Phase IIb study of pembrolizumab combined with S‐1 + oxaliplatin or S‐1 + cisplatin as first‐line chemotherapy for gastric cancer

The KEYNOTE‐659 study evaluated the efficacy and safety of first‐line pembrolizumab plus S‐1 and oxaliplatin (SOX) (cohort 1) or S‐1 and cisplatin (SP) (cohort 2) for advanced gastric/gastroesophageal junction (G/GEJ) cancer in Japan. Herein, we update the results of cohort 1 and describe the results of cohort 2. This open‐label phase IIb study enrolled patients with advanced programmed death‐ligand 1 (PD‐L1)‐positive (combined positive score ≥ 1) human epidermal growth factor receptor 2 (HER2)‐negative G/GEJ adenocarcinoma. The primary end‐point was the objective response rate (ORR). Other end‐points were duration of response (DOR), disease control rate (DCR), progression‐free survival (PFS), overall survival (OS), and safety. One hundred patients were enrolled. In cohorts 1 and 2, median follow‐up time was 16.9 and 17.1 months; ORR (central review), 72.2% and 80.4%; DOR, 10.6 and 9.5 months; DCR (central review), 96.3% and 97.8%; median PFS (central review), 9.4 and 8.3 months; and median OS, 16.9 and 17.1 months, respectively. Treatment‐related adverse events (TRAEs) occurred in all patients, including peripheral sensory neuropathy (94.4%, cohort 1), decreased neutrophil count (82.6%, cohort 2), nausea (59.3% and 60.9% in cohorts 1 and 2), and decreased appetite (61.1% and 60.9% in cohorts 1 and 2). Grade 3 or higher TRAEs were reported by 59.3% (cohort 1) and 78.3% (cohort 2), including decreased platelet count (14.8%, cohort 1) and decreased neutrophil count (52.2%, cohort 2). Pembrolizumab in combination with SOX or SP showed favorable efficacy and safety in patients with PD‐L1‐positive, HER2‐negative G/GEJ adenocarcinoma.     

Effect of acupuncture on adrenocortical hormone production: I. Variation in the ability for adrenocortical hormone production in relation to the duration of acupuncture stimulation.

The effect of acupuncture on adrenocortical hormone production in adult female albino rabbits of New Zealand strain was investigated. There was significant increase compared to the control cortisol and corticosterone following application of acupuncture at the locus Tsu-San-Li. In the non-locus group, such treatment resulted in only a transient raise followed by a significant fall in cortisol and corticosterone. Acupuncture treatment with electric current for 1 hour proved to be unique in that it gave rise to no biphasic change in the 14C uptake of the steroids. These results indicate that adrenal production of corticosterone and cortisol was enhanced by acupuncture and electroacupuncture at the Tsu-San-Li locus.     

Effects of workplace measures against COVID-19 on psychological distress of full-time employees: A 12-month prospective study in the COVID-19 pandemic

ObjectiveThis study aimed to investigate the prospective effects of corporate and organizational workplace measures against COVID-19 on reducing employees’ psychological distress during a 12-month follow-up in the COVID-19 pandemic.MethodsData were retrieved from an online longitudinal panel survey of full-time employees in Japan, with the 1^st survey in March 2020, and the 2^nd to 6^th surveys in May, August, November 2020, February and March 2021, respectively. Seven area-specific workplace measures were assessed using a self-report 23-item scale at the 2^nd follow-up. Psychological distress was measured using an 18-item scale of the Brief Job Stress Questionnaire at each survey. Linear regressions and mixed model analysis were conducted of psychological distress at follow-ups on scores of the area-specific workplace measures, adjusting for psychological distress and other covariates at the 1^st survey.ResultsA total of 941 employees responded at baseline; most of them (86.9–90.9%) participated in the follow-up surveys. Linear regression analysis indicated that workplace measures of facilitating employees’ preventive measures (ie, hygiene behaviors) statistically significantly and negatively correlated with psychological distress at the 5^th survey [b=-0.518, standard error (SE) 0.259, P=0.046]. A statistically significant and negative interaction between the scores and time of follow-up was observed in the mixed model analysis (b=-0.096, SE 0.047, P=0.041). No such correlation or interaction was found for any of other subcategorical workplace measures.ConclusionsThe study provides prospective evidence for a protective effect of workplace measures to facilitate employee’s hygiene behaviors on reducing psychological distress of full-time employees in the COVID-19 pandemic. The association seems stronger at a later follow-up.     

Comparison of the Central Adrenal Vein and the Common Trunk of the Left Adrenal Vein for Adrenal Venous Sampling

PurposeTo compare left adrenal venous sampling (AVS) in two locations: the central adrenal vein and the common trunk.Materials and MethodsA total of 22 patients (12 men and 10 women; mean age, 50 y; range, 26–65 y) who were suspected of having primary aldosteronism (PA) and underwent successful AVS with cortisol concentration measurement and/or venography between November 2010 and August 2011 were retrospectively analyzed. In regard to the left adrenal vein, collections were done at two locations: at the common trunk below the confluence of the inferior phrenic vein and at the central adrenal vein, which was above the confluence. The effects of the inflow from the inferior phrenic vein on plasma aldosterone and cortisol levels were analyzed.ResultsEight patients had bilateral hypersecreting lesions and 13 had a unilateral lesion. One was diagnosed as having secondary hypertension other than PA. The median cortisol levels below and above the confluence were 129 μg/dL (range, 21–400 μg/dL) and 215 μg/dL (range, 21–690 μg/dL), respectively. The median aldosterone levels were 2,120 pg/mL (range, 164–42,700 pg/mL) and 4,275 pg/mL (range, 119–59,000 pg/mL), respectively. The median aldosterone/cortisol (A/C) ratios were 244 (range, 34–2,401) and 278 (range, 25–2,251), respectively. Cortisol and aldosterone levels were significantly higher above the confluence (P = .0050 and P = .0003, respectively), whereas the A/C ratio showed no significant difference (P = .12).ConclusionsAlthough higher levels of cortisol and aldosterone were obtained upstream, A/C ratio was not significantly different between the central adrenal vein and the common trunk.     

Japanese orthopaedic association cervical myelopathy evaluation questionnaire (JOACMEQ): Part 5. Determination of responsiveness

Background

In 1999, the Japanese Orthopaedic Association decided to develop a new Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). The final version of the JOACMEQ, comprising 24 questions and five domains (cervical spine function (CF); upper extremity function (UF); lower extremity function (LF); bladder function (BF); and quality of life (QOL)), was established after three nationwide investigations. The fourth investigation, reported in this paper, was performed to confirm the responsiveness of the questionnaire.

Removal methods of rigid stylets to minimise adverse force and tracheal tube movement: a mathematical and in-vitro analysis in manikins

This study investigated displacement of the tracheal tube caused by different methods of intubating stylet removal, using in-vitro experiments and mathematical analysis. In the first in-vitro experiment, we measured the distance travelled by the tube tip during stylet extraction. Then, we investigated the ideal technique for stylet extraction using mathematical analysis, which would cause minimal tube displacement. Then, using a training manikin, we measured the force applied to the vocal cords and stylet extraction force during tracheal intubation. When the stylet was extracted along a straight path towards the stylet end, the distance travelled by the tube tip significantly increased as the bending angle increased. Mathematical analysis revealed that the stylet should be diagonally extracted (in the sagittal plane) at an appropriate angle, rather than along a straight path towards the direction of the stylet end. In simulated tracheal intubation, extraction force and force applied to the vocal cords both significantly increased as the bending angle increased. Compared with the ‘hockey stick’-shaped stylet, the arcuate-shaped stylet resulted in reduced force. Our results indicate the potential risk for vocal cord injury when using hockey stick-shaped stylets with large bending angles.     

Effect of single bout downhill running on the serum irisin concentrations in rats

Abstract

This study aimed to characterize the effect of different running modes on serum irisin concentrations in rats. A total of 18, 10-week-old rats were divided into three groups; control group, 16° uphill running group (concentric exercise; CON) and, ?16° downhill running group (eccentric exercise; ECC). The running group’s rats ran on the inclined treadmill at 16?m/min, for a total of 90?min. Blood was drawn from the rats, 48?h after running, after which the rats were anesthetized. The serum concentrations of irisin were measured using enzyme-linked immunosorbent assays. Vastus intermedius was collected for immunohistochemical analysis. After multiple comparisons, the ECC showed a significantly high serum irisin concentration (ECC: 28.42?±?6.31?ng/ml, CON: 21.27?±?3.03?ng/ml) and a larger irisin antibody reactive cross-sectional area in vastus intermedius compared to the CON (p?<?0.05). This is the first study to reveal that single bout downhill running increases serum irisin concentrations in rats.