Grade Lesions Research Articles

Value of perilesional biopsies in multiparametric magnetic resonance imaging-targeted biopsy and systematic biopsy in detection of prostate cancer: results of a prospective, non-randomized, surgeon-blinded study

PurposeThe goal of this study is to address if detection rates of clinically significant prostate cancer (csPCa) can be increased by additional perilesional biopsies (PB) in magnetic resonance (MR)/ultrasound fusion prostate biopsy in biopsy-naïve men.MethodsThis prospective, non-randomized, surgeon-blinded study was conducted between February 2020 and July 2022. Patients were included with PSA levels < 20 ng/ml and ≥ one PI-RADS lesion (grades 3–5) per prostate lobe. Prostate biopsy was performed by two urologists. The first performed the MR-fusion biopsy with 3–5 targeted biopsies (TB) and 6 PB in a standardized pattern. The second performed the systematic (12-fold) biopsy (SB) without knowledge of the MR images. Primary outcome of this study is absence or presence of csPCa (≥ ISUP grade 2) comparing TB, PB and SB, using McNemar test.ResultsAnalyses were performed for each PI-RADS lesion (n = 218). There was a statistically significant difference in csPC detection rate of TB + SB between PI-RADS 3, 4 and 5 lesions (18.0% vs. 42.5% vs. 82.6%, p < 0.001) and TB + PB (19.7% vs. 29.1% vs. 78.3%). Comparing only maximum ISUP grade per lesion, even SB plus TB plus PB did not detect more csPCa compared to SB plus TB (41.3% vs. 39.9%, p > 0.05).ConclusionWe present prospective study data investigating the role of perilesional biopsy in detection of prostate cancer. We detected no statistically significant difference in the detection of csPCa by the addition of PB. Therefore, we recommend continuing 12-fold bilateral SB in addition to TB.

Localization and grading of NPDR lesions using ResNet-18-YOLOv8 model and informative features selection for DR classification based on transfer learning

Complications in diabetes lead to diabetic retinopathy (DR) hence affecting the vision. Computerized methods performed a significant role in DR detection at the initial phase to cure vision loss. Therefore, a method is proposed in this study that consists of three models for localization, segmentation, and classification. A novel technique is designed with the combination of pre-trained ResNet-18 and YOLOv8 models based on the selection of optimum layers for the localization of DR lesions. The localized images are passed to the designed semantic segmentation model on selected layers and trained on optimized learning hyperparameters. The segmentation model performance is evaluated on the Grand-challenge IDRID segmentation dataset. The achieved results are computed in terms of mean IoU 0.95,0.94, 0.96, 0.94, and 0.95 on OD, SoftExs, HardExs, HAE, and MAs respectively. Another classification model is developed in which deep features are derived from the pre-trained Efficientnet-b0 model and optimized using a Genetic algorithm (GA) based on the selected parameters for grading of NPDR lesions. The proposed model achieved greater than 98 % accuracy which is superior to previous methods.

Segmentation assisted Prostate Cancer Grading with Multitask Collaborative Learning

Medical image segmentation can provide doctors with more direct information on the location and size of organs or lesions, which can serve as an valuable auxiliary task for prostate cancer grading. Meanwhile, other types of diagnostic data besides images are also essential, such as patient age, Prostate-Specific Antigen (PSA), etc. Currently, there is a lack of in-depth research on how to effectively differentiate and select shared features and task-specific features in multitask learning, as well as how to balance and explore the potential correlations between different tasks. In this paper, we propose a novel Shared Feature Hybrid Gating Experts (SFHGE) architecture for collaborative main (lesion grading) and auxiliary (lesion segmentation) task learning, dynamically selecting shared and task-specific features. To efficiently utilize complementary features, we also introduce a Cross-Task Attention module (CrossTA) to capture cross-task integrated representation. Additionally, recognizing that non-image clinical information often provides crucial diagnostic insights, we further design a Heterogeneous Information Fusion Network (HIFN) to better integrate clinical data, thereby improving grading performance. Extensive experiments on the PI-CAI dataset demonstrate that our approach outperforms mainstream classification and segmentation models.

Quadrivalent HPV vaccine effectiveness against cervical intraepithelial lesion grade 2 or worse in Norway: A registry-based study of 0,9 million Norwegian women.

In Norway, single cohort vaccination with quadrivalent HPV (qHPV) vaccine targeting 12-year-old girls took place from 2009-2016. In 2020, the oldest vaccinated cohort was 23 years old and had approached the age where risk of being diagnosed with cervical intraepithelial lesion grade 2 or worse (CIN2+) increases rapidly. The aim of this cohort study was to assess direct qHPV vaccine effectiveness (VE) against CIN2+ among Norwegian women aged 16-30 in 2007-2020. By using population-based health registries and individual-level data on vaccination status and potential subsequent CIN2+ incidence, we found 82% qHPV VE among women vaccinated before the age of 17.

Correlation of lesion severity with bacterial changes in Treponeme-Associated Hoof Disease from free-roaming wild elk (Cervus canadensis)

BackgroundTreponeme-Associated Hoof Disease (TAHD) is a polybacterial, multifactorial disease affecting free-ranging wild elk (Cervus canadensis) in the Pacific Northwest. Previous studies have indicated a bacterial etiology similar to digital dermatitis in livestock, including isolation of Treponema species from lesions. The lesions appear to progress rapidly from ulcerative areas in the interdigital space or along the coronary band to severe, ulcerative, necrotic, proliferative lesions under-running the hoof wall, perforating the sole, and contributing to hoof elongation, deformity, and overgrowth. Eventually the lesions undermine the laminal structure leading to sloughing of the hoof horn capsule. The objective of this study was to characterize the bacterial communities associated with hoof lesions, which were categorized into 5 stages or disease grade severities, with 0 being unaffected tissue and 4 being sloughed hoof capsule. We also wanted to determine if the etiology of TAHD through morphological changes was dominated by Treponema, as observed in hoof diseases in livestock.ResultsThe bacterial 16S rRNA gene was sequenced from 66 hoof skin biopsy samples representing 5 lesion grades from samples collected by Washington Department of Fish and Wildlife as part of a voluntary hunter program. Analysis of the relative abundance of bacterial sequences showed that lesions were dominated by members of the bacterial phyla Proteobacteria, Firmicutes, Spirochaetes, Bacteroidetes and Actinobacteria. In lesion samples, members of the genus Treponema, Porphyromonas, and Mycoplasma increased with lesion severity. Association analysis indicated frequent identification of Treponema with Porphyromonas, Bacteroides and other anaerobic Gram-positive cocci.ConclusionsThe bacterial 16S rRNA gene sequencing confirmed the presence of Treponema species at all stages of TAHD lesions, treponeme specie-specific PCR and histopathology, indicating that the morphological changes are a continual progression of disease severity with similar bacterial communities. Association and abundance of these other pathogenic genera within lesions may mean synergistic role with Treponema in hoof disease pathogenesis. Characterizing bacteria involved in lesion development, and their persistence during disease progression, provides evidence for science-based management decisions in TAHD infected elk populations.

Comparison of two versus three-screw fixation for biplanar chevron medial malleolar osteotomy.

This study was designed to compare the clinical outcomes and complications of using two versus three screws to fix the biplanar chevron medial malleolar osteotomy (MMO). A retrospective review was conducted on 43 patients (46 ankles) who underwent biplanar chevron MMO to treat talus osteochondral lesions. Of these, MMO was fixed with two parallel screws placed perpendicular to the osteotomy plane in 16 ankles, while in the remaining 30 ankles, MMO was secured with two parallel screws plus an additional third screw inserted parallel to the tibial plafond. Patients were divided into two groups based on the fixation method and clinical outcomes, union and malunion rates, and complications were compared. Demographic and clinical characteristics such as age (p: 0.411), gender distribution (p: 0.119), affected side (p: 0.126), lesion grades (p: 0.056), and lesion sizes (p: 0.310), immobilization (p: 0.119) and weight-bearing periods (p: 0.252) were statistically similar across both groups. Initial malreduction were observed in five cases within the three-screw group and one case in the two-screw group (p: 0.307). However, neither group exhibited any progressive step-off or gap in the follow-up radiographs, and osteotomy union was achieved in all patients. Delayed union was observed in one patient from the three-screw group. Significant improvements in American Orthopedic Foot and Ankle Society scores were observed in both groups, with no functional discrepancies evident at the final follow-up (p: 0.488). The study found no significant differences in union rates, complications, or clinical outcomes between two and three-screw fixation methods for medial malleolar osteotomies (MMO). Both methods allowed for effective MMO fixation without loss or displacement post-surgery, suggesting their safety and efficacy. Level III, retrospective comparison.

Novel clinical risk calculator for improving cancer predictability of mpMRI fusion biopsy in prostates.

Prostate Imaging-Reporting and Data System (PI-RADS) assists in evaluating lesions on multiparametric magnetic resonance imaging (mpMRI), but there are still ongoing efforts in improving the predictive value for the presence of clinically significant PCa (csPCa) with a Gleason grade group ≥ 2 on Fusion-Biopsy. This pilot study intends to propose an easily implementable method for augmenting predictability of csPCa for PI-RADS. A cohort of 151 consecutive patients underwent mpMRI Fusion and random US Biopsy as a result of having at least one PI-RADS lesion grade 3-5 between January 1, 2019 and December 31, 2022. A single radiologist reads all films in this study applying PI-RADS V2. Of the 151 consecutive patients, 49 had a highest lesion of PI-RADS 3, 82 had a highest lesion of PI-RADS 4, and 20 had a highest lesion of PI-RADS 5. For each respective group, 12, 42, and 18 patients had proven csPCa. Two predictive models for csPCa were created by employing a logistical regression with parameters readily available to providers. The models had an AUC of 0.8133 and 0.8206, indicating promising effective models. PI-RADS classification has relevant predictability problems for grades 3 and 4. By applying the presented risk calculators, patients with PI-RADS 3 and 4 are better stratified, and thus, a significant number of patients can be spared biopsies with potential complications, such as infection and bleeding. The presented predictive models may be a valuable diagnostic tool, adding additional information in the clinical decision-making process for biopsies.

The association between human papillomavirus infection, vaginal microecology, and cervical intraepithelial neoplasia in women from Xinjiang, China.

This study analyzes the relationship between human papillomavirus (HPV) infection, vaginal microecology, and cervical lesions to provide a basis for the prevention and treatment of cervical cancer (CC) in the Xinjiang region. Real-time quantitative PCR was used for HPV genotyping and viral load. The Gram staining and dry biochemical enzyme kit were utilized to diagnose vaginal secretions. The χ2 test and Logistic regression analysis were used for statistical analysis. The HPV infection rate among women in the Xinjiang region was 30.29%, of which the single HPV infection accounts for 77%. HPV16 and HPV52 were the main infection types. There was significant differences in the HPV infection rate and infection types among the Han, Uighur, Hui, and Kazakh ethnic groups. The viral load of HPV16 and HPV52 increases with the upgrade of cervical lesions. There were significant differences in vaginal microecology evaluation indicators H2O2, SNA, LE, GUS, trichomonas, clue cells, and lactobacilli among different ethnic groups. HPV negative patients with varying grades of cervical lesions exhibit a notable variance in H2O2 and LE, which is statistically significant. Single HPV infection and high viral load HPV significantly increase the risk of CC. This study indicates that HPV infection and vaginal microecology differ among ethnic groups, which have a strong correlation with the progression of CC, offering guidance on CC screening and interventions in the Xinjiang area.

Abstract 4166: TSPO-targeted near-infrared optical probe for early identification and localization of high-risk premalignant pancreatic lesions

Abstract Background: Pancreatic cancer is the third most prevalent cause of cancer death in the U.S. with a ~10% survival rate. Surgery represents one of the best opportunities for extending survival and potential cures. Fluorescence-guided surgery (FGS) employing near-infrared (NIR) fluorescence-based targeting agents improves resection margins, allowing removal of small lesions not visible under white light. We previously reported a targeted NIR tracer (V-1520) of translocator protein (TSPO) expression that demonstrated proof-of-principle utility in high-grade pancreatic lesions arising in Ptf1a-Cre; LSL-KrasG12D/+; Smad4flox/flox (KCS) of pancreatic cancer. The purpose of the present study is to evaluate the utility of V-1520 to identify low-grade, premalignant yet high risk lesions in KCS mice; in this scenario we attempted to model use of V-1520 to remove lesions likely to manifest as future recurrence. We compared the uptake of the tracer in these mice from weaning to adulthood to systematically evaluate the efficacy of FGS as a function of lesion grade. Experimental: The tracer, V-1520, was synthesized and KCS mice were generated as reported.1 Mice were injected with 30μg of V-1520 intravenously 24 hours before imaging. Images were acquired using the 800nm channel. KCS and WT mice were imaged as a function of from 4 to 11 weeks age. After imaging, tumor tissues and major organs were harvested for ex-vivo imaging, histopathology and Cryo-Fluorescent Tomography (CFT). Summary: We found, V-1520 prominently localized in low-grade, premalignant PanIN cystic lesions with malignancy potential, as well as pancreatic tumors with and without local invasion. In contrast, V-1520 did not accumulate in healthy pancreata of KCS or WT mice. Mice as young as 4 weeks exhibited localized accumulation of the tracer with low grade PanIN and early dysplasia. The fluorescence intensity was further enhanced in mice with higher grade disease, whereby the pathology was characterized by high-grade cyst formation, increased nuclear/cytoplasm ratio, acinar to ductal metaplasia and invasion. Low and high-grade neoplasia was characterized by high TSPO immunoreactivity, consistent with in-vivo imaging. Confocal microscopy was used to colocalize V-1520 accumulation and TSPO immunoreactivity; V-1520 was found to prominently localized to premalignant epithelia pancreatic cancer cells. CFT illustrated that the primary localization of V-1520 included the liver, kidneys, and pancreatic diseases. Conclusion: These studies suggest the utility of V-1520 to identify high-risk pancreatic lesions that could be removed with surgery. Encouragingly, the V-1520 was capable of differentiating tumors from surrounding non-tumor tissue at an early stage, which could lead to better resections and delay and/or prevent recurrence in the future. 1. Clinical Cancer Research 26(22), 15 Nov. 2020 5914-5925 Citation Format: Shilpa Sharma, Denise Hernandez, Xiaoxia Wen, Jianbo Wang, Cong-Dat Pham, Beibei Huang, Henry Charles Manning. TSPO-targeted near-infrared optical probe for early identification and localization of high-risk premalignant pancreatic lesions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4166.

Prospective evaluation of 68 Ga-NODAGA-RGD PET-CT in patients of carcinoma thyroid with thyroglobulin elevated negative radioiodine scintigraphy (TENIS) with a head-to-head comparison with FDG-PET/CT.

This study aimed to examine the expression of RGD binding integrins in patients of elevated serum thyroglobulin (Tg) level with negative radioiodine scintigraphy (TENIS) employing 68 Ga-NODAGA-RGD PET-CT. This was a prospective study involving 30 proven cases of TENIS with histopathological diagnosis of differentiated thyroid carcinoma post-surgery. In addition to observing the lesional concentration on 68 Ga-NODAGA-RGD PET-CT, a 4-point visual grading system (grade I-IV), was undertaken to estimate the degree of radiotracer avidity, for potential of theranostics. On 18 F-FDG-PET/CT, the uptake was seen in 182 lesions out of a total of 200 (91%). 68 Ga-NODAGA-RGD PET-CT showed expression in a total of 110/200 (55%) lesions. On patient-specific analysis, 68 Ga-NODAGA-RGD PET-CT was positive for the disease in 21/30 patients (70%) and negative in 9/30 (30%) patients. The overall patient-specific sensitivity and specificity of 68 Ga-NODAGA-RGDPET-CT were 75% and 100%, respectively. 18 F-FDG PET-CT was positive for the disease in 26/30 patients (86.66%) and negative in 4/30 (13.33%) patients. The overall patient-specific sensitivity and specificity of 18 F-FDG-PET/CT were 92.86% and 100%, respectively. The 4-point visual grading system revealed 14/200 (7%) lesions demonstrating Grade I uptake, 49/200 (24.5%) lesions grade II uptake, 17/200 (8.5%) lesions grade III uptake and 40/200 (20%) lesions grade IV uptake. The results suggested that RGD-binding integrin is expressed in a sizeable fraction of metastatic lesions of TENIS cases, albeit demonstrating a varying degree of uptake. Out of the soft tissue, lung, and bone lesions, metastatic bone lesions showed more RGD affinity than other sites. The patients with substantial RGD uptake on a 4-point visual grading system may be potential targets for RGD-based therapy.

OralEpitheliumDB: A Dataset for Oral Epithelial Dysplasia Image Segmentation and Classification.

Early diagnosis of potentially malignant disorders, such as oral epithelial dysplasia, is the most reliable way to prevent oral cancer. Computational algorithms have been used as an auxiliary tool to aid specialists in this process. Usually, experiments are performed on private data, making it difficult to reproduce the results. There are several public datasets of histological images, but studies focused on oral dysplasia images use inaccessible datasets. This prevents the improvement of algorithms aimed at this lesion. This study introduces an annotated public dataset of oral epithelial dysplasia tissue images. The dataset includes 456 images acquired from 30 mouse tongues. The images were categorized among the lesion grades, with nuclear structures manually marked by a trained specialist and validated by a pathologist. Also, experiments were carried out in order to illustrate the potential of the proposed dataset in classification and segmentation processes commonly explored in the literature. Convolutional neural network (CNN) models for semantic and instance segmentation were employed on the images, which were pre-processed with stain normalization methods. Then, the segmented and non-segmented images were classified with CNN architectures and machine learning algorithms. The data obtained through these processes is available in the dataset. The segmentation stage showed the F1-score value of 0.83, obtained with the U-Net model using the ResNet-50 as a backbone. At the classification stage, the most expressive result was achieved with the Random Forest method, with an accuracy value of 94.22%. The results show that the segmentation contributed to the classification results, but studies are needed for the improvement of these stages of automated diagnosis. The original, gold standard, normalized, and segmented images are publicly available and may be used for the improvement of clinical applications of CAD methods on oral epithelial dysplasia tissue images.

Exploring the potential prompting role of cervical human papilloma virus detection in vulvar lesions: a cross-sectional study in China.

The etiology and clinical presentation of vulvar carcinomas, especially vulvar lesions, are not fully understood. Because the vulva and cervix are anatomically connected, human papillomavirus (HPV) is the main cause of cervical lesions. Thus, this study explored the potential characteristics and effects of specific HPV infection types across vulvar lesions and concurrent cervical lesions. This retrospective, cross-sectional study analyzed patients with cervical HPV or cytological results and concurrent vulvar biopsy who were seen in our hospital colposcopy clinic in Shanxi Province, China, between 2013 and 2023. Data on age, menopause status, vulvar manifestations, and cytology and HPV infection testing results were collected. Attributable fractions and multinominal logistic models were used to evaluate HPV genotyping and clinical characteristics across vulvar lesions. Among the 1,027 participants, 83 (8.1%) had vulvar intraepithelial neoplasia (VIN) of high grade or worse (VIN2+), and 127 (12.4%) had non-neoplastic epithelial disorders of the vulva (NNEDV). A total of 175 patients had either VIN2+ or cervical intraepithelial neoplasia (CIN) lesions of grade 2 or worse (CIN2+). The most common HPV genotypes for VIN2+ or concurrent VIN2+/CIN2+ were HPV16, HPV52, and HPV58, although attributable fractions differed among lesions. Patients with normal cytological or histopathological result were more likely to have NNEDV detected, while abnormal cervical diagnosis was associated with higher detection of VIN2+. Multinominal logistic modeling showed that age and HPV16 infection were risk factors for VIN2+ or concurrent VIN2+/CIN2+; however, only vulvar presentation with depigmentation was a risk factor for NNEDV. Among patients with low-grade CIN1/VIN1, compared with those who were HPV16 negative, those who were HPV16 positive were at 6.63-fold higher risk of VIN2+/CIN2+ [95% confidence interval (CI): 3.32, 13.21]. Vulvar depigmentation was also associated with increased risk of NNEDV (odds ratio: 9.98; 95% CI: 3.02, 33.04). Chinese women may be at specific, high risk for HPV infection types associated with VIN or CIN. The use of cervical cell HPV detection along with vulvar presentation during cervical cancer screening may also contribute to vulvar lesion detection.

The Effect of Rubus idaeus Polyphenols Extract in Induced Endometriosis in Rats.

Endometriosis is a common gynecological condition with a complex physio-pathological background. This study aimed to assess the role of Rubus idaeus leaf extract (RiDE) as a potential therapeutic agent in reducing the size of the endometriotic lesions and modulate the plasma expression of MMP-2, MMP-9, and TGF-β1. The endometriotic lesions were induced in a rat model by the autologous transplant of endometrium. Thirty-six female rats, Wistar breed, with induced endometriosis, were divided into four groups and underwent treatment for 28 days. The CTRL group received 0.5 mL/day of the vehicle; the DG group received 1 mg/kg b.w./day dienogest; the RiDG group received 0.25 mL/kg b.w./day RiDE and the D+RiDG group received 1 mg/kg b.w./day dienogest and 0.25 mL/kg b.w./day RiDE, respectively. Rats' weight, endometriotic lesion diameter and grade, and plasma levels of MMP-2, MMP-9, and TGF-β1 were assessed before and after treatment. The administration of RiDE in association with dienogest vs. dienogest determined a lower weight gain and a reduction in diameter of the endometriotic lesions. RiDE administration restored MMP2 and MMP9 plasma levels to initial conditions. Rubus idaeus extract may help in reducing dienogest-associated weight gain, lower the size of endometriotic lesions, and have anti-inflammatory effects through MMP2 and MMP9 reduction.

Neurodevelopmental Outcome at 3 Years of Age in Very Low Birth Weight Infants According to Brain Development and Lesions.

During the last decades, severe brain lesions affecting very low birth weight (<1500 gr, VLBW) infants were gradually substituted by milder lesions with debatable prognoses. The objective of this study is to define type, frequency and 3 years of neurodevelopmental outcome of prematurity-related brain lesions in a modern cohort of VLBW infants. VLBW infants admitted to our NICU in 5 years period with brain MRI at term-equivalent age were included. MRI scans were reviewed to identify and grade white matter lesions (WML), intraventricular hemorrhage (IVH), and cerebellar hemorrhage (CBH). Linear measurements of brain size, biparietal width (BPW) and trans-cerebellar diameter (TCD) were carried out. Total maturation score (TMS) was calculated. Developmental Coefficients (DQ) on Griffiths Scale at 3 years of age were compared between patients with different types and grades of lesions and patients without lesions; possible correlations between linear brain measurements, brain maturation and outcome were explored. Study included 407 patients. Of them, 187 (46%) had at least one brain lesion on MRI, while 37 (9%) had severe lesions. The most frequent lesion was IVH (28%), followed by WML (21%) and CBH (17%). Mild and severe IVH, moderate and severe WML and all grades of CBH were related to worst outcome at 3 years. In patients without lesions, small BPW and small TCD were associated with worse outcomes. No correlations were observed between TMS and outcome. We have observed that even mild brain lesions have a negative influence on neurological outcome at 3 years of age.

Evaluation of HPV 16 and HPV 18 Oncoprotein Expression as Alternative Diagnostic Tools in Cervical Lesion.

The study aimed to evaluate E6 and E7 oncoproteins of HPV16 and HPV18 expression in formalin - fixed paraffin embedded (FFPE) tissue in different grades of the cervical lesion and evaluate the potential use of E6 and E7 oncoproteins derived from HPV 16 and 18 as diagnostic protein biomarkers for triaging cervical lesions. A total of 102 FFPE cervical tissues were collected from 2 tertiary hospitals and immunohistochemical reactivity staining of E6 and E7 oncoproteins of HPV16 and HPV18 were evaluated using immunoreactive scoring (IRS) system and analysed statistically. The result showed an increased oncoprotein expression with the progression of cervical lesions. There is a statistically significant association between histology grade and HPV16/18-E6 expression (p = 0.028). However, there are no significant association of histological grade to HPV16-E7 immunoreactivity score (p = 0.264) and HPV18-E7 (p=0.080). The immunohistochemical expression of HPV oncoproteins is a potential alternative diagnostic tool applicable in a low-resource laboratory setting. The advantage of the histochemical evaluation is that this method is simpler to apply and less expensive in comparison to in situ mRNA hybridization. Nevertheless, our study also found that antibodies against HPV that are commercially available suffer quite substantial specificity issues such as background staining and inconsistency between different batches. Hence, the utilization of antibody-based staining warrants stringent quality control.

The Role of IL-6, IL-10, and TNF-α in Ocular GVHD Following Allogeneic Transplantation

ABSTRACT Purpose To figure out the roles of tear inflammatory cytokines in Ocular graft-versus-host disease (oGVHD) symptoms by analyzing tear cytokine levels and related factors. Methods This prospective study involved 27 post-HSCT patients and 19 controls with dry eye disease. Analyses included tear cytokine (IL-6, IL-10, and TNF-α), ocular surface evaluation, and conjunctival impression cell examination. Tear cytokine levels were evaluated in three grades of corneal epithelial lesions. The study also analyzed the correlation between tear cytokine levels and ocular surface parameters. Tear cytokine levels were then used in a Receiver Operating Characteristic (ROC) curve and linear regression model to predict oGVHD related factors. Results IL-6 has good diagnostic efficacy in oGVHD related dry eye. Elevated levels of tear IL-6 and TNF-α were observed in the group with severe corneal epithelial lesions. IL-6 levels were positively correlated with corneal fluorescein staining (CFS), eyelid margin hyperemia, conjunctival lesions, and meibum secretion. IL-6 showed excellent predictive ability with Area Under the Curve (AUC) values all greater than 0.70 (p < 0.05). IL-10 and TNF-α were negatively correlated with the meibomian gland proportion and conjunctival goblet cell (GC) density, while TNF-α was positively correlated with CFS and eyelid margin hyperemia. Conclusion Dry eye symptoms related to ocular GVHD, can be partly diagnosed and assessed using various tear cytokine level detection methods.

Comparison of MRI and arthroscopy findings for transitional zone cartilage damage in the acetabulum of the hip joint.

To assess the performance of morphologic and hypointense signal changes on MRI to predict grades and types of acetabular cartilage damage in the chondrolabral transitional zone (TZ) of the hip identified at arthroscopy. This retrospective single-center study reviewed conventional 3T MRI hip studies from individuals with symptomatic femoroacetabular impingement (FAI) and subsequent hip arthroscopy surgery within 6 months. Independent review was made by three radiologists for the presence of morphologic damage or a hypointense signal lesion in the TZ on MRI. Fleiss' kappa statistic was used to assess inter-reader agreement. The degree of TZ surfacing damage (modified Outerbridge grades 1-4) and presence of non-surfacing wave sign at arthroscopic surgery were collected. Relationship between sensitivity and lesion grade was examined. One hundred thirty-six MRI hip studies from 40 males and 74 females were included (mean age 28.5 years, age range 13-54 years). MRI morphologic lesions had a sensitivity of 64.9-71.6% and specificity of 48.4-67.7% for arthroscopic surfacing lesions, with greater sensitivity seen for higher grade lesions. Low sensitivity was seen for wave sign lesions (34.5-51.7%). MRI hypointense signal lesions had a sensitivity of 26.3-62% and specificity of 43.8-78.0% for any lesion. Inter-reader agreement was moderate for morphologic lesions (k = 0.601) and poor for hypointense signal lesions (k = 0.097). Morphologic cartilage damage in the TZ on MRI had moderate sensitivity for any cartilage lesion, better sensitivity for higher grade lesions, and poor sensitivity for wave sign lesions. The diagnostic value of hypointense signal lesions was uncertain.

Mixed Eimeria and Cryptosporidium infection and its effects on pathology and clinical outcomes in juvenile Asian seabass (Lates calcarifer) cultured in Thailand.

Coccidiosis is an important disease in juvenile fish because of severe intestinal injury during infection. We first reported the mixed infection of intestinal coccidia and its association with health status and pathological findings in juvenile Asian seabass (Lates calcarifer) cultured in Thailand. Two groups of Asian seabass, 60-day fish and 90-day fish, were sampled to investigate prevalence and coccidian infection intensity using morphological characterization and PCR. Phylogenetic analysis of 18S rRNA gene amplified from the intestines revealed Eimeria sp. and Cryptosporidium sp. infection. The prevalence of Eimeria sp. and Cryptosporidium sp. in sampled fish was 100%. Clinical outcomes assessed, using health assessment index (HAI) scoring and semi-quantitative grading of intestinal lesions and inflammation, demonstrated that all fish developed variety of pathology and clinical illness; however, infection intensity in 60-day fish was significantly higher (p < .05) than 90-day fish. The HAI score of 60-day fish was poorer than 90-day fish, which correlated to a high infection intensity (r = .397), analysed by Pearson correlation coefficient. Overproduction of intestinal oxidants contributing to mucosal injury was examined by nitrotyrosine expression. The high production of reactive nitrogen species indicated severe inflammatory response, and intestinal injuries occurred mainly in the 60-day fish.

Factors associated with human papillomavirus persistence after loop electrosurgical excision procedure in patients with cervical squamous intraepithelial lesion.

To seek the high-risk factors of human papillomavirus (HPV) persistence and residual lesion or recurrence after loop electrosurgical excision procedure (LEEP) focus on the predictive value of intraoperative human papilloma virus (IOP-HPV) testing. Intraoperative endocervical sample was obtained with a cytobrush from the remained cervix of 292 patients immediately after LEEP. HPV Genotyping was performed using a polymerase chain reaction technique. All patients followed by HPV genotyping and cytology every 3-6 months. The IOP-HPV testing results and possible risk factors such as age, cytology grade, menopause status, margin involvement, preoperative HPV status, and cervical lesion grade were assessed in predicting persistence of HPV and residual lesion or recurrence after surgery. There were 61 (20.9%) patients presented persistent HPV infection. Multivariate analyses showed that IOP-HPV positive, post-menopause and preoperative HPV multiplex infection was strongly associated with HPV persistence after LEEP, IOP-HPV positive and post-menopause was also associated with residua or recurrent disease after LEEP. IOP-HPV positive, post-menopause, and preoperative HPV multiplex infection are independent predictors of HPV persistence in patients with cervical squamous intraepithelial lesion treated by LEEP. IOP-HPV test is a new approach that may potentially allow for early identification of patients at high risk of HPV persistence and residua or recurrent disease after LEEP, thereby possibly facilitate an attenuated follow-up schedule for negative patients those at low risk of persistent HPV infection.

The value of contrast-enhanced ultrasound in the diagnosis of microcirculatory perfusion abnormalities in diabetic foot

Abstract Background Diabetic foot is one of the most serious complications of type 2 diabetes mellitus (T2DM), and its incidence is increasing in China. Early detection of abnormal microcirculation in the foot is very important for the prevention and treatment of diabetic foot. Objective To investigate the value of contrast-enhanced ultrasound (CEUS) in diagnosing microcirculatory alterations in the dorsum of the foot for patients with type 2 diabetes mellitus (T2DM). Methods Eighty-eight T2DM patients were included, among them 30 patients sustained diabetes mellitus without complications (group A), 28 with lesions in the dorsum of the foot (no acute infection) that can be classified as Wagner grade 0 ~ 1 (group B), and 30 with lesions in the dorsum of the foot that can be classified as Wagner grade 2–5 (group C). Another 30 healthy adults were included as the control group. All subjects underwent CEUS to examine the dorsalis pedis arteries and blood perfusion to the underlying soft tissues. Parameters of the time-intensity curve (TIC), including rise time (RT), ascending slope (AS), time to peak (TTP), peak intensity (PI), area under the curve (AUC), and half of drop time (DT/2) were analyzed. Results The analysis of TIC data of the dorsalis pedis arteries showed that group C had decreased AS, PI, and AUC and increased TTP, RT, and DT/2 compared with groups A, B, and the control group; the differences were statistically significant (p &lt; 0.05). The analysis of TIC data of the perfusion to the underlying soft tissues showed that AS, PI, and AUC decreased from the control group through group A, B, and then C; the differences were all statistically significant (p &lt; 0.05). The TIC data were correlated with the severity of microcirculatory impairment in the dorsum of the foot and among them the AUC, PI, and AS had higher predictive value. Conclusions Microcirculatory impairment in the dorsum of the foot in T2DM patients presents itself as “delayed wash-in, delayed wash-out, and weak enhancement” on CEUS images. CEUS can provide quantification of the microcirculatory changes in the soft tissues in the dorsum of the foot and reflect the differences of microcirculatory perfusion across different grades of lesions.