8%. Analyzing the cases, sampling error due to factors associated with ultrasound features, such as larger, more numerous nodes, non-solid, hypoechoic, inhomogeneous, and increased vascularity are the main causes of false-negative diagnosis, while smaller nodules, overlapping cytologic patterns, and overinterpretation by pathologists are associated with false-positive FNAC results. Conclusions: Proper interpretation of cytomorphologic and ultrasound features can improve diagnostic accuracy, and diagnostic misdiagnosis should be carefully observed, the identification of both features should be enhanced to reduce interpretation errors and sampling errors and to reduce the rate of misdiagnosis and missed diagnoses in fine needle aspiration of lymph nodes. [ABSTRACT FROM AUTHOR]

Optical genome mapping (OGM) has been known as an all-in-one technology for chromosomal aberration detection. However, there are also aberrations beyond the detection range of OGM. This study aimed to report the aberrations missed by OGM and analyze the contributing factors. OGM was performed by taking both GRCh37 and GRCh38 as reference genomes. The OGM results were analyzed in blinded fashion and compared to standard assays. Quality control (QC) metrics, sample types, reference genome, effective coverage and classes and locations of aberrations were then analyzed. In total, 154 clinically reported variations from 123 samples were investigated. OGM failed to detect 10 (6.5%, 10/154) aberrations with GRCh37 assembly, including five copy number variations (CNVs), two submicroscopic balanced translocations, two pericentric inversion and one isochromosome (mosaicism). All the samples passed pre-analytical and analytical QC. With GRCh38 assembly, the false-negative rate of OGM fell to 4.5% (7/154). The breakpoints of the CNVs, balanced translocations and inversions undetected by OGM were located in segmental duplication (SD) regions or regions with no DLE-1 label. In conclusion, besides variations with centromeric breakpoints, structural variations (SVs) with breakpoints located in large repetitive sequences may also be missed by OGM. GRCh38 is recommended as the reference genome when OGM is performed. Our results highlight the necessity of fully understanding the detection range and limitation of OGM in clinical practice.

Polymerase chain reaction (PCR) for the detection of nucleic acids is the gold standard test for the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is the probability of false-negative results with this test, which poses a threat to public health. Here, we highlight some important factors that should be considered for reducing the false-negative results of the SARS-CoV-2 PCR test. Copyright © 2022 Sabzevari and Nikbakht. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY 4.0.

The number of coronavirus disease 2019 (COVID-19) cases significantly increased with the emergence of multiple variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This has led to an ongoing effort focused on developing the diagnostic detection tests. Among the currently available tests, real-time reverse transcriptase PCR (RT-PCR) has been considered as the 'golden method' for the detection of SARS-COV-2. However, a significant number of inaccurate (false-negative/false-positive) results have been reported in spite of this method's reliability and effectiveness. These unreliable results may arise because of various issues encountered throughout the entire testing process starting with the sampling phase, going through the PCR process, and ending with the result analysis. This article aims to shed light on the errors that occur during the COVID-19 testing process and suggest ways to overcome them effectively. Accurate testing could be optimized by following the correct swabbing technique, using adequate RT-PCR kits and controls, setting clear lab guidelines, and properly interpreting the results. [ABSTRACT FROM AUTHOR]

Objectives: False‐negatives on cytology may be observed during follow‐ups for patients with persistent cervical intraepithelial neoplasia (CIN); however, the underlying reasons are unknown, and the relationship between the intra‐individual variability of false‐negatives and the menstrual cycle phase has not been elucidated. Therefore, this study aimed to determine whether the menstrual cycle influences cytological results to maximise the accuracy of such tests. Methods: A total of 154 liquid‐based cytological (LBC) samples were obtained during follow‐ups for 26 patients with CIN, and the relationship between cytological results and the menstrual cycle, which was classified into six phases, was analysed. Results: All LBC smears were satisfactory, and 20 of 154 (13.0%) specimens were negative for intraepithelial lesions or malignancy (NILM). A statistically significant association was observed between the cytological results and the phase of the menstrual cycle, χ2(2) = 19.322, P < 0.01. The association was moderately strong (Cramer's V = 0.354). The value of adjusted residuals showed a statistically significant increase in the NILM percentage as a cytological result during the early secretory phase (P < 0.01) and a statistically significant decrease in NILM during the menstrual and proliferative phases (P < 0.01). Conclusions: The present study revealed that false‐negative cytological results were found to more likely to occur during the early secretory phase. More careful and precise microscopic observation of Pap smears collected at the early secretory phase may contribute to a reduction in the occurrence of false‐negatives and improve cytological sensitivity. [ABSTRACT FROM AUTHOR]

Background: Non-invasive prenatal testing (NIPT) has had an incomparable triumph in prenatal diagnostics in the last decade. Over 1400 research articles have been published, predominantly praising the advantages of this test. Methods: The present study identified among the 1400 papers 24 original and one review paper, which were suited to re-evaluate the efficacy of > 750,000 published NIPT-results. Special attention was given to false-positive and false-negative result-rates. Those were discussed under different aspects—mainly from a patient-perspective. Results: A 27: 1 rate of false-positive compared to false-negative NIPT results was found. Besides, according to all reported, real-positive, chromosomally aberrant NIPT cases, 90% of those would have been aborted spontaneously before birth. These findings are here discussed under aspects like (i) How efficient is NIPT compared to first trimester screening? (ii) What are the differences in expectations towards NIPT from specialists and the public? and (iii) There should also be children born suffering from not by NIPT tested chromosomal aberrations; why are those never reported in all available NIPT studies? Conclusions: Even though much research has been published on NIPT, unbiased figures concerning NIPT and first trimester screening efficacy are yet not available. While false positive rates of different NIPT tests maybe halfway accurate, reported false-negative rates are most likely too low. The latter is as NIPT-cases with negative results for tested conditions are yet not in detail followed up for cases with other genetic or teratogenic caused disorders. This promotes an image in public, that NIPT is suited to replace all invasive tests, and also to solve the problem of inborn errors in humans, if not now then in near future. Overall, it is worth discussing the usefulness of NIPT in practical clinical application. Particularly, asking for unbiased figures concerning the efficacy of first trimester-screening compared to NIPT, and for really comprehensive data on false-positive and false-negative NIPT results. [ABSTRACT FROM AUTHOR]

The contemporary practice of monitoring physiologic parameters in the critical care setting is based on alarm systems with high sensitivity but low specificity. A natural consequence of this approach is a massive amount of alarms, which potentially leads to fatigue in the personnel and negatively impacts the quality of care provided. The study objective is to determine the prevalence, types, and determinants of alarms in a neurological critical care unit (NCCU) prototype. During a one-month period corresponding to 272 days of monitoring in 34 patients, nursing staff recorded the type and number of sounding alarms in a university NCCU. Alarms were categorized into three types as type-A alarms that were merely handled by the nursing staff, type-B alarms that were primarily managed by nurses, but the physician was also notified, and type-C alarms that were principally handled by NCCU physicians. There were a total of 9439 alarms, with an average of daily 34.7 alarms per bed, corresponding to one alarm every 41.4 min. Most of the alarms were type-A (57.7%), followed by type-B (39.2%) and type-C (3.1%) alarms. Alarms originated from electrocardiogram (34.6%), pulse oximeter (33.7%), noninvasive blood pressure monitoring (9.8%), respiratory monitoring (9.7%), intravenous fluid pumps (4.5%), ventilator (3.9%), enteral pumps (2.1%) and invasive blood pressure systems (1.7%). A noticeable diurnal variation was observed for type-A pulse oximeter, type-A and -B ECG alarms (increase during morning shifts), and type-A ventilator alarms (decrease during morning shifts). Alarms are highly prevalent in NCCUs and can correspond to an important portion of the workload. [ABSTRACT FROM AUTHOR]

Dengue diagnosis primarily relies on NS1 ELISA and serological (IgG/IgM) tests. There are reports of low and variable sensitivity of the widely used NS1 ELISA tests. Poor sensitivity has been attributed to patient's infection status, prevalent serotypes, and the geographical origin of the samples. We investigated whether NS1 mutations directly have any impact on NS1 ELISA-based dengue virus (DENV) detection in clinical samples. Fifty-eight serum samples were collected from dengue-endemic area during 2015–2017 and tested with three commonly used NS1 ELISA kits. The samples were subjected to diagnostic RT-PCR and sequencing of structural gene(s). Sequencing of NS1 gene revealed amino acid changes which were transferred to respective wild type NS1 backbone to determine their effects on NS1 production and secretion in Huh-7, Vero, and A549 cells. Eighty-seven percent samples were virus RNA-positive but 65% of these were NS1 ELISA-positive. NS1-gene mutations like Val236➔Ala (DENV2) or Trp68➔stop codon in DENV3 were associated with decreased NS1 production and secretion. These mutations were originally identified in NS1 ELISA-negative clinical isolates. All DENV1 and > 80% DENV2 were NS1 ELISA-positive. The three NS1 ELISA could not detect recently circulating DENV3 single infections despite being RNA-positive. Among serotypes 1–3, wild-type NS1 production was highest for DENV1 and lowest for DENV3 in all cell lines tested. Mutations in circulating DENV directly correlated with NS1 production and secretion and, hence, ELISA-based NS1 detection. Further studies to define more NS1 mutations in clinical samples are needed to optimize ELISA kits for more sensitive dengue diagnosis. [ABSTRACT FROM AUTHOR]

A real-time reverse transcriptase polymerase chain reaction (RT-PCR) is the gold standard in diagnosis for infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the false-negative result is the problem in the prevention and control the pandemic of coronavirus disease 2019 (COVID-19). A false-negative of RT-PCR test needs to be evaluated when the patient showed a high clinical suspicion for COVID-19. We report a 36-year-old man with 4 times negative RT-PCR results, but clinical, radiological (chest X-ray and chest CT scan), and serological examinations showed a high suspicion of COVID-19. History of close contacted with COVID-19 confirmed patient was reported, and the wife of our case was also RT-PCR tested positive for SARS-CoV-2 in the next few days strengthen the COVID-19 diagnosis of our case patient. It is important to use the combination of RT-PCR, chest X-ray, chest CT scan, clinical manifestations, antibodies test, and exposure history of patients to diagnose COVID-19 and decide the early isolation and appropriate treatment.

Background: Research studies comparing antibody response from coronavirus disease 2019 (COVID-19) cases that retested positive (RP) using reverse transcription polymerase chain reaction (RT-PCR) and those who did not retest positive (NRP) were used to investigate a possible relationship between antibody response and retesting status. Methods: Seven data bases were searched. Research criteria included cohort and case-control studies, carried out worldwide and published before September 9, 2020, that compared the serum antibody levels of hospitalized COVID-19 cases that RP after discharge to those that did NRP. Results: There is some evidence that immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody levels in RP cases were lower compared with NRP cases. The hypothesis of incomplete clearance aligns with these findings. The possibility of false negative reverse transcription polymerase chain reaction (RT-PCR test results during viral clearance is also plausible, as concentration of the viral ribonucleic acid (RNA) in nasopharyngeal and fecal swabs fluctuate below the limits of RT-PCR detection during virus clearance. The probability of reinfection was less likely to be the cause of retesting positive because of the low risk of exposure where cases observed a 14 day-quarantine after discharge.

Background: The IBCSG 23-01 and AMAROS trials both reported that axillary lymph node dissection (ALND) did not change survival rates in breast cancer patients with positive nodes detected by sentinel lymph node biopsy (SLNB). The aim of this study was to determine whether breast cancer patients with mastectomy and false-negative frozen section (FS) in SLNB could forgo ALND. Materials and Methods: This was a retrospective study of cN0 patients diagnosed with primary invasive breast cancer treated by mastectomy and SLNB at our institute between January 2010 and December 2014. Patients with false-negative FS in SLNB were separated by the following management of axillary lymph node dissection in the non-ALND group (nonprocess or axillary radiation only) and ALND group (with or without radiation). Results: A total of 212 patients were included, 86 and 126 patients in the non-ALND and ALND groups, respectively. The positive rate of non-sentinel lymph nodes (SLNs) was 15.87% (20/126) in the ALND group. In multivariate analysis, we found that patients with larger tumor size (>2 cm) (OR, 1.989; p = 0.030) and multifocal lesions (OR, 3.542; p = 0.029) tended to receive ALND. The positivity of non-SLNs in the ALND group was associated with SLN macrometastasis (OR, 3.551; p = 0.043) and lymphovascular invasion (OR, 6.158; p = 0.003). Also, removing more SLNs (≥3) was related to negativity in non-SLNs (OR, 0.255; p = 0.016). After a median follow-up of 59.43 months, RFS and OS of the two groups were similar (p = 0.994 and 0.441). In subgroup analysis, we found that 97 patients who met the inclusive criteria of the IBCSG 23-01 trial had similar RFS and OS between the non-ALND and ALND groups (p = 0.856 and 0.298). The positive rate of non-SLNs was 9.62% (5/52). Also, in 174 patients who met the criteria of the AMAROS trial, RFS and OS in the non-ALND and ALND groups were similar (p = 0.930 and 0.616). The positive rate of non-SLNs was 18.27% (19/104). Conclusion: ALND can be carefully omitted in selected breast cancer patients with mastectomy and false-negative FS in SLNB. SLNB is relatively sufficient in the IBCSG 23-01-eligible patients, and axillary radiation was an effective option in the AMAROS-eligible patients. [ABSTRACT FROM AUTHOR]

BackgroundThe IBCSG 23-01 and AMAROS trials both reported that axillary lymph node dissection (ALND) did not change survival rates in breast cancer patients with positive nodes detected by sentinel lymph node biopsy (SLNB). The aim of this study was to determine whether breast cancer patients with mastectomy and false-negative frozen section (FS) in SLNB could forgo ALND.Materials and MethodsThis was a retrospective study of cN0 patients diagnosed with primary invasive breast cancer treated by mastectomy and SLNB at our institute between January 2010 and December 2014. Patients with false-negative FS in SLNB were separated by the following management of axillary lymph node dissection in the non-ALND group (nonprocess or axillary radiation only) and ALND group (with or without radiation).ResultsA total of 212 patients were included, 86 and 126 patients in the non-ALND and ALND groups, respectively. The positive rate of non-sentinel lymph nodes (SLNs) was 15.87% (20/126) in the ALND group. In multivariate analysis, we found that patients with larger tumor size (>2 cm) (OR, 1.989; p = 0.030) and multifocal lesions (OR, 3.542; p = 0.029) tended to receive ALND. The positivity of non-SLNs in the ALND group was associated with SLN macrometastasis (OR, 3.551; p = 0.043) and lymphovascular invasion (OR, 6.158; p = 0.003). Also, removing more SLNs (≥3) was related to negativity in non-SLNs (OR, 0.255; p = 0.016). After a median follow-up of 59.43 months, RFS and OS of the two groups were similar (p = 0.994 and 0.441). In subgroup analysis, we found that 97 patients who met the inclusive criteria of the IBCSG 23-01 trial had similar RFS and OS between the non-ALND and ALND groups (p = 0.856 and 0.298). The positive rate of non-SLNs was 9.62% (5/52). Also, in 174 patients who met the criteria of the AMAROS trial, RFS and OS in the non-ALND and ALND groups were similar (p = 0.930 and 0.616). The positive rate of non-SLNs was 18.27% (19/104).ConclusionALND can be carefully omitted in selected breast cancer patients with mastectomy and false-negative FS in SLNB. SLNB is relatively sufficient in the IBCSG 23-01-eligible patients, and axillary radiation was an effective option in the AMAROS-eligible patients.

Intraoperative pathology consultation plays an important role in the management of surgical patients and is also a measure for quality control in surgical pathology. A retrospective study was conducted to review intraoperative consultation during a 5-year period at a single institution. There were 19,145 intraoperative pathology consultation cases, including 19,026 concordant cases, 71 (<1%) frozen discordant cases, 11 (<1%) gross discordant cases, and 37 (<1%) deferred cases. Among frozen discordant cases, the most common cause for discordance was histologic sampling error (52.1%), followed by misinterpretation (42.3%). The most common major (clinically significant) frozen discordance was histologic sampling error for skin margins (32.4%), followed by histologic sampling error for lymph node metastasis (13.5%). Although our discordant rate (0.43%) was lower than that in previously reported studies (2%–8%), our major discordant rate was relatively high (50%). This review suggests that deeper sectioning of the blocks could improve the quality of our intraoperative consultations. [ABSTRACT FROM AUTHOR]

Objective: This study sought to establish the diagnostic utility of performing a second biopsy using an magnetic resonance (MR)-guided percutaneous transthoracic needle biopsy (PTNB) approach in patients with suspicious malignant lung lesions that had already undergone an initial negative computed tomography (CT)-guided biopsy.Materials and Methods: This study evaluated 31 patients with suspicious lung lesions (18 males, 13 females; mean age: 62.1 ± 11.3 years) that had previously undergone CT-guided PTNB with negative pathological findings January 2015-November 2020. A final histopathological diagnosis was made based on resected lung lesion specimens or, when resection was not conducted, on clinical diagnosis following a ≥6-month follow-up. The diagnostic accuracy of MR-guided secondary lung biopsy was determined by comparing the lung biopsy results for each patient to their final diagnosis.Results: 1.0T open MR-guided secondary lung biopsy was performed for 31 lesions (20 central, 11 peripheral; mean size, 5.3 ± 2.0 cm). The pathological results revealed 20/31 (64.5%) lesions to be malignant (14 adenocarcinoma, 4 squamous cell carcinoma, and 2 small-cell lung cancer) as detected by 1.0T open MR-guided PTNB and confirmed by surgical pathology and clinical follow-up. There were three instances of biopsy-induced complications including hemorrhage in 6.5% of the patients (2/31) and pneumothorax in 3.2% of the patients (1/31). No patients experienced severe complications.Conclusion: For individuals with clinically suspicious lung lesions that initially received negative CT-guided PTNB findings, 1.0T open MR-guided secondary lung biopsy is a safe and effective secondary diagnostic approach. [ABSTRACT FROM AUTHOR]

Background: Microorganism identification is critical for the early diagnosis and management of infectious endophthalmitis, but traditional culture can yield false‐negative results. Nanopore targeted sequencing (NTS) is a third‐generation sequencing technique with multiple advantages. This study aimed to test aqueous humour or vitreous fluid samples from presumed cases of infectious endophthalmitis using NTS to evaluate the feasibility of NTS in diagnosing endophthalmitis, especially for culture‐negative cases. Methods: This prospective study enrolled patients who presented to the Department of Ophthalmology of Union Hospital (Wuhan, China) between June 2018 and December 2020. The samples were sent immediately for routine microbiology culture processing and NTS assay. Results: NTS identified microorganisms in 17 of 18 cases (94.4%) (eight culture‐positive cases, nine culture‐negative cases, and one case unavailable for culture). There was a high‐quality match between culture and NTS for culture‐positive cases. In the eight culture‐negative cases and the case unavailable for culture, NTS detected either bacteria, fungi, or a mixture of bacteria and fungi in the intraocular fluids. The average waiting times for the results of bacterial and fungal cultures were 48 and 72 h, respectively. The average time for the NTS results was 12 h. Conclusions: NTS appears to be a promising diagnostic platform for diagnosing infectious endophthalmitis, even for culture‐negative cases. [ABSTRACT FROM AUTHOR]

Abstract Background Positron Emission Tomography with Computed Tomography (PET/CT) is widely used in the assessment of many diseases, particularly including cancer. However, many factors can affect image quality and diagnostic performance of PET scans using FDG or other PET probes. Main body The aim of this pictorial essay is to review PET/CT protocols that can be useful to overcome these confounding factors in routine clinical situations, with a particular focus on pharmacological interventions and problem-oriented CT acquisition protocols. Conclusion Imaging protocols and representative cases will be discussed, in addition to potential contraindications and precautions to be taken.

Abstract Objective FNA is a simple, safe, cost-effective and accurate diagnostic tool for the initial screening of patients with thyroid nodules. The aims of this study were to determine the diagnostic utility of FNAC performed in our institution, assess the cytomorphologic features that contribute to diagnostic errors and propose improvement measures. Methods A total of 2781 FNACs were included in the study, and 1122 cases were compared with their histological diagnoses. We retrospectively reexamined our discordant (both false-negative and false-positive) cases and performed a systematic review of previous studies on causes of misdiagnoses. Results When DC V and DC VI were both considered cytologic-positive, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy were 98.3, 30.9, 94.9, 58.3 and 93.5%, respectively. If DC VI was considered cytologic-positive, the sensitivity, specificity, PPV, NPV and diagnostic accuracy of FNAC were 98.0, 84.0, 99.4, 58.3, and 97.5% respectively. The main cause of false-negative diagnoses was sampling error (13/15, 86.7%), while interpretation error led to the majority of the false-positive diagnoses (38/47, 80.9%). Overlapping cytological features in adenomatous hyperplasia, thyroiditis and cystic lesions were the major factors contributing to interpretation errors, while the size and number of nodules may have led to false-negative diagnoses because of heterogeneity and unsampled areas. Conclusions The sensitivity and PPV of thyroid FNAC in our institution were higher than those in the published data, while the specificity and NPV were lower. Regarding the FNA category DC V, a frozen section analysis during diagnostic lobectomy is necessary. Multiple passes should be performed in various parts of a large nodule or from different nodules to reduce the risk of false-negative findings. Cytopathologists should strengthen their criteria for the identification of adenomatous hyperplasia, thyroiditis and cystic lesions to avoid false-positive diagnoses. NIFTP has little effect on diagnostic accuracy and the distribution of diagnostic errors.

In the short 10 years following the introduction of non-invasive prenatal testing (NIPT), it has been adapted in many countries around the world as a standard screening test. In this review, this development was analyzed with a special focus on Germany. As a result, it can be stated that all known advantages of NIPT apart from “compensating for having no access to centers offering invasive diagnostics” are valid for Germany. In addition, following a review of the international literature, all documented issues with NIPT are also observed in Germany. However, the German Gene Diagnostics Act (GenDG) addresses a number of these issues, for example, the regulations by GenDG hamper induced abortions, based exclusively on an abnormal NIPT result. At the same time, GenDG has created new problems, as a possible collusion between the “right not to know with regard to parts of the examination result” may occur, or that the sex of the fetus must not be reported to the pregnant woman before the 12th week of gestation. Main conclusions drawn are that appropriate training and the continuing education of the physicians providing NIPT-related counseling are needed, as well as the provision of balanced and comprehensive information for the pregnant woman or the couple that is imperative.

The coronavirus disease 2019 (COVID-19) has caused and is still causing tremendous damage to the global economy and human health. Qualitative reverse transcription-PCR (RT-qPCR) is the golden standard for COVID-19 test. However, the SARS-CoV-2 variants may not only make vaccine less effective but also evade RT-qPCR test. Here we suggest an innovative primer design strategy for the RT-qPCR test of SARS-CoV-2. The principle is that the primers should be designed based on both the nucleic acid sequence and the structure of the protein encoded. The three nucleotides closest to the 3′ end of the primer should be the codon which encodes the tryptophan in the structure core. Based on this principle, we designed a pair of primers targeting the nucleocapsid (N) gene. Since tryptophan is encoded by only one codon, any mutation that occurs at this position would change the amino acid residue, resulting in an unstable N protein. This means that this kind of SARS-CoV-2 variant could not survive. In addition, both our data and previous reports all indicate that the mutations occurring at other places in the primers do not significantly affect the RT-qPCR result. Consequently, no SARS-CoV-2 variant can escape detection by the RT-qPCR kit containing the primers designed based on our strategy. [ABSTRACT FROM AUTHOR]

Polymerase chain reaction (PCR) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is necessary for confirming a diagnosis of Coronavirus disease 2019 (COVID-19). Here we present a COVID-19 case of an elderly woman whose SARS-CoV-2 PCR tests showed false negative repeatedly by evaluating with different sampling sites and procedures. Nasopharyngeal swabs, suctioned sputum, and tongue swabs were collected for SARS-CoV-2-PCR. As for tongue swabs, we compared between two different sample conditions; one obtained with dry condition and the other obtained with moistened condition inside the oral cavity. SARS-CoV-2-PCR showed positive for an extended period with suctioned sputum samples compared with nasopharyngeal swabs and tongue swabs. No SARS-CoV-2 from a nasopharyngeal swab sample obtained on day 46 after symptoms onset was isolated despite high viral load (183740.5 copies/5μL). An adequate production of neutralizing antibody in a serum sample on day 46 was also confirmed. The number of RNA copies of the tongue swab samples was higher with moistened condition than with dry condition. The present case suggests that the difference of sampling site or sample condition can affect PCR results. High loads viral RNA detection does not always correlate with infectivity. [ABSTRACT FROM AUTHOR]

Bimodal intraoperative neuromonitoring (IONM), combining transcranial motor-evoked potentials (tcMEP) and somatosensory-evoked potentials (SSEP), enables real-time detection and prevention of spinal cord injury during pediatric spinal deformity correction. Although rare, false-positive and false-negative signal alerts have been reported. However, no previously published accounts have described the use of postoperative neurophysiological testing to both identify new-onset neurological injury and guide reintervention. Here, we describe the case of an 18-year-old young man with achondroplasia, thoracolumbar kyphosis, and L2 wedge vertebra who underwent T12–L4 posterior spinal fusion with L2 vertebral column resection. Despite two intraoperative decreases in tcMEP amplitude, corrective measures on both occasions produced a return of IONM signal. Curiously, despite movement of the bilateral lower extremities upon waking, continued observation demonstrated minimal movement of the left lower extremity. Postoperative neurophysiological testing then identified limited muscle group activation below the left quadriceps, prompting operative reintervention. After cage removal and laminectomy lengthening, the patient recovered bilateral lower extremity function. He later returned to surgery for repeat cage placement at L2 via a retroperitoneal exposure, with no noted IONM changes and subsequent neurological improvement. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) has caused and is still causing tremendous damage to the global economy and human health. Qualitative reverse transcription-PCR (RT-qPCR) is the golden standard for COVID-19 test. However, the SARS-CoV-2 variants may not only make vaccine less effective but also evade RT-qPCR test. Here we suggest an innovative primer design strategy for the RT-qPCR test of SARS-CoV-2. The principle is that the primers should be designed based on both the nucleic acid sequence and the structure of the protein encoded. The three nucleotides closest to the 3′ end of the primer should be the codon which encodes the tryptophan in the structure core. Based on this principle, we designed a pair of primers targeting the nucleocapsid (N) gene. Since tryptophan is encoded by only one codon, any mutation that occurs at this position would change the amino acid residue, resulting in an unstable N protein. This means that this kind of SARS-CoV-2 variant could not survive. In addition, both our data and previous reports all indicate that the mutations occurring at other places in the primers do not significantly affect the RT-qPCR result. Consequently, no SARS-CoV-2 variant can escape detection by the RT-qPCR kit containing the primers designed based on our strategy.

The article provides a methodology for assessing the trustworthiness of health monitoring the dismounted avionics systems with automated test equipment (ATE). The indicators include the probabilities of false-positive, false-negative, true-positive, and true-negative. For the first time, we introduced into consideration the instability of the source of stimulus signal (SSS), the random and systematic component of the measuring channel error, and the reliability characteristics of the systems themselves. We consider a specific case of an exponential distribution of permanent failures and intermittent faults and derive formulas for calculating the trustworthiness indicators. Numerical calculations illustrate how the probabilities of correct and incorrect decisions depend on accuracy parameters. We show that the probabilities of false-positive and false-negative increase much faster than the probabilities of true-positive and true-negative decrease when the standard deviation of stimulus signal increases. For a Very High-Frequency Omni-Directional Range (VOR) receiver, we demonstrate that even with a zero random error generated by the source of the stimulus signal, the probabilities of false-positive and false-negative are different from zero.

Objectives The 2019 ACR/EULAR classification criteria for IgG4-related disease (IgG4-RD) have exclusion criteria including positive disease-specific autoantibodies, and these have been documented to have a high specificity. This study aimed to further validate these criteria as well as identify characteristics of patients showing false-negative results. Methods We retrospectively analysed 162 IgG4-RD patients and 130 mimickers. The sensitivity, specificity and fulfilment rates for each criterion were calculated, and intergroup comparisons were performed to characterize the false-negative cases. Results Both the IgG4-RD patients and mimickers were aged ≥65 years with male predominance. The final diagnoses of mimickers were mainly malignancy, vasculitis, sarcoidosis and aneurysm. The classification criteria had a sensitivity of 72.8% and specificity of 100%. Of the 44 false-negative cases, one did not fulfil the entry criteria, 20 fulfilled one exclusion criterion and 27 did not achieve sufficient inclusion criteria scores. The false-negative cases had fewer affected organs, lower serum IgG4 levels, and were less likely to have received biopsies than the true-positive cases. Notably, positive disease-specific autoantibodies were the most common exclusion criterion fulfilled in 18 patients, only two of whom were diagnosed with a specific autoimmune disease complicated by IgG4-RD. In addition, compared with the true-positive cases, the 18 had comparable serum IgG4 levels, number of affected organs, and histopathology and immunostaining scores despite higher serum IgG and CRP levels. Conclusions The ACR/EULAR classification criteria for IgG4-RD have an excellent diagnostic specificity in daily clinical practice. Positive disease-specific autoantibodies may have limited clinical significance for the diagnosis of IgG4-RD. [ABSTRACT FROM AUTHOR]

Background: Alpha-defensin (AD) is a synovial biomarker included as a minor criterion in the scoring system for diagnosing periprosthetic joint infection (PJI). The purpose of this study is to study the impact of AD on diagnosis and management of PJI.Methods: Synovial fluid from 522 patients after total knee and hip arthroplasty was retrospective reviewed. Synovial white blood cell count, percentage of neutrophils, and culture from the AD immunoassay laboratory were reviewed with serum erythrocyte sedimentation rate and C-reactive protein values from our institution. A modified version of the 2018 scoring system for diagnosis of PJI was used, only scoring white blood cell count, percentage of neutrophils, erythrocyte sedimentation rate, and C-reactive protein. AD was then analyzed with these scores to determine if AD changed diagnostic findings or clinical management.Results: Eight-two patients were categorized as "infected" (score ≥6), of which 76 patients had positive AD. Of the 6 "infected" patients with negative AD, 2 had positive cultures (Staphylococcus epidermidis). Two-hundred thirteen patients were diagnosed as "possibly infected" (score 2-5). Fourteen of these patients had positive AD, of which 5 had positive cultures assisting with the diagnosis. The AD test changed the diagnosis from "possibly infected" to "infected" in 8 patients (1.5%) but only altered treatment plan in 6 patients (1.1%). A score <2 (not infected) was calculated in 227 patients with no patients having positive AD.Conclusion: AD may be beneficial in some cases where laboratory values are otherwise equivocal; however, its routine use for the diagnosis of PJI may not be warranted. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 53-year-old man with diagnosis of type 1 diabetes mellitus and various diabetes complications such as nephropathy, mild retinopathy, and moderate sensory-motor neuropathy. Topics include blood revealing renal insufficiency with secondary hyperparathyroidism and increased hemoglobin; and quantifying the protein fractions based on protein-specific dye binding.

Abstract Metastatic lymph nodes (LNs) may be the origin of systemic metastases. It will be important to develop a strategy that prevents systemic metastasis by treating these LNs at an early stage. False‐negative metastatic LNs, which are found during the early stage of metastasis development, are those that contain tumor cells but have a size and shape similar to LNs that do not host tumor cells. Here, we show that 5‐fluorouracil (5‐FU), delivered by means of a novel lymphatic drug delivery system (LDDS), can treat LNs with false‐negative metastases in a mouse model. The effects of 5‐FU on four cell lines were investigated using in vitro cytotoxicity and cell survival assays. The therapeutic effects of LDDS‐administered 5‐FU on false‐negative metastatic LNs were evaluated using bioluminescence imaging, high‐frequency ultrasound (US), and histology in MHX10/Mo‐lpr/lpr mice. These experimental animals develop LNs that are similar in size to human LNs. We found that all cell lines showed sensitivity to 5‐FU in the in vitro assays. Furthermore, a concentration‐dependent effect of 5‐FU to inhibit tumor growth was observed in tumor cells with low invasive growth characteristics, although a significant reduction in metastatic LN volume was not detected in MHX10/Mo‐lpr/lpr mice. Adverse effects of 5‐FU were not detected. 5‐Fluorouracil administration with a LDDS is an effective treatment method for false‐negative metastatic LNs. We anticipate that the delivery of anticancer drugs by a LDDS will be of great benefit in the prevention and treatment of cancer metastasis via LNs.

Human papillomavirus (HPV) has been the leading cause of cervical cancer for over 25 years. Approximately 5.5–11% of all cervical cancers are reported to be HPV-negative, which can be attributed to truly negative and false-negative results. The truly HPV-negative cervical cancers are almost all cervical adenocarcinomas with unclear etiology. False HPV negativity can arise from histological misclassification, latent HPV infection, disruption of the targeting fragment, non-high risk HPV infection, and HPV testing methods. HPV-negative cervical cancers are often diagnosed at an advanced FIGO stage and have a poor prognosis; thus, the management of these cases requires greater attention.

Background: Research studies comparing antibody response from coronavirus disease 2019 (COVID-19) cases that retested positive (RP) using reverse transcription polymerase chain reaction (RT-PCR) and those who did not retest positive (NRP) were used to investigate a possible relationship between antibody response and retesting status.Methods: Seven data bases were searched. Research criteria included cohort and case-control studies, carried out worldwide and published before September 9, 2020, that compared the serum antibody levels of hospitalized COVID-19 cases that RP after discharge to those that did NRP.Results: There is some evidence that immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody levels in RP cases were lower compared with NRP cases. The hypothesis of incomplete clearance aligns with these findings. The possibility of false negative reverse transcription polymerase chain reaction (RT-PCR test results during viral clearance is also plausible, as concentration of the viral ribonucleic acid (RNA) in nasopharyngeal and fecal swabs fluctuate below the limits of RT-PCR detection during virus clearance. The probability of reinfection was less likely to be the cause of retesting positive because of the low risk of exposure where cases observed a 14 day-quarantine after discharge.Conclusion: More studies are needed to better explain the immune response of recovered COVID-19 cases retesting positive after discharge. [ABSTRACT FROM AUTHOR]

Objective: A standardized procedure of fused REarranged during Transfection (RET) gene detection using fluorescence in situ hybridization (FISH) remains to be established in papillary thyroid carcinoma (PTC). Our purpose was to investigate false-negative and false-positive events and their FISH signal characteristics.Methods: A total of 111 PTC cases were analyzed using break-apart FISH probes for RET status evaluation. All FISH results were validated using fusion-induced asymmetric transcription assay (FIATA)-based reverse transcription droplet digital PCR (RT-ddPCR). Then, suspected RET-positive cases were tested using quantitative reverse transcription-PCR (RT-qPCR), followed by next-generation sequencing (NGS) for recognizing fusion variants.Results: Thirty RET+ cases were revealed, including 20 CCDC6 (exon 1)-RET (exon 12), 6 NCOA4 (exon 8)-RET (exon 12), 1 NCOA4 (exon 7)-RET (exon 12), 1 CCDC186 (exon 7)-RET (exon 12), 1 ERC1 (exon 12)-RET (exon 12) and 1 SPECC1L (exon 9)-RET (exon 12) tumors. All RET fusion cases occurred in the BRAF- population, with a prevalence of 41.7% (30/72). Four cases of 8% to 13% (cutoff was 7.6%) dominant isolated 3' green (IG) FISH signals were RET-. One FISH- case with isolated 5' red (IR) signals with 94% abnormal tumor cells was demonstrated to be positive, harboring the NCOA4 (exon 7)-RET (exon 12) variant. Compared with RET fusions characterized by dominant break-apart signals with 29% to 100% aberrant cells, RET + with dominant IG-signal patterns all showed more frequent FISH+ cells (84%-92%). RET+ PTC with a break-apart signal pattern was more frequently found in unifocal lesions than in multifocal/bilateral tumors (P = 0.049).Conclusions: A false-positive or false-negative event may exist for RET status detection in PTCs using the traditional FISH scoring method with break-apart probes. [ABSTRACT FROM AUTHOR]

Countries responded to the COVID-19 pandemic with various levels of restrictions and lockdown in an effort to save lives and prevent the saturation and collapse of national health systems. Unfortunately, the blockades have entailed hefty socioeconomic costs. In order to contrast the spread of the virus, states have used contact tracing technology, in the form of mobile phone applications designed to track close contacts of those infected with COVID-19. Recent research has shown the effectiveness of this solution, particularly when used in conjunction with manual tracking. Nonetheless, the contact tracing app raises concerns due to the potential privacy implications. The authors have delved into the European legislation that protects privacy through the principles of proportionality and minimization, arguing that in order to quickly resolve the pandemic caused by COVID-19, one cannot blindly trust the exclusive help of technology. Instead, we need the involvement of health personnel, scientists, and no less importantly, the citizenry’s sense of solidarity and the duty to abide by the rules of social distancing, the use of protective devices and hygiene rules to protect public health. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) has been the leading cause of cervical cancer for over 25 years. Approximately 5.5–11% of all cervical cancers are reported to be HPV-negative, which can be attributed to truly negative and false-negative results. The truly HPV-negative cervical cancers are almost all cervical adenocarcinomas with unclear etiology. False HPV negativity can arise from histological misclassification, latent HPV infection, disruption of the targeting fragment, non-high risk HPV infection, and HPV testing methods. HPV-negative cervical cancers are often diagnosed at an advanced FIGO stage and have a poor prognosis; thus, the management of these cases requires greater attention. [ABSTRACT FROM AUTHOR]

Background: Consistency among clinical symptoms, laboratory results and autopsy findings can be a quality measure in the diagnosis of coronavirus disease 2019 (COVID-19). There have been classic clinical cases that have met the case definition of COVID-19 but real-time reverse-transcription polymerase chain reaction (rRT-PCR) tests of nasopharyngeal swabs were negative. Objectives: This study aimed to share pathological observations of autopsies performed at the 37 Military Hospital’s Department of Anatomical Pathology on three presumed COVID-19 cases in Accra, Ghana. Method: Complete autopsies with detailed gross and histopathological analysis were conducted between April 2020 and May 2020 on three suspected COVID-19 cases, of which two had initial negative (rRT-PCR) nasopharyngeal tests. Postmortem bronchopulmonary samples of two cases were collected and tested by rRT-PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results: The two postmortem bronchopulmonary samples tested for SARS-CoV-2 by rRT-PCR were positive. Though no postmortem bronchopulmonary sample was taken from the third case, a close contact tested positive for SARS-CoV-2 in later contact tracing. For all three cases, lung histopathological findings were consistent with Acute Respiratory Distress Syndrome. Conclusion: The outcome of COVID-19 testing is dependent on the sample type and accuracy of sampling amongst other factors. Histopathological findings vary and may be dependent on a patient’s modifying factors, as well as the duration of infection. More autopsies are required to fully understand the pathogenesis of this disease in Ghanaians.

Many studies have shown that re-positive tests for SARS-CoV-2 by RT-PCR in recovered COVID-19 patients are very common. We aim to conduct this review to summarize the clinical and epidemiological characteristics of these patients and discuss the potential explanations for recurrences, the contagiousness of re-detectable positive SARS-CoV-2 virus, and the management of COVID-19 patients after discharge from hospital. The proportion of re-positive tests in discharged COVID-19 patients varied from 2.4 to 69.2% and persisted from 1 to 38 days after discharge, depending on population size, age of patients, and type of specimens. Currently, several causes of re-positive tests for SARS-CoV-2 in recovered COVID-19 patients are suggested, including false-negative, false-positive RT-PCR tests; reactivation; and re-infection with SARS-CoV-2, but the mechanism leading to these re-positive cases is still unclear. The prevention of re-positive testing in discharged patients is a fundamental measure to control the spread of the pandemic. In order to reduce the percentage of false-negative tests prior to discharge, we recommend performing more than two tests, according to the standard sampling and microbiological assay protocol. In addition, specimens should be collected from multiple body parts if possible, to identify SARS-CoV-2 viral RNA before discharge. Further studies should be conducted to develop novel assays that target a crucial region of the RNA genome in order to improve its sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Background Concerns about false-negative (FN) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid amplification tests (NAATs) have prompted recommendations for repeat testing if suspicion for coronavirus disease 2019 (COVID-19) infection is moderate to high. However, the frequency of FNs and patient characteristics associated with FNs are poorly understood. Methods We retrospectively reviewed test results from 15 011 adults who underwent ≥1 SARS-CoV-2 NAATs; 2699 had an initial negative NAAT and repeat testing. We defined FNs as ≥1 negative NAATs followed by a positive NAAT within 14 days during the same episode of illness. We stratified subjects with FNs by duration of symptoms before the initial FN test (≤5 days versus >5 days) and examined their clinical, radiologic, and laboratory characteristics. Results Sixty of 2699 subjects (2.2%) had a FN result during the study period. The weekly frequency of FNs among subjects with repeat testing peaked at 4.4%, coinciding with peak NAAT positivity (38%). Most subjects with FNs had symptoms (52 of 60; 87%) and chest radiography (19 of 32; 59%) consistent with COVID-19. Of the FN NAATs, 18 of 60 (30%) were performed early (ie, ≤1 day of symptom onset), and 18 of 60 (30%) were performed late (ie, >7 days after symptom onset) in disease. Among 17 subjects with 2 consecutive FNs on NP NAATs, 9 (53%) provided lower respiratory tract (LRT) specimens for testing, all of which were positive. Conclusions Our findings support repeated NAATs among symptomatic patients, particularly during periods of higher COVID-19 incidence. The LRT testing should be prioritized to increase yield among patients with high clinical suspicion for COVID-19. [ABSTRACT FROM AUTHOR]

Introduction: During the COVID-19 pandemic, worldwide over 600,000 human beings died due to the cause of the disease. In order to deescalate the transmission rate and to avoid crush loading the countries medical health systems social distancing, face masks, and lockdowns have been considered essential by the majority of governments. Whereas some countries have highly reduced or completely stopped otorhinolaryngological procedures, other countries have continued selected surgeries. The objective of this study was to analyze procedures and outcomes of continuing semielective and emergency surgeries during the COVID-19 pandemic. Methods: Retrospective analysis of n = 750 patients who received semi-elective or emergency surgery between March 26 and June 16, 2020, in the Otolaryngology Department of the Friedrich-Alexander-University of Erlangen-Nürnberg. All patients were screened for COVID symptoms and swabbed for SARS-CoV-2 prior to surgery. Results: Of the n = 750 patients, n = 699 patients received semielective surgery and n = 51 emergency surgery. For 27 patients, the swab result could not be awaited due to a life-threatening condition. In these cases, surgery was performed in full protective equipment. No patient was tested positive during or after the surgery (follow-up 45 to 127 days). No member of the medical personnel showed symptoms or was tested positive after contact with patients. Due to the continuation of surgeries, patients' lives were saved and improvement of long-term quality-of-life and outcomes is anticipated. Conclusions: Continuing selected otorhinolaryngological surgeries is crucial for patients' health, survival, and long-time quality of life, yet, the protection of the medical personnel has to be granted. [ABSTRACT FROM AUTHOR]