Nasu-Hakola disease is a rare autosomal recessive disorder characterized by progressive cognitive decline and bone cyst formation and is commonly associated with triggering receptor expressed on myeloid cells 2 (TREM2) variants. Herein, we report a novel TREM2 frameshift variant in a middle-aged man from a consanguineous Chinese family who presented with early-onset dementia and right ankle pain. Neuroimaging and skeletal examinations revealed cerebral atrophy and bone cystic lesions. Whole-exome sequencing followed by Sanger confirmation identified a homozygous TREM2 c.257del (p.D86Afs*103) variant. The patient was diagnosed with Nasu-Hakola disease, and his cognitive deterioration continued despite treatment with donepezil and memantine. Functional assays in human embryonic kidney 293T cells demonstrated preserved mRNA expression of the mutant construct but markedly reduced protein levels compared with that of wild-type. We also conducted a descriptive literature review of 54 previously reported cases of homozygous or compound heterozygous TREM2 variants to highlight the variability in neurodegenerative and skeletal phenotypes. To the best of our knowledge, this is the first report of a TREM2 c.257del variant in a Chinese family. Our findings expand the mutational spectrum of Nasu-Hakola disease and highlight substantial phenotypic heterogeneity, emphasizing the importance of early genetic testing in patients with unexplained early-onset dementia, even in the absence of bone lesions.

In December 2024, the U.S. Department of Veterans Affairs (VA) and the U.S. Department of Defense (DoD) released a joint update of their 2017 clinical practice guideline (CPG) for the rehabilitation of individuals with lower limb amputation (LLA). This synopsis highlights the key aspects of the guideline development process and describes the CPG recommendations. The VA/DoD Evidence-Based Practice Work Group convened a joint VA/DoD guideline development work group (WG) that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline WG conducted a patient focus group, developed key questions, and systematically searched and evaluated the literature from a eight year time frame (English-language publications from 6 July 2016 to 15 March 2024). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was utilized to evaluate the evidence and formulate recommendations. The WG developed 26 recommendations along with algorithms and supplemental materials to guide providers in providing evidence-based, interdisciplinary, patient-centered care through all phases of LLA rehabilitation. The CPG was reviewed by stakeholders outside the WG prior to approval by the VA/DoD Evidence Based Practice WG. This article summarizes key features of the guideline to help clinicians utilize the CPG to support patient-centered care.

Immune checkpoint inhibitors (ICIs) are widely applied in the treatment of various malignant tumors, leading to notable improvements in patient prognosis. However, with their increased use, various immune-related adverse events (irAEs), including ICI-induced inflammatory arthritis (ICI-IA), may develop, affecting clinical evaluation and treatment decisions. The present report presents 3 cases of ICI-IA and reviews the literature on its clinical features, diagnosis and therapeutic approaches. The first patient, who had been diagnosed with metastatic bladder cancer, developed limb joint pain after undergoing combination therapy involving ICIs and chemotherapy. Laboratory tests showed elevated levels of C-reactive protein and interleukin (IL)-6. Bone scintigraphy excluded bone metastasis, and the symptoms of the patient improved following corticosteroid therapy. The second patient had advanced cervical cancer and a history of rheumatoid arthritis. Following multiple cycles of ICI combined with anti-angiogenic treatment, the patient experienced recurrent joint swelling and pain, accompanied by elevated IL-6 and IL-10 levels. Bone scintigraphy excluded bone metastasis, and the symptoms were controlled with corticosteroid therapy. The third patient had advanced lung cancer and developed persistent pain in the shoulders, knees and ankles during immunotherapy. Corticosteroid therapy effectively controlled the symptoms after bone metastases and autoimmune diseases were excluded. These cases illustrate that ICI-IA is a clinically relevant irAE. Early recognition and management are crucial for improving patient prognosis. A thorough understanding of the pathogenesis of ICI-IA is essential for optimizing treatment strategies and improving quality of life.

» Early postoperative weight bearing initiated within approximately 2 weeks after open reduction and internal fixation of ankle fractures appears safe in selected patients with anatomically reduced fractures and rigid internal fixation and has not been shown to increase complication or hardware failure rates compared with delayed weight bearing in available studies. » These findings, however, should be interpreted cautiously, as most studies do not define fixation adequacy, fracture-specific mechanical characteristics, or actual postoperative loading with sufficient rigor, limiting broad generalizability across fracture patterns and implant constructs. » The most consistent benefit of earlier weight bearing is accelerated short-term recovery, including improved early function, reduced pain, and earlier return to work, while medium- and long-term functional outcomes are generally similar by 6 to 12 months. » Postoperative rehabilitation should be individualized based on fracture morphology, quality of reduction, fixation construct, soft-tissue condition, bone quality, and patient-specific factors such as age, comorbidities, and anticipated compliance, rather than on uniform time-based protocols. » Greater caution is warranted for complex fracture patterns, including trimalleolar fractures, posterior malleolar involvement, syndesmotic fixation, osteoporotic bone, and medically high-risk patients, for whom fracture-specific evidence remains limited. » Future studies should prioritize standardized fracture definitions, objective quantification of postoperative loading, and risk-stratified rehabilitation pathways to better identify which patients derive the greatest benefit from earlier weight-bearing strategies.

Acute posterior tibialis tendon rupture is a rare injury, most often occurring in association with ankle fractures or severe sprains, and isolated traumatic lacerations are exceptionally uncommon. In this study, we present a 53-year-old Iranian female who arrived with persistent medial ankle pain and lameness as her chief complaint following a glass-induced laceration. On physical examination, she exhibited tenderness and swelling along the medial ankle, difficulty performing a single heel-rise, and weakness in foot inversion, while neurovascular status remained intact. MRI evaluation demonstrated complete rupture of both the posterior tibialis and flexor digitorum longus tendons, without any concomitant ankle fractures. Intraoperative findings confirmed the diagnosis, and given the condition of the tendon ends, primary tendon repair was selected as the surgical approach. The ankle was immobilized for six weeks postoperatively, after which physiotherapy was initiated. At the three-month postoperative follow-up, the patient demonstrated significant pain relief, improved inversion strength, and normalization of gait.