Cardiac 123I-MIBG normal uptake values are population-specific: Results from a cohort of controls over 60 years of age.

PURPOSE: Cardiac 123I-MIBG image interpretation is affected by population differences and technical factors. We recruited older adults without cognitive decline and compared their cardiac MIBG uptake with results from the literature. METHODS: Phantom calibration confirmed that cardiac uptake results from Japan could be applied to our center. We recruited 31 controls, 17 individuals with dementia with Lewy bodies (DLB) and 15 with Alzheimer's disease (AD). Images were acquired 20 minutes and four hours after injection using Siemens cameras with medium-energy low-penetration (MELP) collimators. Local normal heart-to-mediastinum (HMR) ratios were compared to Japanese results. RESULTS: Siemens gamma cameras with MELP collimators should give HMRs very close to the calibrated values used in Japan. However, our cut-offs with controls were lower at 2.07 for early and 1.86 for delayed images. Applying our lower cut-off to the dementia patients may increase the specificity of cardiac MIBG imaging for DLB diagnosis in a UK population without reducing sensitivity. CONCLUSIONS: Our local HMR cut-off values are lower than in Japan, higher than in a large US study but similar to those found in another UK center. UK centers using other cameras and collimators may need to use different cut-offs to apply our results.

Advances in image enhancement for sarcoma surgery.

The recurrence rate of soft tissue and bone sarcomas strongly correlates to the status of the surgical margin after excision, yet excessive removal of tissue may lead to distinct, otherwise avoidable morbidity. Therefore, adequate margination of sarcomas both pre- and intra-operatively is a clinical necessity that has not yet fully been met. Current guidance for soft-tissue sarcomas recommends an ultrasound scan followed by magnetic resonance imaging (MRI). For bone sarcomas, two plane radiographs are required, followed similarly by an MRI scan. The introduction of more precise imaging modalities may reduce the morbidity associated with sarcoma surgery; the PET-CT and PET-MRI approaches in particular demonstrating high clinical efficacy. Despite advancements in the accuracy in pre-operative imaging, translation of an image to surgical margins is difficult, regularly resulting in wider resection margins than required. For soft tissue sarcomas there is currently no standard technique for image guided resections, while for bone sarcomas fluoroscopy may be used, however margins are not easily discernible during the surgical procedure. Near infra-red (NIR) fluorescence guided surgery offers an intra-operative modality through which complete tumour resection with adequate tumour-free margins may be achieved, while simultaneously minimising surgical morbidity. NIR imaging presents a potentially valuable adjunct to sarcoma surgery. Early reports indicate that it may be able to provide the surgeon with helpful information on anatomy, perfusion, lymphatic drainage, tumour margins and metastases. The use of NIR fluorochromes have also been demonstrated to be well tolerated by patients. However, prior to widespread implementation, studies related to cost-effectiveness and the development of protocols are essential. Nevertheless, NIR imaging may become ubiquitous in the future, carrying the potential to transform the surgical management of sarcoma.

123I-MIBG scintigraphy utility and cut-off value in a clinically representative dementia cohort.

OBJECTIVE: To determine the utility of 123I-metaiodobenzylguanidine cardiac scintigraphy (MIBG), and optimum heart: mediastinum ratio (HMR) for differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) in a clinically representative population, comparing findings with those of 123I-2ß -carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT) SPECT. METHODS: We recruited subjects with probable DLB (n = 17) and probable AD (n = 16) from clinical services. Each participant underwent clinical examination, cardiac MIBG scintigraphy and FP-CIT SPECT. Diagnosis was made on the basis of clinical symptoms using validated criteria. Cardiac MIBG uptake was measured by the planar HMR, blind to clinical diagnosis, with values below a cut-off taken from a previous study (<2.2 at four hours) defining scans as abnormal. FP-CIT scans were blindly rated according to a visual rating scale. RESULTS: MIBG had a sensitivity, specificity and overall accuracy of 71%, 81% and 76% for distinguishing DLB from AD. FP-CIT demonstrated a sensitivity, specificity and accuracy of 82%, 88% and 85%. Using a lower HMR cut-off to distinguish between abnormal and normal MIBG scans improved the accuracy of MIBG, raising specificity (100%) and overall accuracy (85%) without compromising sensitivity (71%). Neither prescription of potentially interfering medications, nor a history of myocardial infarction (MI), had a significant effect on HMR. CONCLUSION: We found that MIBG did not demonstrate superior sensitivity and overall accuracy to FP-CIT. HMR cut-off influences biomarker utility, and clinical and Caucasian populations may require a lower cut-off than those reported elsewhere. Future MIBG studies should include clinically representative cohorts as neither medications nor previous MI appear to influence HMR.

The introduction of radioactive seed localisation improves the oncological outcome of image guided breast conservation surgery.

INTRODUCTION: Radioactive seed localisation (RSL) has become increasingly popular for localisation of non-palpable breast tumours. This is largely due to advantages it offers in terms of practicality and convenience when compared to guide wire localisation (WL). This institute switched from using WL to RSL in September 2014. The primary aim was to assess whether this change improved the accuracy of excision with regards to inadequate margin rates and weight of excision specimens. The secondary aim was to establish whether there is a "learning curve" associated with RSL technique. METHODS: Retrospective data collection was performed for 333 consecutive cases of unifocal non-palpable invasive breast cancers undergoing excision with WL or RSL. An inadequate margin was defined as tumour <1 mm from an inked radial margin. Patient demographics, tumour characteristics and clinical outcomes were compared between WL and RSL cases. RESULTS: 100 WL and 233 RSL cases were included. Patient demographics and tumour characteristics were similar for both groups. Inadequate margin rates were 18% with WL and 8.6% with RSL (p = 0.013). Median specimen weights were 33.3 g with WL and 28.7 g with RSL (p = 0.014). Subdividing the RSL group into the first 100 cases performed (RSL1) and the subsequent 133 cases (RSL2), inadequate margin rates were 13.0% and 5.3% respectively (p = 0.037). Mean specimen weights were similar. CONCLUSION: Switching from WL to RSL results in a significant reduction in both inadequate margin rates and specimen weights. A procedure-specific learning curve is present on first implementation of RSL and following this, inadequate margin rates are further reduced.

The mortality rate of electroconvulsive therapy: a systematic review and pooled analysis.

OBJECTIVE: Electroconvulsive therapy (ECT) remains underutilized because of fears of cognitive and medical risks, including the risk of death. In this study, we aimed to assess the mortality rate of ECT by means of a systematic review and pooled analysis. METHOD: The study was conducted in adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The ECT-related mortality rate was calculated as the total number of ECT-related deaths reported in the included studies divided by the total number of ECT treatments. RESULTS: Fifteen studies with data from 32 countries reporting on a total of 766 180 ECT treatments met the inclusion criteria. Sixteen cases of ECT-related death were reported in the included studies yielding an ECT-related mortality rate of 2.1 per 100 000 treatments (95% CI: 1.2-3.4). In the nine studies that were published after 2001 (covering 414 747 treatments), there was only one reported ECT-related death. CONCLUSION: The ECT-related mortality rate was estimated at 2.1 per 100 000 treatments. In comparison, a recent analysis of the mortality of general anesthesia in relation to surgical procedures reported a mortality rate of 3.4 per 100 000. Our findings document that death caused by ECT is an extremely rare event.

Cerebral glucose metabolism and cognition in newly diagnosed Parkinson's disease: ICICLE-PD study.

OBJECTIVE: To assess reductions of cerebral glucose metabolism in Parkinson's disease (PD) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their associations with cognitive decline. METHODS: FDG-PET was performed on a cohort of 79 patients with newly diagnosed PD (mean disease duration 8 months) and 20 unrelated controls. PD participants were scanned while on their usual dopaminergic medication. Cognitive testing was performed at baseline, and after 18 months using the Cognitive Drug Research (CDR) and Cambridge Neuropsychological Test Automated Battery (CANTAB) computerised batteries, the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). We used statistical parametric mapping (SPM V.12) software to compare groups and investigate voxelwise correlations between FDG metabolism and cognitive score at baseline. Linear regression was used to evaluate how levels of cortical FDG metabolism were predictive of subsequent cognitive decline rated with the MMSE and MoCA. RESULTS: PD participants showed reduced glucose metabolism in the occipital and inferior parietal lobes relative to controls. Low performance on memory-based tasks was associated with reduced FDG metabolism in posterior parietal and temporal regions, while attentional performance was associated with more frontal deficits. Baseline parietal to cerebellum FDG metabolism ratios predicted MMSE (ß=0.38, p=0.001) and MoCA (ß=0.3, p=0.002) at 18 months controlling for baseline score. CONCLUSIONS: Reductions in cortical FDG metabolism were present in newly diagnosed PD, and correlated with performance on neuropsychological tests. A reduced baseline parietal metabolism is associated with risk of cognitive decline and may represent a potential biomarker for this state and the development of PD dementia.

Subgenual cingulate cortical activity predicts the efficacy of electroconvulsive therapy.

Electroconvulsive therapy (ECT) is the most effective treatment for depression, yet its mechanism of action is unknown. Our goal was to investigate the neurobiological underpinnings of ECT response using longitudinally collected resting-state functional magnetic resonance imaging (rs-fMRI) in 16 patients with treatment-resistant depression and 10 healthy controls. Patients received bifrontal ECT 3 times a week under general anesthesia. We acquired rs-fMRI at three time points: at baseline, after the 1st ECT administration and after the course of the ECT treatment; depression was assessed with the Hamilton Depression Rating Scale (HAM-D). The primary measure derived from rs-fMRI was fractional amplitude of low frequency fluctuation (fALFF), which provides an unbiased voxel-wise estimation of brain activity. We also conducted seed-based functional connectivity analysis based on our primary findings. We compared treatment-related changes in HAM-D scores with pre- and post-treatment fALFF and connectivity measures. Subcallosal cingulate cortex (SCC) demonstrated higher BOLD signal fluctuations (fALFF) at baseline in depressed patients, and SCC fALFF decreased over the course of treatment. The baseline level of fALFF of SCC predicted response to ECT. In addition, connectivity of SCC with bilateral hippocampus, bilateral temporal pole, and ventromedial prefrontal cortex was significantly reduced over the course of treatment. These results suggest that the antidepressant effect of ECT may be mediated by downregulation of SCC activity and connectivity. SCC function may serve as an important biomarker of target engagement in the development of novel therapies for depression that is resistant to treatment with standard medications.

Electroconvulsive therapy is equally effective in unipolar and bipolar depression.

OBJECTIVE: To determine the relative efficacy of electroconvulsive therapy (ECT) in the treatment of bipolar (BP) and unipolar (UP) depressive illness and clarify its role in BP depression. METHOD: Patients referred for ECT with both UP and BP depressions. [classified by Structured Clinical Interview for DSM (SCID-I) criteria for history of mania] were included in a multi-site collaborative, double-masked, randomized controlled trial of three electrode placements - right unilateral, bifrontal or bitemporal - in a permutated block randomization scheme. RESULTS: Of 220 patients, 170 patients (77.3%) were classified as UP and 50 (22.7%) as BP depression in the intent-to-treat sample. The remission and response rates and numbers of ECT for both groups were equivalent. CONCLUSION: Both UP and BP depressions remit with ECT. Polarity is not a factor in the response rate. In this sample ECT did not precipitate mania in depressed patients. Treatment algorithms for UP and BP depression warrant re-evaluation.

Comparison of colonic stenting and open surgery for malignant large bowel obstruction.

BACKGROUND: Colonic stents potentially offer effective palliation for those with bowel obstruction attributable to incurable malignancy, and a "bridge to surgery" for those in whom emergency surgery would necessitate a stoma. The current study compared the outcomes of stents and open surgery in the management of malignant large bowel obstruction. METHODS: A literature search of the Medline, Ovid, Embase and Cochrane databases was performed to identify comparative studies reporting outcomes on colonic stenting and surgery for large bowel obstruction. Random effects meta-analytical techniques were applied to identify differences in outcomes between the two groups. Sensitivity analysis of high quality studies, those reporting on more than 35 patients, those solely concerning colorectal cancer and studies performing intention to treat analysis was undertaken to evaluate the study heterogeneity. RESULTS: A total of 10 studies satisfied the criteria for inclusion, with outcomes reported for 451 patients. Stent insertion was attempted for 244 patients (54.1%), and proved successful for 226 (92.6%). The length of hospital stay was shorter by 7.72 days in the stent group (p < 0.001), which also had lower mortality (p = 0.03) and fewer medical complications (p < 0.001). Stoma formation at any point during management was significantly lower than in the stent group (odds ratio, 0.02; p < 0.001), and "bridging to surgery" did not adversely influence survival. CONCLUSIONS: Colonic stenting offers effective palliation for malignant bowel obstruction, with short lengths of hospital stay and a low rate for stoma formation, but data on quality of life and economic evaluation are limited. There is no evidence of differences in long-term survival between those who have stents followed by subsequent resection and those undergoing emergency bowel resection.

ECT remission rates in psychotic versus nonpsychotic depressed patients: a report from CORE.

OBJECTIVE: To compare the relative efficacy of electroconvulsive therapy (ECT) in psychotic and nonpsychotic patients with unipolar major depression. METHODS: The outcome of an acute ECT course in 253 patients with nonpsychotic (n = 176) and psychotic (n = 77) unipolar major depression was assessed in the first phase of an ongoing National Institute of Mental Health-supported four-hospital collaborative study of continuation treatments after successful ECT courses. ECT was administered with bilateral electrode placement at 50% above the titrated seizure threshold. The remission criteria were rigorous: a score

The influence of age on the response of major depression to electroconvulsive therapy: a C.O.R.E. Report.

As part of a C.O.R.E., multi-site longitudinal study comparing continuation electroconvulsive therapy (ECT) vs. continuation pharmacotherapy, the authors determined the response of 253 patients with major depression to acute-phase, bilateral ECT by use of the 24-item Hamilton Rating Scale for Depression. Remission rates for three age-groups, > or =65 years; 46-64 years; and < or =45 years, were 90 percent, 89.8 percent, and 70 percent, respectively. Age, as a continuous variable, positively influenced response to treatment. Bilateral, dose-titrated ECT is a highly effective acute treatment for major depression, and older age confers a greater likelihood of achieving remission.

Catatonic signs in neuroleptic malignant syndrome.

The study assessed catatonic signs in neuroleptic malignant syndrome (NMS). Records of inpatients meeting both stringent research criteria and DSM-IV criteria (n = 11) or only DSM-IV criteria (n = 5) for NMS were identified. The records were systematically rated on a 23-item rating scale for the presence of catatonic signs. Scores for NMS severity were related to the number of catatonic signs. Fifteen patients met both research criteria for catatonia and DSM-IV motor criteria for organic catatonia. The severity scores of NMS correlated with the number of catatonic signs (Spearman rho = +.71, P < .005). We conclude that multiple catatonic signs are present in NMS and the severity of NMS predicts the number of catatonic signs.

Is Lorazepam a treatment for neuroleptic malignant syndrome?

The authors assessed the ability of lorazepam and other benzodiazepines to affect the course of neuroleptic malignant syndrome (NMS). Records of inpatients who met both stringent research criteria and criteria under the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV) (n=11) or DSM-IV criteria alone (n=5) for NMS were identified. All received lorazepam or related benzodiazepines within 24 hours of NMS onset or hospital admission. The records were reviewed for resolution of clinical signs of NMS. Rigidity and fever abated within 24-48 hours, while secondary features of NMS were relieved within 64 hours. These results compared favorably with prior reports of 5-day to 10-day recovery periods. Benzodiazepine administration appeared to be well tolerated. Lorazepam and related benzodiazepines may reduce recovery time in NMS.

Catatonia and other motor syndromes in a chronically hospitalized psychiatric population.

BACKGROUND: To determine the motor characteristics of chronic catatonia, catatonia and other motor disorders were systematically rated in a long-term hospitalized sample. METHOD: Chronically hospitalized psychiatric inpatients (N = 42) with a clinical diagnosis of catatonic schizophrenia (295.2X) were rated for catatonia with a novel 23-item catatonia rating scale, and for parkinsonism, dyskinesia and akathisia using standard rating scales with scale-based criteria for case definition. RESULTS: Catatonia was the sole motor syndrome in nine cases (21%), co-existed with parkinsonism in five (12%), tardive dyskinesia in four (10%), and both parkinsonism and tardive dyskinesia in 10 (24%). There was no correlation between total scores across the four rating scales. 'Rigidity' was the sole catatonic sign which overlapped with other scales. The symptom profile of catatonia in this chronic sample was similar to previous reports based on acutely ill patients. CONCLUSION: Catatonia is distinguishable from other motor disorders in chronic psychiatric patients using the 23-item catatonia rating scale. The features of chronic catatonia are described, and the distribution of catatonic signs is similar for chronic and acute catatonia.

Synergism of lorazepam and electroconvulsive therapy in the treatment of catatonia.

Electroconvulsive therapy (ECT) and lorazepam are effective treatments for catatonia. ECT combined with benzodiazepines has been associated with reduced efficacy and efficiency and therefore is not recommended in the routine practice of ECT. We report 5 prospectively identified cases of catatonia treated either sequentially or concurrently with lorazepam and ECT. In each case, the combination of lorazepam with ECT was superior to monotherapy. This apparent synergism, its possible mechanisms, and its implications for treating catatonia are discussed.