Assessment of Need for Improved Identification of a Culprit Drug in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.

Importance: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe hypersensitivity reaction. Identifying a culprit drug is critical for patient care, yet identification is based on clinical judgment. Data are limited on the accuracy in or approach to identifying a culprit drug. Objective: To evaluate patient allergy list outcomes, current approaches in identifying culprit drugs, and potential methods of improving culprit drug identification. Design, Setting, and Participants: This retrospective cohort study spanned 18 years (January 2000 to July 2018), was conducted at Brigham and Women's Hospital and Massachusetts General Hospital (Boston), and included patients with clinically and histologically confirmed cases of SJS/TEN overlap and TEN. Main Outcomes and Measures: This study descriptively analyzed potential culprits to SJS/TEN, patients' allergy lists, and currently used approaches that led to those lists. It then tested the theoretical contribution of incorporating various parameters to allergy list outcomes. Results: Of 48 patients (29 women [60.4%]; 4 Asian [8.3%], 6 Black [12.5%], 5 Hispanic [10.4%], and 25 White [52.1%] individuals; median age, 40 years [range, 1-82 years]), the mean (SD) number of drugs taken per patient at disease onset was 6.5 (4.7). Physicians labeled 17 patients as allergic to a single culprit drug. Comparatively, 104 drugs were added to allergy lists across all patients. Physicians' approaches relied largely on heuristic identification of high-notoriety drugs and the timing of drug exposure. Use of a vetted database for drug risk improved sensitivity. Algorithm for Drug Causality for Epidermal Necrolysis scoring was discordant in 28 cases, labeling an additional 9 drugs missed by physicians and clearing 43 drugs labeled as allergens by physicians. Human leukocyte antigen testing could have potentially affected 20 cases. Consideration of infection as a culprit was limited. Conclusions and Relevance: The results of this cohort study suggest that currently used approaches to identify culprit drugs in SJS/TEN are associated with overlabeling patients allergic to likely nonculprit drugs and less commonly missed possible culprit drugs. Incorporation of a systematized unbiased approach could potentially improve culprit drug identification, although ultimately a diagnostic test is necessary.

Breast Cancer Recurrence Risk Assessment: Is Non-Invasive Monitoring an Option?

BACKGROUND: Metastatic breast cancer (MBC) represents a life-threatening disease with a median survival time of 18-24 months that often can only be treated palliatively. The majority of women suffering from MBC are those who had been previously diagnosed with locally advanced disease and subsequently experienced cancer recurrence in the form of metastasis. However, according to guidelines, no systemic follow-up for monitoring purposes is recommended for these women. The purpose of this article is to review current methods of recurrent risk assessment as well as non-invasive monitoring options for women at risk for distant disease relapse and metastasis formation. METHODS: We used PubMed and national guidelines, such as the National Comprehensive Cancer Network (NCCN), to find recently published studies on breast cancer recurrence risk assessment and systemic monitoring of breast cancer patients through non-invasive means. RESULTS: The options for recurrence risk assessment of locally invasive breast cancer has improved due to diverse genetic tests, such as Oncotype DX, MammaPrint, the PAM50 (now known as the "Prosigna Test") assay, EndoPredict (EP), and the Breast Cancer Index (BCI), which evaluate a women's risk of relapse according to certain cancer-gene expression patterns. Different promising non-invasive urinary protein-based biomarkers with metastasis surveillance potential that have been identified are MMP-2, MMP-9, NGAL, and ADAM12. In particular, ααCTX, ßßCTX, and NTX could help to monitor bone metastasis. CONCLUSION: In times of improved recurrence risk assessment of women with breast cancer, non-invasive biomarkers are urgently needed as potential monitoring options for women who have an increased risk of recurrence. Urine as a bioliquid of choice provides several advantages - it is non-invasive, can be obtained easily and frequently, and is economical. Promising biomarkers that could help to follow up women with increased recurrence risk have been identified. In order for them to be implemented in clinical usage and national guideline recommendations, further validation in larger independent cohorts will be needed.