Psoriatic Arthritis and Metabolic Syndrome: Is There a Role for Disease Modifying Anti-Rheumatic Drugs?

Although psoriatic arthritis (PsA) primarily leads to joint and skin damage, it is associated with higher prevalence of metabolic syndrome (MetS) and its components, namely hypertension, dyslipidemia, obesity, and type II diabetes. Additionally, chronic inflammation is known to aggravate these cardiometabolic factors, thus explaining the enhanced cardiovascular (CV) morbidity and mortality in RA. Furthermore, emerging evidence suggest that some risk factors can fuel inflammation, thus pointing to a bidirectional crosstalk between inflammation and cardiometabolic factors. Therefore, dampening inflammation by disease-modifying anti-rheumatic drugs (DMARDs) may be thought to ameliorate MetS burden and thus, CV risk and disease severity. In fact, recommendations for PsA management emphasize the need of considering comorbidities to guide the treatment decision process. However, the existing evidence on the impact of approved DMARDs in PsA on MetS and MetS components is far from being optimal, thus representing a major challenge for the clinical setting. Although a beneficial effect of some DMARDs such as methotrexate, TNF inhibitors and some small molecules is clear, no head-to-head studies are published and no evidence is available for other therapeutic approaches such as IL-23 or IL-17 inhibitors. This narrative review summarizes the main evidence related to the effect of DMARDs on MetS outcomes in PsA patients and identify the main limitations, research needs and future perspectives in this scenario.

Efficacy of Ultrasonography in the Diagnosis of Peritoneal Catheter Obstruction in Children: A Case Series

Catheter obstruction is a serious complication associated with peritoneal dialysis (PD). Diagnostic imaging techniques play a role in the management of patients undergoing PD, mainly in detecting potential catheter-related complications. Imaging can help in the treatment decision process. Visualizing the obstruction and understanding the etiology are crucial for accurate management of patients and in determining therapeutic strategies. Although a PD catheter obstruction can be diagnosed using magnetic resonance imaging (MRI), ultrasonography (US) has been reported to be equally effective. The effectiveness of US and MRI in detecting PD catheter obstructions was compared in four pediatric patients. These cases demonstrate that US was more useful in visualizing PD obstruction compared with MRI. US can be repeated more conveniently and is noninvasive, especially in children. US can be considered an effective tool for diagnosing PD catheter obstruction in children.

Genomic Analysis of Posterior Fossa Meningioma Demonstrates Frequent AKT1 E17K Mutations in Foramen Magnum Meningiomas

Objective Posterior fossa meningiomas are surgically challenging tumors that are associated with high morbidity and mortality. We sought to investigate the anatomical distribution of clinically actionable mutations in posterior fossa meningioma to facilitate identifying patients amenable for systemic targeted therapy trials. Methods Targeted sequencing of clinically targetable AKT1, SMO, and PIK3CA mutations was performed in 61 posterior fossa meningioma using Illumina NextSeq 500 to a target depth of >500 × . Samples were further interrogated for 53 cancer-relevant RNA fusions by the Archer FusionPlex panel to detect gene rearrangements. Results AKT1 (E17K) mutations were detected in five cases (8.2%), four in the foramen magnum and one in the cerebellopontine angle. In contrast, none of the posterior fossa tumors harbored an SMO (L412F) or a PIK3CA (E545K) mutation. Notably, the majority of foramen magnum meningiomas (4/7, 57%) harbored an AKT1 mutation. In addition, common clinically targetable gene fusions were not detected in any of the cases. Conclusion A large subset of foramen magnum meningiomas harbor AKT1 E17K mutations and are therefore potentially amenable to targeted medical therapy. Genotyping of foramen magnum meningiomas may enable more therapeutic alternatives and guide their treatment decision process.

A non-invasive urine exosome gene expression assay (ExoIntelliScore Prostate) to predict pathologic stage and grade in the prostatectomy specimen.

46 Background: Non-invasive screening tools that add predictive value for identifying high-grade, Gleason score (GS) ≥7 should impact on the current diagnostic and subsequent treatment decision process. We have developed standardized processes to isolate exosomal-RNA from first-catch, non-DRE, urine specimens and have validated a three gene signature (ExoIntelliScore Prostate) that reliably differentiates GS7+ from GS6 and benign at the time of an initial biopsy. In addition to the biopsy outcomes, we sought to understand the performance of the assay in predicting objective pathology in the prostatectomy specimen. Methods: Pre-radical prostatectomy first-catch non-DRE urine specimens were collected from 5 urology practices (academic/community practices) without preservative, stored at 2-8C (up to 2 weeks) and shipped on ice to a central laboratory (Exosome Diagnostics, St. Paul, MN). Exosomes were isolated and RNA extraction performed. RT-qPCR RNA copy numbers of ERG and PCA3 were normalized to SPDEF. Spearman and Pearson correlation along with AUC was used to evaluate performance. Results: Pre-RP urine samples from 430 patients were collected: 16% GS6, 45% GS7 (3+4), 39% (>/=GS4+3) and 85% PSA <10 ng/mL. 359 patients had complete clinical and ExoIntelliScore Prostate assay results with comparable demographics. Importantly, the Exo106 significantly correlated with prostatectomy GS (p=0.025; Spearman’s rank-order). In addition, Exo106 significantly correlated with both tumor volume and pathologic stage (p=0.002, Pearson). Conclusions: A previously validated non-invasive urine exosome gene signature (ExoIntelliScore Prostate) accurately reflects what is present within the prostatectomy specimen with respect to grade, stage and tumor volume. Such information could be incorporated into the treatment decision process, including active surveillance.

Treat-Early and Treat-Mild: Role of Fast vs. Slow Escalation of Headaches

This prospective, multi-center, observational study aimed to examine patients' early treatment decision process. Specifically, we assessed if the association between mild headache pain at treatment initiation and early treatment differed by the speed of headache escalation. Patients ( n = 168) were instructed to collect information on their headache experience during the study period via an electronic diary over 30 consecutive days after enrollment. At the time of treatment, patients who treated early were 2.3 times as likely to experience mild headache pain as those who treated late. Controlling for the effect of escalation of headache, patients who treated early were three times as likely to report mild headache pain at dosing as those who treated late. The interaction between fast escalation of headache and mild pain was not statistically significant. Early treatment is associated with mild pain, regardless of the speed of headache escalation.