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Background: Differentiated thyroid cancer (DTC) generally carries an excellent prognosis, yet recurrence occurs in up to 8–9% of patients. Artificial intelligence (AI) models are increasingly proposed to predict DTC recurrence; however, their methodological quality and clinical readiness are poorly defined. We conducted a systematic review to evaluate the methodological quality, risk of bias, and applicability of these models using the PROBAST + AI framework. Methods: We searched Ovid MEDLINE, Embase, Cochrane databases, Scopus, and Web of Science from inception to July 13, 2026. Eligible studies included original research developing or validating AI models for recurrence in DTC. Model quality (for development), risk of bias (for evaluation), and applicability were assessed using the PROBAST + AI framework, with a focus on discrimination, calibration, and validation strategies (PROSPERO; registration number [CRD420251004644]). Results: Of 673 records screened, 34 studies were included (21 unique datasets and 13 UCI-derived publications), encompassing 21,267 patients with a recurrence rate of 7.8%. Most were developed in Asian cohorts (17 of 21 datasets) and were structured clinical/tabular variables (82.4%), including demographic, clinical, laboratory, and pathological data, whereas the remaining models incorporated multimodal inputs such as imaging-derived or radiomic features. Notably, nearly one quarter of included studies (13 of 34, 38%) represented reanalysis of a single dataset. Discrimination was reported in 22 of 34 studies (64.7%) (area under the receiver operating characteristic curve [AUC] 0.67–1.00), though only 10 studies assessed calibration, none with standardized metrics. The PROBAST + AI assessment revealed high overall quality concerns in 26 of 34 (76.5%) development studies due to reliance on single-center cohorts, inadequate handling of missing data, and absence of external validation. Only 6 of 34 included studies (17.6%) were judged to have low overall quality concern, whereas 17 of 34 (50.0%) were rated as having low applicability concern. Conclusions: AI models for predicting DTC recurrence show promising discriminatory performance but have substantial methodological shortcomings in development, and a lack of calibration and external validation necessary for clinical use. Given the guidelines’ emphasis on risk-adapted de-escalation of therapy, the development of robust, validated, and clinically calibrated AI tools is a priority. Current evidence remains insufficient to support routine clinical use.

Aims Knee osteoarthritis (OA) is a common cause of pain and disability in adults. Intra-articular injections are important components in the management of knee OA symptoms, but there are concerns that these injections may be associated with the progression of OA. Therefore, this study determined how the likelihood of progression to arthroplasty is influenced by intra-articular injection of corticosteroid (CS) and/or hyaluronic acid (HA) in patients with knee OA. Methods This population-based cohort study included patients aged 40 to 60 years receiving an initial intra-articular injection of CS and/or HA from 1 January 2000 through 31 December 2010, who resided in Olmsted County, Minnesota, USA. The primary outcome was the likelihood of joint arthroplasty by number of intra-articular injections received evaluated by Cox proportional hazards regression. Results A total of 1,897 patients (n = 2,336 knees) who received 8,600 injections (n = 5,786 CS; n = 2,814 HA) were included (mean age 51.9 years (SD 5.5); 1,515 females (64.9%); mean BMI 34.8 kg/m 2 (SD 8.0)), and 917 (39.3%) subsequently underwent arthroplasty. Accounting for age, BMI, and Kellgren-Lawrence (KL) grade at initial injection, the number of intra-articular injections was associated with an increased likelihood of arthroplasty (hazard ratio (HR) 1.12 (95% CI 1.08 to 1.17)). For patients with early OA (KL grade 0 to 1), CS injections (HR 1.27 (95% CI 1.17 to 1.37)) were associated with an increased likelihood of arthroplasty versus HA (HR 1.12 (95% CI 1.06 to 1.19)). Conclusion Each intra-articular injection was associated with a 12% increased likelihood of arthroplasty. With subgroup analysis, CS injections in early OA were associated with a 27% increased likelihood of arthroplasty. Cite this article: Bone Jt Open 2026;7(11):1462–1470.

Abstract Tumors of neuroendocrine origin are a heterogenous group of related neoplasms which can arise from anywhere in the body. Neuroendocrine neoplasms (NENs) are categorized by site of origin, differentiation status and grade (Ki‐67 expression and/or mitotic rate), with significant prognostic variability accordingly. Historically, the prevalence of bone metastasis is reported to be 6%–12% based on “first generation” (i.e., 111 Indium pentetreotide [Octreoscan®]) somatostatin receptor imaging (SSRI). We conducted a retrospective cohort study including patients with well‐differentiated NENs to determine the clinical and imaging characteristics of osseous metastases when evaluated with higher‐sensitivity 68 Gallium‐DOTATATE positron emission tomography (PET) scans, as well as determining fracture prevalence in selected sub‐cohorts. We also developed a risk score analysis to assess risk of fracture in this cohort. Four hundred twenty‐four patients were identified for inclusion. The median age was 61 years. Most patients were asymptomatic (64%), had sclerotic lesions (77%), Krenning 4 (71%), and had >3 sites (69%) of osseous disease. A high proportion of patients had osseous metastases at sites with high risk for fracture, including vertebra (82%), pelvis (63%), and peri‐trochanteric femur (34%). Fifty‐seven patients (13%) in the entire cohort suffered a fracture. Fracture prevalence was significantly lower in small bowel neuroendocrine tumors (NETs, 7%) and Grades 1 and 2 disease (8% and 9%, respectively), with higher prevalence in pancreatic NETs, paragangliomas/pheochromocytomas, lung carcinoid, and Grade 3 disease (≥20% for each; p ‐values <.05). Our study showed that the rate of osseous metastatic disease approximates 20% in well‐differentiated NENs. Most bone metastases are asymptomatic and the risk of fracture is variable based on the primary site of disease and tumor grade. Our novel risk score analysis for fracture was designed to assist clinician decision making as to management of bone metastasis in this patient population.

Background: The limb symmetry index (LSI) is a measure comparing strength and functional movement between the surgical and nonsurgical limbs, used after anterior cruciate ligament reconstruction (ACLR) to guide rehabilitation and assess return-to-sport readiness. With increasing use of the quadriceps tendon autograft (QT-ACLR), limited data exist on whether the LSI score correlates with patient-reported outcome measures (PROMs). Hypothesis/Purpose: To evaluate the predictive value of postoperative strength and functional LSI tests at 3, 6, and 9 months for short-term PROMs, determine Patient Acceptable Symptom State (PASS) thresholds, and assess differences based on PASS achievement. It was hypothesized that quadriceps strength LSI score would more strongly predict 2-year PROMs than hamstring strength LSI score, and that higher 9-month isokinetic quadriceps LSI scores would be associated with higher International Knee Documentation Committee (IKDC) and Lysholm scores. Study Design: Case series; Level of evidence, 4. Methods: Patients undergoing primary QT-ACLR from 2021 to 2024 with LSI testing during rehabilitation (isometric and isokinetic lower extremity strength, Y-Balance, hop testing) and no revision or additional knee surgery were included. The LSI score was assessed at 3, 6, and 9 months, and PROMs, including Lysholm and IKDC scores, were collected at a mean follow-up of 2.0 ± 0.7 years. Multivariable linear regression was used to evaluate associations between LSI measures and PROMs after adjusting for age, sex, and body mass index (BMI). Receiver operating characteristic analysis was used to determine PASS thresholds. Results: A total of 100 knees in 100 patients (mean age, 25.3 ± 11.2 years; BMI, 25.9 ± 6.5 kg/m 2 ; 52% male) were included. Quadriceps and hamstring strength and functional performance progressively improved from 3 to 9 months, with the LSI score reaching 77% to 81% for quadriceps strength and 98% to 100% for hamstring strength by 9 months postoperatively. At a mean follow-up of 2.0 ± 0.7 years, the mean satisfaction score was 8.4 of 10, the Lysholm score was 90.7, and the IKDC score was 77.8. Linear regression, adjusted for age, sex, and BMI, demonstrated that 3-month isometric quadriceps LSI score had a strong effect on IKDC score, explaining substantial variance (β = 3.9; adjusted R 2 [Adj R 2 ] = 0.36; P < .03); 6-month isokinetic quadriceps and hamstrings showed moderate but significant effects (β = 2.9-3.7; Adj R 2 = 0.13-0.17; P < .05) on IKDC score; and 9-month fast quadriceps had a strong effect explaining substantial variance in Lysholm and IKDC scores (β = 3.9-4.7; Adj R 2 = 0.34-0.35; P ≤ .003). Lysholm and IKDC scores correlated with satisfaction and accurately discriminated PASS thresholds (area under the curve, 0.927-0.937; P < .001). Patients achieving the IKDC PASS demonstrated higher LSI scores across time points and all PROMs. Conclusion: After QT-ACLR, strength-associated LSIs were independently associated with PROMs at a mean 2-year follow-up, after adjusting for age, sex, and BMI. Early isometric quadriceps strength at 3 months predicted higher 2-year IKDC scores, with PASS achievers generally attaining a 60% to 70% LSI score by 3 months. Isokinetic quadriceps strength at 9 months predicted both IKDC and Lysholm scores. These findings highlight the importance of early quadriceps strength recovery and the value of LSI measures in predicting PROMs and informing early rehabilitation.

Abstract Introduction Quantitative interpretation of pediatric brain [ 18 F]-FDG PET is limited by the lack of age-matched normative reference databases, despite substantial developmental variation in cerebral glucose metabolism. This study aimed to construct a large-scale normative pediatric [ 18 F]-FDG PET database and develop an age-specific z-score mapping framework for quantitative evaluation of pediatric epilepsy. Method Pediatric brain PET data were retrospectively derived from clinically acquired whole-body or dedicated [ 18 F]-FDG PET examinations in participants 0–19 years of age without neurologic disease or visible brain abnormalities. A total of 417 PET scans from 341 participants were stratified into five developmental age groups: infancy, early childhood, middle childhood/school age, adolescence, and late adolescence. SUVR maps were generated using whole-brain atlas and brainstem reference regions. Voxel-wise t-test analyses were performed to characterize age- and sex-related metabolic differences. Age-specific voxel-wise mean and standard deviation maps were generated from the normative cohort and used to calculate age-matched hypometabolic z-score maps in 14 pediatric patients with epilepsy. The resulting abnormalities were qualitatively evaluated for concordance with epileptogenic findings identified on clinical MRI and/or PET by expert image review. Results Voxel-wise analyses demonstrated prominent age-dependent SUVR differences, particularly between infancy and older age groups. With whole-brain atlas normalization, older children showed progressively higher relative SUVR in cortical and cerebellar gray matter regions, whereas infancy showed relatively higher SUVR in the occipital cortex, white matter, thalamus, and brainstem. Brainstem normalization produced distinct developmental patterns, emphasizing higher white matter SUVR in infancy and broader gray matter differences in older groups. Sex-related differences were limited and regionally specific. Whole-brain atlas normalization showed lower variability than brainstem normalization and was selected for z-score mapping. In representative epilepsy cases, age-matched z-score maps identified focal or regional hypometabolism corresponding to malformations of cortical development, focal cortical dysplasia, mesial temporal sclerosis, nonlesional MRI cases, remote insult, tumor-related abnormalities, and Sturge-Weber syndrome. Discussion A large-scale normative pediatric [18F]-FDG PET database can support developmentally appropriate quantitative interpretation of pediatric brain PET. Age-matched z-score mapping may complement visual assessment by highlighting abnormal cerebral glucose metabolism in pediatric epilepsy, although findings should be interpreted with MRI, EEG, seizure semiology, and other presurgical data.

Purpose Radioligand therapy (RLT) with [ 177 Lu] Lu-PSMA-617 has shown significant benefits in metastatic castration-resistant prostate cancer (mCRPC), including prolonged overall survival (OS) and progression-free survival (PFS), as well as improved quality of life. For patients previously treated with [ 177 Lu]Lu-PSMA-617 who subsequently experience disease progression, retreatment with [ 177 Lu] Lu-PSMA-617 has emerged as a potential approach, yet data on the outcomes of RLT retreatment remains limited. This study aimed to assess the efficacy and safety of retreatment RLT in mCRPC. Methods Clinical and imaging data of patients who underwent at least two cycles of [ 177 Lu] Lu-PSMA-617, followed by a second course of treatment with [ 177 Lu] Lu-PSMA-617 between March 2018 and December 2024, were retrospectively reviewed. Endpoints included biochemical response, imaging response, toxicity, PSA-PFS, rPFS, and OS. Radiologic and biochemical responses were evaluated using RECIST 1.1 criteria and PSA levels, respectively. Results A total of 589 patients underwent [ 177 Lu] Lu-PSMA-617 RLT, of whom 20 (3.4%, 20/589) received RLT retreatment. The median age was 71.3 years (range: 63.7–95.2), and the median follow-up was 73.3 months (95% CI, 35.7–77.2 months) after the initial treatment and 21.7 months (95% CI, 16.9–26.0 months) after retreatment. The initial treatment involved a median of 4.5 cycles (range: 2–6). Following the first course of RLT, 15 patients (75%, 15/20) had exhibited a &gt;50% decline in PSA levels, including 9 who achieved a &gt;90% decrease. Additionally, 12 patients (60%, 12/20) had demonstrated a complete or partial imaging response, while 3 (15%, 3/20) patients had stable disease, and 5 (25%, 5/20) patients had progressive radiologic disease. Patients received a median of 4 retreatment cycles (range, 1–6), and the median interval between initial RLT and retreatment RLT was 33.1 months (IQR, 16.2–48.9 months; range, 10.7–58.8 months). A PSA decline of ≥50% was observed in 9 out of 20 patients (45%, 9/20). An imaging response was observed in 10 patients (50%, 10/20), with 4 achieving a complete response and 6 achieving a partial response, whereas 10 patients (50%, 10/20) showed progression. The median PSA-PFS was 9.8 months (95% CI, 4.1–17.9 months), and the median rPFS was 8.2 months (95% CI, 3.3–17.9 months). Eight deaths occurred during follow-up. The estimated Kaplan Meier OS rates were 83.6% at 12 months (95% CI, 57.3%–94.4%) and 53.7% at 24 months (95% CI, 28.3%–73.7%). Grade 2 renal toxicity was observed in one patient (5%, 1/20). Three patients (15%, 3/20) developed Grade 2 anemia. Notably, no grade 3 or grade 4 adverse events were observed during either treatment period. Conclusion In our cohort, retreatment with [¹ 77 Lu]Lu-PSMA-617 RLT was associated with biochemical and imaging responses in some patients, with observed survival outcomes that support further investigation. However, given the retrospective single-arm design and small sample size, large prospective studies are needed to more rigorously evaluate the safety, efficacy, and optimal patient selection for retreatment RLT.