Grade Lesions Research Articles

The degree of toxoplasmosis and testicular histomorphometry in rats

AbstractToxoplasma gondii (T. gondii) ranks as the third most common parasitic parasite worldwide, and it is estimated that > 60% of the population is infected with T. gondii worldwide at some point in their lives. So. Therefore, it is highly curious that T. gondii could be a potential cause of idiopathic infertility that is incidental to male partners, who are responsible for nearly 50% of cases. Testicular histomorphometric analysis was developed to investigate fertility problems. The objective of this experimental study was to assess the impact of toxoplasmosis on spermatogenesis indicated by histomorphometric changes in rat testes and its correlation with the degree of infection in the brain. Ninety male Wistar albino rats were infected with T. gondii, and 30 male rats composed the control group. The studied parameters were investigated from the seventh week until the twelfth week postinfection by estimating the body weight, the weight of the testes, histopathological examination, and metric analysis of the testes. Each time, correlations were detected between the investigated parameters and the infection severity calculated by estimating the cyst burden in brain homogenates and brain lesion grading of stained histological sections.Our findings demonstrated a significant adverse impact of toxoplasmosis on absolute body weight, testis weight, and testis histomorphometry. The grading of brain lesions and the number of brain cysts paralleled each other. There was a reverse correlation between the gonado-somatic index and the number of brain cysts and brain lesion grade. There was a statistically significant correlation between the brain cyst count and the brain lesion grade and the indices 20 A, 20b, 250, and 200 of the testes metric analysis. Conclusion: Our results revealed that toxoplasmosis has an adverse impact on male rat spermatogenic cells, which in turn affects spermatogenesis and fertility. This impact is significantly correlated with the degree of latent infection in the brain.

NIMG-30. DEUTERIUM METABOLIC IMAGING (DMI) SHOWS A STRONG RELATION BETWEEN TUMOR GRADE AND GLUCOSE METABOLISM IN PRIMARY BRAIN TUMORS

Abstract BACKGROUND Metabolic imaging using FDG-PET is a key component of disease management in many cancers outside of the brain, but in brain tumors, it often shows low tumor-to-brain contrast because of high background signal from normal brain. Deuterium metabolic imaging (DMI) is a new 2H magnetic resonance spectroscopic imaging-based technique that when combined with administration of 2H-labeled glucose can provide high tumor-to-brain image contrast because it can detect downstream metabolism instead of only glucose uptake. In this observational study, DMI of glucose metabolism was performed in 22 patients with primary brain tumors of different grades, and at different disease stages. METHODS DMI data were acquired using a 4 tesla MRI scanner after oral administration of 0.75g/kg of [6,6’-2H2]-glucose in water. Metabolic maps were generated of 2H-labeled glucose, glutamate+glutamine (Glx), lactate (Lac), and Lac/(Lac+Glx), a proxy for the metabolic shift observed in many cancers known as the Warburg effect. Volumes of interest (VOI) based on contrast-enhancing and non-enhancing tumor regions were created using clinical MRIs and combined with DMI maps to generate tumor-specific values for Lac/(Lac+Glx). Eta-squared was calculated using tumor grade and Lac/(Lac+Glx) as independent and dependent variables; data are reported as mean±SD. Results – Tumor-to-brain image contrast for Lac/(Lac+Glx) was 2.57±0.93 for grade 4 (n=14), 1.74±0.75 for grade 3 (n=6) and 0.94±0.28 for grade 2 lesions (n=3). Lac/(Lac+Glx) was 0.36±0.13 for grade 4; 0.19±0.049 for grade 3; 0.09±0.042 for grade 2 lesions; and 0.14±0.043 for normal brain. Eta-squared between tumor grade and Lac/(Lac+Glx) was 0.52. CONCLUSIONS VOI-based analysis showed a high dependence of metabolism-specific image contrast to tumor grade. The apparent relation between lesion grade and Lac/(Lac+Glx) indicates the potential of DMI to complement anatomical MRI and possibly provide a valuable biomarker indicating active tumor tissue and could improve evaluating disease progression.

Correlation between Fundus Damage and Renal Function Deterioration in Chronic Kidney Disease Patients

Introduction: This study aimed to explore the correlation between the extent of fundus damage and the severity strategies for chronic kidney disease (CKD). Methods: We collected data from 118 CKD patients, including general information, renal function indicators, and fundoscopic examination results. The stages of CKD and degrees of fundus lesions were graded. SPSS 25.0 software facilitated the analysis of correlations using Kendall's tau-b correlation analysis and ordinal regression analysis. Results: Statistically significant differences were observed among multiple CKD stages in the distribution of age, systolic blood pressure, diastolic blood pressure, hemoglobin, total cholesterol, homocysteine, cystatin C, serum creatinine, blood urea, eGFR, 24-hour urine protein, urine microalbumin, urine microalbumin/urine creatinine, and blood β2 microglobulin, complement C3. Notably, the levels of cytokeratin 19 fragment and transforming growth factor β significantly increased in all CKD stages. Kendall's tau-b correlation analysis revealed a significant positive correlation between CKD stage and fundus lesion grade. Ordinal regression analysis indicated that sex differences, total cholesterol levels, and hemoglobin levels were significant predictors of fundus lesion risk. Compared with patients at stage 5 CKD, the risk of fundus damage significantly lower in patients in stage 2 and stage 3, further demonstrating a positive correlation between renal function deterioration and increased risk of fundus damage. Conclusions: Routine fundus screening and early intervention for fundus lesions are vital for assessing CKD deterioration, providing new directions for future related research.

A novel methylation-detection panel for HPV associated high-grade squamous intraepithelial lesion and cervical cancer screening

Cervical cancer (CC) was considered to be the most common gynaecological cancer, with an estimated 342,000 deaths worldwide each year, as the majority of patients were diagnosed at an advanced stage of the disease. The purpose of this study was to evaluate the predictive value of multi-locus methylation assay for the early detection of CC. The cervical exfoliated cell samples from 492 HPV-positive females with cervical lesions were collected and subjected to methylation detection of gene FAM19A4, EPB41L3 and PAX1 after bisulfite conversion. The levels of gene methylation in patients with different severity of cervical lesions were evaluated and compared. The receiver-operating characteristic (ROC) curve was established and efficacy indexes such as sensitivity, specificity and area under the curve (AUC) were calculated to assess the diagnostic value of DNA methylation detection at multiple gene loci for CC. The methylation levels of FAM19A4, EPB41L3 and PAX1 were significantly increased with the grade of cervical squamous intraepithelial lesions. The sensitivities of FAM19A4, EPB41L3 and PAX1 alone for high-grade squamous intraepithelial lesion (HSIL) and CC diagnosis were 84.6%, 86.3% and 88.0%, respectively; when three markers were combined by a logistic regression model, the sensitivity was 88.0%, with a high specificity of 97.7% and AUC of 0.957 (95% CI 0.937–0.977). Methylation status of FAM19A4, EPB41L3 and PAX1 were highly specific and effective for monitoring the progression of cervical lesions and the tri-gene methylation assay could be used as a triage tool for CC early screening.

Distribution of 14 High-Risk HPV Types and p16/Ki67 Dual-Stain Status in Post-Colposcopy Histology Results: Negative, Low- and High-Grade Cervical Squamous Intraepithelial Lesions.

Determining the distribution of high-risk human papillomavirus (HR-HPV) types in histologic low-(LSIL) and high-grade (HSIL/CIN2+) squamous intraepithelial lesions through a diagnostic process in a cervical cancer prevention provides one of the key etiological factors behind further progression and persistence. Incorporating novel high-grade cervical lesion biomarkers such as p16/Ki67 dual staining (DS) alongside HPV typing has become important in detecting cervical precancers. Among 28,525 screening tests and 602 histology results, 559 cases with HR-HPV and histology results obtained from colposcopic biopsy were retrospectively analyzed, together with DS status. The χ2 test with Bonferroni correction evaluated the differences in HR-HPV type prevalence and DS positivity across three histologic study groups. A statistically significant difference in the prevalence of HPV 16 was observed between negative and HSIL/CIN2+ (p = 0.00027) groups, as well as between the LSIL/CIN1 and HSIL/CIN2+ groups (p = 0.00041). However, no significant difference was found between the negative and LSIL/CIN1 groups. Similarly, the DS positivity difference was significant between the negative and HSIL/CIN2+ (p < 0.0001) and between the LSIL/CIN1 and HSIL/CIN2+ groups (p < 0.0001), but there was no significant difference between the negative and LSIL/CIN1 groups. The study highlights the heterogeneous nature of HPV-related cervical pathologies, and the distinct risks associated with different cervical lesion grades, emphasizing the importance of HR-HPV type distribution and DS status.

TLR-2 and TLR-4 mRNA expression in different grades of histopathological lesions of equine endometrium from follicular phase.

Increased synthesis and deposition of collagen(COL) in the extracellular matrix (ECM) of equine endometrium contributes to endometrosis. Toll-like receptors (TLRs) are transmembrane receptors involved in the innate immune response, recognized for their role in antigen recognition and previously associated with equine endometritis. The TLRs not only recognize pathogen-associated molecular patterns but also regulate inflammations, fibrosis and cancer. The aim of this study was to explore the relationship between TLR expression at different stages of Kenney and Doig's (K-D) grading and COL1 expression during the follicular phase of the oestrous cycle. Forty samples of endometrial tissues were collected post-mortem from mares on the follicular phase of the oestrous cycle (10 samples of each K-D category). Relative mRNA transcription of TLR-2, TLR-4 and COL1A2 genes was assessed using qPCR, and COL1 protein expression by Western blot analysis. The COL1A2 transcription increased in category IIB when compared to categories I, IIA and III endometria (p < .01). The relative protein abundance of COL1 showed no significant differences between endometrial categories (p > .05). As for the TLRs mRNA transcription, TLR-2/-4 transcripts increased in IIA when compared to the other K-D endometria categories (p < .05). Our findings suggest that TLRs may be involved in the initiation of the endometrial inflammatory response. Additional studies are needed to explore TLRs' potential role as diagnostic markers for monitoring inflammation progression and fibrosis development, as well as their involvement in the mechanisms underlying fibrotic pathways.

Isolation and Identification Of Candida Albicans In Smokers With Epithelial Dysplasia And Squamous Cell Carcinoma: A Histopathological Correlation

Background:Greater adaptability of Candida to the host niche makes it the most common opportunistic pathogen. Its role as a commensal or pathogen in development of premalignancies and its progression to malignancies is of considerable debate. Present study was undertaken to determine the role of Candida albicans(CA)in progressionof oral cancer by isolation and identification by mycological methods in smokers without oral lesions and histopathologically diagnosed cases of epithelial dysplasia (ED) and oral squamous cell carcinoma (OSCC). Methodology:The study comprised of 120 cases that included study group of 40 smokers with oral lesions, 40 smokers without oral lesions and 40 non-smokers as control group. Clinical examination was followed by oral rinse sample collection and biopsy for histopathological confirmation. Sedimented oral rinse was inoculated on Sabouraud’s dextrose agar (SDA). Isolated Candida colony after identification with Gram stain was subjected to germ tube and chlamydospore formation test for confirmation of CA. The data was statistically analysed using chi square test. Results:Colonisation of CA was 52.5% in the study group and 5% in the control group, was found to be statistically significant (p&lt;0.001).Association of CA in smokers with varying histopathologic grades of oral lesions showed no evidence of a correlation. However, positive correlation was found in OSCC (n=19, 95%) and showed statistical significance (p&lt;0.001). Conclusion:The present study showed an increase in colonization of CA in malignant lesions suggesting that CA in conjunction with tobacco usage may play a role in oral carcinogenesis.

Diagnostic Performance of Host and Viral DNA Methylation Analysis in the Identification of Anal Intraepithelial Neoplasia and Cancer: Systematic Review and Meta-Analysis

Introduction: DNA methylation-based biomarkers have been investigated as useful tools in the carcinogenesis process, including the triage of HPV-associated cancers. In this context, we conducted a systematic review and meta-analysis focused on evaluating the changes in the level of DNA methylation in cases of pre-cancerous (i.e., anal intraepithelial neoplasia, AIN-1, -2., -3) and cancerous (i.e., squamous cell carcinoma, SCC) anal lesions. Methods: A research in the PubMed, Scopus, and Web of Science databases was carried out, following the PRISMA 2020 protocol, using the following keywords: “anal cancer”, “anal intraepithelial neoplasia”, “methylation”, and “epigenetic”. All observational studies that reported the level of DNA methylation by grade of anal lesions and for different target genes were included. The QUADAS-2 tool was used to assess the studies’ quality, whereas pooled prevalence, sensitivity, specificity, and diagnostic odds ratio (DOR) were employed to verify the accuracy of the test in the detection of high-grade lesions. Results: Eight studies met the inclusion criteria, involving a total of 1555 clinical samples. The prevalence of methylation-positive samples by histological grading was 27%, 45%, 54%, and 98% for AIN1, AIN2, AIN3, and SCC, respectively. Similar results were observed for the DOR, with higher ORs in more severe lesions. The pooled AUC (95%CI) for the diagnosis of ≥AIN2 was 0.68 (0.63–0.73). Conclusions: The present review and meta-analysis support the introduction of DNA methylation-based biomarkers in the triage of subjects with low-grade anal lesions and in the monitoring of treatment outcomes. Standardized protocols and a prospective study design are needed to implement methylation tests in clinical practice.

Spontaneous recanalization in acute large core ischemic stroke due to large vessel occlusion: a post-hoc analysis of the ANGEL-ASPECT trial

BackgroundPrevious studies have indicated that a subset of patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) experience spontaneous recanalization (SR), but the prognosis and factors associated...

Abstract C030: Evolutionary and epistatic analyses reveal genic interactions with KRAS during malignant progression of pancreatic ductal adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PDAC) patients face poor prognoses attributable to delayed disease detection, resulting in distant metastases and thereby reducing treatment efficacy. The challenge of detecting PDAC lesions during early stages emanates from an inauspicious trifecta of clinical factors: early-stage malignancies are often asymptomatic, existing biomarkers are insufficiently sensitive, and the physical location of the pancreas stymies reliable screening. A promising strategy towards improving outcomes is the resection of high-risk, pre-malignant lesions deemed likely to progress into carcinomas. Intraductal papillary mucinous neoplasms (IPMNs) are both large enough to be detected during abdominal imaging and can originate PDAC lesions. However, a patient may have many IPMN cysts, many of which will never progress. As pancreatic resection carries with it a high risk of morbidity, distinguishing the the evolutionary trajectories of IPMNs that will and will not progress could inform treatment strategies. Additionally, these trajectories may serve as disruptable targets to manage pre- neoplastic lesions, preventing their progression to PDAC. The vast majority PDAC cases contain mutations in KRAS and GNAS with secondary driver mutations in TP53, SMAD4, CDKN2A, and RNF43. Recent work has compared the frequency of these mutations in PDAC with low-grade and high-grade IPMN lesions, finding that they more common in high than low- grade lesions. Interestingly, unlike KRAS or GNAS, KLF4 mutations are prevalent in low-grade IPMNs, rare in high-grade IPMNs, and almost never observed in full-fledged carcinoma, suggesting distinct evolutionary trajectories possibly mediated by epistatic interactions between KLF4 and KRAS. However, the prevalence of a mutation is not dispositive as to its importance in tumorgenesis. Mutations in TTN, for instance, are frequently observed in PDAC and other cancers, but are widely considered to play a modest role, if any, in these cancers. To understand the contribution of a mutation to the evolution of cancer, we must instead deconvolve selection from baseline mutation rate across genomic sites and among patients to distinguish truly oncogenic mutations from mutations that occur frequently merely due to high underlying mutational rates. Here, we quantify the evolutionary and epistatic interplay between KRAS, KLF4, and other frequent mutations in IPMNs and PDAC during malignant transition. First, we report the cancer effect sizes of single-nucleotide variants in IPMNs at varying dysplastic stages. Then, we infer the synergistic and antagonistic interactions between driver mutations, providing insight into the order in which driver mutations occur. We then corroborate this epistasis-inferred ordering with the ordering of mutations recovered from ancestral state reconstruction derived from time-calibrated phylogenies. Lastly, we probe the mutational processes most responsible for conferring highly oncogenic mutations in IPMNs and PDACs to identify potentially actionable or preventable pathways of disease progression. Metabolism Citation Format: Nic Fisk, Derek Song, Margaret Moore, Cole G Jensen, Vincent L. Cannataro, Mofeed Nagib, Jeffrey D Mandell, Luisa Escobar-Hoyos, John W Kunstman, Jeffrey P Townsend. Evolutionary and epistatic analyses reveal genic interactions with KRAS during malignant progression of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C030.

International Academy of Cytology standardized reporting of breast fine-needle aspiration cytology with cyto-histopathological correlation of breast carcinoma.

The International Academy of Cytology (IAC) has developed a standardized approach for reporting the findings of breast fine-needle aspiration cytology (FNAC). Accordingly, there are five chief categories of breast lesions, C1 (insufficient material), C2 (benign), C3 (atypical), C4 (suspicious), and C5 (malignant). The prognostication and management of breast carcinoma can be performed readily on the basis of this classification system. The aim of this study was to classify various breast lesions into one of the above-named categories and to further grade the C5 lesions specifically using the Robinson system. The latter grades were then correlated with modified Scarff-Bloom-Richardson (SBR) grades. This retrospective study was undertaken in the pathology department of a hospital located in the urban part of the city of Bangalore. All FNAC procedures performed on breast lumps spanning the year 2020 were included in the study. A total of 205 breast lesions was classified according to the IAC guidelines into C1 (6 cases, 2.9%), C2 (151 cases, 73.7%), C3 (13 cases, 6.3%), C4 (5 cases, 2.5%), and C5 (30 cases, 14.6%) groups. The C5 cases were further graded using Robinson's system. The latter showed a significant correlation with the SBR system (concordance=83.3%, Spearman correlation=0.746, Kendall's tau-b=0.736, kappa=0.661, standard error=0.095, p≤.001). A standardized approach for FNAC reporting of breast lesions, as advocated for by the IAC, improves the quality and clarity of the reports and assures diagnostic reproducibility on a global scale. Further, the cytological grading of C5 lesions provides reliable cyto-prognostic scores that can help assess a tumor's aggressiveness and predict its histological grade.

An attentional mechanism model for segmenting multiple lesion regions in the diabetic retina.

Diabetic retinopathy (DR), a leading cause of blindness in diabetic patients, necessitates the precise segmentation of lesions for the effective grading of lesions. DR multi-lesion segmentation faces the main concerns as follows. On the one hand, retinal lesions vary in location, shape, and size. On the other hand, the currently available multi-lesion region segmentation models are insufficient in their extraction of minute features and are prone to overlooking microaneurysms. To solve the above problems, we propose a novel deep learning method: the Multi-Scale Spatial Attention Gate (MSAG) mechanism network. The model inputs images of varying scales in order to extract a range of semantic information. Our innovative Spatial Attention Gate merges low-level spatial details with high-level semantic content, assigning hierarchical attention weights for accurate segmentation. The incorporation of the modified spatial attention gate in the inference stage enhances precision by combining prediction scales hierarchically, thereby improving segmentation accuracy without increasing the associated training costs. We conduct the experiments on the public datasets IDRiD and DDR, and the experimental results show that the proposed method achieves better performance than other methods.

Diabetic Retinopathy Lesion Types and Distribution on Ultrawide Field Imaging and the Risk of Disease Worsening Over Time.

To evaluate the effect of diabetic retinopathy (DR) lesion type [hemorrhages and/or microaneurysms (H/Ma), intraretinal microvascular abnormalities (IRMA), new vessels elsewhere (NVE), venous beading], severity and distribution on disease worsening based on the Early Treatment Diabetic Retinopathy Study (ETDRS)-Diabetic Retinopathy Severity Scale (DRSS). Post-hoc analysis of a multi-center observational study of 544 eyes with nonproliferative DR and an ETDRS-DRSS score of Level 35-53. Disease worsening was defined as ETDRS-DRSS worsening by ≥2 steps from baseline or receipt of DR treatment over 4 years. DR lesions were evaluated based on the entire visible area in the ultrawide field color (UWF-color) and UWF-fluorescein angiography (UWF-FA) images. A significantly greater risk of disease worsening was associated with the presence of more severe lesion grades outside the ETDRS fields for H/Ma (HR:1.74 [95% CI:1.28-2.36]) on UWF-color; and for H/Ma (1.90 [1.38-2.61]), IRMA (1.68 [1.13-2.49]), and NVE (1.99 [1.36-2.93]) on UWF-FA. These results suggest that features on UWF-color and UWF-FA may provide additional prognostic value in determining the risk of disease worsening. The use of UWF-FA improves identification of DR lesions and disease progression. However, the optimal method of disease risk assessment on UWF imaging still needs to be determined.

FAM83D promotes the progression of 4NQO-induced esophageal carcinoma via inhibiting FBWX7

The present study aimed to explore the expression and regulatory role of FAM83D in the different developmental stages of esophageal squamous cell carcinoma (ESCC) to determine the effect of FAM83D on the proliferation, migration, and invasion of ESCC cells and to elucidate its underlying molecular mechanism. Immunohistochemistry (IHC) analysis revealed that the expression of FAM83D was obviously elevated in ESCC tissues compared to adjacent normal tissues. Furthermore, the FAM83D levels was positively correlated with tumor size, TNM stage, T stage, and N stage, while it was negatively correlated with FBXW7 expression, Karnofsky Performance Status (KPS) score, and survival rate. Subsequently, ESCC cell lines with low FAM83D expression were constructed using RNA interference technology to investigate the impact of FAM83D on the biological behavior of ESCC cells. Silencing of FAM83D inhibited the proliferation and migration of ESCC cells but promoted apoptosis. Furthermore, a reduction in FAM83D expression may also induce cell cycle arrest at the G0/G1 phase and regulate the expression of proteins related to epithelial-mesenchymal transition (EMT), the cell cycle, and apoptosis. Further research indicated that silencing FAM83D led to the upregulation of FBXW7 expression. These results suggested that FAM83D may exert its effects on ESCC by downregulating FBXW7. Additionally, using a 4NQO solution in the drinking water to establish an ESCC mouse model, IHC analysis revealed that FAM83D expression levels were positively correlated with the pathological grade of esophageal lesions in the mice and negatively correlated with the expression levels of FBXW7 and E-cadherin. The above results demonstrated that FAM83D may facilitate the progression of ESCC by negatively regulating FBXW7 expression and that FAM83D could represent a promising therapeutic target for ESCC.

Angiogenesis in endometrial cancer: clinical and biological significance

Objective: to summarize the available data on the features of vascularization of endometrioid adenocarcinoma (EAC). Material and Methods. The search for relevant sources was performed in the “PubMed” database using the keywords “endometrium + cancer + angiogenesis”, “endometrium + cancer + angiogenesis + lymph”. Of the selected sources, 78 were included in this review. Results. Angiogenesis is an important and necessary stage in the pathogenesis of the appearance, progression and metastasis of EAC and, thus, the study of tumor vascularization provides an opportunity to improve diagnosis and personalized approach to treatment. Vascular density correlates with advanced stage of EAC, high grade of malignancy, myometrial invasion, cervical and adnexal lesions, vascular invasion, metastases to lymph nodes (LN), the presence of cancer cells in the peritoneal fluid, low overall survival and survival without tumor progression. There are publications that deny the connection of vascularization with the histological type of tumor, its grade, lymphovascular invasion, lymph node metastases, the depth of myometrial invasion, and these publications even prove that microvessel density is not an independent prognostic factor. So, there is still no consensus and final opinion, as evidenced by low or high vascularization of EAC. Recently, there are many drugs that affect both the processes of angiogenesis directly and the inducers and factors that control vascular growth. Unfortunately, all such drugs have a fairly high toxicity, and resistance to them very quickly develops. Conclusion. Despite numerous results of studies devoted to the study of the formation of blood vessels and isolated data on lymphangiogenesis in EAC, there is no data in the literature on studying changes in the vascularization of LN in gynecological cancer. However, proangiogenic and antiangiogenic factors are disseminated throughout the body and must exert their effects in distant organs and tissues. Based on changes in the vascularization of LN, it will apparently become possible to predict the activity of angiogenesis in the primary tumor, assess the prognosis of the disease, and the effectiveness of the treatment. In addition, significant expression of the vascular network in an enlarged lymph node biopsied for diagnosis may be a symptom of the development of a malignant tumor in the lymph collection region, even in the absence of metastases.

Clinical correlates of cerebellar injury in preterm infants with surgical necrotizing enterocolitis.

The preterm infants are at risk of cerebellar injury and the risk factors for necrotizing enterocolitis (NEC) associated cerebellar injury are not fully understood. Determine the risk factors of cerebellar injury in infants with surgical necrotizing enterocolitis (NEC). Retrospective study compared clinical/pathological information between surgical NEC infants with and those without cerebellar injury detected on brain MRI obtained at term equivalent age. Cerebellar Injury patterns that we identified on MRI brain were cerebellar hemorrhage, siderosis and/or cerebellar volume loss. Cerebellar injury (21/65, 32.3%) in preterm infants with NEC was associated with patent ductus arteriosus (PDA) (18/21(85.7%) vs. 25/44(56.8%); p = 0.021), blood culture positive sepsis (13/21 (61.9%) vs. 11/44 (25%); p = 0.004) following NEC, predominantly grew gram positive bacteria (9/21(42.9%) vs. 4/44(9.1%); p = 0.001), greater red cell transfusion, higher rates of cholestasis following NEC and differences in intestinal histopathology (more hemorrhagic and reparative lesions) on univariate analysis. Those with cerebellar injury had higher grade white matter injury (14/21 (66.7%) vs. 4/44(9.1%) p = 0.0005) and higher-grade ROP (70.6% vs. 38.5%; p = 0.027) than those without cerebellar injury.On multilogistic regression, the positive blood culture sepsis (OR 3.9, CI 1.1-13.7, p = 0.03), PDA (OR 4.5, CI 1.0-19.9, p = 0.04) and severe intestinal pathological hemorrhage (grade 3-4) (OR 16.9, CI 2.1-135.5, p = 0.007) were independently associated with higher risk of cerebellar injury. Preterm infants with surgical NEC with positive blood culture sepsis, PDA, and severe intestinal hemorrhagic lesions (grade 3-4) appear at greater risk for cerebellar injury.

Comparing the imaging characteristics of middle-aged patients with multiple sclerosis and CADASIL: A retrospective cross-sectional study

BackgroundFew studies have quantitatively analyzed the imaging disparities between multiple sclerosis (MS) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We aimed to compare the imaging characteristics of MS and CADASIL in middle-aged patients. Materials and MethodsThis retrospective study used a single-center database and included patients aged 40–60 years with MS and CADASIL who underwent the designated imaging protocol including 3D T1-weighted imaging and fluid attenuated inversion recovery (FLAIR), diffusion tensor imaging and susceptibility-weighted imaging between January 2018 and March 2023. Patients with MRI-detected macrobleeds were excluded. ResultsA total of 27 patients with MS (mean age, 46.7 years ± 4.4, 8 men) and 30 patients with CADASIL (mean age, 51.6 years ± 5.8, 14 men) were included. No significant differences were observed in the Fazekas grades of white matter lesions (WMLs). Patients with CADASIL exhibited greater external capsule involvement (56.7% vs.18.5 %; p = 0.006), whereas the MS group had more lesions in the corpus callosum (81.5% vs. 53.3 %, p = 0.02) and brainstem (74.1% vs. 46.7 %, p = 0.04). The CADASIL group exhibited a higher incidence of microbleeds (12.07 vs. 0.11, p = 0.001). The WMLs in the MS group exhibited a lower T1 lesion/cerebrospinal fluid signal index (2.206 vs. 2.882, p < 0.001). A value of ≤2.57 demonstrated a sensitivity of 92.6 % and a specificity of 90.0 % in differentiating MS. Patients with MS had a thinner corpus callosum (7.18 mm vs 7.86 mm, p = 0.04), while patients with CADASIL showed significantly higher mean diffusivity (0.8776 × 10–3 vs. 0.7637 × 10–3 mm2/s, p = 0.03) and lower fractional anisotropy (0.7581 vs. 0.8389, p = 0.04) in the splenium of the corpus callosum. ConclusionMiddle-aged patients with MS and CADASIL showed comparable Fazekas grades for WMLs. However, lesion distribution, T1 signal characteristics, and splenic diffusivity changes can help differentiate between MS and CADASIL.

Assessment of Holmium:YAG, Pulsed-Thulium:YAG and Thulium Fiber Lasers for Urinary Stone Ablation. In Vitro Study.

Objective: To evaluate the ablation speed (AS), laser efficiency and direct thermal lesions during urinary stone lithotripsy with the current available laser technologies: Holmium:YAG (Ho:YAG), pulsed-Thulium:YAG (p-Tm:YAG) and thulium fiber laser (TFL) in vitro using different laser settings. Materials and Methods: Ho:YAG, p-Tm:YAG, and TFL laser system were used in an in vitro ureteral model with a volume of 125 mm3 Begostone. The following parameters were tested across all laser devices: 0.6J/10 Hz (6 W), 0.6 J/20 Hz (12 W), 1.5 J/10 Hz (15 W), and 1.5 J/20 Hz (30 W), employing short pulse width for all lasers and long pulse width for Ho:YAG and p-Tm:YAG. Ten participants conducted the experimental setup during 3-minutes laser on time, combining the laser technology, settings, and pulse widths, with a total of 20 different combinations. The efficiency, AS and ureteral damage resulting from each intervention were analyzed. Results: p-Tm:YAG and TFL demonstrated significantly higher efficiency compared with Ho:YAG (0.049 ± 0.02 Δgr/KJ and 0.042 ± 0.01 Δgr/KJ vs 0.029 ± 0.01 Δgr/KJ; p < 0.05). In all laser sources, as the power increases, the AS also increases (p < 0.05). Furthermore, only at high-energy settings (1.5 J) higher frequency led to increase AS (p < 0.05). Both, p-Tm:YAG and TFL exhibited higher AS compared to Ho:YAG (0.64 ± 0.33 Δgr/s and 0.62 ± 0.31 Δgr/s vs 0.44 ± 0.22 Δgr/s; p < 0.05). Regarding ureteral injuries, as the power increases, there is a higher chance of ureteral damage (p = 0.031). No differences were observed between laser technologies (p = 0.828). Conclusions: Both, p-Tm:YAG and TFL exhibited superior performances during laser lithotripsy compared with Ho:YAG, as they demonstrated higher efficiency and ablation speed. Thermal damage did not appear to be associated with specific laser equipment, but higher grades of lesions are described by increasing power.

The level of expression of HPV16 early transcripts is not associated with the natural history of cervical lesions.

The natural history of cervical cancer is closely linked to that of high-risk human papillomaviruses (HPV) infection. It is recognized that upon HPV DNA integration, partial or complete loss of the E2 open reading frame precludes expression of the corresponding protein, resulting in upregulation of the E6 and E7 viral oncoproteins. To better characterize HPV16 infection at the cervical level, viral load, viral DNA integration, and viral early transcript expression (E2, E5, and E6) were analyzed in a series of 158 cervical specimens representative of the full spectrum of cervical disease. Overall, the frequency of early transcript detection varied from 45% to 90% and tended to increase with lesion severity. In addition, the levels of E2, E5, and E6 transcript expression were slightly higher in high-grade lesions than in cervical specimens without abnormalities. Notably, early transcript expression was clearly associated with viral load, and no inverse correlation was found between the expression of E2 and E6 transcripts. No clear association was found between early transcript expression and HPV16 DNA integration, with the exception that samples with a fully integrated HPV16 genome did not harbor E2 or E5 transcripts. In conclusion, early HPV16 transcript expression appears to be associated with viral load rather than lesion grade. From a practical point of view, quantification of HPV16 early transcripts is difficult to translate into a relevant biomarker for cervical cancer screening.

Exploration of a comprehensive index for predicting cognitive impairment in patients with cerebral small vessel disease and white matter lesions

Background &amp; Objective: The objective of this study was to explore the risk factors for cognitive impairment in patients with cerebral small vessel disease (CSVD), and to construct a predictive model for cognitive impairment in CSVD patients, providing personalized diagnostic and treatment strategies for patients. Methods: Clinical data and blood indicators of CSVD patients admitted to the Department of Neurology at the Second Affiliated Hospital of Shandong First Medical University from February 2022 to February 2023 were collected. Additionally, these patients underwent cranial MRI examinations and completed neurological and psychological assessments, including the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). Based on the MoCA and MMSE results, the patients were divided into the cognitive impairment group and the normal cognitive group. Clinical data, blood indicators, and white matter lesion (WML) grades were compared between the two groups. Univariate logistic regression analysis was performed to identify the risk factors for cognitive impairment in CSVD patients. Using MoCA assessment results as the gold standard and several clinical indicators as independent variables, a logistic regression model was constructed. Predicted values were calculated based on this model, and a receiver operating characteristic (ROC) curve for the comprehensive diagnosis of multiple variables was plotted to evaluate the model’s accuracy. Results: A total of 134 CSVD patients were included, and cognitive impairment occurred in 98 cases, with an incidence rate of 73.13%, while 36 patients did not have cognitive impairment. Univariate logistic regression analysis of the collected variables identified eight factors: age, education level, hypertension, diabetes, cerebral hemorrhage, low-density lipoprotein cholesterol (LDL-C), hyperhomocysteine (HHCY), and WML grading. Multivariate logistic regression analysis identified age, LDL-C, and WML grading as the final predictive factors, establishing a combined diagnostic model to predict the probability of cognitive impairment in patients. The constructed ROC curve for the comprehensive diagnosis of multiple variables yielded an area under the curve of 0.870, indicating good accuracy. To facilitate clinical diagnosis, the combined diagnostic model was simplified into an L score calculation formula, with the optimal cutoff value of 5.223. When the L score is &lt;5.223, the patient can be considered not having cognitive impairment, while an L score &gt;5.223 indicates cognitive impairment, allowing for the prediction of the risk of cognitive impairment in patients. Conclusion: Age, education level, hypertension, diabetes, cerebral hemorrhage, LDL-C, HHCY, and WML grading are related risk factors for cognitive impairment in CSVD patients. Age, LDL-C, and WML grading are independent risk factors for cognitive impairment in CSVD patients. The clinical predictive model for cognitive impairment in cerebral small vessel disease, constructed using the final predictive factors, showed good performance and clinical utility. It facilitates individualized risk assessment for cognitive impairment in CSVD patients and allows for targeted follow-up observation for high-risk individuals.