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.

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.

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.

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.

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.

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.

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.

Differentiation of pyogenic brain abscesses from necrotic glioblastomas with use of susceptibility-weighted imaging.

BACKGROUND AND PURPOSE: A common imaging finding in brain abscess and necrotic glioblastoma is a T2 hypointense margin. The features of this hypointense rim on SWI have not been previously described, to our knowledge. We aimed to differentiate abscesses from glioblastomas by assessing the morphology of their lesion margin by using SWI. MATERIALS AND METHODS: T2WI and SWI were performed in 12 abscesses and 20 rim-enhancing glioblastomas. On T2WI and SWI, the prevalence and the border types (complete versus incomplete) of hypointense rims were qualitatively assessed. On SWI, the contour (smooth versus irregular) and the location of hypointense rims relative to the contrast-enhancing rims as well as the prevalence of the "dual rim sign," defined as 2 concentric rims at lesion margins with the outer one being hypointense and the inner one hyperintense relative to cavity contents, were also analyzed. RESULTS: Prevalence and the border types of the hypointense rims on T2WI were not different between abscesses and glioblastomas. On SWI, there were significantly more hypointense rims that were complete (P < .001) and smooth (P < .001), having the same location as the contrast-enhancing rims (P < .001) for abscesses. A dual rim sign was present in 9 of 12 abscesses but absent in all glioblastomas (P < .001). CONCLUSIONS: SWI may be helpful in differentiating pyogenic abscesses from necrotic glioblastomas. The dual rim sign is the most specific imaging feature distinguishing the 2.

A safe and efficacious alternative: sonographically guided internal jugular vein puncture for intracranial endovascular intervention.

Transvenous interventions for intracranial vascular lesions are usually performed via venous access of a femoral vein puncture. However, the transjugular route is an alternative with a shorter and less tortuous vascular access for intracranial lesions. Although puncture of the internal jugular vein is generally believed to be too dangerous owing to potential hazardous complications, the safety of the sonographically guided retrograde internal jugular vein puncture technique for intracranial intervention has not been fully evaluated in the English literature. We present our experience with a total of 44 transjugular intervention procedures between April 1999 and June 2010. We believe sonographically guided internal jugular vein puncture is a safe and efficacious technique for establishing transvenous access for an intracranial endovascular intervention.

Differentiation of tumefactive demyelinating lesions from high-grade gliomas with the use of diffusion tensor imaging.

BACKGROUND AND PURPOSE: TDLs may be indistinguishable from high-grade gliomas on conventional MR imaging. The role of DTI in differentiating TDLs from high-grade gliomas is not clear, and quantitative comparison between the 2 has not been reported. Here we aimed to differentiate TDLs from high-grade gliomas by using DTI. MATERIALS AND METHODS: DTI was performed in 8 TDLs and 13 high-grade gliomas. The presence of 3 findings (ie, intralesional hyperintensities on the FA map, restricted diffusion in the lesion periphery, and a perilesional hyperintense FA rim) was assessed by visual inspection. The FA and MD values were measured in the central nonenhancing portion, peripheral enhancing portion, and perilesional edema for each lesion and compared between the 2 groups respectively. RESULTS: TDLs had a significantly higher incidence of intralesional hyperintensities on FA maps (P = .049) but a lower incidence of a perilesional hyperintense FA rim (P < .001), compared with those of high-grade gliomas on visual inspection. TDLs had significantly higher FA (P = .004) and lower MD (P = .001) values in the peripheral enhancing portions of the lesions compared with those of high-grade gliomas. In perilesional edema, FA values were significantly higher in high-grade gliomas (P = .001). CONCLUSIONS: DTI is helpful in differentiating TDLs from high-grade gliomas by using visual inspection and quantitative analysis.

Differentiation of brain abscesses from necrotic glioblastomas and cystic metastatic brain tumors with diffusion tensor imaging.

BACKGROUND AND PURPOSE: The differentiation of abscesses from glioblastomas and metastases may not always be possible on the basis of DWI. Our hypothesis was that differences in diffusion properties as detected by DTI allow differentiation of abscess from glioblastomas and metastasis. Furthermore, diagnostic performance of tensor metrics quantifying anisotropy or tensor shapes is better than that of ADC in measuring mean diffusivity for this purpose. MATERIALS AND METHODS: DTI was performed in 15 abscesses, 15 necrotic glioblastomas, and 26 cystic metastases. In each lesion, manually segmented into 4 regions of interest (ie, cystic cavity, enhancing rim, and immediate [edema most adjacent to the enhancing rim] and distant zones of edema), FA, ADC, C(l), C(p), and C(s) values were measured and statistically compared among groups and evaluated with ROC curve analysis. The presence of a hyperintense FA rim (a rim of edematous tissue that was hyperintense on the FA map) was assessed visually. RESULTS: Abscess was significantly different from glioblastoma for all tensor metrics measured in the cystic cavity and immediate zone of edema and for all except C(l) in the enhancing rim. Abscess was significantly different from metastasis for all tensor metrics measured in the cystic cavity and enhancing rim and for FA, ADC, and C(l) in immediate zone of edema. The incidence of a hyperintense FA rim was significantly higher in glioblastoma and metastasis compared with abscess. The 3 tensor metrics with the highest performance in differentiating abscess from glioblastoma and metastasis were FA, C(l), and C(s) of the cystic cavity. CONCLUSIONS: DTI is able to differentiate abscess from glioblastoma and metastasis. FA, C(l), and C(s) outperformed ADC in diagnostic performance comparisons.

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.

Differentiating Components of Cerebral Arteriovenous Malformations Using T1-Weighted Gradient Recall Echo MR Imaging.

Cerebral arteriovenous malformation (AVM) typically shows signal void on conventional MR images, making differentiation of each component difficult. We analyzed the MR signal intensity of AVM components on T1-weighted gradient recalled echo pulse sequence images. We retrospectively studied 29 patients with AVM between 2006 and 2008. Patients were excluded if they had 1) intracranial hemorrhage, 2) previous intervention for AVM. All patients underwent MR study on a 3T system (Magentom TIM Trio, Siemens). Pulse sequences included T1-weighted gradient recalled echo (T1GRE), T2-weighted (T2), time-of-flight (TOF), and contrast-enhanced T1-weighted (cT1) images. Digital subtracted angiography (DSA) was performed in all patients as a diagnostic standard. Signal intensity of each AVM component was recorded and compared between pulse sequences. Nine patients were studied (five men; mean age 39.1 years) and nine AVM were identified (mean size, 3.9 cm). Three different signal intensities (hypo-, iso-, and hyper-intensity) were observed in all nine patients on T1GRE. Only one signal intensity was seen on T2 (flow void) and cT1 images (hyperintensity) in nine patients. Two different signal intensities were observed in all seven patients with TOF images. The T1GRE image showed the largest number of different signal intensities of AVM when compared with other pulse sequences, thus providing clearer structural delineation. Routine use of the T1GRE pulse sequence can help pre-therapeutic planning or follow-up of AVM.

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).