Immunohistochemical Expression of Epidermal Growth Factor Receptor (EGFR) in Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders.

BACKGROUND: Increased epidermal growth factor receptor (EGFR) expression has been implicated in several tumors and is associated with increased tumor advancement as well as a potential drug target. The objective of the study was to compare the immunohistochemical expression of EGFR in oral squamous cell carcinoma (OSCC) with oral potentially malignant disorders (OPMDs) and their demographic and pathologic parameters. METHODS: This study was a comparative cross-sectional analytical study. It was conducted at the Department of Pathology, Peshawar Medical College, Riphah International University, Islamabad, Pakistan, from March 2021 to February 2022. The sample size was calculated through G Power. Thirty-eight cases of oral squamous cell carcinoma and 38 cases of oral potentially malignant disorders (OPMDs) were included in the study. Statistical analysis was performed using the Statistical Package for Social Sciences version 20.0. χ 2 tests and Fisher exact tests were applied to compare categorical variables. RESULTS: Mean age of OSCC was 61.6±13.9, with age range from 26 to 90 years. The male-to-female ratio for OSCC was 2.16:1. Buccal mucosa was the most common site involved (34.2%). The most common histologic type was well-differentiated OSCC (71.05%) followed by poorly differentiated (16%) and moderately differentiated (13.15%). The mean age of OPMDs cases was 59.16 ± 10.81 with a male-to-female ratio of 1:1.2. Buccal mucosa was the common site (55.3%), followed by the tongue (18.4%). The OPMDs with dysplasia were 55.2%, and without dysplasia were 44.8%. A total of 55.7% of cases of OSCC showed positive EGFR expression as compared with 36.9% OPMDs cases. A higher number of low-grade OSCC cases showed increased EGFR positivity (59.3%) as compared with high grade (45.45%). EGFR positivity in OPMD cases without dysplasia was 41.2% as compared with cases with dysplasia (33.3%). The EGFR expression in OPMD cases was higher in the ≤50 age group ( P =0.001) and in females ( P =0.032), which was statistically significant. CONCLUSIONS: EGFR expression by Immunohistochemistry may not be a helpful prognostic marker to determine the risk of OPMDs progressing to higher grades of dysplasia or invasive cancer. However, further studies relating this tumor marker to stage, lymph node metastasis, hematogenous metastasis, survival outcomes, and treatment response may give useful information regarding the utility of this marker.

Malignant peripheral nerve sheath tumours in a patient with Neurofibromatosis-1.

Malignant peripheral nerve sheath tumour (MPNST) is an uncommon type of soft tissue tumour which most commonly arises in the setting of Neurofibromatosis-1 (NF-1) or in the presence of another nerve sheath tumour. NF-1 is an autosomal dominant syndrome which is diagnosed based on clinical criteria. People suffering from NF-1 are at a higher risk of developing tumours, especially MPNST. MPNST can occur anywhere along the distribution of nerve roots but most commonly involves the limbs and trunk. The prognosis of MPNST in the setting of NF-1 is grave as the distant metastasis develops earlier than non-syndromic cases. Pre-operative diagnosis is difficult as there is no gold standard radiologic technique or characteristic radiological features. The diagnosis is established after histological evaluation supplemented by immunohistochemistry of the tumour tissue. We present a case of a 38-year-old female, a known case of NF-1, who presented with a single, irregular, cystic swelling in the left flank which was increasing in size. The patient underwent complete surgical excision of a 6cm tumour which was diagnosed as MPNST after histopathological examination. The rare nature of this tumour makes the diagnosis and treatment extremely hard. Awareness regarding this disease should be increased so that proper treatment plans can be made.

Comparison of PD-L1 Expression in Oral Squamous Cell Carcinoma and Premalignant Lesions of Oral Cavity.

OBJECTIVE: Objectives of this study were to compare  expression of Programmed Death-Ligand 1(PD-L1) protein in oral squamous cell carcinoma (OSCC) and oral potentially malignant disorder (OPMD) cases; and to compare the PD-L1 protein expression in histological grades of OSCC and also in OPMD's with Dysplasia and without Dysplasia. MATERIALS & METHODS: In this study,  25 cases of Oral squamous cell carcinoms, 25 cases of Oral Potentially Malignant Disorders and 10 cases of non-neoplastic oral mucosa (control) cases were included. FFPE blocks of OSCC and OPMD cases were contributed by Department of Pathology, Histopathology Division,Pakistan Institute of Medical Sciences, Islamabad. Immunohistochemical staining of cases with PD-L1 monoclonal antibody (1:100; Dako) was carried out at Histopathology division , PMC Labs,  Peshawar Medical College,Peshawar, Riphah International University, Islamabad . Epithelial cells (membranous and cytoplasmic) positivity was observed for PD-L1 Antibody. Data was analyzed in SPSS version20. For qualitative variables frequencies and percentages were calculated whereas for quantitative variables means and standard deviations were recorded. The Chi-square test was applied to evaluate the significant difference in categorical variables . p-value of ≤0.05 was taken as significant. RESULTS: PD-L1 expression in OSCC cases turned out to be 48% (n=12/25) as compared to 8% of OPMD cases (n=2/25) with a significant p value of 0.002 and all non-neoplastic oral mucosa cases were negative. PD-L1 expression in high grade OSCC cases was quite high (61% n=11/18) as compared to low grade OSCC (14% n=1/7) cases with a significant p value of 0.035. CONCLUSION: A statistically significant increased PD-L1 expression was noted in  OSCC as compared to OPMD. Expression of PD-L1 was more intense in high grade OSCC cases. The relation of PD-L1 expression to age ,gender or location of OSCC and OPMD cases , and presence of dysplasia in OPMD cases was statistically not significant.

Breast T-Lymphoblastic Lymphoma Presenting as a Single Mass in a Young Female with Family History of Breast Cancer.

Breast involvement by lymphoma is rare, constituting ≤0.5% of all breast malignancies, with T-cell lymphomas, comprising 2.5 to 7.5% of all lymphomas involving breast. Several types of T-cell lymphomas have been reported in breast, including anaplastic large-cell lymphoma, breast implant associated anaplastic large cell lymphoma, peripheral T-cell lymphoma not otherwise specified, adult T-cell lymphoma/leukemia, NK/T-cell lymphoma, and T-lymphoblastic lymphoma. Breast involvement by T-lymphoblastic lymphoma is very unusual and when it is observed, it usually occurs as a secondary involvement by known lymphoma.We report the case of a 33-year-old woman with family history of breast cancer who presented with a single right breast mass which was diagnosed as T-lymphoblastic lymphoma. At presentation, the patient was feeling well and did not have any B symptoms or any other signs of lymphoma or leukemia. One month after diagnosis, the patient presented to the emergency room with chest pain and shortness of breath and was found to have a large mediastinal mass with both pleural and pericardial effusions. Subsequent evaluation of peripheral blood smear and bone marrow biopsy showed increased amount of blasts and involvement by T-lymphoblastic lymphoma. The patient was induced with cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone chemotherapy. After two-cycles of chemotherapy, a computed tomography of the thorax showed marked interval decrease in size of anterior mediastinal mass, suggestive of positive treatment response.Here, we report the first well documented case of T-lymphoblastic lymphoma presented as a single breast mass without history of B symptoms and perform an extensive English language literature review.

MALT lymphoma of the tongue: An unusual site that may present a diagnostic challenge.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a low-grade B cell lymphoma that can affect any organ, usually preceded by acquisition of MALT in response to antigenic stimulus provided by infections or autoimmune diseases. Most often, MALT lymphoma involves the stomach (about 35% of cases), followed by the ocular adnexal region, skin, lungs, and salivary glands, but virtually any extranodal site can be involved. MALT lymphomas are less common at sites of normal MALT tissue, such as Waldeyer ring and the ileocecal region of the gastrointestinal tract. Lymphomas involving the tongue are extremely rare and represent approximately 3% of all lymphomas involving the head and neck region. In this study, we discuss potentially challenging diagnostic aspects of MALT lymphoma involving the tongue and review and summarize the available literature about this topic.

CD5+ Diffuse Large B-Cell Lymphoma With Leukemic Transformation: A Rare Case With Central Nervous System Involvement, Treated With R-CHOP and Intrathecal Methotrexate/Cytarabine.

Diffuse large B-cell lymphoma (DLBCL) is one of several subtypes of non-Hodgkin's lymphoma, and one that can present in a myriad of ways. One unique and particularly aggressive presentation is leukemic transformation with CD5 positivity, which leads to systemic symptoms, a relatively high peripheral tumor load, and higher rates of CNS involvement. The prevalence of leukemic transformation has not been determined, as published literature is limited to case reports and small case series. CD5 positivity appears to be even rarer and is only found in a small fraction of DLBCL with leukemic transformation. Treatment regimens for this presentation have not been well-established due to the rarity of the disease and paucity of literature on the subject. Our patient, a 76-year-old female with a history of previously treated stage IIIB follicular lymphoma, was found to have CD5+ DLBCL with leukemic transformation. She was treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) along with intrathecal methotrexate (IT MTX)/cytarabine after CNS involvement was diagnosed. The patient tolerated therapy well, with an objective reduction in leukocytosis and blast count. To our knowledge, this is the first such case of CD5+ DLBCL with leukemic transformation treated with dose-reduced R-CHOP and IT MTX/cytarabine. Her response to therapy indicates that this regimen could be a viable option for the treatment of this exceedingly rare disease presentation.

Aorta-specific DNA methylation patterns in cell-free DNA from patients with bicuspid aortic valve-associated aortopathy.

BACKGROUND: The dilation of the aorta that occurs as a consequence of a congenitally bicuspid aortic valve (BAV) is associated with a risk of dissection, aneurysm or rupture. With progressive aortopathy, surgery is often recommended, but current patient selection strategies have limitations. A blood-based assay to identify those who would most benefit from prophylactic surgery would be an important medical advance. In a proof-of-concept study, we sought to identify aorta-specific differentially methylated regions (DMRs) detectable in plasma cell-free DNA (cfDNA) obtained from patients undergoing surgery for BAV-associated aortopathy. METHODS: We used bioinformatics and publicly available human methylomes to identify aorta-specific DMRs. We used data from 4D-flow cardiac magnetic resonance imaging to identify regions of elevated aortic wall shear stress (WSS) in patients with BAV-associated aortopathy undergoing surgery and correlated WSS regions with aortic tissue cell death assessed using TUNEL staining. Cell-free DNA was isolated from patient plasma, and levels of candidate DMRs were correlated with aortic diameter and aortic wall cell death. RESULTS: Aortic wall cell death was not associated with maximal aortic diameter but was significantly associated with elevated WSS. We identified 24 candidate aorta-specific DMRs and selected 4 for further study. A DMR on chromosome 11 was specific for the aorta and correlated significantly with aortic wall cell death. Plasma levels of total and aorta-specific cfDNA did not correlate with aortic diameter. CONCLUSIONS: In a cohort of patients undergoing surgery for BAV-associated aortopathy, elevated WSS created by abnormal flow hemodynamics was associated with increased aortic wall cell death which supports the use of aorta-specific cfDNA as a potential tool to identify aortopathy and stratify patient risk.

Aripiprazole Lauroxil, a Novel Injectable Long-Acting Antipsychotic Treatment for Adults with Schizophrenia: A Comprehensive Review.

PURPOSE OF REVIEW: This is a comprehensive review of the literature regarding the use of Aripiprazole lauroxil for schizophrenia. This review presents the background, evidence, and indications for using aripiprazole lauroxil to treat schizophrenia in the context of current theories on the development of schizophrenia. RECENT FINDINGS: Schizophrenia is a chronic mental health disorder that currently affects approximately 3.3 million people in the United States. Its symptoms, which must be present for more than six months, are comprised of disorganized behavior and speech, a diminished capacity to comprehend reality, hearing voices unheard by others, seeing things unseen by others, delusions, decreased social commitment, and decreased motivation. The majority of these symptoms can be managed with antipsychotic medication. Aripiprazole lauroxil is a long-acting intramuscular injection that works as a combination of partial agonist activity at D2 and 5-HT1A receptors combined with antagonist activity at 5-HT2A receptors. It can be dosed as a 4-, 6-, or 8-week injection, depending on oral dosage. Aripiprazole lauroxil was FDA approved in October of 2015. SUMMARY: Schizophrenia is a severe psychiatric disorder if left untreated. There are multiple medications to help treat schizophrenia. One antipsychotic agent, aripiprazole lauroxil, offers long duration injections that optimize and improve compliance. Known side effects include weight gain, akathisia, neuroleptic malignant syndrome, tardive dyskinesia, and orthostatic hypotension. Aripiprazole lauroxil is an FDA-approved drug that can be administered monthly, every six weeks, or every two months and has been shown to be both safe and effective.

Ophthalmological Aspects of von-Hippel-Lindau Syndrome.

Background: von Hippel-Lindau (VHL) syndrome is a multisystem neoplastic disorder involving eyes, central nervous system, kidneys, spine, and other tissues. A retinal capillary hemangioma (RCH) is the earliest manifestation of the VHL disease in most cases.Areas covered:This paper aims to provide an up-to-date review of the current literature about von Hippel-Lindau syndrome. Molecular background, systemic and ocular features of the diseases as well as the utility of newer imaging modalities in diagnosis and monitoring of ocular VHL disease have been described. Besides, we have discussed newer treatment modalities and therapeutic targets.Conclusion: Modern imaging technologies like optical coherence tomography and optical coherence tomography angiography are tools of the trade, in making an appropriate diagnosis and monitoring disease activity and response to treatment. Peripheral RCH may be treated using laser photocoagulation in tumors up to 3000 µm. Vascular endothelial growth factor suppression can help in reducing tumor activity and stabilize the tumor size; however, it does not regress the RCH.

Identification of cell-free DNA methylation patterns unique to the human left ventricle as a potential indicator of acute cellular rejection.

Increased levels of donor-derived cell-free DNA (dd-cfDNA) in recipient plasma have been associated with rejection after transplantation. DNA sequence differences have been used to distinguish between donor and recipient, but epigenetic differences could also potentially identify dd-cfDNA. This pilot study aimed to identify ventricle-specific differentially methylated regions of DNA (DMRs) that could be detected in cfDNA. We identified 24 ventricle-specific DMRs and chose two for further study, one on chromosome 9 and one on chromosome 12. The specificity of both DMRs for the left ventricle was confirmed using genomic DNA from multiple human tissues. Serial matched samples of myocardium (n = 33) and plasma (n = 24) were collected from stable adult heart transplant recipients undergoing routine endomyocardial biopsy for rejection surveillance. Plasma DMR levels increased with biopsy-proven rejection grade for individual patients. Mean cellular apoptosis in biopsy samples increased significantly with rejection severity (2.4%, 4.4% and 10.0% for ACR 0R, 1R, and 2R, respectively) but did not show a consistent relationship with DMR levels. We identified multiple DNA methylation patterns unique to the human ventricle and conclude that epigenetic differences in cfDNA populations represent a promising alternative strategy for the non-invasive detection of rejection.

An Advanced AIDS Patient With CD4 <20 and Plasmablastic Lymphoma Achieving Complete Response With the V-EPOCH Regimen.

Plasmablastic lymphoma (PBL) is a rare form of non-Hodgkin lymphoma that is highly aggressive and carries a poor prognosis. Although the standard chemotherapy choice for most diffuse large B-cell lymphomas (DLBCL) is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), subtypes of DLBCL such as PBL are less responsive to this treatment regimen. The preferred regimens for PBL include infusional EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride), HyperCVAD (cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone), or CODOX-M/IVAC (cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine). Recent studies have begun to investigate the addition of other agents to these regimens to improve survival. This case report is about a patient with a history of advanced acquired immunodeficiency syndrome (AIDS) with a cluster of differentiation 4 (CD4) count <20 who had CD20 negative plasmablastic lymphoma and was successfully treated with the combination of bortezomib and dose-adjusted EPOCH (V-EPOCH) and intrathecal chemotherapy, achieving complete response with optimal tolerance. To our knowledge, this is the first case to demonstrate a complete response with V-EPOCH for PBL in advanced AIDS with CD4 <20. We aim to highlight the importance of standardizing effective chemotherapeutic approaches to this cancer entity and augment the effectiveness of V-EPOCH therapy in the literature review.

Everolimus for cardiac rhabdomyomas in children with tuberous sclerosis. The ORACLE study protocol (everOlimus for caRdiac rhAbdomyomas in tuberous sCLErosis): a randomised, multicentre, placebo-controlled, double-blind phase II trial.

INTRODUCTION: Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care. Everolimus has shown positive effects on subependymal giant cell astrocytomas, renal angiomyolipoma and refractory seizures associated with tuberous sclerosis complex. However, evidence supporting efficacy in symptomatic cardiac rhabdomyoma is limited to case reports. The ORACLE trial is the first randomised clinical trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma. METHODS: ORACLE is a phase II, prospective, randomised, placebo-controlled, double-blind, multicentre protocol trial. A total of 40 children with symptomatic cardiac rhabdomyoma secondary to tuberous sclerosis complex will be randomised to receive oral everolimus or placebo for 3 months. The primary outcome is 50% or more reduction in the tumour size related to baseline. As secondary outcomes we include the presence of arrhythmias, pericardial effusion, intracardiac obstruction, adverse events, progression of tumour reduction and effect on heart failure. CONCLUSIONS: ORACLE protocol addresses a relevant unmet need in children with tuberous sclerosis complex and cardiac rhabdomyoma. The results of the trial will potentially support the first evidence-based therapy for this condition.

Textural Properties of Choriocapillaris on OCTA in Healed Inflammatory Choriocapillaropathies.

BACKGROUND AND OBJECTIVE: To evaluate the flow characteristics and textural properties of choriocapillaris (CC) on optical coherence tomography angiography in eyes with resolved inflammatory choriocapillaropathies and Vogt-Koyanagi-Harada (VKH) disease. PATIENTS AND METHODS: A cohort of eyes with healed acute posterior multifocal placoid pigment epitheliopathy (APMPPE), serpiginous choroiditis (SC), and VKH disease were included. A 3 mm × 3 mm OCT angiogram of CC was acquired and graded for flow characteristics and textural properties. RESULTS: This study included 16 patients. Texture was heterogeneous in all eyes in the SC and VKH groups, and in four eyes (40%) in the APMPPE group. Most of the eyes with VKH disease had severe low flow, whereas most of the SC and APMPPE eyes demonstrated mild low flow. Heal duration had a strong negative correlation with severity of CC low flow and a weak, statistically nonsignificant correlation with texture heterogeneity. CONCLUSION: Despite the resolution of active inflammation, partial CC hypoperfusion and texture disruptions persist for longer durations and may resolve in a time dependent manner. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:566-572.].

Beyond efficacy: a qualitative organizational perspective on key implementation science constructs important to physical activity intervention translation to rural community cancer care sites.

PURPOSE: To identify constructs relevant to implementation of evidence-based physical activity (PA) behavior change interventions for rural women cancer survivors from an organizational perspective. METHODS: During the development of a PA intervention implementation toolkit, 11 potential interventionists and 19 community and organizational stakeholders completed focus groups stratified by role. Narratives were audio recorded, transcribed, and coded for Consolidated Framework for Implementation Research (CFIR) constructs. RESULTS: Multiple CFIR constructs were identified: Implementation Process (i.e., Engaging, Reflecting and Evaluating), Intervention Characteristics (i.e., Design Quality and Packaging, Cost, Evidence Strength and Quality, Adaptability, Complexity), Inner Setting (i.e., Implementation Readiness, Implementation Climate, Structural Characteristics), Outer Setting (i.e., Patient Needs and Resources, Cosmopolitanism), and Characteristics of Individuals (i.e., Knowledge and Beliefs, Stage of Change). Narratives identified rural implementation barriers (e.g., transportation) and facilitators (e.g., community-oriented). Unique needs of the cancer survivor (e.g., coping during cancer treatment and long-term effects on physical abilities) were emphasized as important barriers potentially addressed through Adaptability and Readiness implementation strategies. Narratives identified multi-level (i.e., individual-, organizational-, and community-level) strategies for targeting the identified constructs. CONCLUSIONS: Fourteen CFIR constructs emerged as potentially important for organizations to consider when implementing PA interventions. Constructs were integrated into our implementation toolkit and research testing their potential mechanisms of action when implementing PA interventions in rural settings is warranted. IMPLICATIONS: Strategies that target the identified constructs may enhance the implementation of PA programs for rural cancer survivors. Cancer survivors can facilitate these efforts by partnering with their health care providers and community organizations. IMPLICATIONS FOR CANCER SURVIVORS: Organizations promoting physical activity programs for cancer survivors must overcome implementation barriers including but not limited to cost, necessary expertise, and lack of awareness. Cancer survivors can facilitate these efforts by partnering with their health care providers, cancer center, and local community organizations to raise awareness and champion these efforts. It will "take a village", with cancer survivors being their own best advocate, to bring physical activity promotion to a broad range of cancer survivors.

IgG4-Related Sclerosing Pericarditis in a Young Man With Recurrent Chest Pain.

Many cases of immunoglobulin G4 (IgG4)-related disease involving different organ systems have been reported in the literature since the disorder was first described in patients with sclerosing pancreatitis. This report discusses an interesting case of IgG4-related cardiovascular disease that involved the pericardium and resulted in reoccurring chest pain in a 36-year-old man. The challenging diagnosis was made using established diagnostic criteria for other tissue sites and included the presence of elevated serum IgG4, pericardial infiltration by IgG4-positive plasma cells, focal phlebitis, and fibrosis. The patient's symptoms improved with immunosuppressive therapy.

Circulating tumour DNA, microRNA and metabolites in cerebrospinal fluid as biomarkers for central nervous system malignancies.

Central nervous system (CNS) malignancies can be difficult to diagnose and many do not respond satisfactorily to existing therapies. Monitoring patients with CNS malignancies for treatment response and tumour recurrence can be challenging because of the difficulty and risks of brain biopsies, and the low specificity and sensitivity of the less invasive methodologies that are currently available. Uncertainty about tumour diagnosis or whether a tumour has responded to treatment or has recurred can cause delays in therapeutic decisions that can impact patient outcome. Therefore, there is an urgent need to develop and validate reliable and minimally invasive biomarkers for CNS tumours that can be used alone or in combination with current clinical practices. Blood-based biomarkers can be informative in the diagnosis and monitoring of various types of cancer. However, blood-based biomarkers have proven suboptimal for analysis of CNS tumours. In contrast, circulating biomarkers in cerebrospinal fluid (CSF), including circulating tumour DNA, microRNAs and metabolites, hold promise for accurate and minimally invasive assessment of CNS tumours. This review summarises the current understanding of these three types of CSF biomarkers and their potential use in neuro-oncologic clinical practice.

Sex-dependent difference in the relationship between adipose-tissue cholesterol efflux and estradiol concentrations in young healthy humans.

BACKGROUND: Impaired adipose tissue function and lower levels of high density lipoprotein cholesterol (HDL-C) have been implicated in the development of vascular dementia, and metabolic diseases such as hypertension, atherosclerosis, type 2 diabetes (T2D) and metabolic syndrome. Interestingly, both the substrate fluxes in adipose tissue and HDL-C concentration differ between men and women. Moreover, adipose tissue cholesterol efflux has been implicated in modulation of HDL-C levels. Thus, we aimed to determine if the association between serum estradiol levels and adipose tissue cholesterol efflux is sex-dependent. METHOD: We evaluated the serum estradiol levels and adipose tissue cholesterol efflux in young healthy men (n=5) and women (n=3). Adipose tissue cholesterol efflux was determined using subcutaneous microdialysis probes. Linear regression analyses were used to determine the relationship between the parameters, p<0.05 was considered as statistically significant. RESULTS: Our data demonstrated that serum estradiol levels directly associated with adipose tissue cholesterol efflux; however, the relationships may be sex-dependent. We discussed our results in the context of currently available data regarding sex-dependent variability in adipose tissue function and HDL-C metabolism as a potential contributor to higher rates of vascular dementia in men. Further research is required to understand the sex-dependent and -independent variabilities in adipose tissue metabolism to determine novel targets for interventions to prevent the development of vascular dementia.