Apalutamide and Goserelin for Androgen Receptor-Positive Salivary Gland Carcinoma: A Phase II Nonrandomized Clinical Trial, YATAGARASU.

PURPOSE: To assess the efficacy and safety of apalutamide plus goserelin for androgen receptor (AR)-positive unresectable or recurrent/metastatic salivary gland carcinoma. PATIENTS AND METHODS: This trial was an open-label, single-arm, multicenter phase II study. Patients with histologically confirmed unresectable or recurrent/metastatic salivary gland carcinoma with AR expression were included. The primary endpoint was the overall response rate (ORR) according to RECIST v1.1 by an independent central radiology review in the first 24 response-evaluable (RE) patients who had been observed at least 24 weeks from study initiation (primary RE patients). The efficacy was to be declared when at least 8 of the 24 primary RE patients responded. RESULTS: A total of 31 patients were enrolled. In the first 24 primary RE patients with a median follow-up of 7.4 months, confirmed ORR by independent central radiology review was 25.0% [6/24 patients; 95% confidence interval, 9.8%-46.7%; P = 0.11 (one-sided)], which did not meet the predefined criteria of efficacy. Clinical benefit rate (ORR + rate of stable disease for at least 24 weeks) and median progression-free survival were 50.0% and 7.4 months, respectively. Both median duration of response and overall survival were not reached. Exploratory analyses showed a better ORR of 54.5% (6/11) in patients with AR positivity ≥70% and no history of prior systemic therapy. Grade 3 or higher treatment-emergent adverse events were reported in 35.5% (11/31), which included skin rash, anemia, leukopenia, and cancer pain. CONCLUSIONS: Although this study did not meet the predefined efficacy criteria, apalutamide plus goserelin showed clinically meaningful efficacy in a subset of patients with AR-positive salivary gland carcinoma and safety consistent with prior experience in prostate cancer.

Objective Evaluation With Noncontrast Computed Tomography Can Reveal Calcified Plaque Solidity in Peripheral Artery Diseases.

PURPOSE: The presence of severely calcified plaque remains problematic in endovascular therapy, and no specific endovascular treatment strategy has been established. Estimating plaque solidity before the procedure may help operators penetrate calcified plaque with a guide wire. The aim of this study was to establish a method of measuring plaque solidity with noncontrast computed tomography (CT). METHODS: This retrospective, single-center study included consecutive patients who, between October 2020 and July 2022, underwent noncontrast 5 mm and 1 mm CTs before endovascular therapy to penetrate calcified plaque with a wire in the common femoral, superficial femoral, and popliteal arteries. Three cross-sectional CT slices were selected. To target a calcified plaque lesion, the operator identified a region of interest, which corresponded to 24×24 pixels, and Hounsfield unit (HU) values of each pixel were displayed on the CT image. The average HU values and the ratio of number of pixels of lower values (130-599 HU) represented plaque solidity. We used the Mann-Whitney-Wilcoxon rank-sum test and the chi-square test to compare the solidity of plaques penetrated and not penetrated by the wire. RESULTS: We evaluated 108 images of 36 calcified plaque lesions (in 19 patients). The wire penetrated 28 lesions (77.8%) successfully. The average HU value was significantly lower in the lesions that the wire penetrated than in the others, in both the 5 mm CT slices (434.7±86.8 HU vs 554.3±112.7 HU, p=0.0174) and 1 mm slices (497.8±103.1 HU vs 593.5±114.5 HU, p=0.0381). The receiver operating curve revealed that 529.9 and 533.9 HU in the 5 and 1 mm slices, respectively, were the highest values at which wires could penetrate. Moreover, at the lesions that were penetrates successfully, the ratio of number of lower HU value pixels was significantly higher both in 5 mm slice CTs (74.7±13.4 vs 61.7±13.1%, p=0.0347) and 1 mm (68.7±11.8 vs 57.1±11.4%, p=0.0174). CONCLUSION: The use of noncontrast CT to evaluate plaque solidity was associated with successful wire penetration of calcified lesions in peripheral arteries. CLINICAL IMPACT: This study revealed an association between the wire penetration inside calcified plaque and plaque solidity estimated using non-contrasted computed tomography. The mean Hounsfield unit values of three cross-sections in calcified plaques were associated with the successful wire penetration. This wire penetration difficulty is associated with extended procedure time, excessive radiation exposure, usage of extra contrast agents, and increased medical costs. Therefore, estimating calcified plaque solidity before procedure enables us to choose effective and lean procedures. In addition, to predict the success of dilating calcified plaque from the inside is also beneficial when the operator wants to avoid extra scaffold implantation for target lesions.

Relationship between skin autofluorescence levels and clinical events in patients with heart failure undergoing cardiac rehabilitation.

BACKGROUND: Advanced glycation end-products, indicated by skin autofluorescence (SAF) levels, could be prognostic predictors of all-cause and cardiovascular mortality in patients with diabetes mellitus (DM) and renal disease. However, the clinical usefulness of SAF levels in patients with heart failure (HF) who underwent cardiac rehabilitation (CR) remains unclear. This study aimed to investigate the associations between SAF and MACE risk in patients with HF who underwent CR. METHODS: This study enrolled 204 consecutive patients with HF who had undergone CR at our university hospital between November 2015 and October 2017. Clinical characteristics and anthropometric data were collected at the beginning of CR. SAF levels were noninvasively measured with an autofluorescence reader. Major adverse cardiovascular event (MACE) was a composite of all-cause mortality and unplanned hospitalization for HF. Follow-up data concerning primary endpoints were collected until November 2017. RESULTS: Patients' mean age was 68.1 years, and 61% were male. Patients were divided into two groups according to the median SAF levels (High and Low SAF groups). Patients in the High SAF group were significantly older, had a higher prevalence of chronic kidney disease, and more frequently had history of coronary artery bypass surgery; however, there were no significant between-group differences in sex, prevalence of DM, left ventricular ejection fraction, and physical function. During a mean follow-up period of 590 days, 18 patients had all-cause mortality and 36 were hospitalized for HF. Kaplan-Meier analysis showed that patients in the high SAF group had a higher incidence of MACE (log-rank P < 0.05). After adjusting for confounding factors, Cox regression multivariate analysis revealed that SAF levels were independently associated with the incidence of MACE (odds ratio, 1.86; 95% confidence interval, 1.08-3.12; P = 0.03). CONCLUSION: SAF levels were significantly associated with the incidence of MACE in patients with HF and may be useful for risk stratification in patients with HF who underwent CR.

Arterial Stiffness Index and Exercise Tolerance in Patients Undergoing Cardiac Rehabilitation.

Arterial stiffness contributes to the development of cardiovascular disease (CVD). However, the relationship between the arterial stiffness and exercise tolerance in CVD patients with preserved ejection fraction (pEF) and those with reduced EF (rEF) is unclear. We enrolled 358 patients who participated in cardiac rehabilitation and underwent cardiopulmonary exercise testing at Juntendo University Hospital. After excluding 195 patients who had undergone open heart surgery and 20 patients with mid-range EF, the patients were divided into pEF (n = 99) and rEF (n = 44) groups. Arterial stiffness was assessed using arterial velocity pulse index (AVI) and arterial pressure volume index (API) at rest. The patients in the pEF group were significantly older and had a higher prevalence of coronary artery disease than the rEF group. The pEF group had significantly lower AVI levels and higher API levels than the rEF group. In the pEF group, the peak oxygen uptake (peak VO2) and the anaerobic threshold was significantly higher than those in the rEF group. The peak VO2 was significantly and negatively correlated with AVI and API in the pEF group (All, P < 0.05), but not in the rEF group. Multivariate linear regression analyses demonstrated that AVI was independently associated with peak VO2 (ß = -0.34, P < 0.05) in the pEF group. In conclusion, AVI may be a useful factor for assessing exercise tolerance, particularly in CVD patients with pEF.

Gastric xanthoma is correlated with early gastric cancer of previously Helicobacter pylori-infected gastric mucosa.

BACKGROUND AND AIM: Successful Helicobacter pylori eradication has been shown to prevent the development of gastric cancer (GC), but clinical evidence for factors that correlate with GC of previously H. pylori-infected gastric mucosa (after eradication or natural disappearance) is limited. The purpose of our study was to identify these correlative factors. METHODS: We retrospectively examined data from patients with previously H. pylori-infected gastric mucosa. Data from 168 patients who developed early GC and underwent endoscopic submucosal dissection (Group C) and 835 patients with no history of early GC (Group NC) were compared. We extracted data on gender; age; complications from malignant disease and diabetes mellitus; American Society of Anesthesiologists (ASA) physical status classification; and endoscopic characteristics of atrophy (open type), intestinal metaplasia, and gastric xanthoma (GX). Correlations were determined with multivariate logistic regression analysis and propensity score matching. RESULTS: A significantly higher proportion of patients had GX in Group C than in Group NC. Age, male gender, ASA physical status classification of class III or higher, complications from malignant disease, atrophy (open type), and the presence of intestinal metaplasia and GX were identified as factors that correlated independently with GC (odds ratio = 3.65; 95% confidence interval = 2.37-5.61; P < 0.0001). Propensity score matching demonstrated that the prevalence of GC was also significantly higher in patients who were positive for GX (37.2% vs 18.3%; P < 0.0001). CONCLUSION: GX was shown to correlate with early GC of previously H. pylori-infected gastric mucosa.

Voluntary exercise and cardiac remodeling in a myocardial infarction model.

We investigated the effects of voluntary exercise after myocardial infarction (MI) on cardiac function, remodeling, and inflammation. Male C57BL/6J mice were divided into the following four groups: sedentary + sham (Sed-Sh), sedentary + MI (Sed-MI), exercise + sham (Ex-Sh), and exercise + MI (Ex-MI). MI induction was performed by ligation of the left coronary artery. Exercise consisting of voluntary wheel running started after the operation and continued for 4 weeks. The Ex-MI mice had significantly increased cardiac function compared with the Sed-MI mice. The Ex-MI mice showed significantly reduced expression levels of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and IL-10 in the infarcted area of the left ventricle compared with the Sed-MI mice. In the Ex-MI mice, the expression levels of fibrosis-related genes including collagen I and III were decreased compared to the Sed-MI mice, and the expression levels of IL-1ß, IL-6, follistatin-like 1, fibroblast growth factor 21, and mitochondrial function-related genes were significantly elevated in skeletal muscle compared with the Sed mice. The plasma levels of IL-6 were also significantly elevated in the Ex-MI group compared with the Sed-MI groups. These findings suggest that voluntary exercise after MI may improve in cardiac remodeling associated with anti-inflammatory effects in the myocardium and myokine production in the skeletal muscles.

[Multiple gastric adenocarcinoma of fundic gland type after H. pylori eradication: a case report].

A 70-year-old woman received H. pylori eradication therapy in March, 201X-12. She was admitted to our department because early gastric cancer was detected on esophagogastroduodenoscopy, and we performed endoscopic submucosal dissection (ESD) in June, 201X-2. The final diagnosis was well-differentiated tubular adenocarcinoma. Afterwards, we performed ESD two times (in November, 201X-1, and in March, 201X), and final diagnoses were both adenocarcinoma of fundic gland type.

Promotion of oxidative stress is associated with mitochondrial dysfunction and muscle atrophy in aging mice.

AIM: We examined the changes in oxidative stress, mitochondrial function and muscle atrophy during aging in mice. METHODS: We used 6-, 12- and 24-month (6 M, 12 M and 24 M)-old C57BL/6J mice. Skeletal muscles were removed from the lower limb and used for quantitative real-time polymerase chain reaction, immunoblotting and histological analyses. RESULTS: The muscle weight and myocyte cross-sectional area were significantly decreased in the 12 M and 24 M mice compared with those of the 6 M mice. The levels of the oxidative stress markers, nicotinamide adenine dinucleotide phosphate oxidase 2, nicotinamide adenine dinucleotide phosphate oxidase 4, mitochondrial 4-hydroxy-2-nonenal and 3-nitrotyrosine, were significantly higher in the 24 M mice compared with those of the 6 M mice. Furthermore, the 24 M mice had lower levels of mitochondrial markers, peroxisome proliferator-activated receptor gamma coactivator 1 (PGC)-α, peroxisome proliferator-activated receptor gamma coactivator-1ß, sirtuin-1, adenosine triphosphate synthase mitochondria F1 complex α subunit 1 and mitochondrial cytochrome c oxidase 1. The ubiquitin-proteasome pathway genes muscle ring finger-1 and atrogin-1 were significantly upregulated in the 12 M and 24 M mice, and protein synthesis markers (phosphorylated-Akt and -p70 ribosomal S6 kinase) were significantly lower in the 24 M mice compared with the 6 M mice (all P < 0.05). CONCLUSIONS: These findings have important implications for the mechanisms that underlie sarcopenia and frailty processes. Geriatr Gerontol Int 2020; 20: 78-84.

[Anaphylactic shock secondary to the use of macrogol 4000 as a bowel cleanser:a case report].

A 44-year-old man was administered Niflec® containing macrogol 4000 as a bowel cleanser for colonoscopic examination. Immediately after ingestion, he experienced oral cavity discomfort and nasal congestion, followed by acute urticaria and presyncope. His systolic blood pressure and peripheral capillary oxygen saturation dropped to 66mmHg and 89%, respectively. Fluid infusion, as well as steroid and epinephrine administration, improved his symptoms. Skin prick tests were then performed using Niflec®, macrogol 4000, and Actosin® ointment (containing macrogol 4000), all of which were positive. Therefore, the patient was diagnosed with anaphylactic shock caused by macrogol 4000 included in Niflec®. Macrogol present in bowel cleansers used for colonoscopy rarely causes anaphylactic shock. However, clinicians need to be mindful of this risk. Prompt and appropriate treatment is needed should this condition occur.

Synchronous Three Gastric Fundic Gland Polyps with Low-grade Dysplasia Treated with Endoscopic Mucosal Resection after Being Diagnosed to Be Tubular Adenocarcinoma Based on a Biopsy Specimen.

A 51-year-old woman had been taking proton pump inhibitor since August 2008. In May, 2016, endoscopic findings showed no atrophy and no intestinal metaplasia in the stomach, and multiple fundic gland polyps were identified in the stomach. A biopsy of a pedunculated polyp measuring 10 millimeters in diameter at the greater curvature of the middle gastric body demonstrated well differentiated tubular adenocarcinoma. In July 2016, we treated this lesion and two other semipedunculated polyps located near the first polyp and also measuring 10 mm in diameter by endoscopic mucosal resection. The final diagnosis of all lesions was a fundic gland polyp with low grade dysplasia and the cutting end was negative.

[Curative endoscopic submucosal dissection of laterally spreading sporadic tumor in ulcerative colitis:a case report].

A 60-year-old man visited our department because of watery diarrhea that lasted for several months. On colonoscopy, we diagnosed him as ulcerative colitis. Additionally, a laterally spreading tumor (non-granular type) was discovered in the rectum above the peritoneal reflection (Ra). The patient was initially treated with 5-aminosalicylic acid. Four months later, endoscopic submucosal dissection was performed. Histopathology examination showed a sporadic tubular adenoma. Complete en bloc resection was performed.

Gastric Xanthoma Is a Predictive Marker for Early Gastric Cancer Detected after Helicobacter pylori Eradication.

Objective The detection of early gastric cancer (GC) after Helicobacter pylori eradication is expected to increase in Japan. However, the predictive markers for early GC detected after H. pylori eradication have not been extensively studied. We conducted a retrospective, single-center observational study to investigate the predictive markers for early GC detected after H. pylori eradiation. Methods A total of 421 patients underwent endoscopic submucosal dissection for early GC at NTT West Osaka Hospital between June 2006 and August 2017. Data from patients with GC (Group C; n=70) and without GC (Group NC; n=114) after H. pylori eradication were analyzed. Results The proportion of men was significantly higher in Group C than in Group NC (92.9% vs. 65.8%; p<0.0001). Complications with other malignant diseases were more prevalent in Group C than in Group NC. A significantly greater proportion of patients had gastric xanthoma (GX) in Group C than in Group NC (64.3% vs. 14.9%; p<0.0001). Regarding scores for endoscopic findings related to the risk of GC, the atrophy score, intestinal metaplasia score and total score were significantly higher in Group C than in Group NC. A multivariate logistic regression analysis identified male sex, atrophy (open type), the presence of intestinal metaplasia and GX as independent predictors for early GC detected after H. pylori eradication. An atrophy-matched control analysis also identified GX as an independent predictor. Conclusion GX is a novel predictive marker for early GC detected after H. pylori eradication.

Low 1,5-anhydroglucitol levels are associated with long-term cardiac mortality in acute coronary syndrome patients with hemoglobin A1c levels less than 7.0.

BACKGROUND: Diabetes mellitus is considered an important risk factor for cardiovascular diseases. High hemoglobin A1c (HbA1c) levels, which indicate poor glycemic control, have been associated with occurrence of cardiovascular diseases. There are few parameters which can predict cardiovascular risk in patients with well-controlled diabetes. Low 1,5-anhydroglucitol (1,5-AG) levels are considered a clinical marker of postprandial hyperglycemia. We hypothesized that low 1,5-AG levels could predict long-term mortality in acute coronary syndrome (ACS) patients with relatively low HbA1c levels. METHODS: The present study followed a retrospective observational study design. We enrolled 388 consecutive patients with ACS admitted to the cardiac intensive care unit at the Juntendo University Hospital from January 2011 to December 2013. Levels of 1,5-AG were measured immediately before emergency coronary angiography. Patients with early stent thrombosis, no significant coronary artery stenosis, malignancy, liver cirrhosis, a history of gastrectomy, current steroid treatment, moderately to severely reduced kidney function (estimated glomerular filtration rate < 45 ml/min/1.73 m2; chronic kidney disease stage 3B, 4, and 5), HbA1c levels ≥ 7.0%, and those who received sodium glucose co-transporter 2 inhibitor therapy were excluded. RESULTS: During the 46.9-month mean follow-up period, nine patients (4.5%) died of cardiovascular disease. The 1,5-AG level was significantly lower in the cardiac death group compared with that in the survivor group (12.3 ± 5.3 vs. 19.2 ± 7.7 µg/ml, p < 0.01). Kaplan-Meier survival analysis showed that low 1,5-AG levels were associated with cardiac mortality (p = 0.02). Multivariable Cox regression analysis showed that 1,5-AG levels were an independent predictor of cardiac mortality (hazard ratio 0.76; 95% confidence interval 0.41-0.98; p = 0.03). CONCLUSION: Low 1,5-AG levels, which indicate postprandial hyperglycemia, predict long-term cardiac mortality even in ACS patients with HbA1c levels < 7.0%.

Gastric xanthoma is a predictive marker for metachronous and synchronous gastric cancer.

AIM: To investigate predictive markers for metachronous and synchronous gastric cancer (GC), which can develop after endoscopic submucosal dissection (ESD). METHODS: A total of 352 patients underwent ESD for early GC at NTT West Osaka Hospital between June 2006 and February 2016. Exclusion criteria were as follows: Remnant stomach, unknown Helicobacter pylori status, and endoscopic observation of the whole stomach outside our hospital. We analyzed data from 192 patients comprising 109 patients with solitary GC (Group A) and 83 with metachronous and synchronous GC (Group B). We retrospectively investigated the clinicopathological and endoscopic characteristics, and endoscopic risk score as predictive markers for GC. RESULTS: The median age of Group B [72 years (interquartile range 63-78)] was significantly higher than that of Group A [66 years (interquartile range 61-74), respectively, P = 0.0009]. The prevalence of intestinal metaplasia in Group B tended to be higher than that in Group A (57.8% vs 45.0%, P = 0.08). The prevalence of gastric xanthoma (GX) in Group B was significantly higher than that in Group A (54.2% vs 32.1%, P = 0.003). The atrophy score in Group B was significantly higher than that in Group A (P = 0.005). Multivariate analysis revealed that higher age and the presence of GX were independently related to metachronous and synchronous GC [OR = 1.04 (1.01-1.08), P = 0.02; and OR = 2.11 (1.14-3.99), P = 0.02, respectively]. CONCLUSION: The presence of GX is a useful predictive marker for metachronous and synchronous GC.

Decreased circulating dihomo-gamma-linolenic acid levels are associated with total mortality in patients with acute cardiovascular disease and acute decompensated heart failure.

BACKGROUND: Polyunsaturated fatty acids (PUFAs) have important roles in the pathogenesis of cardiovascular diseases. However, the clinical significance of omega-6 PUFAs in acute cardiovascular disease remains unknown. METHODS: We enrolled 417 consecutive patients with acute cardiovascular disease admitted to the cardiac intensive care unit at Juntendo University Hospital between April 2012 and October 2013. We investigated the association between serum PUFA levels and long-term mortality. Blood samples were collected after an overnight fast, within 24 h of admission. We excluded patients who received eicosapentaenoic acid therapy and those with malignancy, end-stage kidney disease, chronic hepatic disease, and connective tissue disease. RESULTS: Overall, 306 patients (mean age: 66.4 ± 15.0 years) were analysed. During the follow-up period of 2.4 ± 1.2 years, 50 patients (16.3%) died. The dihomo-gamma-linolenic acid (DGLA) levels, arachidonic acid (AA) levels, and DGLA/AA ratio were significantly lower in the nonsurvivor group than in the survivor group (DGLA: 23.2 ± 9.8 vs. 31.5 ± 12.0 µg/ml, AA: 151.1 ± 41.6 vs. 173.3 ± 51.6 µg/ml, and DGLA/AA: 0.16 ± 0.05 vs. 0.19 ± 0.06, all p < 0.01). Kaplan-Meier curves showed that survival rates were significantly higher in the higher DGLA, AA, and DGLA/AA groups than in their lower counterparts (DGLA and AA; p < 0.01, DGLA/AA; p = 0.01), although omega-3 PUFAs were not associated with prognosis. Furthermore, in patients with acute decompensated heart failure (ADHF), survival rates were significantly higher in the higher DGLA, AA, and DGLA/AA groups than in their lower counterparts (DGLA and AA; p < 0.01, DGLA/AA; p = 0.04). However, among patients with acute coronary syndrome, none of the PUFA levels were associated with prognosis. Among patients with ADHF, after controlling for confounding variables, DGLA and DGLA/AA were associated with long-term mortality [DGLA: hazard ratio (HR), 0.94; 95% confidence interval (CI), 0.88-0.99; p = 0.01 and DGLA/AA: HR, 0.87; 95% CI, 0.77-0.97; p < 0.01], whereas AA was not associated with prognosis. CONCLUSION: Low omega-6 PUFA levels, particularly DGLA, and a low DGLA/AA ratio predict long-term mortality in patients with acute cardiovascular disease and ADHF. TRIAL REGISTRATION: UMIN-CTR; UMIN000007555 .

A well-differentiated early gastric cancer in a patient confirmed negative for Helicobacter pylori.

A woman in her 70s was an outpatient at our hospital. Esophagogastroduodenoscopy revealed a slightly elevated lesion with erosion, 10mm in diameter, located at the greater curvature of the antrum. Helicobacter pylori testing yielded negative results, and there was no atrophy of the gastric mucosa. Biopsy revealed a well-differentiated tubular adenocarcinoma. Complete en bloc resection was performed via endoscopic submucosal dissection, in accordance with the current Japanese guidelines. The gastric adenocarcinoma of the fundic gland type and coexisting with a hyperplastic or fundic gland polyp was negative according to the histological examination.

Low and exacerbated levels of 1,5-anhydroglucitol are associated with cardiovascular events in patients after first-time elective percutaneous coronary intervention.

BACKGROUND: Postprandial hyperglycemia plays an important role in the pathogenesis of coronary artery disease and cardiovascular events. Serum 1,5-anhydroglucitol (1,5-AG) levels are known to be a clinical marker of postprandial hyperglycemia. However, the impact of 1,5-AG level on cardiovascular events has not been fully investigated. METHODS: We enrolled 240 consecutive patients who had undergone first-time elective percutaneous coronary intervention (PCI) with follow-up angiography within 1 year. We excluded patients with a history of acute coronary syndrome, advanced chronic kidney disease (estimated glomerular filtration rate <30 mL/min/1.73 m2), or uncontrolled diabetes mellitus (HbA1c ≥7.0 %). Fasting blood glucose (FBS), HbA1c, and 1,5-AG levels were measured prior to PCI and at the time of follow-up angiography. Clinical events, including target lesion revascularization, target vessel revascularization, and revascularization of new lesions, were evaluated. RESULTS: Subjects were divided into two groups according to clinical outcomes: the Event (+) group (n = 40) and the Event (-) group (n = 200). No significant differences were observed, except for the number of diseased vessels and the prevalence of statin use, in baseline clinical characteristics between the two groups. Serum levels of 1,5-AG at follow-up were significantly lower in the Event (+) group than in the Event (-) group (P = 0.02). A significant reduction in 1,5-AG level from baseline to follow-up was observed in the Event (+) group compared with the Event (-) group (P = 0.04). The association between 1,5-AG levels at follow-up and clinical events remained significant after adjustment for independent variables, including FBS and HbA1c levels (P = 0.04). CONCLUSIONS: Low and exacerbated levels of 1,5-AG were associated with cardiovascular events in the present study, indicating that postprandial hyperglycemia is an important risk factor for adverse clinical events even in patients with HbA1c < 7.0 %, following first-time elective PCI.

An early gastric cancer concurrent with a hyperplastic polyp in a patient confirmed negative for Helicobacter pylori.

A 58-year-old man was suspected of having a gastric polyp based on an upper gastrointestinal series. Esophagogastroduodenoscopy showed a gastric polyp, approximately 7mm in diameter, located at the greater curvature of the upper gastric body. Helicobacter pylori testing yielded negative results, and there was no atrophy of the gastric mucosa. Biopsy revealed a well differentiated tubular adenocarcinoma (Group 5). Endoscopic submucosal biopsies were performed, and histopathology revealed a well differentiated tubular adenocarcinoma coexisting with a hyperplastic polyp. Complete en bloc resection was performed, in accordance with the current Japanese guidelines.

Elevated Circulating Levels of Inflammatory Markers in Patients with Acute Coronary Syndrome.

Objective. We evaluated inflammatory cytokines and chemokine in peripheral blood mononuclear cells (PBMCs) in patients with either acute coronary syndrome (ACS) or stable coronary artery disease (CAD). Methods. We enrolled 20 ACS patients and 50 stable CAD patients without previous history of ACS who underwent cardiac catheterization. Patients with an estimated glomerular filtration rate of ≤30 mL/min/1.73 m(2) and C-reactive protein of ≥1.0 mg/dL were excluded. Blood samples were collected from the patients just before catheterization, and PBMCs were isolated from the whole blood. The levels of inflammatory cytokines and chemokine were measured by using real-time quantitative polymerase chain reaction and immunoassays. Results. The expression of tumor necrosis factor alpha (TNF-α), interleukin- (IL-) 6, IL-10, IL-23A, IL-27, and IL-37 was significantly higher in the ACS group than in the CAD group (P < 0.05). In contrast, the expression of IL-33 was significantly lower in the ACS group than in the CAD group (P < 0.05). The ACS patients had higher plasma levels of TNF-α, IL-6, and IL-10 in the ACS group than in the CAD group. Conclusion. Circulating levels of pro-/anti-inflammatory cytokines, including IL-23A, IL-27, IL-33, and IL-37, may be associated with the pathogenesis of atherosclerosis in ACS patients.

Changes of Absorptive and Secretory Transporting System of (1 → 3) ß-D-glucan Based on Efflux Transporter in Indomethacin-induced Rat.

Infection and inflammation suppress the expression and activity of several drug transporters in liver. In the intestine, P-glycoprotein (P-gp/MDR1), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP) are important barriers to the absorption of many clinically important drugs. The expression and activity of these proteins were examined under inflammation. Drug transport was determined in jejunum and ileum segments isolated from 1.0 mg/kg, 5.0 mg/kg, and 7.5 mg/kg indomethacin-treated or control rats in diffusion chambers. Transport of laminaran, used as a model compound of (1-3) ß-D-glucan, was measured for 120 min in the presence or absence of inhibitors. Reverse transcription-polymerase chain reaction was used to measure mRNA levels. Compared with controls, levels of Mdr1a mRNA were significantly decreased in the jejunum and ileum of 7.5 mg/kg indomethacin-treated rats. Both reductions in the basolateral to apical efflux of laminaran and increases in the apical to basolateral influx of laminaran were observed, resulting in significant increases in the apical to basolateral absorption of laminaran in 7.5 mg/kg indomethacin-treated rats. The inhibitory effect of verapamil on laminaran transport was observed in control rats but not in indomethacin-treated rats. Fluorescein isothiocyanate dextran 40,000 permeability, membrane resistance, and claudin-4 mRNA level were not altered, indicating no change in the paracellular pathway. These results indicate that indomethacin-induced inflammation reduces the intestinal expression and activity of P-gp in rats, which elicits corresponding changes in the intestinal transport of laminaran. Hence, inflammatory diseases may impose variability in drug bioavailability through alterations in the intestinal expression and activity of drug transporters.