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Aims The use of jumbo femoral heads, defined as those with a diameter of ≥ 40 mm, in primary total hip arthroplasty (THA) has gained popularity, to mitigate dislocation. The aim of this study was to determine the risk of dislocation, implant survival, and clinical outcomes of a large cohort of primary THAs with jumbo femoral heads. Methods We conducted a retrospective analysis of 1,828 primary THAs with jumbo femoral heads, which were undertaken for osteoarthritis, in 1,578 patients between January 2000 and December 2022, at a single academic medical centre. The femoral head diameter was 40 mm in 1,584 THAs (87%) and 44 mm in 244 THAs (13%). The outer diameter of the acetabular component ranged from 52 mm to 72 mm in those with 40 mm heads, and from 54 mm to 78 mm in those with 44 mm heads. The types of bearing included ceramic-on-highly cross-linked polyethylene (1,229 THAs; 67%) and metal-on-polyethylene (599 THAs; 33%). Elevated liners were used in 472 THAs (26%) and 1,083 (59%) were lateralized. The most common operative approach was posterior (1,388 THAs; 76%). Outcomes of interest included the rate of dislocation, revision for dislocation, any revision, any reoperation, and the Harris Hip Score (HHS). The mean age of the patients at the time of THA was 64 years (8 to 94); 1,477 (81%) were male, and their mean BMI was 28 kg/m² (5 to 55). The mean follow-up was six years (2 to 14). Results The ten-year survival free of dislocation was 97% (95% CI 96 to 98; 97% for 40 mm heads (95% CI 95 to 98) and 99% for 44 mm heads (95% CI 97 to 100) (hazard ratio 3 (95% CI 1 to 14); p = 0.106)). The ten-year survival free of revision for dislocation was 99.6% (95% CI 99 to 100) (99.5% for 40 mm heads (95% CI 98 to 100) and 100% for 44 mm heads (p = 0.546)). The ten-year survival free of any revision and any reoperation was 95% (95% CI 94 to 97) and 93% (95% CI 91 to 95), respectively. There were no significant differences in survival free of any revision (p = 0.746) or any reoperation (p = 0.762) between the two groups. Conclusion In this large single-centre study of the use of jumbo femoral heads in primary THAs, the ten-year survival free of dislocation was 97%, with extremely few revisions for dislocation. These results highlight the potential for jumbo femoral heads to reduce the risk of dislocation and enhance implant longevity without compromising other clinical outcomes. Cite this article: Bone Joint J 2025;107-B(7):698–706.

Background: Progressive apraxia of speech (PAOS) is a neurodegenerative disorder most commonly arising from a 4-repeat tauopathy that affects the programming or planning of speech, although many patients develop a Parkinson-plus syndrome. The role of neuroinflammation as a disease mechanism is unknown. We investigated the spatial pattern of neuroinflammation in PAOS using PET and evaluated whether it is associated with disease severity, presence of Parkinson-plus features, and tau PET uptake. Patients and Methods: Twenty-five PAOS patients (13 with Parkinson-plus features) and 30 controls underwent inflammatory 11C-ER176 and tau 18F-flortaucipir PET scans as well as detailed clinical assessments. Multiple linear regression analyses compared the inflammatory standardized uptake value ratio (SUVR) between PAOS and controls and assessed the relationship with clinical test scores. Pearson correlation analysis examined the relationship between inflammatory and tau SUVRs. Results: PAOS had greater neuroinflammatory SUVR than controls in the precentral, supplementary motor area, frontal gyri, putamen, pallidum, subthalamic nucleus, and red nucleus (adjusted P < 0.05). Greater neuroinflammation was associated with worse parkinsonism, and patients who had developed Parkinson-plus features showed a broader pattern of neuroinflammation, extending to prefrontal, temporal and parietal cortices. Neuroinflammation correlated with tau uptake in most (96%) PAOS patients (r > 0.3, P < 0.05). The higher correlation was associated with worse parkinsonism (r = 0.61, P < 0.05) and disease severity (r = 0.54, P < 0.05). Conclusions: 11C-ER176 PET analysis demonstrates neuroinflammation in frontal and subcortical regions in PAOS which is particularly severe and widespread with the development of Parkinson-plus clinical features. The colocalization of neuroinflammation and tau may support a relationship between these disease mechanisms.

Triple-negative breast cancer (TNBC) represents the most malignant subtype of breast cancer. The clinical application of PARP inhibitors (PARPi) is limited by the low frequency of BRCA1/2 mutations in TNBC. Here, we identified that MTAP deletion sensitized genotoxic agents in our clinical cohort of metastatic TNBC. Further study demonstrated that MTAP deficiency or inhibition rendered TNBC susceptibility to chemotherapeutic agents, particularly PARPi. Mechanistically, targeting MTAP that synergized with PARPi by disrupting the METTL16-MAT2A axis involved in methionine metabolism and depleting in vivo s-adenosylmethionine (SAM) levels. Exhausted SAM in turn impaired PARPi-induced DNA damage repair through attenuation of MRE11 recruitment and end resection by diminishing MRE11 methylation. Notably, brain metastatic TNBC markedly benefited from a lower dose of PARPi and MTAP deficiency/inhibition synergy due to the inherently limited methionine environment in the brain. Collectively, our findings revealed a feed-forward loop between methionine metabolism and DNA repair through SAM, highlighting a therapeutic strategy of PARPi combined with MTAP deficiency/inhibition for TNBC.

Metabolic dysfunction–associated steatotic liver disease (MASLD) is the most common pediatric liver disease, affecting approximately 10% of children. Its prevalence is rising at an alarming rate, with cases increasingly identified even in early childhood. While MASLD shares key features across the lifespan, its earlier onset reflects developmental vulnerabilities and unique mechanistic drivers. Perinatal influences, including maternal obesity, gestational diabetes, and early-life nutritional exposures, play a central role by disrupting metabolic programming, driving mitochondrial dysfunction, and inducing epigenetic modifications. These early stressors interact with genetic predispositions, such as PNPLA3 and TM6SF2 variants, to amplify susceptibility and shape disease severity. Pediatric MASLD also exhibits distinct histological features, particularly predominant periportal (zone 1) steatosis, inflammation, and fibrosis, which contrast with the centrilobular or pericentral (zone 3) patterns often seen in adults. These findings provide insight into spatial heterogeneity, developmental pathophysiology, and unique disease progression trajectories in children. Addressing MASLD in children requires pediatric-specific approaches to diagnosis, risk stratification, and intervention. By integrating epidemiological trends, mechanistic insights, and translational advances, this Review highlights opportunities for targeted therapies and prevention strategies aimed at mitigating early-life drivers of MASLD, reducing disease burden, and improving long-term outcomes.

Lay Summary Oral vancomycin shows promise in treating pouchitis in patients with primary sclerosing cholangitis and ulcerative colitis. In this study, vancomycin helped reduce stool frequency, urgency, and incontinence. More research is needed to confirm its long-term benefits and best treatment practices.