An uncommon presentation of chronic myeloid leukemia

Annals of Hematology -     

Preemptive Genotyping of CYP2C8 and CYP2C9 Allelic Variants Involved in NSAIDs Metabolism for Sickle Cell Disease Pain Management

Interindividual variability in analgesic effects of nonsteroidal anti‐inflammatory drugs prescribed for sickle cell disease (SCD) pain is attributed to polymorphisms in the CYP2C8 and CYP2C9 enzymes. We described CYP2C8 and CYP2C9 genotype/phenotype profiles and frequency of emergency department (ED) visits for pain management in an African American SCD patient cohort. DNA from 165 unrelated patients was genotyped for seven CYP2C8 and 15 CYP2C9 alleles using the iPLEX ADME PGx multiplexed panel. CYP2C8*1 (0.806),*2 (0.164), *3 (0.018), and *4 (0.012) alleles were identified. Genotype frequencies were distributed as homozygous wild type (66.7%), heterozygous (27.8%), and homozygous variant/compound heterozygous (5.4%), respectively. CYP2C9*1 (0.824), *2 (0.027), *3 (0.012), *5 (0.009), *6 (0.009), *8 (0.042), *9 (0.061), and *11(0.015) were observed with extensive (68.5%), intermediate (18.1%) and poor predicted metabolizers (0.6%), respectively. Fifty‐two and 55 subjects, respectively had at least one variant CYP2C8 or CYP2C9 allele. Although the distribution of the CYP2C9 (p = 0.0515) phenotypes was marginally significantly in high and low ED users; some CYP2C8 and CYP2C9 allelic combinations observed in 15.2% (25) of the cohort are associated with higher risks for analgesic failure. CYP2C8 and CYP2C9 preemptive genotyping could potentially enable clinicians to identify patients with impaired metabolic phenotypes.     

Evaluation of Central Venous Access with Accelerated Seldinger Technique Versus Modified Seldinger Technique

Background

Central vein catheter (CVC) placement using the modified Seldinger technique is a common procedure in the emergency department, but can be time consuming due to the multiple pieces of equipment included in central line kits and the number of steps in the procedure. Preassembled devices combine a needle, guidewire, dilator, and sheath into one unit and potentially simplify the process and reduce time required for CVC placement using the accelerated Seldinger technique.

Sacituzumab govitecan: breakthrough targeted therapy for triple-negative breast cancer

Introduction: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with an increased risk of recurrence and cancer-related death. Unlike hormone receptor-positive or HER2-positive breast cancers, there are limited targeted therapies available to treat TNBC and cytotoxic chemotherapy remains the mainstay of treatment. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate targeting Trop-2 expressing cells and selectively delivering SN-38, an active metabolite of irinotecan.

Areas covered: This review covers the mechanism of action, safety and efficacy of sacituzumab govitecan in patients with previously treated, metastatic TNBC. Additionally, efficacy data in other epithelial malignancies is included based on a PubMed search for ‘sacituzumab govitecan’ and ‘clinical trial’.

Expert opinion: Sacituzumab govitecan has promising anti-cancer activity in patients with metastatic TNBC previously treated with at least two prior lines of systemic therapy based on a single arm Phase I/II clinical trial. A confirmatory Phase III randomized clinical trial is ongoing. Sacituzumab govitecan has a manageable side effect profile, with the most common adverse events being nausea, neutropenia, and diarrhea. The activity of sacituzumab govitecan likely extends beyond TNBC with promising early efficacy data in many other epithelial cancers, including hormone receptor-positive breast cancer.     

The nature and extent of emotion recognition and empathy impairments in children showing disruptive behaviour referred into a crime prevention programme

Childhood disruptive behaviour has been linked to later antisocial and criminal behaviour. Emotion recognition and empathy impairments, thought to be caused by inattention to the eye region, are hypothesised to contribute to antisocial and criminal behaviour. This is the first study to simultaneously examine emotion recognition and empathy impairments, their relationship, and the mechanism behind these impairments, in children with disruptive behaviour. We hypothesised that children with disruptive behaviour would exhibit negative emotion recognition and cognitive and affective empathy impairments, but that these impairments would not be due to reduced attention to the eye region. We expected these emotion impairments to be driven by disruptive behaviour. We also expected a relationship between emotion recognition and cognitive empathy only. Ninety-two children with disruptive behaviour, who were participating in a police crime prevention programme and rated by their schoolteacher using the Strengths and Difficulties Questionnaire (DB; mean age 8.8 years, 80% male), took part. There was a comparison group of 58 typically developing children (TD; mean age 9.7 years, 78% male). All children completed emotion recognition and empathy tasks, both with concurrent eye tracking to assess social attention. Not only were DB children significantly impaired in negative emotion and neutral emotion recognition, and in cognitive and affective empathy compared to the TD children, but severity of disruptive behaviour also predicted intensity of emotion impairments. There were no differences in social attention to the eye region. Negative emotion recognition and empathy impairments are already present in an identifiable group of children displaying disruptive behaviour. These findings provide evidence to encourage the use of targeted interventions.