Association between antispasmodics and detection of lesions by screening esophagogastroduodenoscopy

BACKGROUND AND AIM: Whether administration of antispasmodics as a component of premedication contributes to detection of lesions by screening esophagogastroduodenoscopy (EGDS) remains unclear. Our primary aim was to investigate this possibility. METHODS: The cohort in this retrospective study comprised consecutive asymptomatic individuals who had undergone screening EGDS as part of a health check-up at the Japanese Red Cross Wakayama Medical Center from October 2015 to September 2020. The investigated lesions comprised esophageal squamous cell carcinoma or adenocarcinoma, gastric adenoma or adenocarcinoma, and duodenal adenoma or adenocarcinoma. RESULTS: Targeted lesions were detected in 72 of 31 484 participants (0.23%), 18 260 and 13 224 of whom had received and not received pre-procedure antispasmodics, respectively. The rates of detection of lesions in these groups were 0.21% (38/18260) and 0.26% (34/13224), respectively (P = 0.40). Multivariate logistic regression analysis showed no association between administration of antispasmodics and rates of detection of targeted lesions [P = 0.24, Odds ratio (95% CI): 1.46 (0.78-2.75)]. CONCLUSIONS: Antispasmodics, which were administered to more than half of the study cohort, did not improve the rate of detection of targeted lesions

Contractile force measurement of human induced pluripotent stem cell-derived cardiac cell sheet-tissue

<div><p>We have developed our original tissue engineering technology “cell sheet engineering” utilizing temperature-responsive culture dishes. The cells are confluently grown on a temperature-responsive culture dish and can be harvested as a cell sheet by lowering temperature without enzymatic digestion. Cell sheets are high-cell-density tissues similar to actual living tissues, maintaining their structure and function. Based on this “cell sheet engineering”, we are trying to create functional cardiac tissues from human induced pluripotent stem cells, for regenerative therapy and <i>in vitro</i> drug testing. Toward this purpose, it is necessary to evaluate the contractility of engineered cardiac cell sheets. Therefore, in the present study, we developed a contractile force measurement system and evaluated the contractility of human iPSC-derived cardiac cell sheet-tissues. By attaching the cardiac cell sheets on fibrin gel sheets, we created dynamically beating cardiac cell sheet-tissues. They were mounted to the force measurement system and the contractile force was measured stably and clearly. The absolute values of contractile force were around 1 mN, and the mean force value per cross-sectional area was 3.3 mN/mm². These values are equivalent to or larger than many previously reported values, indicating the functionality of our engineered cardiac cell sheets. We also confirmed that both the contractile force and beating rate were significantly increased by the administration of adrenaline, which are the physiologically relevant responses for cardiac tissues. In conclusion, the force measurement system developed in the present study is valuable for the evaluation of engineered cardiac cell sheet-tissues, and for <i>in vitro</i> drug testing as well.</p></div

Preparation of fibrin gel sheets.

<p>(A) The handle made by a 3D printer to manipulate a fibrin gel sheet. The unit of measure of the numbers in the figure is mm. (B) The silicone mold in which two handles were put at both ends. The unit of measure of the numbers in the figure is mm. (C) Immediately after fibrin gel solution was poured in the silicone mold, the acrylic plate was put on it. The gel solution was clotted for 20 minutes at room temperature. (D) The prepared fibrin gel sheet.</p

A representative cross-sectional image of a cardiac cell sheet-tissue obtained by OCM system.

<p>The bidirectional arrow (a) indicates the layer of a cardiac cell sheet and the bidirectional arrow (b) indicates the layer of a fibrin gel sheet.</p

Frank-Starling mechanism of cardiac cell sheet-tissues.

<p>(A) Relationship between contractile force and % of stretch. Each value of contractile forces was determined as the mean of those values in one minute. (B) Relationship between beating rate and % of stretch. Each value of beating rates was determined as the mean of those values in one minute. In both figures, the results are presented as mean ± SD for 4 cardiac cell sheet-tissues, prepared from a same differentiation batch. Each value of contractile forces and beating rates was statistically compared to the value at 0% stretch (closed circles) using Student’s t-test (* p < 0.05, ** p < 0.01).</p

The effect of adrenaline administration on the contractility of cardiac cell sheet-tissues.

<p>(A) Representative contractile force traces of a cardiac cell sheet-tissue before and after the administration of 5 μM adrenaline. (B, C) Time course analysis of contractile forces (B) and beating rates (C) of cardiac cell sheet-tissues before and after the administration of 5 μM adrenaline. Each value of contractile forces at a certain time point was determined as the mean of those values in one minute just before that time point. Each value of beating rates at a certain time point was determined as the number of beatings in one minute just before that time point. The results are presented as mean ± SD for 4 cardiac cell sheet-tissues, prepared from a same differentiation batch. Each value of contractile forces and beating rates (open circles) was statistically compared to the value at the time point of adrenaline addition (closed circles) respectively using Student’s t-test (* p < 0.01).</p

Contractile force measurement under electrical pacing.

<p>(A) Relationship between pacing rate and beating rate. Each value of beating rates was determined as the number of beatings in one minute during pacing. The dotted line indicates the equality between pacing rate and beating rate. (B) Relationship between beating rate and contractile force (i.e., force-frequency relationship). Each value of contractile forces was determined as the mean of those values in one minute during pacing. (C) Relationship between beating rate and |dP/dt min|. Each value of |dP/dt min| was determined as the mean of those values in one minute during pacing. In all figures, the results are presented as mean ± SD for 5 cardiac cell sheet-tissues. Among the 5 cardiac cell sheet-tissues, 2 samples were prepared from a same differentiation batch. The other 3 samples were prepared from different 3 differentiation batches respectively. For (B) and (C), each value of contractile forces was statistically compared to the value at 67 bpm (closed circles) using Student’s t-test (* p < 0.05, ** p < 0.01).</p

Confocal fluorescence microscopy of cardiac cell sheets.

<p>The cardiac cell sheet-tissue was fixed with 4% paraformaldehyde at 7 days after cell sheet transfer. Actin filaments (green) and nuclei (blue) were stained fluorescently.</p