ABSTRACT
Objective@#Sitosterolemia is a rare autosomal recessive disease caused by the deleterious variants of adenosine 5'-triphosphate (ATP)-binding cassette sub-family G member 5 (ABCG5) or ATP-binding cassette sub-family G member 8 (ABCG8). There are only few data on the pathogenicity of ABCG5 and ABCG8. This study aimed to propose a scheme for determining variant pathogenicity and to catalog the putative pathogenic variants in sitosterolemia. @*Methods@#This study enrolled 377 consecutive Japanese patients with hyper-low-density lipoprotein cholesterolemia (mean age: 46.5±19.8 years, with 192 men) who have targetedsequenced data on ABCG5 or ABCG8 (among 21 Mendelian lipid genes for any dyslipidemias) and serum sitosterol levels at Kanazawa University Hospital from 2016 to 2021. Serum sitosterol levels were divided by 0.79 in patients treated with ezetimibe, accounting for the average reduction with this drug. ABCG5 or ABCG8 variants were defined as putative pathogenic if associated with serum sitosterol levels ≥5 µg/mL or homozygous if associated with serum sitosterol levels ≥10 µg/mL. @*Results@#Twenty-three ABCG5 or ABCG8 variants (16 missense, 2 nonsense, 2 frameshift, 2 deletion, and 1 splice mutation) were identified. Based on our definition, 11 putative pathogenic variants (median sitosterol level: 10.1 [6.5–17.1] µg/mL) were found in 36 individuals and 12 benign variants (median sitosterol: 3.5 [2.5–4.1] µg/mL) in 14 individuals. @*Conclusion@#The scheme proposed for assessing the pathogenicity of genetic variations (ABCG5 and ABCG8) is useful. Using this scheme, 11 putative pathogenic, and 12 benign variants in ABCG5 or ABCG were classified.
ABSTRACT
Although programmed cell death-ligand 1 (PD-L1) is a prognostic biomarker for nivolumab therapy, it is not very reliable due to its low accuracy. The pharmacological effect of nivolumab involves the cancer immunity cycle, a process that involves T cells, which are strongly associated with nutrition. In this study, we retrospectively investigated whether two measures of nutrition, namely, the Glasgow Prognostic Score (GPS) and the Prognostic Nutritional Index (PNI), could predict response to nivolumab as evaluated in terms of survival time. The subjects were 37 patients treated with nivolumab in the Department of Respiratory Medicine at our hospital between January 2017 and December 2018. Patients were classified into 2 PNI risk groups (low and high risk) and 3 GPS groups (0, 1, and 2), with lower GPS indicating better nutrition. Kaplan-Meier analysis was used to compare differences between the PNI groups and between each possible pairing of GPS groups. Survival time was significantly longer for the low-risk PNI group compared with the high-risk PNI group and for a GPS score of 0 versus 2 and 1 versus 2, but there was no significant difference for a GPS score of 0 versus 1. These results show that GPS and PNI may be potential predictors of response to nivolumab in non-small cell lung cancer.
ABSTRACT
This paper describes a report here the case of an 85-year-old man who developed pneumonia of Mycobacterium conspicuum, a rare nontuberculous mycobacterium. The patient had repeatedly complained of a bad cough and purulent sputum since December 2010. On admission in May 2011, chest x-ray showed multiple infiltrative shadows. Although mycobacterial infection was suspected from Gaffky 9 on the patient’s expectorated sputum smear, Mycobacterium tuberculosis was not detected by polymerase chain reaction (PCR). We found acid-fast bacilli also in the bronchial washing fluids, and identified the mycobacteria as M. conspicuum by Rpo B and hsp 65 methods. The patient was successfully treated with antituberculosis drugs. It is important to identify the pathogenic bacteria by frequent sputum examinations and bronchoscopy in advance of treatments.