Predictors of Improvement in Exercise Capacity After Cardiac Rehabilitation Differ Between Octogenarian and Young-Old Patients With Acute Myocardial Infarction.

BACKGROUND: Whether the magnitude and predictors of improvement in exercise capacity after cardiac rehabilitation (CR) are the same between young-old (YO) and octogenarian (OCT) patients with acute myocardial infarction (AMI) is unknown.Methods and Results: We studied 284 YO (age range 65-69 years; mean [±SD] 67±1 years) and 65 OCT (age range ≥80 years; mean [±SD] 83±2 years) patients who participated in a post-AMI CR program. After 3 months of CR, peak oxygen uptake (PV̇O2) measured during cardiopulmonary exercise testing improved significantly in both age groups (P<0.01), although the percentage increase in PV̇O2(%∆PV̇O2) was significantly smaller in the OCT than YO group (5.4±13.7% vs. 10.0±12.8%; P<0.01). Multiple regression analysis demonstrated that independent predictors of %∆PV̇O2were the number of outpatient CR (OPCR) sessions attended (P=0.015), left ventricular ejection fraction (P=0.028), and baseline PV̇O2(P=0.0007) in the YO group; and the number of sessions attended (P=0.018), atrial fibrillation (P=0.042), and the presence of nutritional risk (Geriatric Nutritional Risk Index ≤98; P=0.036) in the OCT group. CONCLUSIONS: The predictors of improvement in exercise capacity after CR differed between the YO and OCT patients with AMI. To obtain a greater improvement in PV̇O2in CR, frequent OPCR session attendance may be necessary in both groups; in addition, particularly in OCT patients, better nutritional status may be important.

Importance of Bowel Habits in Predicting Inadequate Bowel Preparation: A Prospective Observational Study.

OBJECTIVES: Inadequate bowel preparation (BP) negatively affects the efficacy and quality of colonoscopy. Although constipation has already been reported as one of the most important predictors of inadequate BP, there is limited information on the relation between inadequate BP and bowel habits including constipation-related symptoms, medications, and severity of constipation. METHODS: This single-center, prospective observational study was conducted between August 2019 and May 2020. All participants answered questionnaires regarding personal bowel habits and received low-volume polyethylene glycol plus ascorbic acid for outpatient colonoscopy. Severity of constipation was evaluated by constipation scoring system. Bowel preparation cleansing was evaluated using Boston Bowel Preparation Scale (BBPS). Potential predictors of inadequate BP were analyzed using multivariate logistic regression models. RESULTS: Overall, 1054 patients were enrolled, of which, 105 (10%) had inadequate BP (total BBPS ≤ 6 or any segmental BBPS < 2). The risk of inadequate BP increased with constipation severity (P = 0.01). Multivariate analysis showed that frequent straining (> 25% of defecations) (OR 2.09, 95% CI: 1.33-3.28) and chronic use of stimulant laxatives (OR 2.57, 95% CI: 1.59-4.17) were significant predictors of inadequate BP, among personal bowel habits. CONCLUSION: Frequent straining and chronic use of stimulant laxatives were predictors of inadequate BP. An intensified preparation regimen should be considered for severely constipated patients with straining and chronic use of stimulant laxatives.

Exercise-Based Cardiac Rehabilitation Improves Exercise Capacity Regardless of the Response to Cardiac Resynchronization Therapy in Patients With Heart Failure and Reduced Ejection Fraction.

BACKGROUND: In patients with chronic heart failure with reduced ejection fraction (HFrEF), cardiac resynchronization therapy (CRT) improves left ventricular ejection fraction (LVEF) and exercise-based cardiac rehabilitation (ECR) enhances exercise capacity. This study examined the relationship between the 2 responses.Methods and Results:Sixty-four consecutive HFrEF patients who participated in a 3-month ECR program after CRT were investigated. Patients were categorized according to a median improvement in peak oxygen uptake (PV̇O2) after ECR of 7% as either good (n=32; mean percentage change in PV̇O2[%∆PV̇O2]=23.2%) or poor (n=32; mean %∆PV̇O2=2.5%) responders. There was no significant difference in baseline characteristics between the good and poor responders, except for PV̇O2(51% vs. 59%, respectively; P=0.01). The proportion of good CRT responders was similar between the good and poor responders (%∆LVEF ≥10%; 53% vs. 47%, respectively; P=NS). Overall, there was no significant correlation between %∆LVEF after CRT and %∆PV̇O2after ECR. Notably, among poor CRT responders (n=32), the prevalence of atrial fibrillation (0% vs. 29%; P<0.03) and baseline PV̇O2(48% vs. 57%; P<0.05) were significantly lower among those with a good (n=15) than poor (n=17) response to ECR. CONCLUSIONS: In patients with HFrEF, good ECR and CRT responses are unrelated. A good PV̇O2response to ECR can be achieved even in poor CRT responders, particularly in those with a sinus rhythm or low baseline PV̇O2.

Misoprostol Heals Small Bowel Ulcers in Aspirin Users With Small Bowel Bleeding.

BACKGROUND & AIMS: There is no effective treatment for aspirin-induced small bowel ulcer bleeding. We performed a double-blind, randomized, placebo-controlled trial to determine whether misoprostol can heal small bowel ulcers in patients with small bowel bleeding who require continuous aspirin therapy. METHODS: We performed a prospective study of 84 aspirin users with small bowel bleeding who required continued aspirin therapy in Hong Kong and Japan. Patients with small bowel ulcers or multiple erosions, detected by capsule endoscopy, were randomly assigned to groups that received either misoprostol (200 µg, 4 times daily; n = 42) or placebo (n = 42) for 8 weeks. All patients continued taking aspirin (100 mg, once daily). The primary end point was complete ulcer healing at follow-up capsule endoscopy. Secondary end points included changes in hemoglobin level and number of ulcer/erosions from baseline. RESULTS: Complete healing of small bowel ulcers was observed in 12 patients in the misoprostol group (28.6%; 95% CI, 14.9%-42.2%) and 4 patients in the placebo group (9.5%; 95% CI, 0.6%-18.4%), for a difference in proportion of 19.0% (95% CI, 2.8%-35.3%; P = .026). The misoprostol group had a significantly greater mean increase in hemoglobin than the placebo group (mean difference, 0.70 mg/dL; 95% CI, 0.05-1.36; P = .035). The reduction in medium number of ulcers or erosions was significantly greater in the misoprostol group (from 6.5 [range, 1-85] to 2 [range, 0-25]) than in the placebo group (from 7 [range, 1-29] to 4 [range, 0-19] (P = .005). CONCLUSIONS: In a double-blind, randomized, placebo-controlled trial, we found misoprostol to be superior to placebo in promoting healing of small bowel ulcers among aspirin users complicated by small bowel ulcer bleeding who require continuous aspirin therapy. However, use of misoprostol alone would provide only limited protection against aspirin on the small bowel. ClinicalTrials.gov ID NCT01998776.

Efficacy of Cardiac Rehabilitation in Heart Failure Patients With Low Body Mass Index.

BACKGROUND: Low body mass index (BMI) is a relevant prognostic factor for heart failure (HF), but HF patients with low BMI are reported to be at risk of not receiving optimal drug treatment. We sought to evaluate the efficacy of cardiac rehabilitation (CR) in patients with low vs. normal BMI. Methods and Results: We studied 152 consecutive patients (low BMI, n=32; normal BMI, n=119) who participated in a 3-month CR program. Low BMI was defined as <18.5 kg/m2and normal BMI, as 18.5≤BMI<25 kg/m2. All patients underwent cardiopulmonary exercise testing and muscle strength testing at the beginning and end of the 3-month CR program. After CR, a significantly greater proportion of HF patients with low BMI had a positive change in peak V̇O2than in the normal BMI group (91% vs. 70%; P=0.010). Average percent change in peak V̇O2was significantly greater in patients with low vs. normal BMI (17.1±2.8% vs. 7.8±1.5%; P<0.001). In addition, on multivariable logistic regression, low BMI was an independent predictor of a positive change in peak V̇O2after CR (OR, 3.97; 95% CI: 1.10-14.31; P=0.035). CONCLUSIONS: CR has a greater effect in patients with low than normal BMI, and low BMI is an independent predictor of a positive change in peak V̇O2. Thus, CR should be strongly recommended for HF patients with low BMI.

Combination of Peak Exercise Systolic Blood Pressure and Left Atrial Diameter as a Novel Non-Spirometry Prognostic Predictor Comparable to Peak Oxygen Uptake for Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Although peak oxygen uptake (pV̇O2) is a well-established powerful prognostic predictor in heart failure (HF) patients, implementation of cardiopulmonary exercise testing (CPX) is limited by its complex analysis. We aimed to develop a new bivariate predictor obtained without respiratory gas measurement, comparable to pV̇O2.Methods and Results:We studied 560 consecutive HF patients with ejection fraction (EF) <45% who underwent CPX. During a median follow-up of 49.0 months, the composite of all-cause death or HF hospitalization occurred in 228 patients (40.7%) and all-cause death in 111 (19.8%). pV̇O2was the strongest single predictor of the composite outcome (chi-square, 99.3). Among the bivariate non-spirometry parameters, the ratio of systolic blood pressure at peak exercise to left atrial diameter (pSBP/LAD) was the strongest predictor (chi-square, 112.4). Patients with pSBP/LAD <2.8 mmHg/mm, compared with those with pSBP/LAD ≥2.8 mmHg/mm, had a hazard ratio of 3.84 (95% confidence interval, 2.95-5.04) for the composite outcome and 3.66 (2.50-5.37) for all-cause death. In the subgroup with pV̇O2<14 mL/kg/min (n=149), where pV̇O2had no further predictive value, pSBP was the strongest single predictor, and the predictive power of pSBP/LAD was more enhanced. CONCLUSIONS: pSBP/LAD was a new powerful predictor of HF hospitalization and death, comparable to pV̇O2, in HF with reduced EF. Because of its simplicity and high availability, this index has the potential for more widespread use than pV̇O2.

Similar Efficacy of Proton-Pump Inhibitors vs H2-Receptor Antagonists in Reducing Risk of Upper Gastrointestinal Bleeding or Ulcers in High-Risk Users of Low-Dose Aspirin.

BACKGROUND & AIMS: It is not clear whether H2-receptor antagonists (H2RAs) reduce the risk of gastrointestinal (GI) bleeding in aspirin users at high risk. We performed a double-blind randomized trial to compare the effects of a proton pump inhibitor (PPI) vs a H2RA antagonist in preventing recurrent upper GI bleeding and ulcers in high-risk aspirin users. METHODS: We studied 270 users of low-dose aspirin (≤325 mg/day) with a history of endoscopically confirmed ulcer bleeding at 8 sites in Hong Kong and Japan. After healing of ulcers, subjects with negative results from tests for Helicobacter pylori resumed aspirin (80 mg) daily and were assigned randomly to groups given a once-daily PPI (rabeprazole, 20 mg; n = 138) or H2RA (famotidine, 40 mg; n = 132) for up to 12 months. Subjects were evaluated every 2 months; endoscopy was repeated if they developed symptoms of upper GI bleeding or had a reduction in hemoglobin level greater than 2 g/dL and after 12 months of follow-up evaluation. The adequacy of upper GI protection was assessed by end points of recurrent upper GI bleeding and a composite of recurrent upper GI bleeding or recurrent endoscopic ulcers at month 12. RESULTS: During the 12-month study period, upper GI bleeding recurred in 1 patient receiving rabeprazole (0.7%; 95% confidence interval [CI], 0.1%-5.1%) and in 4 patients receiving famotidine (3.1%; 95% CI, 1.2%-8.1%) (P = .16). The composite end point of recurrent bleeding or endoscopic ulcers at month 12 was reached by 9 patients receiving rabeprazole (7.9%; 95% CI, 4.2%-14.7%) and 13 patients receiving famotidine (12.4%; 95% CI, 7.4%-20.4%) (P = .26). CONCLUSIONS: In a randomized controlled trial of users of low-dose aspirin at risk for recurrent GI bleeding, a slightly lower proportion of patients receiving a PPI along with aspirin developed recurrent bleeding or ulcer than of patients receiving an H2RA with the aspirin, although this difference was not statistically significant. ClincialTrials.gov no: NCT01408186.

Efficacy of a concomitant elemental diet to reduce the loss of response to adalimumab in patients with intractable Crohn's disease.

BACKGROUND AND AIM: Secondary loss of response to adalimumab (ADA-LOR) commonly occurs in patients with Crohn's disease (CD) treated with adalimumab (ADA). We evaluated the efficacy of concomitant elemental diet (ED) therapy to reduce ADA-LOR in adult CD patients. METHODS: Patients were divided into either an ED (≥900 kcal/day) or a non-ED group (<900 kcal/day). Cumulative non-ADA-LOR rates were compared between groups. The effects of ED intake to reduce ADA-LOR were also assessed in antitumor necrosis factor-alpha (TNF-α)-naïve and infliximab (IFX)-intolerant or refractory CD patients. Serum ADA and TNF-α levels were measured. RESULTS: We enrolled 117 CD patients into the ED (n = 25) or non-ED (n = 92) groups. Although the cumulative non-ADA-LOR rate was higher in the ED group than in the non-ED group, ED intake was not an independent reducing factor for ADA-LOR (adjusted hazard ratio = 0.725; 95% confidence interval: 0.448-1.180; P = 0.196) in all patients. ED intake was significantly more effective in reducing ADA-LOR in IFX-intolerant or refractory patients than in anti-TNF-α-naïve patients in a dose-related manner (P for interaction <0.20). Serum ADA levels did not differ between the groups. Serum TNF-α levels were significantly lower in the ED group than in the non-ED group at week 28 (P = 0.044) and week 52 (P = 0.043). CONCLUSIONS: Concomitant ED therapy reduced ADA-LOR in IFX-intolerant or refractory patients in a dose-related manner. Reductions in the TNF-α levels by concomitant ED intake may contribute to reduce ADA-LOR in CD patients.

Predictors of improvements in exercise capacity during cardiac rehabilitation in the recovery phase after coronary artery bypass graft surgery versus acute myocardial infarction.

This study aimed to elucidate the predictors of improvements in exercise capacity during cardiac rehabilitation (CR) in the recovery phase after coronary artery bypass graft surgery (CABG) versus acute myocardial infarction (AMI). We studied 152 patients (91 after AMI and 61 after CABG) who participated in a 3-month CR program. All patients underwent a cardiopulmonary exercise test, blood tests, maximal quadriceps isometric strength (QIS) measurement, and bioelectrical impedance body composition measurement at the beginning and end of the 3-month CR program. At baseline, the percentage of predicted peak oxygen uptake (%pred-PVO2), maximal QIS, and hemoglobin (Hb) were significantly lower, while C-reactive protein (CRP) was significantly higher, in the CABG than the AMI group. After the 3-month CR, %change in PVO2 (%ΔPVO2) was significantly greater in the CABG than the AMI group (18 ± 15% vs 11 ± 12%, P < 0.01). At univariate analysis, baseline plasma brain natriuretic peptide (BNP), %change in maximal QIS after CR (%Δ maximal QIS), and change in plasma hemoglobin (ΔHb) significantly correlated with %ΔPVO2 in the CABG group, whereas only baseline %pred-PVO2 did so in the AMI group. Multiple regression analysis revealed that the same factors were independent and significant predictors of %ΔPVO2 in the CABG and AMI groups. The predictors of improvements in exercise capacity after CR differed between patients after CABG or AMI. Specifically, in CABG patients both enhancing QIS and correcting anemia may contribute to greater improvements in exercise capacity after CR, while a more effective CR program should be designed for CABG patients with high baseline BNP.

Long-term prognosis of expanded-indication differentiated-type early gastric cancer treated with endoscopic submucosal dissection or surgery using propensity score analysis.

BACKGROUND AND AIMS: Although endoscopic submucosal dissection (ESD) for expanded-indication lesions of differentiated-type early gastric cancer (EGC) has been widely accepted, no prospective randomized study has been conducted on this subject. This study aimed to evaluate the long-term outcomes of ESD and surgery for expanded-indication lesions of differentiated-type EGC. METHODS: Between 1997 and 2012, 1500 consecutive patients with EGC were treated in Osaka City University Hospital. Using propensity score matching and inverse probability of treatment weighting (IPTW), we retrospectively evaluated the long-term outcomes, risk factors for mortality, and adverse events for patients with expanded-indication lesions of differentiated-type EGC who underwent ESD or surgical treatments. RESULTS: A total of 308 patients with expanded-indication lesions of differentiated-type EGC confirmed by pathologic examination after ESD or surgery met the eligibility criteria. After matching, the 5-year overall survival rate was higher in the ESD group than in the surgery group (97.1% vs 85.8%; P = .01). We also found that surgery was significantly associated with mortality using both the IPTW method (hazard ratio [HR], 10.89; 95% confidence interval [CI], 1.37-86.6; P < .01), and Cox analysis (HR, 8.60; 95% CI, 1.11-66.52; P = .04) after matching. Significantly fewer adverse events were associated with ESD than with surgery (6.8% vs 28.4%; P < .01). No cause-specific mortality was observed in either group. CONCLUSIONS: Our results indicate that ESD might be an alternative treatment modality for expanded-indication lesions of differentiated-type EGC.

A comparison between capsule endoscopy and double balloon enteroscopy using propensity score-matching analysis in patients with previous obscure gastrointestinal bleeding.

BACKGROUND: Recently, diagnosis of obscure gastrointestinal bleeding (OGIB) has improved greatly due to introduction of capsule endoscopy (CE) and double balloon enteroscopy (DBE). However, the efficacy of CE over DBE in patients with previous OGIB remains unclear. This study aimed to compare, in terms of diagnostic yield, the efficacy of DBE with that of CE in patients with previous OGIB. PATIENTS AND METHODS: We enrolled 223 consecutive patients with previous OGIB who were treated between May 2007 and March 2012. We retrospectively evaluated the respective diagnostic yields of CE and DBE in patients with previous OGIB using propensity score-matching analysis. We compared the diagnostic yield of CE with that of DBE. RESULTS: The diagnostic yields were 41.9% in DBE group and 11.6% in CE group, respectively (p < .01). On logistic regression analysis, DBE was significantly superior to CE after matching (Odds ratio [OR], 4.25; 95% confidence interval [CI], 1.43-12.6; p < .01), even after adjustment for propensity score (OR, 5.65; 95% CI, 1.56?20.5; p < .01). CONCLUSIONS: Our results indicate that DBE might be more useful and perhaps safer than CE in achieving a positive diagnosis in patients with previous OGIB.

Improvement in Exercise Capacity by Exercise Training Associated With Favorable Clinical Outcomes in Advanced Heart Failure With High B-Type Natriuretic Peptide Level.

BACKGROUND: The efficacy of exercise training (ET) programs and its relationship with long-term clinical outcomes in advanced heart failure (HF) patients with high levels of B-type natriuretic peptide (BNP) remain uncertain.Methods and Results:We studied 340 consecutive HF patients with ejection fraction (EF) <45% who completed a 3-month ET program. Patients with BNP ≥200 pg/mL (High-BNP, n=170) had more advanced HF characteristics, including lower EF (25.0±8.6% vs. 28.1±8.0%, P=0.0008), than those with BNP <200 pg/mL. In the High-BNP patients, peak oxygen uptake (V̇O2) was significantly increased by 8.3±16.2% during the ET program, and changes in peak V̇O2inversely correlated with changes in BNP (R=-0.453, P<0.0001) and changes in ventilatory efficiency (V̇E/V̇CO2slope) (R=-0.439, P<0.0001). During a median follow-up of 46 months, patients in the upper tertile of changes in peak V̇O2(≥13.0%), compared with those in the lower tertile (<1.0%), had lower rates of the composite of all-cause death or HF hospitalization (37.9% vs. 54.4%, P=0.036) and all-cause death (8.6% vs. 24.6%, P=0.056). In the multivariate analysis, change in peak V̇O2was a significant independent predictor of the composite outcome and all-cause death. CONCLUSIONS: Even among advanced HF patients with high BNP level, an ET program significantly improved exercise capacity, and a greater improvement in exercise capacity was associated with greater decreases in BNP level and V̇E/V̇CO2slope and more favorable long-term clinical outcomes.

Microbiota Plays a Key Role in Non-Steroidal Anti-Inflammatory Drug-Induced Small Intestinal Damage.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) damage the small intestine by causing multiple erosions and ulcers. However, to date, no established therapies and prophylactic agents are available to treat such damages. We reviewed the role of intestinal microbiota in NSAID-induced intestinal damage and identified potential therapeutic candidates. SUMMARY: The composition of the intestinal microbiota is an important factor in the pathophysiology of NSAID-induced small intestinal damage. Once mucosal barrier function is disrupted due to NSAID-induced prostaglandin deficiency and mitochondrial malfunction, lipopolysaccharide from luminal gram-negative bacteria and high mobility group box 1 from the injured epithelial cells activate toll-like receptor 4-signaling pathway and nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 inflammasome; this leads to the release of proinflammatory cytokines such as tumor necrosis factor-α and interleukin-1ß. Proton pump inhibitors (PPIs) are often used for the prevention of NSAID-induced injuries to the upper gastrointestinal tract. However, several studies indicate that PPIs may induce dysbiosis, which may exacerbate the NSAID-induced small intestinal damage. Our recent research suggests that probiotics and rebamipide could be used to prevent NSAID-induced small intestinal damage by regulating the intestinal microbiota. Key Messages: Intestinal microbiota plays a key role in NSAID-induced small intestinal damage, and modulating the composition of the intestinal microbiota could be a new therapeutic strategy for treating this damage.

Production of insulin-like growth factor-II in hepatocellular carcinoma with recurrent hypoglycemia: a case report.

A 35-year-old woman, who was an HBV carrier, complained of fever for 2 weeks, and thus, she was admitted in our hospital. Both serum AFP and PIVKA-II levels were abnormally high, and an abdominal enhanced CT revealed the presence of multiple masses in both lobes of the liver. She was diagnosed with hepatocellular carcinoma (T4, N0, M0, and Vp4) and was treated with transcatheter arterial infusion chemotherapy. On the 4th day of her illness, her serum glucose level was 26mg/dl. Glucose infusion and intravenous hyperalimentation were not effective, and she experienced repeated hypoglycemic attacks. Based on the low levels of both insulin (0.4µU/ml) and insulin-like growth factor (IGF)-I (14ng/ml), we made a diagnosis of non-islet cell tumor hypoglycemia associated with hepatocellular carcinoma. The patient was orally administered prednisolone at a dose of 20mg/day. On the 49th day of illness, the hepatocellular carcinoma ruptured, and 2 days later, she died because of hemorrhage shock. Postmortem immunohistochemical staining for IGF-II was positive in the tumor cells of the liver. Furthermore, Western immunoblotting revealed the presence of high-molecular-weight form of IGF-II in the serum of the patient.

Tumor necrosis factor α decreases glucagon-like peptide-2 expression by up-regulating G-protein-coupled receptor 120 in Crohn disease.

Glucagon-like peptide (GLP)-2, secreted by L cells in the small intestine, has anti-inflammatory effects in the gastrointestinal tract. A GLP-2 analogue has been an effective treatment for Crohn disease (CD). G-protein-coupled receptor (GPR) 40 and GPR120 are probably involved in GLP-2 production, the mechanisms of which remain unclear. In our experiments, normal ileal mucosa expressed GPR40, but rarely expressed GPR120. However, both GPRs were overexpressed in the L cells of the inflamed ileal mucosa of CD patients. Mucosal inflammation induced the overexpression of GPR40, GPR120, and several inflammatory cytokines, with correlations between ileal concentrations of tumor necrosis factor (TNF)-α and GPR expression levels; however, inflammation did not induce the expression of proglucagon, a precursor of GLP-2 in CD patients. In rat L cells and GLUTag cells, TNF-α treatment increased GPR120 mRNA expression without affecting GPR40 mRNA expression. Dual agonists of GPR40 and GPR120, GW9508 and linoleic acid, respectively, increased GLP-2 production from L cells, but these agonists decreased it in the presence of TNF-α. The GPR40 antagonist, GW1100, inhibited the GW9508-induced increase in GLP-2 production, and silencing GPR120 resulted in further elevation of GLP-2 production. Thus, GPR120-dependent signaling inhibited the stimulatory effects of GPR40 on GLP-2 expression, and TNF-α treatment decreased GLP-2 expression by up-regulating GPR120 expression in L cells.

Regional Clinical Alliance Path and Cardiac Rehabilitation After Hospital Discharge for Acute Myocardial Infarction Patients in Japan　- A Nationwide Survey.

BACKGROUND: The regional clinical alliance path (RCAP) after discharge from an acute-phase hospital is emerging as a tool for bridging acute-phase treatment and chronic-phase disease management. However, the optimal application of RCAP for acute myocardial infarction (AMI) remains unknown in Japan, and therefore a nationwide survey of hospitals was conducted. METHODS AND RESULTS: In 2009, questionnaires were sent to 1,240 cardiology training hospitals authorized by the Japanese Circulation Society. The response rate was 62.9% (780/1,240). Of the 780 responding hospitals, 708 treated AMI, and in these hospitals the number of AMI patients and percutaneous coronary intervention (PCI) procedures performed were, respectively, 59±52 and 200±206 per year. The implementation rate of emergency PCI was high (91%), but that of outpatient cardiac rehabilitation (OPCR) was very low (18%). The implementation rate of RCAP after AMI was significantly lower (10%) than after stroke (57%). Cardiac rehabilitation (CR) was adopted as part of RCAP in only 19% (13/70) of currently operating RCAP programs. CONCLUSIONS: This first Japanese nationwide survey of RCAP after AMI showed that in contrast to the broad dissemination of acute-phase invasive treatment for AMI, there was infrequent implementation of OPCR, RCAP after AMI, and RCAP including CR. It will be necessary to broaden the use of RCAP after AMI, including OPCR. (Circ J 2016; 80: 1750-1755).

Reduction of prostaglandin transporter predicts poor prognosis associated with angiogenesis in gastric adenocarcinoma.

BACKGROUND AND AIM: Prostaglandin (PG) E2 promotes gastrointestinal carcinogenesis and tumor progression. The total amount of biologically active PGE2 in tissues is determined by a balance of PG biosynthesis and degradation pathways, which involve the PG transporter (PGT). We investigated PGT in gastric adenocarcinoma by determining its expression pattern and examining associations of PGT with prognosis and tumor angiogenesis. METHODS: PGT expression was determined by immunohistochemistry in advanced gastric adenocarcinoma specimens obtained from 96 patients who underwent surgical resection. Correlations between PGT expression level and clinicopathological factors were statistically analyzed. Angiogenesis in the tumor tissue was evaluated by counting the number of microvessels. The role of PGT in mRNA and protein expression of vascular endothelial growth factor (VEGF) was examined in gastric cancer cells stimulated by PGE2 . RESULTS: Based on multivariate and Kaplan-Meier analyses, negativity for PGT expression was an independent poor prognostic factor. There were more microvessels in PGT-negative tumors than in PGT-positive tumors. Transfection of AGS and MKN7 gastric cancer cells with PGT-specific siRNA led to increased VEGF mRNA and protein expression accompanied by increased PGE2 in the culture media. CONCLUSIONS: PGT expression is an independent predictor of poor survival and is associated with tumor angiogenesis in gastric adenocarcinoma.

Prediction of Poor Response to Modified Neuroleptanalgesia with Midazolam for Endoscopic Submucosal Dissection for Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIMS: Modified neuroleptanalgesia (m-NLA) with midazolam is often used for sedation and analgesia during endoscopic submucosal dissection (ESD) for gastrointestinal neoplasia. However, interruption due to poor response to midazolam is often experienced during ESD for esophageal squamous cell carcinoma (ESCC) because most patients with ESCC have a history of heavy alcohol intake. We examined the incidence and risk factors for poor response to m-NLA with midazolam and pethidine hydrochloride. METHODS: This retrospective cross-sectional study was conducted at a single institution. Between April 2007 and July 2013, 151 patients with superficial ESCC who underwent ESD under sedation using m-NLA with midazolam and pethidine hydrochloride were enrolled. Poor response to sedation was defined as the use of a second drug when Ramsay Sedation Score 1-2. RESULTS: Poor response to sedation occurred in 66.2% patients. Most cases of poor response were controlled by using additional flunitrazepam. Multivariate logistic regression analysis showed that cumulative alcohol intake and major specimen size were independent risk factors for poor response to sedation (OR 3.63, 95% CI 1.20-10.99, and OR 3.23, 95% CI 1.26-8.25). CONCLUSION: Our study indicated that cumulative alcohol intake and major specimen size were associated with poor response to m-NLA with midazolam and pethidine hydrochloride.

Questionnaire-Based Survey on Diagnostic and Therapeutic Endoscopies and H. pylori Eradication for Elderly Patients in East Asian Countries.

BACKGROUND: Gastrointestinal endoscopy and Helicobacter pylori(H. pylori) eradication therapy are commonly performed even among the elderly population. The aim of this study was to understand the way endoscopists viewed the application of endoscopy and H. pylori eradication in the elderly of East Asian countries. METHODS: Self-administered questionnaires containing 13 questions on endoscopy and H. pylori eradication in the elderly were distributed to major institutions in Japan, South Korea, China, Indonesia, and the Philippines. RESULTS: Two hundred and fifteen endoscopists (111 in Japan, 39 in China, 24 in Korea, 21 in Indonesia, and 20 in the Philippines) participated in this study. In the institutions where these endoscopists were associated, around 50% of patients undergoing endoscopy were above the age of 60 years. The participating endoscopists indicated that the necessity of screening esophagogastroduodenoscopy and colonoscopy was lower in populations aged over 81 than the other age groups. They hesitated to perform therapeutic endoscopy, such as endoscopic submucosal dissection or endoscopic retrograde cholangiopancreatography, more often in patients over 85. They also hesitated to perform H. pylori eradication in patients aged over 81, especially in Japan. CONCLUSION: Endoscopists had significantly different attitudes regarding the indications for screening or therapeutic endoscopy and H. pylori eradication therapy in younger and elderly populations in East Asian countries.

Alteration of Esophageal Microbiome by Antibiotic Treatment Does Not Affect Incidence of Rat Esophageal Adenocarcinoma.

BACKGROUND: Recent studies suggest that chronic inflammation-associated cancer is relevant to microbiome. Esophageal adenocarcinoma arises from an inflammatory condition called Barrett's esophagus, which is caused by gastroesophageal reflux. We hypothesized that esophageal microbiome plays a role in carcinogenesis of esophageal adenocarcinoma. AIM: We investigated whether alteration of microbiome using antibiotics affects the development of esophageal adenocarcinoma in a rat model. METHODS: Seven-week-old male Wistar rats which had undergone esophagojejunostomy were divided into control (n = 21) and antibiotic groups (n = 22) at 21 weeks after surgery. Control animals were given drinking water, while the other group was given penicillin G and streptomycin in drinking water until rats were killed at 40 weeks after operation. Incidence rates of Barrett's esophagus and adenocarcinoma in each group were evaluated by histological analysis. DNA was extracted from a portion of the distal esophagus, and the microbiome was investigated using terminal restriction fragment length polymorphism (T-RFLP) analysis. RESULTS: All rats in both groups developed Barrett's esophagus. Incidence of esophageal adenocarcinoma was similar between both groups with a trend to reduced incidence in the antibiotics group (89 % in the control group, 71 % in the antibiotics group, P = 0.365). T-RFLP analysis showed that esophageal microbiome was different between two groups such as the proportion of Lactobacillales was lower in the antibiotics group and Clostridium cluster XIVa and XVIII was higher in the antibiotics group. CONCLUSIONS: Alteration of microbiome does not affect the incidence of esophageal adenocarcinoma. Microbiome may not contribute to the development of esophageal adenocarcinoma.