Association between changes in disease severity and physical function after surviving a critical illness:A multicentre retrospective observational study

Background: Whilst disease severity can significantly impact functional outcomes, the ability to predict the scale of this impact has not been consistent. Aim: We aimed to investigate whether changes in disease severity within the first 48 h of ICU admission are more strongly associated with physical dysfunction than a single-time assessment of disease severity at ICU admission.Methods: A multicentre retrospective study in seven tertiary ICUs in Japan, including all consecutive adult ICU patients (&gt;48 h ICU stay) between September 2019 and February 2020. The primary outcome was physical function defined as the Barthel Index, which is an ordinal scale (0–100: larger indicates better function) to measure physical independence and performance. The association between Barthel Index score at hospital discharge and the Sequential Organ Failure Assessment (SOFA) scores, measured at ICU admission, the highest recorded score within 48 h of ICU admission, and the level of change between these two timepoints were investigated in multivariable analysis.Results: A total of 199 patients were included. Median SOFA score at ICU admission and the highest recorded score within the first 48 h were 6 (interquartile range: 5–10) and 8 (interquartile range: 6–11), respectively. A quarter of patients had a Barthel Index score of 60 or less at hospital discharge. The highest SOFA score within 48 h of ICU admission and the level of change in SOFA scores between ICU admission and the highest recorded score within 48 h were significantly associated with lower Barthel Index scores at hospital discharge. No significant association was identified with regard to Barthel Index scores and SOFA score at ICU admission. An increase in SOFA score of 1 or more within the first 48 h of ICU admission was the threshold to predict a Barthel Index score of 60 or less at hospital discharge. Larger changes in SOFA scores over the first 48 h of ICU admission were also significantly associated with smaller changes in Barthel Index scores from ICU discharge to hospital discharge.Conclusions: The level of change in SOFA score between ICU admission and the highest recorded score within the first 48 h of ICU stay can more accurately predict the presence of physical dysfunction at hospital discharge than a single-time assessment of disease severity at ICU admission. The larger worsening in SOFA potentially indicates lower recovery after a critical illness.</p

Volumetric Analysis of Glioblastoma for Determining Which CpG Sites Should Be Tested by Pyrosequencing to Predict Temozolomide Efficacy

The aim of the present study was to determine which individual or combined CpG sites among O6-methylguanine DNA methyltransferase CpG 74&ndash;89 in glioblastoma mainly affects the response to temozolomide resulting from CpG methylation using statistical analyses focused on the tumor volume ratio (TVR). We retrospectively examined 44 patients who had postoperative volumetrically measurable residual tumor tissue and received adjuvant temozolomide therapy for at least 6 months after initial chemoradiotherapy. TVR was defined as the tumor volume 6 months after the initial chemoradiotherapy divided by that before the start of chemoradiotherapy. Predictive values for TVR as a response to adjuvant therapy were compared among the averaged methylation percentages of individual or combined CpGs using the receiver operating characteristic curve. Our data revealed that combined CpG 78 and 79 showed a high area under the curve (AUC) and a positive likelihood ratio and that combined CpG 76&ndash;79 showed the highest AUC among all combinations. AUCs of consecutive CpG combinations tended to be higher for CpG 74&ndash;82 in exon 1 than for CpG 83&ndash;89 in intron 1. In conclusion, the methylation status at CpG sites in exon 1 was strongly associated with TVR reduction in glioblastoma

Clinical Application of Comprehensive Genomic Profiling Tests for Diffuse Gliomas

Next-generation sequencing-based comprehensive genomic profiling test (CGPT) enables clinicians and patients to access promising molecularly targeted therapeutic agents. Approximately 10% of patients who undergo CGPT receive an appropriate agent. However, its coverage of glioma patients is seldom reported. The aim of this study was to reveal the comprehensive results of CGPT in glioma patients in our institution, especially the clinical actionability. We analyzed the genomic aberrations, tumor mutation burden scores, and microsatellite instability status. The Molecular Tumor Board (MTB) individually recommended a therapeutic agent and suggested further confirmation of germline mutations after considering the results. The results of 65/104 patients with glioma who underwent CGPTs were reviewed by MTB. Among them, 12 (18.5%) could access at least one therapeutic agent, and 5 (7.7%) were suspected of germline mutations. A total of 49 patients with IDH-wildtype glioblastoma showed frequent genomic aberrations in the following genes: TERT promoter (67%), CDKN2A (57%), CDKN2B (51%), MTAP (41%), TP53 (35%), EGFR (31%), PTEN (31%), NF1 (18%), BRAF (12%), PDGFRA (12%), CDK4 (10%), and PIK3CA (10%). Since glioma patients currently have very limited standard treatment options and a high recurrence rate, CGPT might be a facilitative tool for glioma patients in terms of clinical actionability and diagnostic value

Severe Skin Disorders Due to Sorafenib Use After Nivolumab Treatment in Renal Cell Carcinoma Patients.

Background:We report two cases in which severe skin disorders developed during sorafenib treatment in patients with renal cell carcinoma (RCC) who had previously received nivolumab.Case report:Case 1: A 50-year-old man with RCC received nivolumab as the fifth-line therapy followed by sorafenib as the sixth-line therapy. On day 15 of sorafenib administration, the patient was hospitalized with systemic erythema multiforme, acne-like skin rash, and hand-foot syndrome. Case 2: A 40-year-old man with RCC received nivolumab as the second-line therapy followed by sorafenib as the fifth-line treatment. On day 12 of sorafenib administration, the patient was hospitalized with an acne-like skin rash and hand-foot syndrome. The skin disorders in the two cases improved within 2-3 weeks after sorafenib discontinuation and the start of treatment with topical and oral steroids.Conclusion:When using sorafenib in patients previously treated with nivolumab, close attention should be paid to the onset of serious skin disorders