Assessment of the albumin-bilirubin grade as a prognostic factor in patients with non-small-cell lung cancer receiving anti-PD-1-based therapy.

INTRODUCTION: The albumin-bilirubin (ALBI) grade is a novel indicator of the liver function. Some studies showed that the ALBI grade was a prognostic and predictive biomarker for the efficacy of chemotherapy in cancer patients. The association between the ALBI grade and outcomes in patients with non-small-cell lung cancer (NSCLC) treated with cancer immunotherapy, however, is poorly understood. METHODS: We retrospectively enrolled 452 patients with advanced or recurrent NSCLC who received anti-programmed cell death protein 1 (PD-1)-based therapy between 2016 and 2019 at three medical centers in Japan. The ALBI score was calculated from albumin and bilirubin measured at the time of treatment initiation and was stratified into three categories, ALBI grade 1-3, with reference to previous reports. We examined the clinical impact of the ALBI grade on the outcomes of NSCLC patients receiving anti-PD-1-based therapy using Kaplan-Meier survival curve analysis with log-rank test and Cox proportional hazards regression analysis. RESULTS: The classifications of the 452 patients were as follows: grade 1, n = 158 (35.0%); grade 2, n = 271 (60.0%); and grade 3, n = 23 (5.0%). Kaplan-Meier survival curve analysis showed that the ALBI grade was significantly associated with progression-free survival and overall survival. Moreover, Cox regression analysis revealed that the ALBI grade was an independent prognostic factor for progression-free survival and overall survival. CONCLUSION: The ALBI grade was an independent prognostic factor for survival in patients with advanced or recurrent NSCLC who receive anti-PD-1-based therapy. These findings should be validated in a prospective study with a larger sample size.

Usefulness of the assessment of urinary enzyme leakage in monitoring acute fluoride nephrotoxicity.

A single oral dose of sodium fluoride (NaF) in aqueous solution was given to male Wistar rats. Twenty-four-hour urine samples were collected and examined to evaluate fluoride-induced acute renal damage. The following parameters were measured in 24-h urine: urine volume and urinary excretion of fluoride, N-acetyl-beta-d-glucosaminidase (NAG), alpha-glutathione-S-transferase (alpha-GST), and creatinine (CR). Fluoride exposure produced specific, dose-dependent changes of these parameters. Significant increases of fluoride and fluoride-induced polyuria were observed. NAG as specific marker of proximal convoluted tubule (PCT) function showed a significant increase when the lowest dose of fluoride was administered. At this minimal dose, alpha-GST, a specific marker for the S3 segment, did not show a significant increase but presented the strongest relationship (r = 0. 83) to fluoride dose. No significant changes were measured for CR excretion, which showed a low correlation coefficient (r = 0.36) to administered fluoride. The specific differences in the increase pattern of these parameters show that the PCT is more susceptible to damage by low-dose fluoride than the S3 segment or the glomerulus. We concluded that both NAG and alpha-GST are useful for the diagnosis of fluoride-induced acute nephrotoxicity. Proper evaluation of these urinary indices may be of help to establish the site and extent of kidney injury in acute fluoride toxicity.

Preclinical assessment of a new transdermal delivery system for clonidine (M-5041T).

The effects of a new transdermal delivery system for clonidine (M-5041T) on hypotensive effect, urine volume, plasma renin activity (PRA) and antidiuretic hormone (ADH) in spontaneously hypertensive rats (SHRs) were compared to the effects of the continuous infusion of clonidine. Both M-5041T (1.5 and 4.5 mg/kg) and the continuous infusion of clonidine (250 micrograms/kg/24 h) elicited hypotensive effects persisting for 12 hours or more. These effects were based on consistent plasma concentrations of clonidine. These two treatments produced diuresis followed by antidiuresis, which was remarkably observed by continuous infusion of clonidine. Single subcutaneous injection of clonidine (50 micrograms/kg) produced diuresis accompanied by increases in electrolytes corresponding to plasma levels of clonidine. M-5041T at 1.5 mg/kg did not affect PRA until 12 h, and produced an increase in PRA at 24 h. M-5041T at 4.5 mg/kg and the continuous infusion of clonidine resulted in a decrease in PRA at 2 and 1 h followed by an increase at 12 and 24 h, respectively. M-5041T at 1.5 mg/kg did not affect plasma levels of ADH. Plasma ADH did increase at 2 and 4 h accompanied by diuresis following M-5041T at 4.5 mg/kg or the continuous infusion of clonidine, respectively. Clonidine-induced diuresis was not at least due to the inhibition of ADH release. The decrease in urine volume observed by continuous infusion of clonidine may be due to decrease in renal blood flow based on stimulation of peripheral adorenoceptors of clonidine. These findings suggest that the increases in ADH and PRA are due to the compensatory effects related to both diuresis and the long-lasting hypotensive effect induced by high plasma concentrations of clonidine. Thus, it can be expected that M-5041T at 1.5 mg/kg showing the minimum effective plasma concentration of clonidine will not result in tolerance to the hypotensive effect of clonidine associated with the retention of sodium in SHRs.

[Ultrasonic Doppler assessment of hemodynamics in extra-intracranial arterial anastomosis in children with Moyamoya disease].

Recently the extra-intracranial (EC/IC) arterial bypass operation has been introduced in the treatment of Moyamoya disease and excellent postoperative outcomes have been reported. To assess the cerebral hemodynamic changes after the bypass surgery, ultrasonic Doppler flowmetry was performed in 10 children with Moyamoya disease. Their surgical treatments included superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis or encephalo-duro-arterio-synangiosis. The flow velocity and pattern of the major cerebral arteries and STAs, the donor artery of the bypass, were studied both before and after the operation. The results of Doppler flowmetry were compared with clinical symptoms and angiographical findings. Though the Doppler sonography of the major cerebral arteries showed little change, the flow velocity of the STAs revealed a pronounced and rapid increase after the bypass surgery. The flow pattern of the STAs, which was of the external carotid type preoperatively, changed to the internal carotid type postoperatively. These ultrasonic Doppler findings were thought to be due to a decrease in the peripheral vascular resistance, and suggested a good patency of the bypass arteries. These results of the Doppler flowmetry were in good agreement with clinical and EEG improvement and the findings of the postoperative cerebral angiography. It is suggested that ultrasonic Doppler flowmetry is a noninvasive and reliable method of assessing the function of the EC/IC bypass in children with Moyamoya disease.