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.     

DEVELOPMENT OF INDICATORS TO MEASURE

This paper describes a study to capture the key roles and activities of nephrology nurses across different countries in Europe. The concept of the study and the need to clarify the activities of the nephrology nurse arose as part of a larger study to develop the European Practice Database (EPD) (1). The Research Board (EDTNA/ERCA) needed to identify key questions that would detect significant differences in the role and responsibilities of nephrology nurses in different countries and monitor the evolution over time of nephrology nursing practice in Europe. It was therefore appropriate to devise a separate small study to generate evidence based questions for the EPD and confirm the reliability and usefulness of the information captured.     

Correlating digit span performance and event-related potentials to assess working memory.

Event-related brain potentials (ERPs) were recorded during a computerized and modified version of the Digit Span Backwards (DB) task from the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III). The modified DB version (ERP-DB task) was divided into two sections of 2, 4, 6 and 8 digits in length (Group 1) and 3, 5 and 7 digits in length (Group 2). Each trial had a study phase and a test phase. For the study phase, a series of digits was presented sequentially and aurally to 20 participants (10 for each group). For the test phase, a second series of digits was also presented sequentially and aurally that either corresponded to the reverse order of the digits in the study phase (correct condition) or had one digit in the sequence replaced by an incorrect digit (incorrect condition). The traditional DB task of the WAIS-III was also administered for comparison purposes. A prolonged positive slow wave (PSW) peaking between 450 and 750 ms was elicited to incorrect condition trials. For each participant, a derived measure was calculated from the ERP differentiation between correct and incorrect conditions. The derived measure was defined as the mean of the t-values obtained from the correct and incorrect waveform comparison, within the temporal interval that encompassed this component. The strongest statistical correlations between the derived measure and the traditional DB test scores were found at the Pz site (Group 1: r=0.79; Group 2: r=0.59). This statistical approach shows that it is possible to adequately relate an individual's performance on a traditional measure of working memory and ERP patterns. Overall, we believe that this kind of ERP approach holds promise as a technique for assessing quantitatively non-communicative patients.     

Immunological responses to pneumococcal vaccine in frail older people

Advanced age has been associated with a wide range of defects in both the innate and adaptive immune systems including diminished specific antibody responses that increase the risk of invasive pneumococcal disease (IPD) and limit the effectiveness of vaccines. However, the elderly are a heterogeneous group and measures of overall frailty may be a better indicator of disease susceptibility (or vaccine response) than chronological age alone.     

Amphibian terminal nerve: distribution revealed by LHRH and AChE markers

Immunocytochemical and histochemical studies in the tiger salamander and bullfrog demonstrated the presence of luteinizing hormone-releasing hormone-like immunoreactive (LHRH-ir) material and acetylcholinesterase (AChE) in the terminal nerve (TN). Immunoreactive perikarya and processes were found within the olfactory, vomeronasal and trigeminal nerves and in the nasal epithelium. Central TN projections consisted of fibers terminating in the olfactory bulb and bundles that projected to another group of LHRH-ir perikarya in the preoptic region. Up to 4 weeks following hypophysectomy, the labeling intensity and number of TN-immunoreactive neurons were not altered. Acetylcholinesterase histochemistry in the salamander revealed two distinct groups of neurons associated with the TN: a lightly labeled group of fusiform perikarya was located in the olfactory nerve proper and a more heavily labeled group of larger oval perikarya was found within AChE-positive trigeminal fascicles in the ventral mucosa. This study has demonstrated that the amphibian TN follows olfactory, vomeronasal and trigeminal nerves to reach peripheral targets in the nasal mucosa. The projection of TN fibers to discrete olfactory bulb glomeruli, especially evident in the bullfrog, suggests that the TN functions in odor processing. The TN projection to the preoptic region in both of these amphibians implicates the TN in reproductive processes.     

Effect of a Low-Cost Intervention on Recording Body Mass Index in Patients'' Records

PURPOSE: Evaluate the effectiveness of body mass index (BMI) tables placed in exam rooms as an intervention to encourage providers to calculate and record BMI scores in patients' medical records. DESIGN: In a prospective cohort design, medical record data for 276 adult patients at a federally funded community health center in New England were examined from August 2000 to August 2002 following the intervention. METHODS: Prominent, multicolored, laminated BMI tables were posted in the exam rooms of one of the study site's three primary health care teams. Medical record data collected included documentation of BMI calculation in medical records, documentation of an obesity diagnosis, and inclusion of heights and current weights. Frequency distributions were calculated; chi-square tests were used to identify associations. FINDINGS: In contrast to the comparison teams, patients on the intervention team were more likely to have BMI recorded in the medical record. A statistically significant increase in the diagnosis of obesity was observed throughout the health center after the intervention. CONCLUSIONS: Posting BMI tables in exam rooms contributed to increased BMI documentation in patients' medical records.     

Medication strategies in childhood aggression: a review.

OBJECTIVE: To review studies of psychopharmacological management of aggression in common childhood psychiatric disorders. METHOD: Using OVID software, we searched Medline for studies that were undertaken in the last 30 years. Controlled and uncontrolled data are summarized for each condition. RESULTS: A paucity of evidence-based information currently exists. Even so, specific indications from the existing literature can be suggested for several classes of psychotropics, particularly in conduct disorder (CD), attention-deficit hyperactivity disorder (ADHD), mood disorders, and other conditions. CONCLUSIONS: Clinicians can use findings from reviewed controlled and, where necessary, uncontrolled studies to inform pharmacologic practice. This review offers suggestions for future research directions that will aid clinical practice.