Citations

Abstract Background Isocitrate dehydrogenase (IDH)-mutant gliomas are infiltrative tumors with limited treatment options at recurrence. Early studies suggest IDH inhibition has therapeutic activity. We evaluated clinical outcomes associated with IDH-1 inhibitor ivosidenib in recurrent IDH-1-mutant gliomas and molecular predictors of response. Methods We retrospectively analyzed adults treated with ivosidenib from January 2021 to August 2025 with predominantly recurrent, pretreated CNS WHO grade 2-4 astrocytoma IDH-mutant or grade 2-3 oligodendroglioma, IDH-mutant and 1p/19q codeleted. Prior anticancer treatments, toxicities, enhancement status at ivosidenib initiation, and genomic alterations were collected. The primary endpoint was progression-free survival (PFS); secondary analyses evaluated associations between PFS, genomic complexity, and CDKN2A/B homozygous deletion. Results Ninety-two adults, median age 43, were included: 61 astrocytomas and 31 oligodendrogliomas, mostly grade 2. Before ivosidenib, 69 had surgery, 64 chemotherapy, and 64 radiation. Median time from diagnosis to ivosidenib was 4.8 years, with median of two prior progressions. Median treatment duration was 5.8 months. Median PFS was 15.2, 4.6, and 2.1 months for astrocytoma grades 2-4, 14.0 and 6.9 months for oligodendroglioma grades 2-3. Increasing genomic complexity was associated with shorter PFS in univariate analysis. Patients without CDKN2A/B homozygous deletion had median PFS of 19.2 months. Two patients with homozygous deletion had median PFS of 0.6 months. Conclusions In this retrospective analysis of predominantly recurrent IDH-1-mutant glioma, ivosidenib was associated with longer PFS in lower-grade, non-enhancing tumors that received little or no prior anticancer treatment and less complex genomic profiles. These findings support a context-dependent benefit of IDH inhibition in recurrent disease.

Abstract Background Hyponatremia has long been recognized as a common electrolyte abnormality among skilled nursing facility (SNF) residents. In the literature, hyponatremia is associated with increases in falls, cognitive impairment, hospitalization, and increased mortality. Although many medical conditions and medications contribute to hyponatremia risk, the role of enteral feeding tubes in this population has not been well defined in clinical practice. This study examined the association between enteral feeding tube use and incident hyponatremia and evaluated selected chronic conditions and medication exposures in SNF patients. Methods We conducted a retrospective cohort study using secondary data from a suburban skilled nursing facility. Adults aged ≥ 18 years residing in the SNF with available laboratory data were included (n = 1,256). Exposures included presence of an enteral feeding tube at admission, selected chronic conditions, and high-risk medication exposures. The primary outcome was incident hyponatremia, defined as any corrected serum sodium value < 135 mEq/L occurring after admission. Relative risks were estimated using modified Poisson regression. Results Incident hyponatremia occurred in 34.6% of residents. In adjusted models, enteral feeding tubes (aRR 2.42; 95% CI 1.84–3.19), chronic kidney disease (aRR 1.87; 95% CI 1.43–2.44), and Liver Disease (aRR 1.58; 95% CI 1.20–2.07) remained the significant independent predictors. Congestive Heart Failure, ethnicity, sex, age, and high-risk medication exposure were not significantly associated with risk at the predetermined alpha = 0.01, and no significant interactions were observed between CKD, CHF, and liver disease and enteral feeding tubes on incident hyponatremia. Conclusions Hyponatremia remains a common electrolyte abnormality among SNF residents. Enteral feeding tube use was strongly associated with increased cumulative risk of incident hyponatremia. Both CKD and liver disease also pose risk of incident hyponatremia. SNF residents with enteral feeding tubes may benefit from targeted monitoring and risk stratification in long-term care settings. Clinicians should be aware of these risks while ordering water flushing of enteral tubes and assess these patients regularly for hyponatremia.

The 6th edition of the WHO Classification of Breast Tumours introduces both major and minor changes based on recent advances in our understanding of breast biology, developments in diagnostic modalities, identification of specific molecular targets and new treatment regimens necessitating modifications to pathology reporting and tumour biomarker categorisation. This review summarises the main changes that strive towards a classification of global relevance. In invasive carcinoma, predictive factors increasingly inform modern breast cancer treatment. The 6th edition provides an update on HER2 reporting categories following the DESTINY‐Breast 04 and 06 trials. Terminologies used to classify invasive tumours are clarified, with the term ‘variant’ now reserved for molecular/genetic alterations. Invasive lobular carcinoma (ILC) with extracellular mucin is recognised as a new diagnostic entity with prognostic implications. The diagnosis of mucinous carcinoma (MC) is reserved for mucin secreting carcinomas with grade 1 or 2 morphology and a favourable biomarker profile. The diagnosis of malignant phyllodes tumours requires only four of the original five adverse histological criteria. Classification of neuroendocrine tumours (NETs) is revised, recognising that the unified model, promoted in the 5th edition, is difficult to apply to the breast. New approaches to the classification of adenomyoepithelioma are discussed but the 5th edition system is broadly retained. A new section on ‘Small Diagnostic Samples’ outlines the merits of non‐operative biopsy diagnosis, the B coding system and the importance of multidisciplinary review. Changes to diagnostic practice and the emerging role of artificial intelligence, with advantages and challenges, are discussed in a new section on ‘Digital Pathology’.

Emergence of epidemic viruses in new hosts threatens both human and other animal populations, and often involves virus evolution to overcome barriers that normally prevent efficient infection and spread in that host. After transfer the separated viruses will evolve in parallel as they spread within the original and new hosts. Here we examine the details of a virus involved in such a host-jumping event, where we define the natural evolution of feline panleukopenia virus (FPV) over 60 y, clarify the origins of the new pandemic canine parvovirus (CPV) that arose in the 1970s, and compare the separate evolution of those viruses over 47 y in cats or dogs. Several live-attenuated FPV vaccine viruses originated from early-1960s isolates or were a recombinant of an early virus, and many sequences in databases proved to be vaccine-derived. The sequences of wild viruses showed that FPV-like strains evolved at less than one-third the rate observed for CPV in dogs, and the higher rate of CPV evolution has been consistent since 1979, when a genetic variant became widespread. The common ancestor of the CPV lineage was related to FPVs from Europe and contained several unique host-adaptive capsid changes associated with canine transferrin receptor type-1 binding. Although the FPV vaccine strains are around 60 y old, little selection for antigenic variation was observed. The distinct evolutionary patterns of these closely related viruses circulating for decades in different hosts emphasize the complex evolution associated with viral epidemic emergence and spread in endemic and new hosts.

Abstract Photon-counting detector CT (PCD-CT) directly detects individual photons and measures their energies, enabling the acquisition of multi-energy data from a single x-ray source with higher spatial resolution, thereby allowing visualization of smaller arteries and veins and other important imaging features not seen at conventional CT. It also substantially reduces calcium and stent blooming artifacts. Appropriate patient selection and task-based optimization of acquisition, reconstruction, and interpretation are critical to realize these benefits. Vascular imaging examinations for which early evidence shows that PCD-CT demonstrates higher diagnostic performance compared to conventional CT include coronary CT angiography (CTA) for evaluation of partially calcified plaques or stents, peripheral runoff CTA, detection of cerebrospinal fluid-venous fistulas, and head CTA for evaluation of small intracranial vessels and aneurysms. Current limitations include excessive image noise with the sharpest reconstruction kernels and challenges when adapting conventional CT protocols (eg, requiring sharper kernels, thinner slices, higher matrices, tailored scan modes) to achieve time-efficient image reconstruction and hanging protocols. New solutions and directions will include deep-learning-based image noise reduction, improved spectral separation, strategic triage of specific patient populations to PCD-CT systems, and subspecialty clinical practice recommendations for this new technology.

Background and importance Emergency tracheal intubation in critically ill adults is associated with a high risk of peri-intubation adverse events, making first-attempt success a key safety target. Objective This study aimed to evaluate whether the use of neuromuscular blocking agents (NMBAs) improves the proportion of first-attempt success and reduces adverse events during emergent intubations outside the operating room. Methods This was a systematic review and meta-analysis of randomized clinical trials or nonrandomized studies comparing sedative-hypnotic plus NMBA versus sedative-hypnotic alone in critically ill adults undergoing emergency endotracheal intubation in nonoperative settings. Animal, cadaveric, manikin/simulation, and pediatric studies were excluded. Articles were screened on 21 August 2025, in Ovid MEDLINE, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, and the Web of Science Core Collection. Main results Of 4736 screened citations, 13 studies (8 cohort; 5 before-after studies) were included in the quantitative analysis, with 14 072 participants. NMBA use was associated with higher first-attempt success, which ranged from 69 to 92% (pooled odds ratio, 2.72; 95% onfidence interval: 1.42–5.21; low-certainty evidence). Secondary outcomes related to adverse events were rated as very low certainty due to sparse data, inconsistent reporting, and serious imprecision. Conclusion NMBA use during emergency intubation was associated with improved first-attempt success, although the certainty of evidence was low.