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Purpose The purpose of this analysis is to assess the effect of antiepileptics (AEDs) on seizure prevention and short and long term functional outcomes in patients with acute intracerebral hemorrhage. Method The meta-analysis was conducted using the PRISMA guidelines. A literature search was performed of the PubMed, the Cochrane Library, and EMBASE databases. Search terms included “Anticonvulsants”, “Intracerebral Hemorrhage”, and related subject headings. Articles were screened and included if they were full-text and in English. Articles that did not perform multivariate regression were not included. Overall effect size was evaluated with forest plots and publication bias was assessed with the Begg’s and Egger’s tests. Results A total of 3912 articles were identified during the initial review. After screening, 54 articles remained for full review and 6 articles were included in the final analysis. No significant association between the use of AEDs after ICH and functional outcome (OR 1.53 [95%CI: 0.81–2.88] P = 0.18, I 2 = 81.7%). Only one study evaluated the effect AEDs had in preventing post-ICH seizures. Conclusions The use of prophylactic AEDs was not associated with improved short and long outcomes after acute ICH. This analysis supports the 2015 AHA/ASA recommendation against prophylactic AEDs (class III; level of evidence b).

Foreign body reactions elicit granulomatous inflammation composed of reactive macrophages. We hypothesized that [125I]iodo-DPA-713 single-photon emission computed tomography (SPECT), a low-molecular-weight pyrazolopyrimidine ligand selectively trapped by phagocytes, could be used to detect foreign body reactions in a murine model. C57BL/6 mice intratracheally inoculated with dextran beads, which developed foreign body lesions, were imaged after injection of [125I]iodo-DPA-713 or DPA-713-IRDye800CW using SPECT and optical imaging, respectively. Foreign body lesions were clearly observed in the lungs of the dextran-treated mice on computer tomography imaging and demonstrated significantly higher [125I]iodo-DPA-713 uptake compared with control animals (p

Matrix metalloproteinases (MMPs) degrade extracellular matrix and are implicated in tuberculosis pathogenesis and cavitation. In particular, MMP-7 is induced by hypoxia and highly expressed around pulmonary cavities of Mycobacterium tuberculosis–infected C3HeB/FeJ mice. In this study, we evaluated whether administration of cipemastat, an orally available potent inhibitor of MMP-7, could reduce pulmonary cavitation in M. tuberculosis–infected C3HeB/FeJ mice. We demonstrate that, compared with untreated controls, cipemastat treatment paradoxically increases the frequency of cavitation (32% vs 7%; P = .029), immunopathology, and mortality. Further studies are needed to understand the role of MMP inhibitors as adjunctive treatments for pulmonary tuberculosis.

Whole-body PET/CT was performed using 124I-DPA-713, a radioligand for the 18-kDa translocator protein (TSPO), to determine biodistribution and radiation dosimetry. Methods: Healthy subjects aged 18–65 y underwent whole-body PET/CT either at 4, 24, and 48 h or at 24, 48, and 72 h after intravenous injection of 124I-DPA-713. Time–activity curves were generated and used to calculate organ time-integrated activity coefficients for each subject. The resulting time-integrated activity coefficients provided input data for calculation of organ absorbed doses and effective dose for each subject using OLINDA. Subjects were genotyped for the TSPO polymorphism rs6971, and plasma protein binding of 124I-DPA-713 was measured. Results: Three male and 3 female adults with a mean age of 40 ± 19 y were imaged. The mean administered activity and mass were 70.5 ± 5.1 MBq (range, 62.4–78.1 MBq) and 469 ± 34 ng (range, 416–520 ng), respectively. There were no adverse or clinically detectable pharmacologic effects in any of the 6 subjects. No changes in vital signs, laboratory values, or electrocardiograms were observed. 124I-DPA-713 cleared rapidly (4 h after injection) from the lungs, with hepatic elimination and localization to the gastrointestinal tract. The mean effective dose over the 6 subjects was 0.459 ± 0.127 mSv/MBq, with the liver being the dose-limiting organ (0.924 ± 0.501 mGy/MBq). The percentage of free radiotracer in blood was approximately 30% at 30 and 60 min after injection. Conclusion:124I-DPA-713 clears rapidly from the lungs, with predominantly hepatic elimination, and is safe and well tolerated in healthy adults.

Tuberculous meningitis (TBM) is a devastating form of tuberculosis (TB), and key TB antimicrobials, including rifampin, have restricted brain penetration. A lack of reliable data on intralesional drug biodistribution in infected tissues has limited pharmacokinetic (PK) modeling efforts to optimize TBM treatments. Current methods to measure intralesional drug distribution rely on tissue resection, which is difficult in humans and generally limited to a single time point even in animals. In this study, we developed a multidrug treatment model in rabbits with experi­ mentally induced TBM and performed serial noninvasive dynamic (11)C-rifampin positron emission tomography (PET) over 6 weeks. Area under the curve brain/plasma ratios were calculated using PET and correlated with postmortem mass spectrometry. We demonstrate that rifampin penetration into infected brain lesions is limited, spa­ tially heterogeneous, and decreases rapidly as early as 2 weeks into treatment. Moreover, rifampin concentrations in the cerebrospinal fluid did not correlate well with those in the brain lesions. First-in-human (11)C-rifampin PET performed in a patient with TBM confirmed these findings. PK modeling predicted that rifampin doses (≥30 mg/kg) were required to achieve adequate intralesional concentrations in young children with TBM. These data demonstrate the proof of concept of PET as a clinically translatable tool to noninvasively measure intralesional antimicrobial distribution in infected tissues.

INTRODUCTION Systemic lupus erythematosus (SLE) is an inflammatory disease which affects multiple organs. The respiratory system is compromised in 1.6% to 36% of the patients with SLE. The objective of this study was to know the prevalence of these alterations, their associated variables, and outcomes in patients with SLE between 2012 and 2017. METHODS A cross-sectional study of 200 patients with SLE underwent chest computed tomography (CT). The primary outcome was acute respiratory involvement (ARI). A descriptive, bivariate and multivariate analysis were performed using Stata 12.0 software. RESULTS ARI was present in 40% of the SLE patients undergoing chest CT. The most frequent ARI was pleural effusion in 33%, followed by pneumonia (16.5%), lupus pneumonitis (9%), pulmonary embolism (3%) and pulmonary hemorrhage (2.5%). In bivariate and multivariate analysis a statistically significant association between ARI and nephropathy, hematological impairment, active disease, dead, readmission and prolonged hospital stay was found. CONCLUSION This is the first Colombian study that evaluates ARI in patients with SLE. ARI is an important and frequent condition in patients with SLE, pleural effusion being the most prevalent cause of ARI. There are some variables (nephropathy, hematological impairment and activity disease) that are associated with ARI and could be the basis of intervention.

PURPOSE: Foreign body reactions elicit granulomatous inflammation composed of reactive macrophages. We hypothesized that [(125)I]iodo-DPA-713 single-photon emission computed tomography (SPECT), a low-molecular-weight pyrazolopyrimidine ligand selectively trapped by phagocytes, could be used to detect foreign body reactions in a murine model. PROCEDURES: C57BL/6 mice intratracheally inoculated with dextran beads, which developed foreign body lesions, were imaged after injection of [(125)I]iodo-DPA-713 or DPA-713-IRDye800CW using SPECT and optical imaging, respectively. RESULTS: Foreign body lesions were clearly observed in the lungs of the dextran-treated mice on computer tomography imaging and demonstrated significantly higher [(125)I]iodo-DPA-713 uptake compared with control animals (p < 0.01). Ex vivo studies demonstrated granulomatous reactions in the lungs of dextran-treated mice and localization of DPA-713-IRDye800CW at the diseased sites confirming the imaging findings. CONCLUSION: Radioiodinated DPA-713 may be used as a noninvasive biomarker for the detection of pulmonary foreign body reactions.

Macrophages belong to the mononuclear phagocyte system comprising closely related cells of bone marrow origin. Activated macrophages are critical in several diseases such as tuberculosis, sarcoidosis, Crohn's disease, and atherosclerosis. Noninvasive imaging techniques that can specifically image activated macrophages could therefore help in differentiating various forms of inflammatory diseases and to monitor therapeutic responses.

The novel PET probe 2-deoxy-2-(18)F-fluoro-D-sorbitol ((18)F-FDS) has demonstrated favorable renal kinetics in animals. We aimed to elucidate its imaging properties in two human volunteers. (18)F-FDS was produced by a simple one-step reduction from (18)F-FDG. On dynamic renal PET, the cortex was delineated and activity gradually transited in the parenchyma, followed by radiotracer excretion. No adverse effects were reported. Given the higher spatiotemporal resolution of PET relative to conventional scintigraphy, (18)F-FDS PET offers a more thorough evaluation of human renal kinetics. Due to its simple production from (18)F-FDG, (18)F-FDS is virtually available at any PET facility with radiochemistry infrastructure.

Introduction: Intracranial hemorrhage (ICH) is a devastating form of stroke that leads to development of seizures in up to 2%-40% of patients. Seizure prophylaxis in ICH remains controversial and it is unclear if the benefits of antiepileptic drugs (AEDs) outweigh the risk of potential adverse drug effects. The objective of this analysis is to assess the effect of AED on seizure prevention and long term functional outcomes in patients with acute ICH. Methods: Our group conducted a meta-analysis using the PRISMA guidelines. A literature search was performed of the PubMed, the Cochran Library, and EMBASE databases using the keywords “Anticonvulsants”, “Intracerebral Hemorrhage”, and related subject headings. Articles were screened and included if they assessed the impact of AEDs on long-term functional outcomes in ICH population using multivariate logistic regression analysis. Overall effect sizes were evaluated with forest plots and publication bias was assessed with the Begg’s and Egger’s tests. Long term functional outcomes were assessed at ≥ 3 months post-ICH with either the National Institute of Health Stroke Scale (NIHSS) or the modified Rankin Score (mRS). Results: A total of 3,912 articles were identified during the intimal review. After screening, 54 articles remained for full review and 6 articles were included in the final analysis. The quality assessment criteria ranged from moderate to high for evidence synthesis. A total of 3,193 patients were included in the analysis. There were no significant association between the use of AEDs after ICH and poor outcome defined as mRS ≥3 or NIHSS ≥15 (OR 1.53 [95% CI: 0.81-2.88] p=0.18, I 2 =81.7%). Only one trial evaluated the effect AEDs had in prevent post-ICH seizures. Publication bias was not observed in the analysis (Egger’s bias=2.23, P=0.23). Conclusion: In conclusion, the use of prophylactic AEDs was not associated with improved or worse functional outcomes after acute ICH.

Whole-body PET/CT was performed using (124)I-DPA-713, a radioligand for the 18-kDa translocator protein (TSPO), to determine biodistribution and radiation dosimetry. Methods: Healthy subjects aged 18–65 y underwent whole-body PET/CT either at 4, 24, and 48 h or at 24, 48, and 72 h after intravenous injection of (124)I-DPA-713. Time–activity curves were generated and used to calculate organ time-integrated activity coefficients for each subject. The resulting time-integrated activity coefficients provided input data for calculation of organ absorbed doses and effective dose for each subject using OLINDA. Subjects were genotyped for the TSPO polymorphism rs6971, and plasma protein binding of (124)I-DPA-713 was measured. Results: Three male and 3 female adults with a mean age of 40 ± 19 y were imaged. The mean administered activity and mass were 70.5 ± 5.1 MBq (range, 62.4–78.1 MBq) and 469 ± 34 ng (range, 416–520 ng), respectively. There were no adverse or clinically detectable pharmacologic effects in any of the 6 subjects. No changes in vital signs, laboratory values, or electrocardiograms were observed. (124)I-DPA-713 cleared rapidly (4 h after injection) from the lungs, with hepatic elimination and localization to the gastrointestinal tract. The mean effective dose over the 6 subjects was 0.459 ± 0.127 mSv/MBq, with the liver being the dose-limiting organ (0.924 ± 0.501 mGy/MBq). The percentage of free radiotracer in blood was approximately 30% at 30 and 60 min after injection. Conclusion: (124)I-DPA-713 clears rapidly from the lungs, with predominantly hepatic elimination, and is safe and well tolerated in healthy adults.