Publications by authors named "Naomi Shimizu"

62 Publications

Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone therapy increases carotid intima-media thickness and plaque score with von Willebrand factor activity elevation in patients with malignant lymphoma.

J Chemother 2021 Oct 18:1-6. Epub 2021 Oct 18.

Center for Diabetes, Metabolism and Endocrinology, Toho University Medical Center Sakura Hospital, Chiba, Japan.

An increased risk for atherosclerosis has been noted in cancer survivors; however, studies that focus on the risk of atherosclerosis in patients treated with chemotherapy are scarce. Therefore, we evaluated 32 patients who received rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) therapy for B-cell malignant lymphoma by analysing the changes in atherosclerosis. Just before each treatment course, plasma levels of von Willebrand Factor (vWF) activity were evaluated, and carotid ultrasonography was performed at baseline and after the final treatment. Throughout the follow-up period, plasma vWF levels showed significantly transient increased by approximately 20%-40%. Both mean carotid intima-media thickness (IMT) and plaque score (PS) significantly increased during the 36.6 ± 26.0 weeks of observation (mean IMT: 0.724 ± 0.118 to 0.767 ± 0.129 mm; PS: 4.31 ± 3.53 to 4.87 ± 3.88,  < 0.001). Our study suggests that R-CHOP therapy promotes atherosclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/1120009X.2021.1988202DOI Listing
October 2021

Effect of Conventional Medical Therapy or Laparoscopic Sleeve Gastrectomy on Urinary Albumin in Japanese Subjects with Severe Obesity: An Observational Study.

Obes Facts 2021 Oct 14:1-9. Epub 2021 Oct 14.

Center of Diabetes, Endocrinology and Metabolism, Toho University Sakura Medical Center, Sakura-shi, Japan.

Introduction: In patients with severe obesity, albuminuria can be improved by both conventional medical therapy and bariatric surgery. The purpose of this study was to compare the impact of weight loss achieved through conventional medical therapy or laparoscopic sleeve gastrectomy (LSG) on albuminuria in Japanese subjects with severe obesity and identify the factors involved.

Methods: We retrospectively evaluated the clinical characteristics including the urinary albumin/creatinine ratio (UACR) of 340 consecutive subjects with a body mass index ≥35 who received LSG (n = 242) or medical therapy (n = 98) between 2010 and 2018 and were followed for at least 12 months.

Results: The baseline of the UACR was not different between the 2 groups. At the 12-month follow-up, total weight loss (TWL) and decreases in glycosylated hemoglobin (HbA1c) and loge UACR were greater in the LSG group than in the medical therapy group (body weight; -35.7 kg vs. -8.0 kg, p < 0.001, HbA1c; -1.4% vs. -0.7%, p < 0.001, loge UACR; -0.3 vs. 0.9, p < 0.001). The rate of complete remission of diabetes was significantly higher in the LSG group than in the medical therapy group. At 12 and 36 months (n = 111 in the medical therapy group, n = 56 in the LSG group at 36 months), loge UACR increased in the medical therapy group, while it remained unchanged or decreased in the LSG group. In subjects with microalbuminuria and macroalbuminuria, changes in the loge UACR correlated with percent total body weight loss (%TWL) in both groups at 12 months. Percent TWL contributed independently to the change in the loge UACR, irrespective of whether LSG was performed. In receiver-operating characteristic analysis, a weight loss of 7.8% predicted a decrease in the UACR (∆UACR <0 at 12 months).

Conclusion: Our analysis suggests that albuminuria may increase over time if only medical therapy is continued. To improve albuminuria, weight loss may be more important than whether LSG is performed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000519156DOI Listing
October 2021

Determinants of type 2 diabetes remission after bariatric surgery in obese Japanese patients: a retrospective cohort study.

Diabetol Int 2021 Oct 28;12(4):379-388. Epub 2021 Jan 28.

Center for Diabetes, Endocrine and Metabolism, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura, Chiba 285-0841 Japan.

Objective: Bariatric surgery (BS) improves glycemic control in type 2 diabetes; however, some patients show insufficient improvement. Understanding the pathophysiology of type 2 diabetes in obese patients can facilitate appropriate treatment for type 2 diabetes after BS. The homeostatic model assessment (HOMA) 2 enables the calculation of the values from C-peptide data and evaluation of insulin users. We aimed to evaluate the pathophysiology of type 2 diabetes using pre- and postoperative parameters and HOMA2 in obese patients who underwent BS.

Methods: We retrospectively reviewed data from 45 obese patients with type 2 diabetes who underwent BS. They were followed-up for 12 months. The relationship between the HOMA2 score and complete remission (CR) of type 2 diabetes after BS was analyzed. Patients with and without CR were assigned to the CR and non-CR groups, respectively. Multiple regression analysis was used to identify factors associated with improvement in type 2 diabetes after BS.

Results: BS significantly improved body weight and glucose metabolism. The preoperative glycosylated hemoglobin A1c level and insulin secretion (HOMA2-%B) significantly differed between the CR and non-CR groups. Postoperative weight reduction and improved insulin sensitivity correlated significantly with CR; multiple regression showed that the preoperative HOMA 2-%B independently predicted CR of type 2 diabetes after BS.

Conclusion: Preoperative insulin secretion, improvement in insulin sensitivity, and weight reduction after BS are related to CR of type 2 diabetes after BS. The results better reveal the pathophysiology of and treatment for type 2 diabetes in obese patients who undergo BS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13340-021-00493-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413414PMC
October 2021

High presepsin concentrations in bile and its marked elevation in biliary tract diseases: A retrospective analysis.

Clin Chim Acta 2021 Oct 29;521:278-284. Epub 2021 Jul 29.

Department of Hematology, Toho University Sakura Medical Center, 2858741 Chiba, Japan. Electronic address:

Background: Presepsin is a diagnostic and prognostic biomarker of both bacterial infection and sepsis; however, elevated presepsin levels have also been observed without sepsis. We conducted several analyses to evaluate the clinical laboratory parameters affecting presepsin levels.

Method: We analyzed the association between sequential organ failure assessment (SOFA) scores and plasma presepsin levels and then analyzed clinical laboratory parameters in 567 patients with univariate and multivariate regression analysis and analysis of covariance (ANCOVA). We also determined presepsin in the bile of 11 patients and examined the presepsin immunostaining in liver.

Results: Spearman's rank correlation analysis with log change revealed that presepsin levels were closely associated with log-transformed SOFA score (ρ = 0.541), alkaline phosphatase (ALP); (ρ = 0.454) and gamma-glutamyl transferase; (ρ = 0.505). Multivariate regression analysis revealed that log-transformed SOFA score (β-coefficient = 0.316), ALP level (β-coefficient = 0.380), and creatinine level (β-coefficient = 0.290) independently and significantly affected log presepsin levels. ANCOVA revealed that presepsin levels were significantly higher in patients with hepatobiliary disease. Patients who presented with dilatation of the bile ducts and elevated ALP levels or total bilirubin levels exhibited high presepsin levels in the bile. Presepsin production in liver Kupffer cells was also confirmed by immunostaining.

Conclusion: Presepsin levels is correlated with the elevation of biliary enzymes in patients without renal dysfunction or sepsis. Additionally, presepsin exists with high concentrations in the bile and is positive in Kupffer cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cca.2021.07.025DOI Listing
October 2021

Azacitidine decreases reactive oxygen species production in peripheral white blood cells: A case report.

World J Clin Cases 2020 Nov;8(22):5657-5662

Center for Diabetes, Metabolism and Endocrinology, Toho University Medical Center Sakura Hospital, Sakura 2858741, Japan.

Background: In myelodysplastic syndrome (MDS), oxidative stress is closely related to iron overload and DNA damage. A recent study suggested the possibility that increased oxidative stress causes not only iron overload but also disease progression of MDS with DNA damage. We present a case of MDS with decreased reactive oxygen species (ROS) production in peripheral white blood cells (WBCs) and decreased diacron-reactive oxygen metabolites (d-ROMs) in serum after azacitidine therapy.

Case Summary: A 74-year-old man presented to the hematological department with the chief complaint of anemia. His vital signs were within normal limits at admission with a heart rate of 80 bpm and blood pressure of 135/60 mmHg. Laboratory tests indicated pancytopenia, a WBC count of 2190 cells/µL, a hemoglobin level of 6.2 g/dL and a platelet count of 7.4 × 10/µL. The patient was diagnosed with MDS with fibrosis after a bone marrow examination. This case showed decreased ROS production in WBCs, d-ROMs in serum and Wilms' tumor 1 after azacitidine therapy, after which his hematopoiesis recovered.

Conclusion: Azacitidine therapy can improve hematopoiesis and decrease ROS and d-ROM production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12998/wjcc.v8.i22.5657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716315PMC
November 2020

Importance of doctor-initiated management of the balance between work and treatment for lung cancer patients: Results of a nationwide survey by the Japan Lung Cancer Society.

Cancer Med 2020 09 13;9(17):6186-6195. Epub 2020 Jul 13.

Department of Thoracic Surgery, Kindai University Faculty of Medicine, Osaka, Japan.

Backgrounds: Since the recent development of molecular targeted drugs and immune checkpoint inhibitors has improved lung cancer treatment options and outcomes, supporting patients in balancing work and pharmacotherapy have become even more important in the field of lung cancer treatment. This study sought to identify the current status and roles of doctors in balancing work and treatment for lung cancer patients.

Methods: Patients and doctors were recruited to complete a web-based questionnaire survey by the Japan Lung Cancer Society.

Results: About 287 lung cancer patients and 381 doctors were included in the analysis. About 42.9% of patients responded that "there was no discussion" about their working conditions or work before the initiation of pharmacotherapy, while 22.6% responded that "there was an inquiry from a doctor/health care provider and a discussion that included the doctor was held." About 45.3% of patients took leave or resigned from work at the time of diagnosis. The most common reasons for patients to resign before or during pharmacotherapy were "poor physical condition due to side effects of treatment or illness" and "concern about causing problems in the workplace." To assist in balancing work and pharmacotherapy, patients desired "increased opportunities to consult about work" (36.9%) and "provision of treatment options with few adverse events" (28.9%).

Conclusion: This study highlights the importance of doctor-initiated management of the balance between work and treatment for lung cancer patients. An important first step is for doctors themselves to take an interest in their patients' professions and initiate discussions of work-related topics with their patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.3307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476847PMC
September 2020

New Horizons of Arterial Stiffness Developed Using Cardio-Ankle Vascular Index (CAVI).

J Atheroscler Thromb 2020 Aug 26;27(8):732-748. Epub 2020 Jun 26.

Center of Diabetes, Endocrine and Metabolism, Toho University Sakura Medical Center.

Arterial stiffness is recognized mainly as an indicator of arteriosclerosis and a predictor of cardiovascular events. Cardio-ankle vascular index (CAVI), which reflects arterial stiffness from the origin of the aorta to the ankle, was developed in 2004. An important feature of this index is the independency from blood pressure at the time of measurement. A large volume of clinical evidence obtained using CAVI has been reported. CAVI is high in patients with various atherosclerotic diseases including coronary artery disease and chronic kidney disease. Most coronary risk factors increase CAVI and their improvement reduces CAVI. Many prospective studies have investigated the association between CAVI and future cardiovascular disease (CVD), and proposed CAVI of 9 as the optimal cut-off value for predicting CVD. Research also shows that CAVI reflects afterload and left ventricular diastolic dysfunction in patients with heart failure. Furthermore, relatively acute changes in CAVI are observed under various pathophysiological conditions including mental stress, septic shock and congestive heart failure, and in pharmacological studies. CAVI seems to reflect not only structural stiffness but also functional stiffness involved in acute vascular functions. In 2016, Spronck and colleagues proposed a variant index CAVI, and claimed that CAVI was truly independent of blood pressure while CAVI was not. This argument was settled, and the independence of CAVI from blood pressure was reaffirmed. In this review, we summarize the recently accumulated evidence of CAVI, focusing on the proposed cut-off values for CVD events, and suggest the development of new horizons of vascular function index using CAVI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5551/jat.RV17043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458785PMC
August 2020

Outcomes of a low-osmolar water-soluble contrast pathway in small bowel obstruction.

J Trauma Acute Care Surg 2019 09;87(3):630-635

From the Division of Trauma, Burns, Surgical Critical Care and Emergency General Surgery, Brigham and Women's Hospital, Boston, Massachusetts (H.G.L., M.C-A., M.B., Z.C., D.N., S.L.N., R.A., E.K., N.S., R.R., A.S., J.M.H.).

Background: Adhesive small-bowel obstruction (SBO) is a common surgical condition accounting for a significant proportion of acute surgical admissions and surgeries. The implementation of a high-osmolar water-soluble contrast challenge has repeatedly been shown to reduce hospital length of stay and possibly the need for surgery in SBO patients. The effect of low-osmolar water-soluble contrast challenge however, is unclear. The aim of this study is to evaluate the outcomes of an SBO pathway including a low-osmolar water-soluble contrast challenge.

Methods: A prospective cohort of patients admitted for SBO were placed on an evidence-based SBO pathway including low-osmolar water-soluble contrast between January 2017 and October 2018 and were compared with a historical cohort of patients prior to the implementation of the pathway from September 2013 through December 2014. The primary outcome was length of stay less than 4 days with a secondary outcome of failure of nonoperative management.

Results: There were 140 patients enrolled in the SBO pathway during the study period and 101 historic controls. The SBO pathway was independently associated with a length of stay less than 4 days (odds ratio, 1.76; 95% confidence interval, 1.03-3.00). Median length of stay for patients that were successfully managed nonoperatively was lower in the SBO pathway cohort compared with controls (3 days vs. 4 days, p = 0.04). Rates of readmission, surgery, and bowel resection were not significantly different between the two cohorts.

Conclusion: Implementation of an SBO pathway using a low-osmolarity contrast is associated with decreased hospital length of stay. Rates of readmission, surgery, and need for bowel resection for those undergoing surgery were unchanged. An SBO pathway utilizing low-osmolarity water-soluble contrast is safe and effective in reducing length of stay in the nonoperative management of adhesive small-bowel obstructions.

Level Of Evidence: Therapeutic study, level IV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TA.0000000000002401DOI Listing
September 2019

Pneumatosis Intestinalis After Molecular-Targeted Therapy.

World Neurosurg 2019 05 11;125:312-315. Epub 2019 Feb 11.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address:

Background: Pneumoperitoneum after surgical manipulation of the abdomen implies a perforation. Rare cases of nonoperated cancer patients, largely with gastrointestinal or genitourinary cancers, have been noted to have radiologic findings of pneumatosis intestinalis and/or pneumoperitoneum as a complication of molecular-targeted therapy (MTT) without confounding factors for perforation. We present a patient with a cranial malignancy treated with bevacizumab who subsequently manifested with pneumatosis intestinalis.

Case Description: A 67-year-old man with metastatic melanoma, non-small cell lung cancer, and recurrent cerebellar subependymoma was initiated on bevacizumab treatment for subependymoma recurrence. He subsequently underwent an uncomplicated ventriculoperitoneal shunt for progressive obstructive hydrocephalus, confirmed by a normal postoperative abdominal radiograph. One week later, he returned with worsening lethargy and a computed tomography consistent with pneumomediastinum and pneumoperitoneum. Due to concern for bowel perforation, the patient underwent diagnostic laparoscopy and removal of ventriculoperitoneal shunt. Focal sigmoid pneumatosis was identified without any signs of bowel perforation or ischemia. Bevacizumab was discontinued, and the patient's radiologic and clinical findings improved.

Conclusions: With increasing utilization of MTTs in brain tumor management, we raise MTT as a potential cause for pneumoperitoneum in neurosurgical patients. Pneumoperitoneum after extracranial procedures still requires workup and management for potential bowel perforation, but alternative causes such as bevacizumab should also be considered. Pneumatosis intestinalis patients on MTT can have benign physical examinations and will resolve, in the majority of cases, on discontinuation of the drug.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2019.01.225DOI Listing
May 2019

Bezafibrate Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Hypertriglyceridemic Patients with Type 2 Diabetes Mellitus.

J Atheroscler Thromb 2019 Jul 22;26(7):659-669. Epub 2018 Dec 22.

Center of Diabetes, Endocrinology and Metabolism, Toho University, Sakura Medical Center.

Aim: Cardio-ankle vascular index (CAVI) reflects arterial stiffness and has been established as a useful surrogate marker of atherosclerosis. Contrary to the abundant data indicating slower progression of atherosclerosis with statins, studies on fibrates remain scarce. The aim of this study was thus to clarify the effect of bezafibrate on CAVI as well as on oxidative stress.

Methods: A randomized, open-label, controlled study was performed. 66 hypertriglyceridemic patients with type 2 diabetes were assigned to two groups: bezafibrate (400 mg/day) group and eicosapentaenoic acid (EPA 1.8 g/day) group. Patients were administered the respective treatment for 12 weeks. CAVI, glycolipid metabolic parameters, and diacron-reactive oxygen metabolites (d-ROMs) were evaluated before and after the study period.

Results: Serum triglycerides (TG), remnant-like particle cholesterol (RLP-C), fasting plasma glucose, HbA1c and d-ROMs decreased, while HDL-cholesterol increased significantly in the bezafibrate group but did not change in the EPA group. The decreases in TG, RLP-C, HbA1c and d-ROMs were significantly greater in the bezafibrate group than in the EPA group. CAVI decreased significantly only in the bezafibrate group and the decrease was significantly greater in bezafibrate group than in EPA group. Simple regression analysis showed no significant relationship between the change in CAVI and changes in other variables. Multivariate logistic regression analysis identified high baseline CAVI, low HDL-cholesterol level, and bezafibrate administration as significant independent predictors of CAVI decrease.

Conclusion: Bezafibrate treatment ameliorates arterial stiffness accompanied by improvement of glycolipid metabolism and oxidative stress. These effects potentially have important beneficial health consequences in hypertriglyceridemic patients with type 2 diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5551/jat.45799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629745PMC
July 2019

SIRT2-mediated inactivation of p73 is required for glioblastoma tumorigenicity.

EMBO Rep 2018 11 13;19(11). Epub 2018 Sep 13.

Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan

Glioblastoma is one of the most aggressive forms of cancers and has a poor prognosis. Genomewide analyses have revealed that a set of core signaling pathways, the p53, RB, and RTK pathways, are commonly deregulated in glioblastomas. However, the molecular mechanisms underlying the tumorigenicity of glioblastoma are not fully understood. Here, we show that the lysine deacetylase SIRT2 is required for the proliferation and tumorigenicity of glioblastoma cells, including glioblastoma stem cells. Furthermore, we demonstrate that SIRT2 regulates p73 transcriptional activity by deacetylation of its C-terminal lysine residues. Our results suggest that SIRT2-mediated inactivation of p73 is critical for the proliferation and tumorigenicity of glioblastoma cells and that SIRT2 may be a promising molecular target for the therapy of glioblastoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15252/embr.201745587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6216266PMC
November 2018

PIK3CA and KRAS mutations in cell free circulating DNA are useful markers for monitoring ovarian clear cell carcinoma.

Oncotarget 2018 Mar 22;9(20):15266-15274. Epub 2018 Feb 22.

Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.

Ovarian clear cell carcinoma (OCCC) exhibits distinct phenotypes, such as resistance to chemotherapy, poor prognosis and an association with endometriosis. Biomarkers and imaging techniques currently in use are not sufficient for reliable diagnosis of this tumor or prediction of therapeutic response. It has recently been reported that analysis of somatic mutations in cell-free circulating DNA (cfDNA) released from tumor tissues can be useful for tumor diagnosis. In the present study, we attempted to detect mutations in PIK3CA and KRAS in cfDNA from OCCC patients using droplet digital PCR (ddPCR). Here we show that we were able to specifically detect PIK3CA-H1047R and KRAS-G12D in cfDNA from OCCC patients and monitor their response to therapy. Furthermore, we found that by cleaving wild-type PIK3CA using the CRISPR/Cas9 system, we were able to improve the sensitivity of the ddPCR method and detect cfDNA harboring PIK3CA-H1047R. Our results suggest that detection of mutations in cfDNA by ddPCR would be useful for the diagnosis of OCCC, and for predicting its recurrence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.24555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880602PMC
March 2018

A cadaveric procedural anatomy simulation course improves video-based assessment of operative performance.

J Surg Res 2018 03 11;223:64-71. Epub 2017 Nov 11.

Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address:

Background: Inadequate anatomic knowledge has been cited as a major contributor to declining surgical resident operative competence. We analyzed the impact of a comprehensive, procedurally oriented cadaveric procedural anatomy dissection laboratory on the operative performance of surgery residents, hypothesizing that trainees' performance of surgical procedures would improve after such a dissection course.

Materials And Methods: Midlevel general surgery residents (n = 9) participated in an 8 wk, 16-h surgery faculty-led procedurally oriented cadaver simulation course. Both before and after completion of the course, residents participated in a practical examination, in which they were randomized to perform one of nine Surgical Council on Resident Education-designated "essential" procedures. The procedures were recorded using wearable video technology. Videos were deidentified before evaluation by six faculty raters blinded to examinee and whether performances occurred before or after an examinee had taken the course. Raters used the validated Operative Performance Rating System and Objective Structured Assessment of Technical Skill scales.

Results: After the course residents had higher procedure-specific scores (median, 4.0 versus 2.4, P < 0.0001), instrument-handling (4.0 versus 3.0, P = 0.006), respect for tissue (4.0 versus 3.0, P = 0.0004), time and motion (3.0 versus 2.0, P = 0.0007), operation flow (3.0 versus 2.0, P = 0.0005), procedural knowledge (4.0 versus 2.0, P = 0.0001), and overall performance scores (4.0 versus 2.0, P < 0.0001). Operative Performance Rating System and Objective Structured Assessment of Technical Skill scales averaged by number of items in each were also higher (3.2 versus 2.0, P = 0.0002 and 3.1 versus 2.2, P = 0.002, respectively).

Conclusions: A cadaveric procedural anatomy simulation course covering a broad range of open general surgery procedures was associated with significant improvements in trainees' operative performance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jss.2017.05.067DOI Listing
March 2018

Long-term efficacy of partial splenic embolization for the treatment of steroid-resistant chronic immune thrombocytopenia.

Ann Hematol 2018 Apr 13;97(4):655-662. Epub 2018 Jan 13.

Department of Hematology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan.

Thrombopoietin-receptor agonists have been recently introduced for a second-line treatment of immune thrombocytopenia (ITP). Splenectomy has tended to be avoided because of its complications, but the response rate of splenectomy is 60-80% and it has still been considered for steroid-refractory ITP. We performed partial splenic embolization (PSE) as an alternative to splenectomy. Between 1988 and 2013, 91 patients with steroid-resistant ITP underwent PSE at our hospital, and we retrospectively analyzed the efficacy and long-term outcomes of PSE. The complete response rate (CR, platelets > 100 × 10/L) was 51% (n = 46), and the overall response rate (CR plus response (R), > 30 × 10/L) was 84% (n = 76). One year after PSE, 70% of patients remained CR and R. The group with peak platelet count after PSE ≥ 300 × 10/L (n = 29) exhibited a significantly higher platelet count than the group with platelet count < 300 × 10/L (n = 40) at any time point after PSE. The failure-free survival (FFS) rates at 1, 5, and 10 years were 78, 56, and 52%, respectively. Second PSE was performed in 20 patients who relapsed (n = 14) or had no response to the initial PSE (n = 6), and the overall response was achieved in 63% patients. There were no PSE-related deaths. These results indicate that PSE is a safe and effective alternative therapy to splenectomy for patients with steroid-resistant ITP as it generates long-term, durable responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00277-018-3232-xDOI Listing
April 2018

Successful Treatment of Rapidly Progressive Life-Threatening Esophageal Submucosal Hematoma in a Patient With van der Hoeve Syndrome.

J Clin Med Res 2018 Feb 30;10(2):154-157. Epub 2017 Dec 30.

Center for Diabetes, Metabolism, and Endocrinology, Toho University Medical Center Sakura Hospital, 564-1 Shimoshizu Sakura, Chiba, Japan.

Osteogenesis imperfecta (OI) is a rare inherited disorder of the connective tissue with many reports on its association with bleeding diatheses. OI patients with blue sclera, hearing loss, and bone vulnerability are classified as having van der Hoeve syndrome. Here, we report the first case of rapidly progressing, massive esophageal submucosal hematoma in this syndrome. Bleeding in OI is reportedly due to defective capillary integrity and platelet dysfunction; however, our patient did not show such findings. Multiple factors contributed to the bleeding diathesis, including dysfunction of platelet and platelet-endothelial cell interaction, which could not be proven .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14740/jocmr3270wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5755655PMC
February 2018

7-Ketocholesterol induces ROS-mediated mRNA expression of 12-lipoxygenase, cyclooxygenase-2 and pro-inflammatory cytokines in human mesangial cells: Potential role in diabetic nephropathy.

Prostaglandins Other Lipid Mediat 2018 01 15;134:16-23. Epub 2017 Nov 15.

Center for Diabetes, Endocrinology and Metabolism, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura-City, Chiba 285-8741, Japan. Electronic address:

7-Ketocholesterol (7-KCHO) is a highly proinflammatory oxysterol and plays an important role in the pathophysiology of diabetic nephropathy (DN). Lipoxygenases (LOXs) and cyclooxygenases (COXs) are also involved in the development of DN. The aim of this study was to clarify the effects of 7-KCHO on mRNA expression of LOXs and COXs as well as pro-inflammatory cytokines in human mesangial cells (HMC). We evaluated cell viability by WST-8 assay and measured mRNA expression by reverse transcription-polymerase chain reaction. Intracellular reactive oxygen species (ROS) production was evaluated by flow cytometry. Although 7-KCHO did not affect cell viability of HMC, 7-KCHO stimulated significant increases in mRNA expression of 12-LOX, COX-2 and pro-inflammatory cytokines. 7-KCHO also induced an increase in ROS production, while N-acetylcysteine partially suppressed the increase. The 12-LOX and COX-2 inhibitors also suppressed mRNA expression of cytokines. These findings may contribute to the elucidation of the molecular mechanism of the pathophysiology of DN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prostaglandins.2017.11.002DOI Listing
January 2018

Syndrome of Inappropriate Antidiuretic Hormone Secretion in a Patient with Mucosa-associated Lymphoid Tissue Lymphoma.

Intern Med 2017 Dec 11;56(23):3225-3229. Epub 2017 Oct 11.

Center for Diabetes, Metabolism and Endocrinology, Toho University Sakura Medical Center, Japan.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) may develop in association with several malignancies. However, as an immunohistochemical analysis is not performed in the majority cases, its true cause is often uncertain. We herein report a case of SIADH following chemotherapy due to tumor-derived ADH production in a patient with mucosa-associated lymphoid tissue (MALT) lymphoma. A retrospective immunohistochemical analysis demonstrated ADH expression by lymphoma cells. These findings highlight the importance of using an immunohistochemical analysis to determine ADH production by tumor cells in patients with SIADH. Such analyses play an important role in elucidating the pathogenesis of SIADH and determining the most appropriate treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2169/internalmedicine.9048-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742398PMC
December 2017

The obesity paradox in patients with severe soft tissue infections.

Am J Surg 2017 Sep 9;214(3):385-389. Epub 2016 Jul 9.

Center for Surgery and Public Health, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School and Harvard T. H. Chan School of Public Heath, Boston, MA, USA; Trauma, Burn and Surgical Critical Care Division, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:

Background: The "obesity paradox" has been demonstrated in chronic diseases but not in acute surgery. We sought to determine whether obesity is associated with improved outcomes in patients with severe soft tissue infections (SSTIs).

Methods: The 2006 to 2010 Nationwide Inpatient Sample was used to identify adult patients with SSTIs. Patients were categorized into nonobese and obese (nonmorbid [body mass index 30 to 39.9] and morbid [body mass index ≥ 40]). Logistic regression provided risk-adjusted association between obesity categories and inhospital mortality.

Results: There were 2,868 records with SSTI weighted to represent 14,080 patients. Obese patients were less likely to die in hospital than nonobese patients (odds ratio [OR] = .42; 95% confidence interval [CI], .25 to .70; P = .001). Subanalysis revealed a similar trend, with lower odds of mortality in nonmorbid obesity (OR = .46; 95% CI, .23 to .91; P = .025) and morbid obesity (OR = .39; 95% CI, .19 to .80; P = .011) groups.

Conclusions: Obesity is independently associated with reduced inhospital mortality in patients with SSTI regardless of the obesity classification. This suggests that the obesity paradox exists in this acute surgical population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjsurg.2016.05.006DOI Listing
September 2017

The Elevation of Cardio-Ankle Vascular Index in a Patient With Malignant Lymphoma Treated With a Combination Therapy of Rituximab and Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone.

J Clin Med Res 2017 Aug 1;9(8):729-732. Epub 2017 Jul 1.

Department of Internal Medicine, Mihama Hospital, Chiba, Japan.

An increased risk of arteriosclerosis has been noted in cancer survivors. Currently, there are only a few reports available that consider the risk of arteriosclerosis in patients treated with chemotherapy. Patients with an advanced stage B-cell malignant lymphoma are typically treated with a combination therapy of rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). Complications such as diabetes mellitus (DM), hyperlipidemia (HL), and osteoporosis due to prednisolone and cardiotoxicity due to anthracyclines are well known. However, there are no studies that have investigated the link between R-CHOP therapy and arteriosclerosis. We discussed a patient with follicular lymphoma who was evaluated using cardio-ankle vascular index (CAVI) as an arterial stiffness parameter during R-CHOP therapy in this report. She achived complete remission after the eighth course therapy without complications such as hypertension (HT), HL, DM, and infection. This patient showed elevated CAVI with new plaque formation in the carotid arteries after the end of chemotherapy. These data indicate that R-CHOP therapy may progress the arteriosclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14740/jocmr3071wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5505311PMC
August 2017

The Simultaneous Elevation of Oxidative Stress Markers and Wilms' Tumor 1 Gene during the Progression of Myelodysplastic Syndrome.

Intern Med 2016;55(24):3661-3664. Epub 2016 Dec 15.

Department of Blood Transfusion, Toho University Medical Center Sakura Hospital, Japan.

Oxidative stress is closely related to iron overload in myelodysplastic syndrome (MDS) and induces DNA damage. We evaluated the oxidative stress markers derivatives of reactive oxidative metabolites (dROM) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) during azacitidine treatment in an MDS patient. Simultaneous with an increase in the expression of Wilms' Tumor 1 (WT1) gene in the peripheral blood, the serum dROM level was elevated, and this increase was observed earlier than the increases in ferritin and 8-OHdG. Throughout the clinical course, dROM and 8-OHdG correlated significantly with WT1 and with ferritin, suggesting that changes in the oxidative stress marker levels reflect not only iron overload but also disease progression of MDS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2169/internalmedicine.55.7156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5283969PMC
April 2017

Tensile Comparison of Polydioxanone, Polyglyconate, and Barbed Glycolide-Trimethylene Carbonate Suture in Canine Cadaveric Tensor Fascia Lata.

Vet Surg 2017 Jan 1;46(1):89-94. Epub 2016 Dec 1.

School of Veterinary Sciences, University of Bristol, Bristol, United Kingdom.

Objective: To compare the mode of failure, load at yield, ultimate load to failure and stiffness of non-barbed polydioxanone, non-barbed polyglyconate and barbed glycolide-trimethylene carbonate (GTC) suture in canine cadaveric fascia.

Study Design: Ex vivo biomechanical study.

Sample Population: 18 fascia lata specimens from 9 canine cadavers.

Methods: 6 fascia lata specimens were sutured with polydioxanone, 6 with polyglyconate, and 6 with barbed GTC suture. Load at yield, stiffness, ultimate load to failure were measured using tensile strength testing. Statistical analysis was used to compare outcomes between suture materials. The mode of failure was recorded and described.

Results: The load at yield and ultimate load to failure were significantly greater for polydioxanone than barbed GTC (P=.045 and P=.016, respectively). The load at yield and ultimate load to failure was not significantly different between polydioxanone and polyglyconate (P=.687 and P=.586, respectively). The load at yield and the ultimate load to failure was not significantly different between polyglyconate and barbed GTC (P=.194 and P=.109, respectively). Stiffness was not different between constructs (P=.103). Polydioxanone and polyglyconate failed by suture breakage and suture pullout. Barbed GTC failed by suture slippage and suture breakage.

Conclusion: Our results showed that under the conditions of this study, 4-0 monofilament polydioxanone had a greater load at yield and load to failure than similarly sized, barbed copolymer suture in the fascia lata. This finding may help direct suture choice for fascial closure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/vsu.12580DOI Listing
January 2017

Safety and Efficacy of Granulocyte Colony-Stimulating Factor Monotherapy for Peripheral Blood Stem Cell Collection in POEMS Syndrome.

Biol Blood Marrow Transplant 2017 Feb 10;23(2):361-363. Epub 2016 Nov 10.

Department of Hematology, Chiba University Hospital, Chiba, Japan.

Although autologous stem cell transplantation can achieve excellent responses in patients with POEMS syndrome, the optimal regimen for peripheral blood stem cell (PBSC) collection is still controversial. We retrospectively investigated the safety and efficacy of 41 PBSC collecting procedures in 37 patients with POEMS syndrome. PBSC mobilization was performed using cyclophosphamide + granulocyte colony-stimulating factor (G-CSF) (CG, n = 14) or G-CSF alone (G, n = 27). Twelve (85.7%) patients in the CG group and all (100%) patients in the G group received induction chemotherapy before PBSC collection. The proportions of good mobilizers (≥2.0 × 10 CD34 cells/kg) were comparable between the 2 groups (CG versus G: 78.6% versus 70.4%, P = .71). Two (14.3%) patients in the CG group developed severe capillary leak symptoms during the PBSC mobilization period, whereas no patient in the G group experienced severe adverse events. Appropriate induction therapies followed by the G-CSF monotherapy compose an optimal strategy for PBSC collection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2016.10.024DOI Listing
February 2017

Prognostic impact of serum soluble LR11 in newly diagnosed diffuse large B-cell lymphoma: A multicenter prospective analysis.

Clin Chim Acta 2016 Dec 8;463:47-52. Epub 2016 Oct 8.

Department of Hematology, Chiba University Hospital, 1-8-1 Chuo-ku, Chiba City, Chiba, Japan.

Background: LR11 (also called SorLA or SORL1) is a type I membrane protein, originally identified as a biomarker for atherosclerosis and Alzheimer's disease. We recently found that LR11 was specifically expressed in Diffuse Large B-cell lymphoma (DLBCL) cells, and high serum sLR11 concentrations in retrospective cohort indicated inferior survival. In this study, we prospectively validated the clinical impact of serum sLR11 in 97 patients with newly-diagnosed, untreated DLBCL.

Results: Serum sLR11 concentrations were increased in DLBCL patients compared to normal controls (mean±SD: 21.2±27.6 vs. 8.8±1.8ng/ml, P<0.0001), and significantly reduced at remission (mean±SD: 17.4±16.4 vs. 10.9±4.5ng/ml, P=0.02). Increased serum sLR11 concentrations were affected by tumor burden and bone marrow invasion. The 2-y OS and PFS were significantly lower in patients with high sLR11 concentrations (≤18.1ng/ml vs. >18.1ng/ml; 2-y OS: 89.0% vs. 56.4%, P<0.0001; 2-y PFS: 85.8% vs. 56.9%, P<0.0001).

Conclusions: Serum sLR11 is a tumor-derived biomarker for predicting the survival of newly diagnosed patients with DLBCL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cca.2016.10.008DOI Listing
December 2016

Utility of the "Surprise" Question in Predicting Survival among Older Patients with Acute Surgical Conditions.

J Palliat Med 2017 04 1;20(4):420-423. Epub 2016 Nov 1.

1 Center for Surgery and Public Health, Brigham and Women's Hospital , Boston, Massachusetts.

Background: The surprise question is a validated tool for identifying patients with increased risk of death within one year who could, therefore, benefit from palliative care. However, its utility in surgery is unknown.

Objective: We sought to determine whether the surprise question predicted 12-month mortality in older emergency general surgery patients.

Design: This was a prospective cohort study.

Setting/subjects: Emergency general surgery attendings and surgical residents in or beyond their third year of training at a single tertiary care academic hospital from January to July 2014.

Measurements: Surgeons responded to the surprise question within 72 hours of evaluating patients, ≥65 years, hospitalized with an acute surgical condition. Patient data, including demographic and clinical characteristics, were extracted from the medical record. Mortality within 12 months of initial evaluation was determined by using Social Security death data.

Results: Ten attending surgeons and 18 surgical residents provided 163 responses to the surprise question for 119 patients: 60% of responses were "No, I would not be surprised" and 40% were "Yes, I would be surprised." A "No" response was associated with increased odds of death within 12 months in binary logistic regression (OR 4.8 [95% CI 2.1-11.1]).

Conclusions: The surprise question is a valuable tool for identifying older patients with higher risk of death, and it may be a useful screening criterion for older emergency general surgery patients who would benefit from palliative care evaluation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/jpm.2016.0313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385444PMC
April 2017

Distraction Osteogenesis Correction of Mandibular Ramis Fracture Malunion in a Juvenile Mute Swan ( Cygnus olor ).

J Avian Med Surg 2016 Mar;30(1):30-8

A juvenile mute swan (Cygnus olor) was presented with right lateral deviation of the mandible. Radiographs demonstrated a healed fracture of the right mandibular ramis, which had compromised osteogenesis. A corrective osteotomy was performed and an osteogenic distractor was inserted over the lateral aspect of the right mandible. Dental acrylic implants were fixed to the rhinotheca to correct rotational alignment. A pharyngostomy tube was placed to facilitate administration of nutrition and medication. Postoperative images confirmed correct alignment of the mandible in relation to the maxilla. Implants were removed and postoperative complications were not reported. This is the first report of an osteogenic distractor used to correct mandibular deviation in an avian species. Distraction osteogenesis should be considered as a valid surgical option in juvenile or adult avian patients with pathologic bone shortening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1647/2015-080DOI Listing
March 2016

Acutely deteriorated extravascular volume overload during peripheral blood stem cell mobilization in POEMS syndrome: A case series with cytokine analysis.

Transfus Apher Sci 2016 Apr 4;54(2):276-81. Epub 2015 Nov 4.

Department of Hematology, Chiba University Hospital, Chiba, Japan. Electronic address:

We describe two cases of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome patients with deteriorated extravascular volume overload without increased levels of vascular endothelial growth factor after the administration of cyclophosphamide + granulocyte colony-stimulating factor for stem cell mobilization. We then measured the serum levels of 27 cytokines from these cases using a multiplex suspension array system. The analysis revealed the changes of cytokine profiles before cyclophosphamide + granulocyte colony-stimulating factor and after the development of capillary leak symptoms in both cases. This may improve our current level of understanding of the pathogenesis of POEMS syndrome not driven by vascular endothelial growth factor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.transci.2015.10.016DOI Listing
April 2016

Transmembrane proteoglycans syndecan-2, 4, receptor candidates for the impact of HGF and FGF2 on semaphorin 3A expression in early-differentiated myoblasts.

Physiol Rep 2015 Sep;3(9)

Department of Animal and Marine Bioresource Sciences Kyushu University, Fukuoka, Japan

Regenerative mechanisms that regulate intramuscular motor innervation are thought to reside in the spatiotemporal expression of axon-guidance molecules. Our previous studies proposed an unexplored role of resident myogenic stem cell (satellite cell)-derived myoblasts as a key presenter of a secreted neural chemorepellent semaphorin 3A (Sema3A); hepatocyte growth factor (HGF) and basic fibroblast growth factor (FGF2) triggered its expression exclusively at the early differentiation phase. In order to advance this concept, the present study described that transmembrane heparan/chondroitin sulfate proteoglycans syndecan-2, 4 may be the plausible receptor candidates for HGF and FGF2 to signal Sema3A expression. Results showed that mRNA expression of syndecan-2, 4 was abundant (two magnitudes higher than syndecan-1, 3) in early-differentiated myoblasts and their in vitro knockdown diminished the HGF/FGF2-induced expression of Sema3A down to a baseline level. Pretreatment with heparitinase and chondroitinase ABC decreased the HGF and FGF2 responses, respectively, in non-knockdown cultures, supporting a possible model that HGF and FGF2 may bind to heparan and chondroitin sulfate chains of syndecan-2, 4 to signal Sema3A expression. The findings, therefore, extend our understanding that HGF/FGF2-syndecan-2, 4 association may stimulate a burst of Sema3A secretion by myoblasts recruited to the site of muscle injury; this would ensure a coordinated delay in the attachment of motoneuron terminals onto fibers early in muscle regeneration, and thus synchronize the recovery of muscle fiber integrity and the early resolution of inflammation after injury with reinnervation toward functional recovery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14814/phy2.12553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600393PMC
September 2015

Primary cerebral lymphomatoid granulomatosis progressing to methotrexate-associated lymphoproliferative disease under immunosuppressive therapy.

Intern Med 2015 15;54(5):503-7. Epub 2015 Jan 15.

Department of Hematology, Oami Municipal Hospital, Japan.

Lymphomatoid granulomatosis (LYG) is an angiocentric and angiodestructive lymphoproliferative disease involving extranodal sites. Although LYG cerebral lesions are usually located adjacent to LYG pulmonary lesions, few reports have described the occurrence of primary cerebral LYG. We herein discuss a case of a 40-year-old Japanese woman with primary cerebral LYG that caused various neurological symptoms for more than five years and progressed to methotrexate-associated lymphoproliferative disease under treatment with immunosuppressive therapy. This case suggests that primary cerebral LYG should be considered a lymphoid neoplasm manifesting as a primary brain tumor and a component of the differential diagnosis of chronic neuroinflammatory disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2169/internalmedicine.54.2399DOI Listing
August 2015
-->