International Journal of Clinical Oncology - The practice of cancer diagnosis disclosure to children has been changed with the times. The regulations of clinical trials in the 2000s might change... 相似文献
The WJOG8815L phase II clinical study involves patients with non‐small cell lung cancer (NSCLC) that harbored the EGFR T790M mutation, which confers resistance to EGFR tyrosine kinase inhibitors (TKIs). The purpose of this study was to assess the predictive value of monitoring EGFR genomic alterations in circulating tumor DNA (ctDNA) from patients with NSCLC that undergo treatment with the third‐generation EGFR‐TKI osimertinib. Plasma samples of 52 patients harboring the EGFR T790M mutation were obtained pretreatment (Pre), on day 1 of treatment cycle 4 (C4) or cycle 9 (C9), and at diagnosis of disease progression or treatment discontinuation (PD/stop). CtDNA was screened for EGFR‐TKI‐sensitizing mutations, the EGFR T790M mutation, and other genomic alterations using the cobas EGFR Mutation Test v2 (cobas), droplet digital PCR (ddPCR), and targeted deep sequencing. Analysis of the sensitizing—and T790M—EGFR mutant fractions (MFs) was used to determine tumor mutational burden. Both MFs were found to decrease during treatment, whereas rebound of the sensitizing EGFR MF was observed at PD/stop, suggesting that osimertinib targeted both T790M mutation‐positive tumors and tumors with sensitizing EGFR mutations. Significant differences in the response rates and progression‐free survival were observed between the sensitizing EGFR MF‐high and sensitizing EGFR MF‐low groups (cutoff: median) at C4. In conclusion, ctDNA monitoring for sensitizing EGFR mutations at C4 is suitable for predicting the treatment outcomes in NSCLC patients receiving osimertinib (Clinical Trial Registration No.: UMIN000022076).
BackgroundLocomotive syndrome is a condition of reduced mobility due to problems with locomotive organs. Although lumbar spinal canal stenosis is one of the major diseases constituting locomotive syndrome, only few studies have focused on the association between the two pathologies. We aimed to investigate the effect of surgery on lumbar spinal canal stenosis with respect to locomotive syndrome using various physical function tests, including locomotive syndrome risk tests, before and after surgery.MethodsClinical data of 101 consecutive patients (male = 46; female = 55; mean age, 69.3 years) who underwent surgery for lumbar spinal canal stenosis at our institute were prospectively collected. Results of physical function tests, including stand-up test, two-step test, and 25-Question Geriatric Locomotive Function Scale, and the sagittal vertical axis were evaluated before and 1 year after surgery. The association between several parameters and improvement of risk level in locomotive syndrome was evaluated.ResultsIn the total assessment, 93.1% of cases were in stage 2 and 6.9% in stage 1 preoperatively, while 72.4% were in stage 2, 22.4% in stage 1, and 5.2% in stage 0 at 1 year postoperatively. Postoperative improvement in the total assessment was observed in 28.7% of cases. Several physical function tests and sagittal vertical axis showed significant improvement after surgery. On multiple logistic regression analysis, age >75 years (odds ratio = 10.9, confidence interval = 1.09–109) and postoperative sagittal vertical axis >40 mm (odds ratio = 17.8, confidence interval = 1.78–177) were significant risk factors associated with non-improvement in risk level of locomotive syndrome.ConclusionsSurgical treatment for lumbar spinal canal stenosis improved physical function, including locomotive syndrome. Risk factors associated with non-improvement of locomotive syndrome were later-stage elderly and postoperative sagittal balance impairment. 相似文献
Congenital rubella syndrome (CRS) results from maternal rubella virus infection in early pregnancy. Abnormal neuroimaging findings have been analyzed in a small number of CRS patients in the past; however, their clinical significance has been poorly addressed. Therefore, we have investigated the neuroimaging findings of 31 patients with CRS from previous studies. The most common finding was parenchymal calcification, which was observed in 18 of 31 patients (58.1%). A multivariable logistic regression model showed that it was associated with psychomotor or mental retardation (p = 0.018), suggesting that parenchymal calcification in CRS could be a prognostic factor. 相似文献
<正>Stroke is a leading cause of mortality and severe neurological disability worldwide; however, curative therapeutic options are limited. Although recanalization therapy using endovascular thrombectomy has demonstrated great benefits in the functional outcome of patients with acute ischemic stroke, the rate of excellent clinical outcomes remains limited. Therefore, the current recanalization 相似文献
Moderate to severe atopic dermatitis (AD) has a high disease burden and a significant effect on quality of life. Observational studies are necessary to determine the patient disease burden and long‐term disease control in the Japanese population. ADDRESS‐J is a non‐interventional, observational registry of adult Japanese patients with moderate to severe AD. Herein, we report baseline data from the ADDRESS‐J study describing disease characteristics and current treatment practices. At baseline, 300 adult AD patients with Investigator's Global Assessment (IGA) scores (range, 0–4) of 3 (moderate) or 4 (severe) whose treatments for AD were intensified, were assessed for clinical and patient‐reported outcomes and current AD treatments. The registry patients’ median age was 34.0 years; 60.7% were male and 71.7% had had AD for more than 20 years. At baseline, 220 study patients had an IGA score of 3 and 80 had an IGA score of 4. The median Eczema Area and Severity Index score was 21.7 (range, 0–72), the median body surface area involvement was 46.25%, and the median pruritus numerical rating scale score was 7.0 (range, 0–10); for each of these measures, higher scores represent greater severity. Most registry patients (86.7%) had recently used topical corticosteroids or topical calcineurin inhibitors as treatment for AD. This registry cohort represents a population of Japanese patients with moderate to severe AD and provides an important resource for characterizing the disease burden and evaluating the safety and effectiveness of various AD treatments. 相似文献
Daily exposure to sunlight is known to affect the structure and function of the epidermal basement membrane (BM), as well as epidermal differentiation and epidermal barrier function. The aim of this study is to clarify whether the inhibition of BM‐degrading enzymes such as heparanase and matrix metalloproteinase 9 (MMP‐9) can improve the epidermal barrier function of facial skin, which is exposed to the sun on a daily basis. 1‐(2‐hydroxyethyl)‐2‐imidazolidinone (HEI) was synthesized as an inhibitor of both heparanase and MMP‐9. HEI inhibited not only the BM damage at the DEJ but also epidermal proliferation, differentiation, water contents and transepidermal water loss abnormalities resulting from ultraviolet B (UVB). This was determined in this study by the use of UVB‐induced human cultured skins as compared with the control without HEI. Moreover, topical application of HEI improved epidermal barrier function by increasing water content and decreasing transepidermal water loss in daily sun‐exposed facial skin as compared with non‐treated skins. These results suggest that the inhibition of both heparanase and MMP‐9 is an effective way to care for regularly sun‐exposed facial skin by protecting the BM from damage. 相似文献
Half-life of the antipsychotic vegetamin is very long, partially due to the presence of phenobarbital, and mortality due to phenobarbital poisoning is high. Here, we present the case of a 22-year-old female admitted to the emergency department with disturbed consciousness due to vegetamin overdose. Her blood phenobarbital level was elevated to 123 μg/ml. Phenobarbital undergoes enterohepatic circulation, and its retention in the intestine causes its blood levels to remain sustained. The utility of hemodialysis for drug poisoning has been previously reported; however, its efficiency is not yet established and its efficacy is low for drugs with long half-lives such as phenobarbital. Therefore, we performed a two-tube approach to adsorb phenobarbital in the intestines with activated charcoal delivered via a gastric tube and to remove the phenobarbital-adsorbed activated charcoal using whole bowel irrigation via an ileus tube 2 h later. The patient successfully eliminated the charcoal via stool, the blood phenobarbital level decreased drastically without hemodialysis, and the clinical course improved. We propose that this two-tube approach is suitable for treatment of poisoning with drugs that undergo enterohepatic circulation and have long half-lives. 相似文献
1. The non-clinical pharmacokinetic profiles of rovatirelin, a novel thyrotropin-releasing hormone (TRH) analogue, were investigated in vivo and in vitro.
2. Rovatirelin orally administered to rats and dogs was rapidly absorbed and bioavailability was estimated to be 7.3 and 41.3%, respectively. The extent of plasma protein binding of rovatirelin in rats, dogs, and humans was low in all species (~15%). The permeability of rovatirelin from blood to brain (permeability-surface area) ranged from 1.04?±?0.14 to 1.29?±?0.28?μL/min/g in rats, and rovatirelin was stable in rat plasma and brain homogenates.
3. The metabolite pattern was qualitatively similar in vitro and in vivo. In animals, rovatirelin aminopentanoic acid (rovatirelin-acid), rovatirelin aminopentanone (rovatirelin-ketone), rovatirelin pyrrolidine (4S)-hydroxy (rovatirelin-OH), (thiazoylalanyl)methylpyrrolidine (TAMP), 3-(4-thiazoyl)-l-alanine (TA), and unknown metabolites were observed. In human hepatocytes, TAMP was mainly formed and no unique human metabolite was observed.
4. The radioactivity from administered [14C]rovatirelin was predominantly excreted in faeces in rats and dogs, and almost all radioactivity was recovered 168?h after administration. Absorption, brain penetration, and stability of rovatirelin in the brain were greater than for taltirelin.
5. Thus, orally administered rovatirelin is a potentially improved treatment for spinocerebellar degeneration compared with taltirelin. 相似文献