Management of immune-related adverse events resulting from immune checkpoint blockade

Introduction: Immune checkpoint inhibitors (ICI) are now a standard of care in the treatment of many cancers leading to durable responses in patients with metastatic disease. These agents are generally well tolerated but may lead to the occurrence of immune-related adverse events (irAEs). As any organ may be affected, clinicians should be aware of the broad range of clinical manifestations and symptoms and keep in mind that toxicities may occur late, at any point along a patient’s treatment course. Although the most common irAEs are rarely severe, some of them may be associated with great morbidity and even become life-threatening. The rate of occurrence, type and severity of irAEs may vary with the type of ICI; thus, grade 3 and 4 irAEs are reported in more than 55% of patients treated with the combination of ipilimumab 3 mg/kg and nivolumab 1 mg/kg.

Area covered: This review presents the management of irAEs resulting from checkpoint blockade, with a focus on rare irAEs.

Expert commentary: With the development of immuno-oncology and the expanding role of ICI, physicians have learnt to diagnose and treat most of the irAEs that can occur. This review provides an overview of current guidelines, previously published studies and our multidisciplinary team based practices.     

Automated brain MRI metrics in the EPIRMEX cohort of preterm newborns: Correlation with the neurodevelopmental outcome at 2 years

PurposeThe purpose of this study was to identify in the EPIRMEX cohort the correlations between MRI brain metrics, including diffuse excessive high signal intensities (DEHSI) obtained with an automated quantitative method and neurodevelopmental outcomes at 2 years.Materials and methodsA total of 390 very preterm infants (gestational age at birth ≤ 32 weeks) who underwent brain MRI at term equivalent age at 1.5T (n = 338) or 3T (n = 52) were prospectively included. Using a validated algorithm, automated metrics of the main brain surfaces (cortical and deep gray matter, white matter, cerebrospinal fluid) and DEHSI with three thresholds were obtained. Linear adjust regressions were performed to assess the correlation between brain metrics with the ages and stages questionnaire (ASQ) score at 2 years.ResultsBasal ganglia and thalami, cortex and white matter surfaces positively and significantly correlated with the global ASQ score. For all ASQ sub-domains, basal ganglia and thalami surfaces significantly correlated with the scores. DEHSI was present in 289 premature newborns (74%) without any correlation with the ASQ score. Metrics of DEHSI were greater at 3T than at 1.5T.ConclusionBrain MRI metrics obtained in our multicentric cohort correlate with the neurodevelopmental outcome at 2 years of age. The quantitative detection of DEHSI is not predictive of adverse outcomes. Our automated algorithm might easily provide useful predictive information in daily practice.     

Cannabinoid hyperemesis syndrome in two French emergency departments: a prospective cohort

Chronic cannabis use can be associated with uncontrollable vomiting and abdominal pain. Diagnostic criteria for cannabinoid hyperemesis syndrome (CHS) were defined in 2012 by Simonetto et al. The objectives of this study were to describe the prevalence of CHS, the patients' epidemiological characteristics, and to show the difficulties encountered in caring for these patients in emergency departments, the extent of health care and an unsuitable follow‐up in general practices. A prospective cohort of patients with CHS was recruited among a target population of patients leaving the adult emergency services of the Marseille hospitals Nord and La Timone between October 2017 and July 2018, with abdominal pain syndrome of unidentified etiology. Inclusion criteria for the CHS cohort were chronic cannabis use associated with nausea and vomiting. There were 48 patients included in the CHS cohort who took cannabis daily, in a target population of 2 848 patients (i.e. 1.6%). A hot shower was the most effective symptomatic treatment in 54.2% of cases. Patients suffering from CHS spent significantly more hours in emergency departments (11 vs. 6.5), and, on average, visits were more frequent (4.9 vs. 3). 20.3% of them were hospitalized to continue pain medication. Once out of hospital, follow‐up was limited, and weaning off cannabis, the only etiological treatment, was difficult to set up. Informing patients about CHS is essential, and a hot shower could be systematically proposed, thus limiting an unnecessary extent of health care. CHS is genuine, medical staff should be made aware of it in occupational training, and it should be seriously considered in health policies.     

Multicenter precision of cortical and trabecular bone quality measures assessed by high‐resolution peripheral quantitative computed tomography

High‐resolution peripheral quantitative computed tomography (HR‐pQCT) has recently been introduced as a clinical research tool for in vivo assessment of bone quality. The utility of this technology to address important skeletal health questions requires translation to standardized multicenter data pools. Our goal was to evaluate the feasibility of pooling data in multicenter HR‐pQCT imaging trials. Reproducibility imaging experiments were performed using structure and composition‐realistic phantoms constructed from cadaveric radii. Single‐center precision was determined by repeat scanning over short‐term (<72 hours), intermediate‐term (3–5 months), and long‐term intervals (28 months). Multicenter precision was determined by imaging the phantoms at nine different HR‐pQCT centers. Least significant change (LSC) and root mean squared coefficient of variation (RMSCV) for each interval and across centers was calculated for bone density, geometry, microstructure, and biomechanical parameters. Single‐center short‐term RMSCVs were <1% for all parameters except cortical thickness (Ct.Th) (1.1%), spatial variability in cortical thickness (Ct.Th.SD) (2.6%), standard deviation of trabecular separation (Tb.Sp.SD) (1.8%), and porosity measures (6% to 8%). Intermediate‐term RMSCVs were generally not statistically different from short‐term values. Long‐term variability was significantly greater for all density measures (0.7% to 2.0%; p < 0.05 versus short‐term) and several structure measures: cortical thickness (Ct.Th) (3.4%; p < 0.01 versus short‐term), cortical porosity (Ct.Po) (15.4%; p < 0.01 versus short‐term), and trabecular thickness (Tb.Th) (2.2%; p < 0.01 versus short‐term). Multicenter RMSCVs were also significantly higher than short‐term values: 2% to 4% for density and micro–finite element analysis (µFE) measures (p < 0.0001), 2.6% to 5.3% for morphometric measures (p < 0.001), whereas Ct.Po was 16.2% (p < 0.001). In the absence of subject motion, multicenter precision errors for HR‐pQCT parameters were generally less than 5%. Phantom‐based multicenter precision was comparable to previously reported in in vivo single‐center precision errors, although this was approximately two to five times worse than ex vivo short‐term precision. The data generated from this study will contribute to the future design and validation of standardized procedures that are broadly translatable to multicenter study designs. © 2013 American Society for Bone and Mineral Research.