Mitochondrial Health, Physical Functioning, and Daily Affect: Bioenergetic Mechanisms of Dementia Caregiver Well-Being.

OBJECTIVE: Chronic stress adversely affects mental and physical well-being. However, health outcomes vary among people experiencing the same stressor. Individual differences in physical and emotional well-being may depend on mitochondrial biology, as energy production is crucial for stress regulation. This study investigated whether mitochondrial respiratory capacity corresponds to individual differences in dementia spousal caregivers' mental and physical health. METHODS: Spousal caregivers of individuals with Alzheimer's disease and related dementias ( N = 102, mean age = 71, 78% female, 83% White) provided peripheral blood samples and completed self-report questionnaires on quality of life, caregiver burden, and a 7-day affect scale. Multiple and mixed linear regressions were used to test the relationship between mitochondrial biology and well-being. RESULTS: Spare respiratory capacity ( b = 12.76, confidence interval [CI] = 5.23-20.28, p = .001), maximum respiratory capacity ( b = 8.45, CI = 4.54-12.35, p < .0001), and ATP-linked respiration ( b = 10.11, CI = 5.05-15.18, p = .0001) were positively associated with physical functioning. At average ( b = -2.23, CI = -3.64 to -0.82, p = .002) and below average ( b = -4.96, CI = -7.22 to 2.70, p < .0001) levels of spare respiratory capacity, caregiver burden was negatively associated with daily positive affect. At above average levels of spare respiratory capacity, caregiver burden was not associated with positive affect ( p = .65). CONCLUSIONS: Findings suggest that higher mitochondrial respiratory capacity is associated with better psychological and physical health-a pattern consistent with related research. These findings provide some of the earliest evidence that cellular bioenergetics are related to well-being.

The addition of pretreatment plasma Epstein-Barr virus DNA into the eighth edition of nasopharyngeal cancer TNM stage classification.

The eighth edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) stage classification (TNM) for nasopharyngeal carcinoma (NPC) was launched. It remains unknown if incorporation of nonanatomic factors into the stage classification would better predict survival. We prospectively recruited 518 patients with nonmetastatic NPC treated with radical intensity-modulated radiation therapy ± chemotherapy based on the eighth edition TNM. Recursive partitioning analysis (RPA) incorporating pretreatment plasma Epstein-Barr virus (EBV) DNA derived new stage groups. Multivariable analyses to calculate adjusted hazard ratios (AHRs) derived another set of stage groups. Five-year progression-free survival (PFS), overall survival (OS) and cancer-specific survival (CSS) were: Stage I (PFS 100%, OS 90%, CSS 100%), II (PFS 88%, OS 84%, CSS 95%), III (PFS 84%, OS 84%, CSS 90%) and IVA (PFS 71%, OS 75%, CSS 80%) (p < 0.001, p = 0.066 and p = 0.002, respectively). RPA derived four new stages: RPA-I (T1-T4 N0-N2 & EBV DNA <500 copies per mL; PFS 94%, OS 89%, CSS 96%), RPA-II (T1-T4 N0-N2 & EBV DNA ≥500 copies per mL; PFS 80%, OS 83%, CSS 89%), RPA-III (T1-T2 N3; PFS 64%, OS 83%, CSS 83%) and RPA-IVA (T3-T4 N3; PFS 63%, OS 60% and CSS 68%) (all with p < 0.001). AHR using covariate adjustment also yielded a valid classification (I: T1-T2 N0-N2; II: T3-T4 N0-N2 or T1-T2 N3 and III: T3-T4 N3) (all with p < 0.001). However, RPA stages better predicted survival for PS and CSS after bootstrapping replications. Our RPA-based stage groups revealed better survival prediction compared to the eighth edition TNM and the AHR stage groups.

Intravoxel water diffusion heterogeneity MR imaging of nasopharyngeal carcinoma using stretched exponential diffusion model.

PURPOSE: To determine the utility of stretched exponential diffusion model in characterisation of the water diffusion heterogeneity in different tumour stages of nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Fifty patients with newly diagnosed NPC were prospectively recruited. Diffusion-weighted MR imaging was performed using five b values (0-2,500 s/mm(2)). Respective stretched exponential parameters (DDC, distributed diffusion coefficient; and alpha (α), water heterogeneity) were calculated. Patients were stratified into low and high tumour stage groups based on the American Joint Committee on Cancer (AJCC) staging for determination of the predictive powers of DDC and α using t test and ROC curve analyses. RESULTS: The mean ± standard deviation values were DDC = 0.692 ± 0.199 (×10(-3) mm(2)/s) for low stage group vs 0.794 ± 0.253 (×10(-3) mm(2)/s) for high stage group; α = 0.792 ± 0.145 for low stage group vs 0.698 ± 0.155 for high stage group. α was significantly lower in the high stage group while DDC was negatively correlated. DDC and α were both reliable independent predictors (p < 0.001), with α being more powerful. Optimal cut-off values were (sensitivity, specificity, positive likelihood ratio, negative likelihood ratio) DDC = 0.692 × 10(-3) mm(2)/s (94.4 %, 64.3 %, 2.64, 0.09), α = 0.720 (72.2 %, 100 %, -, 0.28). CONCLUSION: The heterogeneity index α is robust and can potentially help in staging and grading prediction in NPC. KEY POINTS: • Stretched exponential diffusion models can help in tissue characterisation in nasopharyngeal carcinoma • α and distributed diffusion coefficient (DDC) are negatively correlated • α is a robust heterogeneity index marker • α can potentially help in staging and grading prediction.

Correlation between tissue metabolism and cellularity assessed by standardized uptake value and apparent diffusion coefficient in peritoneal metastasis.

PURPOSE: To evaluate the correlation between standardized uptake value (SUV) (tissue metabolism) and apparent diffusion coefficient (ADC) (water diffusivity) in peritoneal metastases. MATERIALS AND METHODS: Patients with peritoneal dissemination detected on (18)F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) were prospectively recruited for MRI examinations with informed consent and the study was approved by the local Institutional Review Board. FDG-PET/CT, diffusion-weighted imaging (DWI), MRI, and DWI/MRI images were independently reviewed by two radiologists based on visual analysis. SUVmax/SUVmean and ADCmin/ADCmean were obtained manually by drawing ROIs over the peritoneal metastases on FDG-PET/CT and DWI, respectively. Diagnostic characteristics of each technique were evaluated. Pearson's coefficient and McNemar and Kappa tests were used for statistical analysis. RESULTS: Eight patients were recruited for this prospective study and 34 peritoneal metastases were evaluated. ADCmean was significantly and negatively correlated with SUVmax (r = -0.528, P = 0.001) and SUVmean (r = -0.548, P = 0.001). ADCmin had similar correlation with SUVmax (r = -0.508, P = 0.002) and SUVmean (r = -0.513, P = 0.002). DWI/MRI had high diagnostic performance (accuracy = 98%) comparable to FDG-PET/CT, in peritoneal metastasis detection. Kappa values were excellent for all techniques. CONCLUSION: There was a significant inverse correlation between SUV and ADC.

Nasopharyngeal carcinoma: comparison of diffusion and perfusion characteristics between different tumour stages using intravoxel incoherent motion MR imaging.

OBJECTIVE: To explore intravoxel incoherent motion (IVIM) characteristics of nasopharyngeal carcinoma (NPC) and relationships with different tumour stages. METHODS: We prospectively recruited 80 patients with newly diagnosed undifferentiated NPC. Diffusion-weighted MR imaging was performed and IVIM parameters (D, pure diffusion; f, perfusion fraction; D*, pseudodiffusion coefficient) were calculated. Patients were stratified into low and high tumour stage groups based on American Joint Committee on Cancer (AJCC) and TNM staging for determination of the predictive powers of IVIM parameters using t test, multiple logistic regression and ROC curve analyses. RESULTS: D, f and D* were all statistically significantly lower in high-stage groups in AJCC, T and N staging. D, f and D* were all independent predictors of AJCC staging, f and D* were independent predictors of T staging, and D was an independent predictor of N staging. D was most powerful for AJCC and N staging, whereas f was most powerful for T staging. Optimal cut-off values (area under the curve, sensitivity, specificity, positive likelihood ratio, negative likelihood ratio) were as follows: AJCC stage, D = 0.782 × 10(-3) mm(2)/s (0.915, 93.3 %, 76.2 %, 3.92, 0.09); T staging, f = 0.133 (0.905, 80.5 %, 92.5 %, 10.73, 0.21); N staging, D = 0.761 × 10(-3) mm(2)/s (0.848, 87.5 %, 66.7 %, 2.62, 0.19). Multivariate analysis showed no diagnostic improvement. CONCLUSION: Nasopharyngeal carcinoma has distinctive intravoxel incoherent motion characteristics parameters in different tumour staging, potentially helping pretreatment staging. KEY POINTS: • Magnetic resonance imaging is increasingly used to assess nasopharyngeal carcinoma (NPC). • NPC has distinctive diffusion/perfusion characteristics at different stages. • Non-invasive MR imaging may help pretreatment staging prediction. • Diffusion properties of NPC best correlate with AJCC and N staging. • Perfusion properties of NPC best correlate with T staging.

Transcultural and psychometric validation of the Dispositional Resilience Scale (DRS-15) in Chinese adult women.

PURPOSE: The aim of this study was to report translation and transcultural adaptation of the 15-item Dispositional Resilience Scale in traditional Chinese (C-DRS-15) and evaluate its psychometric properties. METHODS: The DRS is a self-report instrument that measures psychological hardiness. We followed an international standard of cross-cultural translation and validation of patient-reported outcome measures to create the Chinese version. Then, the translated C-DRS-15 was validated on 542 Chinese women from a population-based sample in Hong Kong. RESULTS: The internal consistency and criterion-related validity were investigated. Exploratory and confirmatory factor analysis revealed that the C-DRS-15 was supported by a modified three-factor structure in our Chinese sample (RMSEA = .06, CFI = .94, TLI = .92, and SRMR = .06). The reliability (Cronbach's α coefficient = .78) and validity were satisfactory. Total resilience score was negatively correlated with depression (p < .001), with non-depressed women scoring higher on the C-DRS-15. CONCLUSIONS: The C-DRS-15 was demonstrated to be a reliable and valid measurement to assess hardiness in Chinese women.

LPS-induced whole-blood cytokine production and depressive symptoms in dementia spousal caregivers: The moderating effect of childhood trauma.

Dementia spousal caregivers are at risk for adverse mental and physical health outcomes. Caregiver burden, anticipatory grief, and proinflammatory cytokine production may contribute to depressive symptoms among caregivers. People who report childhood trauma are more likely to have exaggerated stress responses that may also contribute to depressive symptoms in adulthood. This study aimed to test whether the relationship between whole-blood cytokine production and depressive symptoms is strongest in caregivers who report high levels of childhood trauma. METHODS: A sample of 103 dementia spousal caregivers provided self-report data on demographics, health information, caregiver burden, anticipatory grief, and depressive symptoms. We also determined lipopolysaccharide-induced whole-blood cytokine production as the primary measure of immune cell reactivity. We measured interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) and converted z-scores of each cytokine into a composite panel. We regressed depressive symptoms on proinflammatory cytokine production, caregiver burden, and anticipatory grief, adjusting for demographic and health-related covariates. RESULTS: Whole-blood cytokine production and childhood trauma were associated with depressive symptoms. Childhood trauma moderated the relationship between whole-blood cytokine production and depressive symptoms. Whole-blood cytokine production was only associated with depressive symptoms at mean and high levels of childhood trauma, but not at low levels of childhood trauma. The main effects of burden and anticipatory grief on depressive symptoms were strongest for caregivers reporting high levels of childhood trauma. DISCUSSION: Childhood trauma has lasting impacts on psychosocial experiences later in life and has effects that may confer susceptibility to inflammation-related depression. Our findings contribute to ongoing efforts to identify risk factors for adverse mental health in dementia spousal caregivers.

Intravoxel incoherent motion MR imaging: comparison of diffusion and perfusion characteristics between nasopharyngeal carcinoma and post-chemoradiation fibrosis.

OBJECTIVES: To compare the intravoxel incoherent motion (IVIM) diffusion and perfusion characteristics of nasopharyngeal carcinoma (NPC) and post-chemoradiation fibrosis to aid in their differentiation. METHODS: Fifty-three (64 %) patients with newly diagnosed NPC and 30 (36 %) patients with biopsy-proven post-chemoradiation fibrosis were recruited into tumour and fibrosis groups respectively. Diffusion-weighted magnetic resonance (MR) imaging was performed using 13 b values (0-1,000 s/mm(2)). Their respective IVIM parameters (D, pure diffusion; f, perfusion fraction; D, pseudodiffusion coefficient) were obtained. RESULTS: D and f were significantly lower in NPC (D = 0.752 ± 0.194 × 10(-3) mm(2)/s, P <0.001; f = 0.122 ± 0.095, P <0.001) than in fibrosis (D = 1.423 ± 0.364 × 10(-3) mm(2)/s; f = 0.190 ± 0.120); while D was significantly higher in NPC (111.366 ± 65.528 × 10(-3) mm(2)/s, P <0.001) than in fibrosis (77.468 ± 62.168 × 10(-3) mm(2)/s). Respective cut-off values with sensitivity, specificity and accuracy were: D = 1.062 × 10(-3) mm(2)/s (100 %, 100 %, 100 %); f = 0.132 (66.0 %, 100 %, 78.3 %); D = 85.283 × 10(-3) mm(2)/s (100 %, 90.7 %, 96.4 %). CONCLUSION: NPC and post-chemoradiation fibrosis have distinctive IVIM parameters. IVIM MR imaging is potentially useful in discrimination between NPC and fibrosis. KEY POINTS: • New MRI techniques offer greater help in the assessment of nasopharyngeal carcinoma. • Tumour and post-chemoradiation fibrosis have distinctive intravoxel incoherent motion diffusion/perfusion parameters. • Non-invasive IVIM MRI may help differentiate between tumour and fibrosis. • Pure diffusion is a robust independent discriminating factor which improves diagnostic confidence.

Dynamic contrast-enhanced magnetic resonance imaging for characterising nasopharyngeal carcinoma: comparison of semiquantitative and quantitative parameters and correlation with tumour stage.

OBJECTIVES: To evaluate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for characterising nasopharyngeal carcinoma (NPC). METHODS: Forty-five newly diagnosed NPC patients were recruited. The initial enhancement rate (E R ), contrast transfer rate (k ep ), elimination rate (k el ), maximal enhancement (MaxEn) and initial area under the curve (iAUC) were calculated from semiquantitative analysis. The K (trans) (volume transfer constant), v e (volume fraction) and k ep were calculated from quantitative analysis. Student's t-test was used to evaluate the differences among tumour stages. Pearson's correlation between the two sets of k ep was performed. RESULTS: Comparing tumours of T1/2 stage (n = 18) and T3/4 stage (n = 27), MaxEn (P = 0.030) and iAUC (P = 0.039) were both significantly different; however, the iAUC was the only independent variable with 69.6 % sensitivity and 76.5 % specificity respectively; v e was also significantly different (P = 0.010) with 69.6 % sensitivity and 70.6 % specificity respectively. No significant difference was found among N stages. The two sets of k ep s were highly correlated (r = 0.809, P < 0.001). Forty-three patients had chemoradiation, one palliative chemotherapy and one radiotherapy only. In the four patients with poor outcome, k el, E R, MaxEn and iAUC tended to be higher. CONCLUSIONS: Neovasculature in higher T stage NPC exhibits some parameters of increased permeability and perfusion. Thus, DCE-MRI may be helpful as an adjunctive technique in evaluating NPC. KEY POINTS: • The correct assessment of nasopharyngeal carcinoma (NPC) is important for planning treatment. • Neovasculature in higher T stage NPC exhibits increased permeability and perfusion. • Correlation between quantitative and semi-quantitative analysis validates the robustness of DCE-MRI. • DCE-MRI may be helpful as an adjunctive parameter in evaluating NPC.

Evolving frontiers in severe polytrauma management - refining the essential principles.

This editorial aims to refine the severe polytrauma management principles. While keeping ABCDE priorities, the termination of futile resuscitation and the early use of tourniquet to stop exsanguinating limb bleeding are crucial. Difficult-airway-management (DAM) is by a structured 5-level approach. The computerised tomography (CT) scanner is the tunnel to death for hemodynamically unstable patients. Focused Abdominal Sonography for Trauma-Ultrasonography (FAST USG) has replaced diagnostic peritoneal lavage (DPL) and is expanding to USG life support. Direct whole-body multidetector-row computed tomography (MDCT) expedites diagnosis & treatment. Non-operative management is a viable option in rapid responders in shock. Damage control resuscitation comprising of permissive hypotension, hemostatic resuscitation & damage control surgery (DCS) help prevent the lethal triad of trauma. Massive transfusion protocol reduces mortality and decreases the blood requirement. DCS attains rapid correction of the deranged physiology. Mortality reduction in major pelvic disruption requires a multi-disciplinary protocol, the novel pre-peritoneal pelvic packing and the angio-embolization. When operation is the definitive treatment for injury, prevention is best therapy.

Perceived income inadequacy is associated with Epstein-Barr Virus latency and mental health outcomes in informal caregivers who are also employed in the healthcare industry.

Finances are a prevalent source of stress. In a sample of 799 nursing home workers measured multiple times over 18 months, we found that higher perceived income inadequacy, the perception that one's expenses exceeds one's incomes, was associated with poorer self-reported mental health indicators and Epstein-Barr Virus antibody titers (a marker of cell-mediated immune function). Perceived income inadequacy predicted outcomes over and above the role of other socioeconomic status variables (objective household income and education). Mental health variables were not related to Epstein-Barr Virus antibody titers. Additionally, we found an interaction between perceived income inadequacy and informal caregiver status on our mental health outcomes; informal caregivers with higher perceived income inadequacy had poorer mental health than non-caregivers with the same perceived income inadequacy. Our findings may add nuance to the reserve capacity model, which states that those at lower socioeconomic levels are at higher risk of adverse health outcomes partly because they have fewer resources to address demands and strain. Perceived income inadequacy may significantly predict mental and physical well-being beyond other socioeconomic status variables, especially among lower-income employees. Caregiving stress and perceived income inadequacy may have synergistic effects on mental health.

Diagnostic accuracy of mediastinal width measurement on posteroanterior and anteroposterior chest radiographs in the depiction of acute nontraumatic thoracic aortic dissection.

We aimed to explore the diagnostic accuracy of various mediastinal measurements in determining acute nontraumatic thoracic aortic dissection with respect to posteroanterior (PA) and anteroposterior (AP) chest radiographs, which had received little attention so far. We retrospectively reviewed 100 patients (50 PA and 50 AP chest radiographs) with confirmed acute thoracic aortic dissection and 120 patients (60 PA and 60 AP chest radiographs) with confirmed normal aorta. Those who had prior history of trauma or aortic disease were excluded. The maximal mediastinal width (MW) and maximal left mediastinal width (LMW) were measured by two independent radiologists and the mediastinal width ratio (MWR) was calculated. Statistical analysis was then performed with independent sample t test. PA projection was significantly more accurate than AP projection, achieving higher sensitivity and specificity. LMW and MW were the most powerful parameters on PA and AP chest radiographs, respectively. The optimal cutoff levels were LMW = 4.95 cm (sensitivity, 90 %; specificity, 90 %) and MW = 7.45 cm (sensitivity, 90 %; specificity, 88.3 %) for PA projection and LMW = 5.45 cm (sensitivity, 76 %; specificity, 65 %) and MW = 8.65 cm (sensitivity, 72 %; specificity, 80 %) for AP projection. MWR was found less useful and less reliable. The use of LMW alone in PA film would allow more accurate prediction of aortic dissection. PA chest radiograph has a higher diagnostic accuracy when compared with AP chest radiograph, with negative PA chest radiograph showing less probability for aortic dissection. Lower threshold for proceeding to computed tomography aortogram is recommended however, especially in the elderly and patients with widened mediastinum on AP chest radiograph.

Megalencephalic leukoencephalopathy with cysts without MLC1 defect.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive disease characterized by early infantile macrocephaly and delayed motor and cognitive deterioration. Magnetic resonance imaging (MRI) shows diffusely abnormal and swollen cerebral white matter and subcortical cysts. On follow-up, atrophy ensues. Approximately 80% of MLC patients have mutations in MLC1. We report 16 MLC patients without MLC1 mutations. Eight retained the classical clinical and MRI phenotype. The other 8 showed major MRI improvement. They lacked motor decline. Five had normal intelligence; 3 displayed cognitive deficiency. In conclusion, 2 phenotypes can be distinguished among the non-MLC1 mutated MLC patients: a classical and a benign phenotype.

Clinical outcomes of lamivudine-adefovir therapy in chronic hepatitis B cirrhosis.

GOALS: To determine the clinical outcome of chronic hepatitis B cirrhotics on antiviral therapy. BACKGROUND: The long-term outcome of hepatitis B cirrhotics on therapy remains to be characterized. METHODS: A large clinic cohort of chronic hepatitis B cirrhotic patients were enrolled in a treatment program of lamivudine ± adefovir therapy. Patients were analyzed for clinical outcomes, and predictors of these outcomes were evaluated by multivariate analysis. Clinical outcomes of ascites, encephalopathy, hepatocellular carcinoma (HCC), and progression in Child-Pugh score, Model for End-stage Liver Disease score, and mortality were assessed. Data were analyzed by Kaplan-Meier graphs, log-rank test, and Cox regression. RESULTS: Of 143 chronic hepatitis B cirrhotics, 19.6% had decompensated cirrhosis. At 5 years, the mean survival was 83.6%, development of ascites, HCC, encephalopathy, and deterioration in Child-Pugh score were 7.0%, 15.9%, 10.8%, and 16.9%, respectively. The overall progression of liver-related complications was 32.8% at 5 years. Multivariate analysis showed that ascites, albumin ≤28 g/L, Child-Pugh score ≥7.9, Model for End-stage Liver Disease score ≥10.9 were significantly associated with liver-related complications. Low albumin and low hepatitis B virus DNA were independent factors for liver-associated mortality. Lamivudine resistance did not affect mortality or liver disease progression. When stratified by Child-Pugh status, the mean survival of those with Child C cirrhosis was worse than Child A and B cirrhosis (P<0.001, log-rank test). Early deaths (≤12 mo) were due to liver failure or sepsis, whereas deaths ≥12 mo were mainly due to HCC. CONCLUSION: Decompensated chronic hepatitis B cirrhotics may suffer early mortality despite antiviral treatment, and therefore should be considered for early liver transplantation.

Neuroimaging techniques in epilepsy.

OBJECTIVE: To review state-of-the-art neuroimaging modalities in epilepsy and their clinical applications. DATA SOURCES AND STUDY SELECTION: PubMed literature searches to March 2010, using the following key words: 'epilepsy', 'positron emission tomography (PET)', 'single photon emission computed tomography (SPECT)', 'MR volumetry', 'diffusion tensor imaging', and 'functional MR imaging'. DATA EXTRACTION: All articles including neuroimaging techniques in epilepsy were included in the review. DATA SYNTHESIS: High-field magnetic resonance imaging is fundamental for high-resolution structural imaging. Functional radionuclide imaging (positron emission tomography/single-photon emission computed tomography) can provide additional information to improve overall accuracy, and show good results with high concordance rates in temporal lobe epilepsy. Magnetic resonance spectroscopy is a useful adjunct consistently demonstrating changing metabolites in the epileptogenic region. Magnetic resonance volumetric imaging shows excellent sensitivity and specificity for temporal lobe epilepsy but thus far it has been inconsistent for extratemporal epilepsy. Diffusion tensor imaging with tractography allows visualisation of specific tracts such as connections with the language and visual cortex to enhance preoperative evaluation. Functional magnetic resonance imaging using blood oxygen level-dependent activation techniques is mainly used in presurgical planning for the high-sensitivity mapping of the eloquent cortex. Both contrast-bolus and arterial spin labelling magnetic resonance perfusion imaging show good correlation with clinical lateralisation of seizure disorder. CONCLUSION: Structural imaging is essential in localisation and lateralisation of the seizure focus. Functional radionuclide imaging or advanced magnetic resonance imaging techniques can provide complementary information when an epileptogenic substrate is not identified or in the presence of non-concordant clinical and structural findings.

Coculture of human liver macrophages and cholangiocytes leads to CD40-dependent apoptosis and cytokine secretion.

UNLABELLED: In the vanishing bile duct syndromes (VBDS), primary biliary cirrhosis and chronic allograft rejection, cholangiocyte apoptosis is associated with sustained macrophage infiltration of the liver, suggesting that these cells may mediate tissue damage and contribute to bile duct destruction. We have previously reported that activation of CD40 on cholangiocytes with either soluble CD154 or cross-linking monoclonal antibody to CD40 induces apoptosis in vitro. We have now developed a novel primary human cell coculture model and used it to investigate (1) how macrophages kill cholangiocytes; (2) how paracrine cell interactions can shape the local cytokine milieu within the liver. We report that lipopolysaccharide (LPS) and interferon (IFN) induce sustained expression of CD154 on liver-derived macrophages (LDM) in vitro. Coculture of activated LDM expressing high levels of CD154 (CD40 ligand) with human cholangiocytes resulted in (1) CD40-dependent secretion of proinflammatory cytokines; (2) apoptosis of cholangiocytes that was abolished by antagonistic antibodies directed against human CD40 or human CD154. CONCLUSION: Macrophages are important effector cells in bile duct destruction in VBDS, and this role is dependent on CD40-mediated mechanisms. Thus activation of CD40 on cholangiocytes by activated macrophages provides a molecular mechanism to amplify chronic inflammation and bile duct destruction in liver disease. These data suggest that effective targeting strategies to antagonize CD40/CD154 may have beneficial effects in patients suffering from the VBDS.

Myocardial rupture associated with bolus injection of contrast medium during computed tomographic study in a patient with acute myocardial infarction: a rare but lethal complication.

Well-documented potential cardiovascular complications associated with the use of contrast media include bradycardia, hypotension, arrhythmia, and conduction disturbances. Rupture of the myocardium after acute myocardial infarction is a known cause of death, but has yet to be recognised as a potential complication of the use of a bolus injection of contrast medium. On the contrary, contrast-enhanced computed tomographic studies have been performed widely for the diagnosis and evaluation of myocardial infarction. We report a case of complicated myocardial rupture after a single bolus injection of contrast medium during a computed tomographic study in an elderly woman with acute myocardial infarction, which led to cardiac tamponade and rapid death. Although rare, this should alert us to the need for cautious use of contrast medium in patients with acute myocardial infarction.

Intravoxel incoherent motion MR imaging in nasopharyngeal carcinoma: comparison and correlation with dynamic contrast enhanced MR imaging.

OBJECTIVES: To compare accuracy and assess agreement between intravoxel incoherent motion (IVIM) magnetic resonance (MR) perfusion-related parameters and quantitative dynamic contrast-enhanced (DCE) MR parameters in nasopharyngeal carcinoma (NPC). RESULTS: D, f, D*, Ktrans , Kep and Vp were significantly lower in the high stage group while Ve was significantly higher in the high stage group. Optimal cut-off values were: D=0.749 × 10-3 mm2/s; f=0.145; D*=100.401 × 10-3 mm2/s; Ktrans =0.571/min; Kep =0.8196/min; Ve =0.6556 %; Vp =0.0757 %. D* (p=0.001), Ktrans (p<0.001), Ve (p=0.014) were all reliable independent predictors for AJCC staging. IVIM-MR perfusion-related (f, D*) and DCE-MR (Ktrans , Kep , Ve , Vp ) parameters were significantly correlated (p<0.001). MATERIALS AND METHODS: 75 patients with newly diagnosed NPC were prospectively recruited. Diffusion-weighted MR and DCE-MR imaging were performed with respective IVIM (D, f, D*) and DCE (Ktrans , Kep , Ve , Vp ) MR parameters calculated. Patients were stratified into low and high tumor stage groups according to American Joint Committee on Cancer (AJCC) staging for determination of the predictive powers of IVIM-MR and DCE-MR parameters using t-test, ROC curve analyses and multiple logistic regression analysis. Correlation between IVIM-MR perfusion-related and DCE-MR parameters was assessed using Spearman's rank correlation. CONCLUSION: IVIM-MR perfusion-related and quantitative DCE-MR parameters were significantly correlated in the assessment of NPC and were both reliable independent predictors in the prediction of AJCC staging. IVIM-MR perfusion imaging can be a potential useful non-invasive perfusion imaging tool for clinical use in the assessment of NPC.

Dynamic Contrast-Enhanced Magnetic Resonance Imaging of Regional Nodal Metastasis in Nasopharyngeal Carcinoma: Correlation with Nodal Staging.

Objective: To determine if the perfusion parameters by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of regional nodal metastasis are helpful in characterizing nodal status and to understand the relationship with those of primary tumor of nasopharyngeal carcinoma (NPC). Materials and Methods: Newly diagnosed patients imaged between August 2010 and January 2014 and who were found to have enlarged retropharyngeal/cervical lymph nodes suggestive of nodal disease were recruited. DCE-MRI was performed. Three quantitative parameters, Ktrans, ve, and kep, were calculated for the largest node in each patient. Kruskal-Wallis test was used to evaluate the difference in the parameters of the selected nodes of different N stages. Spearman's correlation was used to evaluate the relationship between the DCE-MRI parameters in nodes and in primary tumors. Results: Twenty-six patients (7 females; 25~67 years old) were enrolled. Ktrans was significantly different among the patients of N stages (N1, n = 3; N2, n = 17; N3, n = 6), P = 0.015. Median values (range) for N1, N2, and N3 were 0.24 min-1 (0.17~0.26 min-1), 0.29 min-1 (0.17~0.46 min-1), and 0.46 min-1 (0.29~0.70 min-1), respectively. There was no significant correlation between the parameters in nodes and primary tumors. Conclusion: DCE-MRI may play a distinct role in characterizing the metastatic cervical lymph nodes of NPC.

Prognostication of serial post-intensity-modulated radiation therapy undetectable plasma EBV DNA for nasopharyngeal carcinoma.

Plasma Epstein-Barr virus (EBV) DNA titers have been used to monitor treatment response and provide prognostic information on survival for nasopharyngeal carcinoma (NPC). However, the long-term prognostic role of pretreatment and posttreatment titers after radical contemporaneous radiation therapy remains uncertain. We recruited 260 evaluable patients with non-metastatic NPC treated with radical intensity-modulated radiation therapy (IMRT) with or without adjunct chemotherapy. Plasma EBV DNA titers at baseline and then 8 weeks and 6 months after IMRT were measured. Cox regression models were employed to identify interaction between post-IMRT 8th week and 6th month undetectable titers and 3-year survival endpoints. Concordance indices (Ct) from time-dependent receiver-operating characteristics (TDROC) were compared between patients with post-IMRT undetectable and those with detectable titers. After a median follow-up duration of 3.4 years (range 1.4-4.6 years), patients with post-IMRT 8th week and 6th month undetectable plasma EBV DNA titers enjoyed longer 3-year survival endpoints than those who had detectable titers at the same time points. Post-IMRT 8th week, and more significantly, post-IMRT 6th month undetectable plasma EBV DNA were the only significant prognostic factors of 3-year survival endpoints. Ct values for all 3-year survival endpoints for both post-IMRT 8th week and 6th month undetectable plasma EBV DNA were significantly higher in those with stage IVA-IVB diseases compared to stage I-III counterparts. Early post-IMRT undetectable plasma EBV DNA titers were prognostic of 3-year survival endpoints in patients with non-metastatic NPC. Intensified treatment should be further explored for patients with persistently detectable titers after IMRT.