Lupus enteritis: A 10-year experience in a single Latin American center.

OBJECTIVE: The objective is to compare the clinical and laboratory characteristics of systemic lupus erythematosus (SLE) patients with and without lupus enteritis (LE) and to identify the factors associated with the occurrence of LE. METHODS: We performed a retrospective, case-control study in hospitalized patients with SLE who were admitted to our tertiary hospital between January 2012 and December 2021. Sixteen LE patients (cases) were matched (1:3 ratio) for sex and birth year with 48 non-LE patients (controls). Univariable and multivariable logistic regression analyses were used to identify the variables associated with LE. RESULTS: Of 2,479 SLE patients who were admitted to our hospital as inpatients, 16 (0.65%) were diagnosed as having LE. All patients, cases and controls, were of Mestizo ethnicity. SLE was diagnosed simultaneously with the first episode of LE in 10 (62.5%) patients. The median time from SLE diagnosis to the first episode of LE was 7 (IQR 0-78) months. LE patients had a shorter median disease duration [7 (0-78) vs 34 (9.5-79) months], and a significantly longer hospital stay (28.3 ± 15.8 vs 6.5 ± 7.9 days, p < 0.001) than non-LE patients. Most LE patients (93.8%) had concomitant lupus nephritis. LE patients had higher SLEDAI-2K scores than those without LE (20.5 ± 9.4 vs 9.8 ± 10.4, p < 0.001). By multivariable analysis, a higher SLEDAI-2K score (OR 1.10, 95% CI 1.02-1.18; p = 0.015) was independently associated with LE occurrence after adjusting for cutaneous involvement, lymphocyte count, serum creatinine, and serum complement C4. Recurrence was observed in two patients (12.5%), both with a bowel wall thickening > 8 mm. The two patients with large intestine-dominant LE developed intestinal pseudo-obstruction. No patient had life-threatening complications (intestinal hemorrhage, infarction, or perforation), and there were no deaths induced directly by LE itself. CONCLUSION: In patients of Mestizo ethnicity, LE occurs during the early course of SLE, frequently is one of the presenting manifestations of SLE, and in most cases, it presents with concomitant lupus nephritis. Higher levels of disease activity at diagnosis were independently associated with LE occurrence and when recurrences occur, they do so in the context of severe wall thickness.

Acute respiratory involvement in Colombian patients with systemic lupus erythematosus undergoing chest computed tomography.

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.

Impact of antiepileptic drugs for seizure prophylaxis on short and long-term functional outcomes in patients with acute intracerebral hemorrhage: A meta-analysis and systematic review.

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, I2 = 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).

Novel Functional Renal PET Imaging With 18F-FDS in Human Subjects.

The novel PET probe 2-deoxy-2-F-fluoro-D-sorbitol (F-FDS) has demonstrated favorable renal kinetics in animals. We aimed to elucidate its imaging properties in 2 human volunteers. F-FDS was produced by a simple 1-step reduction from 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, F-FDS PET offers a more thorough evaluation of human renal kinetics. Due to its simple production from F-FDG, F-FDS is virtually available at any PET facility with radiochemistry infrastructure.

Matrix Metalloproteinase Inhibition in a Murine Model of Cavitary Tuberculosis Paradoxically Worsens Pathology.

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.

Imaging Pulmonary Foreign Body Reaction Using [125I]iodo-DPA-713 SPECT/CT in Mice.

PURPOSE: 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. PROCEDURES: 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. RESULTS: 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 < 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.

Noninvasive 11C-rifampin positron emission tomography reveals drug biodistribution in tuberculous meningitis.

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 experimentally induced TBM and performed serial noninvasive dynamic 11C-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, spatially 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 11C-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.

Biodistribution and Radiation Dosimetry of 124I-DPA-713, a PET Radiotracer for Macrophage-Associated Inflammation.

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.

Imaging Macrophage-associated Inflammation.

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.