Early Clinical Results Research Articles

From Glucose to Neuroprotection: Exploring Antidiabetic Medications as a Novel Approach to Alzheimer's Disease Treatment.

Alzheimer's disease (AD) is a major neurological disorder and a leading cause of dementia, which is characterized by progressive cognitive decline. Emerging research highlights the link between AD and type 2 diabetes mellitus (T2DM), suggesting that shared pathophysiological mechanisms, such as insulin resistance, inflammation, and oxidative stress, contribute to both conditions. This connection has led to the concept of type 3 diabetes.Given these overlaps, antidiabetic drugs are being explored for repurposing as potential AD treatments. Intranasal insulin, metformin, thiazolidinediones, and GLP-1 analogs like liraglutide have shown promise in reducing amyloid-beta levels and inflammation, and improving cognitive functions. Despite encouraging preclinical and early clinical results, challenges remain in translating these findings into safe and effective treatments. Continued research could lead to innovative therapies that address both AD and T2DM, offering improved patient outcomes.

ID: 325486 Lumbar Intervertebral Joint Stabilization by Injectable Load-Sharing Polymers - Early Clinical Results

ID: 325486 Lumbar Intervertebral Joint Stabilization by Injectable Load-Sharing Polymers - Early Clinical Results

A retrospective study on two different surgical robots to assist total knee arthroplasty

To compare early clinical and imaging results of domestic HURWA and imported Brainlab Knee3 surgical robot-assisted knee replacement. A retrospective analysis was performed on 93 patients with knee osteoarthritis (KOA) who underwent robot-assisted descending total knee arthroplasty(TKA) from January 2021 to July 2023, and they were divided into BRATKA group and HRATKA group according to use of robotic system. There were 40 patients in BRATKA group, including 16 males and 24 females, aged from 55 to 90 years old with an average of (64.3±7.0) years old;27 patients with grade Ⅲ and 13 patients with grade Ⅳ according to Kellgren-Lawrence(K-L);18 patients on the right side and 22 patients on the left side;the courses of disease ranged from 1 to 30 years with an average of (15.3±7.6) years;imported Brainlab Knee3 surgical robot assisted system was adopted. There were 53 patients in HRATKA group, including 18 males and 35 females, aged from 52 to 81 years old with an average of (64.4±8.5) years old;30 patients with grade Ⅲ and 23 patients with grade Ⅳ;21 patients on the right side and 32 patients on the left side;the courses of disease ranged from 1 to 32 years with an average of (16.4±7.9) years;HURWA surgical robot assisted system was adopted. Operation time, perioperative total blood loss, incision length and postoperative complications were compared between two groups. Deviation angle of hip-knee-ankle angle(HKAA) before operation and on the first day after operation was compared between two groups. Later tibal component (LTC), frontal femoral component (FFC), later femoral component (LFC) and frontal tibal component(FTC) at 1 day after on the first day after operation was compared between two groups. Knee Society score(KSS), visual analogue scale (VAS) and range of motion (ROM) of knee joint were compared between two groups before operation and on the 3rd and 90th day after operation. Both groups were followed up for 11 to 18 months with an average of (14.4±2.1) months, and the wounds of all patients healed well. Operation time and incision length of BRATKA group were (132.1±34.6) min and (12.9±1.9) cm, while (94.1±10.8) min and (14.8±2.1) cm in HRATKA group, respectively, and the differences between two groups were statistically significant(P<0.05). There were no significant difference in perioperative total blood loss and preoperative deviation angle of HKAA between two groups(P>0.05). Deviation angle of HKAA, FFC angle and LFC angle in BRATKA group were (1.90±0.91) °, (87.90±1.51) ° and(9.00±3.2) °, respectively;while (0.93±1.04) °, (89.03±0.96) ° and (7.63±0.59) ° in HRATKA group, respectively, and the differences between two groups were statistically significant (P<0.05). There were no significant differences in FTC and LTC between two groups(P>0.05). There were no significant differences in VAS of knee rest and exercise, KSS score and ROM of knee joint between two groups before operation and 3 days and 90 days after operation(P>0.05). There was no significant difference in complications between two groups (P>0.05). Postoperative imaging of two robot systems showed good lower limb force line. The domestic HRATKA group had better LFC, FFC angle and HKA deviation angle than the imported BRATKA group, but there were no significant difference in postoperative knee function and pain relief.

Double-Cut Tibial Plateau Leveling Osteotomy for the Management of Cranial Cruciate Ligament Insufficiency in Dogs with an Excessive Plateau Angle: Early Clinical Results in 16 Dogs.

To describe a modification of the tibial plateau leveling osteotomy technique wherein a double cut is made in the same plane to level the tibial plateau (double-cut tibial plateau leveling osteotomy [DCTPLO]) for treating dogs with cranial cruciate ligament (CrCL) and excessive tibial plateau angle (eTPA) diseases. The DCTPLO technique was performed on 18 stifles in dogs with CrCL and an eTPA (>34°). This study evaluated the accuracy of preoperative planning, feasibility of the technique, postoperative clinical outcomes, radiographic examinations at the postoperative follow-up for the first 120 days, evolution of the tibial plateau angle (TPA), time of union of the osteotomy, apposition of the implants, and possible complications. The described technique proved to be feasible for clinical application, with reproducibility from preoperative planning. An effective reduction in the eTPA levels was observed. The mean preoperative and postoperative TPA values were 39.4° (36°-43.5°) and 6.3° (3°-13°), respectively. Radiographic healing time was 60 days in 17/18 of stifles. Minor complications (not requiring surgical review or clinical treatment) were observed in 4/18 of stifles. The DCTPLO technique was effective for treating CrCL disease with TPA of up to 43.5° in dogs.

THE PLACE OF ACELLULAR COLLAGEN MATRIX IN THE TREATMENT OF CARTILAGE DAMAGE OF THE KNEE JOINT

The collagen matrix has established itself as the standard in the treatment of chondral and osteochondral injuries of the knee joint. Purpose: The application of this surgical technique aims at the restoration and regeneration of the defect with hyaline cartilage, which is the basis for achieving good early and long-term clinical results. Material and Methods: We present 36 patients who are surgically treated with this technique. Patients are divided into two groups according to the etiological principle. Results: Results are defined as good and very good and are comparable to the results of other similar retrospective studies. Conclusions: The method is applicable in selected cases of a traumatic and degenerative nature and is an alternative to early knee arthroplasty.

Extended Half-life Antibodies: A Narrative Review of a New Approach in the Management of Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by intense pruritus and eczematous lesions, significantly impacting physical health and quality of life. The pathogenesis of AD involves genetic predisposition, immune dysregulation, and environmental factors, with a defective skin barrier playing a crucial role. Treatment options for AD include both topical and systemic therapies, with advanced treatments like Janus kinase inhibitors and biologics offering significant improvements but facing limitations in safety and dosing frequency. Extended half-life antibodies represent a promising advancement for the management of immune-mediated inflammatory diseases, including AD. These antibodies, engineered for prolonged circulation and reduced dosing frequency, target key cytokines and immune pathways known to be involved in the pathogenesis of AD, offering potential for less frequent administration while maintaining efficacy. Currently, two such agents are in phase2 trials. APG777, targeting interleukin-13 (IL-13), and IMG-007, targeting OX40 receptor, have shown promising preclinical and early clinical results. They demonstrated prolonged half-lives and the potential for less frequent dosage regimen, along with significant improvements in AD symptoms. These therapies could enhance patient adherence and reduce healthcare burdens by decreasing injection frequencies and clinic visits. As research continues, extended half-life antibodies could significantly improve AD management and patient quality of life. Further studies will determine the long-term safety and efficacy of extended half-life antibodies, with ongoing innovations in antibody engineering likely to broaden their applications and benefits.

Randomized Controlled Trial of a Novel Cementless vs. Cemented Total Knee Arthroplasty: Early Clinical and Radiographic Outcomes.

Previous cementless total knee arthroplasty (TKA) designs faced challenges with insufficient initial fixation on tibial side, resulting in inferior functional outcomes and survival rates. The Zoned Trabecular Bone Cementless Knee is a novel implant designed for cementless TKA which aims to achieve excellent initial fixation, promoting effective osseointegration. The aim of this research was to compare the early clinical and radiographic results of this cementless TKA with cemented TKA. Between September 2021 and April 2022, 64 patients (64 knees) were recruited in this prospective randomized controlled trial to receive either cementless 3D-printed trabecular metal TKA or a cemented posterior stabilized TKA. Preoperative and postoperative clinical evaluations, including the range of motion (ROM), Knee Society Score (KSS), and the Reduced Western Ontario and MacMaster Universities Score (WOMAC), were conducted and analyzed for comparison. Radiographs and computed tomography scans were utilized to assess the initial fixation. The complications between the two groups were also recorded and compared. Continuous data were analyzed for significance using independent-samples t-test or the Mann-Whitney U test and categorical data were analyzed using chi-squared or Fisher's exact test. Both groups demonstrated significant enhancement at 12 months follow-up in the ROM compared with baseline (ROM: 94.7 ± 23.4 vs. 113.1 ± 12.3 in cementless group and 96.5 ± 14.7 vs. 111.0 ± 12.8 in cemented group, p < 0.05). However, no statistical differences were observed between the two groups in postoperative ROM, KSS, or WOMAC score. The radiographs and computed tomography scans showed similar results, including radiolucent lines and osteolysis in either femoral or tibial. Additionally, there was no statistical difference in the overall complication rate between the two groups. Notably, one patient in the cementless TKA group required revision for periprosthetic infection as the end point. This novel 3D-printed trabecular metal cementless TKA achieved comparable clinical outcomes and initial fixation to cemented TKA in early stage. Longer-term examination is necessary to validate these results.

Single versus double percutaneous pinning of pediatric distal radius fractures.

The aim of this study was to compare early clinical and radiographic results of single- versus double-pin fixation of unstable pediatric distal radius fractures. A total of 103 consecutive closed distal radius fractures treated with either single or double percutaneous pinning at a tertiary level I pediatric hospital were analyzed. All patients had open physes and had fractures that failed initial closed reduction and casting. Postoperative fracture displacement was assessed by measuring the difference in angulation of the radius in the anteroposterior and lateral views from intraoperative fluoroscopic images to postoperative radiographs taken on the day of pin removal. Complications were identified from the medical record review. In 103 operative distal radius fractures in 101 patients (70 males, 31 females), 52 and 51 distal radius fractures were treated with single and double pinning, respectively. The median [interquartile range (IQR)] age at the time of surgery was 12.1 (9.0-14.0) years, with the single-pinning group being younger by 1.9 years (P < 0.01). Median (IQR) postoperative angulation in the anteroposterior radiograph (coronal plane) was 2° (1-7°) with one pin versus 1° (0-2°) with two pins (P < 0.01). Median (IQR) postoperative angulation in the lateral radiograph (sagittal plane) was 3° (1-10°) with one pin versus 1° (0-2°) with two pins (P < 0.01). There were no significant differences in complications between the single- and double-pinning groups. Double-pin fixation resulted in a statistically significant, but clinically negligible, reduction in postoperative fracture displacement compared with single-pin fixation. Complication rates were similar in both groups. These findings suggest that either single- or double-pinning techniques can be effective, provided appropriate reduction and postoperative immobilization are achieved.

Engaging Mood Brain Circuits with Psilocybin (EMBRACE): a study protocol for a randomized, placebo-controlled and delayed-start, neuroimaging trial in depression

BackgroundMajor depressive disorder (MDD) is a leading cause of disability worldwide across domains of health and cognition, affecting overall quality of life. Approximately one third of individuals with depression do not fully respond to treatments (e.g., conventional antidepressants, psychotherapy) and alternative strategies are needed. Recent early phase trials suggest psilocybin may be a safe and efficacious intervention with rapid-acting antidepressant properties. Psilocybin is thought to exert therapeutic benefits by altering brain network connectivity and inducing neuroplastic changes that endure for weeks post-treatment. Although early clinical results are encouraging, psilocybin’s acute neurobiological effects on neuroplasticity have not been fully investigated. We aim to examine for the first time how psilocybin acutely (intraday) and subacutely (weeks) alters functional brain networks implicated in depression.MethodsFifty participants diagnosed with MDD or persistent depressive disorder (PDD) will be recruited from a tertiary mood disorders clinic and undergo 1:1 randomization into either an experimental or control arm. Participants will be given either 25 mg psilocybin or 25 mg microcrystalline cellulose (MCC) placebo for the first treatment. Three weeks later, those in the control arm will transition to receiving 25 mg psilocybin. We will investigate whether treatments are associated with changes in arterial spin labelling and blood oxygenation level-dependent contrast neuroimaging assessments at acute and subacute timepoints. Primary outcomes include testing whether psilocybin demonstrates acute changes in (1) cerebral blood flow and (2) functional brain activity in networks associated with mood regulation and depression when compared to placebo, along with changes in MADRS score over time compared to placebo. Secondary outcomes include changes across complementary clinical psychiatric, cognitive, and functional scales from baseline to final follow-up. Serum peripheral neurotrophic and inflammatory biomarkers will be collected at baseline and follow-up to examine relationships with clinical response, and neuroimaging measures.DiscussionThis study will investigate the acute and additive subacute neuroplastic effects of psilocybin on brain networks affected by depression using advanced serial neuroimaging methods. Results will improve our understanding of psilocybin’s antidepressant mechanisms versus placebo response and whether biological measures of brain function can provide early predictors of treatment response.Trial registrationClinicalTrials.gov Identifier: NCT06072898. Registered on 6 October 2023.

Advancements in Gene Therapy and Stem Cell Applications in Interventional Cardiology: A Comprehensive Review

Gene therapy and stem cell applications represent the forefront of innovative treatments in interventional cardiology, offering potential solutions for previously intractable cardiovascular conditions. This review explores the current advancements, mechanisms, and clinical implications of gene therapy and stem cell technologies in the treatment of ischemic heart disease, heart failure, and myocardial infarction. The integration of these modalities into interventional procedures has the potential to revolutionize patient outcomes by promoting myocardial repair, enhancing angiogenesis, and improving cardiac function. Despite promising preclinical and early clinical results, challenges such as delivery methods, immunogenicity, and long-term efficacy remain. This article provides a detailed analysis of the latest research, clinical trials, and future directions in the field, highlighting the transformative potential and obstacles that need to be addressed for widespread clinical adoption.

Silicone Arthroplasty as an Alternative to Arthrodesis in the Metatarsophalangeal Degenerative Disease of Hallux Valgus-A 5-Year Observational Study.

Background: Arthroplasty is gaining more and more popularity in the treatment of osteoarthritis (OA) of the metatarsophalangeal I joint (MTP1). The aim of our study was to evaluate the early and long-term objective clinical and radiographic results, as well as the subjective results, of MTP1 arthroplasty in comparison to MTP1 arthrodesis among patients with OA and a valgus deformity of their MTP 1 joint. Methods: Patients with OA MTP1 were examined before surgery and in the 5-year period after surgery. The inclusion criteria for the study were OA of the MTP1 joint and a non-axial position of the toe in valgus between 20 and 40 degrees. Prostheses were created for the patients with higher demands for mobility of their MTP 1 joint and arthrodesis was carried out for those with lower expectations. The treatment outcomes were assessed by clinical examination, radiography, the AOFAS scale, the SEFAS scale, and using patient-related outcome measures (PROM). Results: A total of 39 people, 37 women and 2 men, aged 55 to 67 years old (average, 61 years old) participated in the study. During the follow-up period, there were no complications in the form of infection or a loosening of the implant after both arthroplasty and arthrodesis. The follow-up examination 60 months after the surgery showed an improvement in scores (>20 points) on both the AOFAS and SEFAS scales. All patients, after surgery, reported reduced pain. Conclusions: The use of a silicone prosthesis in the surgical treatment of degenerative changes in the MTPI joint, with appropriate indications and excluding cases with large hallux valgus, gives better results than arthrodesis.

Chimeric antigen receptor T-cell therapy for T-cell acute lymphoblastic leukemia.

Chimeric antigen receptor (CAR) T-cell therapy is a new and effective treatment for patients with hematologic malignancies. Clinical responses to CAR T cells in leukemia, lymphoma, and multiple myeloma have provided strong evidence of the antitumor activity of these cells. In patients with refractory or relapsed B-cell acute lymphoblastic leukemia (ALL), the infusion of autologous anti-CD19 CAR T cells is rapidly gaining standard-of-care status and might eventually be incorporated into frontline treatment. In T-ALL, however, leukemic cells generally lack surface molecules recognized by established CAR, such as CD19 and CD22. Such deficiency is particularly important, as outcome is dismal for patients with T-ALL that is refractory to standard chemotherapy and/or hematopoietic stem cell transplant. Recently, CAR T-cell technologies directed against T-cell malignancies have been developed and are beginning to be tested clinically. The main technical obstacles stem from the fact that malignant and normal T cells share most surface antigens. Therefore, CAR T cells directed against T-ALL targets might be susceptible to self-elimination during manufacturing and/or have suboptimal activity after infusion. Moreover, removing leukemic cells that might be present in the cell source used for CAR T-cell manufacturing might be problematic. Finally, reconstitution of T cells and natural killer cells after CAR T-cell infusion might be impaired. In this article, we discuss potential targets for CAR T-cell therapy of T-ALL with an emphasis on CD7, and review CAR configurations as well as early clinical results.

Gene-Based Therapy for Brain Cancer: Promises and Challenges

Brain cancer, including gliomas and other malignant tumors, represents a devastating and challenging disease with limited treatment options and poor prognosis. Conventional therapies such as surgery, radiation, and chemotherapy have shown limited success, necessitating the exploration of alternative approaches. Gene-based therapy has emerged as a promising frontier in precision medicine, leveraging our growing understanding of the genetic and molecular drivers underlying brain tumor development and progression. This paper provides an overview of recent advancements in gene-based therapies for brain cancer, including gene editing techniques, gene silencing strategies, Immunotherapy, and more. Notably, these approaches aim to target specific oncogenes, tumor suppressor genes, and immune-related genes to inhibit tumor growth, induce apoptosis, and enhance the patient's immune response against cancer cells. Moreover, gene-based therapies offer the potential for personalized treatments tailored to individual patients based on their unique genetic profile, increasing treatment efficacy and minimizing adverse effects. While gene-based therapies have shown promising preclinical and early clinical results, challenges related to delivery, safety, and off-target effects remain to be addressed. This abstract emphasizes the urgent need for further research and large-scale clinical trials to establish the safety and long-term efficacy of gene-based therapies for brain cancer treatment. As the field continues to evolve, gene-based therapy holds great promise in reshaping the landscape of brain cancer management and providing hope for improved patient outcomes in the future.

Comparison of Novel 3D-printed Stepped Porous Metal Cones and Metaphyseal Sleeves for Reconstruction of Severe Knee Bone Defects: Short-term Clinical Outcomes.

Both porous metal cones and metaphyseal sleeves are excellent implants for reconstructing severe bone defects in the knee joint, but they both exhibit design limitations. The porous metal cone, especially, has significant room for improvement in its shape design. The existing porous metal cones often feature a conical external surface with a relatively small taper, potentially compromising both rotational and axial stability. To improve both axial and rotational stability in porous metal cones, we developed a 3D-printed stepped porous metal cone. This study aimed to assess the short-term clinical outcome of the 3D-printed stepped porous metal cone and to compare it with the clinical outcome of patients who underwent revision total knee arthroplasty (rTKA) with the metaphyseal sleeves during the same period. Patients who underwent total knee arthroplasty revision with metaphyseal bone defect reconstruction from 2019 to 2021 were retrospectively analyzed. A total of 61 patients were enrolled in the study, including 15 patients using 3D-printed stepped porous metal cones and 46 patients using metaphyseal metal sleeves. Thirty patients using metaphyseal sleeves were screened by propensity score matching method and compared with those using stepped cones. Analysis included the American Knee Society Score, the Hospital for Special Surgery knee score, the Western Ontario and McMaster Universities Arthritis index, the Short Form 12 (SF-12) health survey, and radiographic assessment with a mean follow-up of 28.5 ± 8.3 months. To conduct comparative analyses, unpaired Student's t-tests were employed for continuous variables, while categorical variables were analyzed using the appropriate Fisher exact or chi-squared test. In this study, the survival rates of both the stepped cone and metaphyseal sleeve were 100%. There was no statistically significant difference in postoperative knee function scores between the two groups (p > 0.05). However, patients in the cone group had significantly higher mental component summary scores on the SF-12 scale (p < 0.05) and higher increases in mean postoperative physical component summary scores than patients in the sleeve group (p < 0.05). In addition, patients in the cone group experienced fewer intraoperative and postoperative complications compared to the sleeve group. The 3D-printed stepped porous metal cone can effectively reconstruct bone defects in complex rTKA and provide satisfactory early clinical and radiographic results. The 3D-printed stepped cone provides a more stable structure similar to the sleeve while maintaining the original benefits of the cone making it a promising choice for rTKA.

Clinical and Radiographic Outcomes of Anterior Lumbar Interbody Fusions Using a Titanium Cage with a Biomimetic Surface.

We analyzed clinical and radiographic outcomes in patients undergoing anterior lumbar interbody fusions (ALIFs) using a new biomimetic titanium fusion cage (Titan nanoLOCK interbody, Medtronic, Minneapolis, Minnesota, United States). This specialized cage employs precise nanotechnology to stimulate inherent biochemical and cellular osteogenic reactions to the implant, aiming to amplify the rate of fusion. To our knowledge, this is the only study to assess early clinical and radiographic results in ALIFs. We conducted a retrospective review of data for patients who underwent single or multilevel ALIF using this implant between October 2016 and April 2021. Indications for treatment were spondylolisthesis, postlaminectomy syndrome, or spinal deformity. Clinical and radiographic outcome data for these patients were collected and assessed. A total of 84 patients were included. The mean clinical follow-up was 36.6 ± 14 months. At 6 months, solid fusion was seen in 97.6% of patients. At 12 months, solid fusion was seen in 98.8% of patients. Significant improvements were seen in patient-reported outcome measures (PROMs; visual analog scale and Oswestry Disability Index) at 6 and 12 months compared with the preoperative scores (p < 0.001). One patient required reoperation for broken pedicle screws 2 days after the ALIF. None of the patients required readmission within 90 days of surgery. No patients experienced an infection. ALIF using a new titanium interbody fusion implant with a biomimetic surface technology demonstrated high fusion rates (97.6%) as early as 6 months. There was significant improvement in PROMs at 6 and 12 months.

Technology Behind Cell Therapy Augmentation of Fracture Healing: Concentrated Bone Marrow Aspirate.

With an aging population, and an anticipated increase in overall fracture incidence, a sound understanding of bone healing and how technology can optimize this process is crucial. Concentrated bone marrow aspirate (cBMA) is a technology that capitalizes on skeletal stem and progenitor cells (SSPCs) to enhance the regenerative capacity of bone. This overview highlights the science behind cBMA, discusses the role of SSPCs in bone homeostasis and fracture repair, and briefly details the clinical evidence supporting the use of cBMA in fracture healing. Despite promising early clinical results, a lack of standardization in harvest and processing techniques, coupled with patient variability, presents challenges in optimizing the use of cBMA. However, cBMA remains an emerging technology that may certainly play a crucial role in the future of fracture healing augmentation.

Long-term results of arthroscopic capsulolabral revision repair for failed anterior shoulder instability repair using suture anchors at a minimum of 10 years follow-up.

Arthroscopic revision anterior shoulder instability repair has been proposed, and early clinical results have been promising. However, long-term results after this procedure and the probable risk factors for failure have not been sufficiently discussed in the literature. Thirty-eight patients who were diagnosed with recurrent anteroinferior shoulder instability after failed Bankart repair, treated with ACRR between September 1998 and November 2003 and able to be contacted were included. Of these patients, 2 were excluded from the study due to the use of SureTak anchors for fixation, and 5 other patients refused to participate in the study due to lack of interest (3 patients) or lack of time (2 patients). The remaining shoulders were clinically examined at a minimum of ten years after surgery via the ASES, Constant, AAOS, Rowe, Dawson and VAS scores for pain and stability. Degenerative arthropathy was assessed with the modified Samilson-Prieto score. All 31 remaining shoulders were evaluated at a mean time of 11.86 years (142.4 months) after surgery. Six patients (19.35%) reported redisolcation after the revision procedure, 4 of whom were affected by a new significant shoulder trauma. The ROWE and Constant scores improved significantly. Moderate to severe dislocation arthropathy was observed in 19.4% of patients. Five patients (16.2%) were not satisfied with the procedure. Long-term follow-up after ACRR shows predictable results, with a high degree of patient satisfaction, good to excellent patient-reported outcome scores and minimal radiological degenerative changes. However, with an average recurrence rate of 19.3% after 11.86 years, the redislocation rate appears high. With careful patient selection, recurrence rates can be significantly reduced.

Abstract PS05-02: PET Imaging of PARP Expression as a Biomarker of Response to Chemotherapy in Breast Cancer: A Nonrandomized Clinical Trial

Abstract Introduction: Poly–(adenosine diphosphate–ribose) polymerase (PARP) proteins are involved in double-stranded break repair, mediated through homologous recombination (HR) and non-homologous end joining (NHEJ). The majority of PARP activity in this context is attributed to PARP-1 (85-90%). PARP-1 binding to damaged DNA, catalytic activity, and subsequent release to allow access for other DNA repair proteins are necessary for efficient DNA repair. The critical function of PARP-1 in these processes makes this protein a unique potential biomarker of DNA repair capability. [18F]FluorThanatrace ([18F]FTT) is an 18F-labeled PARP inhibitor analog that binds to the same site as approved PARPi drugs. We hypothesized that the biologically relevant form of PARP in untreated breast cancer might provide an indication of functional tumor DNA repair capabilities and therefore predict chemotherapy response. Thus, this study aimed to determine whether a non-invasive quantitative measure of in vivo PARP expression correlated with response to chemotherapy in breast cancer. Methods: A single-arm prospective trial enriched for subjects with triple negative breast cancer (TNBC) was conducted at the University of Pennsylvania from May 2017 to March 2022 (NCT03083288 and NCT03846167). Inclusion criteria were primary breast cancer with tumor diameter of at least 1 cm on conventional imaging and willingness to undergo an [18F]FTT-PET scan prior to neoadjuvant chemotherapy. Participants provided written informed consent. [18F]FTT uptake in breast cancer was measured pre-therapy and tested for association with pathologic complete response (pCR). Subjects were scanned on an Ingenuity TF PET/CT (Philips Healthcare) following injection of [18F]FTT using a 20-minute static acquisition. Peak 1 cm3 average uptake (SUVpeak) were recorded from a spherical region-of-interest (ROI) covering the primary malignancy, guided by CT and prior imaging studies. All SUVs were partial volume corrected and normalized using muscle (NM). A Mann-Whitney test was used to determine if [18F]FTT uptake differed by pCR. Receiver operating characteristic (ROC) curves were constructed to test the performance of [18F]FTT uptake in predicting pCR. Statistical analyses utilized STATA v15.1 with significance based on a two-sided alpha level of ≤0.05. Participants: Twenty-six women with stage I-III breast cancer met inclusion criteria with age range of 29-74 years and self-reported race as Asian (1, 4%), Black (9, 37%) or White (16, 60%). One subject had bilateral tumors (ER+ stage IIA and HER2+ stage I) that were evaluated separately (27 total tumors). Breast tumors were pathologically confirmed and included 6 (22%) ER+/HER2-, 5 (19%) HER2+, and 16 (59%) TNBC. Germline sequencing was available for 21 participants. Results: Mean tumor diameter ranged from 15 to 91 mm (median 30 mm). A considerable range of [18F]FTT uptake was seen across subjects (SUVpeak/NM 0.66-6.5). [18F]FTT uptake was independent of subtype (ER+, HER2+, TN) (P=0.35), stage (P=0.39), and between mutations in genes associated with homologous recombination deficiency (i.e., BRCA1/2, PALB2) and wild-type (P=0.73). In the TNBC cohort, pre-treatment [18F]FTT uptake was higher in subjects who went on to have a pCR (n=16, P=0.05), while a trend toward higher uptake was seen when including all tumor types (n=27, P=0.11). ROC analysis of the value of [18F]FTT uptake for predicting pCR revealed an AUC of 0.79 and showed that a threshold SUV ratio &amp;lt; 2.47 predicted pCR in TNBC patients with a 100% specificity and 64% sensitivity. Conclusions: These early clinical results suggest a relationship between [18F]FTT uptake, a measure of PARP expression, and chemotherapy sensitivity in TNBC, warranting future studies to elucidate underlying mechanistic processes and potential clinical implications. Citation Format: Sarah Gitto, Anthony Young, Ira Bleiweiss, Amy Clark, Elizabeth McDonald. PET Imaging of PARP Expression as a Biomarker of Response to Chemotherapy in Breast Cancer: A Nonrandomized Clinical Trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS05-02.

Early Clinical Results for a New Self-Organizing Hybrid Fabric in Congenital Cardiac Surgery

BackgroundWe have developed a new hybrid warp-knit fabric for induction of in situ tissue regeneration that has shown appropriate antideterioration properties and expandability in preclinical studies. This study was performed to assess the clinical efficacy and safety of this fabric in the early postoperative period after congenital cardiac surgery. MethodsThe fabric comprises biodegradable (complete degradation period, 2-3 years) and nonbiodegradable yarns coated with cross-linked gelatin. A multicenter single-arm 3-year study was conducted. The primary end point for regulatory approval was the surgical success rate without death or reintervention related to fabric failure at 1 year after surgery. Secondary end points included the incidence of material-related secondary lesions. ResultsThe fabric was implanted at 41 sites (pulmonary artery, n = 18; right ventricular outflow tract, n = 12; atrial septum, n = 7; and ventricular septum, n = 4) in 34 patients of median age 1 year 11 months (range, 4 months-58 years). The surgical success rate was 100%. There were no abnormal findings for the fabric on echocardiography and no serious adverse events in a median follow-up period of 40 months (range, 36-55 months), other than 3 stenotic lesions that were due to the surgical procedure. These results permitted regulatory approval for use of the fabric in Japan. ConclusionsThe new fabric promoting tissue self-organization through a novel technology showed acceptable efficacy and safety in the early postoperative period after congenital cardiac surgery.

Early Clinical Results From the Japanese Prospective Multicenter Study to Evaluate Zenith Alpha Abdominal Stent Graft for Abdominal Aortic Aneurysm (JUSTICE) Registry Demonstrate Acceptable Limb Patency at 12 Months.

Recent reports of the Zenith Alpha abdominal endovascular graft (Zenith Alpha AAA, Cook, Inc., Bloomington, Indiana) have demonstrated an unexpectedly high incidence of limb graft occlusion (LGO). The purpose of this study was to prospectively evaluate the performance of the Zenith AAA in Japan, with a specific focus on LGO. All endovascular aneurysm repairs (EVARs) for abdominal aortic aneurysms performed using the Zenith Alpha AAA from July 2020 to October 2021 in 23 Japanese hospitals were prospectively evaluated. All computed tomographic images were analyzed in the core laboratory. Late complications were defined as any aneurysm-related events occurring >30 days after EVAR, including aneurysm sac enlargement of >5 mm and any reinterventions performed. Endoleaks without sac enlargement or reintervention were excluded as late complications. During the study period, 147 EVARs were performed using the Zenith Alpha AAA. The mean patient age was 76.5±7.7 years, 84.4% of patients were male, and the mean aneurysm diameter was 52.4±9.2 mm. Instruction-for-use violations were observed in 76 patients (51.7%), primarily associated with a severely angulated proximal neck (>60°). There were six intraoperative complications and 62 additional intraoperative treatments reported, most of which involved preemptive coil embolization of the inferior mesenteric artery (37 cases). Technical success, defined as the absence of type 1 or 3 endoleaks on final angiography, was achieved in 99.3% of patients. At 12 months, there was only one case of type 1/3 endoleak (0.8%) and one aneurysm sac enlargement exceeding 5 mm (0.8%); however, a high incidence of type 2 endoleaks was observed in 35.2% of patients, and aneurysm sac regression exceeding 5 mm was achieved in 30.1% of patients. Nine late complications were observed, and the rate of freedom from late complications at 12 months was 93.5%, encompassing four LGOs and one limb graft stenosis (3.4%). In contrast to recent reports, our Japanese multicenter prospective study demonstrated satisfactory early clinical results, including an acceptable LGO rate, for the low-profile Zenith Alpha AAA. Long-term follow-ups will be performed to confirm the persistence of these outcomes. This study prospectively evaluated the performance of 147 Zenith Alpha AAAs used for endovascular aneurysm repair with core-lab adjudication focusing especially on limb graft occlusion (LGO). At 12 months, aneurysm sac regression exceeding 5 mm was achieved in 30.1% of patients, and there was only one type 1/3 endoleak, one aneurysm sac enlargement (>5 mm), and nine late complications including five LGOs (3.4%), resulting in rate of freedom from late complications at 93.5%. Satisfactory early clinical results, including an acceptable rate of LGO can be achieved, particularly with cautious usage of the Zenith Alpha Spiral-Z Endovascular Leg." 5mm), and nine late complications including five LGOs (3.4%), resulting in rate of freedom from late complications at 93.5%. Satisfactory early clinical results, including an acceptable rate of LGO can be achieved, particularly with cautious usage of the Zenith Alpha Spiral-Z Endovascular Leg.