Decreased peripheral perfusion measured by perfusion index is a novel indicator for cardiovascular death in patients with type 2 diabetes and established cardiovascular disease.

Cardiovascular disease (CVD) is still the major cause of mortality in patients with type 2 diabetes. Despite of recent therapies, mortality and resources spent on healthcare due to CVD is still important problem. Thus, appropriate markers are needed to predict poor outcomes. Therefore, we investigated the role of peripheral perfusion as an indicator for cardiovascular death in patients with type 2 diabetes and established CVD. This retrospective cohort study included 1080 patients with type 2 diabetes and history of CVD recruited from the outpatient clinic at Matsushita Memorial Hospital in Osaka, Japan. Peripheral perfusion is assessed using the perfusion index (PI), which represents the level of circulation through peripheral tissues. The median age and PI values were 74 years (range: 67-79 years) and 2.6% (range: 1.1-4.3%), respectively. During follow-up duration, 60 patients died due to CVD. The adjusted Cox regression analysis demonstrated that the risk of developing cardiovascular death was higher in the first quartile (Hazard ratio, 6.23; 95% CI, 2.28 to 22.12) or second quartile (Hazard ratio, 3.04; 95% CI, 1.46 to 6.85) of PI than that in the highest quartile (fourth quartile) of PI. PI (per 1% decrease) was associated with the development of cardiovascular death (Hazard ratio, 1.39; 95% CI, 1.16 to 1.68). PI could be a novel indicator of cardiovascular death in patients with type 2 diabetes and established CVD.

Peripheral perfusion, measured by perfusion index, is a novel indicator for renal events in patients with type 2 diabetes mellitus.

Diabetic kidney disease (DKD) is one of the leading causes of end stage renal disease. Despite recent therapies, mortality due to DKD and resources spent on healthcare are important problems. Thus, appropriate markers are needed to predict renal outcomes. Therefore, we investigated the role of peripheral perfusion as an indicator for renal events in patients with type 2 diabetes mellitus. This retrospective cohort study included 566 patients who were admitted to Matsushita Memorial Hospital in Osaka, Japan for type 2 diabetes mellitus. Peripheral perfusion was assessed using perfusion index (PI), which represents the level of circulation through peripheral tissues and was measured on each toe using a Masimo SET Radical-7 (Masimo Corporation, Irvine, CA, USA) instrument. The duration of follow up was 3.0 years. The median age of patients was 70 years (IQR range: 61-77 years) and median PI value was 2.9% (IQR range: 1.8-4.8%). Multiple logistic regression analyses showed that PI (per 1% increase) was associated with an odds ratio of composite of end-stage renal disease (ESRD) and/or doubling of serum creatinine level; n = 40 (odds ratio 0.823 [95% CI: 0.680-0.970]), and composite of ESRD, doubling of serum creatinine level, and renal death and/or cardiovascular death; n = 44 (odds ratio 0.803 [95% CI: 0.665-0.944]). The factors which were statistically significant in univariate analysis and those known to be related factors for renal event were considered simultaneously as independent variables for multiple logistic regression analysis. PI can be a novel indicator for renal events in patients with type 2 diabetes mellitus.

Decreased microcirculatory function measured by perfusion index is predictive of cardiovascular death.

BACKGROUND: The importance of microcirculation for adverse outcomes in the early phase of critical illnesses has been reported. Microcirculatory function is assessed using the perfusion index (PI), which represents the level of circulation through peripheral tissues. We investigated the correlation between PI and cardiovascular death to explore whether it can serve as a predictor of cardiovascular death. METHODS AND RESULTS: This retrospective study included 2171 patients admitted to Matsushita Memorial Hospital in Osaka, Japan, for medical treatment. We measured PI for all patients. To examine the effects of PI on cardiovascular death, a Cox proportional hazard model was used. The median age and PI values were 72 years (range 63-79 years) and 2.7% (range 1.4-4.6%), respectively. During the 3927.7 person-years follow-up period, a total of 54 patients died due to cardiovascular disease. PI was positively correlated with BMI (P < 0.0001) and total cholesterol levels (P = 0.004). PI was negatively correlated with age (P < 0.0001), heart rate (P < 0.0001), and creatinine levels (P < 0.0001). Adjusted Cox regression analyses demonstrated that PI was associated with an increased hazard of cardiovascular death (hazard ratio 0.84; 95% CI; range 0.72-0.99). In addition, compared with patients with a high PI (> 3.7%), those with a low PI (≤ 2.0%) had a significantly increased risk of cardiovascular death. This low PI group had a hazard ratio of 3.49 (95% CI 1.73-7.82). CONCLUSIONS: The PI is a valuable predictor for cardiovascular death in a clinical setting.

Decreased microcirculatory function measured by perfusion index is a novel indicator of diabetic kidney disease in patients with type 2 diabetes.

AIMS/INTRODUCTION: Diabetic kidney disease has been considered as an important risk factor of cardiovascular disease. Chronic hypoxia is considered to be the main cause of renal injury. Diminished microcirculatory blood flow could be associated with hypoxia in the kidney. Whether diminished microcirculation is associated with diabetic kidney disease has not yet been reported. Here, we investigated the correlation between microcirculatory function and diabetic kidney disease in patients with type 2 diabetes. MATERIALS AND METHODS: Our cross-sectional study included 574 patients who were admitted to Matsushita Memorial Hospital in Moriguchi, Japan, for type 2 diabetes. Microcirculatory function was assessed using the perfusion index (PI), which represents the level of circulation through peripheral tissues. We measured the PI for all patients. RESULTS: The median age and PI values were 70 years (range 60-77 years) and 2.8% (range 1.6-4.8%). Multiple regression analyses showed that the PI independently correlated with the logarithm of urinary albumin excretion (P = 0.009) and estimated glomerular filtration rate (P = 0.005), respectively. Multiple logistic regression analyses showed that patients with systolic blood pressure (SBP) greater than the median and PI less than or equal to the median (high-low group) had a significantly increased odds of albuminuria compared with those with SBP less than or equal to the median and PI greater than the median (low-high group), and patients with SBP greater than the median and PI less than or equal to the median (high-low group) had a significantly increased odds of estimated glomerular filtration rate <60 mL/min per 1.73 m2 compared with those with SBP less than or equal to the median and PI greater than the median (low-high group) or SBP greater than the median and PI greater than the median (high-high group). CONCLUSIONS: PI could be a novel indicator of diabetic kidney disease in patients with type 2 diabetes.

The perfusion index is a useful screening tool for peripheral artery disease.

The number of people with peripheral artery disease (PAD) has been increasing globally; therefore, it is important to explore more options to screen patients who are at a risk of developing PAD. The perfusion index (PI) represents the degree of circulation through the peripheral tissues and is measured noninvasively. We investigated the correlation between the PI and ankle-brachial index (ABI) to explore whether the PI could be used a screening tool for PAD. This cross-sectional study included 390 patients. We measured the ABI and PI for all patients. The median ABI value was 1.06 (0.92-1.13); the PI was 1.7% (0.9-3.5). The PI was higher in men than in women (P < 0.0001). The PI was positively correlated with the estimated glomerular filtration rate and ABI in both men and women. The sensitivity and specificity of the PI to predict PAD (ABI ≤0.9) were 90.0% and 80.3%, respectively, and the cutoff PI value was 1.5% in men. The sensitivity and specificity of the PI to predict PAD were 82.1% and 79.2%, respectively, and the cutoff PI value was 1.1% in women. PI could be a reliable screening tool for diagnosing PAD because it does not restrict the patient's mobility, can be completed in a short time period, and is associated with reduced costs.

Anatomical classification of breast sentinel lymph nodes using computed tomography-lymphography.

To evaluate the anatomical classification and location of breast sentinel lymph nodes, preoperative computed tomography-lymphography examinations were retrospectively reviewed for sentinel lymph nodes in 464 cases clinically diagnosed with node-negative breast cancer between July 2007 and June 2016. Anatomical classification was performed based on the numbers of lymphatic routes and sentinel lymph nodes, the flow direction of lymphatic routes, and the location of sentinel lymph nodes. Of the 464 cases reviewed, anatomical classification could be performed in 434 (93.5 %). The largest number of cases showed single route/single sentinel lymph node (n = 296, 68.2 %), followed by multiple routes/multiple sentinel lymph nodes (n = 59, 13.6 %), single route/multiple sentinel lymph nodes (n = 53, 12.2 %), and multiple routes/single sentinel lymph node (n = 26, 6.0 %). Classification based on the flow direction of lymphatic routes showed that 429 cases (98.8 %) had outward flow on the superficial fascia toward axillary lymph nodes, whereas classification based on the height of sentinel lymph nodes showed that 323 cases (74.4 %) belonged to the upper pectoral group of axillary lymph nodes. There was wide variation in the number of lymphatic routes and their branching patterns and in the number, location, and direction of flow of sentinel lymph nodes. It is clinically very important to preoperatively understand the anatomical morphology of lymphatic routes and sentinel lymph nodes for optimal treatment of breast cancer, and computed tomography-lymphography is suitable for this purpose.

A Case of Hyperparathyroidism due to a Large Intrathyroid Parathyroid Adenoma with Recurrent Episodes of Acute Pancreatitis.

We report a case of a 66-year-old woman who developed hyperparathyroidism due to a large intrathyroid parathyroid adenoma with episodes of acute pancreatitis. She had previously been treated for acute pancreatitis twice. Serum calcium was 12.4 mg/dL, and intact parathyroid hormone was 253 pg/dL. Ultrasonography and computed tomography of the neck with contrast enhancement revealed a soft tissue mass (28 mm transverse diameter) within the left lobe of the thyroid. 99mTc-MIBI scintigraphy demonstrated focal accumulation due to increased radiotracer uptake in the left thyroid lobe. Left hemithyroidectomy was performed. Histopathology showed no signs of invasion, and this is consistent with parathyroid adenoma. Immunostaining was positive for expression of chromogranin A and parathyroid hormone. The patient had no episode of pancreatitis after the operation. In a patient with recurrent episodes of pancreatitis, the possibility of complication with hyperparathyroidism should be considered.

[A Case of a Rupture of the Carotid Artery Caused by the Lenvatinib Medication].

We report a case of a rupture of the common carotid artery caused by the medication of lenvatinib. The patient, 70-yearold female, was referred to our hospital by unresectable papillary thyroid cancer infiltrated the left common carotid artery. Externalbeam radiotherapy and radioiodine therapy were undergone after totalthyroidectomy. After 1 year 7 months from operation, she admitted our hospital due to left shoulder pain and dysphagia caused by the growing left cervical tumor. The medication of lenvatinib was decided after the careful informed consent. Computed tomography on the eighth day of lenvatinib medication showed the existence of air infiltration into the tumor surrounded left common carotid artery. So, a discontinuance of lenvatinib medication was decided immediately. But, on the ninth day, a rupture of the left common carotid artery occurred and on the tenth day, she died. Lenvatinib medication for the patient with the tumor surrounded artery should be decided carefully.

[Tumor Displacement Resulting from Core Needle Biopsy of Breast Cancer - A Case Report].

Tumor cell displacement is occasionally observed in surgical specimens after core needle biopsy. We report a case involving a 58-year-old woman in whom a microlobulated mass was detected on mammography, after which she underwent an ultrasonography- guided core needle biopsy. Thirty-six days later, a new low-echoic lesion was detected on ultrasonography, located from the original mass to the subcutaneous insertion site of the needle biopsy. Fifty days after the biopsy, breast-conserving surgery was performed. Histopathology showed a main tumor containing 2 components, namely invasive carcinoma of no special type, which showed tubule and gland formation, and invasive papillary carcinoma(WHO Classification). The invasive carcinoma with tubule formation was also observed in the adjacent collagen fibers, suggesting tumor displacement in the needle tracks. It has been suggested that malignant cells displaced by core needle biopsy do not survive. However, based on the present case, we recommend ascertaining the absence of extensive tumor displacement using ultrasonography unless all needle tracks are included in the planned resection area.

[The case of a long-surviving patient with breast cancer and brain metastases treated using multidisciplinary therapy].

We present the case of a 55-year-old-woman who was diagnosed with left breast cancer, and underwent a left mastectomy and left axillary lymph node resection. The histopathological examination indicated scirrhous carcinoma and lesser papillotubular carcinoma[estrogen receptor-negative (ER-), progesterone receptor-negative(PgR-), and human epidermal growth factor receptor 2-positive, grade 3 (HER2, 3+)] with lymph node metastases. Adjuvant chemotherapy consisting of epirubicin and cyclophosphamide (EC) followed by paclitaxel was administered. During the therapy, the patient noticed a mass on her left chest wall. It was diagnosed as a locally recurrent tumor. A computed tomography (CT) scan indicated supraclavicular lymph node metastasis. The patient underwent radiotherapy and was administered chemotherapy with TS-1 and trastuzumab. Brain metastases were found 24 months postoperatively, and the patient underwent surgery and wholebrain radiotherapy. After these, systemic capecitabine and trastuzumab chemotherapy was administered. The therapy was subsequently changed to capecitabine and lapatinib. There have been no subsequent metastatic tumors, and good control has been achieved for a long time after the detection of brain metastases.

[Sentinel lymph node biopsy in male breast cancer - a case report].

We report a case of breast cancer in a man who underwent sentinel lymph node biopsy (SLNB). The patient, a 66-year-old man, observed a tumor under his left areola. The elastic hard tumor had a clear border. Ultrasonography revealed a hypoechoic tumor, approximately 18 mm in diameter, in the left subareolar and outer upper region. On fine needle aspiration cytology (FNAC), the tumor was diagnosed as a ductal carcinoma. The patient underwent a mastectomy (Bt) and an axillaryly mph node dissection(Ax)after the SLNB. The SLNB was performed with the blue dye alone. Based on histopathological observations, estrogen receptor (ER)- and progesterone receptor (PgR)-positive invasive micropapillary carcinoma was diagnosed. The human epidermal growth factor receptor 2(HER2) score was 1+, and Ki-67 labeling index was 30%. Lymph node metastasis was not seen in SLNB (0/1) and Ax (0/13). Postoperatively, the patient received oral tamoxifen therapy. There was no evidence of recurrence during the 9-month follow-up. In this case, computed tomographic (CT) lymphography (CTLG) and SLNB were performed successfully, without incident. We recommend SLNB in cases of male breast cancer with clinically negative nodes.

Ensuring adequate human medical resources during an avian influenza A/H5N1 pandemic.

INTRODUCTION: When countermeasures are taken against an avian influenza (AI) pandemic in a hospital, it is essential to know the potential number of staff who would choose to be absent. The purpose of this study was to clarify how many medical staff would be willing to work during a pandemic, and requirements to secure adequate human resources. METHODS: From September to December 2008, a total of 3,152 questionnaires were sent to five private hospitals and one public hospital, which represent the core hospitals in the regions of Kyoto, Osaka, and Hyogo Prefectures. Participants consisted of hospital staff including: (1) physicians; (2) nurses; (3) pharmacists; (4) radiological technologists (RTs); (5) physical therapists (PTs); (6) occupational therapists (OTs); (7) clinical laboratory technologists (CLTs); (8) caregivers; (9) office clerks; and (10) others. They were queried about their attitude toward pandemics, including whether they would come to the hospital to work, treat patients, and what kinds of conditions they required in order to work. RESULTS: A total of 1,975 persons (62.7%) responded. A total of 204 persons (10.6%) would not come to the hospitals during a pandemic, 363 (18.8%) would perform their duties as usual, unconditionally, 504 (26.1%) would come to hospitals but not treat AI patients, and 857 (44.5%) would report to the hospital and treat AI patients with some essential conditions. These essential conditions were: (1) personal protective equipment (PPE) (80.0%); (2) receipt ofworkmen's compensation (69.3%); (3) receipt of anti-virus medication (58.2%); and (3) receipt of pre-pandemic vaccination (57.8%). CONCLUSION: During a pandemic, all types of health professionals would be lacking, not only physicians and nurses. This study indicates that ensuring sufficient medical human resources would be difficult without the provision of adequate safety and compensation measures.

[Gastritis].

Eradication of Helicobacter pylori (H. pylori) has suggested not only the decrease in the incidence of peptic ulcer diseases and gastric cancer, and but also the improvement of dyspeptic symptoms. Dyspepsia is a common condition in the world, and dyspepsia-related medical cost is high due to consultations, investigations, and drug consumption. Although the role of H. pylori in functional dyspepsia is still unknown, recent studies including meta-analysis have indicated that H. pylori eradication improves dyspeptic symptoms. In addition, the reduction of medical cost by H. pylori eradication has been discussed in the more recent studies.

Establishment of transplantable murine osteosarcoma cell line with endochondral ossification.

Osteosarcoma is defined as a malignant mesenchymal tumor in which tumor cells produce bone matrix. Osteosarcoma cell line (Nishi-Hirosaki osteosarcoma, NHOS) from a spontaneous soft tissue tumor in an athymic mouse was established. The cultured NHOS cells formed a monolayer consisting of spindle to polygonal cells without extracellular matrix formation or mineralization. In contrast, the transplanted NHOS tumor in immunodeficient mice consisted of short spindle and pleomorphic cells, associated with networks of calcified bone and osteoid matrices, as well as small foci of chondroid matrix. Pulmonary metastasis was detected in 22 (42.3%) out of the 52 tumor-bearing mice when NHOS cells were transplanted into the murine flanks. Pulmonary metastasis was detected in all mice (6/6) at post-injection days 21-49 when the cells were injected into the murine tail veins. The NHOS transplantable osteosarcoma cell line with ossifying ability would be useful to clarify the mechanisms of aggressive metastatic potential, as well as for studying the ossification process involved in cell-to-matrix interactions.

Pork peptone stimulates cholecystokinin secretion from enteroendocrine cells and suppresses appetite in rats.

We found that soybean beta-conglycinin peptone (BconP) suppresses food intake through cholecystokinin (CCK) release from enteroendocrine cells in association with binding of the peptone to rat small intestinal brush border membrane (BBM). The aim of the present study was to find new appetite suppressing peptides. Peptones from chicken, pork, beef, beef liver, and egg white were examined for activities to bind with rat BBM, CCK-release from enteroendocrine cell line STC-1, and induce satiety in rats. Chicken and pork peptone (ChickP and PorkP) bound to BBM with highest ability as evaluated with a surface plasmon biosensor. PorkP and ChickP released CCK in higher amounts than BconP from STC-1 cells dose-dependently, with highest stimulation by PorkP. An orogastric preload of PorkP, but not ChickP, suppressed food intake similarly to BconP, dose-dependently. These results suggest that PorkP interacts directly with the small intestinal CCK cells to release CCK, and that it suppresses appetite in rats.

The soybean beta-conglycinin beta 51-63 fragment suppresses appetite by stimulating cholecystokinin release in rats.

We previously demonstrated that soybean beta-conglycinin peptone suppresses food intake and gastric emptying by direct action on rat small intestinal mucosal cells to stimulate cholecystokinin (CCK) release. The aim of the present study was to define the active fragment in beta-conglycinin by using synthetic peptides chosen from the sequence of three beta-conglycinin subunits. We selected the fragments that had multiple nonadjacent arginine residues, and investigated their ability to bind to components of the rat intestinal brush border membrane as well as to stimulate CCK release and appetite suppression. The fragment from 51 to 63 of the beta subunit (beta 51-63) had the strongest binding activity. Intraduodenal infusion of beta 51-63 inhibited food intake and markedly increased portal CCK concentration. The threshold concentration of beta 51-63 to affect food intake was 3 micro mol/L. The CCK-A receptor antagonist abolished the beta 51-63-induced suppression of food intake. Three types of smaller fragments of beta 51-63 (beta 51-59, beta 53-63 and beta 53-59) and two types of fragments similar to beta 51-63 in the beta-conglycinin alpha and alpha' subunits (alpha 212-224 and alpha' 230-240) had less binding ability than did beta 51-63. Model peptides constructed with arginine (R) and glycine (G), such as GRGRGRG, had strong binding affinity, but peptides containing a single R or RR did not. These results indicate that the beta-conglycinin beta 51-63 fragment is the bioactive appetite suppressant in beta-conglycinin, and multiple arginine residues in the fragment may be involved in this effect.

Soybean beta-conglycinin peptone suppresses food intake and gastric emptying by increasing plasma cholecystokinin levels in rats.

Cholecystokinin (CCK) is an important physiologic mediator that regulates satiety and gastric emptying. We demonstrated previously that soybean peptone acts directly on rat small intestinal mucosal cells to stimulate CCK release. In the present study, we examined the effects of beta-conglycinin, a major component of soy protein, and its peptone on food intake and gastric emptying after an intraduodenal infusion of beta-conglycinin peptone in relation to CCK release and interaction with the mucosal cell membrane. Intraduodenal infusion of beta-conglycinin peptone inhibited food intake in a dose-dependent manner, but that of whole soy peptone or camostat did not. The suppression of food intake by beta-conglycinin peptone was abolished by an intravenous injection of devazepide, a selective peripheral CCK receptor antagonist. The beta-conglycinin peptone infusion strongly suppressed gastric emptying with marked increases in portal CCK levels. We also observed that the beta-conglycinin peptone dose dependently and more potently stimulated CCK release from isolated dispersed mucosal cells of the rat jejunum than did beta-conglycinin itself. This stimulation corresponded to the binding activity of the peptide or protein to solubilized components of the rat jejunum membrane as evaluated by surface plasmon biosensor. These results indicate that beta-conglycinin peptone suppresses food intake, and this effect may be due to beta-conglycinin peptone in the lumen stimulating endogenous CCK release with direct acceptance to the intestinal cells.