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Michael J Morris

Publications and source records attributed to Michael J Morris.

2 recordsLinked to original sources
PubMed2026

Phase II Randomized Trial of Radium-223 Dichloride and Cabozantinib in Patients With Renal Cell Carcinoma With Bone Metastases: RADICAL (Alliance A031801).

PURPOSE: Bone metastases (BM) occur in approximately 30% of patients with metastatic renal cell carcinoma (mRCC) and are associated with poor survival and symptomatic skeletal events (SSEs). Radium-223, an alpha-emitting bone-seeking radioisotope, and cabozantinib, a tyrosine kinase inhibitor, have demonstrated activity in BM. RADICAL (Alliance A031801; ClinicalTrials.gov identifier: NCT04071223) evaluated cabozantinib ± radium-223 in mRCC with BM. METHODS: This phase II trial enrolled patients with mRCC of any histology with ≥1 BM. Patients were randomly assigned 1:1 to cabozantinib ± radium-223, stratified by osteoclast-targeted therapy (OTT), prior therapy, opioid use, and International mRCC Database Consortium (IMDC) risk. The primary end point was SSE-free survival (SSE-FS). Secondary end points included safety, objective response rate (ORR), progression-free survival, and overall survival (OS). A target of 124 evaluable patients was planned, with a prespecified interim futility analysis at 50% of expected SSE-FS events; the trial would stop if the stratified hazard ratio (sHR) > 1.0. RESULTS: The prespecified interim futility analysis was conducted after 90 patients were enrolled and crossed the futility boundary, leading to closure at 98 patients. The final analysis included all 98 patients. Median age was 63 years, 82.7% had clear cell histology, and 79.6% were using an OTT. IMDC risk was favorable (18.4%), intermediate (67.3%), and poor (14.3%). Median follow-up was 13.1 months. Median SSE-FS for cabozantinib with radium-223 versus cabozantinib was 16.7 versus 17.6 months (sHR, 1.46 [90% CI, 0.86 to 2.51]). Median OS was 28.3 versus 19.7 months (sHR, 1.40 [95% CI, 0.70 to 2.79]). ORR was 19.4% versus 25.0% (P = .78). Grade ≥3 adverse events were similar across arms (69.6% v 75.5%). CONCLUSION: Radium-223 did not improve SSE-FS when added to cabozantinib. The combination demonstrated a manageable safety profile.

Humans↗
PubMed2026

The Puerperium in the Modern Dairy Cow: A Review.

The puerperium represents a critical physiological period during which the bovine reproductive tract transitions from pregnancy to renewed fertility. In the modern high-producing dairy cow, this transition is challenged by profound metabolic, endocrine, immunological, and structural demands that collectively influence uterine health, ovarian function, and subsequent reproductive performance. This review examines current understanding of the physiology of the puerperium in dairy cattle, with particular emphasis on uterine involution, immune clearance of postpartum contamination, endocrine regulation, and resumption of ovarian cyclicity. Further, it contrasts high-yielding Holsteins with fertility selected dairy populations. Normal uterine involution involves coordinated myometrial contraction, tissue remodelling, endometrial regeneration, and tightly regulated inflammatory responses. Failure of these processes predisposes cows to postpartum uterine disorders, including retained fetal membranes, metritis, endometritis (purulent vaginal discharge with cytological confirmation), and pyometra, which remain major contributors to subfertility and economic loss. Central to the pathophysiology of puerperal disease is negative energy balance, which disrupts immune competence, alters hepatic steroid metabolism, impairs ovarian signalling, and compromises oocyte and embryo quality. Emerging evidence highlights the complex interplay between metabolism, immunity, and the uterine microbiome, shifting current perspectives away from pathogen-centric models toward host resilience. Advances in biomarkers, genomic selection, and precision monitoring offer new opportunities for targeted reproductive management. Ultimately, optimisation of transition period management remains the cornerstone of supporting physiological puerperal recovery and sustaining reproductive efficiency in modern dairy systems.

Animals↗