Validation of the European system for cardiac operative risk evaluation II in a large Taiwan cardiac surgical centre.

BACKGROUND: The European System for Cardiac Operative Risk Evaluation (EuroSCORE II) is a well-established scoring system for predicting mortality in cardiac surgery. This system was derived predominantly from a European patient cohort; however, no validation of this system has been conducted in Taiwan. We sought to assess the performance of EuroSCORE II at a tertiary centre. METHODS: The 2161 adult patients receiving cardiac surgery between 2017 and 2020 in our institution were included. RESULTS: Overall, the in-hospital mortality rate was 7.89%. The performance of EuroSCORE II was assessed using the area under the receiver operator curve (AUC) for discrimination and the Hosmer-Lemeshow (H-L) test for calibration. Data were analysed for type of surgery, risk stratification, and status of the operation. EuroSCORE II had good discriminative power (AUC=0.854, 95% Confidence Interval (CI): 0.822-0.885) and good calibration (χ2=5.19, p=0.82) for all types of surgery except ventricular assist devices (AUC=0.618, 95% CI: 0.497-0.738). EuroSCORE II also showed good calibration for most types of surgery except coronary artery bypass surgery (CABG) combined procedure (P=0.033), heart transplantation (HT) (P=0.017), and urgent operation (P=0.041). EuroSCORE II significantly underestimated the risk for CABG combined procedure and urgent operations, and overestimated the risk for HT. CONCLUSION: EuroSCORE II had satisfactory discrimination and calibration power to predict surgical mortality in Taiwan. However, the model is poorly calibrated for CABG combined procedure, HT, urgent operation, and, likely, lower- and higher-risk patients.

TBK1 p.Y153Qfs*9 variant may be associated with young-onset, rapidly progressive amyotrophic lateral sclerosis through a haploinsufficiency mechanism.

BACKGROUND: TBK1 variants have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia spectrum disorder. The current study elucidated the clinical and molecular genetic features of a novel TBK1 variant identified in a patient with young-onset, rapidly progressive ALS. METHODS: The coding regions of TBK1, SOD1, TARDBP, and FUS were genetically analyzed using Sanger sequencing. Repeat-primed PCR was used to survey the GGGGCC repeat in C9ORF72. The study participant underwent a comprehensive clinical evaluation. The functional effects of the TBK1 variant were analyzed through in vitro transfection studies. RESULTS: We identified a novel frameshift truncating TBK1 variant, c.456_457delGT (p.Y153Qfs*9), in a man with ALS. The disease initially manifested as right hand weakness at the age of 39 years but progressed rapidly, with the revised ALS Functional Rating Scale score declining at an average monthly rate of 1.92 points in the first year after diagnosis. The patient had no cognitive dysfunction. However, Technetium-99m single photon emission tomography indicated hypoperfusion in his bilateral superior and middle frontal cortices. In vitro studies revealed that the p.Y153Qfs*9 variant resulted in a truncated TBK1 protein product, reduced TBK1 protein expression, loss of kinase function, reduced interaction with optineurin, and impaired dimerization. CONCLUSION: The heterozygous TBK1 p.Y153Qfs*9 variant may be associated with young-onset, rapidly progressive ALS through a haploinsufficiency mechanism.

Clinical and genetic characterization of NIPA1 mutations in a Taiwanese cohort with hereditary spastic paraplegia.

OBJECTIVE: NIPA1 mutations have been implicated in hereditary spastic paraplegia (HSP) as the cause of spastic paraplegia type 6 (SPG6). The aim of this study was to investigate the clinical and genetic features of SPG6 in a Taiwanese HSP cohort. METHODS: We screened 242 unrelated Taiwanese patients with HSP for NIPA1 mutations. The clinical features of patients with a NIPA1 mutation were analyzed. Minigene-based splicing assay, RT-PCR analysis on the patients' RNA, and cell-based protein expression study were utilized to assess the effects of the mutations on splicing and protein expression. RESULTS: Two patients were identified to carry a different heterozygous NIPA1 mutation. The two mutations, c.316G>A and c.316G>C, are located in the 3' end of NIPA1 exon 3 near the exon-intron boundary and putatively lead to the same amino acid substitution, p.G106R. The patient harboring NIPA1 c.316G>A manifested spastic paraplegia, epilepsy and schizophrenia since age 17 years, whereas the individual carrying NIPA1 c.316G>C had pure HSP since age 12 years. We reviewed literature and found that epilepsy was present in multiple individuals with NIPA1 c.316G>A but none with NIPA1 c.316G>C. Functional studies demonstrated that both mutations did not affect splicing, but only the c.316G>A mutation was associated with a significantly reduced NIPA1 protein expression. INTERPRETATION: SPG6 accounted for 0.8% of HSP cases in the Taiwanese cohort. The NIPA1 c.316G>A and c.316G>C mutations are associated with adolescent-onset complex and pure form HSP, respectively. The different effects on protein expression of the two mutations may be associated with their phenotypic discrepancy.

Clinical characteristics of patients with pneumonia caused by Klebsiella pneumoniae in Taiwan and prevalence of antimicrobial-resistant and hypervirulent strains: a retrospective study.

Background: We aimed to compare the clinical characteristics of patients with community-acquired pneumonia (CAP), healthcare-associated pneumonia (HCAP), and hospital-acquired pneumonia (HAP) caused by Klebsiella pneumoniae and analyze the antimicrobial resistance and proportion of hypervirluent strains of the microbial isolates. Methods: We conducted a retrospective study on patients with pneumonia caused by K. pneumoniae at the Taipei Veterans General Hospital in Taiwan between January 2014 and December 2016. To analyze the clinical characteristics of these patients, data was extracted from their medical records. K. pneumoniae strains were subjected to antimicrobial susceptibility testing, capsular genotyping and detection of the rmpA and rmpA2 genes to identify hypervirulent strains. Results: We identified 276 patients with pneumonia caused by K. pneumoniae, of which 68 (24.6%), 74 (26.8%), and 134 (48.6%) presented with CAP, HCAP, and HAP, respectively. The 28-day mortality was highest in the HAP group (39.6%), followed by the HCAP (29.7%) and CAP (27.9%) groups. The HAP group also featured the highest proportion of multi-drug resistant strains (49.3%), followed by the HCAP (36.5%) and CAP groups (10.3%), while the CAP group had the highest proportion of hypervirulent strains (79.4%), followed by the HCAP (55.4%) and HAP groups (41.0%). Conclusion: Pneumonia caused by K. pneumoniae was associated with a high mortality. Importantly, multi-drug resistant strains were also detected in patients with CAP. Hypervirulent strains were prevalent in all 3 groups of pneumonia patients, even in those with HAP.