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Importance Accurate prediction of patient mortality after kidney transplant is an unmet need. Objective To develop and validate an integrative prediction model that predicts short- and long-term patient mortality for kidney recipients. Design, Setting, and Participants This international cohort study included patients who underwent transplants between 2004 and 2023 from 14 academic medical centers from Europe and the US. The derivation cohort consisted of 1566 consecutive adult kidney recipients in a deeply phenotyped cohort prospectively recruited in 1 French center between 2004 and 2014. External validation cohorts consisted of 10 951 kidney recipients from 7 centers in France, 3 centers in Europe, and 3 centers in North America who underwent kidney transplants between 2006 and 2023. Data were analyzed from January 2023 to June 2025. Main Outcome and Measures All-cause mortality was assessed, and 121 candidate prognostic factors, comprising demographics and clinical, biological, imaging, and immunological parameters, were collected. Results Among 12 517 kidney transplant recipients, including 1566 in the derivation cohort (mean [SD] age, 50.05 [14.31] years; 942 male [60.15%]) and 10 951 in validation cohorts (mean [SD] age, 53.32 [13.97] years; 6766 male [61.78%]), 2486 patients (19.9%) died after a median (IQR) follow-up of 5.08 (2.97-7.00) years. Fourteen prognostic factors (including clinical, biological, and imaging risk factors) were independently associated with patient death (eg, patient age: hazard ratio per 1-year increase in age, 1.07 [95% CI, 1.06-1.08]; P < .001) and were combined into a risk prediction model (mBox). The model exhibited accurate calibration and discrimination in the derivation cohort, with C statistics of 0.82 (95% CI, 0.77-0.87) and 0.80 (95% CI, 0.78-0.82) at 1 and 10 years, respectively, after the transplant. Abbreviated models were developed and validated to ensure model generalizability. Performance of abbreviated models was confirmed in external validation cohorts from France (C statistic, 0.76 [95% CI, 0.73-0.78]), Europe (C statistic, 0.74 [95% CI, 0.72-0.76]), the US (C statistic, 0.74 [95% CI, 0.70-0.78]), the Greater Paris University Hospital database (C statistic, 0.79 [95% CI, 0.77-0.81]), and the University of California at San Francisco database (C statistic, 0.70 [95% CI, 0.65-0.74]). The model was also validated in a series of subpopulations (eg, women vs men: C statistic, 0.81 [95% CI, 0.77-0.84] vs 0.79 [95% CI, 0.77-0.82]) and clinical scenarios (eg, before COVID-19 era: C statistic, 0.79 [95% CI, 0.77-0.81]) with good and stable performance. Conclusions and Relevance In this study, an accurate prediction model for mortality among kidney recipients, computable at the time of transplant, was developed and externally validated. Results suggest that this model may help stratify patient risk of death, allowing for improved medical decisions.

BACKGROUND AND OBJECTIVES: Perioperative protocols facilitate earlier discharge without compromising safety in nonfunctioning pituitary adenomas, but no large multicenter studies in the United States have investigated protocols regarding Cushing disease (CD). We sought to characterize perioperative protocols and how their implementation influences clinical outcomes in patients with CD. METHODS: A retrospective analysis was conducted using data from the Registry of Adenomas of the Pituitary and Related Disorders consortium comprising 13 US academic pituitary centers. Institutions were surveyed regarding perioperative procedures for patients undergoing transsphenoidal tumor resection for CD. The impacts of institutional procedures and approaches to implementation on length of stay (LOS) and unplanned 90-day readmission were evaluated. RESULTS: Thirteen institutions contributed survey responses and clinical data for a total of 832 patients meeting inclusion criteria. Ten (76.9%) institutions reported having a postoperative protocol, 9 (69.2%) used a formal document to outline their protocol, and 3 (23.1%) had protocols implemented into hospital policy. Mean LOS was significantly reduced in centers with an established protocol (3.14 vs 3.42 days, P = .032), and more so with a formal document (3.10 vs 3.48 days, P = .001) or hospital policy (2.72 vs 3.36 days, P < .001). Patients treated after protocol implementation experienced shorter LOS ( P < .001). Other factors associated with reduced LOS were presence of a separate CD pathway, intraoperative checklist specific to pituitary surgery, non-narcotic pain regimen, Foley removal order, dedicated outpatient advanced practice provider follow-up, and target discharge date ≤2 days. Intraoperative checklist ( P = .045), non-narcotic pain regimen ( P = .048), nasal packing ( P = .005), and 1-day target discharge date ( P = .032) were important factors against readmission. Compared with microscopic surgery, endoscopic surgery was associated with shorter LOS but increased readmission odds. CONCLUSION: This is the first multicenter study to illustrate that implementation of perioperative protocols is associated with a reduction in LOS and readmission risk in patients with CD.

Abstract Background Metabolic dysfunction–associated steatotic liver disease (MASLD) is increasingly recognized among people with human immunodeficiency virus (PWH), which is likely related to metabolic alterations and fat redistribution. Anthropometric measures such as body mass index (BMI) and waist circumference (WC) are commonly used for assessing metabolic risk. However, their predictive accuracy for MASLD in this population remains uncertain. Method This multicenter cross-sectional study enrolled adults with HIV who underwent transient elastography with controlled attenuation parameter (CAP) measurement. Anthropometric and metabolic indices, including BMI, WC, hip circumference, waist-to-hip ratio (WHR), and visceral adiposity index (VAI), were collected from the study participants. Receiver operating characteristic (ROC) curve analyses were performed to determine the diagnostic performance of these indices for detecting hepatic steatosis, defined as CAP value of ≥248 dB/m. Analyses were stratified by sex assigned at birth. Results Altogether, 256 participants were included. WC demonstrated the numerically highest discrimination for CAP-defined steatosis (area under the ROC curve 0.769), followed by BMI and hip circumference, whereas WHR and VAI showed weaker performance. In sex-stratified analyses, WC remained the numerically highest-performing measure among males, whereas BMI, WC, hip circumference, and VAI showed similar discrimination among females. Conclusions Simple anthropometric measures, particularly WC, show fair ability to discriminate CAP-defined hepatic steatosis in PWH and may facilitate targeted fatty liver screening in routine HIV care.

Background: Stable osteochondritis dissecans (OCD) lesions are primarily treated nonoperatively. Nonoperative treatment includes several recommendations, including the use of an unloader brace. However, little is known about the clinical effectiveness of unloader bracing and its influence on OCD healing, return to sports, and patient-reported outcomes (PROs). The purpose of this investigation was to evaluate the impact of unloader bracing on patients with stable medial femoral condyle (MFC) OCD lesions treated nonoperatively. Purpose: To investigate the influence of valgus unloader bracing on the success of treating stable MFC OCD with nonoperative treatment strategies. Study Design: Cohort study; Level of evidence, 2. Methods: The authors used a prospective cohort of patients receiving nonoperative care for stable MFC knee OCD lesions. The primary variable of interest was the efficacy of bracing. The primary outcomes were transition from nonoperative care to surgical intervention, return-to-play (RTP) clearance, and PROs. Bivariate testing was used to determine if there were differences between groups. Chi-square testing was used to determine if there were differences in rates of transition to surgery by group. The timing of the transition by each group was assessed using a Wilcoxon rank-sum test, given the nonparametric nature of the data. Kaplan-Meier survival analysis was used to calculate time at risk, incidence rate, and survival times for each group. Results: A total of 185 knees (bracing group: 123 [66.5%] knees; no-bracing group: 62 [33.5%] knees) were analyzed. Overall, 142 (76.8%) knees were successfully treated nonoperatively. Transition to surgery occurred in 43 (23.2%) knees. There were no differences in transition to surgery by groups, with no differences seen by group. Of the knees that did not transition to surgical care, 65 (71.4%) in the bracing group and 38 (74.5%) in the no-bracing group received RTP clearance ( P = .693). PRO scores were similar between the 2 groups at the time of RTP clearance. Conclusion: The inclusion of an unloader brace in the nonoperative treatment for stable MFC OCD lesions did not decrease the likelihood of patients undergoing surgical intervention or improve their PRO scores at the time of RTP clearance. Registration: NCT02771496 (ClinicalTrials.gov identifier).

OBJECTIVE This study investigated the relationship between diabetes and the incidence of postoperative dysphagia following cervical spine surgery (CSS). METHODS A prospectively collected multi-institutional quality registry was retrospectively reviewed. Patients who underwent CSS were categorized on the basis of diabetes status, and correlations with preoperative and postoperative Eating Assessment Tool-10 (EAT-10) dysphagia questionnaire scores were assessed. Mixed-effects logistic regressions were performed to examine the impact of preoperative diabetes on postoperative dysphagia. RESULTS Of the 2001 patients who met the inclusion criteria, 400 (20%) had diabetes. Baseline dysphagia rates were not significantly different between groups (18% vs 14%, p = 0.08). Patients with diabetes had a significantly higher incidence of dysphagia at 1 month (66% vs 54%, p = 0.002), 3 months (39% vs 26%, p < 0.001), and 12 months (33% vs 24%, p = 0.004) after surgery compared to patients without diabetes. Including baseline dysphagia as a fixed effect, multivariable analysis indicated that diabetes was a significant predictor of postoperative dysphagia at 1 month (OR 1.46, p = 0.041) and 3 months (OR 1.63, p = 0.001) but not at 12 months (OR 1.21, p = 0.3). In patients with no baseline dysphagia, those with diabetes (329 of 400 [82.3%]) had a significantly higher incidence of new dysphagia than nondiabetics at 1 month (62% vs 50%, p = 0.003), 3 months (34% vs 21%, p < 0.001), and 12 months (27% vs 18%, p = 0.001). The mean change in EAT-10 scores between baseline and 12 months was significantly worse in patients with preoperative diabetes (2.440 ± 5.013 vs 1.688 ± 4.139, p = 0.025). Multivariable analysis indicated that diabetes was a significant predictor of new postoperative dysphagia at 1 month (OR 1.49, p = 0.040) and 3 months (OR 1.81, p < 0.001) but not at 12 months (OR 1.31, p = 0.2). CONCLUSIONS Diabetes is a significant risk factor for experiencing postoperative dysphagia following CSS. Diabetes correlated with higher incidence of dysphagia at all postoperative time points and was a strong independent predictor of postoperative dysphagia at 1 and 3 months.

Abstract Most oncolytic viruses are delivered by intratumoural injection, and local administration can induce regression of both injected and distant tumours in mice and patients. However, the mechanisms by which local viral infection reprograms systemic immunity remain poorly understood. Here we show that intratumoural RP1, an oncolytic HSV-1 encoding GM-CSF and GALV-GP-R ⁻ , drives regression of injected and uninjected murine melanoma tumours and prolongs survival. RP1 elicits coordinated CD4 ⁺ and CD8 ⁺ T cell infiltration accompanied by local cytokine remodelling, reshaping the immune landscape at both tumour sites. Leveraging the Timer of Cell Kinetics and Activity (Tocky) system and Kaede photoconvertible protein technology, we resolve the temporal dynamics of CD8 ⁺ T cell responses following local virotherapy and identify two systemically induced, virus-driven CD8 ⁺ T cell populations distinguished by TCR engagement kinetics: antigen-engaged Timer-positive ‘viral-induced precursors’ (VIPs) and Timer-negative KLRG1 ⁺ ‘viral-induced terminal effectors’ (VITEs). Single-cell transcriptomic and pseudotime analyses reveal divergent differentiation trajectories; VIPs exhibit sustained antigen engagement within the tumour microenvironment (TME), a transcriptional programme associated with self-renewal, and preferential homing to draining lymph nodes. A VIP-associated gene signature correlates with clinical response to RP1 plus PD-1 blockade in the IGNYTE trial of RP1 and nivolumab in PD-1-refractory melanoma and is independently associated with response to immune checkpoint inhibitor (ICI) therapy in melanoma. These findings establish a mechanistic link between local oncolytic virotherapy, systemic CD8 ⁺ T cell reprogramming, and durable regression of distant lesions in patients.

Background: Contemporary rotating-hinge total knee arthroplasties (RH-TKAs) have shown reasonable short-term survivorship in smaller series, but concerns remain regarding risks of aseptic and septic failure. The purpose of this study was to assess outcomes of contemporary RH-TKAs in one of the largest series to date. Methods: We retrospectively identified 575 RH-TKAs (60% used for aseptic etiologies and 40% used during reimplantation in 2-stage treatment of periprosthetic joint infection [PJI]) from 2002 to 2021 at a single institution. The mean age was 67 years, 58% were female, and the mean body mass index was 33 kg/m 2 . Sixty-five percent had Anderson Orthopaedic Research Institute (AORI) type-2B or 3 bone loss. Kaplan-Meier survivorship analyses were performed. The mean follow-up was 6 years (range, 2 to 19 years). Results: Survivorship free from any revision was 76% at 5 years and 64% at 10 years. The most common revision indications were PJI (54%) and aseptic loosening (20%). RH-TKA used in the primary setting showed better survivorship compared with RH-TKA used during reimplantation after PJI (79% versus 60% at 10 years). Survivorship free from revision for aseptic loosening was 96% at 5 years and 90% at 10 years. Survivorship free from revision for PJI was 84% at 5 years and 81% at 10 years. Survivorship free from revision for PJI was even lower for RH-TKAs used during reimplantation, 74% at 5 years and 73% at 10 years. RH-TKA used during reimplantation in the treatment of PJI was associated with an increased risk of any revision (HR = 2, p < 0.001). Radiographic analysis of 425 knees that were not revised and had radiographs available for review showed that 6% of femoral components and 8% of tibial components had evidence of loosening at the time of final follow-up. The mean Knee Society Score improved from 33 to 69 at 2 years (p < 0.001). Conclusions: The 10-year survivorship free from aseptic loosening was 90% in this large series of RH-TKAs. This represents one of the best survivorships free from aseptic loosening published to date. Knees with prior PJI had markedly poorer survivorship than knees treated for aseptic etiologies, with double the risk of revision. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Abstract Background Recently, a posterior pathway for fluid drainage from the retina to the meningeal lymphatics in the optic nerve (ON) sheath was identified in rodents using intravitreal imaging tracers directly injected into the ocular-globe. Fluid and solute clearance along this pathway may be associated with many diseases. However, intravitreal tracers are rarely used in clinical imaging. As intravenous Gadolinium-based-contrast-agent (GBCA) can enter the globe via the blood-ocular-barriers, it may provide an alternative approach to image this pathway. Purpose To establish a clinically feasible intravenous GBCA-based MRI approach for tracking fluid and solute transport along the posterior lymphatic pathway in the ocular glymphatic system. Materials&Methods This prospective study was conducted from March 2021 to September 2022 in healthy participants. Dynamic-susceptibility-contrast-in-the-CSF (cDSC) MRI was performed before, immediately and 4 hours after intravenous-GBCA administration to track GBCA distribution in aqueous humor (AH) and cerebrospinal fluid (CSF) in regions-of-interest (ROIs) in the globe (anterior-cavity, vitreous-body), in the intraorbital and extraorbital ON, and in the intracranial CSF space proximal to the ON (chiasmatic-cistern, interpeduncular-cistern). Kruskal–Wallis tests with post-hoc Dunn’s tests were used for group comparisons. Results Sixteen healthy participants (mean age±SD: 51±21 years, 5 men) were recruited. Intravenous-GBCA enhancement was observed in all ROIs immediately after injection. At 4-hour-post-GBCA, the vitreous body showed a trend of smaller enhancement area (55±11% versus 49±11%, P =.14) and lower GBCA-concentration (0.044±0.014 versus 0.028±0.010 mmol/L, P =.07) compared to immediate-post-GBCA. The intraorbital ON showed more widespread enhancement (39±5% versus 59±6%, P =.01) and significantly higher GBCA-concentration (0.023±0.009 versus 0.059±0.015 mmol/L, P <.001) at 4-hour-post-GBCA. Conclusion Dynamic fluid and solute transportation along the posterior lymphatic pathway in the ocular glymphatic system in healthy participants was measured by tracking intravenous-GBCAs entering the globe via the blood-ocular-barriers using cDSC-MRI. Summary Statement Dynamic fluid and solute transportation along the posterior lymphatic pathway in the ocular glymphatic system in healthy participants was measured by tracking intravenous-Gadolinium-based-contrast-agents entering ocular-globe via blood-ocular-barriers using dynamic-susceptibility-contrast-in-the-CSF (cDSC)-MRI. Key Results In this prospective study of sixteen participants, Gadolinium-based-contrast-agent (GBCA)-induced signal changes were detected in the aqueous-humor and cerebrospinal fluid immediately following intravenous administration using dynamic-susceptibility-contrast-in-the-CSF (cDSC)-MRI. At 4-hour-post-GBCA, the vitreous-body showed a trend of smaller enhancement area (55±11% versus 49±11%, P =.14) and lower GBCA-concentration (0.044±0.014 versus 0.028±0.010 mmol/L, P =.07) compared to immediate-post-GBCA. The intraorbital-optic-nerve showed more widespread enhancement (39±5% versus 59±6%, P =.01) and higher GBCA-concentration (0.023±0.009 versus 0.059±0.015 mmol/L, P <.001) at 4-hour-post-GBCA.