The metabolic parameters based on volume in PET/CT are associated with clinicopathological N stage of colorectal cancer and can predict prognosis.

BACKGROUND: A combination of positron emission tomography and computed tomography (PET/CT) is an important modality for the diagnosis of carcinoma. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have been reported as metabolic parameters in PET/CT since the late 1990s, and they are expected to be useful in diagnosing diverse cancers and as prognostic biomarkers. We evaluated the potential of these parameters in the prognosis of colorectal cancer (CRC) by comparing them with conventional parameters, including the maximum standardized uptake value (SUVmax). We enrolled 84 patients who underwent surgery for CRC without distal metastasis between April 2015 and April 2019. SUVmax, MTV, and TLG were measured by 18F-fluorodeoxyglucose (FDG)-PET/CT. To find an optimal threshold value related to prognosis, the volume of interest in the primary carcinoma was measured at fixed relative and absolute thresholds based on SUVmax (30%, 40%, and 50%; 2.5, 3.0, and 3.5, respectively), tumor-to-liver standardized uptake ratios, TLR (1.0, 1.5, and 2.0), and SUV normalized to lean body mass, SUL (2.0, 2.5, and 3.0). After classifying the patients into two groups according to pathological N stage, the optimal threshold values of all metabolic parameters were compared between groups using a non-parametric comparison test. RESULT: The most suitable thresholds for MTV were a SUVmax of 3.5 and a TLR 2.0. TLG with a SUVmax value of 40% showed the most significant difference. The MTV standard uptake ratio of 2.0 was significantly associated with pathological N stage. CONCLUSION: Our results suggest that an MTV TLR 2.0 on PET/CT reflects pathological N stage in local patients with CRC.

Attempt to delineate occluded arteries with initial plain computed tomography in acute cerebral arterial occlusion.

BACKGROUND: We used initial plain computed tomography to delineate acutely occluded internal carotid arteries or horizontal segments of middle cerebral arteries. If affected arteries could be delineated using initial plain computed tomography, useful information might be obtained that could support endovascular thrombectomies. METHODS: In 15 patients with occluded internal carotid arteries or horizontal segments of middle cerebral arteries, the affected middle cerebral artery was automatically traced using the extender function for blood vessel tracing with reference to the default value (window setting, 40; window width, 90) on Ziostation 2 (Ziosoft Inc., Tokyo, Japan) based on initial plain computed tomography data. RESULTS: The horizontal and sylvian segments of the middle cerebral artery were delineated in 15 and nine patients, respectively, based on plain computed tomography volume data. Images of occluded vessels delineated by plain computed tomography closely correlated with digital subtraction angiography. CONCLUSIONS: Initial plain computed tomography combined with a new generation workstation enabled the rapid delineation of occluded segments of intracranial vessels and could provide useful information that might improve the safety of endovascular thrombectomy.

An examination of co-infection in acute gastroenteritis and histo-blood group antigens leading to viral infection susceptibility.

The aim of the present study was to evaluate co-infection in the gastrointestinal tract in terms of viruses, bacteria and the ABO blood group. We hypothesized that a combination of norovirus (NV) and bacteria in the gastrointestinal tract could affect the likelihood of an individual to contracting NV. Histo-blood group antigens (HBGAs) are considered to act as receptors that can lead to NV susceptibility. In addition to genetics, co-infection in the gastrointestinal tract may be associated with this mechanism. A total of 370 patients with acute gastroenteritis presenting with diarrhea (14-89 years) were recruited. The male/female ratio was 20/17. Single infection (bacteria or virus), co-infection with two viruses, and co-infection with one virus and one bacterium were statistically analyzed. In total, 88 of the 376 subjects (23.4%) were positive for one virus, and 50 (13.3%) were positive for one bacterium. Co-transfection with bacteria and a virus were detected in 46 (47.9%) of the 96 bacterial gastroenteritis cases. Statistical analysis revealed that co-infection of bacteria and NV was not significant in all viral infections (P=0.768). In terms of the ABO histo-blood group type and NV infection, the frequency in the O type was not significantly increased (P=0.052). Co-infection of bacteria and a virus occurred frequently in the gastrointestinal tract. The ABO blood phenotype expression was not a significant factor in NV infection in the present case series and the results did not suggest an affinity of NV for specific bacteria.

Hyperglycemia and Inflammatory Property of Circulating Monocytes are Associated with Inflammatory Property of Carotid Plaques in Patients Undergoing Carotid Endarterectomy.

AIM: This study aims to determine the association between glucose metabolism and proinflammatory/anti-inflammatory properties of circulating monocytes or those of carotid plaques in patients who underwent carotid endarterectomy. METHODS: Clinical characteristics and expression levels of proinflammatory/anti-inflammatory markers in circulating monocytes/carotid plaques were examined in 12 patients with diabetes and 12 patients without diabetes. RESULTS: Circulating monocytes from patients with diabetes revealed higher tumor necrosis factor (TNF)-α and lower interleukin (IL)-10 expression levels compared with those from patients without diabetes, which was also observed in carotid plaques from patients with diabetes. Hyperglycemia revealed positive and negative correlations with the ratios of IL-6＋ and IL-10＋ cells in carotid plaques, respectively. Moreover, we determined a positive correlation between circulating monocytes and carotid plaques with respect to TNF-α and IL-6 expressions. CONCLUSIONS: The inflammatory property of circulating monocytes was associated with that of carotid plaques. Hyperglycemia increased inflammatory properties and decreased anti-inflammatory properties of carotid plaques.

A scabies outbreak in a diabetic and collagen disease ward: Management and prevention.

Scabies is an infection caused by Sarcoptes scabiei. In developed countries, scabies remains an important public health problem in hospitals and care facilities among elderly or immunocompromised patients. There are a number of medical providers who have not experienced scabies and there has been confusion surrounding its management and prevention. Therefore, the aim of the present study was to identify the optimal approach for the management and prevention of scabies. A scabies outbreak occurred between June 2014 and October 2014 in the Toho University School of Medicine, Omori Hospital (Tokyo, Japan), and the current study investigates factors concerning the outbreak, such as disease recognition, diagnostic strategy, medical staff experience and correspondence after the outbreak occurred. Six patients were newly diagnosed with scabies including patients, medical staff and family of the medical staff. An infection control committee was implemented and required a follow-up survey of 181 people (144 patients and 37 medical staff). It took ~4 months to resolve the outbreak. Scabies is highly infectious, and sufficient knowledge is required to care for the patients and prevent the infection of healthy people. In this example, the spread of infection was controlled by prompt action.

Thrombospondin 1 as a novel biological marker of obesity and metabolic syndrome.

CONTEXT: Thrombospondin 1 (THBS1 or TSP-1) is an adipose-derived matricellular protein, which has recently been highlighted as a potential mediator of insulin resistance and adipose inflammation in obesity. OBJECTIVE: In this study, we aimed to determine the clinical significance of THBS1 as a novel biological marker of visceral obesity, metabolic syndrome, and diabetes. METHODS: The THBS1 mRNA level was quantified with real-time PCR in human adipose tissues obtained from 16 non-obese subjects. The relationships between serum THBS1 level and obesity/diabetes traits as well as the diagnostic components of metabolic syndrome were assessed in 164 normal-weight or overweight/obese subjects (78 males and 86 females; mean age, 50.4; mean BMI, 29.8) with analysis of covariance (ANCOVA) and regression analyses. RESULTS: THBS1 was predominantly expressed in visceral adipose tissues relative to subcutaneous adipose tissues (P<0.001). The visceral THBS1 expression was positively associated with the body mass index (BMI; γs=0.54, P=0.033). ANCOVA demonstrated that the THBS1 level is associated with abdominal obesity (P<0.001), hyperglycemia (P=0.02), and hypertension (P=0.04). Multivariable regression analysis suggested an association between serum THBS1 and fasting plasma glucose levels. The associations between serum THBS1 levels and obesity/diabetes traits were found preferentially in women (BMI, γs=0.30, P=0.05; FPG, γs=0.26, P=0.016). Subanalyses demonstrated that the association with obesity traits was predominantly found in premenopausal women (BMI, γs=0.41, P=0.007), whereas the association with diabetes traits was predominant in postmenopausal women (HbA1c, γs=0.38, P=0.01). During medical weight reduction treatment, the change in the serum THBS1 level was associated with the change in BMI and HbA1c in pre- and postmenopausal women, respectively. CONCLUSIONS: Serum THBS1 is a useful biological marker of obesity and metabolic syndrome in Japanese subjects, particularly in women. THBS1 may act as a critical circulating factor that couples obesity with metabolic syndrome and diabetes in humans.

[Assessing the influence of reconstruction kernel in plaque imaging in computed tomography].

Plaque imaging using computed tomography (CT) is an important diagnostic method for predicting the risk of vascular events. However, the CT value variability of plaques, which depends on the scan parameters, remains a key challenge. The aim of this study was to evaluate the effect of reconstruction properties on the CT value, area, and shape reproducibility of plaques. In general, the types of reconstruction kernels in a CT system are limited, thus impeding the acquisition of the necessary resolution properties (modulation transfer functions: MTFs). We therefore obtained images with eight types (smoothed to edge-enhanced) of resolution property by applying frequency processing to the original CT images. We made phantoms of simulated 6-mm-diameter vessels with plaque and scanned them at different doses. The CT values, areas, and shape reproducibility of plaques were measured from each processed image. Enhanced-type resolution with no edge enhancement (not exceeding 1.0) effectively raised the CT value and shape reproducibility accuracies. However, edge-enhancement type resolution caused errors in the CT value, area and shape reproducibility.

An increase in the EPA/AA ratio is associated with improved arterial stiffness in obese patients with dyslipidemia.

AIM: Previous epidemiological studies demonstrated that the ratio of n-6 to n-3 polyunsaturated fatty acids is associated with cardiovascular diseases. We herein investigated whether the beneficial effect of highly purified eicosapentaenoic acid(EPA) on arterial stiffness is associated with changes in the ratio of polyunsaturated fatty acids, such as EPA, docosahexaenoic acid(DHA) and dihomo-γ-linolenic acid(DGLA), relative to arachidonic acid(AA), in obese Japanese patients with dyslipidemia. METHODS: The EPA/AA, DHA/AA and DGLA/AA ratios were compared between obese patients with(n=94) and without (n=31) dyslipidemia. Among the former group, 88 patients received either highly purified EPA treatment(1.8g daily, n=45) or treatment without EPA(control, n=43). RESULTS: At baseline, the ratios of DHA/AA and DGLA/AA were significantly(P＜0.05) higher in obese patients with dyslipidemia than in those without, while the EPA/AA ratio was similar between patients with and without dyslipidemia. EPA significantly reduced the hemoglobin A1c, total cholesterol, triglycerides, CRP, cardio-ankle vascular index(CAVI)(an index of arterial stiffness) and the DGLA/AA ratio relative to the control at three months after the treatment. On the other hand, EPA significantly increased the adiponectin level and EPA/AA ratio(P＜0.05). A multivariate regression analysis revealed that only age, an increase in the EPA/AA ratio and a decrease in the CRP level were significant determinants of a reduction of the CAVI by EPA. CONCLUSION: These findings suggest that EPA improves the arterial stiffness in association with an increase in the EPA/AA ratio and a decrease in inflammation in obese patients with dyslipidemia.

Effects of weight reduction therapy on obstructive sleep apnea syndrome and arterial stiffness in patients with obesity and metabolic syndrome.

AIM: Obesity and metabolic syndrome (MetS) and obstructive sleep apnea (OSA), which are often accompanied by obesity, are each independently associated with cardiovascular disease (CVD). However, the influence of OSA on arterial stiffness in obese patients remains unclear. We herein examined the relationships between the severity of OSA and CVD risk factors, including the severity of MetS and arterial stiffness, in obese patients. In addition, we evaluated the effects of weight reduction therapy on OSA and arterial stiffness. METHODS: Among the 60 overweight or obese Japanese outpatients enrolled, 46 (76.7%) met the MetS criteria. RESULTS: The apnea-hypopnea index (AHI) and cardio-ankle vascular index (CAVI), a new index of arterial stiffness, were significantly higher in the MetS patients than in the non-MetS patients, whereas there were no significant differences in body mass index, blood pressure or the low-density lipoprotein cholesterol level. A multivariate regression analysis revealed that waist circumference, the C-reactive protein level and CAVI were independently correlated with AHI. In addition, age, SBP, IRI and AHI were independently correlated with CAVI. Furthermore, weight reduction therapy, including diet and exercise, over a three-month period significantly decreased the AHI and CAVI values in parallel with a reduction in BMI. CONCLUSIONS: This study demonstrated that the severity of OSA is significantly correlated with the severity of MetS and arterial stiffness in obese patients. Short-term weight reduction therapy improves not only metabolic dysfunction, but also the severity of OSA and arterial stiffness, as measured according to the CAVI. Such changes may help to prevent atherosclerosis in obese patients.

Effects of natural S-equol supplements on overweight or obesity and metabolic syndrome in the Japanese, based on sex and equol status.

OBJECTIVES: Epidemiologic studies indicate that soy intake has an important role in the prevention of age-related health problems. Daidzein, the principal isoflavone contained in soy, is converted to S-equol by the intestinal bacteria. Not all individuals, however, can produce S-equol, which is considered the most biologically active metabolite. We studied the effects of a natural S-equol supplement on metabolic parameters associated with overweight or obesity and metabolic syndrome. METHODS: The study was a randomized, double-blinded, placebo-controlled, crossover design with no washout period. All subjects were considered overweight or obese if they had a body mass index ≥ 25 kg/m(2) . Placebo or natural S-equol tablets containing 10 mg S-equol were orally ingested each day for 12 weeks. A total of 54 Japanese overweight or obese outpatients were enrolled. The equol phenotype was determined, and various metabolic parameters, including cardio-ankle vascular index (CAVI), were measured. RESULTS: Equol non-producers comprised 67.9% of the overweight or obese subjects. The ratio of equol non-producers in this overweight or obese subject group was higher than the previously reported ratio of equol non-producers (approximately 50%) in the general population. Compared with the placebo group, intervention with natural S-equol led to a significant decrease in HbA1c, serum low-density lipoprotein cholesterol (LDL-C) levels and CAVI score. Furthermore, the effect was more prominent in the subgroup of female equol non-producers. CONCLUSION: The ratio of equol non-producers in overweight or obese populations might be higher than generally reported. Natural S-equol might have a role in glycaemic control and in the prevention of cardiovascular disease by its effects to lower LDL-C levels and CAVI scores in overweight or obese individuals.

A dipeptidyl peptidase-4 inhibitor, sitagliptin, exerts anti-inflammatory effects in type 2 diabetic patients.

AIMS/HYPOTHESIS: Glucagon-like peptide-1 (GLP-1) exerts beneficial effects on the cardiovascular system. Here, we examined the effect of sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, on systemic inflammation and pro-inflammatory (M1)/anti-inflammatory (M2)-like phenotypes of peripheral blood monocytes in diabetic patients. METHODS: Forty-eight type 2 diabetic patients were divided into the following two groups: sitagliptin-treatment (50mg daily for 3months) (n=24) and untreated control (n=24) groups. Measurements were undertaken to assess changes in glucose-lipid metabolism, serum levels of inflammatory cytokines such as serum amyloid A-LDL (SAA-LDL), C-reactive protein (CRP), interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α). Furthermore, the effects of sitagliptin treatment on M1/M2-like phenotypes in peripheral blood monocytes were examined. RESULTS: Treatment with sitagliptin significantly decreased fasting plasma glucose, hemoglobin A1c (HbA1c), serum levels of inflammatory markers, such as SAA-LDL, CRP, and TNF-α. In contrast, sitagliptin increased serum IL-10, an anti-inflammatory cytokine, as well as plasma GLP-1. In addition, sitagliptin increased monocyte IL-10 expression and decreased monocyte TNF-α expression. Multivariate regression analysis revealed that the sitagliptin treatment was the only factor independently associated with an increase in monocyte IL-10 (ß=0.499; R(2)=0.293, P<0.05). However, other factors including the improvement of glucose metabolism were not associated with the increase. CONCLUSIONS/INTERPRETATION: This study is the first to show that a DPP-4 inhibitor, sitagliptin, reduces inflammatory cytokines and improves the unfavorable M1/M2-like phenotypes of peripheral blood monocytes in Japanese type 2 diabetic patients.

Highly purified eicosapentaenoic acid increases interleukin-10 levels of peripheral blood monocytes in obese patients with dyslipidemia.

OBJECTIVE: It has recently been highlighted that proinflammatory (M1) macrophages predominate over anti-inflammatory (M2) macrophages in obesity, thereby contributing to obesity-induced adipose inflammation and insulin resistance. A recent clinical trial revealed that highly purified eicosapentaenoic acid (EPA) reduces the incidence of major coronary events. In this study, we examined the effect of EPA on M1/M2-like phenotypes of peripheral blood monocytes in obese dyslipidemic patients. RESEARCH DESIGN AND METHODS: Peripheral blood monocytes were prepared from 26 obese patients without and 90 obese patients with dyslipidemia. Of the latter 90 obese patients with dyslipidemia, 82 patients were treated with or without EPA treatment (1.8 g daily) for 3 months. RESULTS: Monocytes in obese patients with dyslipidemia showed a significantly lower expression of interleukin-10 (IL-10), an M2 marker, than those without dyslipidemia. EPA significantly increased serum IL-10 and EPA levels, the EPA/arachidonic acid (AA) ratio, and monocyte IL-10 expression and decreased the pulse wave velocity (PWV), an index of arterial stiffness, compared with the control group. After EPA treatment, the serum EPA/AA ratio was significantly correlated with monocyte IL-10 expression. Only increases in monocyte IL-10 expression and serum adiponectin were independent determinants of a decreased PWV by EPA. Furthermore, EPA significantly increased the expression and secretion of IL-10 in human monocytic THP-1 cells through a peroxisome proliferator-activated receptor (PPAR)γ-dependent pathway. CONCLUSIONS: This study is the first to show that EPA increases the monocyte IL-10 expression in parallel with decrease of arterial stiffness, which may contribute to the antiatherogenic effect of EPA in obese dyslipidemic patients.

Unfavorable blood rheology is closely associated with arterial stiffness in obese patients.

Little information on the relationship between blood rheology and atherosclerosis indicators in obese patients is available. We examined blood rheology as assessed by the blood passage time (BPT) with the microchannel method in 109 obese patients. BPT was correlated well with the extent of each metabolic syndrome component. A multivariate regression analysis revealed that the independent contributors to BPT were pulse-wave velocity, an index of arterial stiffness, body mass index and red blood cell. Furthermore, weight reduction intervention significantly decreased BPT. Assessment of rheology may be associated with pulse-wave velocity, and useful to manage obese patients.