Association Between the Presence of Coronary Artery Disease or Peripheral Artery Disease and Left Ventricular Mass in Patients Who Have Undergone Coronary Computed Tomography Angiography.

Background: Left ventricular mass (LVM) is a critical marker of future cardiovascular risk. We determined the association between LVM measured by coronary computed tomography angiography (CCTA) and the presence of coronary artery disease (CAD) or peripheral artery disease (PAD) in patients who had undergone CCTA for screening of CAD. Methods: We enrolled 1,307 consecutive patients (66 ± 12 years old, 49% males) who underwent CCTA for screening of CAD at the Fukuoka University Hospital (FU-CCTA registry), and either were clinically suspected of having CAD or had at least one cardiovascular risk factor. Patients with coronary stenosis of ≥ 50% by CCTA were diagnosed as CAD. Patients with an ankle brachial pressure index < 0.9 or who had already been diagnosed with PAD were considered to have PAD. Left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF), end-diastolic volume (EDV) and end-systolic volume (ESV) were measured. The patients were divided into CAD (-) and CAD (+) or PAD (-) and PAD (+) groups. Results: The prevalences of CAD and PAD in all patients were 50% and 4.8%, respectively. Age, %males, %hypertension (HTN), %dyslipidemia (DL), %diabetes mellitus (DM), %smoking and %chronic kidney disease in the CAD (+) group were significantly higher than those in the CAD (-) group. Age, %males, %HTN, %DM and %smoking in the PAD (+) group were significantly higher than those in the PAD (-) group. CAD was independently associated with LVMI (odds ratio (OR): 1.01, 95% confidence interval (CI): 1.01 - 1.02, P < 0.01) in addition to age, male, HTN, DL, DM, and smoking. PAD was also independently associated with LVMI (OR: 1.01, 95% CI: 1.0 - 1.02, P = 0.018) in addition to age, DM, and smoking. Conclusions: LVMI determined by CCTA may be useful for predicting atherosclerotic cardiovascular diseases including both CAD and PAD, although there were considerable differences between %CAD and %PAD in all patients.

Comparisons of Nonhyperemic Pressure Ratios: Predicting Functional Results of Coronary Revascularization Using Longitudinal Vessel Interrogation.

OBJECTIVES: The aim of this study was to investigate the accuracy of pre-percutaneous coronary intervention (PCI) predicted nonhyperemic pressure ratios (NHPRs) with actual post-PCI NHPRs and to assess the efficacy of PCI strategy using pre-PCI NHPR pullback. BACKGROUND: Predicting the functional results of PCI is feasible using pre-PCI longitudinal vessel interrogation with the instantaneous wave-free ratio (iFR), a pressure-based, adenosine-free NHPR. However, the reliability of novel NHPRs (resting full-cycle ratio [RFR] and diastolic pressure ratio [dPR]) for this purpose remains uncertain. METHODS: In this prospective, multicenter, randomized controlled trial, vessels were randomly assigned to receive pre-PCI iFR, RFR, or dPR pullback (50 vessels each). The pre-PCI predicted NHPRs were compared with actual NHPRs after contemporary PCI using intravascular imaging. The number and the total length of treated lesions were compared between NHPR pullback-guided and angiography-guided strategies. RESULTS: The predicted NHPRs were strongly correlated with actual NHPRs: iFR, r = 0.83 (95% confidence interval: 0.72 to 0.90; p < 0.001); RFR, r = 0.84 (95% confidence interval: 0.73 to 0.91; p < 0.001), and dPR, r = 0.84 (95% confidence interval: 0.73 to 0.91; p < 0.001). The number and the total length of treated lesions were lower with the NHPR pullback strategy than with the angiography-guided strategy, leading to physiological improvement. CONCLUSIONS: Predicting functional PCI results on the basis of pre-procedural RFR and dPR pullbacks yields similar results to iFR. Compared with an angiography-guided strategy, a pullback-guided PCI strategy with any of the 3 NHPRs reduced the number and the total length of treated lesions. (Study to Examine Correlation Between Predictive Value and Post PCI Value of iFR, RFR and dPR; UMIN000033534).

Postocclusional Hyperemia for Fractional Flow Reserve After Percutaneous Coronary Intervention.

BACKGROUND: Postocclusional hyperemia caused by balloon occlusion is a potential alternative method of inducing hyperemia for measuring post-percutaneous coronary intervention fractional flow reserve (FFR). The aim of this study was to investigate postocclusional hyperemia as a method of inducing hyperemia. METHODS AND RESULTS: FFR measured by postocclusional hyperemia (FFRoccl) caused by balloon occlusion after percutaneous coronary intervention was compared with FFR measured by drug-induced hyperemia (FFR measured by intravenous ATP; and FFR measured by intracoronary papaverine injection [FFRpap]) in 98 lesions from 98 patients. The hyperemia duration was also measured for FFRoccl and FFRpap. The correlation coefficient between FFRoccl, FFR measured by intravenous ATP (r=0.973; P<0.01), and FFRpap (r=0.975; P<0.01) showed almost identical values to those obtained for the correlation coefficient between FFR measured by intravenous ATP and FFRpap (r=0.967; P<0.01). No clear difference was observed on Bland-Altman analysis. Hyperemia duration was significantly longer with FFRoccl than with FFRpap (70±22 versus 51±25 s; P<0.01). CONCLUSIONS: Strong correlations were found between FFRoccl and FFR measured by intravenous ATP and FFRoccl and FFRpap. Hyperemia caused by FFRoccl was significantly longer than that caused by FFRpap.

Normal serum IgE levels and eosinophil counts exhibited during Strongyloides stercoralis infection.

Infections with parasites, such as Strongyloides stercoralis, typically cause elevated levels of serum immunoglobulin E (IgE) and eosinophils; however, co-infection with human T cell lymphotropic virus type 1 (HTLV-1) can cause lower levels of serum IgE during S. stercoralis infection. We conducted this study to determine whether serum IgE levels and eosinophil counts could also be related to other patient characteristics or symptoms. Between 1991 and 2014, we measured and compared the symptoms of 237 patients and evaluated serum IgE levels and eosinophil counts of 199 patients who were infected with S. stercoralis at the Ryukyu University Hospital and the Nishizaki Hospital. Medical records were reviewed and blood samples were taken before treatment with the anthelminthic, ivermectin, 2weeks following the first dosage, and 2weeks following the second dosage. Commonly reported symptoms included abdominal pain, diarrhea, and general fatigue. Serum IgE levels were found to be normal in patients co-infected with HTLV-1. Additionally, females and patients younger than 70years old exhibited normal serum IgE levels when infected with S. stercoralis. No factor included in our analysis was found to affect eosinophil counts. Serum IgE levels can remain within the normal range for some patients infected with S. stercoralis. Therefore, physicians should not eliminate S. stercoralis infection from the differential diagnosis solely according to findings of normal or low IgE levels.

Factors associated with visceral fat accumulation in the general population in Okinawa, Japan.

AIM: To investigate the clinical and biochemical factors associated with visceral fat accumulation in the general population. METHODS: We enrolled 1004 subjects who underwent a medical health checkup between April 2008 and March 2009. The medical health checkup included the following tests: Height, body weight, waist circumference (WC), systolic blood pressure, diastolic blood pressure, urinalysis, blood-cell counts, blood chemistry, electrocardiography, chest radiography, and abdominal computed tomography (CT) for visceral fat accumulation. The patients' medical history and lifestyle factors were collected privately by nurses using a self-administered questionnaire, and they included questions regarding physical activity, sleep duration, dietary habits, smoking, and alcohol consumption. Visceral fat area (VFA) was defined as the sum of the intraperitoneal fat area at the level of the umbilicus with CT density in the range of -150 to -50 Hounsfield units. RESULTS: The mean age and body mass index (BMI) of the study subjects were 57.0 years and 24.4 kg/m(2). In both male and females, VFA was significantly and positively correlated with WC (r = 0.532, P < 0.01; r = 0.612, P < 0.01). Subjects with high levels of VFA were primarily male with significantly higher age, height, body weight, BMI, systolic blood pressure (BP), diastolic BP, and hemoglobin in all subjects (P < 0.05). A multivariate logistic regression analysis revealed that VFA had a positive relationship with age ≥ 56, BMI ≥ 25 kg/m(2), and triglyceride level ≥ 149 in males (P < 0.05), whereas it had a positive relationship with age ≥ 58, BMI ≥ 24.4 kg/m(2), high-density lipoprotein cholesterol level < 40 mg/dL, and current drinking in females (P < 0.05). CONCLUSION: These results suggest that gender differences exist in the clinical and biochemical parameters associated with visceral fat accumulation.

Relationship Among Strongyloides stercoralis Infection, Human T-Cell Lymphotropic Virus Type 1 Infection, and Cancer: A 24-Year Cohort Inpatient Study in Okinawa, Japan.

This study evaluated the prevalence of Strongyloides stercoralis infection and human T-cell lymphotropic virus type 1 (HTLV-1) infection in the population. In addition, this study investigated the relationship between S. stercoralis infection or HTLV-1 infection and a patient's risk of developing related cancers. This is a retrospective cohort study of 5,209 patients. The prevalence of S. stercoralis infection was 5.2% among all patients. The prevalence among men (6.3%) was significantly higher than among women (3.6%, P < 0.001). The prevalence of HTLV-1 infection among this population was 13.6% and the prevalence among women (15.5%) was significantly higher than that of men (12.3%, P < 0.001). HTLV-1 seroprevalence was higher in patients with liver cancer (P = 0.003, odds ratio [OR]: 1.91, 95% confidence interval [CI]: 1.24, 2.95) and in those with lymphoma other than adult T-cell leukemia/lymphoma (ATLL) (P = 0.005, adjusted OR: 2.76, 95% CI: 1.36, 5.62) if compared with patients without any neoplasm. The prevalence of both S. stercoralis and HTLV-1 in the Okinawan population has been steadily decreasing over the past 24 years. HTLV-1 infection significantly increases the odds of developing liver cancer and lymphomas other than ATLL.

Evaluation of a multiplex PCR assay for detection of cytomegalovirus in stool samples from patients with ulcerative colitis.

AIM: To evaluate a multiplex PCR assay for the detection of bacterial and viral enteropathogens in stool samples from patients with ulcerative colitis (UC). METHODS: We prospectively analyzed 300 individuals, including immunocompetent patients, immunocompromised patients, and patients with UC. Stool samples were collected from the recto-sigmoid region of the colon by endoscopy. The samples were qualitatively analyzed for bacterial and viral enteropathogens with a multiplex PCR assay using a Seeplex(®) Kit. Additional clinical and laboratory data were collected from the medical records. RESULTS: A multiplex PCR assay detected 397 pathogens (191 bacteria and 206 viruses) in 215 samples (71.7%). The most frequently detected bacteria were Escherichia coli H7, 85 (28.3%); followed by Aeromonas spp., 43 (14.3%); and Clostridium perfringens, 36 (12.0%) samples. The most prevalent viruses were Epstein-Barr virus (EBV), 90 (30.0%); followed by human herpes virus-6 (HHV-6), 53 (17.7%); and cytomegalovirus (CMV), 37 (12.3%) samples. The prevalence rate of CMV infection was significantly higher in the immunocompromised group than in the immunocompetent group (P < 0.01). CMV infection was more common in patients with UC (26/71; 36.6%) than in the immunocompetent patients excluding UC (6/188; 3.2%) (P < 0.01). CMV infection was more prevalent in UC active patients (25/58; 43.1%) than in UC inactive patients (1/13; 7.7%) (P < 0.05). Among 4 groups which defined by the UC activity and immunosuppressive drugs, the prevalence rate of CMV infection was highest in the UC active patients with immunosuppressive drugs (19/34; 55.8%). Epstein-Barr virus (EBV) infection was more common in the immunocompromised patients excluding UC (18/41; 43.9%) than in the immunocompetent patients excluding UC (47/188; 25.0%) (P < 0.05). The simultaneous presence of CMV and EBV and/or HHV6 in UC active patients (14/58; 24.1%) was greater than in immunocompromised patients excluding UC (5/41; 12.2%) (P < 0.05). CONCLUSION: The multiplex PCR assay that was used to analyze the stool samples in this study may serve as a non-invasive approach that can be used to exclude the possibility of CMV infection in patients with active UC who are treated with immunosuppressive therapy.

Peritoneal Malignant Mesothelioma with Epithelioid Type, Demonstrating High Serum and Ascitic KL-6 Levels: Immunohistochemical Analyses.

We report a case of KL-6 producing peritoneal malignant mesothelioma. A 56-year-old woman was referred to our hospital on November 2005 with severe abdominal distention. Peritoneal malignant mesothelioma with epithelioid type was diagnosed by clinical symptoms, laboratory investigations, imaging studies, and immunohistochemical examination of known tumor markers. In addition, high serum and ascitic KL-6 levels were observed and the immunostaining of the tumor for KL-6 was evident. We thus consider KL-6 to be a potential novel marker for peritoneal malignant mesothelioma with epithelioid type.

Acute respiratory distress syndrome due to Strongyloides stercoralis infection in a patient with cervical cancer.

A 62-year-old woman complained of diarrhea and vomiting after receiving chemotherapy for cervical cancer in association with high doses of corticosteroids. Two months later, the patient developed acute respiratory distress syndrome, and numerous Strongyloides stercoralis parasites were found in the intrabronchial discharge. Ivermectin was administered daily until nematodes were no longer detected in the sputum, and the patient's condition was successfully rescued. Antibodies for human T-cell lymphotropic virus-1 (HTLV-1) were positive. HTLV-1 infection and the administration of corticosteroids are known risk factors for strongyloides hyperinfection syndrome. Therefore, physicians should consider this disease in the differential diagnosis of patients from endemic areas who present with gastrointestinal symptoms under these risk factors.

Fucoidan enhances intestinal barrier function by upregulating the expression of claudin-1.

AIM: To evaluate the protective effects of fucoidan on oxidative stress-induced barrier disruption in human intestinal epithelial cells. METHODS: In Caco-2 cell monolayer models, the disruption of barrier function by oxidative stress is mediated by H2O2. The integrity of polarized Caco-2 cell monolayers was determined by measuring the transepithelial resistance (TER) and permeability was estimated by measuring the paracellular transport of FITC-labeled 4-kDa dextran (FD4). The protective effects of fucoidan on epithelial barrier functions on polarized Caco-2 cell monolayers were evaluated by TER and FD4 flux. The expression of tight junction (TJ) proteins was assessed using reverse-transcription polymerase chain reaction (RT-PCR) and immunofluorescence staining. RESULTS: Without H2O2 treatment, fucoidan significantly increased the TER compared to control (P < 0.05), indicating a direct enhancement of intestinal epithelial barrier function. Next, H2O2 disrupted the epithelial barrier function in a time-dependent manner. Fucoidan prevented the H2O2-induced destruction in a dose-dependent manner. Fucoidan significantly decreased H2O2-induced FD4 flux (P < 0.01), indicating the prevention of disruption in paracellular permeability. RT-PCR showed that Caco-2 cells endogenously expressed claudin-1 and -2, and occludin and that H2O2 reduced the mRNA expression of these TJ proteins. Treatment with fucoidan attenuated the reduction in the expressions of claudin-1 and claudin-2 but not occludin. Immunofluorescence staining revealed that the expression of claudin-1 was intact and high on the cell surface. H2O2 disrupted the integrity of claudin-1. Treatment with fucoidan dramatically attenuated the expression of claudin-1. CONCLUSION: Fucoidan enhanced intestinal epithelial barrier function by upregulating the expression of claudin-1. Thus, fucoidan may be an appropriate therapy for the treatment of inflammatory bowel diseases.

Diagnosis of intestinal tuberculosis using a monoclonal antibody to Mycobacterium tuberculosis.

AIM: To investigate the utility of immunohistochemical (IHC) staining with an antibody to Mycobacterium tuberculosis (M. tuberculosis) for the diagnosis of intestinal tuberculosis (TB). METHODS: We retrospectively identified 10 patients (4 males and 6 females; mean age = 65.1 ± 13.6 years) with intestinal TB. Clinical characteristics, including age, gender, underlying disease, and symptoms were obtained. Chest radiograph and laboratory tests, including sputum Ziehl-Neelsen (ZN) staining, M. tuberculosis culture, and sputum polymerase chain reaction (PCR) for tubercle bacilli DNA, as well as Tuberculin skin test (TST) and QuantiFERON-TB gold test (QFT), were examined. Colonoscopic records recorded on the basis of Sato's classification were also reviewed, in addition to data from intestinal biopsies examined for histopathological findings, including hematoxylin and eosin staining, and ZN staining, as well as M. tuberculosis culture, and PCR for tubercle bacilli DNA. For the present study, archived formalin-fixed paraffin-embedded (FFPE) intestinal tissue samples were immunohistochemically stained using a commercially available species-specific monoclonal antibody to the 38-kDa antigen of the M. tuberculosis complex. These sections were also stained with the pan-macrophage marker CD68 antibody. RESULTS: From the clinical data, we found that no patients were immunocompromised, and that the main symptoms were diarrhea and weight loss. Three patients displayed active pulmonary TB, six patients (60%) had a positive TST, and 4 patients (40%) had a positive QFT. Colonoscopic findings revealed that all patients had type 1 findings (linear ulcers in a circumferential arrangement or linear ulcers arranged circumferentially with mucosa showing multiple nodules), all of which were located in the right hemicolon and/or terminal ileum. Seven patients (70%) had concomitant healed lesions in the ileocecal area. No acid-fast bacilli were detected with ZN staining of the intestinal tissue samples, and both M. tuberculosis culture and PCR for tubercle bacilli DNA were negative in all samples. The histopathological data revealed that tuberculous granulomas were present in 4 cases (40%). IHC staining in archived FFPE samples with anti-M. tuberculosis monoclonal antibody revealed positive findings in 4 patients (40%); the same patients in which granulomas were detected by hematoxylin and eosin staining. M. tuberculosis antigens were found to be mostly intracellular, granular in pattern, and primarily located in the CD68(+) macrophages of the granulomas. CONCLUSION: IHC staining with a monoclonal antibody to M. tuberculosis may be an efficient and simple diagnostic tool in addition to classic examination methods for the diagnosis of intestinal TB.

Endoscopic and histopathological features of gastrointestinal amyloidosis.

Amyloidosis is a rare disorder, characterized by the extracellular deposition of an abnormal fibrillar protein, which disrupts tissue structure and function. Amyloidosis can be acquired or hereditary, and systemic or localized to a single organ, such as the gastrointestinal (GI) tract. Clinical manifestations may vary from asymptomatic to fatal forms. Primary amyloidosis (monoclonal immunoglobulin light chains, AL) is the most common form of amyloidosis. AL amyloidosis has been associated with plasma cell dyscrasias, such as, multiple myeloma. Secondary amyloidosis is caused by the deposition of fragments of the circulating acute-phase reactant, serum amyloid A protein (SAA). Common causes of AA amyloidosis are chronic inflammatory disorders. Although GI symptoms are usually nonspecific, histopathological patterns of amyloid deposition are associated with clinical and endoscopic features. Amyloid deposition in the muscularis mucosae, submucosa, and muscularis propria has been dominant in AL amyloidosis, leading to polypoid protrusions and thickening of the valvulae conniventes, whereas granular amyloid deposition mainly in the propria mucosae has been related to AA amyloidosis, resulting in the fine granular appearance, mucosal friability, and erosions. As a result, AL amyloidosis usually presents with constipation, mechanical obstruction, or chronic intestinal pseudo-obstruction while AA amyloidosis presents with diarrhea and malabsorption Amyloidotic GI symptoms are mostly refractory and have a negative impact on quality of life and survival. Diagnosing GI amyloidosis requires high suspicion of evaluating endoscopists. Because of the absence of specific treatments for reducing the abundance of the amyloidogenic precursor protein, we should be aware of certain associations between patterns of amyloid deposition and clinical and endoscopic features.

[A case of 5-fluorouracil-induced hyperammmonia after chemotherapy for metastatic colon cancer].

A 79-year-old woman with colon cancer and multiple liver metastases was admitted to our hospital for systemic chemotherapy. She underwent first cycle of modified FOLFOX6 chemotherapy. She was confused on treatment day 5. Blood test revealed her serum ammonia level to be 121 microg/dl. We diagnosed 5-fluorouracil (5FU)-induced hyperammonemia. Conservative treatment resulted in improvement of metal status. The reason for hyperammonemia after administration of 5FU was the excess production of ammonium from metabolites of 5FU.