Accuracy of circulating histones in predicting persistent organ failure and mortality in patients with acute pancreatitis.

BACKGROUND: Early prediction of acute pancreatitis severity remains a challenge. Circulating levels of histones are raised early in mouse models and correlate with disease severity. It was hypothesized that circulating histones predict persistent organ failure in patients with acute pancreatitis. METHODS: Consecutive patients with acute pancreatitis fulfilling inclusion criteria admitted to Royal Liverpool University Hospital were enrolled prospectively between June 2010 and March 2014. Blood samples were obtained within 48 h of abdominal pain onset and relevant clinical data during the hospital stay were collected. Healthy volunteers were enrolled as controls. The primary endpoint was occurrence of persistent organ failure. The predictive values of circulating histones, clinical scores and other biomarkers were determined. RESULTS: Among 236 patients with acute pancreatitis, there were 156 (66·1 per cent), 57 (24·2 per cent) and 23 (9·7 per cent) with mild, moderate and severe disease respectively, according to the revised Atlanta classification. Forty-seven healthy volunteers were included. The area under the receiver operating characteristic (ROC) curve (AUC) for circulating histones in predicting persistent organ failure and mortality was 0·92 (95 per cent c.i. 0·85 to 0·99) and 0·96 (0·92 to 1·00) respectively; histones were at least as accurate as clinical scores or biochemical markers. For infected pancreatic necrosis and/or sepsis, the AUC was 0·78 (0·62 to 0·94). Histones did not predict or correlate with local pancreatic complications, but correlated negatively with leucocyte cell viability (r = -0·511, P = 0·001). CONCLUSION: Quantitative assessment of circulating histones in plasma within 48 h of abdominal pain onset can predict persistent organ failure and mortality in patients with acute pancreatitis. Early death of immune cells may contribute to raised circulating histone levels in acute pancreatitis.

Non-malignant haematology research in the UK: looking forward to new opportunities.

Over the last few years there has been rapid and radical change in the way clinical research in the UK is funded and supported within the NHS. This has resulted from restructuring and major new investment in research infrastructure, co-ordinated through Clinical Local Research Networks (CLRNs) and equivalent organisations in the devolved nations. CLRNs have resources to support local researchers undertake studies that have been adopted on to the national research portfolio. For example, CLRNs can help with gaining local approvals or provide research nurses to recruit patients, undertake study procedures and perform data entry. CLRNs can establish Local Speciality Groups in a number of areas of medicine, including nonmalignant haematology. These new networks offer non-malignant haematology access to significant new resources and a major opportunity to support clinical research for the benefit of our patients.

MRS as an Aid to Diagnose Malignant Transformation in Low-Grade Gliomas with Increasing Contrast Enhancement.

BACKGROUND AND PURPOSE: Increased contrast enhancement has been used as a marker of malignant transformation in low-grade gliomas. This marker has been found to have limited accuracy because many low-grade gliomas with increased contrast enhancement remain grade II. We aimed to investigate whether MR spectroscopy can contribute to the diagnosis of malignant transformation in low-grade gliomas with increased contrast enhancement. MATERIALS AND METHODS: Patients with low-grade gliomas who had contemporaneous MR spectroscopy and histopathology for tumor regions with increased contrast enhancement between 2004 and 2015 were retrospectively reviewed. Clinical data collected were sex and age, Karnofsky Performance Scale, histologic subtypes, isocitrate dehydrogenase 1 mutation status, disease duration, adjuvant therapy, and post-radiation therapy duration. Imaging data collected were contrast-enhancement size, whole-tumor size, MR spectroscopy metabolite ratios, and tumor grades of regions with increased contrast enhancement. Diagnostic values of these factors on malignant transformation of low-grade gliomas were statistically analyzed. RESULTS: A total of 86 patients with 96 MR spectroscopy studies were included. Tumor grades associated with increased contrast enhancement were grade II (n = 42), grade III (n = 27), and grade IV (n = 27). On multivariate analysis, the NAA/Cho ratio was the only significant factor (P < .001; OR, 7.1; 95% CI, 3.2-16.1) diagnostic of malignant transformation. With 0.222 as the cutoff value, the sensitivity, specificity, and accuracy of NAA/Cho for diagnosing malignant transformation were 94.4%, 83.3%, and 89.6%, respectively. CONCLUSIONS: MR spectroscopy complements conventional MR imaging in the diagnosis of malignant transformation in a subgroup of low-grade gliomas with increased contrast enhancement.

Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology.

The diagnosis of disseminated intravascular coagulation (DIC) should encompass both clinical and laboratory information. The International Society for Thrombosis and Haemostasis (ISTH) DIC scoring system provides objective measurement of DIC. Where DIC is present the scoring system correlates with key clinical observations and outcomes. It is important to repeat the tests to monitor the dynamically changing scenario based on laboratory results and clinical observations. The cornerstone of the treatment of DIC is treatment of the underlying condition. Transfusion of platelets or plasma (components) in patients with DIC should not primarily be based on laboratory results and should in general be reserved for patients who present with bleeding. In patients with DIC and bleeding or at high risk of bleeding (e.g. postoperative patients or patients due to undergo an invasive procedure) and a platelet count of <50 x 10(9)/l transfusion of platelets should be considered. In non-bleeding patients with DIC, prophylactic platelet transfusion is not given unless it is perceived that there is a high risk of bleeding. In bleeding patients with DIC and prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), administration of fresh frozen plasma (FFP) may be useful. It should not be instituted based on laboratory tests alone but should be considered in those with active bleeding and in those requiring an invasive procedure. There is no evidence that infusion of plasma stimulates the ongoing activation of coagulation. If transfusion of FFP is not possible in patients with bleeding because of fluid overload, consider using factor concentrates such as prothrombin complex concentrate, recognising that these will only partially correct the defect because they contain only selected factors, whereas in DIC there is a global deficiency of coagulation factors. Severe hypofibrinogenaemia (<1 g/l) that persists despite FFP replacement may be treated with fibrinogen concentrate or cryoprecipitate. In cases of DIC where thrombosis predominates, such as arterial or venous thromboembolism, severe purpura fulminans associated with acral ischemia or vascular skin infarction, therapeutic doses of heparin should be considered. In these patients where there is perceived to be a co-existing high risk of bleeding there may be benefits in using continuous infusion unfractionated heparin (UFH) due to its short half-life and reversibility. Weight adjusted doses (e.g. 10 mu/kg/h) may be used without the intention of prolonging the APTT ratio to 1.5-2.5 times the control. Monitoring the APTT in these cases may be complicated and clinical observation for signs of bleeding is important. In critically ill, non-bleeding patients with DIC, prophylaxis for venous thromboembolism with prophylactic doses of heparin or low molecular weight heparin is recommended. Consider treating patients with severe sepsis and DIC with recombinant human activated protein C (continuous infusion, 24 microg/kg/h for 4 d). Patients at high risk of bleeding should not be given recombinant human activated protein C. Current manufacturers guidance advises against using this product in patients with platelet counts of <30 x 10(9)/l. In the event of invasive procedures, administration of recombinant human activated protein C should be discontinued shortly before the intervention (elimination half-life approximately 20 min) and may be resumed a few hours later, dependent on the clinical situation. In the absence of further prospective evidence from randomised controlled trials confirming a beneficial effect of antithrombin concentrate on clinically relevant endpoints in patients with DIC and not receiving heparin, administration of antithrombin cannot be recommended. In general, patients with DIC should not be treated with antifibrinolytic agents. Patients with DIC that is characterised by a primary hyperfibrinolytic state and who present with severe bleeding could be treated with lysine analogues, such as tranexamic acid (e.g. 1 g every 8 h).

Combined hepatocellular cholangiocarcinoma: prognostic factors investigated by computed tomography/magnetic resonance imaging.

This study was designed to assess the clinical usefulness of imaging for predicting the prognosis of patients with combined hepatocellular cholangiocarcinoma (cHCC-CC). Between 1999 and 2004, 30 patients with histopathologically proven cHCC-CC underwent computed tomography (CT) or magnetic resonance imaging (MRI). The imaging data and survival were analysed. Univariate log-rank analysis of imaging findings revealed that tumour necrosis, bile duct invasion, major vascular branch invasion, multiplicity, bilobar distribution, regional lymph node involvement, regional organ invasion, distant metastasis and ascites had adverse influences on overall survival. Multivariate Cox proportional hazard analysis demonstrated that major vascular branch invasion, regional organ invasion, nodal and distant metastases were independent prognostic factors that adversely affected overall survival rates. Overall cumulative survival rates at 1, 3 and 5 years were 53%, 26% and 12%, respectively. Analysing the survival of our patients by using clinical stages of the newly updated American Joint Committee on Cancer (AJCC) classification for liver neoplasm based on the imaging findings, we found significant differences between stages I/II and III (p < 0.001) and between stages III and IV (p = 0.040). We conclude CT or MRI can be used to identify the prognostic factors and to estimate the outcomes of patients with cHCC-CC.

Early-Stage Glioblastomas: MR Imaging-Based Classification and Imaging Evidence of Progressive Growth.

BACKGROUND AND PURPOSE: The serial imaging changes describing the growth of glioblastomas from small to large tumors are seldom reported. Our aim was to classify the imaging patterns of early-stage glioblastomas and to define the order of appearance of different imaging patterns that occur during the growth of small glioblastomas. MATERIALS AND METHODS: Medical records and preoperative MR imaging studies of patients diagnosed with glioblastoma between 2006 and 2013 were reviewed. Patients were included if their MR imaging studies showed early-stage glioblastomas, defined as small MR imaging lesions detected early in the course of the disease, demonstrating abnormal signal intensity but the absence of classic imaging findings of glioblastoma. Each lesion was reviewed by 2 neuroradiologists independently for location, signal intensity, involvement of GM and/or WM, and contrast-enhancement pattern on MR imaging. RESULTS: Twenty-six patients with 31 preoperative MR imaging studies met the inclusion criteria. Early-stage glioblastomas were classified into 3 types and were all hyperintense on FLAIR/T2-weighted images. Type I lesions predominantly involved cortical GM (n = 3). Type II (n = 12) and III (n = 16) lesions involved both cortical GM and subcortical WM. Focal contrast enhancement was present only in type III lesions at the gray-white junction. Interobserver agreement was excellent (κ = 0.95; P < .001) for lesion-type classification. Transformations of lesions from type I to type II and type II to type III were observed on follow-up MR imaging studies. The early-stage glioblastomas of 16 patients were pathologically confirmed after imaging progression to classic glioblastoma. CONCLUSIONS: Cortical lesions may be the earliest MR imaging-detectable abnormality in some human glioblastomas. These cortical tumors may progress to involve WM.

Acute necrotizing encephalopathy of childhood: correlation of MR findings and clinical outcome.

BACKGROUND AND PURPOSE: The clinical outcome of acute necrotizing encephalopathy of childhood (ANEC), an encephalopathy characterized by symmetrical involvement of the thalami, has historically been poor, but recent studies have reported better outcomes. By devising a MR imaging scoring system, we determined the relationship between characteristic MR findings and clinical outcome of patients with ANEC. METHODS: MR studies of 12 patients with ANEC were retrospectively reviewed. A MR imaging score was calculated for each patient according to the presence of hemorrhage, cavitation, and location of lesions. Clinical outcome of the patients was assessed, yielding outcome categories based on health state utility value. Spearman rank test was used to correlate the MR imaging score with clinical outcome of the patients. RESULTS: Statistically significant correlation (r = 0.76, P = .001) was found between the MR score and the outcome category. The thalami were involved in all 12 patients, brain stem in 10, cerebral white matter in 8, and cerebellar white matter in 4. Hemorrhage was present in 5 patients and cavitation in 4. Clinical outcome category was 1 in 2 patients, 2 in 8 patients, and 3 in 2 patients. No patients were in category 4. CONCLUSION: There is a significant and positive correlation between the clinical outcome and the MR imaging score in patients with ANEC. The relation between clinical outcome and each individual MR feature remains to be determined. Patients with ANEC may have a better clinical outcome than has been previously reported.

Autocrine VEGF mediates the antiapoptotic effect of CD154 on CLL cells.

CD154 is an important regulator of chronic lymphocytic leukaemia (CLL)-cell survival. In CLL, high serum levels of VEGF are a feature of advanced disease, and we and others have previously shown that CLL cells produce and secrete this growth factor. Since CD154 stimulates VEGF production in other cell types, and VEGF is known to promote cell survival, we examined whether the cytoprotection of CLL cells by CD154 involves VEGF. We report for the first time that treatment of CLL cells with CD154 results in increased VEGF production and demonstrate involvement of NF-kappaB in this process. Moreover, we show that CD154-induced CLL-cell survival is reduced by anti-VEGF-neutralising antibody and by inhibiting VEGF receptor (VEGFR) signalling with SU5416. However, addition of exogenous VEGF alone or blocking secreted autocrine VEGF had little or no effect on CLL-cell survival. We therefore conclude that CLL-cell cytoprotection in the presence of CD154 requires combined signalling by both CD40 and VEGFR. This combined signalling and resulting cytoprotection were shown to involve NF-kappaB activation and increased survivin production. In conclusion, our findings identify autocrine VEGF as an important mediator of the antiapoptotic effect of CD40 ligation, and thus provide new insights into CLL-cell rescue by CD154 in lymphoreticular tissues.

Laboratory evidence of disseminated intravascular coagulation is associated with a fatal outcome in children with cerebral malaria despite an absence of clinically evident thrombosis or bleeding.

BACKGROUND: A procoagulant state is implicated in cerebral malaria (CM) pathogenesis, but whether disseminated intravascular coagulation (DIC) is present or associated with a fatal outcome is unclear. OBJECTIVES: To determine the frequency of overt DIC, according to ISTH criteria, in children with fatal and non-fatal CM. METHODS/PATIENTS: Malawian children were recruited into a prospective cohort study in the following diagnostic groups: retinopathy-positive CM (n = 140), retinopathy-negative CM (n = 36), non-malarial coma (n = 14), uncomplicated malaria (UM), (n = 91), mild non-malarial febrile illness (n = 85), and healthy controls (n = 36). Assays in the ISTH DIC criteria were performed, and three fibrin-related markers, i.e. protein C, antithrombin, and soluble thrombomodulin, were measured. RESULTS AND CONCLUSIONS: Data enabling assignment of the presence or absence of 'overt DIC' were available for 98 of 140 children with retinopathy-positive CM. Overt DIC was present in 19 (19%), and was associated with a fatal outcome (odds ratio [OR] 3.068; 95% confidence interval [CI] 1.085-8.609; P = 0.035]. The levels of the three fibrin-related markers and soluble thrombomodulin were higher in CM patients than in UM patients (all P < 0.001). The mean fibrin degradation product level was higher in fatal CM patients (71.3 µg mL(-1) [95% CI 49.0-93.6]) than in non-fatal CM patients (48.0 µg mL(-1) [95% CI 37.7-58.2]; P = 0.032), but, in multivariate logistic regression, thrombomodulin was the only coagulation-related marker that was independently associated with a fatal outcome (OR 1.084 for each ng mL(-1) increase [95% CI 1.017-1.156]; P = 0.014). Despite these laboratory derangements, no child in the study had clinically evident bleeding or thrombosis. An overt DIC score and high thrombomodulin levels are associated with a fatal outcome in CM, but infrequently indicate a consumptive coagulopathy.

Temporal changes in factors associated with neutrophil elastase and coagulation in intensive care patients with a biphasic waveform and disseminated intravascular coagulation.

Summary. The biphasic waveform is an early marker of disseminated intravascular coagulation (DIC). Neutrophil elastase (NE) cleaves coagulation factors; thus, elevated elastase levels or its dysregulation by alpha-1-protease inhibitor (Alpha1PI) may be linked to DIC. Time courses over a period were determined for factors associated with NE and coagulation in 14 Intensive Care Unit patients with a biphasic waveform who developed DIC. The data were analyzed using a random coefficient linear regression model to predict the variables' mean values on day 0 and their mean rates of change over the period in which the biphasic waveform appeared. The biphasic waveform was normal on day 0, maximized on day 1, and approached normal again by day 4. Alpha1PI/NE complex levels were 2.5-fold greater than normal for the entire period. The A1PI activity, antigen, and specific activity levels were normal on day 0 and increased thereafter by 21.0, 10.5, and 8.9% of normal per day, respectively. Factor II, V, VII, IX, and X activity levels were, respectively, 57, 46, 46, 77, and 46% of normal on day 0, whereas factor VIII and fibrinogen levels were normal. All coagulation factor levels trended upward with time but not significantly. The prothrombin time, but not the activated partial thromboplastin time, was prolonged, and the platelet counts and hematocrits were below normal on day 0 and remained so thereafter. We conclude that events associated with neutrophil activation, elastase release, and perturbations of coagulation precede both the appearance of the biphasic waveform and the diagnosis of DIC in these patients.

Early identification and prognostic implications in disseminated intravascular coagulation through transmittance waveform analysis.

Efforts to improve the prognosis in disseminated intravascular coagulation (DIC) have been hampered by the lack of an early, useful and rapidly available diagnostic marker. More recently, a characteristic bi-phasic change in the light transmittance waveform profile of the APTT assay has been associated with DIC. In this prospective study, we have assessed the utility of this assay in the routine clinical setting. 1,470 samples were analysed from 747 patients and 41 patients had DIC. The sensitivity and specificity of the bi-phasic waveform pattern for DIC was 97.6% and 98% respectively. The appearance of a bi-phasic waveform preceded the development of abnormalities in the standard laboratory tests for DIC and waveform changes correlated closely with clinical events. In conclusion, transmittance waveform analysis is not only useful as an early diagnostic and single monitoring marker of DIC but the quantifiable and standardisable changes also allow for prognostic applicability in clinical management.

Activation of protein C and its distribution between its inhibitors, protein C inhibitor, alpha 1-antitrypsin and alpha 2-macroglobulin, in patients with disseminated intravascular coagulation.

Activation and inactivation of protein C during the clinical course of disseminated intravascular coagulation (DIC) was studied in three patients by qualitative (Western blotting) and quantitative (ELISA) analysis and the intensity of procoagulant activity monitored by the measurement of thrombin and factor Xa antithrombin III complexes. In one patient, inhibitor complexes of APC with protein C inhibitor (PCI) and alpha 1-antitrypsin (alpha 1-AT) were observed and the latter predominated at presentation. Both disappeared during the development of remission but the loss of alpha 1-AT complexes preceded PCI complexes which on Western blotting appeared to increase in intensity prior to disappearance. The two other patients bled to death from uncontrollable haemorrhage. In both cases, APC/inhibitor complexes with alpha 2-macroglobulin (alpha 2-M) in addition to PCI and alpha 1-AT were detected and persisted until death. Although PCI appeared to be the primary inhibitor in all three cases, alpha 1-antitrypsin and particularly alpha 2-macroglobulin appeared to assume greater roles in the two fatal cases. These data are similar to previous findings in an experimental animal model of DIC that suggested that alpha 2-macroglobulin and alpha 1-antitrypsin become more important inhibitors of APC as the primary inhibitor PCI is consumed in the face of a sustained procoagulant challenge.

Postnatal screening for thrombophilia in women with severe pregnancy complications.

OBJECTIVE: To examine the prevalence of maternal thrombophilia in women with severe preeclampsia/eclampsia, placental abruption, fetal growth restriction, and unexplained stillbirth. METHODS: We studied 102 women who had pregnancy complications and 44 healthy women with uncomplicated pregnancies. All women were tested 10 weeks postpartum for mutations of factor V Leiden, methylenetetrahydrofolate reductase (MTHFR) C677T, and G20210A prothrombin gene; deficiencies of protein C, protein S, and antithrombin III; and the presence of lupus anticoagulant and anticardiolipin antibodies. We aimed to recruit 100 cases and 300 controls to detect a 10% difference in thrombophilia between the groups. However, we were able to recruit only 44 controls. RESULTS: Abnormal thrombophilia screen was found in 54 women with pregnancy complications (53%) and in 17 women (39%) with normal pregnancies (odds ratio [OR] 1.8; 95% confidence interval [CI] 0.87, 3.67). Mutations encoding for factor V Leiden, G20210A prothrombin gene, and MTHFR C677T (homozygous) were identified in 18% of women with complications compared with 16% of controls (OR 1.1; 95% CI 0.44, 2.94). Activated protein C resistance, not due to factor V Leiden mutation, was the most common thrombophilic defect, found in 26% of women with pregnancy complications compared with 18% of controls (OR 1.5; 95% CI 0.63, 3.73). Twenty women with complications (20%) had multiple thrombophilic defects compared with four controls (9%) (OR 2.4; 95% CI 0.78, 7.61). CONCLUSION: In our cohort of women with pregnancy complications, maternal thrombophilia was less common than previously thought, and multiple thrombophilias were not a major additional risk factor.

A longitudinal study of maternal dose response to low molecular weight heparin in pregnancy.

OBJECTIVE: To assess the maternal response to low molecular weight heparin during pregnancy, by estimation of plasma anti-Xa activity, at three specified gestation points and in the nonpregnant state. METHODS: A longitudinal, prospective, observational study was set in a tertiary referral recurrent miscarriage clinic. Twenty-four women, attending consecutively, were invited to participate and gave informed consent. Each woman had a history of recurring pregnancy loss and positive preconception screening for antiphospholipid syndrome. After confirmation of a viable pregnancy all subjects began taking 5000 IU of dalteparin once daily subcutaneously. Serial measurement of plasma anti-Xa activity after administration of dalteparin was performed at three standard gestation points (12, 24, and 36 weeks) and in the nonpregnant state (6 weeks postpartum). RESULTS: Peak anti-Xa levels occurred at 4 hours postbolus in pregnancy, as compared with 2 hours in the nonpregnant state. The mean anti-Xa levels at 12, 24, and 36 weeks' gestation were significantly reduced, at 2 hours postinjection, as compared with the nonpregnant state (P <.001, P <.01, P <.001, respectively). The lowest dose-response curve was at 36 weeks' gestation. A repeated-measures analysis of variance found a significant difference (P <.05) between the 36-week group and the postterm group but not between any of the other groups. CONCLUSION: During pregnancy, differences in the pharmacokinetics of low molecular weight heparin were observed, with an overall reduction in anti-Xa activity. On the basis of this study it is questionable to extrapolate dosing and lack of dose monitoring, in pregnant women, using data derived from a nonpregnant population.

Assessment of angiographic vascularity of meningiomas with dynamic susceptibility contrast-enhanced perfusion-weighted imaging and diffusion tensor imaging.

BACKGROUND AND PURPOSE: The roles of DTI and dynamic susceptibility contrast-enhanced-PWI in predicting the angiographic vascularity of meningiomas have not been studied. We aimed to investigate if these 2 techniques could reflect the angiographic vascularity of meningiomas. MATERIALS AND METHODS: Thirty-two consecutive patients with meningiomas who had preoperative dynamic susceptibility contrast-enhanced-PWI, DTI, and conventional angiography were retrospectively included. The correlations between angiographic vascularity of meningiomas, classified with a 4-point grading scale, and the clinical or imaging variables-age and sex of patient, as well as size, CBV, fractional anisotropy, and ADC of meningiomas-were analyzed. The meningiomas were dichotomized into high-vascularity and low-vascularity groups. The differences in clinical and imaging variables between the 2 groups were compared. Receiver operating characteristic curve analysis was used to determine the diagnostic performance of these variables. RESULTS: In meningiomas, angiographic vascularity correlated positively with CBV but negatively with fractional anisotropy. High-vascularity meningiomas demonstrated significantly higher CBV but lower fractional anisotropy as compared with low-vascularity meningiomas. In differentiating between the 2 groups, the area under the curve values were 0.991 for CBV and 0.934 for fractional anisotropy on receiver operating characteristic curve analysis. CONCLUSIONS: CBV and fractional anisotropy correlate well with angiographic vascularity of meningiomas. They may differentiate between low-vascularity and high-vascularity meningiomas.

Differentiation of primary central nervous system lymphomas and glioblastomas: comparisons of diagnostic performance of dynamic susceptibility contrast-enhanced perfusion MR imaging without and with contrast-leakage correction.

BACKGROUND AND PURPOSE: Contrast leakage results in underestimation of the CBV of brain tumors. Our aim was to compare the diagnostic performance of DSC perfusion MR imaging without and with mathematic contrast-leakage correction in differentiating PCNSLs and glioblastomas. MATERIALS AND METHODS: Perfusion parameters-CBV, corrected CBV, and leakage coefficient-were measured in enhancing tumor portions and contralateral NAWM of 15 PCNSLs and 20 glioblastomas, respectively. The ratios of CBV and corrected CBV were calculated by dividing the tumor values by those obtained from contralateral NAWM. A paired t test was used to compare tumor K2 and NAWM K2, as well as tumor CBV ratios without and with leakage correction. Comparisons of CBV, corrected CBV, and K2 between PCNSLs and glioblastomas were done by using a 2-sample t test. The diagnostic performance of DSC perfusion MR imaging without and with contrast-leakage correction was assessed with receiver operating characteristic curve analysis. RESULTS: PCNSLs and glioblastomas demonstrated higher K2 than those in their contralateral NAWM. Corrected CBV ratios were significantly higher than the uncorrected ones for both tumors. PCNSLs had lower CBV ratios (P < .001), lower corrected CBV ratios (P < .001), and higher K2 (P = .001) compared with glioblastomas. In differentiating between PCNSLs and glioblastomas, the area under the curve of the CBV ratio, corrected CBV ratio, and K2 were 0.984, 0.940, and 0.788, respectively. CONCLUSIONS: PCNSL can be differentiated from glioblastoma with CBV ratios, corrected CBV ratios, and K2. CBV without contrast-leakage correction seems to have the best diagnostic performance in differentiating the 2 tumors.

Cerebral diffusion tensor MR tractography in tuberous sclerosis complex: correlation with neurologic severity and tract-based spatial statistical analysis.

BACKGROUND AND PURPOSE: The neurologic significance of residual cerebral white matter tracts, identified on diffusion tensor tractography, has not been well studied in tuberous sclerosis complex. We aimed to correlate the quantity of reconstructed white matter tracts with the degree of neurologic impairment of subjects with the use of DTI and determined differences in white matter integrity between patients with tuberous sclerosis complex and controls with the use of voxelwise analysis. MATERIALS AND METHODS: In this case-control study, 16 patients with tuberous sclerosis complex and 12 control subjects underwent DTI. Major white matter tracts, comprising bilateral PF and CF, were reconstructed and assessed for quantity, represented by NOP and NOF. A neurologic severity score, based on the presence of developmental disability, seizure, autism, and other neuropsychiatric disorders, was calculated for each subject. We then correlated this score with white matter quantity. Voxelwise tract-based spatial statistics was used to determine differences in FA, axial, and radial diffusivity values between the tuberous sclerosis complex group and the control subjects. RESULTS: NOP and NOF of CF, bilateral PF, and MWT in the tuberous sclerosis complex group were all significantly lower than those in the control subjects (P < .05). The neurologic severity score was moderately negatively correlated with NOF and NOP regarding CF (r = -.70; r = -.75), bilateral PF (r = -.66; r = -.68), and MWT (r = -.71; r = -.74). Tract-based spatial statistics revealed that patients with tuberous sclerosis complex showed a widespread reduction (P < .05) in FA and axial diffusivity in most cerebral white matter regions. CONCLUSIONS: Patients with tuberous sclerosis complex with reduced residual white matter were neurologically more severely affected. Tract-based spatial statistics revealed decreased FA and axial diffusivity of the cerebral white matter in the tuberous sclerosis complex group, suggesting reduced axonal integrity.

Guidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines.

Three guidelines have recently been published for the diagnosis and treatment of disseminated intravascular coagulation (DIC) in adults. This communication seeks to harmonize the recommendations in these guidelines using a modified GRADE system. The scoring system for diagnosis of DIC using global coagulation tests is known to correlate with key clinical observations and outcomes (Moderate quality). The cornerstone of DIC treatment is the treatment of the underlying condition (Moderate quality). In general, transfusion of platelets or plasma (components) in patients with DIC should be reserved for patients who are bleeding (Low quality). Therapeutic doses of heparin should be considered in cases of DIC where clinical features of thrombosis predominate. Heparin is not recommended in those patients with a high risk of bleeding, (Moderate quality). However, prophylactic doses of unfractionated heparin or low molecular we ight heparin is recommended in critically ill and non-bleeding patients with DIC for prevention of venous thromboembolism (Moderate to High quality). Although further prospective evidence from randomized controlled trials is required, administration of antithrombin or recombinant thrombomodulin may be considered in certain patients with DIC. In general, patients with DIC should not be treated with antifibrinolytic agents (Low quality). However those who present with severe bleeding, that is characterized by a markedly hyperfibrinolytic state such as leukemia (Low quality) and trauma (Moderate quality), may be treated with antifibrinolytic agents. © 2013 International Society on Thrombosis and Haemostasis.