Microneedle Radiofrequency Induces Extracellular Matrix Remodeling Through Fibroblast Activation
MRF predominantly promotes the synthesis of Collagen I and Collagen III, increasing the Collagen I/III ratio, and regulates the expression of MMP-1, MMP-3, MMP-9, TGF-ß, and EGF. These factors collectively drive fibroblast activation, migration, and ECM remodeling. These changes are indicative of the potential for MRF to support skin regeneration and rejuvenation. Preliminary findings suggest that ADSCs may contribute to these regenerative processes.
Summary
A Histological Study in a Porcine Model.
[Posted 26/Aug/2025]
AUDIENCE: General Surgery, Dermatology, Family Medicine
KEY FINDINGS: MRF predominantly promotes the synthesis of Collagen I and Collagen III, increasing the Collagen I/III ratio, and regulates the expression of MMP-1, MMP-3, MMP-9, TGF-ß, and EGF. These factors collectively drive fibroblast activation, migration, and ECM remodeling. These changes are indicative of the potential for MRF to support skin regeneration and rejuvenation. Preliminary findings suggest that ADSCs may contribute to these regenerative processes.
BACKGROUND: Microneedle radiofrequency (MRF) is a promising skin rejuvenation treatment. However, the mechanisms underlying its effects on extracellular matrix (ECM) remodeling remain unclear. This study aimed to investigate the immediate histological effects of MRF under varying settings, its short-term impact on collagen and elastin synthesis, and the roles of fibroblasts and adipose-derived stem cells (ADSCs).
DETAILS: Porcine abdominal skin was treated with an MRF device containing 49 insulated microneedles using varying energy parameters (8-12 W; 100-300 ms). Immediate histological responses to treatment were evaluated through hematoxylin and eosin (H&E) staining. Short-term changes in collagen and elastin synthesis at Days 7 and 28 posttreatment were assessed via picrosirius red and Victoria blue staining. Additionally, expression and distribution of ECM remodeling-related proteins (MMPs, TGF-ß, EGF, Ki67) and ADSCs were analyzed by multiplex immunohistochemistry (mIHC) and western blot analysis. H&E staining revealed thermal coagulation zones in the dermis immediately after MRF treatment, with zone size increasing with higher power and longer pulse durations (p < 0.05). By Day 28, Collagen I and III densities and organization significantly improved, with the Collagen I/III ratio rising to 7.05 ± 1.21 in the treatment area (p < 0.01) and 3.90 ± 0.37 in the surrounding dermis (p < 0.001). Elastic fibers also showed increased density. mIHC staining demonstrated significant upregulation of MMP-1, MMP-3, and MMP-13 expression in treated and surrounding dermal regions by Day 7 (p < 0.01); however, by Day 28, MMP-1, MMP-9, and MMP-13 expression significantly decreased (p < 0.05), whereas MMP-3 remained elevated. Furthermore, expression levels of TGF-ß, EGF, and Ki67 significantly increased by Day 28 (p < 0.05). mIHC analysis of the fibroblast marker FSP-1 coexpression, along with Western blot analysis of Collagen I, Collagen III, MMP-1, MMP-3, TGF-ß, and EGF, revealed similar trends. Notably, significant expression of ADSC markers was detected at Day 7 posttreatment (p < 0.01).
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Source: Yidan, X., Yi, Z., Hao, W., et al. (2025). Microneedle Radiofrequency Induces Extracellular Matrix Remodeling Through Fibroblast Activation: A Histological Study in a Porcine Model. Lasers Surg. Med.. 2025; 57(6): 528-543. Published: August, 2025. DOI: 10.1002/lsm.70033.
Fracture Risk Remains High and Largely Unaddressed After Kidney Transplantation
Kidney transplant recipients had a 21% 10-year fracture risk, unchanged over two decades. Twenty-eight percent of those with a fracture sustained another fracture, with the highest incidence at 6-12 months. Only 10% received anti-osteoporosis therapy and 17% underwent DXA within 1 year, highlighting an unmet need for post-fracture risk assessment and intervention.
KEY FINDINGS: Kidney transplant recipients continue to experience substantial fracture risk, with approximately one in five developing a fracture within 10 years after transplantation. Fracture rates remained largely unchanged over two decades, and an initial fracture was followed by a particularly high risk of another fracture. The limited use of anti-osteoporosis therapy and DXA assessment after fracture highlights an important gap in post-transplant bone health management.
BACKGROUND: Kidney transplant recipients remain at increased risk of fractures compared with the general population. However, the magnitude of this risk in the current transplant era and the likelihood of subsequent fractures after an initial event have not been fully characterized. This study evaluated post-transplant fracture risk and prognosis over two decades.
DETAILS: This retrospective cohort study included all adults who underwent a first single-organ kidney transplant between 2000 and 2022 in Denmark. Nationwide health registries provided demographic, diagnostic, procedural, prescription, transplantation, and mortality data. The study assessed cumulative incidence of first and subsequent fractures, with death treated as a competing risk, and examined fracture incidence across different transplant periods.
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The cohort comprised 3977 kidney transplant recipients, with a median age of 50 (40, 60) years; 1487 (37%) were female. Before transplantation, 503 (13%) had a history of any fracture and 176 (4%) had experienced a major osteoporotic fracture.
Among 3977 kidney transplant recipients, 788 experienced a post-transplant fracture. The 10-year risk of any fracture was 21% (95% confidence interval 20–23). Crude fracture incidence remained unchanged across the study period from 2000 to 2022, although age- and sex-standardized estimates showed a slight decline. Fractures occurred predominantly at peripheral skeletal sites.
Twenty-eight percent of patients who sustained a fracture experienced a subsequent fracture, with the greatest incidence occurring 6–12 months after the initial event. The 2-year cumulative incidence of any subsequent fracture was 13% (95% CI 11–16), increasing to 24% (95% CI 21–28) at 5 years.
Despite the fracture burden, only 10% of patients received anti-osteoporosis therapy within 1 year after a fracture, and 17% underwent dual-energy X-ray absorptiometry (DXA) within 1 year.
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Source: Ystrøm, I. K., Christiansen, C. F., Ivarsen, P., et al. Fracture Risk After Kidney Transplantation: Unchanged and Unaddressed: A Registry-Based Cohort Study Across Two Decades. Clinical Kidney Journa. 2026; 19(3): sfag029. Published: March, 2026. DOI: 10.1093/ckj/sfag029.
FDA Approves Engineered Viral Immunotherapy for Treatment-Resistant Advanced Melanoma
FDA approved Tudriqev, an engineered HSV-1-based viral immunotherapy, for adults with treatment-resistant advanced melanoma. The therapy produced tumor responses in 24.2% of patients with a median response duration of 14.1 months. Ongoing Phase III evaluation will further assess long-term efficacy and safety.
KEY FINDINGS: FDA approval of Tudriqev introduces an engineered viral immunotherapy option for adults with treatment-resistant advanced melanoma. By combining direct tumor destruction with immune activation, this therapeutic approach expands the available immunotherapy landscape for patients with limited options after progression on standard treatments. Continued evaluation through confirmatory studies will determine its long-term clinical role in melanoma management.
BACKGROUND: Patients with advanced melanoma whose disease progresses despite available systemic therapies have limited treatment options and significant unmet clinical needs. The U.S. Food and Drug Administration (FDA) approved a new engineered viral immunotherapy designed to provide a treatment option for adults with advanced melanoma that is resistant to prior therapies.
DETAILS: The FDA approved Tudriqev (vusolimogene oderparepvec, formerly RP1), an engineered oncolytic viral immunotherapy developed by Replimune, for adults with unresectable or metastatic melanoma that has progressed following treatment with an anti–PD-1 therapy and, when appropriate, targeted therapy for BRAF-mutated disease. Tudriqev is an engineered herpes simplex virus type 1 (HSV-1)-based therapy administered through intratumoral injection. The treatment is designed to selectively replicate within tumor cells, promote tumor cell destruction, and stimulate an immune response against cancer cells. The FDA approval was based on clinical evidence demonstrating tumor responses in patients with advanced melanoma who had limited therapeutic alternatives. The therapy represents an additional immunotherapeutic approach that uses direct tumor targeting combined with immune system activation. In clinical evaluation, Tudriqev demonstrated tumor reduction or elimination in 24.2% of treated patients, with a median duration of response of 14.1 months. The FDA approval provides a new treatment option for patients with advanced melanoma whose disease has become resistant to prior immunotherapy approaches. A confirmatory Phase III study is ongoing to further evaluate the therapy’s clinical benefit and long-term outcomes.
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High-Quality Donor Kidneys Frequently Allocated to Adults Despite Pediatric Priority
Among deceased-donor kidneys with KDPI-10 below 35%, 23.4% were allocated to higher-priority adults. For ideal pediatric-quality kidneys, this proportion was 34.3%, with 77.5% received by multiorgan transplant recipients. KDPI-8 is unlikely to materially change pediatric access to ideal donor kidneys.
KEY FINDINGS: Despite pediatric allocation priority, a substantial proportion of high-quality donor kidneys continues to be allocated to adults with greater priority, predominantly multiorgan transplant recipients. The revised KDPI-8 calculation is not expected to materially alter the proportion of ideal pediatric-quality kidneys prioritized for children, although it changes the clinical composition of the donor pool by increasing the proportion of HCV-seropositive donors and reducing the proportion of donors after circulatory death. These findings highlight persistent limitations of KDPI-based allocation for pediatric candidates and support continued evaluation of policies that balance equity, donor-recipient matching, and long-term transplant outcomes.
BACKGROUND: Children receive allocation priority for deceased-donor kidneys with a kidney donor profile index (KDPI) <35%, although certain adult candidates retain higher priority. The recent transition from the 10-variable KDPI (KDPI-10) to the revised 8-variable KDPI (KDPI-8), which excludes donor race and hepatitis C virus (HCV) status, raised questions regarding its potential effect on pediatric access to high-quality donor kidneys.
DETAILS: This retrospective cohort study analyzed 60,587 deceased donors and their kidney recipients recorded in the Organ Procurement and Transplantation Network registry from January 1, 2018, through December 31, 2023. The investigators compared donor characteristics and kidney allocation patterns using KDPI-10 and KDPI-8. Ideal pediatric-quality donors were defined as donors with a KDPI <35%, donation after brain death, age <35 years, creatinine <=1.5 mg/dL, and no infectious risk, diabetes, or hypertension. Among kidneys from donors with KDPI-10 <35%, 23.4% were allocated to adults in categories with greater priority than pediatric candidates. Among ideal pediatric-quality kidneys, 34.3% were allocated to these higher-priority adult recipients, and 77.5% of these transplants were received by multiorgan transplant recipients. The proportion of donors meeting ideal pediatric-quality criteria was similar with KDPI-10 and KDPI-8 calculations (32.7% vs 33.5%). However, the KDPI-8 group included more Black donors (15.3% vs 9.9%) and HCV-seropositive donors (11.1% vs 3.6%) and fewer donors after circulatory death (12.7% vs 20.3%).
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Source: Sonnenberg, E. M., Amaral, S., Zhang, S., et al. Allocation of Kidney Allografts From Donors With Kidney Donor Profile Index <35% and the Impact of Kidney Donor Profile Index Revisions on Access to Transplantation for Children. American Journal of Kidney Diseases. 2026; Published: August 22, 2026. DOI: 10.1053/j.ajkd.2026.02.643.
Accuracy of Fetal Echocardiography for Detecting Associated Lesions and Predicting Surgical Management in Dextro-Transposition of the Great Arteries and Double Outlet Right Ventricle with Subpulmonary Ventricular Septal Defect
In a cohort of 99 fetuses with D-TGA or DORV-SPV, fetal echocardiography showed high diagnostic accuracy for simple D-TGA but lower accuracy for complex lesions. Serial assessment frequently altered VSD characterization, while fetal aortic measurements and aortic-to-pulmonary artery ratios (AUC above 0.9) accurately predicted postnatal CoA repair.
KEY FINDINGS: Fetal echocardiography demonstrated excellent diagnostic performance for simple D-TGA but substantially lower accuracy in complex D-TGA and DORV-SPV with associated lesions. Serial fetal assessment frequently altered qualitative VSD size estimation, while many small postnatally confirmed VSDs did not require surgical repair. Quantitative fetal aortic measurements and aortic-to-pulmonary artery ratios showed strong discriminatory ability (AUC >0.9) for identifying fetuses requiring postnatal CoA repair, supporting their role in improving prenatal risk stratification and surgical planning.
BACKGROUND: Associated cardiac lesions, including ventricular septal defect (VSD), coarctation of the aorta (CoA), and pulmonary stenosis (PS), substantially influence prenatal counseling and postnatal surgical management in fetuses with dextro-transposition of the great arteries (D-TGA) and double outlet right ventricle with subpulmonary ventricular septal defect (DORV-SPV). This study assessed the diagnostic accuracy of fetal echocardiography (FE) for identifying associated lesions and predicting the postnatal surgical approach.
DETAILS: This single-center retrospective cohort study included 99 fetuses with D-TGA or DORV-SPV managed at Lucile Packard Children's Hospital (Palo Alto, California, USA) between January 2013 and January 2024. Eligible fetuses were liveborn, had a documented prenatal surgical plan, and underwent postnatal management at the study center. In 65% of cases, serial fetal echocardiograms were available. Prenatal diagnoses and predicted surgical plans were compared with postnatal echocardiographic findings and the surgical procedures ultimately performed. Receiver-operating characteristic (ROC) analysis evaluated the predictive performance of fetal aortic and pulmonary artery measurements for postnatal CoA repair. Among the 99 fetuses, postnatal diagnoses included 45 with simple D-TGA, 38 with complex D-TGA, 15 with DORV, and 1 case reclassified from prenatal DORV-SPV to truncus arteriosus. Diagnostic concordance between fetal and postnatal echocardiography was highest for simple D-TGA (95% (42/44)) and D-TGA with VSD and PS (100% (3/3)), followed by D-TGA with VSD (93% (25/27)). Lower concordance was observed for DORV-SPV (60% (3/5)), DORV-SPV with CoA (40% (4/10)), D-TGA with VSD and CoA (29% (2/7)), D-TGA with isolated CoA (0% (0/2)), and DORV-SPV with PS (0% (0/1)). Surgical-plan prediction showed a similar pattern, with the greatest accuracy in simple D-TGA and D-TGA with VSD and PS. Qualitative assessment of VSD size frequently changed across serial fetal examinations, with defects generally appearing larger prenatally but often smaller on postnatal echocardiography. Only 50% of small VSDs identified postnatally required repair. All infants undergoing postnatal CoA repair had an associated VSD. ROC analysis demonstrated that fetal aortic measurements and aortic-to-pulmonary artery dimension ratios achieved area under the curve values greater than 0.9 for predicting the need for postnatal CoA repair.
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Source: Chandrasekar, H., Kaplinski, M., Maskatia, S. A., et al. Accuracy of Fetal Echocardiography in Detecting Lesions Associated With, and Predicting Surgical Plan for, Dextro-Transposition of the Great Arteries and Double Outlet Right Ventricle With Subpulmonary Ventricular Septal Defect and Predicted Transposition Physiology. Ultrasound in Obstetrics & Gynecology. 2026; 68(1):v79-87. Published: January 30, 2026. DOI: 10.1002/uog.70169
Single-Encounter Augmented Reality-Guided Localization for Resection of Suspected Early-Stage Lung Cancer
Single-encounter augmented reality (AR)-guided localization demonstrated noninferiority to conventional CT-guided localization for successful sublobar resection in patients with suspected early-stage lung cancer. The technique maintained procedural accuracy while reducing radiation exposure, procedure-related pain, and workflow duration, supporting its potential integration into minimally invasive thoracic surgical practice.
KEY FINDINGS: This randomized clinical trial demonstrated that single-encounter AR-guided localization was noninferior to conventional CT-guided localization for achieving successful sublobar resection of suspected early-stage lung cancer. In addition to maintaining localization accuracy, the AR-guided approach reduced radiation exposure, procedural pain, and workflow time, supporting its potential as an alternative localization strategy for minimally invasive lung surgery.
BACKGROUND: Accurate preoperative localization is critical for successful sublobar resection of small pulmonary nodules suspicious for early-stage lung cancer. Conventional computed tomography (CT)-guided localization typically requires multiple encounters, including localization in the CT suite followed by transfer to the operating room, increasing patient discomfort, radiation exposure, and procedural complexity. This randomized clinical trial evaluated whether a single-encounter augmented reality (AR)-guided localization strategy could achieve surgical outcomes comparable to standard CT-guided localization while improving procedural efficiency and patient experience.
DETAILS: This multicenter, randomized, noninferiority trial was conducted at 5 centers in China between August 8, 2024, and September 30, 2025. Among 296 randomized patients, 270 were included in the modified intention-to-treat analysis, with 134 assigned to single-encounter AR-guided localization and 136 to conventional multiple-encounter CT-guided localization. Eligible participants had CT-detected pulmonary nodules suspicious for early-stage lung cancer requiring preoperative localization before sublobar resection. The primary endpoint was successful sublobar resection, defined as R0 resection with protocol-specified adequate surgical margins. Secondary outcomes included localization accuracy, radiation exposure, localization-related complications, patient-reported pain, and procedural efficiency. The median (IQR) patient age was 59 (50-67) years, and 172 participants (63.7%) were women. Successful sublobar resection was achieved in 132 of 134 AR-guided procedures (98.5%) and 135 of 136 CT-guided procedures (99.3%), yielding a risk difference of -0.8 percentage points (95% CI, -2.7 to 3.9) and meeting the prespecified criterion for noninferiority. Localization accuracy was similar between groups, with a median (IQR) localization error of 3.0 (0.0-5.0) in the AR group and 3.0 (2.0-6.0) in the CT group. Compared with CT guidance, AR-guided localization significantly reduced radiation exposure (456.50 [378.75-631.85] vs 1260.11 [1026.48-1544.53] mGy·cm; P<.001), preoperative pain (0 [0-0] vs 5 [4-6]; P<.001), puncture time (0.63 [0.50-0.83] vs 6.50 [5.00-8.75] minutes; P<.001), and localization-to-incision interval (2.00 [1.50-2.00] vs 33.50 [18.00-63.00] minutes; P<.001). Pneumothorax occurred in 40 of 136 CT-guided cases (29.4%), whereas no clinically significant complications associated with AR-guided localization were reported.
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