Citations

The TransMet trial and Norwegian studies have shown excellent outcomes in highly selected patients undergoing liver transplant (LT) for unresectable colorectal liver metastases (uCRLM). Our aim is to provide an updated analysis of the current state of LT for uCRLM in the United States. Adult patients with a diagnosis of uCRLM listed for LT between December 2017 and March 2025 were identified from the United Network for Organ Sharing database and analyzed. An analysis of living donor LT (LDLT) and deceased donor LT (DDLT) was performed. During this period, 222 patients were listed, and 158 received an LT across 33 centers. Of these, 76 (48.1%) underwent LDLT, and 82 patients (51.9%) underwent DDLT. Of the 82 deceased donors, 56 (68.2%) were out-of-sequence offers. Overall, the 3-year survival and disease-free survival rates were 66.7% and 44.0%, respectively. The 3-year survival for LDLT and DDLT was 74.1% and 57.3% ( p =0.04), respectively. While these results have not yet reached the acceptable threshold established for other LT indications, they have improved and are expected to continue improving after the implementation of prioritization points. Given the potential variability of oncologic selection criteria and graft quality, we call for the standardization of nationally accepted selection criteria for listing patients for LT with uCRLM and for providing early access to high-quality organs. To achieve this, it is imperative to create, update, and maintain national databases that allow for the collection of more granular oncological variables.

Purpose: To present a case of a dislocated posterior lamellar graft into the vitreous cavity in an eye that was postpars plana vitrectomy. Methods: Retrospective case report. Results: A middle-aged man underwent pars plana vitrectomy, pars plana lensectomy, and scleral-sutured intraocular lens fixation after a traumatic eye injury. The patient required subsequent Descemet stripping automated endothelial keratoplasty for corneal edema, and the posterior lamellar graft was lost intraoperatively into the posterior segment. The graft was surgically retrieved 1 week later, followed by a successful placement of a new posterior lamellar graft. Histopathologic examination of the retrieved graft after 1 week in the vitreous cavity revealed viable endothelial cells, a novel finding in a posteriorly dislocated Descemet stripping automated endothelial keratoplasty graft. The newly placed graft remained attached and healed well, with the patient achieving a visual acuity of 20/80 at 3 months postoperatively. Conclusion: Posteriorly dislocated grafts may be suitable for transplantation to the corneal stroma after prompt retrieval from the vitreous cavity. Prompt retrieval and appropriate surgical techniques are critical for optimizing outcomes in such clinical scenarios.

Cartilage defects remain a prevalent and challenging clinical problem, especially in young, active individuals. Existing treatments such as microfracture or autologous chondrocyte implantation either lack durability or require multiple surgeries and extensive cell culture. To address these limitations, we developed RECLAIM—a one-stage, two-cell-type procedure combining allogeneic mesenchymal stromal cells and autologous chondrons. RECLAIM harnesses the trophic and immunomodulatory properties of MSCs to stimulate autologous chondron-driven tissue repair, minimizing invasiveness while optimizing biologic regeneration. This article reviews the preclinical discovery, clinical translation, trial results, and platform potential of RECLAIM, which was recognized with the 2025 Arnold I. Caplan Award for Distinguished Research in OrthoBiologics. Our work builds on Professor Caplan's pioneering conceptualization of MSCs as “medicinal signaling cells” and establishes a model for academic, investigator-driven translation of regenerative science into clinical practice.

PURPOSE Human epidermal growth factor receptor 2 (HER2), a transmembrane receptor with kinase activity involved in cell signaling through the RAS pathway, is expressed in osteosarcoma (OST). Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate with a HER2-targeting monoclonal antibody, trastuzumab, linked to a topoisomerase I inhibitor. We report results of a phase II study of T-DXd in adolescents and young adults with HER2-positive relapsed, unresectable OST (ClinicalTrials.gov identifier: NCT04616560 ). METHODS Patients age 12-39 years with relapsed, unresectable OST were eligible for centrally evaluated HER2 expression screening by immunohistochemistry. Patients with >10% of OST cells with cytoplasmic or membranous HER2 expression of any intensity were eligible to receive T-DXd at 5.4 mg/kg intravenously once every 3 weeks for up to 2 years. The study used a 9 + 15 Simon's optimal two-stage design with a primary end point of event-free survival at 24 weeks. RESULTS Fifty patients were screened for HER2, and 41 met the inclusion criteria of 10% of OST cells having membranous or cytoplasmic HER2 expression. Nine eligible patients, two younger than 18 years, were enrolled and received T-DXd. With a single patient having more than 24 weeks of stable disease (SD) of the nine planned in the first stage, this study did not meet criteria to progress to stage II. The estimated SD rate at 24 weeks is 11.1%. The median (range) number of cycles of therapy was 2 (2-12). Grade 3 and 4 possibly related adverse events occurred in three of nine patients and included nausea, vomiting, tumor hemorrhage, cytopenias (n = 3), wound infection, and hypertension. CONCLUSION T-DXd did not demonstrate sufficient activity to expand enrollment to the planned second stage in patients with OST. No new safety signals were observed.

Abstract Pulmonary fibrosis is increasingly understood to involve dysfunction within and across multiple cellular compartments, with recent attention highlighting the involvement of pulmonary vascular dysfunction in failed repair and progression of fibrosis. Formulation and delivery of lung-targeting lipid nanoparticles (LNPs) may provide a means to selectively target the lung but not systemic vasculature. However, the feasibility and efficacy of such approaches in the fibrotic lung are unknown. We sought to test whether intravenously administered lung-targeting LNPs can safely deliver mRNA to the healthy and fibrotic lung vasculature in young and aged mice and whether delivery of mRNA encoding a matricellular protein could promote fibrosis resolution. We used a selective organ targeting LNP formulation and characterized cell-specificity of delivery after bleomycin-induced lung fibrosis. We then delivered Ccn3 mRNA (encoding cellular communication network factor 3) to aged mice in the setting of established lung fibrosis and evaluated fibrotic regression and vascular repair. The matricellular protein encoded by Ccn3 was previously identified by our group as an important regulator of lung endothelial function. We found that LNP delivery was lung specific and predominantly endothelial targeting in the setting of lung fibrosis. Delivery of Ccn3 mRNA to aged mice via LNPs modestly reduced fibrosis and improved microvascular density in the lungs. Our results support the concept that cell-specific and repair-promoting cargos delivered via lung-targeting LNPs may have utility for treatment of established fibrosis.

ImportanceAlthough incarceration is associated with worse cancer outcomes, little is known about quality of cancer care among people with a history of incarceration.ObjectiveTo describe quality of cancer care among those diagnosed with cancer during or immediately after incarceration.Design, Setting, and ParticipantsThis longitudinal cohort study used Connecticut Tumor Registry data linked to Department of Correction rosters from 2005 through 2016. Patients diagnosed with cancer while incarcerated were matched to those diagnosed within 12 months after incarceration and to those with no history of incarceration. Analysis was performed between March 2024 and January 2025.ExposuresIncarceration status at time of cancer diagnosis.Main Outcomes and MeasuresThe main outcomes were treatment initiation within 60 days and receipt of recommended pretreatment and therapeutic care, ascertained from medical records and tumor registries. Logistic regression was used to evaluate odds of treatment initiation by 60 days. The proportion of recommended elements of pretreatment and therapeutic care received was calculated, and group differences were assessed using χ2 tests.ResultsThe sample included 690 individuals (233 diagnosed during incarceration, 221 diagnosed within 12 months after incarceration, and 236 with no incarceration history). The mean (SD) age was 49.7 (12.1) years, and 611 (88.6%) were male. Compared with those with no history of incarceration, those diagnosed with cancer during incarceration were less likely to initiate treatment within 60 days (169 of 209 [80.9%] vs 131 of 189 [69.3%]; OR, 0.49 [95% CI, 0.31-0.79]). Initiation of treatment within 60 days was not statistically different for those diagnosed after incarceration vs those with no history of incarceration (144 of 187 [77.0%]; OR, 0.81 [95% CI, 0.49-1.34]). Those diagnosed with local and regional cancers during incarceration received 49.2% of recommended treatment-related care (31 of 63 measures), while those diagnosed after incarceration received 45.3% (34 of 75 measures), compared with 66.7% (36 of 54 measures) among those with no history of incarceration (P < .001). People diagnosed with local and regional cancers during incarceration received 80.6% of recommended pretreatment evaluation (54 of 67 measures), and those diagnosed after received 96.8% (59 of 68 measures), compared with 78.1% (50 of 64 measures) among those with no history of incarceration (P = .01).Conclusions and RelevanceIn this cohort study of people with a history of incarceration, incarceration was associated with lower likelihood of receiving timely, high-quality cancer treatment. Along with other published literature, this work suggests that gaps in quality of care may contribute to observed disparities in outcomes.

Abstract Background After high‐level spinal cord injury (SCI), motor recovery of wrist extensors has significant functional consequences as it can facilitate grasp through tenodesis. A small seminal study from 1993 established widely used prognostic rules for wrist extensor recovery, though these have not been replicated with larger, real‐world samples since inception. Objective To determine the prognostic value of initial C5 sharp‐dull discrimination, C5 motor strength, and C6 motor strength on predicting 1‐year ipsilateral wrist extensor motor recovery for patients with SCI with neurological level of C4 or C5. Design Retrospective cohort replication study. Setting SCI Model Systems. Participants 35,675 total individuals with acute traumatic SCI with 219 cases of initial wrist extensor weakness (0/5–2/5) meeting inclusion criteria. Intervention Not applicable. Main outcome measure Recovery of wrist extensor strength to ≥3/5 at 1 year. Results The positive predictive and negative predictive values were 57% (95% CI, 47.4%–66.1%) and 66% (56.0%–75.1%) if initial C5 sharp‐dull discrimination was present, 61% (52.7%–69.3%) and 82% (71.4%–89.7%) if initial C5 myotome strength was at least antigravity, and 74% (63.7%–82.5%) and 74% (65.5%–81.4%) if initial C6 myotome strength was at least a 1/5 or 2/5. Synthesizing these three rules, an updated branched nomogram for functional wrist extensor recovery prediction was created. Conclusions In isolation, none of the previously established wrist extensor motor recovery predictive rules had as high of a prognostic value when using a larger dataset. As such, singular reliance on these prediction rules to identify who will gain 1‐year antigravity wrist extension should be approached with decreased certainty. The best positive and negative predictors were trace C6 strength and absent C5 strength, respectively. An updated nomogram provides more nuanced prognostic information to guide clinical care following acute SCI.