State-of-the-art minimally invasive in utero interventions involving stem cell, protein, and nucleic acid-based therapies represent a new frontier in medicine, which offers hope for devastating fetal diagnoses and promises the restoration of lifetimes. Yet they also introduce serious concerns regarding health risks posed to mother, fetus, and future generations. Recent international consensus statements provide general guidance for structuring trials to maximize health and minimize the risk of experimental treatments for both a pregnant mother and fetus. This article offers additional ethical guidance for translating interventions from first-in-human studies by focusing on a more holistic and nondirective consent process and encouraging pretrial publication of proposed studies to increase dialogue, fine-tune protocols, and potentially improve access.
Publications by Year: 2025
2025
Cite this article as: Ashkani-Esfahani S, Aslan L. AOTT special issue Editorial. Acta Orthop Traumatol Turc., 2025;59(6):337-339.
Three-dimensional printing has rapidly evolved into an important technology in orthopedic surgery, enabling the creation of patient-spe cific instruments, implants, and anatomical models. As printing has become more affordable and accessible, point-of-care manufacturing has increasingly allowed clinicians to design and produce surgical aids directly within clinical units. This development, combined with advances in computed tomography (CT)-based imaging and segmentation software, has significantly expanded the use of patient-specific surgical guides (PSGs), particularly in foot and ankle surgery, where complex multiplanar deformities, poor soft-tissue, and limited visu alization often create technical challenges. Patient-specific surgical guides are generated from thin-slice CT data and allow surgeons to accurately transfer preoperative planning to the operative field. Their use has been reported across a wide range of procedures, including deformity correction, joint fusion, ankle arthroplasty, etc. Across these applications, studies consistently demonstrate improved osteot omy accuracy, enhanced deformity correction, reduced operative time, lower fluoroscopy exposure, and greater reproducibility between surgeons. The increasing adoption of weight-bearing CT has further strengthened the accuracy of preoperative planning by capturing true functional alignment. Despite these advantages, several limitations persist, including increased preoperative imaging requirements, higher initial costs, and dependency on manufacturing logistics. Most published studies remain level III-IV, with limited long-term data on clinical outcomes and cost-effectiveness. Nevertheless, as technological capabilities improve and workflows become more efficient, PSGs are poised to become an integral component of personalized foot and ankle surgery, with the potential to enhance both surgical precision and patient outcomes. Cite this article as: Kavak S, Ozturk B, Ogut T, DiGiovanni CW, Esfahani SA, Karaismailoglu B. Application of patient-specific surgical guides in foot and ankle surgery. Acta Orthop Traumatol Turc., 2025;59(6):340-348.
BACKGROUND: Nearly one fifth of the US population resides in rural areas. Although endovascular therapy can substantially improve clinical outcomes in patients treated with large vessel occlusion acute ischemic stroke, the penetration and outcomes of this therapy in rural US populations remain incompletely characterized.
METHODS: From the nationwide Get With The Guidelines Stroke registry, incorporating select social determinants of health (SDOH) by the Institute for Health Metrics and Evaluation registry (2016-2019), we identified patients with acute ischemic stroke and transient ischemic attack who were transferred from their presenting hospitals to other hospitals with the intention of thrombectomy evaluation, for patients residing in rural and nonrural areas. The primary outcome was the likelihood of undergoing intra-arterial catheter-based therapy after transfer, adjusted for stroke severity, age, baseline ambulatory status, and select SDOH, by multivariable logistic regression.
RESULTS: Among 24 620 patients meeting inclusion criteria, 5.1% resided in rural areas. Patients residing in rural areas transferred for endovascular therapy evaluation experienced less favorable SDOH than patients residing in nonrural areas (P<0.01, each, for education, income, homeownership, poverty, and unemployment). Patients in both groups presented with moderate/severe stroke and similar vascular risk factors. Patients residing in rural areas were 15% less likely to undergo endovascular therapy, when adjusting for stroke severity, age, baseline ambulatory status, and select SDOH (40.8% versus 49.4%; adjusted odds ratio [aOR], 0.85 [95% CI, 0.74-0.99]). Patients residing in rural areas experienced similar incidence of reported transfer delays as patients residing in non-rural areas (0.1%, each; aOR, 1.36 [95% CI, 0.56-6.84]).
CONCLUSION: In this nationwide cohort study, patients living in rural areas with acute ischemic stroke or transient ischemicattack who were transferred to other hospitals for endovascular therapy evaluation were less likely to undergo intra-arterial catheter-based therapy, despite similar incidence of transfer delays, and when adjusting for select SDOH commonly associated with rurality.
BACKGROUND: The blood biomarkers GFAP (glial fibrillary acidic protein) and D-dimer have been shown to accurately diagnose large vessel occlusion ischemic stroke. The Upfront DX LVOne is a novel lateral flow-based point-of-care test used for the detection of GFAP and D-dimer. This study sought to (1) assess the performance of LVOne against commercially available point-of-care test platforms, which independently detect GFAP and D-dimer (Abbott iSTAT TBI Plasma and LumiraDx D-dimer), and to (2) assess the diagnostic performance of LVOne in large vessel occlusion detection.
METHODS: Manufacturer-reported detection thresholds of the LVOne test for GFAP and D-dimer (213 pg/mL and 600 ng/mL, respectively) were compared against commercial hospital-based point-of-care test platforms using 20 randomly selected plasma samples for each biomarker. D-dimer correlation between LVOne and LumiraDx was assessed using Spearman's Rank correlation coefficient; GFAP correlation between LVOne and the Abbott iSTAT TBI results were assessed using point biserial correlation. Diagnostic performance of the LVOne point-of-care test in conjunction with clinical assessment for detection of large vessel occlusion in plasma samples from 210 patients with suspected stroke was validated.
RESULTS: There was a strong positive correlation (Rho = 0.86, P<0.001) between the qualitative scoring of the lateral flow test and serum GFAP concentrations. Similarly, there was a significant positive correlation between the D-dimer quantification and LVOne semiquantitative measurements (Rho = 0.90; P<0.0001). In our cohort of 210 patients with suspected stroke, the LVOne test in conjunction with clinical assessment had a sensitivity of 75% (95% CI, 51%-91%), a specificity of 92% (95% CI, 87%-95%), a positive predictive value of 48% (95% CI, 30%-67%), and a negative predictive value of 97% (95% CI, 94%-99%) for detection of large vessel occlusion.
CONCLUSION: Our results validate detection thresholds for the LVOne test in a representative cohort of plasma samples of patients with suspected stroke. Further studies are required to demonstrate the efficacy, safety, and diagnostic performance of LVOne in capillary blood during emergency care/clinical triage.
Antibody (Ab)-based therapeutics have become powerful tools across diverse disease areas, with advances in bioengineering giving rise to next-generation molecules designed to outperform conventional Abs. Yet, large-scale production and purification of such complex proteins remain costly and can restrict patient access. A promising alternative is to improve in vivo expression capabilities, which will reduce manufacturing burdens and improve safety and tolerability. Multiple gene delivery platforms - ranging from mRNA and viral vectors to engineered cell therapies - have matured considerably, as a direct result of years of clinical experience and growing regulatory confidence. The rapid deployment of mRNA vaccines against SARS-CoV-2, the clinical success of adeno-associated virus (AAV)- and lentiviral-based interventions, and the approval of chimeric antigen receptor (CAR)-T cell therapies highlight the potential of these technologies to transform how we deliver Ab therapeutics. While these approaches hold the promise to treat genetic aberrations in patients, they may also contribute considerably to advancing conventional Ab therapeutics against viral infections and other diseases through local persistence of the proteins. Looking forward, in situ expression may confer even more benefits for engineered Ab-like molecules, thereby compensating for possibly shorter half-lives and overcoming challenges in in vitro production and purification. Therefore, in this review, we critically evaluate how these established and emerging gene therapy platforms can be harnessed to expand access, and discuss possibilities to improve in situ availability through the choice of transient or stable expression systems to increase the efficacy of Abs and other therapeutic proteins. Furthermore, we explore the current landscape of technological advancements, identify key translational challenges, and project future directions for optimizing these approaches towards widely applicable clinical interventions.
BACKGROUND: Serum hepatic injury markers indexes are altered in COVID-19 patients. We aimed to explore the factors that could be associated with abnormal serum hepatic injury markers in adult COVID-19 patients.
METHODS: Eight main hepatic injury markers were examined. Demographic and hematological information, mean CT values (MCTVs) of liver and pancreas, and abdominal subcutaneous fat thickness were recorded. Regression analysis was conducted to identify factors related to abnormal hepatic injury markers.
RESULTS: 1,007 adult COVID-19 patients (444 males and 563 females) were included, among whom 697 patients (69.2%) had at least one abnormal hepatic injury markers marker. Females had lower risks of elevated Total Bilirubin (TBil), Direct Bilirubin (Dbil), ALT, AST, GGT and decreased albumin, with ORs of 0.61 (95%CI: 0.42-0.89), 0.36 (95%CI: 0.16-0.83), 0.20 (95%CI: 0.12-0.32), 0.42 (95%CI: 0.30-0.58), 0.36 (95%CI: 0.22-0.60) and 0.40 (95%CI: 0.30-0.54). Patients with greater ratios of subcutaneous fat thickness to abdominal diameters also had lower risks of abnormalities in these six markers. Older patients had higher serum levels of AST but lower levels of albumin and ALT. The risks of abnormal DBil and AST were 3.26 and 1.62 times higher in patients with a history of HBV infection. Patients with many abnormal hepatic injury markers indexes had significantly lower MCTVs of liver and pancreas and higher levels of fibrinogen and LDH in blood.
CONCLUSIONS: Sex, age, HBV infection, fibrinogen, LDH, liver and pancreas MCTVs, and ratio of abdominal subcutaneous fat thickness to the sum of the abdominal diameters were independently associated with many abnormal serum hepatic injury markers in adult COVID-19 patients.
BACKGROUND: Patients with heart failure (HF) treated with mechanical thrombectomy (MT) for acute ischemic stroke were underrepresented in clinical trials on MT. Our systematic review and meta-analysis aim to assess differences in outcomes between patients with HF and their counterparts without HF treated with MT for acute ischemic stroke.
METHODS: A systematic review of the English language literature from inception up to March 7, 2024, was conducted using PubMed, Embase, Cochrane Library, and Web of Science databases. Studies focused on patients with and without HF who were treated with MT for acute ischemic stroke were included. The primary outcome of interest was the rate of modified Rankin Scale scores of 0-2 at 90 days. Secondary outcomes of interest included rates of 90-day mortality, successful reperfusion, and symptomatic intracranial hemorrhage.
RESULTS: Of 5394 initially retrieved studies, 5 studies were included in the systematic review with a final population of 44 385 patients with ischemic stroke with and without HF treated with MT. Four studies were combined for the primary outcome and showed comparable rates of 0-2 modified Rankin Scale scores between patients with HF and patients without HF (odds ratio, 0.86 [95% CIs, 0.70-1.06]; P = 0.15). Ninety-day mortality was significantly higher in the HF group (odds ratio, 1.92 [95% CIs, 1.66-2.23]; P<0.0001) although the sample size was small (n of study = 3) and only unadjusted estimates were used. Successful reperfusion and symptomatic intracranial hemorrhage rates were similar between the groups.
CONCLUSION: In this systematic review and meta-analysis, patients with HF experienced worse 90-day mortality post-MT. Our data encourage further research on MT outcomes in patients with large vessel-occlusion ischemic stroke and concomitant HF.