Citations

Abstract Aims Systemic ventricular (SV) strain imaging improves early detection of systolic dysfunction in patients with congenital heart disease and biventricular circulation. However, its role for risk stratification in the Fontan population has not been systematically studied. We hypothesized that among Fontan patients with normal SV ejection fraction (Echo_EF) at baseline, those with reduced SV longitudinal strain (Echo_LS) would have a higher risk of progressive SV systolic dysfunction, greater neurohormonal activation, and cardiovascular events (heart failure hospitalization/death/transplant) during follow-up. Methods and results We studied adults with Fontan palliation and normal SV systolic function (Echo_EF >50%) at baseline who underwent follow-up echocardiogram >36 months after the baseline echocardiogram. Echo_LS was assessed from the apical 4-chamber window using speckle tracking echocardiography. Patients were divided into reduced vs. normal Echo_LS groups, using −18% as the cut-off point. Echo_LS, Echo_EF, and NT-proBNP were assessed at baseline and follow-up encounters. Of 272 patients (age, 28 ± 8 years), 98 (36%) and 174 (64%) had reduced vs. normal Echo_LS. The reduced_Echo_LS group had progressive SV systolic dysfunction [worse temporal decline in Echo_EF (relative_Δ_Echo_EF −12.8% vs. −2.1%, P < 0.001)], and higher prevalence of new-onset SV systolic dysfunction [30% (29/98) vs. 8% (13/174), P < 0.001]. The reduced Echo_LS group also had greater neurohormonal activation [relative Δ_ NT-proBNP 36 (95%CI, 27–43) % vs. 17 (95%CI, 11–23) %, P < 0.001], and higher risk of cardiovascular events (adjusted hazard ratio 1.84, P = 0.009). Conclusion Echo_LS improves risk stratification in Fontan patients with normal Echo_EF and may provide an opportunity for early interventions to improve outcomes.

Abstract Overall response (OR) that combines complete (CR) and partial responses (PR) is the conventional end point for acute graft-versus-host disease (GVHD) trials. Because PR includes heterogeneous clinical presentations, reclassifying PR could produce a better end point. Patients in the primary treatment cohort from the Japanese Society for Transplantation and Cellular Therapy (JSTCT) were randomly divided into training and validation sets. In the training set, a classification and regression tree algorithm generated day 28 refined response (RR) criteria based on symptoms at treatment and day 28. We then evaluated RR for primary and second-line treatments, using the area under the receiver operating characteristic curve (AUC) and negative predictive value (NPV) for 6-month nonrelapse mortality as performance measures. RR considered patients with grade 0/1 at day 28 without additional treatment as responders. RR for primary treatment produced higher AUCs than OR with small improvement of NPVs in both validation sets: JSTCT (AUC, 0.73 vs 0.69 [P < .001]; NPV, 92.0% vs 89.6% [P < .001]) and the Mount Sinai Acute GVHD International Consortium (MAGIC; AUC, 0.71 vs 0.68 [P = .032]; NPV, 90.9% vs 89.8% [P = .009]). RR for second-line treatment produced similar AUCs but much higher NPVs than OR in both validation sets of JSTCT (AUC, 0.64 vs 0.63 [P = .775]; NPV, 74.5% vs 66.0% [P < .001]) and MAGIC (AUC, 0.67 vs 0.64 [P = .105]; NPV, 86.8% vs 76.1% [P = .004]). Classifying persistent but mild skin symptoms as responses and residual lower gastrointestinal GVHD as nonresponses were major drivers in improving the prognostic performance of RR. Our externally validated day 28 RR would serve as a better end point than conventional criteria in future first- and second-line treatment trials.

Abstract We conducted a post hoc analysis of data from Blood and Marrow Transplant Clinical Trials Network 1506 (MORPHO), a randomized trial of gilteritinib vs placebo as posttransplantation maintenance for patients with FLT3-ITD–mutated acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (HCT), focusing the interactions between conditioning regimen intensity, measurable residual disease (MRD), and NPM1 comutation status reported from diagnosis. Comparing FLT3-ITD MRD before and after conditioning, there was no difference between myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC) in eradication or reduction of FLT3-ITD MRD. For participants who were FLT3-ITD MRD negative before HCT, there was no difference in the cumulative incidence of relapse during follow-up between those receiving MAC vs RIC. NPM1 comutation was associated with the largest magnitude of relapse-free survival benefit from post-HCT gilteritinib, and in these participants, post-HCT gilteritinib in the setting of RIC appeared to be as effective as MAC at preventing relapse. MAC appeared superior to RIC in preventing relapse only in participants who were NPM1 wild type at diagnosis and FLT3-ITD MRD positive before HCT. Our findings suggest that only a subset of patients with FLT3-ITD AML undergoing HCT may benefit from MAC and that, similar to AML therapy before HCT, the intensity of the HCT regimen should be adapted according to the molecular features of the disease. This trial was registered at www.clinicaltrials.gov as #NCT02997202.

Background: Secondary shoulder deformities are the most frequent sequelae of upper trunk-type brachial plexus birth injury (BPBI). Coracoid process dysplasia was recently described as being associated with glenoid retroversion and was recognized to block successful humeral head relocation. There are little to no reports on coracoid process deformity causing anterior shoulder pain. Our hypothesis is that coracoid process impingement causes anterior shoulder pain in BPBI, which is relieved by coracoid excision. This study presents the short-term results of this new technique in BPBI patients. Methods: A retrospective review identified BPBI patients who underwent coracoid excision from 2000 to 2022. Indications for this procedure include BPBI patients with anterior shoulder pain limiting the range of motion, localized tenderness over a prominent coracoid process, a dysplastic coracoid process seen on imaging, and persistent pain despite activity modification, medication, and therapy. Patient characteristics, preoperative shoulder pain score, range of motion, degree of glenohumeral subluxation, patient-reported outcomes measurement information system (PROMIS) scores for pain interference, and physical and upper extremity function were collected from chart review. Postoperative pain scores, range of motion, and PROMIS scores were collected at an average of 1 year after excision. Results: Five upper trunk BPBI patients, ages 10 to 25 years old, with anterior shoulder pain underwent coracoid excision. All had statistically significant pain relief from 6.5–8.5/10 before to 0–3/10 after the procedure. Forward flexion and external rotation improved by an average of 18 degrees. The pain interference score decreased by 25%. There was a 33% improvement in physical function scores and a 31% increase in upper extremity function scores. No complications or recurrence were observed at 7.5 months to 1 year and 7 months after surgery. Conclusions: Coracoid excision is a simple procedure that can relieve localized shoulder pain caused by coracoid impingement in adolescent/adult BPBI. Continued follow-up of all patients will be undertaken to determine long-term recurrence rates and complications. Level of Evidence: Level IV.

Background/Objectives: Spinoplastic surgery is an emerging multidisciplinary field developed to address and reduce the complication of pseudoarthrosis following complex spinal reconstructions. While the number of spinal fusion procedures continues to rise every year, fusion failure rates remain as high as 40%. Although pseudoarthrosis may not always manifest clinically, it remains a leading cause of persistent pain and need for subsequent revision surgeries. The multidisciplinary collaboration between spine and plastic surgeons in spinoplastic surgery has therefore emerged as a proactive strategy aimed at preventing complications, particularly in patients identified as high-risk for pseudoarthrosis. As the patient population expands and spinoplastic surgery continues to evolve, refining patient selection criteria becomes essential for achieving optimal surgical outcomes. This review aims to provide a comprehensive overview of recent advancements in spinoplastic surgery, highlighting current indications, surgical techniques, recent case reports, and strategies for identifying suitable candidates. Methods: We performed a narrative review of English language literature through April 2025. Spinoplastic case reports and case series published within the last 20 years were included in the review. Results: Indications for use of a spinoplastic approach clustered into prior fusion failure, extensive oncologic resection, severe spinal deformity, procedures requiring extensive spinal involvement, and/or patients at risk for impaired bone healing. Succesful radiographic union and improvement of symptoms were widely reported across all 9 case reports/series. Conclusions: Although evidence is presently limited, spinoplastic surgery appears to achieve high bone graft fusion rates with acceptable morbidity and functional improvement in a carefully selected group of high-risk spinal reconstruction patients. Still, larger prospective studies are warranted to refine patient selection and validate functional benefit.

Segmental bone loss reconstruction using frozen bone allografts has a great advantage over amputation. Unfortunately, frozen allografts are avascular, and their use often results in infection, non-union, or fracture. We have attempted to overcome these complications by revascularizing the bone using gene therapy. Segmental tibial bone transplants were performed in 16 Yucatan minipigs. An arteriovenous (AV) bundle was placed intramedullary inside the allografts, which were transfected with growth factors vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) in 8 out of the 16 pigs. Survival time was set at 20 weeks. Bone remodeling and biomechanical properties were tested using histology, compression testing, bone mineralization, and gait analysis. In the growth factor group, five out of eight pigs developed cutaneous vascular tumors, causing excessive bleeding, which led to the exclusion of one pig. Bone remodeling was significantly more present in the VEGF group compared to the control group. This correlated with the amount of pressure the pig allowed on the operated leg for 10 weeks, which was also significantly more (p = 0.029) than the control. Both bone mineralization (p = 0.156) of the area inside the cortex and the amount of stress the allograft could endure before breaking (p = 0.078) seemed to be no different for the VEGF group compared to its healthy contralateral side, which was the control group. We have shown that growth factor-induced frozen allograft bone revascularization using an intramedullary AV bundle results in significantly more bone remodeling and better biomechanical bone properties. However, we encountered benign vascular cutaneous tumors in five out of eight pigs, making the clinical application of this technique impossible at this time.

The translation of AI-generated brain metastases (BM) segmentation into clinical practice relies heavily on diverse, high-quality annotated medical imaging datasets. The BraTS-METS 2023 challenge has gained momentum for testing and benchmarking algorithms using rigorously annotated internationally compiled real-world datasets. This study presents the results of the segmentation challenge and characterizes the challenging cases that impacted the performance of the winning algorithms. Untreated brain metastases on standard anatomic MRI sequences (T1, T2, FLAIR, T1PG) from eight contributed international datasets were annotated in stepwise method: published UNET algorithms, student, neuroradiologist, final approver neuroradiologist. Segmentations were ranked based on lesion-wise Dice and Hausdorff distance (HD95) scores. False positives (FP) and false negatives (FN) were rigorously penalized, receiving a score of 0 for Dice and a fixed penalty of 374 for HD95. The mean scores for the teams were calculated. Eight datasets comprising 1303 studies were annotated, with 402 studies (3076 lesions) released on Synapse as publicly available datasets to challenge competitors. Additionally, 31 studies (139 lesions) were held out for validation, and 59 studies (218 lesions) were used for testing. Segmentation accuracy was measured as rank across subjects, with the winning team achieving a LesionWise mean score of 7.9. The Dice score for the winning team was 0.65 ± 0.25. Common errors among the leading teams included false negatives for small lesions and misregistration of masks in space. The Dice scores and lesion detection rates of all algorithms diminished with decreasing tumor size, particularly for tumors smaller than 100 mm3. In conclusion, algorithms for BM segmentation require further refinement to balance high sensitivity in lesion detection with the minimization of false positives and negatives. The BraTS-METS 2023 challenge successfully curated well- annotated, diverse datasets and identified common errors, facilitating the translation of BM segmentation across varied environments and providing the tools for future development of personalized volumetric reports to patients undergoing BM treatment.

Study Design This study is part of the AO Spine Metastatic Tumor Research and Outcomes Network [MTRON], an international multicenter prospective observational registry including patients with spinal metastases. Objectives This study aims to elucidate the incidence of surgical complications, their risk factors and consequent effects on survival outcomes, hospital length of stay, and overall health-related quality of life (HRQOL) parameters in a large cohort of patients affected by spinal metastases who were surgically treated. Methods Available data from February 2017 to July 2023 were analyzed. The primary outcome of this study was the evaluation of the incidence of intraoperative and postoperative adverse events (AEs). The secondary outcomes included the assessment of risk factors for surgery-related AEs and the impact of AEs on survival, length of hospital stay and quality of life. Results Among the 1267 patients analyzed, 6.9% experienced intraoperative AEs and 19.3% experienced at least 1 postoperative AE. Several factors resulted to be associated to the occurrence of postoperative AEs: age, smoking habit, poor Eastern Cooperative Oncology Group (ECOG) Performance status, previous radiation therapy at the index target, duration of surgery, number of instrumented levels, simultaneous anterior and posterior approach, presence of metastases at other sites, multiple spinal metastases. Postoperative AEs were associated with reduced survival rates, increased hospital length of stay and poorer HRQOL outcomes, particularly in domains such as neurological function and mental health. In general, surgery substantially improves HRQOL across multiple domains, with these benefits persisting over time despite the occurrence of AEs. However, patients with preoperative risk factors, including comorbidities, smoking, neurological impairment, and prior radiation therapy, experienced less improvement. Conclusions The negative impact of AEs on overall survival and HRQOL could be associated with the presence of some preoperative parameters of frailty that are detected as risk factors for AEs occurrence. This finding emphasizes the need for personalized preoperative assessments and optimized perioperative care strategies.