Relationship between Chemotherapy-Induced Diarrhea and Intestinal Microbiome Composition.

BACKGROUND AND AIM: Fluoropyrimidines (FPs) are key drugs in many chemotherapy regimens; however, recipients are often prone to diarrhea due to gastrointestinal toxicity. Disruption of the intestinal epithelial barrier function by FPs leads to dysbiosis, which may exacerbate intestinal epithelial cell damage as a secondary effect and trigger diarrhea. However, despite studies on chemotherapy-induced changes in the intestinal microbiome of humans, the relationship between dysbiosis and diarrhea is unclear. In this study, we aimed to investigate the relationship between chemotherapy-induced diarrhea and the intestinal microbiome. METHODS: We conducted a single-center prospective observational study. Twenty-three patients who received chemotherapy, including FPs as first-line chemotherapy for colorectal cancer, were included. Stool samples were collected before the start of chemotherapy and after one cycle of treatment to analyze intestinal microbiome composition and perform PICRUSt predictive metagenomic analysis. RESULTS: Gastrointestinal toxicity was observed in 7 of 23 patients (30.4%), diarrhea was observed in 4 (17.4%), and nausea and anorexia were observed in 3 (13.0%). In 19 patients treated with oral FPs, the α diversity of the microbial community decreased significantly following chemotherapy only in the diarrheal group. At the phylum level, the diarrheal group showed a significant decrease in the abundance of Firmicutes and a significant increase in the abundance of Bacteroidetes with chemotherapy (p = 0.013 and 0.011, respectively). In the same groups, at the genus level, Bifidobacterium abundance was significantly decreased (p = 0.019). In contrast, in the non-diarrheal group, Actinobacteria abundance increased significantly with chemotherapy at the phylum level (p = 0.011). Further, Bifidobacterium, Fusicatenibacter, and Dorea abundance significantly increased at the genus level (p = 0.006, 0.019, and 0.011, respectively). The PICRUSt predictive metagenomic analysis revealed that chemotherapy caused significant differences in membrane transport in KEGG pathway level 2 and in 8 KEGG pathway level 3, including transporters and oxidative phosphorylation in the diarrhea group. CONCLUSION: Organic-acid-producing bacteria seem to be involved in diarrhea associated with chemotherapy, including FPs.

Therapeutic Drug Monitoring of Golimumab for the Prediction of Long-Term Clinical Remission in Patients with Ulcerative Colitis.

BACKGROUND AND AIMS: A considerable number of patients with ulcerative colitis (UC) who initially respond to golimumab (GLM), an anti-TNF-α antibody, gradually lose clinical response. Therapeutic drug monitoring has been proposed to optimize serum anti-TNF-α antibody concentrations before the loss of response; however, little is known about ideal serum GLM concentrations. We aimed to evaluate whether the serum GLM trough levels (TLs) early after the initiation of induction therapy affect the long-term outcomes in UC and to identify the early GLM TLs that should be targeted for better long-term outcomes. METHODS: Thirty-one patients were prospectively evaluated. The primary outcome was clinical remission at 54 weeks, and we measured the serum GLM TLs at weeks 6, 10, and 14. Receiver operating characteristic (ROC) curves were constructed to identify optimal GLM TL thresholds early after induction therapy that were associated with clinical remission at week 54. RESULTS: The GLM TL at week 14, but not at weeks 6 or 10, was significantly associated with clinical remission at week 54 (median [IQR] 1.6 [1.3-1.6] µg/mL vs. 0.9 [0.6-1.3] µg/mL; p = 0.04). The area under the ROC curve for GLM TLs at week 14 was 0.78. We identified a week-14 GLM TL of 1.1 µg/mL as the target threshold for achieving clinical remission at week 54. CONCLUSION: Our results demonstrate the value of early serum GLM TLs in predicting the long-term outcomes of GLM for patients with UC.

Risk Factors for Nephrotoxicity due to Tacrolimus Therapy for Ulcerative Colitis.

BACKGROUND AND AIMS: The calcineurin inhibitor tacrolimus is reportedly effective for moderate/severe ulcerative colitis (UC); however, it is also reportedly associated with nephrotoxicity. We investigated the risk factors for tacrolimus-induced nephrotoxicity and whether renal impairment adversely affected the outcomes of tacrolimus treatment in patients with UC. METHODS: We conducted a retrospective study of 93 patients with UC who were administered tacrolimus leading to high trough levels (10-15 ng/mL) for 2 weeks and low trough levels (5-10 ng/mL) for 3 months. RESULTS: Acute kidney injury (AKI) occurred in 44 patients (47.3%) during tacrolimus treatment. Of these patients, 34 (36.6%) developed AKI during the high trough phase and 17 (18.3%) developed AKI when the trough value exceeded the original target value of 15 ng/mL. Multivariate logistic regression analysis revealed that the male sex was significantly associated with AKI (p = 0.002, AOR = 4.38, 95% CI [1.69-11.3]). Clinical remission rate after 4, 8, 12, and 24 weeks of tacrolimus treatment in patients with AKI was lower than that in patients without AKI. Six patients (6.5%) had chronic kidney disease (CKD) after tacrolimus treatment completion, and all patients with CKD developed AKI during treatment. The median duration of treatment with no improvement in AKI was significantly longer in patients with CKD than in those without CKD (p = 0.016). CONCLUSION: We revealed the risk factors for tacrolimus-induced nephrotoxicity. Renal impairment occurrence adversely affected the tacrolimus treatment outcome; therefore, it is important to carefully administer tacrolimus to prevent renal impairment.

Effect of a proton-pump inhibitor on intestinal microbiota in patients taking low-dose aspirin.

BACKGROUND AND AIM: Low-dose aspirin (LDA) administration prevents cerebral infarction and myocardial infarction, but many studies found an association with mucosal injury. Proton-pump inhibitors (PPIs) can prevent gastric and duodenal mucosal damage, but they may exacerbate small-intestinal mucosal injury by altering the microbiota. We aimed to assess the effect of PPIs on the intestinal flora of LDA users. METHODS: Thirty-two recruited patients, who received LDA (100 mg/day) but did not take PPIs, were divided into 15 patients additionally receiving esomeprazole (20 mg/day) and 17 patients additionally receiving vonoprazan (10 mg/day). On days 0, 30, 90, and 180, the microbiota of each patient was examined by terminal restriction fragment length polymorphism analysis, and the serum gastrin, hemoglobin, and hematocrit levels were measured. RESULTS: Additional PPI administration increased the proportion of Lactobacillales in the microbiota of LDA users. This trend was more prevalent in the vonoprazan group (p < 0.0001) than in the esomeprazole group (p = 0.0024). The Lactobacillales proportion was positively correlated with the gastrin level (r = 0.5354). No significant hemoglobin or hematocrit level reduction was observed in subjects receiving LDA with additional PPI. CONCLUSIONS: Additional PPI administration increased the Lactobacillales proportion in the microbiota of LDA users. The positive correlation between the gastrin level and the proportion of Lactobacillales suggested that the change in the intestinal flora was associated with the degree of suppression of gastric acid secretion. Additional oral PPI did not significantly promote anemia, but the risk of causing PPI-induced small-intestinal mucosal injury in LDA users should be considered.

Clinical relevance of innovative immunoassays for serum ustekinumab and anti-ustekinumab antibody levels in Crohn's disease.

BACKGROUND AND AIM: Ustekinumab is a human monoclonal antibody to the p40 subunit of human IL-12/IL-23. The purpose of this report is to verify the newly developed immunoassays for serum ustekinumab and anti-ustekinumab antibody (AUA) concentrations and assess their clinical utility. METHODS: Serum ustekinumab trough levels and AUA levels were measured using new immunoassays in 38 patients with Crohn's disease under ustekinumab maintenance injection. RESULTS: Mean ustekinumab trough levels were 2.54 ± 2.1 µg/mL, and 3 of 38 patients (7.9%) were positive for AUAs. There was no association between ustekinumab trough levels and AUA levels. The optimal trough level of ustekinumab to maintain negative C-reactive protein levels (≤ 0.3 mg/dL) was 1.67 µg/mL determined by receiver operating characteristic curve analysis. Ustekinumab trough level negatively but significantly correlated with C-reactive protein, erythrocyte sedimentation rate, and Crohn's disease activity index and positively and significantly correlated with serum albumin levels. Ustekinumab trough levels were significantly higher in biologics-naïve patients than in biologics-experienced patients, although there was no difference in AUA levels. CONCLUSIONS: We developed new assays for serum ustekinumab trough and AUA levels. These assays might provide new insights into therapeutic drug monitoring-based management of Crohn's disease patients under ustekinumab therapy.

Efficacies and Related Issues of Ustekinumab in Japanese Patients with Crohn's Disease: A Preliminary Study.

INTRODUCTION: Ustekinumab (UST) is an antibody to the p40 subunit of interleukins 12 and 23 in Crohn's disease (CD) patients. Few reports are available on CD in the Asian scenario. OBJECTIVE: We evaluated UST's efficacy in inducing remission and its maintenance in Japanese CD patients. METHODS: This retrospective study was conducted in UST-treated CD patients at our center. The primary endpoint was the clinical remission rate at week 8; the major secondary endpoints were the clinical remission rate at week 24 or 48, change in CD activity index (CDAI) and biomarkers, endoscopic efficacy, and cumulative remission maintenance rate. RESULTS: The clinical remission rates at weeks 8, 24, and 48 were 44.4, 66.7, and 50.0%, respectively. Delayed response was shown by 22.2% of the patients; they achieved remission by week 24. The baseline CDAI was significantly lower in the remission group than in the nonremission group at week 8 (95% CI 0.89-0.99; p = 0.03). The cumulative remission maintenance rates at 6 and 12 months were 82.4 and 49.8%, respectively. Loss of response (LOR) was noted in 22.2% of the patients within 1 year. The endoscopic response and mucosal healing rate were 52.6 and 5.3%, respectively. Rapid improvements in serum albumin levels were observed at weeks 8 (p = 0.06), 24 (p < 0.01), and 48 (p = 0.01) from the baseline in active cases at baseline. CONCLUSIONS: UST is effective for remission induction and maintenance, especially in those with lower CD activity, however, may result in delayed response or LOR.

Isoliquiritigenin Ameliorates Indomethacin-Induced Small Intestinal Damage by Inhibiting NOD-Like Receptor Family, Pyrin Domain-Containing 3 Inflammasome Activation.

Activation of the NOD-Like Receptor Family, Pyrin Domain-Containing 3 (NLRP3) inflammasome, which consists of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1, triggers pro-caspase-1 cleavage promoting the processing of pro-interleukin (IL)-1ß into mature IL-1ß, which is critical for the development of non-steroidal anti-inflammatory drug (NSAID)-induced enteropathy. We investigated the effects of isoliquiritigenin, a flavonoid derived from the roots of Glycyrrhiza species, on NSAID-induced small intestinal damage and the inflammasome activation. To induce enteropathy, mice were administered indomethacin by gavage with or without isoliquiritigenin pretreatment. Some mice received an intraperitoneal injection of recombinant murine IL-1ß in addition to isoliquiritigenin and indomethacin. Indomethacin induced small intestinal damage and increased protein levels of cleaved caspase-1 and mature IL-1ß in the small intestine. Treatment with 7.5 and 75 mg/kg isoliquiritigenin inhibited indomethacin-induced small intestinal damage by 40 and 56%, respectively. Isoliquiritigenin also inhibited the indomethacin-induced increase in cleaved caspase-1 and mature IL-1ß protein levels, whereas it did not affect the mRNA expression of NLRP3, ASC, caspase-1, and IL-1ß. Protection against intestinal damage in isoliquiritigenin-treated mice was completely abolished with exogenous IL-1ß. NLRP3-/- and caspase-1-/- mice exhibited resistance to intestinal damage, and isoliquiritigenin treatment failed to inhibit the damage in NLRP3-/- and caspase-1-/- mice. Isoliquiritigenin prevents NSAID-induced small intestinal damage by inhibiting NLRP3 inflammasome activation.

Does discontinuation of antithrombotics affect the diagnostic yield of small bowel capsule endoscopy in patients demonstrating obscure gastrointestinal bleeding?

A large proportion of patients demonstrating obscure gastrointestinal bleeding (OGIB) are antithrombotic users and need to undergo small bowel capsule endoscopy (SBCE). We examined the effect of discontinuation of antithrombotics on the diagnostic yield of SBCE. Additionally, we assessed predictive factors associated with positive SBCE findings. Our study included 130 patients using antithrombotics who underwent SBCE for overt OGIB. The primary endpoint was the difference in the rate of positive SBCE findings between patients who continued and those who discontinued antithrombotics. Secondary endpoints were to investigate the effect of discontinuation of antithrombotics using a propensity score analysis, and to assess predictive factors associated with a positive SBCE. Among the 73 patients who continued use of antithrombotics, 36 (49.3%) patients demonstrated positive findings, while among the 57 patients who discontinued antithrombotics, 35 (61.4%) patients showed positive findings. Rates of positive SBCE findings didn't differ between the two groups. After we performed propensity score matching, discontinuation didn't affect the rate of positive SBCE findings. The lowest hemoglobin level was the only independent predictive factor associated with positive SBCE findings. In conclusion, discontinuation of antithrombotic therapy didn't affect the diagnostic yield of SBCE in patients presenting with overt OGIB.

Energetic performance analysis of staged palliative surgery in tricuspid atresia using vector flow mapping.

BACKGROUND: Staged palliative surgery markedly shifts the balance of volume load on a single ventricle and pulmonary vascular bed. Blalock-Taussig shunt necessitates a single ventricle eject blood to both the systemic and pulmonary circulation. On the contrary, bidirectional cavopulmonary shunt release the single ventricle from pulmonary circulation. CASE PRESENTATION: We report a case of tricuspid atresia patient who underwent first palliative surgery and second palliative surgery. Volume loading condition was assessed by energetic parameters (energy loss, kinetic energy) intraoperatively using vector flow mapping. These energetic parameters can simply indicate the volume loading condition. CONCLUSION: Vector flow mapping was useful tool for monitoring volume loading condition in congenital heart disease surgery.

Clinical impact of ultrathin colonoscopy for Crohn's disease patients with strictures.

BACKGROUND AND AIM: Mucosal healing is now the ideal treatment goal for patients with Crohn's disease (CD) and endoscopy is suitable for both visualizing the intestinal mucosa and optimizing treatment according to the objective endoscopic findings; however, passing through strictures with a conventional colonoscope is sometimes difficult. An ultrathin colonoscope (outer diameter 9.2 mm) has been developed for superior insertion performance. METHODS: CD patients with strictures that could not be passed with a conventional colonoscope were eligible for entry into the study. We investigated the rate of passage of the ultrathin colonoscope beyond strictures. We also investigated the clinical impact of optimizing the treatment strategy according to the endoscopic findings beyond the stricture. RESULTS: Of 49 patients, the ultrathin colonoscope could pass the stricture in 59.2% (29/49). The main reason for failure compared with the "pass" group was anal stricture (P = 0.005). When including finger bougie for severe anal stricture, passage of the stricture was achieved in 83.7% (41/49) of cases and the oral mucosa beyond the stricture was visualized. In these cases, 56.1% (23/41) had treatment efficacy confirmed and 43.9% (18/41) required a change of treatment. Importantly, half (9/18) of them were in clinical remission. There were no complications of the study. CONCLUSION: The ultrathin colonoscope could provide optimized treatment based on objective findings of the activity of the oral-side mucosa in CD patients complicated with stricture. Selection of the appropriate endoscope to visualize the responsible lesion is essential to optimize the treatment strategy in each case of CD.

[The treatment strategy for hypoplastic left heart syndrome].

In the recent years, the outcomes of treatment for hypoplastic left heart syndrome (HLHS) is improved because of perioperative management and procedure. We adopt a strategy of the primary Norwood procedure basically for neonates with HLHS, however bilateral pulmonary artery banding precede in patients with risk factors. In the Norwood procedure, aortic arch is reconstructed without artificial prostheses and pulmonary blood flow is supplied from the Blalock-Taussig shunt or the right ventricle-pulmonary artery shunt by case. We administer high dose vasodilators and nitric oxide gas with low resistance strategy after the Norwood procedure. The survival rate of patients with HLHS after 2005 is 84.2% in this strategy.

Comparing the Effects of Anti-TNF Agent and Ustekinumab on Small Bowel Inflammation in Crohn's Disease: Inverse Probability Weighting With Stabilized Weights of Propensity Scores.

Background: Endoscopic mucosal healing serves as a critical predictor for achieving long-term remission in Crohn's disease treatment. Recent data indicate that the effectiveness of healing varies based on the location of gastrointestinal inflammation. Additionally, reports suggest that antitumor necrosis factor-α (anti-TNF-α) agents exhibit reduced efficacy in treating small intestinal inflammation compared to colorectal inflammation. Conversely, limited research exists regarding the impact of the anti-IL12/23 agent ustekinumab (UST) on small intestinal inflammation. This study aimed to compare the effects of anti-TNF-α agents and UST on small intestinal inflammation using propensity score analysis. Methods: This retrospective observational study involved 70 patients with Crohn's disease who had inflammation in the small intestine and had initiated treatment with either anti-TNF agents or UST between March 2015 and August 2021. Endoscopic findings were evaluated before treatment commencement and at 1-2 years post-treatment initiation. The propensity score was employed to compare the efficacy of TNF agents and UST on small bowel inflammation. Results: Ustekinumab exhibited greater improvement in the small intestinal endoscopy score than anti-TNF-α antibodies according to the propensity score analysis (inverse probability weighting; P = .0448). However, no significant disparity was observed in the overall improvement of endoscopic scores between UST and anti-TNF-α antibodies (P = .5938). Conclusions: This study suggests that UST might be more effective than anti-TNF-α agents in treating small intestinal inflammation in Crohn's disease.

Gut microbiota shifts from onset to remission in immune checkpoint inhibitor-induced enterocolitis: a case report.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are crucial in cancer treatment; however, they carry the risk of immune-related adverse events (irAEs), such as enteritis. CASE PRESENTATION: This study investigated the role of the gut microbiota during the onset and remission of irAE enteritis in a patient with stage IV melanoma undergoing anti-PD-1 and anti-CTLA-4 therapy. Following commencement of ICI treatment, the patient developed severe diarrhea and was diagnosed with grade 3 irAE enteritis. Steroid and probiotic treatments provided swift symptom relief and remission, as confirmed by reduced fecal calprotectin levels and gastrointestinal imaging. Microbiota diversity analysis conducted via 16S rRNA gene sequencing identified a decrease in Streptococcus prevalence with improvement in enteritis symptoms. Conversely, genera Fusobacterium, Faecalibacterium, Bacteroides, Prevotella, and Bifidobacterium showed increased representation after remission. These genera are associated with anti-inflammatory properties and fibrous substrate degradation, aiding gut health. Immunological assessment demonstrated fluctuations in cytokine expression and the modulation of costimulatory molecules, aligning with therapeutic interventions and microbiota alterations. CONCLUSIONS: Our findings indicate a significant correlation between gut microbiota and immune responses in irAE enteritis. This underscores the potential utility of microbiome profiling in predicting irAE occurrence and in providing treatment strategies, thereby promoting a more comprehensive approach to managing the adverse effects of ICIs.

[Re-right ventricular outflow reconstruction].

The timing and indication of re-right ventricular outflow tract reconstruction (reRVOTR) remains controversial. The main cause for reRVOTR is pulmonary stenosis and pulmonary regurgitation. A pressure gradient of more than 50 mmHg between right ventricle and pulmonary artery or a right ventricular systolic pressure/left ventricular systolic pressure ratio higher than 0.7~0.8 is the threshold for recommending reoperation. Pulmonary regurgitation is difficult to quantify and is not an indication for reoperation until there was evidence of increasing right ventricular dilatation. That is, reoperation is recommended when there are mild to moderate pulmonary regurgitation with mild to moderate right ventricular dilatation and severe pulmonary regurgitation with or without right ventricular dilatation. ReRVOTR should be undertaken in maintaining normal right ventricular function, that is,under remaining free of symptoms. Therefore the right ventricular function needs to be assessed over time.

Neuroendocrine carcinoma of the small intestine diagnosed as a result of paraneoplastic neurological syndrome.

Paraneoplastic neurological syndromes, a diverse group of neurological syndromes, are associated with small cell lung, testicular, ovarian, and breast cancers; however, their association with neuroendocrine carcinoma of the small intestine remains unreported. In this report, we present the case of a 78-year-old man diagnosed with neuroendocrine carcinoma of the small intestine and experienced symptoms such as subacute progressive numbness of the extremities and impaired gait. These symptoms were diagnosed as tumor-associated neurological syndrome. The patient had also undergone pyloric gastrectomy for early-stage gastric cancer several years prior to the appearance of the neurological symptoms. Therefore, we could not determine whether the tumor-related neurologic syndrome was owing to gastric cancer or neuroendocrine carcinoma of the small intestine; however, one of these conditions was the cause of the neuropathy. The gait disturbance and numbness relatively improved after surgery for the neuroendocrine carcinoma of the small intestine, suggesting that the neuroendocrine carcinoma of the small intestine likely caused the paraneoplastic neurological syndrome. Collectively, we present a unique report highlighting the putative relationship between small bowel neuroendocrine carcinoma and tumor-associated neurologic syndromes.

Biomarkers for Monitoring of Changes in Disease Activity in Ulcerative Colitis.

BACKGROUND: In recent years, various biomarkers of ulcerative colitis (UC) have emerged; however, few studies have simultaneously examined the utility of multiple biomarkers for monitoring disease activity. Additionally, serum leucine-rich alpha-2 glycoprotein (LRG), a new biomarker, may show a blunt response to anti-TNF antibody therapy. This prospective study explored effective biomarkers that could monitor disease activity changes in patients with UC. In addition, we examined the effect of anti-TNF antibody therapy on changes in LRG. METHODS: Blood and stool samples were collected twice from patients with UC: at baseline and at least 8 weeks later. Changes in serum LRG, interleukin (IL)-6, prealbumin (pre-Alb), high-sensitivity C-reactive protein (hs-CRP), CRP, and fecal calprotectin (FC) were measured and correlated with changes in disease activity. The relationship between anti-TNF antibody therapy and LRG levels was also examined in patients with the same disease activity. RESULTS: Forty-eight patients with UC (96 samples) were analyzed. ΔLRG and ΔIL-6 correlated strongly with the change in the partial Mayo (pMayo) score between the two time points (ΔpMayo) (r = 0.686, 0.635, respectively). In contrast, FC and IL-6 were particularly accurate predictors of clinical remission, and their area under the curves (AUCs) were significantly higher than that of CRP (AUC: 0.81, 0.76 vs. 0.50; p = 0.001, 0.005). No association was found between the administration of anti-TNF antibody preparations and the LRG values. CONCLUSIONS: Correlations were found between changes in UC disease activity and LRG, IL-6, pre-Alb, hs-CRP, CRP, and FC. LRG reflects disease activity during anti-TNF antibody therapy.

Efficacy of Switching to Adalimumab for Maintenance of Remission Following Induction Therapy with Tacrolimus in Patients with Ulcerative Colitis.

BACKGROUND: Tacrolimus (TAC) effectively induces remission in refractory ulcerative colitis (UC). However, TAC therapy usually lasts for 3 months. Although azathioprine (AZA) is often used in maintenance therapy, the relapse rate remains high. Herein, we evaluated the efficacy of adalimumab (ADA) for remission maintenance in patients with UC after induction therapy with TAC. METHODS: We prospectively enrolled patients with moderate-to-severe UC who achieved clinical remission after 3 months of TAC therapy with endoscopic non-mucosal healing (Cohort A). After TAC discontinuation, the remission maintenance rate up to 1 year after starting ADA therapy was examined. We retrospectively enrolled patients with UC treated with TAC (Cohort B). Among patients in clinical remission after TAC treatment for 3 months, those who received AZA as remission maintenance therapy after TAC discontinuation constituted the AZA group. Patients in Cohort A who received ADA and AZA as remission maintenance therapy after TAC discontinuation constituted the ADA + AZA group. We compared the remission maintenance rates in the AZA and ADA + AZA groups for up to 5 years after TAC discontinuation. RESULTS: In Cohort A, of the 46 patients with UC treated with TAC, 17 were eligible for analysis after receiving ADA as remission maintenance therapy. A notable 88.2% (15/17) were still in remission 1 year after starting ADA. The ADA + AZA group (n = 16) exhibited a significantly higher relapse-free rate than the AZA group (n = 26) (p < 0.05; log-rank test). CONCLUSION: switching to ADA for remission maintenance in patients with refractory UC who achieved clinical remission with TAC is clinically useful.

Engineering analysis of the effects of bulging sinuses in a newly designed pediatric pulmonary heart valve on hemodynamic function.

The purpose of this study was to examine the hemodynamic characteristics of expanded polytetrafluoroethylene (ePTFE) pulmonary valves with bulging sinuses quantitatively in a pediatric pulmonary mechanical circulatory system designed by us, in order to propose the optimal design for clinical applications. In this study, we developed a pediatric pulmonary mock circulation system, which consisted of a pneumatic right ventricular model, a pulmonary heart valve chamber, and a pulmonary elastic compliance tubing with resistive units. The hemodynamic characteristics of four different types of ePTFE valves and a monoleaflet mechanical heart valve were examined. Relationships between the leaflet movements and fluid characteristics were evaluated based on engineering analyses using echocardiography and a high-speed video camera under the pediatric circulatory conditions of the mock system. We successfully performed hemodynamic simulations in our pediatric pulmonary circulatory system that could be useful for quantitatively evaluating the pediatric heart valves. In the simulation study, the ePTFE valve with bulging sinuses exhibited a large eddy in the vicinity of the leaflets, whereas the straight tubing exhibited turbulent flow. The Reynolds number obtained in the valve with bulging sinuses was calculated to be 1667, which was smaller than that in the straight tubing (R (e) = 2454).The hemodynamic characteristics of ePTFE pediatric pulmonary heart valves were examined in our mock circulatory system. The presence of the bulging sinuses in the pulmonary heart valve decreased the hydrodynamic energy loss and increased the systolic opening area. Based on an in vitro experiment, we were able to propose an optimal selection of pulmonary valve design parameters that could yield a more sophisticated pediatric ePTFE valve shape.

[Two cases of thiopurine-induced acute pancreatitis in inflammatory bowel disease].

Thiopurine drugs have been widely used in the treatment of inflammatory bowel disease. However, their use is limited by adverse effect that can lead to cessation of therapy. We report 2 cases of thiopurine-induced acute pancreatitis in patients with inflammatory bowel disease. Both patients complained of abdominal pain, showed elevated pancreatic enzymes, and swollen pancreases on computed tomography. The patients' signs and symptoms resolved uneventfully after withdrawal of the thiopurine drugs. Although the mechanism of thiopurine-induced pancreatitis remains unclear, close monitoring and early recognition of acute pancreatitis is important in the management of new thiopurine users.