olaparib (myChoice CDx)

Real-world uptake of gBRCA testing as a companion diagnostic for olaparib in patients with high-risk HER2-negative early breast cancer in Japan: a cross-sectional multicenter study (BRCAwareness).

Taji Tomoe T, Uemura Yukari Y, Kimura Yuri Y, Maeda Noriko N et al.

Adjuvant olaparib significantly improves invasive disease-free and overall survival in high-risk human epidermal growth factor receptor 2 (HER2)-negative, early breast cancer patients carrying germline breast cancer susceptibility gene 1/2 (gBRCA) pathogenic variants (PVs). Timely gBRCA testing as a companion diagnostic for adjuvant olaparib is essential. However, its real-world uptake remains unclear. We enrolled patients with invasive HER2-negative early breast cancer who underwent curative surgery during 2023 in Japan. Eligibility was based on the OlympiA trial criteria. Estrogen receptor (ER)-positive patients required ≥ 4 positive nodes after surgery or non-pathological complete response (non-pCR) with clinical and pathologic stage (CPS) and estrogen receptor status and histologic grade (EG) score ≥ 3 following neoadjuvant chemotherapy (NAC). ER-negative patients required invasive tumor > 2 cm or ≥ 1 nodal metastasis after surgery, or non-pCR after NAC. The primary outcome was gBRCA testing rate; secondary outcomes included a proportion of patients with gBRCA PVs and a proportion of patients starting adjuvant olaparib. We also explored factors associated with not undergoing testing. Of 824 patients enrolled from 46 facilities, 691 were analyzed after random sampling and exclusions. The testing rate was 63.2% (95% confidence interval 59.5-66.9). Among 254 untested patients, 168 (66%) were not informed-mainly due to physician oversight in recognizing eligibility (57%) or physician-perceived patient ineligibility (40%). Of 69 informed but untested patients, reasons included psychological distress (46%), testing cost (35%), and familial concerns (12%). Of 42 patients (9.6%) with gBRCA PVs, 32 received olaparib. Multivariable analysis (female only) showed that age ≥ 65 years, postmenopausal status, major comorbidities, upfront surgery, absence of family history of hereditary breast and ovarian cancer-related cancers, and absence of bilateral or multiple primary breast cancers were associated with lower testing rates. Greater physician awareness of companion diagnostic is needed to ensure timely gBRCA testing and equitable access to adjuvant olaparib.

Diagnosis of acetaminophen and codeine poisoning in a dog using earwax analysis by headspace gas chromatography-mass spectrometry (HS/GC-MS).

de Vicente Monica Chacon MC, Barros Alexandre Có Mangoni ACM, de Souza Gabriela Scarpin GS, di Pauli Taborda Prado Lais L et al.

Poisoning of companion animals resulting from exposure to analgesics intended for human use is a frequent and clinically relevant problem in veterinary practice, usually associated with administration without professional supervision. This can induce severe systemic toxicity. Diagnostic confirmation can be particularly challenging in cases presenting with nonspecific clinical signs or when conventional biological samples are unavailable. This case report describes the innovative use of earwax as a non-invasive biological matrix for toxicological confirmation in veterinary medicine. A 9-year-old male mixed-breed dog was admitted following a traumatic accident and subsequent administration by its owner of a human medication containing acetaminophen and codeine. Clinical evaluation revealed lethargy, hypersalivation, hyporexia, dehydration, and neurological abnormalities. Laboratory findings demonstrated neutrophilic leukocytosis and marked increases in hepatic enzyme activities, consistent with acute hepatocellular injury. Toxicological investigation using headspace gas chromatography-mass spectrometry detected acetaminophen-related signatures in an earwax sample, supporting suspected exposure to the drug. Intensive treatment was promptly initiated and included fluid therapy, antidotal treatment with N-acetylcysteine, opioid antagonism, analgesia, and supportive care. The patient showed progressive clinical improvement, with complete resolution of clinical signs and full recovery. This case highlights the significant risks of administering human medications to companion animals and underscores the need to improve owner awareness of self-medication practices. Furthermore, it demonstrates the diagnostic potential of earwax as a non-invasive biological matrix for toxicological confirmation, expanding the range of complementary diagnostic tools available for veterinary toxicology and supporting improved clinical decision-making in cases of suspected pharmaceutical intoxication.

Corrigendum to "Phylogenetic and phylodynamic analysis of respiratory syncytial virus strains circulating in children less than five years of age in Karachi-Pakistan" [Infection, Genetics and Evolution, 2024, volume 126, article 105694].

Aziz Fatima F, Farooqui Nida N, Abbas Tanveer T, Javaid Mahnoor M et al.

Obesity in CKD: Core Curriculum 2026.

Kramer Holly J HJ, Lavenburg Linda-Marie LM, Navaneethan Sankar D SD

Obesity is a chronic disease the requires lifelong care. The prevalence of obesity has surpassed diabetes and hypertension and is now the most common risk factor for chronic kidney disease (CKD) and its progression. Excess weight not only increases CKD risk but also heightens the risk for heart failure, sleep apnea, steatotic liver disease, osteoarthritis, and a myriad of other chronic conditions. The interplay between obesity, kidney, cardiovascular, and metabolic health has been termed the cardiovascular-kidney-metabolic syndrome. However, obesity is not just a driver of cardiovascular events because it also increases the risk of multiple types of cancers, osteoarthritis, and inhibited physical functioning. Among patients with kidney failure, obesity poses challenges to dialysis treatments, precludes access to transplantation, and contributes to frailty. Helping patients safely achieve and maintain weight loss could have cascading positive effects on kidney health and overall well-being. Medical and surgical therapies now provide clinicians with opportunities to treat obesity, but such treatments need to be coupled with team-based approaches. In this Core Curriculum, we provide a review of the diagnosis of obesity and its surrounding controversies, and we outline steps for obesity management in the setting of CKD.