Abnormal Blood Vessels Research Articles

Correlation between the degree of leukoaraiosis and hyperlipidemia in post-ischemic stroke patients

Leukoaraiosis is a neurological imaging in the periventricular area and the centrum semiovale. This condition occurs due to abnormalities in the small blood vessels in the brain that lead to hypoxia. It is often observed in patients with ischemic stroke and accompanied by risk factors for hyperlipidemia. This study aimed to evaluate the correlation between the degree of leukoaraiosis and hyperlipidemia in post-ischemic stroke patients. A cross-sectional study retrospectively was conducted on post-ischemic stroke patients who underwent brain MRI (magnetic resonance imaging) on T2 and FLAIR (fluid-attenuated inversion recovery) sequence at the Department of Radiology, Dr. Sardjito General Hospital, Yogyakarta, from January 2021 to March 2022. A total of 36 patients were involved in this study. The leukoaraiosis of patient was examined by brain MRI. Degree of the leukoaraiosis was determined based on Fazekas classification. Serum cholesterol, HDL (high-density lipoprotein), LDL (low-density lipoprotein), and triglyceride levels of patients were then examined. The data obtained were then analyzed using Spearman correlation test. A positive correlation was observed between the degree of leukoaraiosis and triglyceride level (p = 0.042; r = 0.292) and age (p= 0.004; r = 0.464). However, no correlation was observed between the degree of leukoaraiosis and cholesterol, HDL, and LDL (p>0.05). In conclusion, the leukoaraiosis degree is correlated with serum triglyceride levels and age in post-ischemic stroke patients.

Visual diagnosis of female genital schistosomiasis in Zambian women from hand-held colposcopy: agreement of expert image review and association with clinical symptoms.

Background:Female genital schistosomiasis (FGS) can occur in S. haematobiuminfection and is caused by egg deposition in the genital tract. Confirming a diagnosis of FGS is challenging due to the lack of a diagnostic reference standard. A 2010 expert-led consensus meeting proposed visual inspection of the cervicovaginal mucosa as an adequate reference standard for FGS diagnosis. The agreement of expert human reviewers for visual-FGS has not been previously described. Methods: In two Zambian communities, non-menstruating, non-pregnant, sexually-active women aged 18-31 years participating in the HPTN 071 (PopART) Population-Cohort were enrolled in a cross-sectional study. Self-collected genital swabs and a urine specimen were collected at a home visit; trained midwives performed cervicovaginal lavage (CVL) and hand-held colposcopy at a clinic visit. S. haematobiumeggs and circulating anodic antigen (CAA) were detected from urine. Twosenior physicians served asexpert reviewers and independently diagnosed visual-FGS as the presence of sandy patches, rubbery papules or abnormal blood vessels in cervicovaginal images obtained by hand-held colposcopy. PCR-FGS was defined as SchistosomaDNA detected by real-time PCR in any genital specimen (CVL or genital swab). Results: Of 527 women with cervicovaginal colposcopic images, 468/527 (88.8%) were deemed interpretable by Reviewer 1 and 417/527 (79.1%) by Reviewer 2. Visual-FGS was detected in 35.3% (165/468) of participants by expert review of colposcopic images by Reviewer 1 and in 63.6% (265/417) by Reviewer 2.Cohen's kappa statistic for agreement between the two reviewers was 0.16, corresponding to "slight" agreement. The reviewers made concordant diagnoses in 38.7% (204/527) participants (100 negative, 104 positive) and discordant diagnoses in 31.8% (168/527) participants. Conclusions:The unexpectedly low level of correlation between expert reviewers highlights the imperfect nature of visual diagnosis for FGS based on cervicovaginal images. This finding is a call to action for improved point-of-care diagnostics for female genital schistosomiasis.

Liquid Embolic Agents for Endovascular Embolization: A Review

Endovascular embolization (EE) has been used for the treatment of blood vessel abnormalities, including aneurysms, AVMs, tumors, etc. The aim of this process is to occlude the affected vessel using biocompatible embolic agents. Two types of embolic agents, solid and liquid, are used for endovascular embolization. Liquid embolic agents are usually injectable and delivered into the vascular malformation sites using a catheter guided by X-ray imaging (i.e., angiography). After injection, the liquid embolic agent transforms into a solid implant in situ based on a variety of mechanisms, including polymerization, precipitation, and cross-linking, through ionic or thermal process. Until now, several polymers have been designed successfully for the development of liquid embolic agents. Both natural and synthetic polymers have been used for this purpose. In this review, we discuss embolization procedures with liquid embolic agents in different clinical applications, as well as in pre-clinical research studies.

ANALGESIC EFFICACY OF EXPRESSED BREAST MILK, 10% DEXTROSE AND STERILE WATER IN PREVENTION OF PAIN DURING SCREENING OF RETINOPATHY OF PREMATURITY- A THREE LIMBED DOUBLE BLINDED RANDOMIZED CONTROL TRIAL

Introduction : Retinopathy of prematurity is a potentially blinding eye disorder that primarily affects premature infants weighing about 1750 gm or less or born before 34 weeks of gestation. It occurs when abnormal blood vessel grows and spread throughout retina. Aim: To compare efcacy of analgesia during screening of Rtinopathy of Prematurity by EBM, 10% Dextrose and Sterile Water in preterm neonates as measured by prematurity infant pain prole (PIPP) score. Material and Methods: The present study was a three-limbed randomized controlled double-blinded study. This Study was conducted over 2 years at Dept. of Paediatrics (NICU) and RIO, IGIMS, Patna. A total of 75 patients were included in this study who were eligible for ROP screening as per NNF 2020 guidelines. Result: Data of our study showed that almost all patients had Oxygenation [74 (98.7%)] and Respiratory Distress [73 (97.3%)]. Apnea was observed to be absent in more than half of the cases [42 (56%)]. In this study ROP staging was applicable for 39 cases and out of them most common stage identied was ROP Stage 2; the distribution of pain palliative method was observed to be 10% Dextrose in 26 cases (34.7%), EBM in 24 cases (32%) and sterile water in 25 cases (33.3%). The distribution of PIPP score inference elucidated that a signicantly higher number of patients had moderate pain (6-12 score) [53 (70.7%)]. In our study, higher number of patients had moderate pain (6-12) as per PIPP Score with Expressed Breast Milk [21 (91.3%)] compared to Sterile Water [17 (59.3%)] and 10% Dextrose [16 (61.5%)] and this was statistically signicant (p=0.0444). In our study Total PIPP score was highest in Sterile Water [11.4615± 1.3633] compared to 10% Dextrose [9.4231± 2.5640] and Expressed Breast Milk [9.0000± 2.3741] and this nding was statistically signicant (p=0.0002). Conclusion: EBM was found to be signicantly better in pain palliation during ROP screening as compared to 10 % Dextrose and Sterile water

D-dimer correlation as a marker of coagulopathy with neuroimaging abnormalities on head CT scans of COVID-19 patients

Background: COVID-19 is a coronavirus disease with the main symptoms in the respiratory tract which can cause hypoxia. The duration and severity of the hypoxia can lead to oxidative stress that can affect the brain. The phenomenon of thromboembolism was also found in the form of an increase in coagulopathy markers which can cause abnormalities in small blood vessels in various organs, including the brain. Methods: We conducted a prospective crossectional study of 23 samples that met the inclusion criteria. Duration of hypoxia, degree of hypoxia based on oxygen saturation, and D-Dimer level as independent variables underwent Spearman correlation test with neuroimaging abnormalities on head CT scan. Results: The sample population consisted of 14 men (60.90%) and 9 women (39.10%), with the highest age group being 61 – 80 years old (56.50%) who underwent a head CT scan without contrast administration. Eighteen samples were found to have brain infarction, while 5 samples were without abnormalities. The Spearman correlation test found a correlation (p=0.003) with moderate correlation (r=0.558) between the D-Dimer level as a coagulopathy marker and abnormal findings on the head CT scan of samples. Where 15 samples with high D-Dimer levels (D-Dimer values above the normal level) and 3 samples with normal D-Dimer levels were found to have brain infarction. Meanwhile, the duration and degree of hypoxia based on the oxygen saturation value did not show a significant correlation with neuroimaging abnormalities (p>0.05). Conclusion: There was a moderate correlation between the D-Dimer value. No significant correlation was found between the duration of hypoxia and the degree of oxygen saturation toward neuroimaging abnormalities in COVID-19 patients.

Magnetic Resonance Imaging of Mouse Cerebral Cavernomas Reveal Differential Lesion Progression and Variable Permeability to Gadolinium.

Cerebral cavernous malformations, also known as cavernous angiomas, are blood vessel abnormalities comprised of clusters of grossly enlarged and hemorrhage-prone capillaries. The prevalence in the general population, including asymptomatic cases, is estimated to be 0.5%. Some patients develop severe symptoms, including seizures and focal neurological deficits, whereas others remain asymptomatic. The causes of this remarkable presentation heterogeneity within a primarily monogenic disease remain poorly understood. We established a chronic mouse model of cerebral cavernous malformations, induced by postnatal ablation of Krit1 with Pdgfb-CreERT2, and examined lesion progression in these mice with T2-weighted 7T magnetic resonance imaging (MRI). We also established a modified protocol for dynamic contrast-enhanced MRI and produced quantitative maps of gadolinium tracer gadobenate dimeglumine. After terminal imaging, brain slices were stained with antibodies against microglia, astrocytes, and endothelial cells. These mice develop cerebral cavernous malformations lesions gradually over 4 to 5 months of age throughout the brain. Precise volumetric analysis of individual lesions revealed nonmonotonous behavior, with some lesions temporarily growing smaller. However, the cumulative lesional volume invariably increased over time and after about 2 months followed a power trend. Using dynamic contrast-enhanced MRI, we produced quantitative maps of gadolinium in the lesions, indicating a high degree of heterogeneity in lesional permeability. MRI properties of the lesions were correlated with cellular markers for endothelial cells, astrocytes, and microglia. Multivariate comparisons of MRI properties of the lesions with cellular markers for endothelial and glial cells revealed that increased cell density surrounding lesions correlates with stability, whereas denser vasculature within and surrounding the lesions may correlate with high permeability. Our results lay a foundation for better understanding individual lesion properties and provide a comprehensive preclinical platform for testing new drug and gene therapies for controlling cerebral cavernous malformations.

Low-intensity focused ultrasound targeted microbubble destruction reduces tumor blood supply and sensitizes anti-PD-L1 immunotherapy.

Immune checkpoint blockade (ICB) typified by anti-PD-1/PD-L1 antibodies as a revolutionary treatment for solid malignancies has been limited to a subset of patients due to poor immunogenicity and inadequate T cell infiltration. Unfortunately, no effective strategies combined with ICB therapy are available to overcome low therapeutic efficiency and severe side effects. Ultrasound-targeted microbubble destruction (UTMD) is an effective and safe technique holding the promise to decrease tumor blood perfusion and activate anti-tumor immune response based on the cavitation effect. Herein, we demonstrated a novel combinatorial therapeutic modality combining low-intensity focused ultrasound-targeted microbubble destruction (LIFU-TMD) with PD-L1 blockade. LIFU-TMD caused the rupture of abnormal blood vessels to deplete tumor blood perfusion and induced the tumor microenvironment (TME) transformation to sensitize anti-PD-L1 immunotherapy, which markedly inhibited 4T1 breast cancer's growth in mice. We discovered immunogenic cell death (ICD) in a portion of cells induced by the cavitation effect from LIFU-TMD, characterized by the increased expression of calreticulin (CRT) on the tumor cell surface. Additionally, flow cytometry revealed substantially higher levels of dendritic cells (DCs) and CD8+ T cells in draining lymph nodes and tumor tissue, as induced by pro-inflammatory molecules like IL-12 and TNF-α. These suggest that LIFU-TMD as a simple, effective, and safe treatment option provides a clinically translatable strategy for enhancing ICB therapy.

The frequency and macromorphological classification of abnormal blood vessel impressions and periosteal appositions of the dura mater in an early modern osteological collection from Poland

ObjectiveThe macromorphological characteristics and frequency of endocranial abnormal blood vessel impressions (ABVI) and periosteal appositions of dura mater (PADM), and their association with sex, age-at-death and scurvy-like lesions were studied. The possible etiologies of these lesions were discussed. MaterialsA total of 144 adult skulls excavated from an early modern (16th-19th c. CE) cemetery at the Czysty Square in Wrocław (Poland) were examined, most of which were intact. MethodsThe endocranial surface was inspected with an endoscope for the presence, location, and severity of ABVI and PADM. Frequencies of ABVI and PADM were grouped by sex and age-at-death. ResultsA little more than a half (53.5 %) of the examined skulls were affected by ABVI and/or PADM. PADM were more frequent in females. However, both alteration types occurred with similar frequencies across all age-at-death categories. ConclusionsThe high frequency of ABVI and PADM suggests that meningeal infections and/or hemorrhage among inhabitants of early modern Wrocław, especially in females, were common. SignificanceThe paper emphasizes the need for using an endoscope in standard anthropological analysis of intact skulls, as it allows for a nondestructive inspection of the endocranial surface. LimitationsThe endoscope did not allow for an accurate examination of the middle cranial fossa. Suggestions for further researchComparative studies with other historical populations are necessary to better understand the possible etiologies of macromorphological and demographic characteristics of ABVI and PADM.

Exercise protects vascular function by countering senescent cells in older adults.

Blood vessels are key conduits for the transport of blood and circulating factors. Abnormalities in blood vessels promote cardiovascular disease (CVD), which has become the most common disease as human lifespans extend. Aging itself is not pathogenic; however, the decline of physiological and biological function owing to aging has been linked to CVD. Although aging is a complex phenomenon that has not been comprehensively investigated, there is accumulating evidence that cellular senescence aggravates various pathological changes associated with aging. Emerging evidence shows that approaches that suppress or eliminate cellular senescence preserve vascular function in aging-related CVD. However, most pharmacological therapies for treating age-related CVD are inefficient. Therefore, effective approaches to treat CVD are urgently required. The benefits of exercise for the cardiovascular system have been well documented in basic research and clinical studies; however, the mechanisms and optimal frequency of exercise for promoting cardiovascular health remain unknown. Accordingly, in this review, we have discussed the changes in senescent endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) that occur in the progress of CVD and the roles of physical activity in CVD prevention and treatment.

Associations of human papillomavirus genotypes and cervical vascular abnormality in a cohort of women underwent colposcopy, a retrospective study of 6716 patients.

Abnormal vessel patterns are specific signs in patients with early cervical abnormality and cervical cancer(CC) by colposcopy, but the impact of human papillomavirus (HPV) infections on abnormal vessel patterns remains unknown. A total of 6716 female patients with HPV infections or cytological abnormalities who underwent a colposcopy following abnormal CC screening results were included in the study. The final pathological diagnosis was confirmed to be the most severe pathological grade across cervical biopsy, endocervical canal curettage (ECC) and conization. Univariate and multivariate logistic regression analyses were used to investigate the association between HPV infections and abnormal vessel patterns, adjusting for age, gravidity and parity. There were 6124 normal vascular cases by colposcopy and 592 cases with cervical vascular abnormality. The prevalence of HPV infections was 4284 (70%) in normal patients, and the prevalence of HPV infections was 479 (80%) in cervical vascular abnormality patients. HPV high-risk type 16 infection alone increased the risk of cervical heteromorphic blood vessels (aOR=3.66, 95%CI: 2.54~5.27). HPV 16 and 33 alone (other than the commonly recognized subtype of 18) or coinfection of these two genotypes could increase the risk of cervical punctate vascular and cervical vascular mosaic features and abnormal cervical blood vessels. An increased risk of abnormal cervical lesions was observed for HPV 16 and 33 alone or combined in coinfection compared to the negative group. The risk of cervical vascular abnormality was increased 10-fold by coinfection with HPV 16 and 33 (aOR=10.67, 95% CI: 4.54~25.09, P<0.001). HPV 16, 33 alone or combined in coinfection were associated with an increased risk of lesions more advanced than high-grade squamous intraepithelial lesion (HSIL) when compared to the negative group. The risk of lesions more advanced than HSIL was up to 26-fold higher in the coinfection with HPV 16 and 33 group than in the negative group (aOR=26.23, 95%CI: 11.23~61.27, P<0.001). HPV16 and 33 are the most dangerous HPV genotypes correlated with abnormal vascular patterns. Combined HPV16 and HPV33 infection increases the risk of abnormal vascular patterns. Combined HPV16 and HPV33 infection increases the risk of developing HSIL+.

Anti-vascular endothelial growth factor for neovascular glaucoma.

Anti-vascular endothelial growth factor for neovascular glaucoma.

Colon-targeted bacterial hydrogel for tumor vascular normalization and improved chemotherapy.

The endogenous H2S plays an important role in the occurrence and development of colon cancer, and is related to the abnormal blood vessels. Here, we reported on a sulfhydryl hyaluronid-based hydrogel (HA-SH) synthesized by amide reaction and further obtained a bacterial hydrogel by loading Thiobacillus denitrificans to the hydrogel for targeting adhesion to the colon. It was found that the loaded bacteria in HA-SH hydrogel can scavenge excess H2S in colon cancer, then promote tumor vascular normalization and improve the delivery of chemotherapy drug CPT to inhibit tumor progression. Both in vivo and in vitro experiments show that the self-crosslinked bacterial hydrogel has satisfactory effects in inhibiting tumor progression and promoting tumor vascular normalization in colon cancer. This study presents an efficient method to target the colon and consume overexpressed H2S in colon cancer to inhabit tumor progression, providing a new way for oral drug treatment of colon cancer.

Tumor spheroid-based and microtumor-based vascularized models for replicating the vascularized tumor microenvironment

BackgroundTumor vasculature is a crucial pathway for supplying nutrients and oxygen to tumors during their progression, as well as facilitating the delivery of anticancer drugs or immunotherapeutic agents. Microfluidic technology has emerged as a powerful tool in creating microenvironments within 3D cell cultures that more closely resemble in vivo conditions, by enabling precise control of fluid flow. As a result, microfluidic devices have made significant progress in replicating both the structural and functional characteristics of the tumor microenvironment in vitro. Methods and ResultsIn this study, we present two approaches for reconstructing the tumor vasculature using tumor spheroids or microtumors, with a particular focus on in vivo functional mimicry and experimental reproducibility. Tumor spheroid-based vascular models provide an observatory window into tumor vasculature centered on tumor spheroids, enabling quantitative measurement of the degree of abnormality of blood vessels developing around the tumor spheroid and the invasiveness of metastatic tumors. Microtumor-based vascular models, on the other hand, have the potential to enhance our comprehension of advanced and metastatic cancers at the single-cell level by elucidating the proliferative and metastatic capacities of tumor cells, as well as the vascular permeability that is contingent upon the subtypes of tumor cells. ConclusionOur platforms provide valuable insights into the development of novel in vitro models for studying the tumor microenvironment and advancing our understanding of cancer biology.

Abstract P6-12-05: The role of endothelial-specific AXL and its associated signaling pathways in the tumor microenvironment

Abstract Most breast cancer deaths result from the development of metastases. The complex tumor microenvironment provides signals that can instruct both breast cancer cells to invade and tumor blood vessels to be leaky, hence supporting metastasis. We identified the receptor tyrosine kinase (RTK) AXL to be essential for metastasis. Genetic ablation of Axl in mouse models of HER2+ breast cancer, either globally or specifically in mammary epithelial cells, blunts metastasis but not primary tumor growth. We found that Axl expressed in tumor cells contributes to the remodeling of the tumor microenvironment, including immune cell recruitment and abnormal blood vessels. Hence, AXL in epithelial cells promotes cell invasion and shapes a pro-metastatic microenvironment that would be poorly responding to treatments such as immunotherapy. While AXL is known to be expressed on endothelial cells, its endothelial function has yet to be clearly defined. This project aims to address the hypothesis that AXL expressed on endothelial cells promotes processes that lead to abnormal blood vessel formation to promote metastasis. To address this hypothesis, we first studied the specific intracellular interactions between two RTKs, AXL and the known pro-angiogenic receptor VEGFR. Our preliminary analyses indicates that GAS6 can not only induce the phosphorylation of the permeability marker eNOS on its own but can also potentiate the VEGF’s response. The index of linearity of the endothelial tight junctions upon GAS6 stimulation show increased permeability of the endothelial cells. To further characterize the signaling pathways controlled by these receptors, we plan to perform a phosphoproteomics screen. We will focus on studying the AXL+VEGFR phosphoproteome and define the signaling pathways that impact vascular permeability. The most interesting candidate(s) will be studied in the context of mouse tumor models. In parallel, we are generating a conditional deletion of Axl in endothelial cells by crossing Axlfx/fx mice with Pdgfb:iCreER animals. With this, we will study the specific endothelial effects of Axl in vivo, specifically with vessel permeability and retinal angiogenesis assays. Multiple anti-angiogenic therapies for cancer failed in the clinic highlighting the need for new strategies to target endothelial cells in cancer. This project will provide essential information on the role of endothelial specific AXL, in the context of the HER2 breast cancer, and of its downstream effectors. With more specific targets, anti-angiogenic therapies could decrease their off-target effects and increase their efficacy in the clinic. This project has the potential to uncover therapeutic targets that could reduce the metastatic burden in breast cancer patients, and therefore better the prognostic for the HER2 cancer subtype. Citation Format: Andréane Lalonde, Jean-François Côté. The role of endothelial-specific AXL and its associated signaling pathways in the tumor microenvironment [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-12-05.

Granzyme B Contributes to Choroidal Neovascularization and Age-Related Macular Degeneration Through Proteolysis of Thrombospondin-1

Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in the elderly. The pathology of neovascular age-related macular degeneration (nAMD), also known as wet AMD, is associated with an abnormal blood vessel growth in the eye and involves an imbalance of proangiogenic and antiangiogenic factors. Thrombospondin (TSP)-1 and TSP-2 are endogenous matricellular proteins that inhibit angiogenesis. TSP-1 is significantly diminished in eyes with AMD, although the mechanisms involved in its reduction are unknown. Granzyme B (GzmB) is a serine protease with an increased extracellular activity in the outer retina and choroid of human eyes with nAMD-related choroidal neovascularization (CNV). This study investigated whether TSP-1 and TSP-2 are GzmB substrates using in silico and cell-free cleavage assays and explored the relationship between GzmB and TSP-1 in human eyes with nAMD-related CNV and the effect of GzmB on TSP-1 in retinal pigment epithelial culture and an explant choroid sprouting assay (CSA). In this study, TSP-1 and TSP-2 were identified as GzmB substrates. Cell-free cleavage assays substantiated the GzmB proteolysis of TSP-1 and TSP-2 by showing dose-dependent and time-dependent cleavage products. TSP-1 and TSP-2 proteolysis were hindered by the inhibition of GzmB. In the retinal pigment epithelium and choroid of human eyes with CNV, we observed a significant inverse correlation between TSP-1 and GzmB, as indicated by lower TSP-1 and higher GzmB immunoreactivity. In CSA, the vascular sprouting area increased significantly with GzmB treatment and reduced significantly with TSP-1 treatment. Western blot showed significantly reduced expression of TSP-1 in GzmB-treated retinal pigment epithelial cell culture and CSA supernatant compared with that in controls. Together, our findings suggest that the proteolysis of antiangiogenic factors such as TSP-1 by extracellular GzmB might represent a mechanism through which GzmB may contribute to nAMD-related CNV. Future studies are needed to investigate whether pharmacologic inhibition of extracellular GzmB can mitigate nAMD-related CNV by preserving intact TSP-1.

Prognostic factors for the development and progression of proliferative diabetic retinopathy in people with diabetic retinopathy.

Prognostic factors for the development and progression of proliferative diabetic retinopathy in people with diabetic retinopathy.

A Clinicopathological Review of 203 Cases of Atypical Polypoid Adenomyoma of the Uterus.

To provide a reference for the diagnosis and treatment of atypical polypoid adenomyoma (APA). This was a retrospective study of 203 APA patients from 2011 to 2021. The clinicopathological characteristics, treatments, and prognosis were analyzed. The average age at diagnosis of APA patients was 39.30 ± 11.01 years, and premenopausal women accounted for 81.3%. Abnormal uterine bleeding or menorrhagia were the most common clinical manifestations of APA. The uterine fundus (78.3%), followed by the lower segment of the uterus (11.8%), was the most common location of the APA lesions. Abnormal blood vessels were seen on the surface of 28 APA tumors. APA can coexist with atypical endometrial hyperplasia (18.2%) and endometrial cancer (10.8%). Immunohistochemical analysis was performed on 99 samples. In the glandular component, ER (94.8%), PR (94.8%), Ki-67 (51.5%), p53 (45.6%), PTEN (18.8%), and mismatch repair proteins (96.4%) were positively expressed. Stromal immunophenotype expression was exhibited as follows: CD10-(89.5%), p16+(86.9%), h-caldesmon-(66.7%), Desmin+(75%), and Vimentin+(88.9%). Fifty-five APA patients received TCR, and 33 of them received adjuvant therapy after the operation. The postoperative recurrence rate (9.1% vs. 36.4%, p < 0.05) and malignant transformation rate (3.0% vs. 18.2%, p < 0.05) of the treated group were significantly lower than the untreated group. APA usually occurs in women of childbearing age, and the diagnosis is based on pathological morphology. APA has a low malignant potential, and those who have fertility requirements can undergo conservative TCR treatment, supplemented by progesterone treatment after surgery and close follow-up. Total hysterectomy is the treatment of choice for APA patients with atypical endometrial hyperplasia around the lesion.

Molecular Mechanisms Behind the Role of Plasmacytoid Dendritic Cells in Systemic Sclerosis

Systemic sclerosis (SSc) is a debilitating autoimmune disease that affects multiple systems. It is characterized by immunological deregulation, functional and structural abnormalities of small blood vessels, and fibrosis of the skin, and, in some cases, internal organs. Fibrosis has a devastating impact on a patient's life and lung fibrosis is associated with high morbimortality. Several immune populations contribute to the progression of SSc, and plasmacytoid dendritic cells (pDCs) have been identified as crucial mediators of fibrosis. Research on murine models of lung and skin fibrosis has shown that pDCs are essential in the development of fibrosis, and that removing pDCs improves fibrosis. pDCs are a subset of dendritic cells (DCs) that are specialized in anti-viral responses and are also involved in autoimmune diseases, such as SSc, systemic lupus erythematosus (SLE) and psoriasis, mostly due to their capacity to produce type I interferon (IFN). A type I IFN signature and high levels of CXCL4, both derived from pDCs, have been associated with poor prognosis in patients with SSc and are correlated with fibrosis. This review will examine the recent research on the molecular mechanisms through which pDCs impact SSc.

Genetic testing in the evaluation of individuals with clinical diagnosis of atypical Sturge-Weber syndrome.

Sturge-Weber Syndrome (SWS) is a rare vascular malformation disorder characterized by abnormal blood vessels in the brain, skin, and eye. SWS is most commonly caused by a somatic mosaic GNAQ-p.Arg183Gln variant. In this series, 12 patients presented for clinical evaluation of SWS but were noted to have atypical features, and therefore germline and/or somatic genetic testing was performed. Atypical features included extensive capillary malformation on the body as well as the face, frontal bossing, macrocephaly, telangiectasia, overgrowth of extremities, absence of neurologic signs and symptoms, and family history of vascular malformations. Five patients had a somatic GNAQ or GNA11 pathogenic variant, one patient had a somatic mosaic likely-pathogenic variant in PIK3CA, and another one had a somatic mosaic deletion that disrupted PTPRD. The other five patients had germline variants in RASA1, EPHB4, or KIT. Our findings suggest that patients presenting for SWS evaluation who have atypical clinical characteristics may have pathogenic germline or somatic variants in genes other than GNAQ or GNA11. Broad germline and somatic genetic testing in these patients with atypical findings may have implications for medical care, prognosis, and trial eligibility.

Visual diagnosis of female genital schistosomiasis in Zambian women from hand-held colposcopy: agreement of expert image review.

Female genital schistosomiasis (FGS) can occur in S. haematobium infection and is caused by parasite egg deposition in the genital tract. Confirming a diagnosis of FGS is challenging due to the lack of a diagnostic reference standard. A 2010 expert-led consensus meeting proposed visual inspection of the cervicovaginal mucosa as an adequate reference standard for FGS diagnosis. The agreement of expert human reviewers for visual-FGS has not been previously described. Methods: In two Zambian communities, non-menstruating, non-pregnant, sexually-active women aged 18-31 years participating in the HPTN 071 (PopART) Population-Cohort were enrolled in a cross-sectional study. Self-collected genital swabs and a urine specimen were collected at a home visit; trained midwives performed CVL and hand-held colposcopy at a clinic visit. S. haematobium eggs and circulating anodic antigen (CAA) were detected from urine. Two expert reviewers independently diagnosed visual-FGS as the presence of sandy patches, rubbery papules or abnormal blood vessels in digital cervicovaginal images obtained by hand-held colposcopy. PCR-FGS was defined as Schistosoma DNA detected by real-time PCR in any genital specimen (CVL or genital swab). Results: Of 527 women with cervicovaginal colposcopic images, 468/527 (88.8%) were deemed interpretable by Reviewer 1 and 417/527 (79.1%) by Reviewer 2. Visual-FGS was detected in 35.3% (165/468) of participants by expert review of colposcopic images by Reviewer 1 and in 63.6% (265/417) by Reviewer 2. Cohen's kappa statistic for agreement between the two expert reviewers was 0.16, corresponding to "slight" agreement. The reviewers made concordant diagnoses in 38.7% (204/527) participants (100 negative, 104 positive) and discordant diagnoses in 31.8% (168/527) participants. Conclusions: The unexpectedly low level of correlation between expert reviewers highlights the imperfect nature of visual diagnosis for FGS based on cervicovaginal images obtained with a hand-held colposcope. This finding is a call to action for improved point-of-care diagnostics for female genital schistosomiasis.