ABSTRACT
Background: Neuropathic adverse events occur frequently in linezolid-containing regimens, some of which remain irreversible after drug discontinuation. Objective: We aimed to identify and validate a host RNA-based biomarker that can predict linezolid-associated neuropathy before multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment initiation and to identify genes and pathways that are associated with linezolid-associated neuropathy. Methods: Adult patients initiating MDR/RR-TB treatment including linezolid were prospectively enrolled in 3 independent cohorts in Germany. Clinical data and whole blood RNA for transcriptomic analysis were collected. The primary outcome was linezolid-associated optic and/or peripheral neuropathy. A random forest algorithm was used for biomarker identification. The biomarker was validated in an additional fourth cohort of patients with MDR/RR-TB from Romania. Results: A total of 52 patients from the 3 identification cohorts received linezolid treatment. Of those, 24 (46.2%) developed peripheral and/or optic neuropathies during linezolid treatment. The majority (59.3%) of the episodes were of moderate (grade 2) severity. In total, the expression of 1,479 genes differed significantly at baseline of treatment. Suprabasin (SBSN) was identified as a potential biomarker to predict linezolid-associated neuropathy. In the validation cohort, 10 of 42 (23.8%) patients developed grade ≥3 neuropathies. The area under the curve for the biomarker algorithm prediction of grade ≥3 neuropathies was 0.63 (poor; 95% confidence interval: 0.42 - 0.84). Conclusions: We identified and preliminarily validated a potential clinical biomarker to predict linezolid-associated neuropathies before the initiation of MDR/RR-TB therapy. Larger studies of the SBSN biomarker in more diverse populations are warranted.
ABSTRACT
Ipsilateral pneumothoraces are a common complication after transbronchial forceps biopsy. In this case report, a contralateral tension pneumothorax and a pneumoperitoneum occurred following transbronchial forceps biopsy in addition to an ipsilateral pneumothorax.
Subject(s)
Biopsy , Bronchoscopy , Pneumothorax , Biopsy/adverse effects , Bronchoscopy/adverse effects , Bronchoscopy/instrumentation , Humans , Pneumothorax/etiology , Surgical InstrumentsABSTRACT
OBJECTIVES: Language functional magnetic resonance imaging (fMRI) represents the clinical standard for language lateralization assessment in presurgical epilepsy evaluation, but still many patients experience postoperative language deficits. Event-related potentials (ERPs), especially the negative component around and after 400ms, are related to language processing and could therefore represent a complementary method of language lateralization assessment. METHODS: Scalp EEG was recorded from 64 locations in 36 epilepsy patients and 37 controls during three visually presented language tasks: A short-term language memory task (differentiation memorized vs. unknown words), a phonological task (detection of rhymes in word pairs), and a semantic decision task (differentiation words vs. pseudowords). ERPs were analyzed in the 300ms-800ms epoch. Language fMRI was routinely obtained in patients. RESULTS: ERPs were significantly more negative over the left compared to the right hemisphere in all three tasks in patients and controls. Laterality indices showed highest concordance with fMRI for the Word/Pseudoword Task. CONCLUSIONS: ERPs of language processing were lateralized to the left hemisphere in the majority of epilepsy patients and controls. In patients, single-subject laterality indices showed high concordance with fMRI results. SIGNIFICANCE: Results indicate that scalp-derived ERPs are a promising tool to investigate lateralization of language function in epilepsy patients.
