A case of delayed exacerbation of interstitial lung disease after discontinuation of temsirolimus

Temsirolimus is an inhibitor of mammalian target of rapamycin and interstitial lung disease (ILD) is known to be one of the adverse events associated with temsirolimus, which usually improves rapidly after discontinuation of the drug and rarely worsens thereafter. Herein, we report a case of delayed exacerbation of ILD after discontinuation of temsirolimus for metastatic renal cell carcinoma in an 86-year-old male with chronic ILD. The patient developed gradually worsening dyspnea five weeks after an initiation of temsirolimus and was admitted to our facility. On his admission, although a pulmonary function test revealed a decreased diffusion capacity, there was no obvious progression of ILD on HRCT scan. His dyspnea once improved after discontinuation of temsirolimus, but it recurred and acute exacerbation of ILD was diagnosed 40 days after his last administration of temsirolimus. He received high-dose steroid therapy, however, he deteriorated and died. Histopathological examination of the lungs at autopsy revealed overlapping diffuse alveolar damage with chronic interstitial changes. In the present case, since there were no specific factors that could have caused acute exacerbation of ILD except for temsirolimus, it was considered to contribute to the exacerbation of underlying ILD. In conclusion, physicians should be aware of the possibility of temsirolimus-induced ILD not only while the medication is administered, but also even after it is discontinued. It is important to carefully interview the patient and to recognize the value of physiological tests, such as respiratory function tests and blood gas analysis, as well as imaging findings on HRCT

OATP1B3 expression is strongly associated with Wnt/β-catenin signalling and represents the transporter of gadoxetic acid in hepatocellular carcinoma.

BACKGROUND & AIMS: In the current era of emerging molecular targeted drugs, it is necessary to identify before treatment the specific subclass to which a tumour belongs. Gadoxetic acid is a liver-specific contrast agent that is preferentially taken up by hepatocytes. Therefore, gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) should provide precise molecular information about hepatocellular carcinomas (HCCs). The aim of this study was to investigate the transporters of gadoxetic acid in HCC comprehensively and to analyse the molecular regulatory mechanism of such transporters. METHODS : Expression levels of transporters, transcriptional factors and Wnt target genes in clinical samples were examined by quantitative real-time reverse transcription polymerase chain reaction and immunohistochemistry. LiCl treatment of the HCC cell line KYN-2 was conducted in vitro to assess the effects of Wnt signalling activity. RESULTS: Comprehensive analyses of transporter mRNAs and protein expressions revealed that the organic anion transporting polypeptide 1B3 (OATP1B3) had the strongest correlation with tumour enhancement in hepatobiliary-phase images of EOB-MRI. Association analysis with OATP1B3 expression revealed significant correlation with the expression of Wnt/β-catenin target genes. Further, LiCl treatment induced OATP1B3 mRNA expression in KYN-2 cells, indicating a strong association between OATP1B3 expression and Wnt/β-catenin signalling. The sensitivity and specificity to predict Wnt/β-catenin-activated HCC using tumour enhancement in EOB-MRI were 78.9% and 81.7%, respectively. CONCLUSIONS: OATP1B3 was confirmed as the most important transporter mediating HCC enhancement in EOB-MRI. OATP1B3 expression showed a strong association with the expression of Wnt/β-catenin target genes, therefore, OATP1B3-upregulated HCC likely represents a specific subclass of Wnt/β-catenin-activated HCC

Clinical practice competencies for standard critical care nursing: consensus statement based on a systematic review and Delphi survey

Objectives A clear development process and scientifically validated clinical practice competencies in standard critical care nursing (SCCN) have not yet been developed in Japan. Thus, this study aimed to develop a consensus-based set of SCCN competencies to provide a framework for critical care nursing education, training and evaluation.Design Multistep, modified Delphi study (a systematic review, focus group interviews, a three-round web-based Delphi survey and an external validation process).Participants A systematic review of 23 studies, focus group interviews by 12 experts, a Delphi survey by 239 critical care experts (physicians, nurses and physical therapists) and an external validation by 5 experts (physicians and nurses).Results A systematic review identified 685 unique competencies. The focus group interviews resulted in the addition of 3 performance indicator items, a synthesis of 2 subdomains and 10 elements. Of the 239 participants, 218 (91.2%), 209 (98.9%) and 201 (96.2%) responded in rounds 1, 2 and 3 of the Delphi survey, respectively. After round 3, 57 items were below the consensus level and were removed in the final round. External validation process feedback was received from experts after two revisions to ensure that the final competencies were valid, applicable, useful and clear. The final set of competencies was classified into 6 domains, 26 subdomains, 99 elements and 525 performance indicators.Conclusions This study found a set of SCCN competencies after a multistep, modified Delphi study. The results of this study are robust, and the competency framework can be used in multiple areas to improve clinical practice, including the assessment, training and certification of standard critical care nurses