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Contains fulltext : 288062.pdf (Publisher’s version ) (Closed access) There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, pFWE = 0.037; right: d = -0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, pFWE

IntroductionA considerable burden of the tuberculosis (TB) epidemic is found in adolescents. The reasons for increased susceptibility to TB infection and higher incidence of TB disease in adolescence, compared with the 5–10 years old age group, are incompletely understood. Despite the pressing clinical and public health need to better understand and address adolescent TB, research in this field remains limited.Methods and analysisTeen TB is an ongoing prospective observational cohort study that aims to better understand the biology, morbidity and social context of adolescent TB. The study plans to recruit 50 adolescents (10–19 years old) with newly diagnosed microbiologically confirmed pulmonary TB disease and 50 TB-exposed controls without evidence of TB disease in Cape Town, South Africa, which is highly endemic for TB. At baseline, cases and controls will undergo a detailed clinical evaluation, chest imaging, respiratory function assessments and blood collection for viral coinfections, inflammatory cytokines and pubertal hormone testing. At 2 weeks, 2 months and 12 months, TB disease cases will undergo further chest imaging and additional lung function testing to explore the patterns of respiratory abnormalities. At week 2, cases will complete a multicomponent quantitative questionnaire about psychological and social impacts on their experiences and longitudinal, in-depth qualitative data will be collected from a nested subsample of 20 cases and their families.Ethics and disseminationThe study protocol has received ethical approval from the Stellenbosch University Health Research Ethics Committee (N19/10/148). The study findings will be disseminated through peer-reviewed publications, academic conferences and formal presentations to health professionals. Results will also be made available to participants and caregivers.

Neuroimaging studies point to neurostructural abnormalities in youth with anxiety disorders. Yet, findings are based on small-scale studies, often with small effect sizes, and have limited generalizability and clinical relevance. These issues have prompted a paradigm shift in the field towards highly powered (i.e., big data) individual-level inferences, which are data-driven, transdiagnostic, and neurobiologically informed. Here, we built and validated neurostructural machine learning (ML) models for individual-level inferences based on the largest-ever multi-site neuroimaging sample of youth with anxiety disorders (age: 10-25 years, N=3,343 individuals from 32 global sites), as compiled by three ENIGMA Anxiety Working Groups: Panic Disorder (PD), Generalized Anxiety Disorder (GAD), and Social Anxiety Disorder (SAD). ML classifiers were trained on MRI-derived regional measures of cortical thickness, surface area, and subcortical volumes to classify patients and healthy controls (HC) for each anxiety disorder separately and across disorders (transdiagnostic classification). Modest, yet robust, classification performance was achieved for PD vs. HC (AUC=0.62), but other disorder-specific and transdiagnostic classifications were not significantly different from chance. However, above chance-level transdiagnostic classifications were obtained in exploratory subgroup analyses of male patients vs. male HC, unmedicated patients vs. HC, and patients with low anxiety severity vs. HC (AUC 0.59-0.63). The above chance-level classifications were based on plausible and specific neuroanatomical features in fronto-striato-limbic and temporo-parietal regions. This study provides a realistic estimate of classification performance in a large, ecologically valid, multi-site sample of youth with anxiety disorders, and may as such serve as a benchmark.

Purpose Ventilation–perfusion single-photon emission computed tomography (VP SPECT) plays an important role in pulmonary embolism diagnosis. Rapid results may be obtained using same-day ventilation followed by perfusion imaging, but generally requires careful attention to achieving an optimal count rate ratio (P/V ratio) of ≥ 3:1. This study investigated whether the ratio of counts simultaneously acquired in adjacent primary and Compton scatter energy windows (Eratio) on V SPECT was predictive of final normalised perfusion count rate (PCRnorm) on P SPECT using [99mTc]Tc-macroaggregated albumin (MAA), thus allowing for optimisation of P/V ratios. Methods Same-day VP SPECT studies acquired using standard protocols in adult patients during a 2-year period (training dataset) were assessed. Studies were included provided they were acquired with correct imaging parameters, and injection site imaging and laboratory records were available for quality control and normalised count rate corrections. Extraction of DICOM information, and linear regression were performed using custom Python and R scripts. A predictive tool was developed in Microsoft Excel. This tool was then validated using a second (validation) dataset of same-day studies acquired over a subsequent 7-month period. Accuracy of the prediction tool was assessed by calculating the mean absolute percentage error (MAPE). Results Of 643 studies performed, the scans of 342 participants (median age 30.4 years, 318 female) were included in the training dataset, the analysis of which yielded a significant regression equation (F(1,340) = 1057.3, p R2 of 0.756 and MSE of 0.001089. A prediction tool designed for routine clinical use was developed for predicting final P/V ratio. Of an additional 285 studies, 198 were included in the second (validation) dataset (median age 29.7 years, 188 female). The Excel-based tool was shown to be 91% accurate (MAPE: 9%) in predicting P/V ratio. Conclusion The relationship between the ratio of simultaneously acquired counts in adjacent energy windows on V SPECT and perfusion count rate after administration of a known activity of [99mTc]Tc-MAA can be linearly approximated. A predictive tool based on this work may assist in optimising the dose and timing of [99mTc]Tc-MAA administration in same-day studies to the benefit of patients and workflows.

IntroductionPositron emission tomography-computed tomography (PET-CT) imaging is commonly used to identify nodal involvement in locally advanced cervical carcinoma, but its appropriateness for that purpose among HIV-positive patients has rarely been studied. We analyzed PET-CT findings and subsequent treatment prescribed in patients with locally advanced cervical carcinoma in Cape Town, South Africa.MethodsWe identified a cohort of consecutive cervical carcinoma patients International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IIIB at our cancer center who underwent a planning 18-fluorodeoxyglucose (18FDG) PET-CT scan from January 2015 through December 2018. Demographics, PET-CT findings, and subsequent treatment prescribed were recorded. Patients were selected for PET-CT only if they had no signs of distant disease on staging chest X-ray or abdominal ultrasound; were deemed suitable for radical chemoradiation by the multi-disciplinary team; and had normal renal function. HIV-positive patients ideally had to have been established on continuous antiviral therapy for more than 3 months and to have a CD4 cell count above 150 cells/μL. Small cell and neuroendocrine carcinoma cases were excluded from the study. Differences in demographic and clinical measures between HIV-positive and HIV-negative patients were evaluated by means of t-tests for continuous variables and χ2 tests for categorical variables.ResultsOver a 4 year period, 278 patients—192 HIV-negative (69.1%) and 86 HIV-positive (30.9%)—met the inclusion criteria. HIV-positive patients had a median CD4 count of 475 cells/µL (IQR 307–612 cells/µL). More than 80% of patients had pelvic nodal involvement, and more than 40% had uptake in common iliac and/or para-aortic nodes. Nodal involvement was not associated with HIV status. Fifty-four patients (19.4%) had at least one site of distant metastatic disease. Overall, 235 patients (84.5%) were upstaged following PET-CT staging scan. Upstaging was not associated with HIV status (HIV-negative 83.9% vs HIV-positive 87.2%; p=0.47). Ten patients who did not return for radiotherapy were excluded from the analysis. Following their PET-CT scan, treatment intent changed for 124 patients (46.3%): 53.6% of HIV-positive patients and 42.9% of HIV-negative patients (p=0.11).ConclusionWe found no differences between HIV-positive or HIV-negative patients in nodal involvement or occult metastases, and PET-CT imaging did not lead to, or justify, treatment differences between the two groups. Future studies will evaluate survival and correlation of upstaging with outcome.

PurposeVentilation-perfusion single photon emission computed tomography (VP SPECT) plays an important role in pulmonary embolism diagnosis. Rapid results may be obtained using same-day ventilation followed by perfusion imaging, but generally requires careful attention to achieving an optimal count rate ratio (P/V ratio) of ~3:1. This study investigated whether the ratio of counts simultaneously acquired in adjacent primary and Compton-scatter energy windows (E_ratio) on V SPECT was predictive of final normalised perfusion count rate (PCRnorm) on P SPECT using [99mTc]Tc-macroaggregated albumin (MAA), allowing optimisation of P/V ratio. MethodsSame-day VP SPECT studies acquired using standard protocols in adult patients during a 2-year period were assessed. Studies were included provided they were acquired with correct imaging parameters, and injection site imaging and laboratory records were available for quality control and normalised count rate corrections. Extraction of DICOM information, and linear regression were performed using custom Python and R scripts. A predictive tool was developed in Microsoft Excel.ResultsOf 643 studies performed, the scans of 343 participants (median age 30.4 years, 318 female) met inclusion criteria. A single outlier with high influence was excluded after an obvious cause was identified. Final analysis of the remaining 342 scans yielded a significant regression equation (F(1,340) = 1057.3, p 2 of .756 and MSE of 0.001089. A prediction tool designed for routine clinic use was developed for predicting final P/V ratio.ConclusionThe ratio of simultaneously acquired counts in adjacent energy windows on V SPECT is linearly related to perfusion count rate after administration of a known activity of [99mTc]Tc- MAA. A predictive tool based on this work may assist in optimising the dose and timing of [99mTc]Tc-MAA administration in same-day studies to the benefit of patients and workflows.

Introduction Parathyroidectomy is the choice of treatment for patients with primary and tertiary hyperparathyroidism. Scintigraphic, preoperative localization of hyperfunctioning parathyroid tissue depends on either a delayed washout technique, a subtraction technique, or a combination of the two. The rationale for adopting a combination approach is its presumed superior sensitivity, but there is limited evidence to support this strategy at the cost of patient inconvenience and impact on departmental workflows. Objective To determine whether a combined technique detects any additional lesions during scan interpretation compared to using subtraction-only technique in patients undergoing parathyroid scintigraphy before surgery. Methods A retrospective analysis was performed of parathyroid scans at Tygerberg Hospital between January 2012 and April 2018. Scans were reinterpreted by consensus by three readers, blinded to the original interpretation. A McNemar discordant pairs analysis was then performed. Results A total of 97 participant scans were reviewed (female: 71; mean age: 50.8 years). The number of patients with primary, secondary, and tertiary hyperparathyroidism were 63, 21, and 13, respectively. A total of 192 lesions were identified in this study. While both combined and subtraction-only approaches identified hyperfunctioning parathyroid lesions, only four lesions were identified using the combined technique that were missed by the subtraction technique. This result was not statistically significant (P = 0.125). Conclusion Based on our findings, the combined parathyroid scintigraphic technique does not improve lesion detection and may be dispensed with. Doing so will enhance patient convenience and comfort and improve departmental workflows without compromising lesion detection.

We present an unusual case of syphilitic pancreatitis and ascending aortitis in a 41-year-old HIV-negative male patient presenting to a tertiary institution with obstructive jaundice. After a battery of investigations that included computed tomography (CT) and 18F-labelled fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) imaging, syphilis serology and histology, a diagnosis of tertiary syphilis was made. The patient responded favourably to antibiotics, with resolution of all lesions on FDG PET/CT 13 weeks after initiation of therapy. Even though tertiary syphilis is a rare entity, it should be earmarked as a mimicker of other pathological conditions, including, in this case, primary pancreatic malignancy.

Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA‐Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA‐Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA‐Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders., Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA‐Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA‐Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders.

Background: Staging for breast cancer patients, as defined by the American Joint Committee on Cancer (AJCC), has historically been limited to anatomical staging. However, the eighth version of the AJCC guidelines has been altered to include tumour biology. Anatomical staging still has a place especially in low-middle income countries where the majority of patients present with locally advanced or metastatic disease. Aim: This review article considers which newly diagnosed breast cancer patients should be referred for anatomical staging and the pros and cons of the different modalities available in South Africa. Method: The different modalities available were reviewed with respect to metastatic screening for asymptomatic women. The usefulness of the modalities were considered with reference to organ-specific disease rather than the stage of the patient. Results: Any person with newly diagnosed breast cancer and symptoms suggestive of systemic involvement should be investigated. All symptomatic women who present with a tumour larger than 5 cm, radiological or clinical evidence of nodal disease, triple negative or HER2+ve tumours should have metastatic screening. This gives information about the primary as well as the metastatic status. Conclusion: However, increasingly, the major determinant of treatment is the biology of the cancer and not the anatomical stage. In future, this trend is likely to increase with anatomical staging becoming less important.

While there is mounting evidence of abnormal reactivity of several brain regions in social anxiety disorder, and disrupted functional connectivity between these regions at rest, relatively little is known regarding resting regional neural activity in these structures, or how such activity is affected by pharmacotherapy. Using 2-deoxy-2-(F-18)fluoro-D-glucose positron emission tomography, we compared resting regional brain metabolism between SAD and healthy control groups; and in SAD participants before and after moclobemide therapy. Voxel-based analyses were confined to a predefined search volume. A second, exploratory whole-brain analysis was conducted using a more liberal statistical threshold. Fifteen SAD participants and fifteen matched controls were included in the group comparison. A subgroup of SAD participants (n = 11) was included in the therapy effect comparison. No significant clusters were identified in the primary analysis. In the exploratory analysis, the SAD group exhibited increased metabolism in left fusiform gyrus and right temporal pole. After therapy, SAD participants exhibited reductions in regional metabolism in a medial dorsal prefrontal region and increases in right caudate, right insula and left postcentral gyrus. This study adds to the limited existing work on resting regional brain activity in SAD and the effects of therapy. The negative results of our primary analysis suggest that resting regional activity differences in the disorder, and moclobemide effects on regional metabolism, if present, are small. While the outcomes of our secondary analysis should be interpreted with caution, they may contribute to formulating future hypotheses or in pooled analyses.

Objectives PET-CT imaging is commonly used as a staging tool to identify nodal involvement in locally advanced cervical carcinoma (LACC). The value of PET-CT for staging HIV-infected patients with locally advanced CC has not been previously described. We analyzed PET-CT findings in a cohort of patients with LACC in Cape Town, SA. Methods Patients with LACC FIGO Stage IIb or IIIB, and were referred, on the basis of stage and the availability of bookings, for PET-CT/radiotherapy planning CT from January 2015 to December 2018. A team of expert nuclear medicine physicians and radiologists reported the PET-CT examinations. Descriptive statistics and chi-squared tests were used to compare patients with and without HIV. Results A total of 286 patients underwent PET-CT. Eighty-nine patients (31.2%) were HIV-positive. Pelvic nodal involvement was notably found in 205 patients (72.4%), including 77.3% of those who had HIV and 70.3% of those who did not (p=0.22); para-aortic nodal disease in 114 patients (42.7% of HIV+ vs 38.8% HIV-, p=0.53); and distant disease in 55 patients (23.6% of HIV+ vs 17.3% HIV-; p=0.22). In total, 223 patients (79.3%), including 81.8% of patients without and 75.0% of patients with HIV (p=0.31), were prescribed standard fractionation EBRT. Twenty-two patients (7.8%) were prescribed hypofractionated EBRT, and 36 patients (12.8%) palliative therapy. Five patients (1.7%) did not return. Conclusions PET-CT imaging found no differences between LACC patients, with and without HIV, in nodal involvement or occult metastases and did not lead to, or justify, treatment differences.

A case of a 50-year-old woman who was referred for the evaluation of possible ACTH-dependent Cushing’s syndrome (CS) is described. The localisation of ACTH-dependent CS remains difficult despite many advances in diagnostic approaches. No single test can accurately determine the location of ACTH excess and therefore a combination of non-invasive imaging, stimulation and suppression tests are advised. The recent advances, current utility and pitfalls of each of these tests are reviewed. If non-invasive tests fail to confidently localise the source of ACTH excess, inferior petrosal sinus sampling (IPSS) should follow. Recent advances improving the diagnostic accuracy of IPSS, such as DDAVP stimulation and simultaneous sampling for prolactin is discussed. Where ectopic ACTH production is suspected, newer nuclear medicine techniques, such as somatostatin receptor imaging that recently became available in South Africa, can be utilised. The role of nuclear medicine imaging in identifying ectopic ACTH production is discussed briefly.Keywords: ACTH, cushing’s disease, pituitary