Magnetic resonance imaging is a valuable tool to evaluate the therapeutic efficacy of burosumab in children with X-linked hypophosphatemia.

Purpose: To examine the MRI diagnostic performance in the assessment of therapeutic response to burosumab in children with X-linked hypophosphatemia (XLH).

Design: Prospective longitudinal open cohort.

Patients: Seventeen children with XLH, average age of 10.

Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2).

ARIEL2 (NCT01891344) is a single-arm, open-label phase 2 study of the PARP inhibitor (PARPi) rucaparib in relapsed high-grade ovarian carcinoma. In this post hoc exploratory biomarker analysis of pre- and post-platinum ARIEL2 samples, RAD51C and RAD51D mutations and high-level BRCA1 promoter methylation predict response to rucaparib, similar to BRCA1/BRCA2 mutations. BRCA1 methylation loss may be a major cross-resistance mechanism to platinum and PARPi.

Population exposure-efficacy and exposure-safety analyses for rucaparib in patients with recurrent ovarian carcinoma from Study 10 and ARIEL2.

Objective: To evaluate correlations between rucaparib exposure and selected efficacy and safety endpoints in patients with recurrent ovarian carcinoma using pooled data from Study 10 and ARIEL2.

Methods: Efficacy analyses were limited to patients with carcinomas harboring a deleterious BRCA1 or BRCA2 mutation who had received ≥2 prior lines of chemotherapy. Safety was evaluated in all patients who received ≥1 rucaparib dose.

Neurologic Adverse Events of Immune Checkpoint Inhibitors: A Systematic Review.

Objective: To define the clinical characteristics, management, and outcome of neurologic immune-related adverse events (n-irAEs) of immune checkpoint inhibitors (ICIs).

Methods: Systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Results: A total of 694 articles were identified.

Effectiveness And Safety Of Ustekinumab Intensification At 90 Mg Every Four Weeks In Crohn's Disease: A Multicenter Study.

Introduction: The approved maintenance regimens for ustekinumab in Crohn's disease (CD) are 90 mg every 8 or 12 weeks. Some patients will partially respond to ustekinumab or will experience a secondary loss of response. It remains poorly known if these patients may benefit from shortening the interval between injections.

Development and Validation of the Gene Expression Predictor of High-grade Serous Ovarian Carcinoma Molecular SubTYPE (PrOTYPE).

Purpose: Gene expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features.

Prognostic gene expression signature for high-grade serous ovarian cancer.

Background: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC.

Tumor-associated macrophages and macrophage-related immune checkpoint expression in sarcomas.

Early trials for immune checkpoint inhibitors in sarcomas have delivered mixed results, and efforts to improve outcomes now look to combinatorial strategies with novel immunotherapeutics, including some that target macrophages. To enhance our understanding of the sarcoma immune landscape, we quantified and characterized tumor-associated macrophage infiltration and expression of the targetable macrophage-related immune checkpoint CD47/SIRPα across sarcoma types. We surveyed immunohistochemical expression of CD68, CD163, CD47, and SIRPα in tissue microarrays of 1242 sarcoma specimens (spanning 24 types).

A long-term evaluation of a training program on breaking bad news in pediatric neurosurgery: a pilot study.

Objective: Breaking bad news is a difficult task in medical practice. Several breaking-bad-news training programs have been proposed. However, long-term results of such training have rarely been investigated.

Maintenance of Remission Among Patients With Inflammatory Bowel Disease After Vedolizumab Discontinuation: A Multicentre Cohort Study.

Background And Aim: It is unclear whether vedolizumab therapy can be discontinued in patients with inflammatory bowel disease [IBD] after achieving steroid-free clinical remission. The aim was to assess the risk of relapse after vedolizumab therapy was discontinued.

Methods: This was a retrospective observational study, collecting data from 21 tertiary centres affiliated with the GETAID from January 2017 to April 2019.

Antitumor activity of the poly(ADP-ribose) polymerase inhibitor rucaparib as monotherapy in patients with platinum-sensitive, relapsed, -mutated, high-grade ovarian cancer, and an update on safety.

Objective: To report results from an integrated efficacy and safety analysis supporting the European Commission's approval of the poly(ADP-ribose) polymerase inhibitor rucaparib as monotherapy treatment for relapsed, platinum-sensitive, -mutated ovarian cancer.

Methods: Efficacy was analyzed in platinum-sensitive patients from Study 10 (NCT01482715) and ARIEL2 (NCT01891344) who had high-grade serous or endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer and a deleterious or mutation and received two or more prior chemotherapies (including two or more platinum-based therapies). The primary end point was investigator-assessed, confirmed objective response rate (visit cut-off: April 10, 2017).

Real-World Delivery of Rucaparib to Patients with Ovarian Cancer: Recommendations Based on an Integrated Safety Analysis of ARIEL2 and Study 10.

Treatment options for women with recurrent ovarian cancer who have received two or more prior lines of chemotherapy have recently expanded with the U.S. Food and Drug Administration (FDA) and European Commission (EC) approvals of the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib.

Additive or Synergistic Interactions Between IL-17A or IL-17F and TNF or IL-1β Depend on the Cell Type.

IL-17A has effects on several cell types and is a therapeutic target in several inflammatory diseases. IL-17F shares 50% homology and biological activities with IL-17A. It is now of interest to target both cytokines.

Expression of lymphocyte immunoregulatory biomarkers in bone and soft-tissue sarcomas.

Despite advances in our understanding of the underlying molecular drivers of sarcomas, few treatments are available with proven benefit for advanced metastatic sarcomas. Immunotherapy has value in this setting for some types of cancers, but sarcomas, with their multiplicity of rare types, have not been characterized in detail for their expression of targetable immune biomarkers. This study provides the most systematic evaluation to date of tumor-infiltrating lymphocytes and immune checkpoint biomarker expression in sarcomas.

The Large-Scale Organization of Gestures and Words in the Middle Temporal Gyrus.

The middle temporal gyrus (MTG) has been shown to be recruited during the processing of words, but also during the observation of actions. Here we investigated how information related to words and gestures is organized along the MTG. To this aim, we measured the BOLD response in the MTG to video clips of gestures and spoken words in 17 healthy human adults (male and female).

Vedolizumab Therapy is Ineffective for Primary Sclerosing Cholangitis in Patients With Inflammatory Bowel Disease: A GETAID Multicentre Cohort Study.

Background: Whether vedolizumab may be effective as a treatment for primary sclerosing cholangitis [PSC] in patients with inflammatory bowel disease [IBD] remains controversial.

Methods: We performed a retrospective observational study of consecutive patients with IBD and PSC, treated with vedolizumab for at least 30 weeks in 22 centres of GETAID from January 2015 to June 2016. The outcomes included a decrease in the serum alkaline phosphatase [ALP] concentration of at least 50% from baseline to Week 30 or 54, a change in any serum liver enzymes concentrations, and an assessment of the efficacy and safety of vedolizumab in IBD.

Concentrations of Ustekinumab During Induction Therapy Associate With Remission in Patients With Crohn's Disease.

Ustekinumab is approved for treatment of Crohn's disease (CD). Few data are available to assess the usefulness of monitoring inflammatory biomarkers and therapeutic drug monitoring to predict response to ustekinumab. We conducted a prospective study to assess the relationships between these parameters and the clinical outcome at week 16 in active CD patients receiving ustekinumab.

Usefulness of confocal laser endomicroscopy for predicting postoperative recurrence in patients with Crohn's disease: a pilot study.

Background And Aims: Confocal laser endomicroscopy (CLE) has been shown to predict relapse in inflammatory bowel disease, but its value in the detection of postoperative recurrence in Crohn's disease (CD) is unknown. The aims of this pilot study performed in patients with CD after ileocolonic resection were to compare the macroscopic appearance of the neoterminal ileum, according to the endoscopic Rutgeerts score, with the microscopic findings provided by CLE 6 to 12 months after surgery and to assess the predictive values of CLE-generated parameters for predicting further recurrence in patients with postoperative endoscopic remission.

Methods: In 25 consecutive patients with CD within 6 to 12 months of surgery, the neoterminal ileum was examined by standard white-light endoscopy (Rutgeerts scale) followed by CLE (Watson grade).

Loss of the sphingolipid desaturase DEGS1 causes hypomyelinating leukodystrophy.

Sphingolipid imbalance is the culprit in a variety of neurological diseases, some affecting the myelin sheath. We have used whole-exome sequencing in patients with undetermined leukoencephalopathies to uncover the endoplasmic reticulum lipid desaturase DEGS1 as the causative gene in 19 patients from 13 unrelated families. Shared features among the cases include severe motor arrest, early nystagmus, dystonia, spasticity, and profound failure to thrive.

A norming study of high-quality video clips of pantomimes, emblems, and meaningless gestures.

Recent years have witnessed a growing interest in behavioral and neuroimaging studies on the processing of symbolic communicative gestures, such as pantomimes and emblems, but well-controlled stimuli have been scarce. This study describes a dataset of more than 200 video clips of an actress performing pantomimes (gestures that mimic object-directed/object-use actions; e.g.

Reversion Mutations in Circulating Tumor DNA Predict Primary and Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma.

A key resistance mechanism to platinum-based chemotherapies and PARP inhibitors in -mutant cancers is the acquisition of reversion mutations that restore protein function. To estimate the prevalence of reversion mutations in high-grade ovarian carcinoma (HGOC), we performed targeted next-generation sequencing of circulating cell-free DNA (cfDNA) extracted from pretreatment and postprogression plasma in patients with deleterious germline or somatic mutations treated with the PARP inhibitor rucaparib. reversion mutations were identified in pretreatment cfDNA from 18% (2/11) of platinum-refractory and 13% (5/38) of platinum-resistant cancers, compared with 2% (1/48) of platinum-sensitive cancers ( = 0.