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.

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.

UNASSIGNED: 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.
UNASSIGNED: 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 DWI-negative ischemic stroke were pooled. For binary variables, odds ratios (ORs) were computed using the random-effects model.
UNASSIGNED: 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.
UNASSIGNED: DWI-negative findings were present in a significant proportion of ischemic stroke patients and may be utilized as a marker for favorable prognosis.

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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 radiology-pathology concordance. A proposed management algorithm for MRI-guided biopsy results will also be discussed.

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.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by the deletion or mutation of the survival motor neuron 1 (SMN1) gene. The establishment of effective newborn screening (NBS) for SMA is important for early diagnosis so that treatment can be administered in the pre-symptomatic or early disease stages. Polymerase chain reaction (PCR)-based genetic testing with dried blood spots has been used in NBS to detect the homozygous deletion of exon 7 in SMN1, however, this methodology is not able to detect newborn infants with heterozygous deletions and/or point mutations in SMN1. We report the case of a male infant who was diagnosed with SMA despite the NBS being negative for all conditions including SMA. The patient presented with severe hypotonia and muscle weakness from around 14 days of age. SMA was suspected and sequence analysis of SMN1 and SMN2 was conducted using the multiplex ligation-dependent probe amplification (MLPA) method, which revealed compound heterozygous mutations of SMN1. The patient was diagnosed with SMA and started on modulating agents including gene therapy. His motor function improved slightly with treatment, however, his motor development remained prominently retarded by 5 months of age. This case highlights the importance of investigating SMA as a potential diagnosis even when the NBS result is negative.

In infants as well as in older children, persistent or recurrent atelectasis remains a classic indication for sweat testing, even if neonatal screening for cystic fibrosis has been considered normal. Atelectasis is a common complication of cystic fibrosis. Yet, it has rarely been reported in infants. In cystic fibrosis, chronic atelectasis worsens the prognosis, especially when involving a lower lobe. Therefore, early and effective intervention is required. Antibiotic therapy, intensive chest physiotherapy together with inhaled mucolytics often allow to relieve bronchial obstruction but bronchoscopy with local aspiration and Dornase alpha instillation is sometimes necessary. In a two-month-old infant, we describe here the first reported case of false-negative cystic fibrosis newborn screening in Belgium.
Chez le nourrisson comme chez l’enfant plus âgé, une atélectasie persistante ou récidivante reste une indication classique de test à la sueur, même si le dépistage néonatal de la mucoviscidose a été considéré comme normal. Rarement rapportées chez le nourrisson, les atélectasies sont une complication commune de la mucoviscidose. Dans cette affection, l’atélectasie chronique d’un territoire péjore le pronostic, en particulier si elle concerne un lobe inférieur. Une intervention précoce et efficace est donc requise. Antibiothérapie, kinésithérapie respiratoire intensive et recours aux fluidifiants par voie de nébulisation suffisent souvent à lever l’obstruction bronchique, mais une endoscopie avec aspiration locale et instillation de dornase alpha est parfois nécessaire. Chez un nourrisson de 2 mois, nous rapportons ici le premier cas de faux-négatif du programme belge de dépistage néonatal de la mucoviscidose.

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.

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.
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.
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.
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.