Citations

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.

Abstract Aims The increasing adoption of transcatheter tricuspid valve replacement (TTVR) offers a promising therapeutic option for patients with severe tricuspid regurgitation. However, many of these patients have pre-existing cardiac implantable electronic devices (CIEDs), raising concerns about potential lead-related complications. Despite these concerns, limited data exist on the impact of TTVR on CIED integrity and function. This study aimed to evaluate the impact of TTVR on CIED lead function, including pacing thresholds, sensing, and impedance, in patients undergoing TTVR with the EVOQUE valve system. Methods and results A retrospective observational study was conducted at Mayo Clinic Rochester, including 32 consecutive patients who underwent TTVR with pre-existing CIEDs. A total of 32 patients were included, with a mean age of 79.2 ± 8.4 years; 59% were female. A total of 62.5% had a permanent pacemaker, 12.5% had an implantable cardioverter-defibrillator, 15.6% had a cardiac resynchronization therapy pacemaker, and 9.4% had a cardiac resynchronization therapy defibrillator. Following TTVR, 10 (31%) of patients developed lead function changes during a median device follow-up of 210 days (IQR: 43–307 days). The right ventricular lead was primarily affected, with only one case involving an atrial lead. Neither the Ottawa score nor the anatomical lead position reliably predicted lead abnormality (P = 0.86 and P = 0.53, respectively). R-wave sensing changes were the most common lead change observed, affecting 55% of cases. In 67% of these cases, R-wave sensing alterations occurred as an isolated finding, with no significant change in impedance or thresholds, and were managed conservatively without any need for device reprogramming. Four patients (13%) had findings concerning for a lead insulation breach, in which one (3%) required a lead revision. Among five patients with follow-up exceeding 600 days, two patients exhibited a statistically significant gradual decline in impedance without other lead dysfunction, suggesting potential subclinical lead degradation. Conclusion Transcatheter tricuspid valve replacement with the EVOQUE system in the setting of cardiac device leads is associated with lead function changes in 31%. The majority of lead-related changes were managed conservatively, but 13% of patients had findings concerning for an insulation breach. Future studies should focus on refining implantation techniques and defining optimal strategies for managing device-lead interactions in this population.

Abstract INTRODUCTION Increased white matter hyperintensity (WMH) volume is a common but non‐specific finding in AD. This study investigates the effect of baseline WMH volume and APO E ε4 on magnetic resonance imaging (MRI)‐visible hemorrhagic lesion emergence. METHODS We included A4 participants with 0/1 hemorrhagic lesion at baseline and >1 post‐baseline MRI. We examined age, sex, amyloid, WMH, APOE ε4, and cardiovascular risk as predictors of whether people would accrue ≥2 hemorrhagic lesions by their last MRI. RESULTS Among 1097 individuals with 0/1 baseline lesion, 120 had at least two hemorrhagic lesions on their last MRI. Elevated baseline WMH (odds ratio [OR] = 2.3, p = 0.002) and APOE ɛ4/ɛ4 (OR = 4.8, p < 0.001) independently predicted membership to this group. Both hetero‐ and homozygous APOE ɛ4 carriers with low WMH volume had a low risk of accumulating hemorrhagic lesions. DISCUSSION These results support the independent consideration of WMH and APOE ɛ4 in the natural history of hemorrhagic lesion accumulation and suggest that individuals with low WMH volume have a low short‐term risk, irrespective of APOE genotype. Trial Registration : NCT02008357 Highlights Elevated baseline white matter lesion volume is related to the risk of ARIA‐H emergence. The effects of white matter lesion volume and APOE ɛ4 on ARIA‐H are independent. APOE ɛ4 carriers with low white matter lesion volume had a low risk of ARIA‐H emergence.