Mature Tissue Research Articles

Angiofibrolipoma in the Head and Neck Region: A Case Report and Literature Review.

Angiofibrolipomas are rare, benign soft tissue tumors composed of mature fat cells, blood vessels, and fibrous connective tissue. Typically occurring in subcutaneous locations, this case report presents a unique instance of an angiofibrolipoma arising in the pharynx. According to our review of the literature, it is the second reported case in the pharynx and the sixth in the head and neck region. A 58-year-old woman presented with a 1 year history of globus sensation and an incidentally-discovered extra-oral polyp. Endoscopic examination revealed the polyp originating from the upper esophagus and extending into the pharynx. Magnetic resonance imaging confirmed the nature and extent of the lesion. The polyp was successfully removed via endoscopic resection, and histopathological analysis confirmed the diagnosis of angiofibrolipoma. This case highlights the rarity of pharyngeal angiofibrolipomas and underscores the importance of endoscopic evaluation for patients presenting with ambiguous pharyngeal symptoms. While surgical resection is generally recommended for such tumors, endoscopic removal can be a safe and effective option for smaller pedunculated lesions.

Induced pluripotent stem cell-derived cardiomyocyte in vitro models: benchmarking progress and ongoing challenges.

Recent innovations in differentiating cardiomyocytes from human induced pluripotent stem cells (hiPSCs) have unlocked a viable path to creating in vitro cardiac models. Currently, hiPSC-derived cardiomyocytes (hiPSC-CMs) remain immature, leading many in the field to explore approaches to enhance cell and tissue maturation. Here, we systematically analyzed 300 studies using hiPSC-CM models to determine common fabrication, maturation and assessment techniques used to evaluate cardiomyocyte functionality and maturity and compiled the data into an open-access database. Based on this analysis, we present the diversity of, and current trends in, in vitro models and highlight the most common and promising practices for functional assessments. We further analyzed outputs spanning structural maturity, contractile function, electrophysiology and gene expression and note field-wide improvements over time. Finally, we discuss opportunities to collectively pursue the shared goal of hiPSC-CM model development, maturation and assessment that we believe are critical for engineering mature cardiac tissue.

Micropropagation and in vitro rejuvenation of Eucalyptus cloeziana F. Muell.

Micropropagation is an important tool for the propagation for recalcitrant species, like Eucalyptus cloeziana. This is a first reported about a complete study of the E. cloeziana, it includes the vegetative rescue protocol of mature trees, its micropropagation up to the implementation of a mini-garden and clonal micro-garden and evaluation of adventitious rooting of their propagules. The in vitro rejuvenation of E. cloeziana genotypes (03, 05, 06, 13 and 15), over 21 successive subcultures, was evaluated by comparing minicutting and microcutting techniques and the efficiency of this biotechnological tool for cloning of the mature trees. The results provide evidence of the in vitro rejuvenation occurring in the mature E. cloeziana trees during micropropagation, leading to increases in the multiplication ratios of the microstumps of three genotypes (03, 05 and 15). The survival and callogenesis percentages of the mini and microcuttings of E. cloeziana were higher than 80% upon exiting of the greenhouse (30-days old) in the three cutting times. The results suggesting that factors beyond tissue maturity influence the adventitious rooting of the E. cloeziana because minicuttings and microcuttings of the 05 and 13 elite genotypes exhibited rooting percentages lower than 20%. These findings provided a theoretical basis for realizing the micropropagation of the epicormic shoots of the mature trees and, subsequently, its in vitro rejuvenation by axillary bud proliferation.

Embryo movement is required for limb tendon maturation

IntroductionFollowing early cell specification and tenocyte differentiation at the sites of future tendons, very little is known about how tendon maturation into robust load-bearing tissue is regulated. Between embryonic day (E)16 and E18 in the chick, there is a rapid change in mechanical properties which is dependent on normal embryo movement. However, the tissue, cellular and molecular changes that contribute to this transition are not well defined.MethodsHere we profiled aspects of late tendon development (collagen fibre alignment, cell organisation and Yap pathway activity), describing changes that coincide with tissue maturation. We compared effects of rigid (constant static loading) and flaccid (no loading) immobilisation to gain insight into developmental steps influenced by mechanical cues.ResultsWe show that YAP signalling is active and responsive to movement in late tendon. Collagen fibre alignment increased over time and under static loading. Cells organise into end-to-end stacked columns with increased distance between adjacent columns, where collagen fibres are deposited; this organisation was lost following both types of immobilisation.DiscussionWe conclude that specific aspects of tendon maturation require controlled levels of dynamic muscle-generated stimulation. Such a developmental approach to understanding how tendons are constructed will inform future work to engineer improved tensile load-bearing tissues.

Bilateral Dermoid Ovarian Cysts in a Young Woman - A Case Report and Literature Review.

Ovarian tumors are a common type of neoplasm in women, with mature cystic teratomas being the most frequent variant. These tumors occur bilaterally in approximately 10% of cases. However, bilateral and multiple occurrences are rarely reported. A 22-year-old nulliparous woman presented with amenorrhea and sudden, generalized, dull lower abdominal pain. Diagnostic imaging, including ultrasound and computed tomography (CT) scans, revealed large solid-cystic lesions in both ovaries, with internal hyperechoic foci consistent with fat and calcification, along with thin internal septations. A laparoscopic cystectomy was successfully performed, preserving ovarian function. Histopathological examination confirmed the presence of stratified keratinized squamous epithelium, sebaceous glands, hair follicles, mature adipose tissue, blood vessels, and lymphatic vessels within the resected cysts, with no evidence of malignancy. This unique case provides valuable insights into the understanding and management of bilateral dermoid cysts, highlighting the importance of preserving ovarian function in young women.

Clinical efficacy of platelet-rich fibrin, injectable platelet-rich fibrin, and advanced platelet-rich fibrin in regenerative endodontics: A case series

Background: This series investigates the efficacy of regenerative endodontic therapy (RET) using various platelet-rich fibrin (PRF) formulations in treating apical periodontitis and necrotic pulp in immature permanent teeth. Aim: This study aims to evaluate the effectiveness of different PRF formulations in RET. Materials and Methods: Three cases involving patients aged 15–16 with immature teeth and necrotic pulp were treated with RET using PRF, injectable PRF, and advanced PRF. The procedure included inducing bleeding with a Hedstrom file, applying PRF variants, and sealing with mineral trioxide aggregate and composite resin. Patients were followed up at 1, 3, 6, 12 and 18 months. Results: Radiographic evidence showed apical closure, root maturation, and healing of periapical tissues in all cases. However, pulp sensibility tests were negative. Conclusion: RET using PRF variants promotes root development and apical healing in immature teeth. Further research with larger sample sizes is needed to understand these therapies’ potential and limitations.

Incretin-responsive human pancreatic adipose tissue organoids: a functional model for fatty pancreas research.

Infiltration of adipocytes into the pancreatic parenchyma has been linked to impaired insulin secretion in individuals with increased genetic risk of T2D and prediabetic conditions. However, the study of this ectopic fat depot has been limited by the lack of suitable in vitro models. Here, we developed a novel 3D model of functionally mature human pancreatic adipose tissue organoids by aggregating human pancreatic adipose tissue-derived stromal vascular fraction (SVF) cells into organoids and differentiating them over 19 days. These organoids carry biological properties of the in situ pancreatic fat, presenting levels of adipogenic markers comparable to native pancreatic adipocytes and improved lipolytic and anti-lipolytic response compared to conventional 2D cultures. The organoids harbour a small population of immune cells, mimicking in vivo adipose environment. Furthermore, they express GIPR, allowing investigation of incretin effects in pancreatic fat. In accordance, GIP and the dual GLP1R/GIPR agonist tirzepatide stimulate lipolysis but had distinct effects on the expression of proinflammatory cytokines. This novel adipose organoid model is a valuable tool to study the metabolic impact of incretin signalling in pancreatic adipose tissue, revealing potential therapeutic targets of incretins beyond islets. The donor-specific metabolic memory of these organoids enables examination of the pancreatic fat-islet crosstalk in a donor-related metabolic context.

Carbon isotope composition of biomass and water use efficiency in young plants of Jatropha curcas L. under irrigated or water deficit conditions

Jatropha curcas L. is a non-food crop quoted as a promising natural feedstock for biodiesel production in tropical and subtropical regions. Although an efficient mechanism of drought avoidance through stomatal control of transpiration has been demonstrated in this species, low carbon assimilation and growth rates preclude any advantage of such strategy under water limitation. Two greenhouse experiments were conducted with the objective of investigating varietal differences in water use as the trade-off between carbon isotope composition (δ13C) in different tissues and water use efficiency, in young plants of J. curcas. The first experiment was a survey with seven provenances of J. curcas under non-limiting water availability. There were no significant differences among provenances for leaf gas exchange rates, growth and whole-plant transpiration (T). However, significant effects of provenance and tissue (stem bark or leaf) in δ13C were demonstrated. The provenances CNPAE183 and CNPAE222 were selected for the second experiment, as variations in water use traits and δ13C between the two provenances were observed. Soil water deficit, imposed for 18 days, led to significant physiological, biochemical, and morphological changes. An early and sharp response to water deficit in CNPAE183 as compared to CNPAE222 was observed, as indicated by a 44% higher rate of decrease of T in the former. In addition, water deficit led to increase of δ13C, which was more pronounced in CNPAE222 (13% in young leaves) when compared to CNPAE183 (11% in young leaves). In both provenances, δ13C was less negative in young as compared to mature tissues. Significant and direct correlations between stem bark and leaf δ13C and leaf-level intrinsic water use efficiency were observed. Contrasting results, particularly on T and δ13C, suggest the existence of genetic diversity for water relations and metabolic traits linked to drought tolerance in J. curcas. Using stem bark or leaf δ13C measurements as the basis for large-scale screening of water-use efficient genotypes should be considered.

Targeted CRISPR Regulation of ZNF865 Enhances Stem Cell Cartilage Deposition, Tissue Maturation Rates, and Mechanical Properties in Engineered Intervertebral Discs

Cell and tissue engineering based approaches have garnered significant interest for treating intervertebral disc degeneration and associated low back pain due to the substantial limitations of currently available clinical treatments. Herein we present a clustered regularly interspaced short palindromic repeats (CRISPR)-guided gene modulation strategy to improve the therapeutic potential of cell and tissue engineering therapies for treating intervertebral disc disease. Recently, we discovered a zinc finger (ZNF) protein, ZNF865 (BLST), which is associated with no in-depth publications and has not been functionally characterized. Utilizing CRISPR-guided gene modulation, we show that ZNF865 regulates cell cycle progression and protein processing. As a result, regulating this gene acts as a primary titratable regulator of cell activity. We also demonstrate that targeted ZNF865 regulation can enhance protein production and fibrocartilage-like matrix deposition in human adipose-derived stem cells (hASCs). Furthermore, we demonstrate CRISPR-engineered hASCs ability to increase GAG and collagen II matrix deposition in human-size tissue-engineered discs by 8.5-fold and 88.6-fold, respectively, while not increasing collagen X expression compared to naive hASCs dosed with growth factors. With this increased tissue deposition, we observe significant improvements in compressive mechanical properties, generating a stiffer and more robust tissue. Overall, we present novel biology on ZNF865 and display the power of CRISPR-cell engineering to enhance strategies treating musculoskeletal disease. STATEMENT OF SIGNIFICANCE: This work reports on a novel gene, ZNF865 (also known as BLST), that when regulated with CRISPRa, improves cartilagenous tissue deposition in human sized tissue engineering constructs. Producing tissue engineering constructs at human scale has proven difficult, and this strategy presents a broadly applicable tool to enhance a cells ability to produce tissue at these scales, as we saw an ∼8-88 fold increase in tissue deposition and significantly improved biomechanics in large tissue engineered intervertebral disc compared to traditional growth factor differentiation methods. Additionally, this work begins to elucidate the biology of this novel zinc finger protein, which appears to be critical in regulating cell function and activity.

Hypergravity as a Possible Way of Bone Tissue Engineering in Osteoblastic Differentiation from Mesenchymal Stem Cells: A Systematic Review

Background: Tissue engineering development has become a highlight in recent decades. One of the key areas of focus is producing mature bone tissue to overcome orthopedic problems, such as bone defects. Various cultures have been implemented on stem cells; some induce osteoblastic differentiation markers, while others have the opposite effect. Microgravity has been proven in several studies to inhibit the expression of osteogenic differentiation markers. Conversely, hypergravity is expected to have the opposite impact, supporting stem cells in the osteogenesis pathway. Methods: A literature search was conducted using online databases including Sciencedirect, PubMed, and Proquest, covering the period from 2008 to 2022. This search considered only experimental studies published in English. The keywords used in this research were "hypergravity" and "mesenchymal stem cell." All acquired data were processed and analyzed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (2020). Results: Initially, 190 studies were collected from online databases based on relevant keywords. After screening, 5 studies were included in the final analysis, focusing on hypergravity treatment and its effects on mesenchymal stem cells (MSCs). Conclusion: Hypergravity shows a significant and strong impact on osteoblastic differentiation. This study revealed that a gravity force of 30G and a culture duration of 7 to 14 days are the most optimal combination for inducing osteoblastic differentiation in MSCs.

A history-dependent integrase recorder of plant gene expression with single-cell resolution

During development, most cells experience a progressive restriction of fate that ultimately results in a fully differentiated mature state. Understanding more about the gene expression patterns that underlie developmental programs can inform engineering efforts for new or optimized forms. Here, we present a four-state integrase-based recorder of gene expression history and demonstrate its use in tracking gene expression events in Arabidopsis thaliana in two developmental contexts: lateral root initiation and stomatal differentiation. The recorder uses two serine integrases to mediate sequential DNA recombination events, resulting in step-wise, history-dependent switching between expression of fluorescent reporters. By using promoters that express at different times along each of the two differentiation pathways to drive integrase expression, we tie fluorescent status to an ordered progression of gene expression along the developmental trajectory. In one snapshot of a mature tissue, our recorder is able to reveal past gene expression with single cell resolution. In this way, we are able to capture heterogeneity in stomatal development, confirming the existence of two alternate paths of differentiation.

Topical Application of Melatonin in a Grapeseed Oil-based Microemulsion Accelerated Wound Healing in Rat Models

Objective: Melatonin has been associated with accelerated tissue regeneration and grapeseed oil has abundant unsaturated fatty acids, particularly linoleic acid that makes it a strong antioxidant, having the potential to promote wound healing by enhancing the presence of free radicals at the wound site. The study is aimed to evaluate the potential of a microemulsion gel using grapeseed oil as the organic phase and melatonin encapsulated in the vesicles to exhibit synergistic wound healing in Swiss albino rats. Materials and Method: Microemulsion containing grapeseed oil encapsulating melatonin was developed using the water-titration method. The surfactant and co-surfactant ratio (Smix) were fixed at 1:1. A pseudo-ternary diagram was used to determine the microemulsion zone and the developed microemulsion was further incorporated in carbopol 934P gel. The formulations were evaluated for their physicochemical properties and cytotoxicity assay. The optimized formulation was topically applied to cutaneous wounds of Swiss albino rat models. 30 Swiss albino rats were divided into five groups of 6 animals each: (i) Negative control group, (ii) Standard marketed formulation treated group, (iii) Optimized microemulsion containing Grapeseed oil and melatonin treated group, (iv) Grapeseed oil treated group and (v) Melatonin treated group. All the rats in each group were topically applied with the desired formulations daily for up to 14 days. Results: The treatment with a formulation comprising 10.18% Grapeseed oil, 24.88% water, and 64.94% Smix exhibited the highest entrapment efficiency of 86.65 ± 1.88% with an enhanced in vitro drug release of up to 83.02 ± 1.09%, also demonstrating first-order release kinetics. Furthermore, it did not inhibit L929 mouse fibroblast cell proliferation up to 500 μg/mL and promoted wound closure prior to other groups. Additionally, increased tissue maturation with higher collagen deposition was mostly seen by day 7. Thus demonstrating it is suitable for dermal application and sustained release of melatonin. The in vivo wound healing study and histological investigations on rat models demonstrated comparable results as observed in the marketed formulation of melatonin. Conclusion: The results showed that GSO oil based microemulsion encapsulating MEL could be a promising wound treatment option to exhibit accelerated wound healing effects.

Molecules in Motion: Unravelling the Dynamics of Vascularization Control in Tissue Engineering.

Significant progress has been made in tissue engineering (TE), aiming at providing personalized solutions and overcoming the current limitations of traditional tissue and organ transplantation. 3D bioprinting has emerged as a transformative technology in the field, able to mimic key properties of the natural architecture of the native tissues. However, most successes in the area are still limited to avascular or thin tissues due to the difficulties in controlling the vascularization of the engineered tissues. To address this issue, several molecules, biomaterials, and cells with pro- and anti-angiogenic potential have been intensively investigated. Furthermore, different bioreactors capable to provide a dynamic environment for in vitro vascularization control have been also explored. The present review summarizes the main molecules and TE strategies used to promote and inhibit vascularization in TE, as well as the techniques used to deliver them. Additionally, it also discusses the current challenges in 3D bioprinting and in tissue maturation to control in vitro/in vivo vascularization. Currently, this field of investigation is of utmost importance and may open doors for the design and development of more precise and controlled vascularization strategies in TE.

Study of the technological factors influence on the process of maturation of muscle tissue of silver carp (Hypophthalmichthys)

Study of the technological factors influence on the process of maturation of muscle tissue of silver carp (Hypophthalmichthys)

An Unusual Skin Finding in a Rare Case of Goltz Syndrome

Abstract Introduction/Objective Goltz Syndrome (Focal Dermal Hypoplasia) is a rare X linked dominant genetic disorder with various dermatologic, musculoskeletal and neurologic manifestations, secondary to a mutation in the PORCN gene. Skin findings include telangiectasias, raspberry-like papillomas (angiofibroma like lesions), nodular fat herniation, xerosis and photosensitivity. Lesions are bilateral, and asymmetrically distribututed along the lines of Blasco. The adipocytic lesions can be diagnosed via a skin biopsy showing adipose tissue in the superficial epidermis and dermis or via molecular techniques showing a mutation in the PORCN gene. Here we report a case of Goltz Syndrome with unique dermal findings. Methods/Case Report A male infant presented at birth with mild diffuse xerosis, large hypopigmented and depigmented atrophic patches and plaques and multiple pink yellow red exophyitic soft papules distributed asymetrically across the body along the lines of Blascho. Additionally the patient had clinodactly, widely spaced nipples, extra pads of fat in the toes and philtrum and fingernails with longitudal ridges and lateral nail plate deviation. A diagnosis of Goltz syndrome was made via molecular analysis that showed mosiacism at C.502G>A (p.Gly168Arg) in the PORCN gene. The patient had a very superficial 2-3 mm erosion at the intersection between the scrotum and perineum. At 18 months, this had grown to finger like projections and eventually grew into multiple tan red exophytic warty papillomatous telangactatic like lesions measuring 3.0 x 0.8 cm that were painful and bled easily. A biopsy of this lesion showed focal mild epidermal hyperplasia and elongation of the rete ridges with wide spread diffuse vascular proliferation with multiple ectactic vessels along with mild dermal and perivascular inflammatory infiltrates. Also noted was infiltration of mature adipose tissue in the superficial epidermis and dermis. We preformed elastin and trichrome stains to identify if this lesion was reactive in nature or de novo. Our results showed retained elastin staining with a negative trichrome eluding to a denovo process. Additionally GLUT1 was negative, ruling out an infantile hemangioma. The above findings in this lesion do not represent any previously described dermatologic entity. Results (if a Case Study enter NA) NA Conclusion This is a rare and unique dermatologic finding of a case of Goltz sydrome, which itself is a rare disorder. In our literature review, this is the only case of Goltz Syndrome thusfar to have presented with this unique skin lesion.

Copper‐infused zinc porphyrin supramolecular polymersomes for triple synergistic combat against wound bacterial biofilm infections

AbstractBacterial biofilm infections (BBI) on wound surfaces and implants pose a significant clinical challenge due to the impermeable nature of biofilms and obstacles in tissue repair. Traditional photothermal therapy (PTT) or chemodynamic therapy (CDT), whether used alone or in combination, often causes damage to surrounding normal tissues from high operating temperatures or elevated levels of reactive oxygen species, leading to unsatisfactory anti‐biofilm effects. This study introduces a novel copper ions loaded zinc porphyrin polymer vesicle (Cu‐PPS) that employs a triple synergistic approach involving PTT, CDT, and bacterial cuproptosis‐like death (BCD). Cu‐PPS exhibits exceptional photothermal efficiency of 51.06%, promoting the release of copper ions under photothermal stimulation, enhancing CDT and BCD effectiveness, and facilitating mature biofilm clearance and tissue repair. This approach achieves a bactericidal rate exceeding 99% and an anti‐biofilm rate of 93.32% in vitro and also excellent efficacy in treating BBI in vivo. This study presents an innovative therapeutic strategy for combating biofilm infections, addressing the challenges encountered in the clinical management of BBI.

PLASMA CELL NEOPLASM IN BREAST: A RARE CASE REPORT

Abstract Introduction/Objective Breast carcinoma continues to be the most common malignancy in women however plasma cell neoplasms are rare in breast tissue. Most of these recorded cases are from patients with Multiple myeloma (1). We present a rare case of a new breast lesion in a 69 year female incidentally found on imaging. She had a history of adenocarcinoma of lung with brain metastasis undergoing treatment. Methods/Case Report The patient’s breast lesion presentation was unusual without any pain or associated symptoms, but a new right breast mass was incidentally discovered on CT-Chest Abdomen-Pelvis. Mammogram revealed a 1.4 cm circumscribed mass in lower, outer breast with scattered calcifications. With the suspicion for a primary breast malignancy or metastatic disease from her lung cancer the patient’s breast lesion was biopsied. On histology, abnormal proliferation of cells with ovoid nuclei, vesicular chromatin and variable cytoplasm was noted with a background of mature adipose tissue. Immunohistochemistry showed neoplastic cells positive for plasma cell associated markers including CD38 (patchy), CD56, CD138, and MUM1 with a kappa restriction on ISH. The Ki67 showed 20% proliferation index. EBER was negative and SMARC4 and INI were preserved. Other immunohistochemical stains were performed to rule out differentials and were all negative. The morphology and IHCs were consistent with the diagnosis of Plasma cell neoplasm with kappa-restriction. Subsequently this patient developed a shoulder lesion which on biopsy showed a plasma cell neoplasm expressing plasma cell markers and kappa light chain overexpression. Results (if a Case Study enter NA) NA Conclusion It is critical to distinguish a breast plasma cell neoplasm from other primary and metastatic breast lesions in order to avoid unnecessary surgery and cytotoxic chemotherapy. Rarely, plasma cell neoplasm can manifests as a breast lesion, which in this case turned out to be the early manifestation of multiple myeloma.

Juvenile hormone signaling is indispensable for late embryogenesis in ametabolous and hemimetabolous insects

BackgroundJuvenile hormone (JH) is an insect-exclusive hormone involved in regulating diverse aspects of insect physiology, and the evolution of its diverse function is widely interesting. Studying embryogenesis in basal wingless insects is important to understand the functional evolution of JH; however, experimental studies in this regard are scarce. In this study, we conducted CRISPR/Cas9-mediated knockout (KO) of genes involved in JH biosynthesis and signaling cascades in the ametabolous firebrat, Thermobia domestica. Additionally, we investigated whether the primitive action of JH is conserved in the hemimetabolous cricket, Gryllus bimaculatus.ResultsWe observed that KO of JHAMT, CYP15A1, Met, and Kr-h1 resulted in embryonic lethality in T. domestica. Deprivation of JH or JH signaling arrested the progression of extraembryonic fluid resorption after dorsal closure and hatching, which is consistent with the gene expression pattern showing high Kr-h1 expression in the late embryos of T. domestica. The embryos deficient in JH signaling displayed wrinkled and weak legs. Comparative transcriptome analysis revealed that JH signaling promotes embryonic leg maturation through inducing energy supply and muscle activity, as validated by transmission electron microscopy (TEM). In addition, JH signaling exhibited similar embryonic effects in G. bimaculatus.ConclusionsThis study reveals the indispensable role of JH signaling in facilitating the maturation of terminal tissues during late embryogenesis, as demonstrated by the regulation of leg development, in ametabolous and hemimetabolous insects. These findings further indicate that the embryonic functions of JH evolved earlier than its anti-metamorphic functions during postembryonic development.

Effect of a novel cannulation device for vascular access on AVF maturation in a goat carotid-jugular fistula model.

The Ark is a 3-D printed titanium device designed to be implanted around the draining vein of an arteriovenous fistula (AVF) to facilitate vascular access. The purpose of this study was to assess AVF maturation after Ark implantation in a large animal model. End-to-side AVFs were created between the carotid artery and jugular vein in nine pygmy goats that included three control (AVF only) and six experimental (AVF and Ark device) animals. For experimental animals, an Ark device was implanted approximately 10 cm downstream of the anastomosis at the time of AVF creation. Postoperative ultrasounds and cannulations of the jugular vein fistula were performed over 12 months. At the conclusion of the study, the AVF was ligated and Ark devices along with a segment of the arterialized vein and surrounding tissues were explanted for gross and histological assessment. The control and experimental Ark groups exhibited increased dilation and flow as well as diminished depth underscoring the parallel developments in vascular attributes and AVF maturation between the two groups. Gross pathology, histology, and micro-CT imaging revealed intact endothelium, mature tissue integration throughout the porous Ark device, and no underlying stenosis. No adverse events such as foreign body reaction, skin or vessel erosion were identified. The study showed maturation without stenosis of the fistula in all animals. This study confirmed that the Ark device functions as a scaffold around the access vein, allows fistula maturation, and can be consistently cannulated without infiltrations over a 12-month period in a large animal model.

6963 A Rare Case Presentation of Untreated Congenital Adrenal Hyperplasia with Bilateral Giant Myelolipoma

Abstract Disclosure: F. Omran: None. S. Bromley: None. M. Ilahi: None. M. Zena: None. W. Al-Refaie: None. J. Delto: None. A. Singh,: None. Background: Adrenal myelolipoma is a rare benign neoplasm predominantly composed of mature adipose tissue and intermixed myeloid tissue, often associated with conditions like Congenital Adrenal Hyperplasia. The etiology of this neoplasm is not definitively known although there are numerous hypotheses, including research suggesting that excess ACTH could be responsible for the pathogenesis. Clinical Case: A 40-year-old female with a history of congenital adrenal hyperplasia noncompliant with treatment. She presented with cholelithiasis (s/p laparoscopic cholecystectomy), abdominal imaging revealed incidental finding of a large right retroperitoneal mass. She was noted to have generalized excessive hirsutism in male distribution, small breasts, enlarged clitoris, male body habitus, and amenorrhea after stopping steroids years prior. Laboratory workup showed the following hormonal abnormalities: elevated ACTH (1080 pg/ml), elevated testosterone (243 ng/dl) and free testosterone (31.3 pg/ml), elevated androstenedione (23.431 ng/ml), and low LH (<0.02 miu/ml), low FSH (<0.02 miu/ml). CT abdomen showed right lobulated retroperitoneal mass of 4x14.3x20cm with internal fat and soft tissue components, left lobulated retroperitoneal mass of 13.7x4.7x7.5cm with soft tissue and fat components. CT guided-biopsy showed pathology consistent with adrenal myelolipoma: fatty areas with interspersed hematopoietic tissue components, peripheral rim of normal adrenal cortical tissue. Given the large size of the mass and compressive effects on surrounding organs, patient underwent exploratory laparotomy with resection of right retroperitoneal mass, nephrectomy, and adrenalectomy. Discharged on hydrocortisone and fludrocortisone, instructed to follow up by endocrinologist, always wear medical alert bracelet, and provided with hydrocortisone emergency kit. Conclusion: This case serves as a classic presentation of a rare disease state. Adrenal myelolipomas, a rare benign adrenal neoplasm, have been found in several disorders associated with chronic ACTH hypersecretion including congenital adrenal hyperplasia. Most CAH patients with myelolipomas have untreated or poorly treated CAH. Adrenal myelolipomas that are asymptomatic and <5cm in size are usually monitored if one is certain there is no occult malignancy. If these tumors are symptomatic or >7cm, patients should undergo surgical excision. These patients should be followed by endocrinology. Importantly, further guidelines should be further developed for management. Presentation: 6/3/2024