Canada's First Joint Oncology-Allergy Clinic: Successful Desensitization to Trastuzumab Following Severe Anaphylactic Reaction in Which Epinephrine Was Inappropriately Withheld.

BACKGROUND: Recognition of anaphylaxis and differentiation from other infusion reactions in an oncology setting is imperative; epinephrine is the recommended treatment for anaphylaxis and should be administered immediately to patients in whom anaphylaxis is suspected. Trastuzumab has a potentially tremendous oncological benefit, and when hypersensitivity reactions occur, rechallenge with desensitization protocols has become more common. Oncology presents a unique situation in which repeat drug exposure after a serious adverse reaction is often warranted due to the mortality risk of untreated cancer-allergists can assist with both symptom assessment and risk mitigation. CASE PRESENTATION: This case showcases successful desensitization in a 43-year-old female with locally advanced HER2-positive breast cancer following a severe anaphylactic reaction to trastuzumab, in which epinephrine was not administered. We report the establishment of the Medical Oncology and Allergy Clinic: Canada's first multidisciplinary clinic aimed at expediting the assessment and management of oncology patients with adverse drug reactions (including chemotherapy, contrast media, antimicrobials) and those with primary and acquired immunodeficiency. CONCLUSIONS: We propose this multidisciplinary clinic model as a treatment framework moving forward, with the goal of continuing first-line therapies in cancer patients who develop drug-hypersensitivity (i.e., through desensitization). This case highlights the unmet need for a multidisciplinary approach to the management of oncology patients who experience hypersensitivity reactions.

Systematic Review of Enhanced Recovery After Surgery in Patients Undergoing Cranial Surgery.

BACKGROUND: Enhanced Recovery after Surgery (ERAS) pathways are increasingly being integrated in neurosurgical patient management. The full extent of ERAS in cranial surgery is not well studied. We performed a systematic review examining ERAS in cranial surgery patients to 1) identify the extent to which ERAS is integrated in cranial neurosurgical procedures and 2) assess effectiveness of ERAS interventions for patients undergoing these procedures. METHODS: A systematic review of MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, PsychInfo, and Google Scholar was conducted according to PRISMA guidelines (CRD42020197187). Studies eligible for inclusion assessed patients undergoing any cranial surgical procedure using an ERAS or ERAS-like pathway, defined by ≥2 ERAS protocol elements per the ERAS Society's RECOvER Checklist and the recommendations of Hagan et al. 2016 (not including patient education, criteria for discharge, or tracking of postdischarge outcomes). RESULTS: Nine studies were included in qualitative synthesis, 2 of which were randomized controlled trials. All studies showed a moderate risk of bias. The most common ERAS elements used were screening and/or optimization and formal discharge criteria. The least common ERAS elements used were fasting/carbohydrate loading and antithrombotic prophylaxis. Complication rates were similar in studies comparing ERAS with non-ERAS groups. ERAS interventions were associated with reduced length of stay, with comparable and/or improved patient satisfaction. CONCLUSIONS: ERAS is a safe and potentially favorable perioperative pathway for select patients undergoing cranial surgery. Future studies of ERAS in cranial surgery patients should emphasize postoperative optimizations and patient-reported outcome measures as key features.

Increased Efficiency for Biallelic Mutations of the CCR5 Gene by CRISPR-Cas9 Using Multiple Guide RNAs As a Novel Therapeutic Option for Human Immunodeficiency Virus.

CCR5 is a coreceptor of human immunodeficiency virus type 1 (HIV-1). Transplantation of hematopoietic stem cells homozygous for a 32-bp deletion in CCR5 resulted in a loss of detectable HIV-1 in two patients, suggesting that genetic strategies to knockout CCR5 expression would be a promising gene therapy approach for HIV-1-infected patients. In this study, we targeted CCR5 by CRISPR-Cas9 with a single-guide (sgRNA) and observed 35% indel frequency. When we expressed hCas9 and two gRNAs, the Surveyor assay showed that Cas9-mediated cleavage was increased by 10% with two sgRNAs. Genotype analysis on individual clones showed 11 of 13 carried biallelic mutations, where 4 clones had frameshift (FS) mutations. Taken together, these results indicate that the efficiency of biallelic FS mutations and the knockout of the CCR5 necessary to prevent viral replication were significantly increased with two sgRNAs. These studies demonstrate the knockout of CCR5 and the potential for translational development.