BACKGROUND: One million children develop tuberculosis (TB) each year and a quarter of these die. TB meningitis (TBM) is the most severe form of TB disease and even if diagnosed and treated, 20% die and over 50% of survivors are left with permanent neurological disability. Much of the morbidity and mortality associated with TBM is due to infarction yet, despite this, our understanding of the pathogenesis of infarction in TBM remains limited, especially in children. METHODS: The iThemba study (Understanding ischemia in children with tuberculous meningitis), aims to recruit 100 children with probable or confirmed TBM and obtain samples of blood and cerebrospinal fluid (CSF). All children will undergo MRI and FDG PET/CT at baseline and will have repeat MRI with further blood and CSF samples collected at 2 weeks’ follow-up. MRI will then be carried out at 24 weeks with neurodevelopmental assessment at 48 weeks. Neuroimaging will focus on methods to identify and characterize ischemic penumbra and evaluate how this correlates with clinical outcomes. RNA sequencing of blood and CSF will be used to identify differentially expressed genes and identify implicated biological pathways between children with and without infarction. Targeted proteomic profiling will be performed on plasma and CSF to determine differences in protein abundance, with a focus on proteins involved in coagulation and endothelial function. Finally, we will integrate transcriptomic, proteomic and radiomic data to generate a comprehensive understanding of the pathogenesis of infarction in children with TBM. We aim to group children into relevant biological/anatomical phenotypes, each of which may benefit from a different therapeutic approach. Using computer simulation, we will then explore the impact of potential therapeutic interventions on biological pathways for each distinct phenotype. This work may pave the way for the development of point-of-care tests at diagnosis that could allow for stratified novel therapeutic approaches in future. DISCUSSION: A more comprehensive understanding of the pathophysiology of infarction in children with TBM would permit targeted host-directed therapies, with the potential to moderate or eliminate the consequences of this devastating condition.

INTRODUCTION:This computational study evaluates the accuracy of kinetic models and acquisition schemes in dynamic PET imaging using simulations of 18 F-fallypride PET in the human brain on the real-world data. METHODS:We employed a 2-tissue 4-k model to generate ideal tissue curves for three regions (putamen, thalamus, and temporal cortex) and a reference region (cerebellum), incorporating a simulated metabolite-corrected input function. Realistic measurements were simulated over a 240-min PET scan by defining acquisition protocols (frame timings and durations), modeling tracer decay, and adding noise. Distribution volume ratios (DVRs) were calculated using the Logan reference analysis and the simplified reference tissue model (SRTM), the relative error in DVR was also assessed across various acquisition protocols. Rate constants from the 2-tissue model were varied, and Bland-Altman analysis was quantified to determine bias relative to ground-truth DVR. RESULTS:Results indicate that, under low noise conditions, the Logan reference method performed optimally with a protocol involving a 60-min dynamic scan, a 60-min break, a 30-min scan, another 60-min break, and a final 30-min scan. In noisier conditions, the SRTM yielded the best results with a 150-min effective scan time incorporating three breaks. CONCLUSION:These findings highlight the impact of noise and acquisition strategy on model performance, informing optimal PET imaging protocols.

For certain clinical scenarios accurate and precise GFR measurement is required. In the majority of situations this is calculated from the plasma clearance of an exogenous marker that undergoes glomerular filtration, using the slope-intercept (SI) or single-sample (SS) methods. This paper is intended to complement a previous Seminars paper with a specific focus on practical ways to avoid potential pitfalls and quality control measures that can be implemented to minimize the risk of GFR measurement errors. The underlying causes of GFR errors can be understood in terms of measurement errors or procedural errors. All measurements are accompanied by inherent errors that are related to the finite precision of the measuring instruments used. Kept within an acceptable range, measurement errors make a small contribution to GFR error when compared to expected biological variation. Procedural errors consist of a diverse group of deviations from correct procedure ranging from selection of an inappropriate methodology through to missteps at many points in the investigation procedure. Procedural errors can significantly affect the accuracy of GFR measurements. Errors are primarily avoided by regular equipment quality control and careful adherence to clear standard operating procedures. Quality control parameters integrated into a calculation spreadsheet can play a useful secondary role to flag potential measurement or procedural errors.

BackgroundNeuropsychiatric systemic lupus erythematosus (NPSLE) is a major contributor to morbidity and mortality in systemic lupus erythematosus (SLE) patients. To date no single clinical, laboratory or imaging test has proven accurate for NPSLE diagnosis which is a testament to the intricate and multifactorial pathophysiological mechanisms suspected to exist. Functional imaging with FDG PET-CT has shown promise in NPSLE diagnosis, detecting abnormalities prior to changes evident on anatomical imaging. Research indicates that NPSLE may be more aggressive in people of African descent with higher mortality rates, making rapid and correct diagnosis even more important in the African context.MethodsIn this narrative review, we provide a thorough appraisal of the current literature on the role of FDG PET-CT in NPSLE. Large, well-known databases were searched using appropriate search terms. Manual searches of references of retrieved literature were also included.FindingsA total of 73 article abstracts were assessed, yielding 26 papers that were directly relevant to the topic of FDG PET-CT in NPSLE. Results suggest that FDG PET-CT is a sensitive imaging test for NPSLE diagnosis and may play a role in assessing treatment response. It is complementary to routine anatomical imaging, particularly in diffuse manifestations of the disease. Newer quantitative analyses are commonly used for interpretation and can detect even subtle abnormalities, missed on visual inspection. Findings of group-wise analyses of FDG PET-CT scans in NPSLE patients are important in furthering our understanding of the complicated pathophysiological mechanisms involved. Limitations of FDG PET-CT include its lack of specificity, high cost and poor access.ConclusionFDG PET-CT is a sensitive test for NPSLE diagnosis but is hampered by lack of specificity. It is a valuable tool for clinicians managing SLE patients, particularly when anatomical imaging is negative. Its exact application will depend on the local context and clinical scenario.

BackgroundRapid eye movement sleep behavior disorder (RBD) is an established prodrome and symptom of synucleinopathies. The pathophysiology of this disorder has been well studied but there is a lack of functional imaging data to illustrate the dysfunction in vivo. ObjectivesWe aimed to investigate the functional changes of RBD, by performing ictal REM sleep SPECT, comparing subjects with Parkinson's Disease (PD) and evidence of RBD to subjects with PD and no RBD. MethodsParticipants underwent a targeted clinical assessment, followed by video polysomnography (vPSG). Ictal 99mTc-HMPAO SPECT was performed by injecting the tracer during vPSG confirmed REM sleep in seven cases (PD with RBD) and five controls (PD without RBD). Voxel-wise, whole brain regional relative perfusion changes between both groups were assessed using statistical parametric mapping. ResultsNo difference in relative regional brain perfusion was demonstrated at a family wise error corrected p-value of 0.05 between the case and control groups. At an uncorrected P-value of <0.01, combined with a cluster extent threshold of 300 voxels, four clusters of increased perfusion were identified in the case group compared to the control group. The clusters were seen in the motor, somatosensory association, and prefrontal cortices. The reverse contrast did not show any significant clusters. ConclusionsIncreased perfusion of the motor cortex is in keeping with previous publications and motor phenomena seen in RBD. However, clusters included additional cortical regions. These findings demonstrate RBD as a wider sleep network dysfunction, rather than a manifestation of simple pontomedullary interruption.

Background The evolution of tuberculosis (TB) disease during the clinical latency period remains incompletely understood. Methods 250 HIV-uninfected, adult household contacts of rifampicin-resistant TB with a negative symptom screen underwent baseline 18 F-Fluorodeoxyglucose positron emission and computed tomography (PET/CT), repeated in 112 after 5-15 months. Following South African and WHO guidelines, participants did not receive preventive therapy. All participants had intensive baseline screening with spontaneous, followed by induced, sputum sampling and were then observed for an average of 4.7 years for culture-positive disease. Baseline PET/CT abnormalities were evaluated in relation to culture-positive disease. Results At baseline, 59 (23.6%) participants had lung PET/CT findings consistent with TB of which 29 (11.6%) were defined as Subclinical TB, and 30 (12%) Subclinical TB-inactive. A further 83 (33.2%) had other lung parenchymal abnormalities and 108 (43.2%) had normal lungs. Over 1107-person years of follow-up 14 cases of culture-positive TB were diagnosed. Six cases were detected by intensive baseline screening, all would have been missed by the South African symptom-based screening strategy and only one detected by a WHO-recommended chest X-Ray screening strategy. Those with baseline Subclinical TB lesions on PET/CT were significantly more likely to be diagnosed with culture-positive TB over the study period, compared to those with normal lung parenchyma (10/29 [34.5%] vs 2/108 [1.9%], Hazard Ratio 22.37 [4.89-102.47, p<0.001]). Conclusions These findings challenge the latent/active TB paradigm demonstrating that subclinical disease exists up to 4 years prior to microbiological detection and/or symptom onset. There are important implications for screening and management of TB.

Objectives PET-CT imaging is an ideal staging modality to identify nodal involvement in locally advanced cervical carcinoma (LACC). Previous work from this group has shown that PET-CT findings did not differ by HIV status and that PET-CT was a useful tool in this setting. The cohort was subsequently followed for survival outcomes. Methods Patients with LACC FIGO Stage IIb or IIIB were referred for fluorine-18 fluorodeoxyglucose PET-CT based on stage and booking availability between January 2015 and December 2018. Descriptive statistics and Kaplan-Meier estimates were generated to evaluate overall survival (OS) after 2 years of follow-up. All patients were censored by December 2020. Results Of the 278 patients included in the cohort, 86 (30.9%) were HIV-positive. 105 (37.8%) had pelvic nodal lesions, and 77 (27.7%) had additional para-aortic adenopathy (PAN). Overall survival (OS) for the cohort, including those found to have distant disease, was 52.9% (HIV-negative) and 42.4% (HIV-positive) (p=0.12). For the 192 patients who received radical treatment, 2-year OS by stage and HIV status (negative vs. positive) was as follows: IIIB 75% vs 62.5% (p=0.86); IIIc1r 72.5% vs 54.2% (p=0.09) and IIIc2r 43.9% vs 41.2% (p=0.86). Survival rates were (marginally) associated with HIV status only in stage IIIc1r. PAN involvement conferred a poor prognosis. Conclusions PET-CT findings of para-aortic lymphadenopathy in LACC were prognostic for a poor outcome at 2 years, irrespective of HIV status. PET-CT remains a valuable tool in the HIV-positive patient group.

Glomerular filtration rate (GFR) can be estimated from the plasma concentration of endogenous substances such as creatinine, and it is simple and cost-effective to do so, but the error on these estimates on an individual patient basis is high. Thus, GFR measurement is indicated in any clinical situation in which greater accuracy is required especially if the result will impact treatment decisions. Outside of the United States the radiopharmaceutical that has been most commonly used for measurement of GFR is 51Cr-EDTA. However, due to a recent reduction in supply, there has been a shift to 99mTc-DTPA. The differences in clearance between these two tracers are small, and their clearance is comparable to the non-radiopharmaceutical markers inulin, iohexol and iothalamate. A few PET GFR tracers are currently under investigation for clinical use. Measurement of the urinary clearance of a tracer is the historical gold standard technique, however this method is prone to error due to difficulties with urine collection and inaccuracies associated with measuring residual activity in the bladder and renal drainage systems. Plasma clearance techniques provide a more practical and robust alternative and have good precision despite overestimating GFR slightly. Measurement of the area under the full plasma clearance curve is the reference method but due to the large number of blood samples required, it is largely limited to research settings. The slope-intercept and single-sample methods are simpler yet accurate alternatives that can be used in most patients. However, in patients with expanded third spaces or very low GFR (<25 mL/min/1.73 m2), different calculation methods are used that require blood sampling up to 24 hours. Camera-based methods are currently not recommended due to their imprecision. For the purposes of interpreting a GFR result, reliable reference data is available for adults and children, mostly derived from 51Cr-EDTA clearance measurements, but applicable to 99mTc-DTPA GFR. GFR has notable biological variation and is susceptible to measurement errors, the combination of which translates into a high coefficient of variation for repeat measurements. Consequently, when serial measurements are performed, large changes (>20%) are required before a change can be regarded as significant. While biological variation is largely fixed, measurement errors can be minimized through careful work in combination with a system of thorough quality control checks.

Glomerular filtration rate (GFR) is usually estimated rather than measured as this only requires measurement of an endogenous filtration marker. In certain clinical settings a more accurate measure of GFR is essential. The most commonly used endogenous filtration marker is creatinine. Exogenous filtration markers include nonradiopharmaceuticals such as inulin, iohexol and unlabelled iothalamate, or radiopharmaceuticals such as 51Crethylenediaminetetraacetic acid (51Cr-EDTA) and 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA). Inulin is considered an ideal filtration marker but the clearance of iothalamate, 99mTc-DTPA, 51Cr-EDTA and iohexol have all been shown to have sufficient accuracy for measuring GFR. For radiopharmaceuticals, a well counter is required to measure the amount of activity in patient samples. Iohexol or unlabelled iothalamate require samples to be measured using high performance liquid chromatography with ultraviolet detection (HPLC-UV), liquid chromatography-tandem mass spectrometry (LC-MS/MS) or x-ray fluorescence (XRF). Due to the practical challenges of measuring urinary clearance, measurement of GFR in clinical settings is almost exclusively based on plasma clearance of a filtration marker. This can follow a long-established approach based on the ratio of the tracer administered to the area under the plasma concentration curve. Alternatively, a single plasma sample giving an apparent volume of distribution at a given time point can be used to accurately measure GFR. While techniques exist for the measurement of GFR in a number of African countries, preliminary evidence suggests that facilities are very limited. There is a need for support for both equipment and training to establish GFR measurement facilities in several centres on the continent.

Background: Bone marrow biopsy (BMB) plays a crucial role in the diagnosis and assessment of treatment response in patients with multiple myeloma (MM). 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has been shown to be a complimentary measure of marrow involvement in patients with Hodgkin and diffuse large B cell lymphomas. However, only limited information is available on its relationship with BMB in MM.Aim: To assess the association between bone marrow involvement on 18F-FDG PET/CT, and BMB in patients with MM and other plasma cell neoplasms.Setting: Cape Town, South Africa.Methods: Hundred and three patients undergoing 18F-FDG PET/CT and BMB were included. Plasma cell infiltration (PCI) on BMB was compared for three visual patterns of 18F-FDG bone marrow uptake (irregular, diffuse less than or equal to the liver and diffuse greater than liver).Results: Eighty-four patients had diffuse bone marrow uptake. Of these, 25/84 had uptake greater than liver, all having PCI ≥ 60% and a median value of 85%. Of the 84 patients, the 59 patients with uptake less than or equal to liver had PCI 10% in 57.6% (34/59), and ≥ 10% in 42.4% (25/59) with a median value of 8%. Nineteen patients had irregular bone marrow uptake. Of these, 4/19 (21.1%) had PCI of 10% and 15/19 (78.9%) had PCI ≥ 10%, with the median value of 23%. The median percentage of PCI across the three described patterns of FDG uptake was significantly different (p = 0.0001).Conclusion: 18F-fluorodeoxyglucose positron emission tomography/computed tomography might avoid the need of repeat BMB in most of the patients with diffuse and irregular patterns of 18F-FDG uptake.

Objectives: 18F-Fluorodeoxyglucose (FDG) Positron Emission Tomography- Computed Tomography (PET/CT) scans can be used to assess healing following treatment for spinal tuberculosis (TB) but have limited accessibility and high cost. This study investigated the association between immune biomarkers and FDG-PET/CT activity after >= 9 months of treatment for spinal TB. Methods: Patients who had completed >= 9 months of treatment for spinal TB were recruited from a major hospital in the Western Cape, South Africa. Participants underwent a FDG-PET/CT scan and FDG- PET/CT activity was quantified for all spinal and extra-spinal sites. Participants also provided a blood sample, which was evaluated for 19 cytokines along with erythrocyte sedimentation rate (ESR). Correlations and multiple regression analyses were used to investigate the association between biomarkers and PET/CT measures. Results: Twenty-eight patients were recruited, of whom 24 (86%) had spinal and/or extra-spinal FDG-PET/CT activity. In the strongest multiple regression model, CXCL10/IP-10, VEGFA, IFN-gamma, CRP and Factor D/Adipsin explained 52% of the variation in overall maximal FDG uptake. Conventional monitoring marker ESR showed no significant association with PET/CT measures. Conclusions: The current findings offered encouragement that biomarkers to predict FDG-PET/CT activity may show some promise and identified candidate biomarkers for further investigation in this regard.

Positron emission tomography combined with X-ray computed tomography (PET-CT) has an established role in the management of brain disorders, but may be underutilised in South Africa. Possible barriers to access include the limited number of PET-CT facilities and the lack of contemporary guidelines for the use of brain PET-CT in South Africa. The current review aims to highlight the evidence-based usage of brain Positron emission tomography (PET) in dementia, movement disorders, brain tumours, epilepsy, neuropsychiatric lupus, immune-mediated encephalitides, and brain infections. While being areas of research, there is currently no clinical role for the use of PET-CT in traumatic brain injury or in psychiatric or neurodevelopmental disorders. Strategies to expand the appropriate use of PET-CT in brain disorders are discussed in this article.

Objective Glomerular filtration rate (GFR) measurement remains an integral investigation in clinical practice and is particularly important in the prediction and follow-up of renal side-effects of nephrotoxic chemotherapy in cancer patients. Knowing the coefficient of variation (CV) of a test is vital for the correct interpretation of serial studies. Recent difficulties with 51 Cr-EDTA availability have renewed interest in 99m Tc-DTPA, but there is a paucity of data on the test-retest variability of this radiopharmaceutical. Furthermore, the authors are unaware of published repeatability data in cancer patients. The aim of this study was to determine the CV of repeat 99m Tc-DTPA GFR measurements in a clinical patient population that included cancer patients. Methods Patients who had undergone ≥2 GFR studies at our department between January 2009 and December 2019 were retrospectively identified. Patients with chronic kidney disease and those who had received chemotherapy, radiotherapy or surgery between measurements were excluded. The CV for each patient was calculated and the mean CVs of cancer and prospective renal donor groups were calculated and compared. Results Fifty-four patients were included in the final analysis. The mean CV in the cancer group (38 patients) was 8.5% [95% confidence interval (CI) 6.9–10.2%] and in the renal donor group (16 patients) 7.1% (95% CI 4.2–10.1%). These figures did not differ significantly ( P = 0.37). The groups were combined to calculate the final overall mean CV of 8.1% (95% CI 6.7–9.6%). Conclusion In both non-cancer and cancer patients the CV of GFR studies performed with 99m Tc-DTPA was comparable with mostly 51 Cr-EDTA figures presented in literature.

Background. The Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations are two commonly used formulae to estimate glomerular filtration rate (GFR) in adults. The CKD-EPI equation is recommended in current international and local guidelines for the diagnosis and management of chronic kidney disease (CKD), unless an alternative equation has been shown to have superior accuracy. Validation and comparison of the equations in local populations are therefore required. Previous studies have reported on the accuracy of these prediction equations in black South Africans and those of Indian ancestry. Objectives. To evaluate the MDRD and CKD-EPI equations in South African (SA) adults of mixed ancestry. Methods. In all participants, GFR was measured (mGFR) from plasma clearance of 99m Tc-diethylenetetraaminepenta-acetic acid ( 99m Tc-DTPA), using a standardised technique. Serum creatinine assays were isotope dilution mass spectrometry traceable. GFR was estimated (eGFR) using the MDRD and CKD-EPI equations, with and without the black ethnicity factor. The agreement, bias, precision and accuracy of each equation was determined. Results. Eighty adults were included (30 male, median age 39 years, median GFR 59 mL/min/1.73 m 2 ). Sixty-eight had a diagnosis of CKD, 10 were potential kidney donors, and 2 were healthy volunteers. Both equations, without the black ethnicity factor, had good agreement with measured GFR. The equations tended to overestimate GFR, with bias of 1.6 and 7.9 mL/min/1.73 m 2 for the MDRD and CKD-EPI equations, respectively. The interquartile ranges of the differences were 15.9 and 20.2 mL/min/1.73 m 2 , and as a measure of accuracy, the percentages of estimates that fell within 30% of the mGFR (P30) were 80% and 72.5% ( p =0.18). For identification of individuals with a GFR <60 mL/min/1.73 m 2 , the sensitivity of MDRD eGFR was 97.3% and that of CKD-EPI eGFR was 97.1%. Conclusions. The MDRD and CKD-EPI equations have shown satisfactory and comparable performance in this SA mixed-ancestry adult population, with the MDRD equation marginally less biased than the CKD-EPI.

Creatinine-based glomerular filtration rate (GFR)-estimating equations frequently do not perform well in populations that differ from the development populations in terms of mean GFR, age, pathology, ethnicity, and diet. After first evaluating the performance of existing equations, the aim of this study was to demonstrate the utility of an in-house modification of the equations to better fit a specific population. Estimated GFR using 8 creatinine-based equations was first compared to 2-sample 51Cr-ethylenediaminetetra-acetic acid plasma clearance in non-cancer and cancer groups independently. The groups were then divided into development and validation sets. Using the development set data, the Microsoft® Excel SOLVER add-in was used to modify the parameters of 7 equations to better fit the data. Using the validation set data, the performance of the original and modified equations was compared. Two hundred fifty-six GFR measurements were performed in 160 children. GFR was overestimated in both groups (non-cancer 4.3–22.6 ml/min/1.73 m2, cancer 17.2–46.6 ml/min/1.73 m2). The root mean square error (RMSE) was 19.1–21.8 ml/min/1.73 m2 (non-cancer) and 18.6–20.8 ml/min/1.73 m2 (cancer). The P30 values were 49.1–73.0% (non-cancer) and 19.6–66.0% (cancer). Modifying the parameters of seven equations resulted in significant improvements in the P30 values in the non-cancer (65.0–85.0%) and cancer (79.6–87.8%) groups. Modifying the parameters of pediatric GFR estimating-equations using a simple Excel-based tool significantly improved their accuracy in both non-cancer and cancer populations.

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 read with interest the recently published European Society for Vascular Surgery (ESVS) guidelines on management of vascular graft infections.1Chakfé N. Diener H. Lejay A. Assadian O. Berard X. Caillon J. et al.Editor's choice – European Society for Vascular Surgery (ESVS) 2020 clinical practice guidelines on the management of vascular graft and endograft infections.Eur J Vasc Endovasc Surg. 2020; 59: 339-384Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar We agree that white cell scintigraphy (WCS) is useful in the workup of suspected vascular graft/endograft infection (VGEI). However, we would like to point out that the criterion for WCS scan positivity highlighted in the ESVS guidelines, namely an increase in intensity or size with time (progressive white cell accumulation over 20–24 h), while validated in other infections,2Erba P.A. Glaudemans A.W.J.M. Veltman N.C. Sollini M. Pacilio M. Galli F. et al.Image acquisition and interpretation criteria for 99 mTc-HMPAO-labelled white blood cell scintigraphy: results of a multicentre study.Eur J Nucl Med Mol Imaging. 2014; 41: 615-623Crossref PubMed Scopus (59) Google Scholar has not been validated in the context of VGEI. Indeed, the European Association of Nuclear Medicine guideline on WCS, to which the ESVS guidelines refer, emphasises the importance of early (3 h) images when performing WCS for suspected VGEI, not specifying a role for 24 h imaging.3Signore A. Jamar F. Israel O. Buscombe J. Martin-Comin J. Lazzeri E. Clinical indications, image acquisition and data interpretation for white blood cells and anti-granulocyte monoclonal antibody scintigraphy: an EANM procedural guideline.Eur J Nucl Med Mol Imaging. 2018; 45: 1816-1831Crossref PubMed Scopus (52) Google Scholar In a recent study, aimed at evaluating the predictive role of progressive accumulation in WCS for suspected VGEI, evidence was found that reliance on this criterion may, in fact, lead to misdiagnosis. After institutional review board approval, a retrospective analysis of suspected VGEI cases undergoing WCS at Tygerberg Hospital was performed. Tc-99m WCS scans performed for suspected VGEI from January 2004 to June 2018 were included in the analysis if dual timepoint imaging was performed and if a reference standard was available. A composite reference standard was used based on the results of microbiological cultures, other imaging modalities, surgical findings, and clinical follow up. Scans were reported by consensus, by two nuclear medicine physicians and a resident blinded to clinical details. Firstly, the 3 h images were classified as positive or negative based on visual evaluation (VE) for the presence or absence of white cell activity at the site of the vascular graft. Next, by comparing 3 h and decay corrected next day (20–24 h) images, scans were scored as either positive or negative, based on the presence or absence of progressive white cell accumulation (increase in number of counts at site of graft), both visually looking at uptake relative to other tissues (VE_L), and semi-quantitatively (SQ_AI) using an accumulation index ([late uptake – early uptake]/early uptake) derived from regions of interest drawn on planar images and corrected for background, decay, camera collimator sensitivity, and acquisition duration. Twenty-eight scans were identified, of which five were excluded (incomplete imaging in two, inadequate data for a reference standard in three). A total of 23 scans (21 patients) with 24 suspected VGEIs were included in the analysis. VGEI was suspected on the basis of infection in overlying soft tissue (18 patients) and/or fever (five patients). Five of the 24 grafts had been inserted within the preceding four months. The mean age of participants was 61 ± 14 years (13 men [62%]). Three grafts were axillofemoral, two aortic arch, 13 aortobifemoral, two femoropopliteal, one femoral, one femorofemoral, one bilateral ilioprofunda, and one iliofemoral. Based on the reference standard, infection was present in 18 grafts and absent in six. Visual analysis of the 3 h images alone (VE) performed better than both visual analysis of the early and late images (VE_L) and the accumulation index (SQ_AI) with sensitivity of 100%, 72%, and 50%; specificity of 83%, 83%, and 50%; accuracy of 96%, 75%, and 50%; positive predictive values of 95%, 93%, and 75%; and negative predictive values of 100%, 50%, and 25%, respectively. Receiver operating characteristic (ROC) analysis (Fig. 1) found that VE had the best diagnostic performance followed by VE_L, whereas SQ_AI had no diagnostic utility. On the pairwise comparison of the ROC curves, VE was statistically more accurate than VE_L (p = .011) and SQ_ AI (p = .001). It is noteworthy that several proven VGEI cases demonstrated a time dependent decrease in activity over 20–24 h. It is hypothesised that this may relate to reverse neutrophil migration away from inflammatory sites and neutrophil reverse transendothelial migration, back into the vasculature, which has been observed in certain settings.4de Oliveira S. Rosowski E.E. Huttenlocher A. Neutrophil migration in infection and wound repair: going forward in reverse.Nat Rev Immunol. 2016; 16: 378-391Crossref PubMed Scopus (428) Google Scholar For unclear reasons, it is speculated that reverse migration cascades may be more active in VGEI than in other types of infection. Other factors that might contribute to this phenomenon include differences in causative pathogens (with varying virulence factors that directly alter neutrophil recruitment and biofilm formation); number of organisms; degree of inflammation; and associated complications such as graft erosion and stenosis. Finally, more chronic infections with a wider variety of immune cells participating in the immune response may affect neutrophil migration over time. Study limitations include its relatively small sample size, its retrospective nature, that inter- and intra-observer variability were not measured or controlled for, and the non-availability of information on graft material. In conclusion, contrary to its value in other soft tissue infections, the criterion of progressive white cell accumulation over 20–24 h may not improve diagnostic accuracy in the context of suspected VGEI, and caution should be exercised in excluding infection on this basis. None. Internal divisional funding.