Reva Medical (United States)

Objective: This comparative analysis aims to evaluate the patterns of radiological complications in bacterial meningitis against those seen in tuberculous meningitis. Materials and Methods: A retrospective review of imaging and clinical data was conducted. The frequency of complications such as hydrocephalus, infarcts, tuberculomas, abscesses, and cerebritis was analyzed in both cohorts. Results: Hydrocephalus was significantly more frequent in TBM (46.9%) compared to ABM (23%, p < 0.001). Tuberculomas were exclusive to TBM (57.3%, p < 0.001), while abscesses (6.3%) and subdural collections (8.4%) were unique to ABM (p < 0.05). Infarcts occurred at similar rates in both groups (27% vs. 28.1%, p = 0.88). Logistic regression identified TBM as an independent predictor of hydrocephalus (OR: 3.4, 95% CI: 2.1–5.8,p < 0.001) and tuberculomas (OR: 18.7, 95% CI: 11.4–30.9, p < 0.001). These findings emphasize the distinct radiological complication patterns in ABM and TBM, aiding in tailored management strategies. Conclusion: The use of regression analysis provided new insights into predictors of complications; while cerebral infarcts are common in both ABM and TBM, TBM showed a greater burden of complications, particularly hydrocephalus and tuberculomas. The findings highlight the importance of early diagnosis and tailored treatment strategies to reduce morbidity and mortality in both forms of meningitis.

BackgroundDopamine (D) and serotonin (5‐HT) pathways contribute to psoriasis pathobiology. Disruptions incite increased inflammatory mediators, keratinocyte activation and deterioration, and worsening symptoms. Brilaroxazine (RP5063), which displays potent high binding affinity to D2/3/4 and 5‐HT1A/2A/2B/7 receptors and a moderate affinity to serotonin transporter (SERT), may affect the underlying psoriasis pathology.MethodsAn imiquimod‐induced psoriatic mouse model (BALB/c) evaluated brilaroxazine's activity in a topical liposomal‐aqueous gel (Lipogel) formulation. Two of the three groups (n = 6 per) underwent induction with 5% imiquimod, and one group received topical brilaroxazine Lipogel (Days 1–11). Assessments included (1) Psoriasis Area and Severity Index (PASI) scores (Days 1–12), skin histology for Baker score based on H&E stained tissue (Day 12), and serum blood collection for serum cytokine analysis (Day 12). One‐way ANOVA followed by post hoc Dunnett's t‐test evaluated significance (p < 0.05).ResultsImiquimod‐induced animal Baker scores were higher versus Sham non‐induced control's results (p < 0.001). Brilaroxazine Lipogel had significantly (p = 0.003) lower Baker scores versus the induced Psoriasis group. Brilaroxazine PASI scores were lower (p = 0.03) versus the induced Psoriasis group (Days 3‐12), with the greatest effect in the last 3 days. The induced Psoriasis group showed higher Ki‐67 and TGF‐β levels versus non‐induced Sham controls (p = 0.001). The brilaroxazine Lipogel group displayed lower levels of these cytokines versus the induced Psoriasis group, Ki‐67 (p = 0.001) and TGF‐β (p = 0.008), and no difference in TNF‐α levels versus Sham non‐induced controls.ConclusionBrilaroxazine Lipogel displayed significant activity in imiquimod‐induced psoriatic animals, offering a novel therapeutic strategy.

Real-world re-treatment intervals for botulinum toxins vary, but most subjects receive treatment less frequently than the manufacturer-recommended minimum intervals. In subjects receiving treatment with AbobotulinumtoxinA (ABO) less frequently, high levels of satisfaction and psychosocial improvements in well-being, self-confidence, and quality of life are observed. To evaluate subject satisfaction with a twice yearly re-treatment schedule. This open-label, multicenter, interventional study evaluated subject satisfaction following injections of ABO 50 U in the glabellar lines at baseline and 6 months. The primary end point was subject satisfaction at 12 months. Secondary endpoints included subject satisfaction, FACE-Q scales, and glabellar line severity scale (GLSS). Ninety-five percent of the 120 subjects were "highly satisfied" or "satisfied" with their treatment outcomes at 12 months. FACE-Q total scores suggested that subjects were less bothered by glabellar lines and felt better about their facial appearance with each treatment versus baseline. Approximately half of subjects had ≥1-grade improvement from baseline in GLSS at 12 months. Median onset of effect was 2 days. The majority of subjects (95%) were satisfied with ABO treatment every 6 months; results were supported by high subject satisfaction, long duration, rapid onset, natural-looking results, and overall psychological wellness and safety.

Determination of therapeutic benefit in intracranial tumors is intimately dependent on serial assessment of radiographic images. The Response Assessment in Neuro-Oncology (RANO) criteria were established in 2010 to provide an updated framework to better characterize tumor response to contemporary treatments. Since this initial update a number of RANO criteria have provided some basic principles for the interpretation of changes on MR images; however, the details of how to operationalize RANO and other criteria for use in clinical trials are ambiguous and not standardized. In this review article designed for the neuro-oncologist or treating clinician, we outline essential steps for performing radiographic assessments by highlighting primary features of the Imaging Charter (referred to as the Charter for the remainder of this article), a document that describes the clinical trial imaging methodology and methods to ensure operationalization of the Charter into the workings of a clinical trial. Lastly, we provide recommendations for specific changes to optimize this methodology for neuro-oncology, including image registration, requirement of growing tumor for eligibility in trials of recurrent tumor, standardized image acquisition guidelines, and hybrid reader paradigms that allow for both unbiased measurements and more comprehensive interpretation.

Background: Patients with IPF experience varying degrees of decline in lung function over time. The rate of decline can vary between patients and across over time and at present there is no reliable way to predict which subjects will decline faster. Aim: This study explores whether short term change in QLF score can predict fast from vs slow FVC decline. Methods: In an open-label phase 2 trial in patients with IPF subjects underwent standardized HRCT scans (QLF) and spirometry (FVC) performed at baseline and every 24 and 12 weeks, respectively. QLF was measured whore for the whole lung and worst lobe. Mixed effect models were used to estimate and compare against the reduction in FVC over repeated measurements with linear or quadratic growth models. Results: The aAnnual rate of reduction in mean FVC was 3.5% for the Week 24week QLF changes of Conclusion: Change in QLF of 4 percent at 6 months isn predictive of rapid FVC decline within 12 to 15 months

Abstract Background: Cabozantinib is an oral inhibitor of MET and VEGFR2 and at a dose of 100 mg qd has demonstrated high rates of partial or complete bone scan resolution in CRPC patients with bone metastases, as assessed by manual visual reads. No accepted approach exists for the assessment of bone scan response in prostate cancer patients. An FDA 510(k) approved image analysis package has been developed that includes a computer-aided detection (CAD) system to detect pixels associated with bone lesions on bone scan with high accuracy, thus facilitating quantitative assessment of tumor burden with advantages of objectivity and consistency over manual approaches. A change in total Bone Scan Lesion Area of 30% or greater has been previously established as a cutoff point to distinguish responders from non-responders [1]. Methods: Original Digital Imaging and Communications in Medicine (DICOM) format images of baseline and week 6 bone scan assessments were collected and analyzed by the automated CAD system then reviewed by a physician experienced with bone scan interpretation as part of an ongoing clinical study of single agent cabozantinib at a lower starting dose of 40 mg qd in CRPC subjects with evidence of bone metastases. All subjects had undergone standard of care whole body scintigraphy, 2–4 hours post-injection of 20–25 mCi of Tc MDP. All images underwent intensity normalization to a bone scan reference to account for differences in radiotracer dosing levels and scan timing to improve reproducibility. Lesions consistent with metastatic foci of disease were automatically segmented based on anatomic region-specific intensity thresholds. Each segmented image was reviewed by a nuclear medicine physician for removal of any remaining false positive regions (e.g. areas of degenerative joint disease). Quantitative assessment of lesion burden was then determined. Results: 10 CRPC subjects showing evidence of bone metastasis were treated in an ongoing dose-ranging study with cabozantinib and were evaluable for bone scan response assessment at week 6. Reductions in the following parameters (median and range) were observed at week 6 relative to baseline: total Bone Scan Lesion Area (168.5 cm2 [20, 864] to 54 cm2 [0, 431]; 68% reduction), Bone Scan Lesion Count (34 [3, 74] to 3 [0, 64]; 91% reduction), and mean normalized Bone Scan Lesion Intensity (92.2 [56.5, 155.0] to 57.0 [0, 90.5]; 38% reduction). All 10 subjects had a reduction in Bone Scan Lesion Area, with 9 achieving a bone scan response at the week 6 timepoint as assessed by both the CAD system and visual review by the investigator. Conclusion: A significant reduction in apparent bone scan abnormality was demonstrated by the automated CAD system. The results demonstrate the potential for objective measurement of cabozantinib treatment effects in bone, laying the foundation for further validation against other clinically relevant outcome measures such as pain and overall survival. Reference: 1. G. H. Chu, M. S. Brown, H. J. Kim, M. Auerbach, C. Poon, B. Ramakrishna, A. Vidovic, D. W. Gjertson, M. J. Morris, S. M. Larson, J. G. Goldin, H. I. Scher. Initial analytic validation of automated bone scan measures for treatment response assessment in patients with metastatic castration-resistant prostate cancer (CRPC). J Clin Oncol 29: 2011 (suppl; abstr e15174). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B114.