ABSTRACT
BACKGROUND: The faecal immunochemical test (FIT) was introduced to triage patients with low-risk symptoms of possible colorectal cancer in English primary care in 2017, underpinned by little primary care evidence. METHODS: All healthcare providers in the South West of England (population 4 million) participated in this evaluation. 3890 patients aged ≥50 years presenting in primary care with low-risk symptoms of colorectal cancer had a FIT from 01/06/2018 to 31/12/2018. A threshold of 10 µg Hb/g faeces defined a positive test. RESULTS: Six hundred and eighteen (15.9%) patients tested positive; 458 (74.1%) had an urgent referral to specialist lower gastrointestinal (GI) services within three months. Forty-three were diagnosed with colorectal cancer within 12 months. 3272 tested negative; 324 (9.9%) had an urgent referral within three months. Eight were diagnosed with colorectal cancer within 12 months. Positive predictive value was 7.0% (95% CI 5.1-9.3%). Negative predictive value was 99.8% (CI 99.5-99.9%). Sensitivity was 84.3% (CI 71.4-93.0%), specificity 85.0% (CI 83.8-86.1%). The area under the ROC curve was 0.92 (CI 0.86-0.96). A threshold of 37 µg Hb/g faeces would identify patients with an individual 3% risk of cancer. CONCLUSIONS: FIT performs exceptionally well to triage patients with low-risk symptoms of colorectal cancer in primary care; a higher threshold may be appropriate in the wake of the COVID-19 crisis.
Subject(s)
Colorectal Neoplasms/diagnosis , Feces/chemistry , Occult Blood , Primary Health Care , Anemia, Iron-Deficiency/complications , Colorectal Neoplasms/complications , Colorectal Neoplasms/physiopathology , England , Female , Hemoglobins/analysis , Humans , Male , Middle Aged , Risk Factors , Sensitivity and Specificity , Weight LossABSTRACT
Brain metastases are the most common neurological complications of adult cancers, accounting for more than half of brain tumors. The incidence of brain metastases may be increasing due to improved detection of small lesions by advanced imaging technologies. Given the fast evolution of targeted and immunotherapy regimens, it is essential to serially assess brain malignancies during the disease course for disease monitoring and tailoring of the therapeutic management. For such serial and repetitive assessment, cerebrospinal fluid (CSF) could be the biological fluid of choice to supplement cytology examination for the presence or absence of CNS malignancy, as well as provide extensive information on tumor mutational profile for personalization of treatment. The case described here emphasizes the importance of CSF-ctDNA analysis with the CellMax SMSEQ technology that led to treatment adjustment resulting in clinical remission of the patient.
ABSTRACT
The filamentous fungus Aspergillus niger exhibits great diversity in its phenotype. It is found globally, both as marine and terrestrial strains, produces both organic acids and hydrolytic enzymes in high amounts, and some isolates exhibit pathogenicity. Although the genome of an industrial enzyme-producing A. niger strain (CBS 513.88) has already been sequenced, the versatility and diversity of this species compel additional exploration. We therefore undertook whole-genome sequencing of the acidogenic A. niger wild-type strain (ATCC 1015) and produced a genome sequence of very high quality. Only 15 gaps are present in the sequence, and half the telomeric regions have been elucidated. Moreover, sequence information from ATCC 1015 was used to improve the genome sequence of CBS 513.88. Chromosome-level comparisons uncovered several genome rearrangements, deletions, a clear case of strain-specific horizontal gene transfer, and identification of 0.8 Mb of novel sequence. Single nucleotide polymorphisms per kilobase (SNPs/kb) between the two strains were found to be exceptionally high (average: 7.8, maximum: 160 SNPs/kb). High variation within the species was confirmed with exo-metabolite profiling and phylogenetics. Detailed lists of alleles were generated, and genotypic differences were observed to accumulate in metabolic pathways essential to acid production and protein synthesis. A transcriptome analysis supported up-regulation of genes associated with biosynthesis of amino acids that are abundant in glucoamylase A, tRNA-synthases, and protein transporters in the protein producing CBS 513.88 strain. Our results and data sets from this integrative systems biology analysis resulted in a snapshot of fungal evolution and will support further optimization of cell factories based on filamentous fungi.