Oral challenge vs routine care to assess low-risk penicillin allergy in critically ill hospital patients (ORACLE): a pilot safety and feasibility randomised controlled trial.

PURPOSE: Critically ill patients are vulnerable to penicillin allergy labels that may be incorrect. The validity of skin testing in intensive care units (ICUs) is uncertain. Many penicillin allergy labels are low risk, and validated tools exist to identify those amenable to direct oral challenge. This pilot randomised controlled trial explored the feasibility, safety, and validity of direct enteral challenge for low-risk penicillin allergy labels in critical illness. METHODS: Consenting patients with a low-risk penicillin allergy label (PAL) (PEN-FAST risk assessment score < 3) in four ICUs (Melbourne, Australia) were randomised 1:1 to penicillin (250 mg amoxicillin or implicated penicillin) direct enteral challenge versus routine care (2-h post-randomisation observation for each arm). Repeat challenge was performed post -ICU in the intervention arm. Patients were reviewed at 24 h and 5 days after each challenge/observation. RESULTS: We screened 533 patients. 130 (24.4%) were eligible and 80/130 (61.5%) enrolled (age median 64.5 years (interquartile range, IQR 53.5, 74), PEN-FAST median 1 (IQR 0,1)), with 40 (50%) randomised to direct enteral challenge. A positive challenge rate of 2.5% was identified. No antibiotic-associated serious adverse events were identified. 32/40 (80%) received a repeat challenge (zero positive). Post-randomisation, 13 (32%) of the intervention arm and 4 (10%) of the control arm received penicillin (odds ratio, OR 4.33 [1.27, 14.78] p = 0.019). CONCLUSION: These findings support the safety, validity, and feasibility of direct enteral challenge for critically ill patients with PEN-FAST assessed low-risk penicillin allergy. The absence of false negative results was confirmed by subsequent negative repeat challenges. A relatively low recruitment to screened ratio suggests that more inclusive eligibility criteria and integration of allergy assessment into routine ICU processes are needed to optimise allergy delabelling in critical illness.

Immunotherapy in the context of immune-specialized environment of brain metastases.

Brain metastases (BrM) develop in 20-40% of patients with advanced cancer. They mainly originate from lung cancer, melanoma, breast cancer, and renal cell carcinoma, and are associated with a poor prognosis. While patients with BrM traditionally lack effective treatment options, immunotherapy is increasingly gaining in importance in this group of patients, with clinical trials in the past decade demonstrating the efficacy and safety of immune checkpoint blockade in BrM originating from specific tumor types, foremost melanoma. The brain is an immune-specialized environment with several unique molecular, cellular, and anatomical features that affect immune responses, including those against tumors. In this review we discuss the potential role that some of these unique characteristics may play in the efficacy of immunotherapy, mainly focusing on the lymphatic drainage in the brain and the role of systemic anti-tumor immunity that develops due to the presence of concurrent extracranial disease in addition to BrM.

Feasibility of in-home electroencephalographic and actigraphy recordings in dogs.

Introduction: Idiopathic epilepsy is a prevalent neurological disease in dogs. Dogs with epilepsy often present with behavioral comorbidities such as aggression, anxiety, and fear. These behaviors are consistent with pre, post, or interictal behaviors, prodromal changes, seizure-precipitating factors, or absence and focal seizures. The overlap in behavior presentations and lack of objective research methods for quantifying and classifying canine behavior makes determining the cause difficult. Behavioral comorbidities in addition to the task of caring for an epileptic animal have a significant negative impact on dog and caregiver quality of life. Methods: This pilot study aimed to assess the feasibility of a novel technology combination for behavior classification and epileptic seizure detection for a minimum 24-h recording in the dog's home environment. It was expected that combining electroencephalography (EEG), actigraphy, and questionnaires would be feasible in the majority of trials. A convenience sample of 10 community-owned dogs was instrumented with wireless video-EEG and actigraphy for up to 48 h of recording at their caregiver's home. Three questionnaires (maximum 137 questions) were completed over the recording period by caregivers to describe their dog's everyday behavior and habits. Results: Six of the 10 included dogs had combined EEG and actigraphy recordings for a minimum of 24 h. Discussion: This shows that in-home EEG and actigraphy recordings are possible in community-owned dogs and provides a basis for a prospective study examining the same technology combination in a larger sample size.