Viable Tissue Research Articles

The distally anchored connective tissue graft platform for papilla enhancement: A case report

AbstractBackgroundAs the need for using dental implants to replace single missing teeth grows, so does the demand for greater esthetic results. However, achieving complete interproximal papillae fill in single‐tooth implant restorations remains a challenge. The distally anchored connective tissue platform is a novel soft tissue augmentation technique that consists of harvesting an autogenous connective tissue graft from the palate, folding it, and positioning it at the level of the distal occlusal and buccal surfaces with the help of a distal sling suture to the adjacent distal tooth.MethodsThis case report describes how a maxillary central incisor with compromised hard and soft tissues were replaced using a comprehensive treatment plan.ResultsThe clinical outcomes showed stable mucosal margin levels and complete papillae fill. The patient expressed satisfaction with the achieved results.ConclusionsThe distally anchored connective tissue graft platform performed at the time of implant placement emerges as a viable and effective soft tissue augmentation technique that yields highly esthetic results.Key pointsWhy is this case new information? To the best of our knowledge, this is the first case report in the literature using the distally anchored connective tissue platform. What are the keys to successful management of this case? Adequate diagnosis and decision‐making, resulting in a treatment plan focused on reconstructing both soft and hard tissues in a single‐tooth implant within the esthetic area, yield favorable clinical, radiological, and patient‐reported outcomes. What are the primary limitations to success in this case? The primary limitation of this study is its reliance on a single case report.

3D-printed tool for creating standardized burn wounds in ex vivo skin tissues

IntroductionThe development of biomaterials and medical devices for burn wound treatment necessitates thorough investigation through in vitro/ex vivo models before transitioning to animal studies. Establishing a standardized and high-throughput burn wound model in ex vivo skin presents a considerable challenge. Our objective was to address this challenge by developing a practical and cost-effective 3D-printed burn wound tool capable of uniformly inducing burns in 12 skin samples simultaneously. Material and methodsUtilizing Autodesk Inventor software, we designed a 3D model comprising a plate-base component (PBC) and a rod-base component (RBC). The design was exported as a Standard Triangulation Language (STL) file, processed through "Slicer" software to generate a G-code file tailored for 3D printing. ResultsThe Rod-Base component underwent iterative design modifications to optimize weight, airflow, and material consumption, resulting in a final design featuring a unique star shape for enhanced airflow. Simultaneously, the Plate-Base component design evolved to enable easy and secure plate placement, demonstrating compatibility with 12-well plates. The average production time for the model was 14.5 h, with a production cost of approximately $20 (USD), covering printing material and steel rods. ConclusionIn conclusion, this study provides valuable insights into the required equipment and software, empowering researchers to efficiently produce their accurate and cost-effective 3D-printed tool for controlled and reproducible burn wound creation in ex vivo viable skin tissues.

Ex vivo assessment of cellular mass response for personalized therapy selection of hyperthermic intraperitoneal chemotherapy (HIPEC) agents.

3132 Background: Despite progress in the development of HIPEC protocols for the treatment of peritoneal carcinomatosis, agent selection remains largely empiric with few biomarkers for guiding treatment. Ex vivo assessment of drug response using single-cell mass measurements offers a promising option for therapy selection. Previously, we have shown that mass response testing (MRT) is a malignancy- and drug-agnostic means of assessing drug response (1) and can predict a patient’s clinical response to therapy in a range of solid and hematological malignancies (2). Methods: Tissue specimens were collected from patients with peritoneal carcinomatosis as part of an ancillary study for a HIPEC clinical trial (NCT04847063) to explore the feasibility of performing MRT with these specimen types. Briefly, after overnight shipment of viable tumor tissue, tumor cells were isolated and treated with various therapies ex vivo. Single-cell mass distributions of vehicle and drug-treated populations were compared to determine the functional activity of each agent. Results: MRT was attempted for 60 patients with metastatic disease, 10 of whom had peritoneal carcinomatosis and ultimately received HIPEC. The HIPEC cases included histologies such as peritoneal mesothelioma (n=4), colorectal cancer (n=3), ovarian cancer (n=2), and small bowel adenocarcinoma (n=1). In total, 8 out of 10 peritoneal specimens had a sufficiently high tumor cell count, viability, and purity to perform MRT. These specimens displayed clear and statistically distinguishable mass response patterns of response and non-response to several different agents commonly used for HIPEC treatment such as cisplatin, oxaliplatin, doxorubicin, and mitomycin C. Study design:These feasibility results serve as the foundational data for launching a single-site phase II interventional study at the NCI’s Center for Cancer Research. The study will evaluate the potential benefit of personalized treatment regimens determined by MRT for patients with peritoneal carcinomatosis, particularly mesothelioma, a context where therapeutic options have relative equipoise in clinical efficacy. Tumor biopsies will be obtained via laparoscopy prior to HIPEC and submitted to a CLIA-certified lab for MRT to assess the responses of various clinically acceptable agents. The HIPEC regimen will be selected based on these MRT results returned within two days of sample collection. Enrolled patients will then undergo cytoreduction and HIPEC, and progression-free and overall survival will be monitored. As a single-arm, non-randomized trial, patient responses will be compared with a matched synthetic control to assess the impact of MRT on efficacy of HIPEC regimens. Conclusions: MRT is feasible for peritoneal carcinomatosis tissues, with future studies focusing on its role in guiding HIPEC treatment. 1. Nat Comm Bio,2022. 2. JCO PO, 2024. Clinical trial information: NCT04847063 .

Computed tomography as a predictive tool for ventricular tachycardia

Abstract Background Sudden cardiac death is the main cause of mortality worldwide. It is often linked with ventricular tachycardia (VT). To prevent VT, high-risk patients are typically equipped with intracardiac defibrillators (ICDs). Currently, left ventricular ejection fraction (LVEF) is the standard for determining a patient's risk level. Objective We hypothesized that the use of imaging software analyzing cardiac CT-scans could enhance the detection of patients with an increased risk of VT. Methods and Results In this study, 132 patients with ischemic cardiomyopathy (average age 66.2±11.4 years, with an average LVEF of 36.6±10.3%), all with implanted cardiac devices, underwent CT scans. We developed software to automatically analyze the heart's wall tissue thickness, cardiac fat, and calcification levels (Figure.1.A). A viable cardiac wall thickness of less than 3mm typically indicates a ventricular wall predominantly composed of scar tissue with minimal viable tissue remaining. In contrast, a viable wall thickness of less than 5mm includes regions with more viable tissue and therfore represents the total scar. Over an average follow-up of 6.6 years (79.8 ± 30.5 months) via live telemedicine, we observed that patients with VT had a significant difference in wall thickness ratio (3mm/5mm; no VT 0.31±0.18 vs, VT 0.44±0.18, p<0.01)) and higher calcification (0.10±0.38ml vs. 0.47±1.57ml, p=0.039). The amount of cardiac fat did not significantly differ between the no VT and VT groups (1.14±1.38ml vs.1.21±1.01ml, p=0.771). Logistic regression determined a critical cutoff for wall thickness at a ratio of 0.3 for 3mm and 5mm thickness. Kaplan Meyer analysis contrasted this wall thickness ratio of 0.3 (figure.1.B) against the established LVEF threshold of 35% (figure.1.C) for predicting VT-free survival, revealing a notable disparity favoring wall thickness ratio (p<0.01) over LVEF (p=0.77). Conclusions The findings suggest that a higher proportion of regions of thin viable tissue or dense scar in the total scar is a more effective predictor of VT-free survival than LVEF, potentially improving the identification of patients at risk for sudden cardiac death.Figure. 1

Cardiac magnetic resonance - aided ventricular tachycardia substrate ablation

Abstract Objectives To assess feasibility and reliability of Cardiac magnetic resonance (CMR)-derived pixel signal intensity (PSI) maps obtained by Three Dimensional (3D)- Late Gadolinium Enhancement (LGE) images for detecting potential targets for VT substrate ablation procedures. Background Parametric imaging with color-coded PSI maps obtained from pre-ablation 3D LGE -CMR imaging can be used for identification and characterization of arrhythmic abnormal substrate. Recent publications have shown that PSI maps permit visualization of border zone areas inside the scar. Specifically, corridors of viable tissue within the scar connecting healthy myocardium define VT corridors that may be the electrical equivalent of the abnormal conducting channels on the electroanatomical mapping (EAM). Methods 8 patients with scar-dependent monomorphic VTs who underwent 3D-LGE CMR imaging prior to substrate ablation were included in the study. The studies were performed at 1.5T scanner. We obtained two data sets of 3D whole heart LGE imaging with high resolution. Patients underwent two acquisitions: the conventional respiratory navigated, electrocardiographically-gated 3D fast gradient echo (1.3slice thickness, 256x256 matrix acquisition) and the image-navigated isotropic high resolution 3D GE with Dixon water-fat separation. 3D LGE-CMR images were processed with ADAS-VT software to produce a 3-dimensional model of the heart with 10 layers from the endocardium to epicardium and PSI maps color-coded from the LGE data projected to each of the shells (Figure 1). In the LGE-CMR PSI maps, VT corridors were obtained automatically by the ADAS VT software. Subsequently, data were given to the electrophysiologists and merged with the CARTO3 system EAM data obtained for the ablation (Figure2). CMR information was used to facilitate the identification of target ablation sites in the areas identified by CMR as abnormal substrate and radiofrequency was applied in the presence of both a pathological electrogram (EGM) and a VT corridor as identified by CMR. Results There was a 95% agreement between the abnormal conducting channels as detected by abnormal electrograms in the EAM and the VT corridors identified by 3D LGE CMR imaging. In two occasions, there was one VT corridor that did not correlate with abnormal electrograms and was not ablated. The two 3D LGE sequences used for ADAS-VT corridors analysis showed complete agreement in the number and location of VT corridors. Mean acquisition time for 3D LGE imaging was 11±4minutes for the conventional fast gradient echo sequence, and 5±2minutes for the novel 3D self-image navigated LGE sequence. The image quality of 3D LGE was superior with the Dixon fat-water separation. Overall CMR-aided VT ablation reduced the procedural and fluoroscopy time by 40%. Conclusions CMR-aided VT ablation is feasible, reliable and significantly reduces the procedural time.

Abstract PO2-18-07: Ultrasound – guided Interstitial Laser therapy for Stage I Breast Cancer: a phase 2 trial

Abstract Background: Screening programs are changing the scope of breast cancer, with a growing number of patients diagnosed at a nearly stage. The current standard treatment (breast conservation and radiation therapy) offers an excellent prognosis for these patients. Besides tumor removal, other techniques can be used to destroy a mass in place. A range of minimally invasive techniques holds promise on local breast tumor ablation (i.e. thermotherapy, cryotherapy, and irreversible electroporation). Previous studies with Interstitial laser thermotherapy (ILT) for breast cancer report mean ablation rates between 33% to 87%. Most common cited causes for failure are equivocal tumor size estimation, inadequate technique and the learning curve. Objective: Improve the ILT technique and achieve better ablation rates through the evaluated procedure. Methods: A prospective study with 15 patients with Stage I invasive breast cancer, presented as a unique lesion as inclusion criteria was conducted. MRI and US were used to estimate the primary tumor volume and rule out multicentric/multifocal disease. ILT ablation was performed using an Echolaser unit (Elesta) through percutaneous laser optical fibers with a US-guided insertion in the lesion center. All procedures were performed under local anesthesia and sedation. The post procedure image reevaluation included an immediate US after the ablation and a new MRI about 3 hours after the procedure. The definitive proposed surgical treatment was carried out 8-13 days after the ILT ablation. Results: Eighteen patients were included in the study, of whom 14 (with 15 lesions) completed the protocol. The mean tumor size measured by MRI was 13.7 (4-20) mm. The mean treatment time was 10.1 minutes and all patients went home the same day, reporting only mild (78%) or moderate (22%) pain, controlled with analgesics. The mean ablation index, evaluated by H&E and CK8/18, was 61,5% (0 -93%) and when only tumors under 15 mm were considered the mean ablation index was 75% (30%-93%). The MRI performed after ablation procedure showed a large area of edema around the clip in all cases. The sensitivity and specificity to detect residual tumors were 1.0 and 0.84, respectively, when the residual tumors were larger than 15% of the original tumor size . Conclusions: These preliminary results suggest that laser therapy can eliminate viable neoplastic tissue in vivo. To achieve better results, standardization in patient selection, power and energy applied, should be considered. There are several advantages of ILT for breast cancer treatment, including preserving the structure and function of breast, no bleeding, no scaring and no radiation. More studies refining the technique should be conducted to allow the implementation of ILT as an alternative to surgical treatment in early breast cancer. Citation Format: Danielle Matsumoto, Silvio Bromberg, Marcus Corpa, Rodrigo Garcia, Guilherme Mariotti, Monica Rudner, Angela Waitzberg, Afonso Nazário, Gil Facina. Ultrasound – guided Interstitial Laser therapy for Stage I Breast Cancer: a phase 2 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 PO2-18-07.

Utilizing Low-cost Vacuum-assisted Closure as Adjuvant Therapy in Soft Tissue Reconstruction for a Mangled Upper Extremity

Summary: Soft tissue reconstruction using flaps in managing mangled injuries is occasionally insufficient due to large defects and low flap viability. Conversely, delaying the closure of the defect can elevate the risk of infection. Adjuvant therapy becomes essential in the management of mangled injuries. We aim to present the use of low-cost vacuum-assisted closure (VAC) as an adjuvant therapy for mangled injuries. We reported the case of a 20-year-old man who sustained a mangled injury to his left forearm in a traffic accident 4 hours before admission. The mangled extremity severity score was 9; however, the patient declined amputation. Although the initial reconstruction was done, the flap could only cover vital structures. VAC was utilized to address the uncovered portion of the defect, to promote optimal granulation and prevent infection. The reconstruction proceeded with a skin graft and wrist arthrodesis. At 1-year follow-up, viable tissue was obtained but contracture occurred at the metacarpophalangeal and proximal interphalangeal joints. We intend to perform functional reconstruction at a later stage. Although the benefits of VAC in wound management are well established, reports regarding its advantages in mangled injury management remain relatively scarce. The high cost of VAC is a limiting factor, particularly in developing countries. This prompts the need for an affordable VAC innovation with comparable efficiency to the commercial model. Reverse Aqua Pump VAC, our innovative low-cost VAC, shows satisfactory outcomes in managing patients with mangled injuries with mangled extremity severity score indicating amputation.

Current aspects of the treatment of combat surgical trauma

Objective. The history of providing assistance to victims with gunshot wounds dates back more than one century, but nevertheless surgical treatment of gunshot wounds is still relevant to this day. High-quality primary surgical treatment of a gunshot wound is the key to a speedy recovery of the patient (N.I. Pirogov). The pathogenesis of gunshot wounds determines the specific tactics of surgical treatment. Gunshot wounds are zonal in nature. According to the results of morphological studies, it can be concluded that a significant part of the changes in the zone of molecular concussion of the wound canal are reversible, and the complexity of pathogenesis and the lack of reliable criteria for assessing the condition of tissues does not exclude the possibility of leaving areas with reduced viability in the wound after treatment. For maximum effect during surgical treatment of gunshot wounds, non-viable tissues should be removed with minimal damage to viable ones. To meet these requirements, it is often impossible to visually assess the boundary between damaged and parabiotic tissues objectively intraoperatively. The use of modern physical methods of wound wrapping and preparing them for plastic closure, such as low-frequency ultrasound, hydrosurgical methods and VAC therapy allows you to radically clean the wound surface with minimal damage to viable tissues and perform plastic closure operations on soft tissue defects at an early date.Purpose of a study: to improve the methods of primary surgical treatment in patients with combat surgical trauma using low-frequency ultrasound.Material and methods. Our study is based on the analysis of the treatment results of 93 patients aged 10 and 70 years old. All patients had combat surgical trauma of various etiology and localization. Of these, 36 (38.7%) patients in main group underwent ultrasound cavitation of the wound canal and wound defects during primary surgical treatment (PST), followed by primary or primary delayed plastic surgery within a period not exceeding 48 hours after PST. Methods of plastic wound closure were both flaps with axial circulation and autodermotransplantation. In the remaining 57 (61.3%) patients of comparison group, primary surgical treatment was not performed, or was performed at the stages of evacuation, with further conservative treatment. Upon admission to the clinic, he underwent secondary surgical treatment, opening of purulent lumps, as well as staged necrectomies, while wound plastic surgery was performed after wound cleansing and was mainly represented by autodermotransplantation.Results. It was revealed that in the main group, the treatment time of patients in the main group was reduced by 2 times compared with the comparison group (16.3 and 34.2 bed days, respectively). The effectiveness of engraftment of autodermotransplants was evaluated according to V.I. Petrov's scheme. Lysis of autodermotransplants was noted 1.9 times less frequently in the main study group. It was also noted that there were no purulent complications in main group, unlike comparison group – 20.6%, the number of marginal necrosis was 2.6% in main group and 22.4% – in comparison group, lysis of autodermotransplanates in main group was 7.8%, in comparison group – 13.8%.Conclusion. This study allows us to conclude that the advantage of using ultrasonic cavitation during the usual surgical treatment of gunshot wounds followed by primary or primary delayed plastic surgery.

Effects of early debridement and conservative eschar removal followed by wound coverage with acellular dermal matrix in the treatment of children with deep burns

Effects of early debridement and conservative eschar removal followed by wound coverage with acellular dermal matrix in the treatment of children with deep burns

Efficacy of mesenchymal stem cells cultured low oxygen tension ameliorates apoptotic inhibitors, viability, and differentiation of ovarian tissue: A study in a rat model with ovarian failure

Background In cases of ovarian failure due to malnutrition, stem cell therapy is ineffective due to the lack of viability and differentiation of transplanted cells, resulting in low adaptation and survival rates. This study aimed to investigate whether stem cells cultured under low oxygen (O2) tension improve the adaptability and viability of cells in rats with ovarian failure. Methods After four days of culturing mesenchymal stem cells (MSCs) in 21% oxygen (normoxia) as the T2 group and 1% oxygen (low O2 or hypoxia) as the T1 group, 200 million bone marrow-derived MSCs per rat were transplanted into female rats with ovarian failure (15 rats per treatment group). A total of 15 fertile and 15 infertile rats were categorized as the C+ and C− groups, respectively. Results The slight increase gradually in cells expressing HSP70, VEGF-1, and GDF-9 was reported in C+, T2, T1, and C− groups, respectively. Caspase-3 expression was reported to decrease gradually in C+, T2, T1, and C− groups. Meanwhile, Graafian follicle count was reported to increase gradually in C+, T2, T1, and C− groups, respectively. Conclusions Based on those parameters, MSCs cultured under low O2 tension were more effective than those cultured under normoxic conditions as a treatment for female rats with ovarian failure.

Unraveling a rare medical anomaly: a case report on the incidental discovery of a mixed fungal ball with parasitic elements

Fungal ball is a type of fungal rhinosinusitis (FRS) that is chronic, non-invasive, and extramucosal. A fungal ball is a non-invasive accumulation of dense conglomeration of fungal hyphae in one sinus cavity Sinonasal fungal ball is known to be the most common form of fungal sinusiti. It typically affects immunocompetent individuals and appears as a unilateral lesion between the fourth and sixth decades of life. The most commonly involved sinus is the maxillary sinus. Patients are often asymptomatic, but some patients develop chronic mucopurulent rhinorrhea. Treatment is surgical, with removal of the fungal contents of the involved sinus, and no subsequent treatment is indicated, given the process is noninvasive. Here in we report the case of a 64-year-old gentleman diagnosed with fungal ball of maxillary sinus. Patient was asymptomatic and the fungal ball was identified as an incidental finding on imaging for stroke. The histopathological examination necrotizing lesion showing entangled septate, aseptate and pigmented fungal structures and non-viable parasitic structures noted. No viable tissue was seen.

Abstract 5474: Biorepository yields potential for personalized medicine approach in pediatric brain cancer patients

Abstract Childhood brain cancer, with a 12% mortality rate, stands as the most lethal cancer among children. Out of the annual 4,000 diagnoses, 30% involve low-grade gliomas, with a troubling 10% progressing to lethal high-grade gliomas within 2 years. While surgery can often cure the remaining 90%, 50% necessitate adjuvant therapies like chemotherapy and molecular targeting, with radiation sparingly used. Alarmingly, 66% of survivors grapple with long-term health, mental, and cognitive issues due to treatment toxicity, emphasizing the urgent need for innovative biological therapies in pediatric glioma treatment.Our proposed strategy involves the acute analysis of freshly discarded tissue from brain cancer craniotomies, departing from the use of FFPE-preserved tissue, which may exhibit suboptimal quality. All patients provided informed consent, and by prospectively preserving viable tissue, we enable its utilization in ten or more subsequent analyses. These encompass cell-culture-based assays, viability assays, bulk, single cell, and single nucleus RNA sequencing, DNA sequencing, single-cell proteome analyses, flow cytometry, and immunofluorescence.Our findings highlight a direct correlation between surgical sample size and analysis feasibility. Bulk RNA sequencing proves valuable in acutely isolated surgical tissue and cryostored or flash-frozen tissue for identifying novel therapeutic targets in individual patients. Viable cells retrieved from cryopreserved tissue of the same patient allow ex vivo functional validation of therapeutic targets, eliminating the need for establishing patient-derived cell lines and xenografts, particularly challenging for low-grade gliomas. These findings establish the feasibility of a personalized bedside-to-bench approach, contingent on an adequate supply of surgical material.Expanding this approach to encompass all childhood brain cancer types, we plan to investigate using our comprehensive biorepository, housing viable tissue and single-cell suspensions from 122 childhood brain cancer patients. Among these, 51 cases yielded tissue for single-cell RNA-seq and viable cryoprotection. The most common tumor histology identified was low-grade glioma (32), primarily pilocytic astrocytoma (19), followed by embryonal (12) and ependymal tumors (4).In summary, we developed a standard operating procedure for analyzing fresh and cryopreserved surgical discards, identifying novel targets in childhood brain cancer tissue, and functionally validating them in patient-matched samples. This personalized medicine approach holds promise in circumventing the tedious development of patient-derived models. Citation Format: Anna Pronina, Emon Nasajpour, Caitlynn Tran, Troy Schouten, Eden Gibson, Jeffrey Nirschl, Laura Marie Prolo, Kelly Mahaney, Hannes Vogel, Claudia Katharina Petritsch. Biorepository yields potential for personalized medicine approach in pediatric brain cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5474.

Abstract 7550: KB-0742, an oral highly selective CDK9 inhibitor, demonstrates preclinical activity in transcription factor fusion driven adenoid cystic carcinoma patient-derived models

Abstract Adenoid Cystic Carcinoma (ACC) is an aggressive rare type of cancer of the secretory glands with no approved targeted therapy and high unmet clinical need. Deregulated transcription driven by MYB-NFIB or MYBL1-NFIB transcription factor (TF) fusions are a hallmark of ACC pathogenesis. More aggressive disease and resistance to therapy has been associated with co-mutation in NOTCH. Although direct targeting of oncogenic TF fusions has remained challenging, targeting of their activity via transcriptional cofactors has emerged as an attractive and clinically actionable strategy. Cyclin-dependent kinase 9 (CDK9) is a key potentiator of TF activity via its ability to act both as an upstream regulator of TF expression and a downstream cofactor. KB-0742 is a potent, selective, and orally bioavailable inhibitor of CDK9 with a long plasma half-life. KB-0742 is being studied in an ongoing Phase 1/2 study (NCT04718675) in advanced solid tumors including ACC. KB-0742 has demonstrated on-mechanism, single agent anti-tumor activity and a manageable safety profile in heavily pre-treated patients (0-11 prior lines of therapy) with transcriptionally addicted solid tumors. Here we present the preclinical rationale for targeting of oncogenic fusion TF activity in ACC. XenoSTART Patient-Derived Xenograft (XPDX) models were established from viable human tumor tissue for in vivo and ex vivo testing. Cell viability was assessed by CellTiter GLO reagent and phase imaging. Changes in MYB-fusion transcripts were assessed by RNA-Seq. Tumor Fragments (~70 mg) from ACCx5M1, ACCx6, ACCx9, ACCx11 models were implanted into athymic nude mice. Animals were treated with either vehicle (normal saline) or 60 mg/kg KB-0742 on a Q3D/week until tumors reached 2500 mm3 or up to 60 days post start of treatment. In a retrospective analysis using real world data, ACC has a low incidence of genomic instability and high rates of MYB fusions detectable by RNA-seq, making immunotherapy challenging but creating an opportunity for targeting MYB transcription. In primary MYB-fusion positive and NOTCH co-mutated patient-derived spheroid models, KB-0742 treatment induced strong antiproliferative activity and cytotoxicity. Importantly, KB-0742 demonstrated stronger cytotoxic effects when compared to historical control agents. In XPDXs, CDK9 inhibition with KB-0742 resulted in antiproliferative activity and stronger tumor growth inhibition in MYB-fusion positive and NOTCH co-mutated tumor models compared to MYB-fusion positive only models.These data demonstrate KB-0742 is effective in preclinical models of ACC suggesting KB-0742 may be a promising therapeutic option for ACC patients. KB-0742 is currently being evaluated in a phase 1/2 dose-escalation and cohort expansion trial in patients with ACC and other transcriptionally addicted tumors (NCT04718675). Citation Format: Michael R. McKeown, Luis A. Carvajal, Tressa R. Hood, Nicole S. Burr, Jeffrey Kaufman, Adam Boynton, Kameron Mori, Tessa DesRochers, Michael Wick, Charles Y. Lin, Jorge F. DiMartino. KB-0742, an oral highly selective CDK9 inhibitor, demonstrates preclinical activity in transcription factor fusion driven adenoid cystic carcinoma patient-derived models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7550.

Sinonasal Tumors Masquerading as Invasive Fungal Sinusitis (IFS).

Fungal tissue invasion in the setting of sinonasal malignancy has been rarely described in the literature. Only a handful of studies have discussed cases of suspected chronic and acute IFS (CIFS and AIFS, respectively), having an underlying undifferentiated sinonasal carcinoma, sinonasal teratocarcinosarcoma, and NK/T-cell lymphoma. Here, we describe 3 cases of carcinoma mimicking IFS from a single institution. Each of our patients presented with sinonasal complaints as an outpatient in the setting of immunosuppression. Intranasal biopsies consistently were predominated by necrotic debris, with and without fungal elements, ultimately leading to a delay of oncologic care. The final pathologies included NK/T-cell lymphoma and SNEC. All patients were followed by radiation and chemotherapy, with 1 case of mortality. We aim to emphasize the importance of obtaining viable tissue as pathology specimens as the presence of necrosis with fungal elements may limit the diagnosis and ultimately delay the care of an underlying sinonasal carcinoma.

Long-Term Outcomes of Ascending Sliding Arch Aortoplasty.

Background: Coarctation of the aorta can be associated with significant hypoplasia of the aortic arch. In contrast to patch aortoplasty, ascending sliding arch aortoplasty uses viable autologous tissue for potential growth in children. We reviewed the mid- to long-term outcomes of this technique. Methods: Between 2002 and 2023, 28 patients underwent ascending sliding arch aortoplasty for the patients with coarctation of the aorta (n = 22) and interrupted aortic arch (n = 2). Four patients underwent previous surgical coarctation repair at other institutions. The median patient age and body weight were 28.5 months (3 weeks to 15.6 years) and 13.4 kg (3.7-70 kg), respectively. Results: Although one patient had a recurrent nerve injury postoperatively, there were no other major morbidities or mortalities. The last follow-up echocardiography demonstrated that the mean peak velocity improved from 3.9 ± 0.6 to 0.9 ± 0.8 m/s, and the pressure gradient improved from 63.6 ± 21.5 to 7.1 ± 7.7 mm Hg. The postoperative diameters of the ascending aorta, proximal arch, distal arch, and isthmus all increased significantly. The mean postoperative length of stay was 5.9 ± 2.1 days, and the median follow-up time was 7.3 years (10 days to 20.5 years). No reoperation or catheterization-based intervention was performed for residual coarctation. Conclusions: Ascending sliding arch aortoplasty is safe and effective for treating coarctation of the aorta with aortic arch hypoplasia. This technique is applicable for children ranging in size from neonates to older children (or adolescents), recurrent coarctation cases, and provides complete relief of narrowing by utilizing viable native aortic tissue.

Femtosecond Laser Cutting of Human Crystalline Lens Capsule and Decellularization for Corneal Endothelial Bioengineering.

The bioengineering of corneal endothelial grafts consists of seeding in vitro cultured corneal endothelial cells onto a thin, transparent, biocompatible, and sufficiently robust carrier which can withstand surgical manipulations. This is one of the most realistic alternatives to donor corneas, which are in chronic global shortage. The anterior capsule of the crystalline lens has already been identified as one of the best possible carriers, but its challenging manual preparation has limited its use. In this study, we describe a femtosecond laser cutting process of the anterior capsule of whole lenses in order to obtain capsule discs of 8 mm diameter, similar to conventional endothelial grafts. Circular marks made on the periphery of the disc indicate its orientation. Immersion in water for 3 days is sufficient to completely remove the lens epithelial cells and to enable the seeding of corneal endothelial cells, which remain viable after 27 days of culture. Therefore, this method provides a transparent, decellularized disc ready to form viable tissue engineered endothelial grafts.

Melanocortin Derivatives Induced Vascularization and Neuroglial Proliferation in the Rat Brain under Conditions of Cerebral Ischemia.

Stroke remains the second leading cause of death worldwide. The development of new therapeutic agents focused on restoring vascular function and neuroprotection of viable tissues is required. In this study the neuroprotective activity of melanocortin-like ACTH(4-7)PGP and ACTH(6-9)PGP peptides was investigated in rat brain at 24 h after transient middle cerebral artery occlusion (tMCAO). The severity of ischemic damage, changes in the proliferative activity of neuroglial cells and vascularization of rat brain tissue were analyzed. The administration of peptides resulted in a significant increase in the volume density of neurons in the perifocal zone of infarction compared to rats subjected to ischemia and receiving saline. Immunohistochemical analysis of the proliferative activity of neuroglia cells using PCNA antibodies showed a significant increase in the number of proliferating cells in the penumbra and in the intact cerebral cortex of rats receiving peptide treatment. The effect of peptides on vascularization was examined using CD31 antibodies under tMCAO conditions, revealing a significant increase in the volume density of vessels and their sizes in the penumbra after administration of ACTH(4-7)PGP and ACTH(6-9)PGP. These findings confirm the neuroprotective effect of peptides due to the activation of neuroglia proliferation and the enhancement of collateral blood flow.

(159) Factors and Management Strategies for Addressing Reduced Glans Engorgement Following Inflatable Penile Prosthesis: A Scoping Review

Abstract Introduction Inflatable penile prosthesis (IPP) provides a reliable stiffness along the length of the penile shaft, yet patients may express dissatisfaction as it may still differ from their recollection of their previously normal erections. A common complaint is reduced engorgement of the glans penis, which can manifest as subjective reduction in penile length or the feeling of a cold insensitive glans. Patient factors often ensure a sound justification for this complaint, namely vasculogenic erectile dysfunction (ED) or their corporo-glandular morphology despite a well-sized and well-positioned implant. Objective In this study, we sought to identify factors that may contribute to reduced glans engorgement and possible management strategies. Methods Intervention: Any method of treating or avoiding reduced glans engorgement post-IPP. Population: Men undergoing IPP insertion or men with glans complaints post-operatively Inclusion Criteria: Articles published in English with full text available and objective outcome measures Search Strategy: Literature search was performed in June 2023 using Medline, PubMed, Embase and Scopus. PubMed search included both “Mesh” protocols and “free text” to capture the correct study population and intervention utilized. Review Type & Analysis: Although an initial systematic model was considered, a scoping model was ultimately selected due to the limited literature and inconsistent outcome measures. This approach aimed to identify gaps in knowledge and provide an overview of the existing literature, thus informing future studies in this area. The variability in outcome measures across studies prevented higher-powered analyses from being conducted. Results Initial search strategy retrieved 98 non-duplicate studies with 40 being selected for initial screening after applying inclusion criteria. Ultimately, a total of 7 articles were included and categorized by theme: Cavernous-sparing technique (1–3); Pharmacotherapy for post-IPP glans complaints (4–7) (Table 1 & 2). The cavernous-sparing technique described aims to limit disruption of cavernous tissue around the implanted cylinder. This was achieved by omitting dilatation and using Furlow directly for measurements, or by intraoperative intracavernosal (IC) prostaglandin followed by dilatation only with size 7 or 8 Hegar alone. In all studies that compared penile dimensions, girth was significantly greater in the cavernous-sparing group. A higher proportion of men in this group also had detectable cavernous arteries, thicker residual corporal tissue, better residual tumescence post-IPP and demonstrated significant increases in both PSV and EDV post-PDE5i, compared to no PDE5i. Men who had standard dilatation also responded to post-IPP PDE5i but fewer had identifiable cavernous artery and had significant increase in only PSV, compared to no PDE5i. Other articles relating to post-IPP pharmacotherapy unanimously demonstrated that post-IPP glans engorgement was improved. This equated to reported statistically improved satisfaction when compared to the IPP alone groups, as measured by IIEF and EDITS questionnaires. Post-IPP PDE5i were better tolerated than intraurethral alprostadil, which was associated with discomfort. Conclusions Post-IPP pharmacotherapy appears to enhance residual erectile tissue engorgement. It can be used as an adjunctive after-care measure. Cavernous-sparing techniques show the importance of viable residual tissue for improved prosthetic erections. More comprehensive studies are needed to enhance patient experience and explore the microanatomical and hemodynamic role of residual tissue post-IPP. Disclosure No.

TOXICITY TESTING OF CHITOSAN OF PAPUYU FISH SCALE (Anabas testudineus) TOWARD BHK-21 FIBROBLAST CELLS

Background: Pulp capping is a treatment that aims to maintain the viability of the pulp tissue. Calcium hydroxide (Ca(OH)2 is a material that is often used for pulp capping procedures. However, this material does not provide a good adaptation to dentin. Therefore, an alternative material that is more biocompatible is needed, one of which is by using papuyu fish scale chitosan. papuyu fish as an alternative material must be proven to have no toxic effects. Purpose: to analyze whether the chitosan of papuyu fish scales (Anabas testudineus) is toxic to BHK-21 fibroblast cells using the MTT assay method. Methods: This study was a pure experimental study with a post-test-only design with a control group design consisting of 12 groups. The group given the chitosan treatment of papuyu fish scales consisted of 10 groups with concentrations of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% and 100% with 2 control groups namely control cells. and media control. Results: The results showed that the chitosan of papuyu fish scales did not have a toxic effect on BHK-21 fibroblast cells because the percentage value of cell viability of the entire treatment group was > 60% and the IC50 value was > 0.1%, which was 5.405 %. Conclusion: There was no toxic effect after administration of papuyu fish scales chitosan (Anabas testudineus) with concentrations of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, and 100% on cells BHK-21 fibroblasts. Keywords: BHK-21 fibroblast cells, Papuyu fish scale chitosan, Toxicity test

Traumatic scrotal sac hematoma after a fall injury

Introduction and Importance: Traumatic scrotal sac hematoma is an uncommon medical condition following a fall injury. Symptoms include swelling, pain, and discoloration. Accurate and immediate diagnosis is crucial to avoid complications and prevent testis loss, abscess formation, erectile dysfunction, and infection. This case highlights the importance of prompt evaluation and treatment to prevent complications and ensure optimal patient outcomes. Case Presentation: A 56-year-old man without prior medical history presented to the emergency department with scrotal pain and swelling 10 h after a traumatic event. The patient underwent a series of examinations, including radiological studies, before undergoing scrotal exploration and hematoma evacuation under subarachnoid block anesthesia. As of now, the patient has not experienced any complications that have impacted his quality of life. Clinical Discussion: Scrotal sac hematoma is formed following a blunt trauma when a significant force is transferred during contact with a solid object, impact from sports equipment, road traffic accidents, or falls from a height. If early exploration is delayed, then it can lead to complications like testicular atrophy, abscess formation, and infection. Hence, prompt diagnosis with clinical and radiological evaluation followed by immediate surgical intervention can result in better outcomes. Conclusion: Scrotal sac hematoma from blunt trauma is rare but can cause significant morbidity and psychological distress. Early surgical intervention is often necessary, especially if a testicle has ruptured, to salvage viable testicular tissue and control bleeding, resolve pain faster, shorten hospital stays, and improve the quality of life for patients.