We studied the effect of Kampo for the size-limitation of myocardial infarct with morphometrical analysis, utilizing total of 19 male swine. A hand made metal-coil (2×1mm) was inserted in the left anterior descending coronary artery (LAD) of swine with catheterization, in order to induce acute myocardial infarction (AMI). After occurrence of AMI, the swine were divided into two groups, experimental group: Saiko-ka-ryukotsu-borei-to (n=10) and control (n=9). This Kampo formula (0.66/kg/day) was administered via stomach tubes for 4 weeks. The control group received basal rations alone. After serial cross sections of heart, total infarct areas were weighed.
An infarct weight to heart weight of the experimental group (2.9±1.6%, n=10) was significantly decreased than that of the control group (8.2±4.8%, n=9). The infarct weight to left ventricular weight of the experimental group (4.9±2.6%) was significantly decreased than that of the control group (13.4±8.0%). Thus the infarct size of the experimental group was significantly smaller than that of the control. The histological character of the infarct in the control was numerous inflammatory cell infiltration and foci of fresh coagulate necrosis in the border zone, while the infarct of the experimental group was apparent in the border zone with marked fibrosis and few inflammatory cells. Angiogenesis in both the infarct and border zone was marked in the experimental group than in the control. We summarize that this Kampo formula inhibits size development of AMI in animal model.

Sixteen male swine were utilized to study the occurrence of acetylcholine (ACh) induced coronary spasm using catheters. The left anterior descending coronary arteries (LAD) of the swine were denudated by catheterization under anesthesia. The swine were divided into three groups and fed for four weeks. Group A received Tokishakuyaku-san (0.66g/kg/day; Tsumura Co. Ltd.; n=6) in addition to the basal rations; group B received Mokuboi-to (0.25g/kg/day; Tsumura Co. Ltd; n=5) in addition to the basal rations; and the control group were fed for four weeks on the basal rations alone. The Kampo formulas were administered via stomach tubes in groups A and B.
Coronary spasms induced by catheter administration of ACh (100-250μg) were evaluated by elevation of the ST segment as measured by electric cardiography, and vasoconstriction of the LAD as ascertained by cineangiography.
The ACh-induced coronary spasms were found to either be of the diffuse type or LAD segmental type. Coronary spasms were noted to occur at a frequency of 5/13 in group A, 5/12 in group B and 7/13 in the control group, without significant differences among the groups. Groups A and B, however, exhibited a tendency towards a decreased rate of coronary spasm (40%) when compared to the control group (53.8%).
The vasoconstriction rate (VCR) was also calculated, interpreted as a morphological index of spasms as proposed by Takeuchi (1974). The VCR was higher in the spastic segment of the LAD than in the non-spastic LAD. It was suggested that Tokishakuyaku-san and Mokuboi-to have antispasmodic effects and may reduce the occurrence rate of spasms in swine LAD.

The size of myocardial infarct has been proposed as one of the important prognosis factors. In this study, we examined the effect of Kampo for the size limitation of myocardial infarct. Twenty male swine were used. A metal-coil was inserted in the left anterior descending coronary artery (LAD) of swine, in order to induce acute myocardial infarction (AMI). After occurrence of AMI, the swine were divided into four groups: Saiko-ka-ryukotsu-borei-to (TJ-12) group (n=5), Tokishakuyaku-san (TJ-23) group (n=5), Mokuboi to (TJ-36) group (n=5), and control group (n=5). Three kinds of Kampo formula were administrated via stomach tubes for four weeks. The control group received basal rations alone. The infarct size of the TJ-36 group was significantly smaller than that of the control (p<0.05). Each size of the TJ-12 and TJ-23 group had smaller tendency than that of the control, without significant difference. The histological character of the infarct in the control was numerous inflammatory cell infiltration and small foci of fresh coagulative necrosis in the border zone, which was not apparent in any Kampo administration group. We summarize that these Kampo, especially Moku-boi-to, inhibit the infarct size development. This inhibition is probably caused by suppression of harmful free radicals production from inflammatory cells, or by microcirculation improvement. This inhibitory effect by Kampo medicine led to rescue the border zone indicated as “jeopardized zone”.

BACKGROUND/AIMS: Anti-tumor necrosis factor drugs (anti-TNF) and thiopurines are important treatment options in patients with inflammatory bowel disease (IBD), including during pregnancy. However, there are limited data on the benefit/risk profile of anti-TNF and thiopurines during pregnancy in Asia. The aim of this study was to analyze pregnancy outcomes of female Japanese IBD patients treated with anti-TNF and/or thiopurines. METHODS: This cross-sectional study assessed pregnancy outcomes in 72 women with IBD. Pregnancy outcomes were compared among 31 pregnancies without exposure to infliximab (IFX), adalimumab (ADA), or thiopurines; 24 pregnancies with exposure to anti-TNF treatment (23 IFX, 1 ADA); 7 pregnancies with exposure to thiopurines alone; and 10 pregnancies with exposure to both IFX and thiopurines. RESULTS: Thirty-five of the 41 pregnancies (85.3%) that were exposed to anti-TNF treatment and/or thiopurines resulted in live births after a median gestational period of 38 weeks. Of the 35 live births, 3 involved premature deliveries; 7, low birth weight; and 1, a congenital abnormality. There were 6 spontaneous abortions in pregnancies that were exposed to anti-TNF treatment (17.7%). Pregnancy outcomes among the 4 groups were similar, except for the rate of spontaneous abortions (P =0.037). CONCLUSIONS: Exposure to anti-TNF treatment or thiopurines during pregnancy was not related to a higher incidence of adverse pregnancy outcomes in Japanese IBD patients except for spontaneous abortion.
Adalimumab ; Abortion, Spontaneous ; Asia ; Asian Continental Ancestry Group ; Congenital Abnormalities ; Cross-Sectional Studies ; Female ; Humans ; Incidence ; Infliximab ; Infant, Low Birth Weight ; Infant, Newborn ; Inflammatory Bowel Diseases* ; Japan* ; Live Birth ; Necrosis* ; Pregnancy ; Pregnancy Outcome* ; Pregnancy*

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract, with increasing prevalence worldwide. IBD Ahead is an international educational program that aims to explore questions commonly raised by clinicians about various areas of IBD care and to consolidate available published evidence and expert opinion into a consensus for the optimization of IBD management. Given differences in the epidemiology, clinical and genetic characteristics, management, and prognosis of IBD between patients in Japan and the rest of the world, this statement was formulated as the result of literature reviews and discussions among Japanese experts as part of the IBD Ahead program to consolidate statements of factors for disease prognosis in IBD. Evidence levels were assigned to summary statements in the following categories: disease progression in CD and UC; surgery, hospitalization, intestinal failure, and permanent stoma in CD; acute severe UC; colectomy in UC; and colorectal carcinoma and dysplasia in IBD. The goal is that this statement can aid in the optimization of the treatment strategy for Japanese patients with IBD and help identify high-risk patients that require early intervention, to provide a better long-term prognosis in these patients.
Asian Continental Ancestry Group ; Colectomy ; Colitis, Ulcerative ; Colorectal Neoplasms ; Consensus ; Crohn Disease ; Disease Management* ; Disease Progression ; Early Intervention (Education) ; Epidemiology ; Expert Testimony ; Gastrointestinal Tract ; Hospitalization ; Humans ; Inflammatory Bowel Diseases* ; Japan* ; Prevalence ; Prognosis

Purpose: Thyroid transcription factor 1 (TTF-1) expression is a useful predictor of treatment efficacy in advanced non-squamous non–small cell lung cancer (NSCLC). This study aimed to evaluate whether TTF-1 could predict the effectiveness of chemotherapy versus chemoimmunotherapy in patients with non-squamous NSCLC with programmed death ligand-1 (PD-L1) expression between 1% and 49%. Materials and Methods: We conducted a retrospective study of patients with NSCLC who were treated with chemotherapy or chemoimmunotherapy between March 2016 and May 2023. The patients had histologically confirmed NSCLC, stage III-IV or postoperative recurrence, TTF-1 measurements, and PD-L1 expression levels between 1% and 49%. Clinical data were analyzed to evaluate the effect of TTF-1 expression on treatment efficacy. Results: This study included 283 of 624 patients. TTF-1–positive patients showed longer progression-free survival (PFS) and overall survival (OS) (PFS: 6.4 months [95% confidence interval (CI), 5.0 to 9.4] vs. 4.1 months [95% CI, 2.7 to 6.1], p=0.03; OS: 17.9 months [95% CI, 15.2 to 28.1] vs. 9.4 months [95% CI, 6.3 to 17.0], p < 0.01) in the chemotherapy cohorts (n=93). In the chemoimmunotherapy cohort (n=190), there was no significant difference in PFS and OS between TTF-1–positive and –negative groups (PFS: 7.6 months [95% CI, 6.4 to 11.0] vs. 6.0 months [95% CI, 3.6 to 12.6], p=0.59; OS: 25.0 months [95% CI, 18.0 to 49.2] vs. 21.3 months [95% CI, 9.8 to 28.8], p=0.09). Conclusion In patients with NSCLC with PD-L1 expression between 1% and 49%, TTF-1 expression was a predictor of chemotherapeutic, but not chemoimmunotherapeutic, efficacy.

Purpose: Thyroid transcription factor 1 (TTF-1) expression is a useful predictor of treatment efficacy in advanced non-squamous non–small cell lung cancer (NSCLC). This study aimed to evaluate whether TTF-1 could predict the effectiveness of chemotherapy versus chemoimmunotherapy in patients with non-squamous NSCLC with programmed death ligand-1 (PD-L1) expression between 1% and 49%. Materials and Methods: We conducted a retrospective study of patients with NSCLC who were treated with chemotherapy or chemoimmunotherapy between March 2016 and May 2023. The patients had histologically confirmed NSCLC, stage III-IV or postoperative recurrence, TTF-1 measurements, and PD-L1 expression levels between 1% and 49%. Clinical data were analyzed to evaluate the effect of TTF-1 expression on treatment efficacy. Results: This study included 283 of 624 patients. TTF-1–positive patients showed longer progression-free survival (PFS) and overall survival (OS) (PFS: 6.4 months [95% confidence interval (CI), 5.0 to 9.4] vs. 4.1 months [95% CI, 2.7 to 6.1], p=0.03; OS: 17.9 months [95% CI, 15.2 to 28.1] vs. 9.4 months [95% CI, 6.3 to 17.0], p < 0.01) in the chemotherapy cohorts (n=93). In the chemoimmunotherapy cohort (n=190), there was no significant difference in PFS and OS between TTF-1–positive and –negative groups (PFS: 7.6 months [95% CI, 6.4 to 11.0] vs. 6.0 months [95% CI, 3.6 to 12.6], p=0.59; OS: 25.0 months [95% CI, 18.0 to 49.2] vs. 21.3 months [95% CI, 9.8 to 28.8], p=0.09). Conclusion In patients with NSCLC with PD-L1 expression between 1% and 49%, TTF-1 expression was a predictor of chemotherapeutic, but not chemoimmunotherapeutic, efficacy.

Purpose: Thyroid transcription factor 1 (TTF-1) expression is a useful predictor of treatment efficacy in advanced non-squamous non–small cell lung cancer (NSCLC). This study aimed to evaluate whether TTF-1 could predict the effectiveness of chemotherapy versus chemoimmunotherapy in patients with non-squamous NSCLC with programmed death ligand-1 (PD-L1) expression between 1% and 49%. Materials and Methods: We conducted a retrospective study of patients with NSCLC who were treated with chemotherapy or chemoimmunotherapy between March 2016 and May 2023. The patients had histologically confirmed NSCLC, stage III-IV or postoperative recurrence, TTF-1 measurements, and PD-L1 expression levels between 1% and 49%. Clinical data were analyzed to evaluate the effect of TTF-1 expression on treatment efficacy. Results: This study included 283 of 624 patients. TTF-1–positive patients showed longer progression-free survival (PFS) and overall survival (OS) (PFS: 6.4 months [95% confidence interval (CI), 5.0 to 9.4] vs. 4.1 months [95% CI, 2.7 to 6.1], p=0.03; OS: 17.9 months [95% CI, 15.2 to 28.1] vs. 9.4 months [95% CI, 6.3 to 17.0], p < 0.01) in the chemotherapy cohorts (n=93). In the chemoimmunotherapy cohort (n=190), there was no significant difference in PFS and OS between TTF-1–positive and –negative groups (PFS: 7.6 months [95% CI, 6.4 to 11.0] vs. 6.0 months [95% CI, 3.6 to 12.6], p=0.59; OS: 25.0 months [95% CI, 18.0 to 49.2] vs. 21.3 months [95% CI, 9.8 to 28.8], p=0.09). Conclusion In patients with NSCLC with PD-L1 expression between 1% and 49%, TTF-1 expression was a predictor of chemotherapeutic, but not chemoimmunotherapeutic, efficacy.