Dynamic Temporal Change of Cerebral Microbleeds: Long-Term Follow-Up MRI Study

Background: Cerebral microbleeds (MBs) are understood as an important radiologic marker of intracerebral hemorrhage. We sought to investigate the temporal changes of MBs and clinical factors associated with the changes using long-term follow-up MRI. Methods/Principal Findings: From October 2002 to July 2006, we prospectively enrolled patients with stroke or transient ischemic attack, and followed-up their brain MRIs with an interval.12 mo. We compared demographic factors, vascular risk factors, laboratory findings, and radiologic factors according to the presence or changes of MBs. A total of 224 patients successfully completed the follow-up examinations (mean, 27 months). Newly developed MBs were noted in 10 patients (6.8%) among those without MBs at baseline (n = 148), and in those with MBs at baseline (n = 76), the MB count had decreased in 11 patients (14.5%), and increased in 41 patients (53.9%). The estimated annual rate of change of MB numbers was 0.80 lesions per year in all patients, a value which became greater in those patients who exhibited MBs at baseline (MBs$5, 5.43 lesions per year). Strokes due to small vessel occlusion and intracerebral hemorrhage, as well as white matter lesions were independently associated with an increased MB count, whereas the highest quartile of low-density lipoprotein (LDL) cholesterol was associated with a decreased MB count. Conclusion: During the follow-up period, most of MBs showed dynamic temporal change. Symptomatic or asymptomati

Clinical significance of preoperative serum vascular endothelial growth factor, interleukin-6, and C-reactive protein level in colorectal cancer

<p>Abstract</p> <p>Background</p> <p>Angiogenesis is a multistep process in which many growth factors and cytokines have an essential role. Vascular endothelial growth factor (VEGF) is a potent angiogenic agent that acts as a specific mitogen for vascular endothelial cells through specific cell surface receptors. The interleukin-6 (IL-6) pathway is another mechanism linking angiogenesis to malignancy. C-reactive protein (CRP), a representative marker for inflammation, is known for its association with disease progression in many cancer types. The aim of this study was to determine preoperative serum levels of VEGF, IL-6, and CRP in colorectal carcinoma, and to correlate them with disease status and prognosis.</p> <p>Methods</p> <p>A 132 of 143 patients who underwent curative resection for colorectal cancer were enrolled in this study. 11 patients with resection margin positive were excluded. Factors considered in analysis of the relationship between VEGF, IL-6, and CRP and histological findings. Patient prognosis was investigated. Serum levels of VEGF and IL-6 were assessed using Enzyme-Linked Immuno-Sorbent Assay (ELISA), and CRP was measured using immunoturbidimetry.</p> <p>Results</p> <p>Median follow-up duration was 18.53 months (range 0.73-43.17 months) and median age of the patients was 62 years (range, 26-83 years). Mean and median levels of VEGF and CRP in colorectal cancer were significantly higher than in the normal control group; 608 vs. 334 pg/mL and 528 (range 122-3242) vs. 312 (range 16-1121) (<it>p </it>< 0.001); 1.05 mg/dL vs. 0.43 mg/dL and 0.22 (range 0.00-18.40) vs. 0.07 (range 0.02-6.94) (<it>p </it>= 0.002), respectively. However mean and median level of IL-6 in patients were not significantly higher than in control; 14.33 pg/mL vs. 5.65 pg/mL and 6.00 (range 1.02-139.17) vs. 5.30 (4.50-13.78) (<it>p </it>= 0.327). Although IL-6 and CRP levels were not correlated with other pathological findings, VEGF level was significantly correlated with tumor size (<it>p </it>= 0.012) and CEA (<it>p </it>= 0.038). When we established the cutoff value for VEGF (825 pg/mL), IL-6 (8.09 pg/mL), and CRP (0.51 mg/dL) by Receiver Operating Characteristic (ROC) curve, we noted that high VEGF levels tended to reduce overall survival (<it>p </it>= 0.053), but not significantly. However, IL-6 and CRP demonstrated no significance with regard to disease free survival (<it>p </it>= 0.531, <it>p </it>= 0.701, respectively) and overall survival (<it>p </it>= 0.563, <it>p </it>= 0.572, respectively). Multivariate analysis showed that VEGF (<it>p </it>= 0.032), CEA (<it>p </it>= 0.012), lymph node metastasis (<it>p </it>= 0.002), and TNM stage (<it>p </it>= 0.025) were independently associated with overall survival.</p> <p>Conclusions</p> <p>Preoperative serum VEGF and CRP level increased in colorectal cancer patients. High VEGF level has been proposed as a poor prognostic factor for overall survival in patients with colorectal cancer.</p

Ultrasound-guided supraclavicular brachial plexus block in pediatric patients -A report of four cases-

Supraclavicular brachial plexus blocks are not common in pediatric patients due to the risk of pneumothorax. Ultrasonography is an important tool for identifying nerves during regional anesthesia. Directly visualizing the target nerves and monitoring the distribution of the local anesthetic are potentially significant. In addition, ultrasound monitoring helps avoid complications, such as inadvertent intravascular injection or pneumothorax. This paper reports four cases of pediatric patients who received ultrasound-guided supraclavicular brachial plexus block for upper limb surgery

Autoimmune Hemolytic Anemia in a Patient with Primary Ovarian Non-Hodgkin's Lymphoma

The primary ovarian lymphoma is a rare disease with poor prognosis. The incidence of autoimmune hemolytic anemia in patients with non-Hodgkin's lymphoma is estimated at 3%. However, a substantial portion of the previously reported cases of ovarian lymphoma actually represented ovarian involvement by more diffuse lymphomatous process. If stringent criteria are used for case selection, true primary ovarian lymphoma usually carries a favorable prognosis. We present a primary malignant lymphoma of ovary accompanied by autoimmune hemolytic anemia in a 29-yr-old patient. After ablative surgery, the hemoglobin level and the reticulocyte count were normalized. One year following surgery and chemotherapy, the patient is alive and disease free

Circulating endothelial progenitor cells as a new marker of endothelial dysfunction or repair in acute stroke

BACKGROUND AND PURPOSE: Understanding on distinct subsets of endothelial progenitor cells may provide insights of endothelial dysfunction or repair in the acute ischemic event. Recent in vitro data have reported the colony-forming unit (CFU) and outgrowth cell population as a subset of endothelial progenitor cells. In this study, we undertook to validate the significance of CFU number and outgrowth cell yield in acute stroke. METHODS: Mononuclear cells were isolated from the peripheral blood of 75 patients with acute stroke, 45 patients with chronic stroke, and 40 age-matched healthy volunteers. CFU numbers were counted after culturing them for 7 days, and outgrowth cell appearance was measured during the 2 months of culture. Endothelial progenitor cell function was also evaluated by matrigel plate assays. Independent parameters predicting CFU number and outgrowth cell yield were assessed using logistic regression analysis. RESULTS: The CFU numbers and tube formation abilities in matrigel assays were significantly reduced in patients with acute stroke compared with patients with chronic stroke or healthy control subjects. Moreover, patients with large artery atherosclerosis had much lower CFU numbers and functional activities than ones with cardioembolism. Outgrowth cells were isolated from 10% of healthy control subjects and 22% of patients with chronic stroke during the cultures, but from 71% of patients with stroke. Multivariate analysis identified glycosylated hemoglobin and National Institutes of Health Stroke Scale on admission as significant independent predictors of a low CFU number and a high isolation frequency of outgrowth cells, respectively. CONCLUSIONS: CFU number may thus represent an accumulated endothelial progenitor cell dysfunctional status, whereas outgrowth cell appearance may reflect the resilience of the systemic circulation to acute ischemic stress

Reduction of cycles of neoadjuvant chemotherapy for advanced epithelial ovarian, fallopian or primary peritoneal cancer (ROCOCO): study protocol for a phase III randomized controlled trial

Primary debulking surgery (PDS) and adjuvant chemotherapy is the standard treatment for advanced ovarian, fallopian or primary peritoneal cancer. However, neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) has been introduced as an alternative, showing similar efficacy and decreased postoperative complications compared with PDS. Although there is still no evidence for whether three or four cycles of NAC used clinically could be adequate, reducing one cycle of NAC is expected to remove more visible tumours and thereby improve prognosis. Thus, we proposed with this study to evaluate the efficacy and safety of reducing one cycle of NAC for advanced ovarian, fallopian or primary peritoneal cancer. This study is a prospective, multi-centre, open-label, randomized phase III trial. A total of 298 patients with advanced ovarian, fallopian or primary peritoneal cancer will be recruited and randomly assigned to either three (control group) or two cycles of NAC (experimental group). After the NAC, we will conduct IDS with maximal cytoreduction and then administer the remaining three or four cycles for a total of six cycles of adjuvant chemotherapy. The primary end point is progression-free survival, and the secondary end points are time to tumour progression, overall survival, tumour response after NAC, IDS and adjuvant chemotherapy, radiologic investigation after IDS, tumour response by positron emission tomography-computed tomography after NAC, quality of life, adverse events, success rate of optimal cytoreduction, surgical complexity, postoperative complications and safety of IDS. We will assess these factors at screening, at every cycle of chemotherapy, at IDS, after the completion of chemotherapy, every 3 months for the first 2 years after the planned treatment and every 6 months thereafter for 3 years. We hypothesize that reducing one cycle of NAC will contribute to more resection of visible tumours despite 10% reduction of optimal cytoreduction, which could improve survival. Moreover, two cycles of NAC may increase postoperative complications by 5% compared with three cycles, which may be acceptable. This study has been prospectively registered at ClinicalTrials.gov on Oct. 2nd, 2018 (NCT03693248, URL: https://clinicaltrials.gov/ct2/show/NCT03693248).Shin Poong. Pharm. Co., Ltd. plays no role in the study design, data collection, data analysis, data interpretation, or writing for the current study

Increased Circulating Endothelial Microparticles and Carotid Atherosclerosis in Obstructive Sleep Apnea

Background and Purpose Endothelial impairment is a linking mechanism between obstructive sleep apnea (USA) and cardiovascular diseases Profiles of endothelial micropanicles (EMPs) and endothelial progenitor cells (EPCs) reflect the degree of endothelial impairment The aims of this study were to measure the levels of EMI`s and progenitor cells in USA, determine the correlations between these factors and USA severity and the deuce of atherosclerosis, and document any changes in these factors after therapy Methods Subjects with (n=82) and without (n=22) OSA were recruited prospectively We measured the number of colony-forming units (CM) in cell cultuie as the endothelial progenitor cell index, and the number of EMPs using flow cytometry with CD31 [platelet endothelial cell adhesion molecule (PECAM)], CD42 (platelet glycoprotem), annexm V, and CD62E (E-selectin) antibodies at baseline and Act 4-6 weeks of continuous positive airway pressure (CPA P) therapy Carotid int ima-media thickness (IMT) was regarded as a marker of atherosclerosis Results The levels of PECAM(+)CD42(-) (p<0 001). PECAM(+)annexin V(+) (p<0 001), and E-selectin(+) micropamcles (p=0 001) were higher in USA subjects than in non-USA subjects The number of CRJ did not differ between the two groups OSA severity independently predicted the levels of PECAM(+)CD42(-) (p=0 02) and PECA(+)annexin V(+) (p=0 004) Carotid IMT was correlated with USA severity (p<0 001), PECAM(+)CD42: (p=0 03), and PECAM(+)annexin (p=0 01) Neither USA severity nor carotid IMT was correlated with either the number of CFI) or E-selectin(+) CPAP therapy decreased the occurrence of E-selecte (p<0 001) in 21 of the USA subjects, but had no effect on the other micioparticles of the number CFU Conclusions USA led to the overproduction of EMI`s, which moderately correlated with USA seventy and the degree of atherosclerosis, and partly responded to therapy The endothelial impairment might contribute to future cardiovascular events J Clin Neurol 2010;6`89-98This research was supported by the Stem Cell Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea (#SC4120).de Lima AMJ, 2010, RESPIRATION, V79, P370, DOI 10.1159/000227800Jung KH, 2009, ANN NEUROL, V66, P191, DOI 10.1002/ana.21681Ayers L, 2009, EUR RESPIR J, V33, P574, DOI 10.1183/09031936.00107408Akinnusi ME, 2009, AM J RESP CRIT CARE, V179, P328Christou K, 2009, SLEEP MED, V10, P87, DOI 10.1016/j.sleep.2007.10.011Barcelo A, 2008, THORAX, V63, P946, DOI 10.1136/thx.2007.093740Dorkova Z, 2008, CHEST, V134, P686, DOI 10.1378/chest.08-0556Robinson GV, 2008, THORAX, V63, P855, DOI 10.1136/thx.2007.088096Somers VK, 2008, CIRCULATION, V118, P1080, DOI 10.1161/CIRCULATIONAHA.107.189375Hirschi KK, 2008, ARTERIOSCL THROM VAS, V28, P1584, DOI 10.1161/ATVBAHA.107.155960Daniel L, 2008, NEPHROL DIAL TRANSPL, V23, P2129, DOI 10.1093/ndt/gfn029Martin K, 2008, LUNG, V186, P145, DOI 10.1007/s00408-008-9073-yAmabile N, 2008, AM J RESP CRIT CARE, V177, P1268, DOI 10.1164/rccm.200710-1458OCHeiss C, 2008, J AM COLL CARDIOL, V51, P1760, DOI 10.1016/j.jacc.2008.01.040Chu K, 2008, STROKE, V39, P1441, DOI 10.1161/STROKEAHA.107.499236Jelic S, 2008, CIRCULATION, V117, P2270, DOI 10.1161/CIRCULATIONAHA.107.741512Lee ST, 2008, NEUROLOGY, V70, P1510Bakouboula B, 2008, AM J RESP CRIT CARE, V177, P536, DOI 10.1164/rccm.200706-840OCLopez-Jimenez F, 2008, CHEST, V133, P793, DOI 10.1378/chest.07-0800de la Pena M, 2008, RESPIRATION, V76, P28, DOI 10.1159/000109643WON CHJ, 2008, P AM THORAC SOC, V5, P193Kloner RA, 2007, CIRCULATION, V116, P1306, DOI 10.1161/CIRCULATIONAHA.106.678375El Solh AA, 2007, AM J RESP CRIT CARE, V175, P1186, DOI 10.1164/rccm.200611-1598OCIBER C, 2007, AASM MANUAL SCORINGMONTSERRAT JM, 2007, AM J RESP CRIT CARE, V176, P6Pirro M, 2006, ARTERIOSCL THROM VAS, V26, P2530, DOI 10.1161/01.ATV.0000243941.72375.15Ryan S, 2006, AM J RESP CRIT CARE, V174, P824, DOI 10.1164/rccm.200601-066OCBoulanger CM, 2006, HYPERTENSION, V48, P180, DOI 10.1161/01.HYP.0000231507.00962.b5Arteaga RB, 2006, AM J CARDIOL, V98, P70, DOI 10.1016/j.amjcard.2006.01.054Robinson GV, 2006, EUR RESPIR J, V27, P1229, DOI 10.1183/09031936.06.00062805Werner N, 2005, NEW ENGL J MED, V353, P999Mezentsev A, 2005, AM J PHYSIOL-HEART C, V289, pH1106, DOI 10.1152/ajpheart.00265.2005Minoguchi K, 2005, AM J RESP CRIT CARE, V172, P625, DOI 10.1164/rccm.200412-1652OCMassa M, 2005, BLOOD, V105, P199, DOI 10.1182/blood-2004-05-1831Kim J, 2004, AM J RESP CRIT CARE, V170, P1108, DOI 10.1164/rccm.200404-519OCJy W, 2004, J THROMB HAEMOST, V2, P1842Tramontano AF, 2004, BIOCHEM BIOPH RES CO, V320, P34, DOI 10.1016/j.bbrc.2004.05.127Ip MSM, 2004, AM J RESP CRIT CARE, V169, P348, DOI 10.1164/rccm.200306.767OCBarba C, 2004, LANCET, V363, P157Bernal-Mizrachi L, 2003, AM HEART J, V145, P962, DOI 10.1016/S0002-8703(03)00103-0Jimenez JJ, 2003, THROMB RES, V109, P175, DOI 10.1016/S0049-3848(03)00064-1Hill JM, 2003, NEW ENGL J MED, V348, P593Preston RA, 2003, HYPERTENSION, V41, P211, DOI 10.1161/01.HYP.0000049760.15764.2DSabatier F, 2002, DIABETES, V51, P2840, DOI 10.2337/diabetes.51.9.2840El-Solh AA, 2002, CHEST, V121, P1541Boulanger CM, 2001, CIRCULATION, V104, P2649Barbe F, 2001, ANN INTERN MED, V134, P1015Chin K, 2000, AM J MED, V109, P562Lusis AJ, 2000, NATURE, V407, P233Ohga E, 1999, J APPL PHYSIOL, V87, P10YOUNG T, 1993, NEW ENGL J MED, V328, P1230JOHNS MW, 1991, SLEEP, V14, P540