The applicability of the "surprise question" as a prognostic tool in patients with severe chronic comorbidities in a university teaching outpatient setting.

BACKGROUND: Life expectancy in recent decades has increased the prevalence of chronic diseases in the population, requiring an approach to new health topics, such as discussions on quality of life and expectations about death and dying. The concept of advance directives (ADs) gives individuals the opportunity to make known their decisions about the treatments they would like to receive at the end of life. Despite the recognition of relevance in clinical practice, the applicability of the concept presents challenges, including establishing the appropriate prognosis for each patient and the ideal time to approach the patient. Some prognostic tools were developed, such as the surprise question (SQ): "Would you be surprised if your patient died in 12 months?", which is used in some clinical settings to predict patient deaths and to make decisions regarding ADs. The main objective of the present study was to evaluate the behavior of second-year resident physicians (PGY-2) when the SQ was applied. METHOD: In our observational study, from July 1, 2016, to February 28, 2017, (PGY-2) in the Internal Medicine Residency Program (IMRP) applied SQ to all patients with multiple and varied chronic no communicable comorbidities, who were followed up at the general medicine outpatient clinic (GMOC) of a tertiary university hospital in São Paulo- Brazil. The frequency of the outcome (death or non-death within 12 months) was analyzed by correlating it with the clinical data (impact of the studied variables). RESULTS: Eight hundred forty patients entered the study. Fitfty-two of them (6.2%) died within one year. PGY-2 predicted that two hundred and fourteen patients (25.5% of total) would die within a year (answer No to SQ), of which, 32 (14.9%) did so. The correct residents' prognosis for the subgroup of 626 patients (answer "Yes" to SQ) was NPV = 96.8% (CI = 95.4%-98.2%) and PPV = 14.9% (CI 10.1%-19, 6%). Answering "Yes" to SQ correlated negatively to addressing AD while the outcomes death and the answer No to SQ were positively correlated, according to the number of comorbidities. CONCLUSION: The SQ, in addition to care, contributed to health education, communication and care planning shared by the doctor and patient.

A 3D endometrial organotypic model simulating the acute inflammatory decidualisation initiation phase with epithelial induction of the key endometrial receptivity marker, integrin αVß3.

STUDY QUESTION: Is it possible to develop a simplified physiological in vitro system representing the key cell-types associated with a receptive endometrial phenotype? SUMMARY ANSWER: We present a new concept to investigate endometrial receptivity, with a 3D organotypic co-culture model to simulate an early and transient acute autoinflammatory decidual status that resolves in the induction of a receptive endometrial phenotype. WHAT IS KNOWN ALREADY: Embryo implantation is dependent on a receptive uterine environment. Ovarian steroids drive post-ovulation structural and functional changes in the endometrium, which becomes transiently receptive for an implanting conceptus, termed the 'window of implantation', and dysregulation of endometrial receptivity is implicated in a range of reproductive, obstetric, and gynaecological disorders and malignancies. The interactions that take place within the uterine microenvironment during this time are not fully understood, and human studies are constrained by a lack of access to uterine tissue from specific time-points during the menstrual cycle. Physiologically relevant in vitro model systems are therefore fundamental for conducting investigations to better understand the cellular and molecular mechanisms controlling endometrial receptivity. STUDY DESIGN SIZE DURATION: We conducted an in vitro cell culture study using human cell lines and primary human cells isolated from endometrial biopsy tissue. The biopsy tissue samples were obtained from three women attending gynaecological outpatient departments in NHS Lothian. The work was carried out between December 2016 and April 2019, at the MRC Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh. PARTICIPANTS/MATERIALS SETTING METHODS: An endometrial stromal cell (ESC) line, and endometrial epithelial cells (EECs) isolated from endometrial biopsy tissue and expanded in vitro by conditional reprogramming, were used throughout the study. Immunocytochemical and flow cytometric analyses were used to confirm epithelial phenotype following conditional reprogramming of EECs. To construct an endometrial organotypic co-culture model, ESCs were embedded within a 3D growth factor-reduced Matrigel structure, with a single layer of conditionally reprogrammed EECs seeded on top. Cells were stimulated with increasing doses of medroxyprogesterone acetate, cAMP and oestradiol, in order to induce ESC decidual transformation and endometrial receptivity. Decidual response and the induction of a receptive epithelial phenotype were assessed by immunocytochemical detection and quantitative in-cell western analyses, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: A transient up-regulation of the interleukin-33 receptor protein, ST2L, was observed in ESCs, indicating a transient autoinflammatory decidual response to the hormonal stimulation, known to induce receptivity gene expression in the overlying epithelium. Hormonal stimulation increased the EEC protein levels of the key marker of endometrial receptivity, integrin αVß3 (n = 8; *P < 0.05; ***P < 0.0001). To our knowledge, this is the first demonstration of a dedicated endometrial organotypic model, which has been developed to investigate endometrial receptivity, via the recapitulation of an early decidual transitory acute autoinflammatory phase and induction of an epithelial phenotypic change, to represent a receptive endometrial status. LIMITATIONS REASONS FOR CAUTION: This simplified in vitro ESC-EEC co-culture system may be only partly representative of more complex in vivo conditions. WIDER IMPLICATIONS OF THE FINDINGS: The 3D endometrial organotypic model presented here may offer a valuable tool for investigating a range of reproductive, obstetric, and gynaecological disorders, to improve outcomes for assisted reproductive technologies, and for the development of advances in contraceptive methods. STUDY FUNDING/COMPETING INTERESTS: This work was supported in part by a Medical Research Council Centre Grant (project reference MR/N022556/1). R.F. was the recipient of a Moray Endowment award and a Barbour Watson Trust award. C.-J.L. is a Royal Society of Edinburgh Personal Research Fellow, funded by the Scottish Government. The authors have no conflicts of interest to declare.

Expression of miR-217 and HIF-1α/VEGF pathway in patients with diabetic foot ulcer and its effect on angiogenesis of diabetic foot ulcer rats.

OBJECTIVE: To investigate the expression of miR-217 and HIF-1α/VEGF pathway in patients with diabetic foot ulcer (DFU) and its effect on angiogenesis in DFU rats. METHODS: The serum levels of miR-217, HIF-1α and VEGF were detected in DFU and simple diabetes mellitus (DM) patients, and healthy controls. DFU rat models were established and treated with miR-217 inhibitors and/or HIF-1α siRNA. The ulcer healing of DFU rats was observed. Besides, ELISA method was performed to detect the serum level of HIF-1α, VEGF and inflammatory factors, immunohistochemical (IHC) method to test the micro-vessel density (MVD), as well as qRT-PCR and Western blot to determine expressions of miR-217, HIF-1α, VEGF, VEGFR2, eNOS, MMP-2, and MMP-9 in tissues. RESULTS: The serum levels of miR-217 were up-regulated while HIF-1α and VEGF were down-regulated in DFU patients and rats when compared with DM and healthy controls (all P < 0.05). Dual-luciferase reporter gene assay confirmed that HIF-1α was the direct target gene of miR-217. DFU rats treated with miR-217 inhibitors had decreased foot ulcer area and accelerated ulcer healing, with significantly reduced inflammatory factors (IL-1ß, TNF-α and IL-6), as well as elevated HIF-1α and VEGF (all P < 0.05); meanwhile, they remarkably increased the MVD in foot dorsum wound tissues and the protein expressions of HIF-1α, VEGF, VEGFR2, eNOS, MMP-2, and MMP-9 (all P < 0.05). CONCLUSION: Inhibiting miR-217 could up-regulate HIF-1α/VEGF pathway to promote angiogenesis and ameliorate inflammation of DFU rats, thereby effectively advancing the healing of ulcerated area.

Down-regulation of natural resistance-associated macrophage protein-1 (Nramp1) is associated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/1-methyl-4-phenylpyridinium (MPP+ )-induced α-synuclein accumulation and neurotoxicity.

AIMS: The accumulation of α-synuclein is a hallmark in the pathogenesis of Parkinson's disease (PD). Natural resistance-associated macrophage protein-1 (Nramp1) was previously shown to contribute to the degradation of extracellular α-synuclein in microglia under conditions of iron overload. This study was aimed at investigating the role of Nramp1 in α-synuclein pathology in the neurone under 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/1-methyl-4-phenylpyridinium (MPP+ ) treatment. METHODS: The expression of Nramp1 and pathological features (including iron and α-synuclein accumulation) were examined in the dopaminergic neurones of humans (with and without PD) and of mice [with and without receiving chronic MPTP intoxication]. The effects of Nramp1 expression on low-dose MPP+ -induced α-synuclein expression and neurotoxicity were determined in human dopaminergic neuroblastoma SH-SY5Y cells. RESULTS: Similar to the findings in the substantia nigra of human PD, lower expression of Nramp1 but higher levels of iron and α-synuclein were identified in the dopaminergic neurones of mice receiving chronic MPTP intoxication, compared to controls. In parallel to the loss of dopaminergic neurones, the numbers of glial fibrillary acidic protein- and ionized calcium-binding adapter molecule-1-positive cells were significantly increased in the substantia nigra of MPTP-treated mice. Likewise, in human neuroblastoma SH-SY5Y cells exposed to low-dose MPP+ , Nramp1 expression and cathepsin D activity were decreased, along with an increase in α-synuclein protein expression and aggregation. Overexpression of functional Nramp1 restored cathepsin D activity and attenuated α-synuclein up-regulation and neuronal cell death caused by MPP+ treatment. CONCLUSIONS: These data suggest that the neuronal expression of Nramp1 is important for protecting against the development of MPTP/MPP+ -induced α-synuclein pathology and neurotoxicity.

Application of Time-Resolved 3D Digital Subtraction Angiography to Plan Cerebral Arteriovenous Malformation Radiosurgery.

BACKGROUND AND PURPOSE: Time-resolved 3D-DSA (4D-DSA) enables viewing vasculature from any desired angle and time frame. We investigated whether these advantages may facilitate treatment planning and the feasibility of using 4D-DSA as a single imaging technique in AVM/dural arteriovenous fistula radiosurgery. MATERIALS AND METHODS: Twenty consecutive patients (8 dural arteriovenous fistulas and 12 AVMs; 13 men and 7 women; mean age, 45 years; range, 18-64 years) who were scheduled for gamma knife radiosurgery were recruited (November 2014 to October 2015). An optimal volume of reconstructed time-resolved 3D volumes that defines the AVM nidus/dural arteriovenous fistula was sliced into 2D-CT-like images. The original radiosurgery treatment plan was overlaid retrospectively. The registration errors of stereotactic 4D-DSA were compared with those of integrated stereotactic imaging. AVM/dural arteriovenous fistula volumes were contoured, and disjoint and conjoint components were identified. The Wilcoxon signed rank test and the Wilcoxon rank sum test were adopted to evaluate registration errors and contoured volumes of stereotactic 4D-DSA and integration of stereotactic MR imaging and stereotactic 2D-DSA. RESULTS: Sixteen of 20 patients were successfully registered in Advanced Leksell GammaPlan Program. The registration error of stereotactic 4D-DSA was smaller than that of integrated stereotactic imaging (P = .0009). The contoured AVM volume of 4D-DSA was smaller than that contoured on the integration of MR imaging and 2D-DSA, while major inconsistencies existed in cases of dural arteriovenous fistula (P = .042 and 0.039, respectively, for measurements conducted by 2 authors). CONCLUSIONS: Implementation of stereotactic 4D-DSA data for gamma knife radiosurgery for brain AVM/dural arteriovenous fistula is feasible. The ability of 4D-DSA to demonstrate vascular morphology and hemodynamics in 4 dimensions potentially reduces the target volumes of irradiation in vascular radiosurgery.

[Radiofrequency ablation combined with systemic chemotherapy in the management of nasopharyngeal carcinoma with liver metastasis].

Objective: To determine the treatment efficacy of systemic chemotherapy combined with sequential CT-guided radiofrequency ablation (chemo-RFA) in the management of nasopharyngeal carcinoma (NPC) with liver metastasis. Methods: A total of 427 NPC patients diagnosed with liver metastasis at Sun Yat-sen University Cancer Center between January 2000 and December 2013 were enrolled. Of the patients, 340 cases were male, 87 cases were female, the median age was 45 years (range 18-80 years), all patients received systemic chemotherapy and part of them also received RFA treatment. Patients were evaluated for response every two cycles during systemic chemotherapy and then every three months until death. One-to-one matched pairs between chemo-RFA group with chemo-only group were generated using propensity score matching; survival analysis was further conducted. Results: Of all the enrolled patients, 56 patients (13.1%) received combined treatment, 371 patients (86.9%)received chemotherapy alone. After propensity score matching, 56 pairs of well-matched liver metastatic NPC patients were selected from different treatment groups. The 1-, 3-, 5- year overall survival (OS) rates for chemo-RFA group were 89.2%, 45.5% and 32.5% and chemo-only group were 77.1%, 27.5% and 4.8% respectively; the 1-, 3-, 5- year progression-free survival (PFS) rates for chemo-RFA group were 64.0%, 25.4% and 10.7% and chemo-only group were 44.1%, 5.5% and 5.5% respectively.The adjusted hazard ratio in OS and PFS of the choice for chemo-RFA approach to chemo-only was HR 0.43, 95% CI 0.25-0.73 and HR 0.44, 95% CI 0.28-0.71 respectively. Conclusion: CT-guided RFA combined with chemotherapy approach could improve the survival rate for NPC patients with liver metastasis.

Glucocorticoid exposure and fracture risk in patients with new-onset rheumatoid arthritis.

Retrospective claims analysis indicated that high levels of daily and cumulative doses of systemic glucocorticoids were associated with elevated fracture risk in a large cohort of new RA patients under age 65. Heightened risk began to decline within months of discontinuation. Findings were similar among patients age <50 years. INTRODUCTION: We evaluated the impact of systemic glucocorticoid exposure on fracture risk among relatively young patients with new-onset rheumatoid arthritis (RA). METHODS: Using administrative data, we identified 42,127 RA patients diagnosed January 1, 2005-December 31, 2012, age 18-64 years, with benefits coverage for ≥12 months before RA diagnosis. Follow-up extended to clinical fracture, cancer diagnosis, or December 31, 2012. Glucocorticoid users were new to therapy. Fracture incidence rates (IR) were stratified by glucocorticoid exposure expressed as prednisone equivalent doses. Cox's proportional hazards models estimated fracture risk adjusted for demographics and baseline clinical characteristics to assess dose-response relationships with current (daily) and prior (cumulative) dose, and by time since discontinuation. RESULTS: Most patients (85 %) had glucocorticoid exposure. Exposed and unexposed patients were demographically similar (74 % female; mean age 49.7 and 48.8 years); 1 % had prior fracture. Fracture IRs (95 % confidence intervals) were 5 to 9 per 1000 person-years at doses <15 mg/day, 16.0 (11.0, 22.6) at doses ≥15 mg/day, and 13.4 (10.7, 16.7) at cumulative doses ≥5400 mg. Adjusted fracture risk was approximately 2-fold higher at highest dose levels compared with 0 mg/day current daily dose and <675 mg cumulative dose, respectively. Fracture risk was 29 % lower at 60-182 days post-discontinuation compared with ongoing use and was similar to unexposed patients by 12 months. Findings were similar among patients age <50 years. CONCLUSIONS: Among younger, new-onset RA patients, fracture risk was significantly elevated at high levels of daily and cumulative dose, and was similar to unexposed patients by 12 months post-discontinuation.

The clinical characteristics and manifestations of cytomegalovirus esophagitis.

Esophagitis is the second most common gastrointestinal manifestation of cytomegalovirus (CMV) infection after colitis. CMV esophagitis has been reported in patients who have undergone transplantation, are on long-term renal dialysis, or who have the human immunodeficiency virus infection. This study aimed to investigate the clinical characteristics and manifestations of CMV esophagitis in patients who underwent diagnostic endoscopy. A total of 16 patients with histologically proven CMV infection were identified from 1539 patients with esophageal ulcers and analyzed retrospectively (January 2006 to December 2013). Patients' personal data (age, smoking, and alcohol consumption), underlying systemic diseases (diabetes mellitus, end-stage renal disease, and chronic obstructive pulmonary disease), malignancy, indication for esophagogastroduodenoscopy, endoscopic characteristics, and diagnostic methods (pathological or serological findings) were collected for further analysis. Among the patients with CMV esophagitis, the mean age was 59.94 years (range, 23-84 years). The male : female ratio was 1.67:1. Odynophagia and epigastralgia were common symptoms. Of the 16 patients, 3 (18.75%) were infected with the human immunodeficiency virus and 9 (56.25%) had an underlying malignancy, including lung cancer (6 patients), esophageal cancer (2 patients), gastric cancer (1 patient), ampulla of Vater cancer (1 patient), and lymphoma (1 patient). Six of the 9 patients (66.7%) with malignancy had been administered concurrent chemoradiotherapy (CCRT). In this study, patients with malignancy who had been administered CCRT were at increased risk for CMV esophagitis, which had not been reported before in the literature. CMV esophagitis should be considered as a potential treatment-related complication of CCRT.

Clinical epidemiology and molecular profiling of human bocavirus in faecal samples from children with diarrhoea in Guangzhou, China.

To understand the clinical epidemiology and molecular characteristics of human bocavirus (HBoV) infection in children with diarrhoea in Guangzhou, South China, we collected 1128 faecal specimens from children with diarrhoea from July 2010 to December 2012. HBoV and five other major enteric viruses were examined using real-time polymerase chain reaction. Human rotavirus (HRV) was the most prevalent pathogen, detected in 250 (22·2%) cases, followed by enteric adenovirus (EADV) in 76 (6·7%) cases, human astrovirus (HAstV) in 38 (3·4%) cases, HBoV in 17 (1·5%) cases, sapovirus (SaV) in 14 (1·2%) cases, and norovirus (NoV) in 9 (0·8%) cases. Co-infections were identified in 3·7% of the study population and 23·5% of HBoV-positive specimens. Phylogenetic analysis revealed 14 HBoV strains to be clustered into species HBoV1 with only minor variations among them. Overall, the detection of HBoV appears to partially contribute to the overall detection gap for enteric infections, single HBoV infection rarely results in severe clinical outcomes, and HBoV sequencing data appears to support conserved genomes across strains identified in this study.

Radiation doses of cerebral blood volume measurements using C-arm CT: A phantom study.

BACKGROUND AND PURPOSE: Parenchymal blood volume measurement by C-arm CT facilitates in-room peritherapeutic perfusion evaluation. However, the radiation dose remains a major concern. This study aimed to compare the radiation dose of parenchymal blood volume measurement using C-arm CT with that of conventional CTP using multidetector CT. MATERIALS AND METHODS: A biplane DSA equipped with C-arm CT and a Rando-Alderson phantom were used. Slab parenchymal blood volume (8-cm scanning range in a craniocaudal direction) and whole-brain parenchymal blood volume with identical scanning parameters, except for scanning ranges, were undertaken on DSA. Eighty thermoluminescent dosimeters were embedded into 22 organ sites of the phantom. We followed the guidelines of the International Commission on Radiation Protection number 103 to calculate the effective doses. For comparison, 8-cm CTP with the same phantom and thermoluminescent dosimeter distribution was performed on a multidetector CT. Two repeat dose experiments with the same scanning parameters and phantom and thermoluminescent dosimeter settings were conducted. RESULTS: Brain-equivalent dose in slab parenchymal blood volume, whole-brain parenchymal blood volume, and CTP were 52.29 ± 35.31, 107.51 ± 31.20, and 163.55 ± 89.45 mSv, respectively. Variations in the measurement of an equivalent dose for the lens were highest in slab parenchymal blood volume (64.5%), followed by CTP (54.6%) and whole-brain parenchymal blood volume (29.0%). The effective doses of slab parenchymal blood volume, whole-brain parenchymal blood volume, and CTP were 0.87 ± 0.55, 3.91 ± 0.78, and 2.77 ± 1.59 mSv, respectively. CONCLUSIONS: The dose measurement conducted in the current study was reliable and reproducible. The effective dose of slab parenchymal blood volume is about one-third that of CTP. With the advantages of on-site and immediate imaging availability and saving procedural time and patient transportation, slab parenchymal blood volume measurement using C-arm CT can be recommended for clinical application.

Prognostic significance of the number of examined lymph nodes in node-negative gastric adenocarcinoma.

AIM: In this study, we investigated the prognostic significance of the number of examined lymph nodes in node-negative gastric adenocarcinoma (GC). PATIENTS AND METHODS: A total of 1194 node-positive and 1030 node-negative GC patients undergoing potentially curative gastrectomy was enrolled in this study. Patients were stratified into 3 groups according to the number of examined lymph nodes: group 1, ≤ 15; group 2, 16-25; group 3, >25. RESULTS: Patients with node-negative GC had significantly favorable survival compared with those with node-positive. Among patients with node-negative T2-T4 disease, the percentage of locoregional relapse was higher in those with <25 examined lymph nodes than in those with ≥ 25 examined lymph nodes. The number of examined lymph nodes affected the overall survival rates for patients with node-negative T2-T4 GC but not for patients with T1 lesions. Tumor size, tumor location, the number of examined lymph nodes, T status, and the presence of perineural invasion were significant prognostic factors as determined by multivariate analysis in node-negative GC. CONCLUSIONS: No survival benefit of examining ≥ 15 lymph nodes was noted for patients with node-negative T1 GC. Extensive lymphadenectomy in patients with node-negative T2-T4 lesions in whom the number of examined lymph nodes was >25 had favorable survival.

Evaluation of the outcomes of endovascular management for patients with head and neck cancers and associated carotid blowout syndrome of the external carotid artery.

AIM: To evaluate factors related to the technical and haemostatic outcomes of endovascular management in patients with head and neck cancers (HNC) associated with carotid blowout syndrome (CBS) of the external carotid artery (ECA). MATERIALS AND METHODS: Between 2002 and 2011, 34 patients with HNC with CBS involving branches of the ECA underwent endovascular therapy. Treatment included embolization with microparticles, microcoils, or acrylic adhesives. Fisher's exact test was used to examine demographic features, clinical and angiographic severities, and clinical and imaging findings as predictors of endovascular management outcomes. RESULTS: Technical success and immediate haemostasis were achieved in all patients. Technical complications were encountered in one patient (2.9%). Rebleeding occurred in nine patients (26.5%). Angiographic vascular disruption grading from slight (1) to severe (4) revealed that the 18 patients with acute CBS had scores of 2 (2/18, 11.1%), 3 (3/18, 16.7%), and 4 (13/18, 72.2%). The 16 patients with impending and threatened CBS had scores of 1 (1/16, 6.25%), 2 (5/16, 31.25%), and 3 (10/16, 62.5%; p = 0.0003). For the 25 patients who underwent preprocedural computed tomography (CT)/magnetic resonance imaging (MRI) examinations within 3 months of treatment, the agreement between clinical and imaging findings reached the sensitivity, specificity, and kappa values for recurrent tumours (1, 0.7143, 0.7826), soft-tissue defect (0.9091, 0.3333, 0.2424), and sinus tract/fistula (0.4737, 0, 0.4286). CONCLUSION: Endovascular management for patients with CBS of the ECA had high technical success and safety but was associated with high rebleeding rates. We suggest applying aggressive post-procedural follow-up and using preprocedural CT/MRI to enhance the periprocedural diagnosis.

Can iterative reconstruction improve imaging quality for lower radiation CT perfusion? Initial experience.

BACKGROUND AND PURPOSE: Initial results using IR for CT of the head showed satisfactory subjective and objective imaging quality with a 20-40% radiation dose reduction. The aim of our study was to compare the influence of IR and FBP algorithms on perfusion parameters at standard and lowered doses of CTP. MATERIALS AND METHODS: Forty patients with unilateral carotid stenosis post-carotid stent placement referred for follow-up CTP were divided into 2 groups (tube currents were 100 mAs in group A and 80 mAs in group B). Datasets were reconstructed with IR and FBP algorithms; and SNRs of gray matter, white matter, and arterial and venous ROIs were compared. CBF, CBV, and MTT means and SNRs were evaluated by using linear regression, and qualitative imaging scores were compared across the 2 algorithms. RESULTS: The mean effective radiation dose of group B (2.06 mSv) was approximately 20% lower than that of group A (2.56 mSv). SNRs for ROIs in the dynamic contrast-enhanced images were significantly higher than those for the FBP images. Correlations of the SNRs for CBF, CBV, and MTT across the 2 algorithms were moderate (R² = 0.46, 0.23, and 0.44, respectively). ROIs in gray matter rather than the IR algorithm predicted increasing SNRs in all CBF, CBV, and MTT maps. Two cases of significant restenosis were confirmed in both algorithms. CBV, CBF, and MTT imaging scores did not differ significantly across algorithms or groups. CONCLUSIONS: Lower dose CTP (20% below normal dose) without IR can effectively identify oligemic tissue in poststenting follow-up. IR does not alter the absolute values or increase the SNRs of perfusion parameters. Other methods should be attempted to improve SNRs in settings with low tube currents.

Monitoring peri-therapeutic cerebral circulation time: a feasibility study using color-coded quantitative DSA in patients with steno-occlusive arterial disease.

BACKGROUND AND PURPOSE: Intracranial hemodynamics are important for management of SOAD. This study aimed to monitor peri-stent placement intracranial CirT of patients with SOAD. MATERIALS AND METHODS: Twenty-five patients received stent placement for extracranial ICA stenosis, and 34 patients with normal CirT were recruited as controls. Their color-coded DSAs were used to define the Tmax of selected intravascular ROI. A total of 20 ROIs of the ICA, OphA, ACA, MCA, FV, PV, OV, SSS, SS, IJV, and MCV were selected. rTmax was defined as the Tmax at the selected region of interest minus Tmax at the cervical segment of the ICA (I1 on AP view and IA on lateral view). rTmax of the PV was defined as intracranial CirT. Intergroup and intragroup longitudinal comparisons of rTmax were performed. RESULTS: rTmax values of the normal cohorts were as follows: ICA-AP, 0.12; ICA-LAT, 0.10; A1, 0.28; A2, 0.53; A3, 0.81; M1, 0.40; M2, 0.80; M3, 0.95; OphA, 0.35; FV, 4.83; PV, 5.11; OV, 5.17; SSS, 6.16; SS, 6.51; IJV, 6.81; and MCV, 3.86 seconds. Before stent placement, the rTmax values of arterial ROIs, except A3 and M3, were prolonged compared with values from control subjects (P < .05). None of the rTmax of any venous ROIs in the stenotic group was prolonged with significance. After stent placement, the rTmax of all arterial ROIs shortened significantly, except A1and M3. Poststenting rTmax was not different from the control group. CONCLUSIONS: Without extra contrast medium and radiation dosages, color-coded quantitative DSA enables real-time monitoring of peri-therapeutic intracranial CirT in patients with SOAD .

Radiofrequency ablation for hepatocellular carcinoma: use of low vs maximal radiofrequency power.

OBJECTIVES: To investigate whether radiofrequency (RF) ablation with low power (LP) or maximal power (MP) for hepatocellular carcinoma (HCC) can achieve optimal ablation and fewer adverse effects. METHODS: RF ablation was performed with MP in 101 patients (129 tumours) and with LP in 46 patients (61 tumours). MP RF ablation used power of >120 W. RF power below this was designated as LP. Clinical outcomes were also analysed in subgroups of high-risk tumours near the bile duct and blood vessels. RESULTS: Primary effectiveness was achieved in 91.8% in the LP group and 89.9% in the MP group (p = 0.795). 1 and 2-year local tumour progression rates were 28% and 30%, respectively, in the LP group, and 24% and 29%, respectively, in the MP group (p = 0.70). 1 and 2-year survival rates were 98% and 98%, respectively, in the LP group, and 93% and 90%, respectively, in the MP group (p = 0.216). The MP group had more adverse effects, with post-RF ablation syndrome, asymptomatic pleural effusion and ascites, than the LP group (20% vs 39% in the MP group; p = 0.027); however, there was no significant difference in major complication rates (6% in the MP and LP groups; p = 0.497). Among the patients with high-risk tumours, RF ablation using MP vs LP was comparable in primary effectiveness (91.7% vs 95.2%; p = 0.618), local tumour progression (42.9% vs 29.2%; p = 0.304) and overall complications (5% vs 8%; p=0.618). CONCLUSION: RF ablation with LP and MP are comparable in clinical outcomes but considerably fewer adverse effects were encountered in the LP group.

Combined endovascular and surgical approach for the treatment of palpebral arteriovenous malformations: experience of a single center.

BACKGROUND AND PURPOSE: Palpebral AVMs (pAVMs) are rare vascular lesions for which the treatment is challenging. Our aim was to present the technical aspects of the presurgical treatment by interventional neuroradiology of pAVMs and to report the clinical and angiographic results of combined (interventional neuroradiology/surgery) treatment of these malformations. MATERIALS AND METHODS: Nine patients (5 females, 4 males) with a mean age of 22 years (range, 12-35 years) were treated in our department from December 1992 to April 2007 for superficial pAVMs. Seven patients presented with isolated pAVMs, while 2 had hemifacial AVMs. Ten TAE procedures, by using a liquid embolic agent (glue or Onyx) or microparticles, were performed in 7 patients. Six patients underwent absolute alcohol, glue, or sclerotic agent injection by direct puncture in 8 procedures. Clinical and angiographic follow-up were performed with a mean delay of, respectively, 6.3 and 5 years. RESULTS: Three patients had a single EVT. Iterative procedures were performed in 5 patients. In 1 patient, EVT was not performed because of the risk of occlusion of the central retinal artery. No complication occurred except 1 case of transient palpebral hematoma. No visual acuity loss related to an endovascular procedure was reported. Exclusion of the AVMs at the end of the procedure was >75% in all cases and total in 3/8 cases. All the patients except 2 underwent at least 1 surgical procedure after the embolization. Good clinical regression of the mass was obtained in all patients at long-term follow-up. CONCLUSIONS: Combined endovascular and surgical treatment of pAVMs is an effective and safe technique with good clinical results at long-term follow-up.

Apical membrane rupture and backward bile flooding in acetaminophen-induced hepatocyte necrosis.

Morphological changes of hepatocyte death have so far only been described on cells in culture or in tissue sections. Using a high-resolution and high-magnification multiphoton microscopic system, we recorded in living mice serial changes of acetaminophen (APAP)-induced hepatocyte necrosis in relevance to metabolism of a fluorogenic bile solute. Initial changes of hepatocyte injury included basal membrane disruption and loss of mitochondrial membrane potential. An overwhelming event of rupture at adjacent apical membrane resulting in flooding of bile into these hepatocytes might ensue. Belbs formed on basal membrane and then dislodged into the sinusoid circulation. Transmission electron microscopy disclosed a necrotic hepatocyte depicting well the changes after apical membrane rupture and bile flooding. Administration of the antidote N-acetylcysteine dramatically reduced the occurrence of apical membrane rupture. The present results demonstrated a hidden but critical step of apical membrane rupture leading to irreversible APAP-induced hepatocyte injury.

Toward an ideal animal model to trace donor cell fates after stem cell therapy: production of stably labeled multipotent mesenchymal stem cells from bone marrow of transgenic pigs harboring enhanced green fluorescence protein gene.

The discovery of postnatal mesenchymal stem cells (MSC) with their general multipotentiality has fueled much interest in the development of cell-based therapies. Proper identification of transplanted MSC is crucial for evaluating donor cell distribution, differentiation, and migration. Lack of an efficient marker of transplanted MSC has precluded our understanding of MSC-related regenerative studies, especially in large animal models such as pigs. In the present study, we produced transgenic pigs harboring an enhanced green fluorescent protein (EGFP) gene. The pigs provide a reliable and reproducible source for obtaining stable EGFP-labeled MSC, which is very useful for donor cell tracking after transplantation. The undifferentiated EGFP-tagged MSC expressed a greater quantity of EGFP while maintaining MSC multipotentiality. These cells exhibited homogeneous surface epitopes and possessed classic trilineage differentiation potential into osteogenic, adipogenic, and chondrogenic lineages, with robust EGFP expression maintained in all differentiated progeny. Injection of donor MSC can dramatically increase the thickness of infarcted myocardium and improve cardiac function in mice. Moreover, the MSC, with their strong EGFP expression, can be easily distinguished from the background autofluorescence in myocardial infarcts. We demonstrated an efficient, effective, and easy way to identify MSC after long-term culture and transplantation. With the transgenic model, we were able to obtain stem or progenitor cells in earlier passages compared with the transfection of traceable markers into established MSC. Because the integration site of the transgene was the same for all cells, we lessened the potential for positional effects and the heterogeneity of the stem cells. The EGFP-transgenic pigs may serve as useful biomedical and agricultural models of somatic stem cell biology.

Stenting in the remnant of the third aortic arch in a case of post-irradiation occluded internal carotid artery.

Collateral networks between the external carotid artery and internal carotid arteries become crucial for cerebral perfusion after occlusion of internal carotid arteries. We report the first case of a patient who received percutaneous transluminal angioplasty and stenting in a collateral vessel between the external and internal carotid artery for treatment of radiation induced severe stenosis of the internal carotid artery in the context of a contralateral internal carotid artery occlusion.