Coil spring-powered pump with inertial microfluidic chip for size-based isolation and enrichment of biological cells.

Microfluidic chips have been widely used for in vitro diagnostics using pretreatment of biological samples; however, biologists and clinical researchers have difficulties using them in resource-limited settings. Sample injection systems for microfluidic chips are bulky, expensive, electricity-powered, and complex. A coiled spring-powered device, which can be used to isolate variously sized cells with high efficiency continuously and passively, was developed for portable, low-cost, electricity-free, and simple sample injection. The flow driving power was provided by releasing the compression spring in the mechanical syringe driver with a one-click action. In general, a syringe pump generates a stable passive flow rate. However, the syringe pumps are large in size and expensive because they have many functions such as infusion/withdrawal flow injection and the use of syringes of various sizes, allowing them to be applied in a variety of applications performed in the laboratory. In addition, it is not suitable for portable devices because of the considerable amount of electric power required. To overcome these drawbacks, we developed a device prototype that sorts different-sized particles and separates rare tumor cells or blood cells from blood with high efficiency. The performance of the coiled spring-powered device was evaluated and found to be comparable with that of syringe pump-powered devices. In situations where trained personnel cannot handle microfluidic chips for isolating circulating biomarkers (CTCs, WBCs, or plasma) from blood samples, the coiled spring-powered device can provide diagnostic tools, especially in resource-limited countries.

Spatial ensemble modeling for predicting the potential distribution of Lymantria dispar asiatica (Lepidoptera: Erebidae: Lymantriinae) in South Korea.

The spongy moth, Lymantria dispar, is a pest that damages various tree species throughout North America and Eurasia, has recently emerged in South Korea, threatening local forests and landscapes. The establishment of effective countermeasures against this species' outbreak requires predicting its potential distribution with climate change. In this study, we used species distribution models (CLIMEX and MaxEnt) to predict the potential distribution of the spongy moth and identify areas at risk of exposure to a sustained occurrence of the pest by constructing an ensemble map that simultaneously projected the outcomes of the two models. The results showed that the spongy moth could be distributed over the entire country under the current climate, but the number of suitable areas would decrease under a climate change scenario. This study is expected to provide basic data that can predict areas requiring intensive control and monitoring in advance with methodologically improved modeling technique.

Automatically Controlled Microfluidic System for Continuous Separation of Rare Bacteria from Blood.

Bloodstream infection by microorganisms is a major public health concern worldwide. Millions of people per year suffer from microbial infections, and current blood culture-based diagnostic methods are time-consuming because of the low concentration of infectious microorganisms in the bloodstream. In this study, we introduce an efficient automated microfluidic system for the continuous isolation of rare infectious bacteria (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa) from blood. Bacteria received a balanced force between a fluidic drag force and a periodically controlled dielectrophoretic (DEP) force from tilted electrodes to minimize cell adhesion to the electrodes, which prevented the loss of rare infectious bacteria. Target bacteria were efficiently segregated from the undesired blood cells to ensure that only the bacteria received the DEP force under the hypotonic condition, while the blood cells received no DEP force and exited the channel via a laminar flow. Thus, the bacteria were successfully extracted from the blood with a high recovery yield of 91.3%, and the limit of the bacteria concentration for isolation was 100 cfu/ml. We also developed an automated system that performed every step from blood-sample loading to application of electricity to the microfluidic chip for bacteria separation. It reduced the standard deviation of the bacteria recovery yield from 6.16 to 2.77 compared with the conventional batch process, providing stable bacteria-extraction performance and minimizing errors and bacteria loss caused by user mistakes. © 2019 International Society for Advancement of Cytometry.

Pretreatment Lymphopenia, Poor Performance Status, and Early Courses of Therapy Are Risk Factors for Severe Bacterial Infection in Patients with Multiple Myeloma during Treatment with Bortezomib-based Regimens.

The aim of this study was to identify the risk factors associated with severe bacterial infection (SBI) in multiple myeloma (MM) patients during treatment with bortezomib-based regimens. A total of 98 patients with MM were evaluated during 427 treatment courses. SBI occurred in 57.1% (56/98) of the patients and during 19.0% (81/427) of the treatment courses. In the multivariate analysis for the factors associated with the development of SBI in each treatment course, poor performance status (Eastern Cooperative Oncology Group ≥ 2, P < 0.001), early course of therapy (≤ 2 courses, P < 0.001), and pretreatment lymphopenia (absolute lymphocyte count < 1.0 × 10(9)/L, P = 0.043) were confirmed as independent risk factors. The probability of developing SBI were 5.1%, 14.9%, 23.9% and 59.5% in courses with 0, 1, 2, and 3 risk factors, respectively (P < 0.001). In conclusion, we identified three pretreatment risk factors associated with SBI in each course of bortezomib treatment. Therefore, MM patients with these risk factors should be more closely monitored for the development of SBI during bortezomib-based treatment.

Monoclonal and polyclonal gammopathy measured by serum free light chain and immunofixation subdivide the clinical outcomes of diffuse large B-cell lymphoma according to molecular classification.

Elevated serum free light chain (FLC) is known to be an adverse prognostic factor for diffuse large B-cell lymphoma (DLBCL). We hypothesized that monoclonal gammopathy (MG; elevated kappa [κ] or lambda [λ] FLC with an abnormal κ/λ ratio or a positive IF [immunofixation]) and polyclonal gammopathy (PG; elevated κ and/or λ FLC with a normal κ/λ ratio and a negative IF) would have different clinical outcome according to the molecular classification of DLBCL. In addition, MG would be a poor prognostic factor in patients with activated B-cell like type of DLBCL. Molecular classification of DLBCL, such as germinal center B-cell (GCB) type and non-GCB type, was performed according to the Hans algorithm. Among 175 newly diagnosed DLBCL patients, 96 (54.9 %) patients had an elevated FLC. MG and PG were observed in 34 and 68 patients, respectively. The 2-year overall survival (OS) and event-free survival (EFS) rates were 79.0 % and 71.6 %, respectively. In multivariate analysis, high-intermediate/high International Prognostic Index score and elevated FLC were significant for the OS (P = 0.002, P = 0.005, respectively) and EFS (P < 0.002, P = 0.010, respectively). MG and PG were also associated with inferior OS (P = 0.002, P = 0.011, respectively) and EFS (P = 0.002, P = 0.013, respectively). Ninety-six patients from a total 133 evaluable patients were classified to the non-GCB type. Patients with PG showed inferior clinical outcome for OS and EFS in patients with the GCB type (P = 0.006, P = 0.035, respectively). MG was a significant poor prognostic factor for OS and EFS in patients with the non-GCB type (P = 0.017, P = 0.004, respectively). MG was a poor prognostic maker in patients with the non-GCB type and PG was a poor prognostic indicator for the GCB type of DLBCL who were treated with R-CHOP.

Interobserver variability in the CT assessment of honeycombing in the lungs.

PURPOSE: To quantify observer agreement and analyze causes of disagreement in identifying honeycombing at chest computed tomography (CT). MATERIALS AND METHODS: The institutional review board approved this multiinstitutional HIPAA-compliant retrospective study, and informed patient consent was not required. Five core study members scored 80 CT images with a five-point scale (5 = definitely yes to 1 = definitely no) to establish a reference standard for the identification of honeycombing. Forty-three observers from various subspecialties and geographic regions scored the CT images by using the same scoring system. Weighted κ values of honeycombing scores compared with the reference standard were analyzed to investigate intergroup differences. Images were divided into four groups to allow analysis of imaging features of cases in which there was disagreement: agreement on the presence of honeycombing, agreement on the absence of honeycombing, disagreement on the presence of honeycombing, and other (none of the preceding three groups applied). RESULTS: Agreement of scores of honeycombing presence by 43 observers with the reference standard was moderate (Cohen weighted κ values: 0.40-0.58). There were no significant differences in κ values among groups defined by either subspecialty or geographic region (Tukey-Kramer test, P = .38 to >.99). In 29% of cases, there was disagreement on identification of honeycombing. These cases included honeycombing mixed with traction bronchiectasis, large cysts, and superimposed pulmonary emphysema. CONCLUSION: Identification of honeycombing at CT is subjective, and disagreement is largely caused by conditions that mimic honeycombing.

Quantitative assessment of change in regional disease patterns on serial HRCT of fibrotic interstitial pneumonia with texture-based automated quantification system.

OBJECTIVES: To evaluate the usefulness of a texture-based automated quantification system (AQS) for evaluating the extent and interval change of regional disease patterns on initial and follow-up high-resolution computed tomographies (HRCTs) of fibrotic interstitial pneumonia (FIP). METHODS: Eighty-nine patients with clinically and/or biopsy confirmed usual interstitial pneumonia (UIP) (n = 71) and non-specific interstitial pneumonia (NSIP) (n = 18) were included. An AQS to quantify five disease patterns (ground-glass opacity [GGO], reticular opacity [RO], honeycombing [HC], emphysema [EMPH], consolidation [CONS]) and normal lung was developed. The extent and interval changes of each disease pattern, FS (fibrosis score), TA (total abnormal lung fraction) of entire lung on initial and 1-year follow-up HRCTs were quantified. The agreement between the results of AQS and two readers was assessed. Results of AQS were correlated with forced vital capacity (FVC) and carbon monoxide diffusing capacity (DLco). RESULTS: The Intraclass correlation coefficient (ICC) study revealed acceptable agreement between visual assessment and AQS (r = 0.78, 0.66 for HC; 0.76, 0.61 for FS; 0.64, 0.68 for TA, initial and follow-up HRCTs, respectively). Linear regression analysis revealed the extent of HC, TA on initial CT, interval changes of FS contributed negatively to DLco, and interval changes of FS, TA contributed negatively to FVC. CONCLUSIONS: Our AQS is comparable with visual assessment for evaluating the disease extent and the interval changes of FIP on HRCT.

Influence of Root Color and Tissue on Phytochemical Contents and Antioxidant Activities in Carrot Genotypes.

This study monitored changes in major carotenoids (lutein, ⍺-carotene, and ß-carotene), free sugars (fructose, glucose, and sucrose), ascorbic acid, vitamin E, phytosterols (campesterol, stigmasterol, and ß-sitosterol), fatty acid composition, total phenol content (TPC), total flavonoid content (TFC), total anthocyanin content, and antioxidant activities (AA); ferric-reducing antioxidant power (FRAP) and 2,2'-azino-bis (3-ethylbenzothiazoline-6sulfonic acid) [ABTS] assays, in the inner and outer root tissues of nine carrot genotypes with orange, white, and purple roots. The results showed a differential accumulation of bioactive compounds and antioxidant activities depending on root tissue and color. Carotenoids, free sugars, and total phytosterol contents were higher in genotypes with orange roots than in other genotypes. Ascorbic acid, TPC, TFC, total anthocyanin, and AA were highest in purple-colored carrots while vitamin E content was higher in white/purple carrots. Root color was highly related to the accumulation of individual carotenoids, vitamin E isomers, and total anthocyanin content most prominently among the analyzed bioactive compounds and AA. Free sugar and carotenoid contents were relatively higher in outer tissues than in inner tissues. Furthermore, ascorbic acid, TPC, TFC, and AA were statistically higher or similar in outer tissues when compared to inner tissues in all genotypes. In contrast, trends in vitamin E and phytosterol content were inconsistent between the inner and outer tissues, depending on the genotype. Although fatty acid composition was affected by both root color and tissue, the results were not significant. Thus, the phytochemical profile and content were highly dependent on root color and tissue in carrot genotypes. This may be useful in the food processing and pharmaceutical industries for the extraction of targeted bioactive compounds.

Evaluation of computer-aided detection and dual energy software in detection of peripheral pulmonary embolism on dual-energy pulmonary CT angiography.

PURPOSE: To evaluate the sensitivity of computer-aided detection(CAD) and dual-energy software('Lung PBV', 'Lung Vessels') for detecting peripheral pulmonary embolism(PE). MATERIALS AND METHODS: Between Jan-2007 and Jan-2008, 309 patients underwent dual-energy CT angiography(DECTA) for the evaluation of suspected PE. Among them, 37 patients were retrospectively selected; 21 with PE at segmental-or-below levels and 16 without PE according to clinical reports. A standard computer assisted detection (CAD) package and two new types of software('Lung PBV', 'Lung Vessels') were applied on a dedicated workstation. This resulted in four alternative tests for detecting PE: DECTA alone and DECTA with CAD, 'Lung Vessels' and 'Lung PBV'. Two radiologists independently read all cases at different reading sessions. Two thoracic radiologists set the reference standard by combining all information from DECTA and software. The sensitivity of detection for all, segmental and subsegmental-or-below PE were assessed. RESULTS: The reference standard contained 136 PE(segmental 65, subsegmental-or-below 71). With DECTA alone, the sensitivity of detection for all, segmental and subsegmental-or-below pulmonary arteries was 54.5%/73.7%/34.4%; DECTA with CAD, 57.8%/76.8%/37.9%; DECTA with 'Lung PBV', 61.1%/79.9%/41.4%; DECTA with 'Lung Vessels', 64.0%/78.3%/48.5% respectively. CONCLUSION: The use of CAD, Lung Vessels and Lung PBV shows improved capability to detect peripheral PE.

Effect of leukopenia induced by cyclophosphamide on the initial stage of arterial thrombosis in mice.

INTRODUCTION: Leukocytes are found in organizing thrombi and are associated with thrombus growth. However, their role in the initial stage of thrombus formation is not well known. We investigated the role of leukocytes in the early stage of arterial thrombosis by inducing leukopenia. METHODS: In this double-blind, randomized, placebo-controlled study, 72 Institute of Cancer Research mice were randomly treated with intraperitoneal 100 mg/kg cyclophosphamide or normal saline. The primary outcome was time to occlusion after FeCl3 treatment. We also compared thrombus size, histological composition, and association with peripheral blood cell counts between cyclophosphamide and control groups. RESULTS: Cyclophosphamide treatment significantly decreased leukocyte counts by 82.8% compared to placebo (P < 0.001). The time to occlusion was significantly longer in the cyclophosphamide group (3.31 ± 1.59 min) than in the control group (2.30 ± 1.14 min; P = 0.003). The immunoreactivity for Ly6G-positive cells, intracellular histone H3, and released histone H3 in thrombi was significantly reduced in the cyclophosphamide group by 92.8%, 50.2%, and 34.3%, respectively. Time to occlusion had a moderate negative correlation with leukocyte count in peripheral blood (r = -0.326, P = 0.022) in the entire group. CONCLUSIONS: Cyclophosphamide-induced leukopenia attenuated thrombus formation during the early stage of arterial thrombosis. Our findings suggest the potential role of leukocytes in the initial stage of arterial thrombosis.

Slope of emphysema index: an objective descriptor of regional heterogeneity of emphysema and an independent determinant of pulmonary function.

OBJECTIVE: The purpose of this study was to compare quantitative and visual assessments of regional heterogeneity of emphysema and to investigate the influence of regional heterogeneity on pulmonary function in smoking-related emphysema. MATERIALS AND METHODS: We developed an automatic computerized algorithm to quantitatively assess heterogeneity in the upper-lower, anterior-posterior, and central-peripheral directions. The emphysema index was plotted with a linear function (emphysema index slopes: slope of emphysema index in upper-lower direction, slope of emphysema index in anterior-posterior direction, and slope of emphysema index in central-peripheral direction) for consecutive 1-pixel-thick slices using volumetric CT data of 59 patients (58 men and one woman; mean age, 65.7 years). Emphysema index was defined as the percentage area of lung with attenuation values below -950 HU. Visual assessment was performed using a 5-point scoring system. Quantitative and visual assessments were compared. Multiple linear regression was performed to evaluate the influence of emphysema index and emphysema index slopes on the pulmonary function test. RESULTS: Quantitative and visual assessments were significantly correlated in both upper-lower (r(2) = 0.40 and r(2) = 0.67 for observers 1 and 2, respectively) and central-peripheral (r(2) = 0.51 and r(2) = 0.47, respectively) directions. Multiple linear regression revealed that emphysema index, slope of emphysema index in upper-lower direction, and slope of emphysema index in anterior-posterior direction were independent determinants of forced expiratory volume in 1 second (FEV(1)) (r(2) = 0.30; p < 0.001). Emphysema index and slope of emphysema index in upper-lower direction were independent determinants of the ratio of FEV(1) to forced vital capacity (FEV(1)/FVC) (r(2) = 0.32; p < 0.001). In addition to higher emphysema index, lower and posterior lung dominance was associated with a decrease in FEV(1) and FEV(1)/FVC. CONCLUSION: Computerized, quantitative assessment using the emphysema index slope is comparable to visual assessment in the evaluation of regional heterogeneity of emphysema. In addition to the emphysema index, regional heterogeneity of smoking-related emphysema contributes to impairment of pulmonary function.

Agranular platelets as a cardinal feature of ARC syndrome.

We aimed to describe abnormal platelet morphology and its clinical significance in infants who were diagnosed with arthrogryposis renal dysfunction and cholestasis (ARC) syndrome. We collected all of the cases of ARC syndrome referred to a single pediatric referral center. In all patients, platelet counts and analysis of platelet morphology were performed with peripheral blood smear specimens. Electron microscopy images were obtained to examine the ultrastructure of the platelets. Over the 12-year period, 12 cases of ARC syndrome were identified. The sex ratio (male:female) was 1:1. The median birth weight was 3.15 kg (range, 2.3 to 3.8 kg). Failure to thrive was observed in all the patients. The major cause of death was recurrent febrile illness and pneumonia. The median age at death was 8.9 months (range, 2.6 to 28.8 kg). Their median body weight at death was 3.1 kg (range, 2.6 to 6.0 kg). Close examination of their peripheral blood smear (n=11) specimens showed large, pale, agranular platelets similar to those seen in gray platelet syndrome. Electron microscopic images of the platelets (n=7) revealed a lack of alpha; granules. Agranular platelets are a common finding in ARC syndrome. Agranular platelets should be considered as a cardinal feature of ARC syndrome and can be useful as a noninvasive diagnostic marker for ARC syndrome.

Cancer cell-induced neutrophil extracellular traps promote both hypercoagulability and cancer progression.

INTRODUCTION: Neutrophils can generate extracellular net-like structures by releasing their DNA-histone complexes and antimicrobial peptides, which is called neutrophil extracellular traps (NETs). Various stimuli can induce NET formation. In particular, neutrophils and NET formation are abundant in tumor tissue. This study investigated how cancer cells induce NET formation and whether this NET formation promotes plasma thrombin generation and cancer progression. METHODS: Induction of NET formation by a pancreatic cancer cell line (AsPC-1) was assessed by measuring the histone-DNA complex level. The endogenous thrombin potential (ETP) was measured by thrombin generation assay. In vitro migration, invasion, and tubule formation assays were performed. The circulating levels of NET markers and hypercoagulability markers were assessed in 62 patients with pancreatobiliary malignancy and 30 healthy controls. RESULTS: AsPC-1 significantly induced NET formation in a dose-dependent manner. Conditioned medium (CM) from AsPC-1 also induced NETs. Interestingly, NET-formation was abolished by heat-inactivated CM, but not by lipid-extracted CM, suggesting an important role of protein components. A reactive oxygen species inhibitor did not inhibit cancer cell-induced NET formation, but prostaglandin E1 (PGE1, cyclic adenosine monophosphate inducer) and antithrombin did. NETs significantly increased ETP of normal plasma. Of note, NETs promoted cancer cell migration and invasion as well as angiogenesis, which were inhibited by histone-binding agents (heparin, polysialic acid), a DNA-degrading enzyme, and Toll-like receptor neutralizing antibodies. In patients with pancreatobiliary malignancy, elevated NET markers correlated well with hypercoagulability makers. CONCLUSION: Our findings indicate that cancer cell-induced NET formation enhances both hypercoagulability and cancer progression and suggest that inhibitors of NET formation such as PGE1 and antithrombin can be potential therapeutics to reduce both hypercoagulability and cancer progression.

Inter-observer agreement in identifying traction bronchiectasis on computed tomography: its improvement with the use of the additional criteria for chronic fibrosing interstitial pneumonia.

PURPOSE: To assess inter-observer variability in identifying traction bronchiectasis on computed tomography (CT) using additional criteria for chronic fibrosing interstitial pneumonia. METHODS: Seven experts categorized CT image set representing 39 patients into three groups on the basis of the presence of traction bronchiectasis, using a three-point scale: 3-definitely/probably yes; 2-possibly yes; and 1-definitely/probably no. This scale served as a reference standard. The image set included cases of chronic fibrosing interstitial pneumonia, non-interstitial lung disease, and difficult-to-determine cases. Forty-eight observers similarly assessed the same image set, first according to the Fleischner Society definition, and second with additional criteria, in which traction bronchiectasis was observed exclusively in chronic fibrosing interstitial pneumonia. The agreement level between the reference standard and each observer's evaluation in each session was calculated using weighted kappa values which were compared between the two sessions using a paired t test. RESULTS: The mean weighted kappa value for all observers was significantly higher in the second reading session (mean 0.75) than in the first reading session (mean 0.62) (p < 0.001). CONCLUSION: Inter-observer agreement in identifying traction bronchiectasis improves when using the additional criteria which specify chronic fibrosing interstitial pneumonia as the underlying disease.

Clinical utility of dual-energy CT in the evaluation of solitary pulmonary nodules: initial experience.

PURPOSE: To determine the clinical utility of dual-energy computed tomography (CT) in evaluating solitary pulmonary nodules (SPNs). MATERIALS AND METHODS: This study was approved by the institutional review board, and informed consent was obtained. CT scans were obtained before and 3 minutes after contrast material injection in 49 patients (26 men, 23 women; mean age, 60.39 years +/- 12.24 [standard deviation]) by using a scanner with a dual-energy technique. Image sets that included nonenhanced weighted average, enhanced weighted average, virtual nonenhanced, and iodine-enhanced images were reconstructed. CT numbers of SPNs on virtual nonenhanced and nonenhanced weighted average images were compared, and CT numbers on iodine-enhanced image and the degree of enhancement were compared. Diagnostic accuracy for malignancy by using CT number on iodine-enhanced image and the degree of enhancement were compared. On the virtual nonenhanced image, the number and size of calcifications were compared with those on the nonenhanced weighted average image. Radiation dose was compared with that of single-energy CT. RESULTS: CT numbers on virtual nonenhanced and nonenhanced weighted average images and CT numbers on the iodine-enhanced image and the degree of enhancement showed good agreements (intraclass correlation coefficients: 0.83 and 0.91, respectively). Diagnostic accuracy for malignancy by using CT numbers on iodine-enhanced image was comparable to that by using the degree of enhancement (sensitivity, 92% and 72%; specificity, 70% and 70%; accuracy, 82.2% and 71.1%, respectively). On virtual nonenhanced image, 85.0% (17 of 20) of calcifications in the SPN and 97.8% (44 of 45) of calcifications in the lymph nodes were detected, and the apparent sizes were smaller than those on the nonenhanced weighted average image. Radiation dose (average dose-length product, 240.77 mGy cm) was not significantly different from that of single-energy CT (P = .67). CONCLUSION: Dual-energy CT allows measurement of the degree of enhancement and detection of calcifications without additional radiation dose.

Digital tomosynthesis of the chest for lung nodule detection: interim sensitivity results from an ongoing NIH-sponsored trial.

The authors report interim clinical results from an ongoing NIH-sponsored trial to evaluate digital chest tomosynthesis for improving detectability of small lung nodules. Twenty-one patients undergoing computed tomography (CT) to follow up lung nodules were consented and enrolled to receive an additional digital PA chest radiograph and digital tomosynthesis exam. Tomosynthesis was performed with a commercial CsI/a-Si flat-panel detector and a custom-built tube mover. Seventy-one images were acquired in 11 s, reconstructed with the matrix inversion tomosynthesis algorithm at 5-mm plane spacing, and then averaged (seven planes) to reduce noise and low-contrast artifacts. Total exposure for tomosynthesis imaging was equivalent to that of 11 digital PA radiographs (comparable to a typical screen-film lateral radiograph or two digital lateral radiographs). CT scans (1.25-mm section thickness) were reviewed to confirm presence and location of nodules. Three chest radiologists independently reviewed tomosynthesis images and PA chest radiographs to confirm visualization of nodules identified by CT. Nodules were scored as: definitely visible, uncertain, or not visible. 175 nodules (diameter range 3.5-25.5 mm) were seen by CT and grouped according to size: < 5, 5-10, and > 10 mm. When considering as true positives only nodules that were scored definitely visible, sensitivities for all nodules by tomosynthesis and PA radiography were 70% (+/- 5%) and 22% (+/- 4%), respectively, (p < 0.0001). Digital tomosynthesis showed significantly improved sensitivity of detection of known small lung nodules in all three size groups, when compared to PA chest radiography.

Radiologic and clinical findings of Behçet disease: comprehensive review of multisystemic involvement.

Behçet disease is a chronic, relapsing, systemic disorder of unknown etiology, characterized by recurrent oral and genital ulcers, uveitis, and other clinical manifestations in multiple organ systems. Although the diagnosis is made on the basis of the combination of typical clinical symptoms, radiologic findings of Behçet disease show characteristic features of its involvement in the gastrointestinal, neurologic, cardiovascular, and thoracic organ systems. In the gastrointestinal tract, Behçet disease may produce various types of ulcers in the esophagus, stomach, and small and large intestines, as well as deeply penetrating ulcerations in the ileocecal region, with frequently accompanying enteric fistulas. Neurologic involvement includes typical and atypical parenchymal neurobehcet disease, dural sinus thrombosis, cerebral arterial aneurysm, occlusion, dissection, and meningitis. Vascular involvement is divided into three subsets including venous occlusion, arterial occlusion, and arterial aneurysm. Cardiac manifestations include intracardiac thrombus, endomyocardial fibrosis, periaortic pseudoaneurysm, and rupture of the sinus of Valsalva. Manifestations of Behçet disease in the thorax include pulmonary arterial aneurysm, pulmonary arterial thromboembolism, thrombosis in the superior vena cava, pulmonary infarction, hemorrhage, and vasculitis of the pleura and pericardium. These various manifestations of Behçet disease respond to steroid treatment; however, one of the characteristics of Behçet disease is the high rate of complications and recurrence after surgery. Familiarity with its various radiologic and clinical characteristics is essential in making an accurate early diagnosis and for prompt treatment of patients with Behçet disease.

Transfusion-associated iron overload as an adverse risk factor for transplantation outcome in patients undergoing reduced-intensity stem cell transplantation for myeloid malignancies.

Transfusion-associated iron overload could be an important risk factor in myeloablative hematopoietic stem cell transplantation. However, few studies have evaluated the effect of iron overload in reduced-intensity stem cell transplantation (RIST). We evaluated 38 patients with myeloid malignancies, 16 with and 22 without iron overload, who received RIST. We used pretransplant serum ferritin as a marker of iron overload. There was a positive correlation between the number of transfused packed red blood cells and pretransplant serum ferritin levels (21.5 units and 1,578.7 microg/l in the iron overload group vs. 12 units and 739.3 microg/l in the iron non-overload group; p <0.01). Engraftment day and chimerism analysis were not affected by iron overload (p = 0.71 and 0.47, respectively). There were no differences in treatment-related mortality (p = 0.94), veno-occlusive disease (p = 0.99), acute and chronic graft versus host disease (p = 0.58 and 0.99, respectively) according to iron overload. There was a significant difference in disease-free and overall survival (35.8 and 27% in the iron overload group vs. 80.6 and 54.6% in the iron non-overload group; p = 0.01 and 0.03, respectively). We conclude that transfusion-associated iron overload is an adverse risk factor in RIST for myeloid malignancies. The clinical outcomes according to iron overload in RIST were different in myeloablative hematopoietic stem cell transplantation. A serial follow-up of serum ferritin level and judicious iron chelation therapy will be needed to manage the side effect of iron overload in RIST and improve transplantation outcomes.

Analysis of clinical presentations of Bruton disease: a review of 20 years of accumulated data from pediatric patients at Severance Hospital.

PURPOSE: X-linked agammaglobulinemia (XLA) is a humoral immunodeficiency disease caused by a mutation in the Bruton tyrosine kinase (BTK) gene resulting in defective B cell differentiation. Because it is a relatively rare disorder, it is difficult for clinicians to have a comprehensive understanding of XLA due to a lack of exposure to the disease. Clinical presentations of patients with XLA were analyzed and discussed to improve care plans. MATERIALS AND METHODS: During a 20 year period, from January 1987 to June 2006, a total of 19 patients were diagnosed as XLA in the Department of Pediatrics at Severance Hospital, Seoul, Korea. A retrospective analysis of the clinical presentations of those patients was performed. RESULTS: The mean age of the XLA patients included in the study was 4.89 years, with a range of 6 months to 13 years. Twelve patients were diagnosed before age 5, while the other 7 patients were diagnosed after age 5. Recurrent infections observed in the patients included pneumonia, acute otitis media, septic arthritis, skin infection, sepsis, sinusitis, acute gastroenteritis, cervical lymphadenitis, epididymitis, meningitis, osteomyelitis, urinary tract infection and encephalitis. Frequency of admissions was variable from 0 to 12 times, depending on the time at which immunoglobulin therapy was started. Six cases had family histories positive for XLA. BTK gene mutations were found in 8 cases. CONCLUSION: The overall prognosis of XLA is good as long as patients are diagnosed and treated early with regular intra venous gamma globulin therapy before the sequelae of recurrent infections appear.