The effect of statins on the risk of anti-tuberculosis drug-induced liver injury among patients with active tuberculosis: A cohort study.

BACKGROUND: Tuberculosis (TB) remains prevalent worldwide, and anti-TB drugs are associated with drug-induced liver injury (DILI). Statins have pleiotropic effects which may decrease inflammation and achieve immunomodulation. However, few studies have investigated the pleiotropic effects of statins on the risk of DILI. The purpose of this study was to investigate whether statins prevent anti-tuberculosis DILI among active TB patients on standard anti-TB drug therapy. METHODS: We conducted a hospital-based retrospective cohort study using claims data from the Integrated Medical Database of National Taiwan University Hospital (NTUH-iMD). Patients with a positive TB culture were included. The use of statins was defined as a daily equivalent dose >0.5 mg of pitavastatin. Deterioration in liver function was evaluated according to elevated liver enzyme levels. The primary and secondary endpoints were the DILI and the severe DILI. The prognostic value of statins was evaluated by Kaplan-Meier analysis, and Cox proportional hazards models. RESULTS: A total of 1312 patients with a diagnosis of TB and receiving anti-TB treatment were included. During the study period, 193 patients had the DILI and 140 patients had the severe DILI. Kaplan-Meier analysis showed a significant difference between the usual statin users and controls in the DILI. In multivariable Cox proportional hazards analysis, statins showed a protective effect against the primary and secondary endpoints. In addition, the protective effect of statins showed a dose-response relationship against the DILI. CONCLUSION: Statin treatment had a protective effect against the risk of anti-TB DILI with a positive dose-response relationship.

Comparison of post-COVID-19 vaccination hypermetabolic lymphadenopathy on 18F-fluorodeoxyglucose PET/CT between virus-vector vaccine and mRNA vaccine.

PURPOSE: We compared hypermetabolic lymphadenopathy (HLN) on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) after virus-vector and mRNA vaccines for coronavirus disease 2019 (COVID-19). METHODS: This retrospective study included 573 participants who underwent FDG PET/CT after receiving a virus-vector vaccine (ChAdOx1, AstraZeneca [AZ] group) or an mRNA vaccine (mRNA-1273, Moderna [M] group) from July 2021 to October 2021. The incidence and avidity of HLN were evaluated and correlated with clinical features and vaccine type. The final analysis was conducted with 263 participants in the AZ group and 310 participants in the M group. RESULTS: The HLN incidence was significantly lower in the AZ group than in the M group (38/263 [14%] vs. 74/310 [24%], p = 0.006). The FDG avidity of HLN was comparable between the two groups. The HLN incidence in both groups was significantly higher within 4 weeks after the vaccination compared with more than 4 weeks. The HLN incidence within 4 weeks of the vaccination was significantly higher in the M group than in the AZ group (p = 0.008), whereas a difference in HLN incidence between the two groups was not observed after the same duration (p = 0.11). CONCLUSIONS: The mRNA mRNA-1273 COVID-19 vaccine was found to be associated with higher glucose hypermetabolism in regional lymph nodes within the first 4 weeks compared with the virus-vector vaccine, as indicated by the presence of HLN on FDG PET/CT. The degree of glucose hypermetabolism was comparable between the two vaccines.

Diagnostic Effect of Attenuation Correction in Myocardial Perfusion Imaging in Different Coronary Arteries: A Systematic Review and Meta-Analysis.

Background: The aim of this study was to determine whether, and if so how, attenuation correction (AC) improves the diagnostic performance of myocardial perfusion imaging (MPI) in different coronary artery-supplied territories, using coronary angiography as the reference standard. Methods: PubMed and EMBASE were searched until December 2020 for studies evaluating AC MPI for the diagnosis of coronary artery disease (CAD) with vessel-based data. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. For each study, the sensitivity, specificity, diagnostic odds ratios and areas under summary receiver operating characteristic curves (AUC) with 95% confidence intervals were calculated to determine the diagnostic accuracy of AC compared to non-AC MPI. A bivariate mixed-effects model was used to pool the data. Subgroup analyses considering the type of radiotracer and type of AC were performed. Results: A total of 264 articles were screened, of which 22 studies (2,608 patients) were enrolled. Significant improvements in specificity [0.78 vs. 0.58 in overall CAD, 0.87 vs. 0.61 in right coronary artery (RCA)] and diagnostic odds ratios (16 vs. 8 in overall CAD, 18 vs. 7 in RCA) after AC were shown in overall CAD at a patient level and RCA stenosis. Improvements in AUC were also noted. MPI had a similar diagnostic performance for detecting left anterior descending and left circumflex coronary artery stenosis with or without AC. There were trends of decreased sensitivity after AC, but none were significant. Diagnostic odds ratio showed significant improvement after AC only in the technetium-99m subgroup. Conclusion: The results of this study suggest that AC should be applied to MPI to improve the diagnosis of CAD regardless of which type of radiotracer, and that AC MPI can improve the specificity of detecting RCA stenosis.

Long-term prognostic value of computed tomography-based attenuation correction on thallium-201 myocardial perfusion imaging: A cohort study.

BACKGROUND: Myocardial perfusion imaging (MPI) is a well-established diagnostic tool to evaluate coronary artery disease (CAD) and also an effective prognostic tool for patients with CAD. However, few studies investigated the prognostic value of attenuation correction (AC) in MPI, and the results were controversial. OBJECTIVES: To investigate the prognostic value of computed tomography (CT)-based AC thallium-201 (Tl-201) MPI. METHODS: A total of 108 consecutive patients who underwent Tl-201 MPI and received coronary angiography within 90 days were included. Medical records were reviewed and missing information was completed after telephone contact. The prognostic value was evaluated by Kaplan-Meier analysis, univariable and multivariable Cox proportional hazards model. RESULTS: After a mean follow-up of 7.72 ± 3.72 years, 27 patients had died, 41 had been readmitted for cardiovascular (CV)-related events and 44 had reached the composite of death plus CV-related re-admission. Kaplan-Meier curves for all-cause mortality for SSS with a cutoff value of 13 for AC and 16 for non-AC (NAC) images showed a significant difference between the two curves for both AC and NAC images (p = 0.011 for AC and p = 0.021 for NAC). In the multivariable model, SSS and SRS showed similar independent predictive values in predicting all-cause mortality and composite of all-cause mortality plus CV-related re-admission, in both AC and NAC images. Subgroup analysis implicated that AC MPI possibly provided better risk stratification in obese patients. CONCLUSION: CT-based AC and NAC MPI showed similar value and were the only significant predictors for the composite of mortality and CV events.

NP-59 Adrenal Scintigraphy as an Imaging Biomarker to Predict KCNJ5 Mutation in Primary Aldosteronism Patients.

Purpose: Somatic KCNJ5 mutation occurs in half of unilateral primary aldosteronism (PA) and is associated with more severe phenotype. Mutation status can only be identified by tissue sample from adrenalectomy. NP-59 adrenal scintigraphy is a noninvasive functional study for disease activity assessment. This study aimed to evaluate the predictive value of NP-59 adrenal scintigraphy in somatic KCNJ5 mutation among PA patients who received adrenalectomy. Methods: Sixty-two PA patients who had NP-59 adrenal scintigraphy before adrenalectomy with available KCNJ5 mutation status were included. Two semiquantitative parameters, adrenal to liver ratio (ALR) and lesion to contralateral ratio of bilateral adrenal glands (CON) derived from NP-59 adrenal scintigraphy, of mutated and wild-type patients were compared. Cutoff values calculated by receiver-operating characteristic (ROC) analysis were used as a predictor of KCNJ5 mutation. Results: Twenty patients had KCNJ5 mutation and 42 patients were wild type. Patients harboring KCNJ5 mutation had both higher ALR and CON (p = 0.0031 and 0.0833, respectively) than wild-type patients. With ALR and CON cutoff of 2.10 and 1.95, the sensitivity and specificity to predict KCNJ5 mutation were 85%, 57% and 45%, 93%, respectively. Among 20 patients with KCNJ5 mutation, 16 showed G151R point mutation (KCNJ5- G151R) and 4 showed L168R point mutation (KCNJ5-L168R), which former one had significantly lower ALR (p=0.0471). Conclusion: PA patients harboring somatic KCNJ5 mutation had significantly higher NP-59 uptake regarding to ALR and CON than those without mutation. APAs with KCNJ5-L168R point mutation showed significantly higher ALR than those with KCNJ5-G151R point mutation.

Diagnostic performance of FDG PET/CT in critically ill patients with suspected infection: A systematic review and meta-analysis.

BACKGROUND/PURPOSE: Nuclear imaging, including gallium scintigraphy and fluorodeoxyglucose (FDG) positron emission tomography (PET), has been widely used to identify focus of infection in fever of unknown origin. However, little is known about its role in critically ill patients, who are usually with multiple inflammatory foci and unable to tolerate long image acquisition time. This systematic review aimed to evaluate the diagnostic performance of FDG PET for suspected infection in critically ill patients. METHODS: PubMed and Embase were searched up to July 24th, 2019 to identify studies evaluating the diagnostic performance of FDG PET for finding infection focus in critically ill patients following the PRISMA guidelines. The bivariate mixed-effects model was used to pool the measure for diagnostic performance. Publication bias was evaluated by Deeks' method. RESULTS: A total of 4 studies with 87 patients were included. All the four studies evaluated FDG PET. Majority of the patients were either mechanically ventilated (76%) or shocked requiring vasopressors (61%). Test and transportation related adverse events were rare (2%). The summary sensitivity and specificity were 0.94 (95% CI, 0.79-0.99) and 0.66 (95% CI, 0.45-0.83), respectively. The AUC for summary ROC curve was 0.83. CONCLUSION: FDG PET was a very sensitive tool with acceptable specificity for detecting the origin of infection in critically ill patients. However, current available studies have limitation in evaluating safety issue. Further research should investigate both benefit and risk of doing this test for this group of vulnerable patients.

Predicting tumor responses and patient survival in chemoradiotherapy-treated patients with non-small-cell lung cancer using dynamic contrast-enhanced integrated magnetic resonance-positron-emission tomography.

PURPOSE: We investigated whether radiologic parameters by dynamic contrast-enhanced (DCE) integrated magnetic resonance-positron-emission tomography (MR-PET) predicts tumor response to treatment and survival in non-metastatic non-small-cell lung cancer (NSCLC) patients receiving chemoradiotherapy (CRT). METHODS: Patients underwent DCE integrated MR-PET imaging 1 week before CRT. The following parameters were analyzed: primary tumor size, gross tumor volume, maximal standardized uptake value (SUVmax), total lesion glycolysis (TLG), apparent diffusion coefficient (ADC), volume transfer constant (Ktrans), reverse reflux rate constant (kep), extracellular extravascular volume fraction (ve), blood plasma volume fraction (vp), and initial area under the time-concentration curve defined over the first 60 s post-enhancement (iAUC60). CRT responses were defined using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). RESULTS: Thirty patients were included. Non-responders demonstrated higher baseline TLG (p = 0.012), and lower baseline Ktrans (p = 0.020) and iAUC60 (p = 0.016) compared to responders, indicating the usefulness of DCE integrated MR-PET to predict treatment responses. Receiver operating characteristic curve indicated that TLG has the best differentiation capability to predict responders. By setting the threshold of TLG to 277, the sensitivity, specificity, and accuracy were 66.7%, 83.3%, and 75.0%, respectively, with an area under the curve of 0.776. The median follow-up time was 19.6 (range 7.8-32.0) months. In univariate analyses, baseline TLG >277 (p = 0.005) and baseline Ktrans <254 (10-3 min-1; p = 0.015) correlated with poor survival after CRT. In multivariate analysis, baseline TLG >277 remained the significant factor in predicting progression (p = 0.012) and death (p = 0.031). CONCLUSIONS: The radiologic parameters derived from DCE integrated MR-PET scans are useful for predicting treatment response in NSCLC patients treated with CRT; furthermore, these parameters are correlated with clinical and survival outcomes including tumor progression and death.

Improved diagnostic accuracy of thallium-201 myocardial perfusion single-photon emission computed tomography with CT attenuation correction.

BACKGROUND: The benefits of attenuation correction (AC) in technetium-99m myocardial perfusion imaging (MPI) have been well established. However, the value of thallium (Tl-201) AC and routine computed tomography AC (CTAC) were less well established. The aims of this study were to evaluate the diagnostic performance of thallium (Tl-201) MPI with additional CTAC and to determine which participants would benefit most. METHODS AND RESULTS: A total of 108 consecutive patients who underwent Tl-201 MPI and received coronary angiography within 3 months were enrolled. Diagnostic performance was determined by sensitivity, specificity, and receiver operating characteristic curve analysis. Subgroup analyses were performed using gender and obesity. CTAC improved the area under the curve (0.84 vs. 0.77, P = 0.037 at patient level), primarily due to a significant improvement in specificity (0.78 vs. 0.57, P = 0.013) and no significant difference in sensitivity (0.79 vs. 0.82, P = 0.75). In subgroup analysis, CTAC was most helpful in obese subjects, men, and especially right coronary artery lesions. CONCLUSIONS: CTAC significantly improved diagnostic performance primarily by increasing the specificity, and the improvements were significantly greater in obese patients and male patients. These findings suggest that CTAC should be applied to Tl-201 MPI as routine clinical practice.

Response assessment of stereotactic body radiation therapy using dynamic contrast-enhanced integrated MR-PET in non-small cell lung cancer patients.

PURPOSE: To evaluate the response in patients undergoing SBRT using dynamic contrast-enhanced (DCE) integrated magnetic resonance positron emission tomography (MR-PET). Stereotactic body radiation therapy (SBRT) is efficacious as a front-line local treatment for non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We prospectively enrolled 19 lung tumors in 17 nonmetastatic NSCLC patients who were receiving SBRT as a primary treatment. They underwent DCE-integrated 3T MR-PET before and 6 weeks after SBRT. The following image parameters were analyzed: tumor size, standardized uptake value (SUV), apparent diffusion coefficient, Ktrans , kep , ve , vp , and iAUC60 . Chest computed tomography (CT) was performed at 3 months after SBRT. RESULTS: SBRT treatment led to tumor changes including significant decreases in the SUVmax (-61%, P < 0.001), Ktrans mean (-72%, P = 0.005), Ktrans standard deviation (SD; -85%, P = 0.046), kep mean (-53%, P = 0.014), kep SD (-63%, P = 0.001), and vp SD (-58%, P = 0.002). The PET SUVmax was correlated with the MR kep mean (P = 0.002) and kep SD (P < 0.001). The percentage reduction in Ktrans mean (P < 0.001) and kep mean (P = 0.034) at 6 weeks post-SBRT were significantly correlated with the percentage reduction in tumor size, as measured using CT at 3 months after SBRT. Univariate analyses revealed a trend toward disease progression when the initial SUVmax > 10 (P = 0.083). CONCLUSION: In patients with NSCLC who are receiving SBRT, DCE-integrated MR-PET can be used to evaluate the response after SBRT and to predict the local treatment outcome. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:191-199.

Diagnostic Performance of Attenuation-Corrected Myocardial Perfusion Imaging for Coronary Artery Disease: A Systematic Review and Meta-Analysis.

Myocardial perfusion imaging (MPI) with SPECT is a well-established tool for the diagnosis of coronary artery disease (CAD). However, soft-tissue attenuation is a common artifact that limits the diagnostic accuracy of MPI. The aim of this study was to determine whether attenuation correction (AC) improved the diagnostic performance of MPI, using coronary angiography as a reference standard. METHODS: MEDLINE and EMBASE were searched until March 2015 for studies evaluating AC MPI for the diagnosis of CAD. Methodologic quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. For each study, the sensitivity, specificity, and diagnostic odds ratio, along with 95% confidence intervals (CIs), were calculated to determine the diagnostic accuracy of AC versus non-attenuation-corrected (NAC) MPI. A bivariate mixed-effects model was applied for pooling the data. RESULTS: Of 201 articles, 17 studies (1,701 patients) were identified, including 5 studies that used CT AC, 12 studies that used radionuclide source AC (RAC), and 15 studies that reported NAC results. The pooled sensitivities across studies were 0.80 (95% CI, 0.64-0.91), 0.85 (95% CI, 0.81-0.88), 0.84 (95% CI, 0.79-0.88), and 0.80 (95% CI, 0.75-0.85) for CT AC, RAC, all AC, and NAC, respectively. The pooled specificities were 0.83 (95% CI, 0.71-0.91), 0.81 (95% CI, 0.73-0.86), 0.80 (95% CI, 0.74-0.85), and 0.68 (95% CI, 0.61-0.74). Both sensitivities and specificities resulted in a pooled diagnostic odds ratio of 20 (95% CI, 12-34), 24 (95% CI, 13-43), 22 (95% CI, 13-35), and 9 (7-11). Significant differences in specificity and diagnostic odds ratios were noted when AC (including CT AC, RAC, and all AC) was compared with NAC. CONCLUSION: The results from this study suggested that AC should be applied to MPI to improve the diagnosis of CAD, especially the specificity.

Search of Unknown Fever Focus Using PET in Critically Ill Children With Complicated Underlying Diseases.

OBJECTIVES: PET/CT with F-fluorodeoxyglucose can be used to image cellular metabolism and has been used for evaluating fever of unknown origin in adults. However, there are limited studies about the role of F-fluorodeoxyglucose PET/CT in evaluation of fever of unknown origin in critically ill children, especially those presenting with complicated underlying diseases under treatment. Here, we report our preliminary experience using F-fluorodeoxyglucose PET/CT in this specific group of patients. DESIGN: Retrospective observational study. SETTING: PICUs of a university hospital. PATIENTS: Nineteen critically ill children (mean age, 5.7 yr old) with complicated underlying diseases requiring intensive care support underwent F-fluorodeoxyglucose PET/CT to evaluate fever of unknown origin. The median hospitalized stay was 34 days (range, 15-235 d) and fever of at least 7 days (mean, 21.6 d; range, 7-52 d). The PET scan was advocated after all routine microbiology, and conventional imaging showed negative or inconclusive results. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The F-fluorodeoxyglucose PET/CT findings (blinded to the final clinical diagnosis) were compared with final histopathology, culture, serology results, or follow-up imaging. A final diagnosis was made in 16 patients (84.2%). F-fluorodeoxyglucose PET/CT accurately localized the source of fever in 14 patients, confers to a sensitivity of 87.5% (14 of 16; 95% CI, 0.604-0.978). A false-positive scan in a patient led to subsequent unnecessary investigations. Two false-negative F-fluorodeoxyglucose PET/CT images were later attributed to relapse of underlying disease in the bone marrow and renal abscesses, respectively. In the other two patients where F-fluorodeoxyglucose PET/CT also showed negative findings, fever subsided shortly thereafter without treatment. CONCLUSIONS: Our preliminary experience suggests that F-fluorodeoxyglucose PET/CT may be clinically beneficial in evaluating fever of unknown origin in children with complicated underlying diseases mandating intensive support in ICUs if usual investigative methods are unsuccessful. Further large prospective studies are needed to validate these findings.

Evaluation of circulating adipokines and abdominal obesity as predictors of significant myocardial ischemia using gated single-photon emission computed tomography.

OBJECTIVE: Coronary artery disease (CAD) is associated with abdominal obesity and metabolic syndrome. Adipocytes secrete adipokines, including the newly discovered adipocyte fatty acid binding protein (A-FABP) and chemerin. Adipokines contribute to the pathogenesis of CAD. In patients with CAD, the presence of significant ischemia predicts adverse outcomes. It is unknown whether adipokines can be better predictors of the presence of significant myocardial ischemia than conventional risk factors. This study aimed to compare adipokines with clinical risk factors and abdominal obesity as predictive factors for significant myocardial ischemia. METHODS: One hundred and ninety-six adults with suspected, but unproven, CAD were consecutively enrolled. The main measures were clinical and biochemical parameters and stress myocardial perfusion imaging with gated myocardial perfusion single-photon emission computed tomography (SPECT), with computed tomography (CT) attenuation correction. The abdominal visceral fat area was examined using a hybrid SPECT/CT scanner. Serum levels of high-sensitivity C-reactive protein (hs-CRP) and adipokines (adiponectin, A-FABP, and chemerin) were evaluated. RESULTS: A-FABP levels correlated significantly with adiponectin, hs-CRP, body mass index, waist circumference, and visceral fat area. A-FABP was significantly associated with metabolic syndrome (OR 3.2, 95% CI 1.6-6.4, p = 0.001), significant myocardial ischemia (OR 1.9, 95% CI 1.0-3.4, p = 0.05), and stress lung-to-heart ratio (ß = 0.03, p = 0.03) on SPECT. Chemerin was significantly associated with serum triglyceride levels but not with metabolic syndrome, significant ischemia, or stress lung-to-heart ratio on SPECT. A-FABP was better at detecting significant inducible ischemia than other biomarkers, although this was a modest improvement (area under ROC curve 0.579, 95% CI 0.46-0.69). CONCLUSIONS: Serum A-FABP concentrations correlate significantly with visceral fat area, metabolic syndrome, and predicted significant myocardial ischemia on SPECT. This may help to more accurately assess CAD risk, especially in patients with metabolic syndrome.

Neuroimaging findings in a brain with Niemann-Pick type C disease.

Niemann-Pick type C disease (NPC) is a rare autosomal recessive lipid storage disorder caused by impaired cellular functions in processing and transporting low-density lipoprotein-cholesterol. In this report, we present magnetic resonance imaging (MRI), magnetic resonance spectrography (MRS) and 18-fluoro-2-deoxyglucose positron emission tomography (PET) imaging results for a 22-year-old male NPC patient. The patient's two MRI studies (at age 19 years and 22 years) demonstrated progressive changes of brain atrophy that were more prominent at the frontal lobes, and hyperintense signals in bilateral parietal-occipital periventricular white matter. MRS (at age 19 years) revealed no significant decrease in N-acetyl aspartate/choline ratio in the left frontal central white matter. PET (at age 22 years) showed significant bilateral hypometabolism in the prefrontal cortex and dorsomedial thalamus, and hypermetabolism in the parietal-occipital white matter, lenticular nucleus of the basal ganglia, cerebellum and pons. The imaging findings noted by MRI, MRS and 18-fluoro-2-deoxyglucose PET offered a possible supplementary explanation for the clinical neurological symptoms of this NPC patient.

FDG PET/CT findings in purely cutaneous Rosai-Dorfman disease.

PET/CT showed accurate localization of increased glucose metabolism.

Gallium-67 SPECT/CT for abdominal abscess.

An 80-year-old woman, who had suffered from end-stage renal disease under peritoneal dialysis, was presented with intermittent fever, leukocytosis, and elevated C-reactive protein for 4 months. She did not have symptom of abdominal pain. Culture of ascites showed Klebsiella pneumoniae. Abdominal utrasonography was negative. Whole-body gallium-67 imaging showed a segmental uptake mimicking bowels in right abdomen. SPECT/CT revealed the uptake in a soft tissue density beneath the abdominal wall instead of bowels. Contrast-enhanced CT demonstrated a low-density mass with peripheral enhancement at the aforementioned area. Her clinical condition stabilized gradually after CT-guided percutaneous drainage of pus from the abscess.