Ontogenetic and interelemental study of appendicular bones of Caiman latirostris Daudin, 1802 sheds light on osteohistological variability in crocodylians.

The osteohistology of vertebrates provides a reliable source to deduce biological information, particularly regarding growth and development. Although osteohistological studies in Neosuchia (Crocodyliformes, Mesoeucrocodylia) are relatively numerous, the number of species studied within the group is still small. Extant crocodilians are known to exhibit intraspecific variability linked to environmental conditions, habitat, feeding, and other intrapopulation factors. Here, we analyzed the osteohistology of the living South American Caiman latirostris throughout posthatching ontogeny. The histology of several appendicular bones of 13 different-sized captive and wild individuals were examined. Although some thin sections revealed the classic lamellar, parallel-fibered, or woven bone matrices, others showed a variation and a mix between the organization of the bone tissue. These histological differences are likely related to variability in the growth dynamics of caimans. In some bones of the juveniles studied, remnants of embryonic bone were observed. Osteohistological variation related to prevailing environmental conditions is documented. Furthermore, our results show ontogenetic variation in the type of bone tissues deposited throughout the development of C. latirostris. This study offers a broad framework for life history interpretations for C. latirostris and provides insight into the evolutionary history and ontogenetic growth of extinct crocodylian lineages.

Deciphering the role of female reproductive tract microbiome in reproductive health: a review.

Relevant studies increasingly indicate that female reproductive health is confronted with substantial challenges. Emerging research has revealed that the microbiome interacts with the anatomy, histology, and immunity of the female reproductive tract, which are the cornerstone of maintaining female reproductive health and preventing adverse pregnancy outcomes. Currently, the precise mechanisms underlying their interaction and impact on physiological functions of the reproductive tract remain elusive, constituting a prominent area of investigation within the field of female reproductive tract microecology. From this new perspective, we explore the mechanisms of interactions between the microbiome and the anatomy, histology, and immunity of the female reproductive tract, factors that affect the composition of the microbiome in the female reproductive tract, as well as personalized medicine approaches in managing female reproductive tract health based on the microbiome. This study highlights the pivotal role of the female reproductive tract microbiome in maintaining reproductive health and influencing the occurrence of reproductive tract diseases. These findings support the exploration of innovative approaches for the prevention, monitoring and treatment of female reproductive tract diseases based on the microbiome.

Follicular Psoriasis: A Case Report and Review of Literature.

Introduction: Psoriasis is an autoimmune papulosquamous disorder characterized by erythematous plaques. There are various subtypes, of which follicular psoriasis (FP) is an underreported entity, presenting as scaly follicular papules. Only a few cases have been reported, with limited dermoscopy findings having been described. This report aims to review the literature and emphasize the role of dermoscopy in the diagnosis of this rare variant. Case Report: A 31-year-old diabetic and obese male presented with symmetrical, itchy, scaly follicular lesions on his axillae, elbows, and knees for 6 months. Clinical differentials included follicular pityriasis rosea, pityriasis versicolor, or eczema. Dermoscopy revealed white scales and erythematous areas with multiple red dots present around hair follicles. Histopathology showed distended follicular infundibula with parakeratotic scales and psoriasiform changes, leading to a diagnosis of FP. Treatment with topical mometasone furoate and oral levocetirizine led to complete resolution within a month. Discussion: FP is a relatively uncommon subtype of psoriasis, manifesting differently in adults and juveniles. Although its exact cause remains unknown, hair follicle immune cells and/or keratin 17 (K17) may be involved. Dermoscopy can help distinguish it by revealing typical features including perifollicular white scales and vascular structures. Further epidemiological studies and long-term follow-up are needed for a comprehensive understanding of FP.

The 2-tier grading system identifies canine cutaneous and/or subcutaneous mast cell tumors with aggressive biological behavior regardless of growth model.

Histologic grading of canine cutaneous mast cell tumors (cMCTs) has prognostic and therapeutic implications, yet validation for subcutaneous MCTs (scMCTs) is lacking. For scMCTs with or without dermal invasion, determining their biological behavior remains poorly standardized and sometimes sparks controversy. This prospective study aimed to assess the prognostic utility of the 2-tier histologic grading system in MCTs with different growth models (GMs) and explore the prognostic impact of the GM itself. We assessed 6 histologic GM categories: solely cMCT (C-SC0), cMCT with superficial (C-SC1) or deep subcutaneous (C-SC2) involvement, solely scMCT (SC-C0), and scMCT with deep (SC-C1) or superficial (SC-C2) infiltration of the dermis. Ninety-one MCTs from 76 dogs undergoing excision and regional/sentinel lymphadenectomy were examined. GM classification identified 11 (12%) C-SC0 tumors, 12 (13%) C-SC1, 15 (16%) C-SC2, 21 (23%) SC-C0, 15 (16%) SC-C1, and 17 (19%) SC-C2. Mitotic count, 2-tier grade, nodal involvement, surgical margins, and outcome were stratified according to GM. scMCTs lacking dermal invasion, historically associated with a benign clinical course, had a poor prognosis in 10% of cases. cMCTs exhibiting deep subcutaneous involvement included the largest percentage of high-grade tumors (33%), had the highest occurrence of overt nodal metastases (33%), and had the lowest 1-year survival rate (86%). Histologic grade was confirmed as a relevant prognostic factor, surpassing nodal involvement and histologic margin status. The 2-tier histologic grading enabled the identification of all MCTs with aggressive biological behavior, regardless of their cutaneous or subcutaneous location.

Evaluating the Role of Nanoparticles in Enhancing Bone Regeneration in Dental Implantology.

Background: Dental implantology has witnessed substantial progress in recent years, driven by a growing emphasis on optimizing bone regeneration around dental implants. Nanoparticles have emerged as a potential tool for enhancing osseointegration and bone tissue regeneration. Materials and Methods: This human clinical trial enrolled 60 adult participants requiring dental implants. Patients were randomly assigned to one of two groups: a control group receiving conventional dental implants, and an experimental group receiving dental implants with nanoparticle-coated surfaces. Radiographic imaging, histological analysis of bone biopsies, and implant stability assessments were conducted at three and six months post-implantation. Results: Histological examination of bone biopsies revealed a statistically significant increase in new bone formation in the experimental group compared to the control group at both three and six months (P < 0.05). Radiographic assessment demonstrated a 25% higher bone density around nanoparticle-coated implants (P < 0.01) at the six-month mark. Implant stability quotient (ISQ) measurements indicated a 20% greater stability in the experimental group (P < 0.05) at the same time point. Conclusion: This human clinical trial provides strong evidence that the incorporation of nanoparticles on dental implant surfaces enhances bone regeneration and osseointegration in a human population.

Histological characterization and development of mesial surface sulci in the human brain at 13-15 gestational weeks through high-resolution histology.

Cellular-level anatomical data from early fetal brain are sparse yet critical to the understanding of neurodevelopmental disorders. We characterize the organization of the human cerebral cortex between 13 and 15 gestational weeks using high-resolution whole-brain histological data sets complimented with multimodal imaging. We observed the heretofore underrecognized, reproducible presence of infolds on the mesial surface of the cerebral hemispheres. Of note at this stage, when most of the cerebrum is occupied by lateral ventricles and the corpus callosum is incompletely developed, we postulate that these mesial infolds represent the primordial stage of cingulate, callosal, and calcarine sulci, features of mesial cortical development. Our observations are based on the multimodal approach and further include histological three-dimensional reconstruction that highlights the importance of the plane of sectioning. We describe the laminar organization of the developing cortical mantle, including these infolds from the marginal to ventricular zone, with Nissl, hematoxylin and eosin, and glial fibrillary acidic protein (GFAP) immunohistochemistry. Despite the absence of major sulci on the dorsal surface, the boundaries among the orbital, frontal, parietal, and occipital cortex were very well demarcated, primarily by the cytoarchitecture differences in the organization of the subplate (SP) and intermediate zone (IZ) in these locations. The parietal region has the thickest cortical plate (CP), SP, and IZ, whereas the orbital region shows the thinnest CP and reveals an extra cell-sparse layer above the bilaminar SP. The subcortical structures show intensely GFAP-immunolabeled soma, absent in the cerebral mantle. Our findings establish a normative neurodevelopment baseline at the early stage.

Monitoring pediatric eosinophilic esophagitis disease activity using an unsedated blind esophageal brushing model: A pilot study.

BACKGROUND: Recurrent upper endoscopies are essential for monitoring therapy response and disease activity in patients with eosinophilic esophagitis (EoE), leading to increased costs, procedural complications, and anesthesia exposure. The aim of this study was to examine an office-based model using serial sedation-free blind esophageal epithelial brushing (BEEB) to monitor therapy response through eosinophil-derived neurotoxin (EDN) levels and guide therapy plans in pediatric EoE patients. METHODS: EoE patients (≤21 years of age) were enrolled in this prospective study. Subjects were placed on dietary, pharmacologic, or combination therapy with the goal of inducing or maintaining remission. To assess response to sequential interventions, subjects underwent sequential sedation-free BEEBs through nasogastric tubes to measure EDN levels. Based on serial brushings, an individual plan of diet, medications, or a combination of both was created for each subject, and a final endoscopy was then performed to validate the accuracy of the individual plans. RESULTS: Twenty-four subjects completed the study. The average peak eosinophil count in patients with active EoE was 58.1 ± 30.8 eosinophils per high-power field and mean EDN level was 165.2 ± 191.3 µg/mL. A total of 42 BEEBs were completed. Individual therapy plans based on sequential BEEB were accurate in 19 out of the 24 patients (79%) and specifically nine out of 10 patients (90%) treated with elimination diets. CONCLUSION: This study suggests that office-based sedation-free BEEBs can be used to monitor therapy response and disease activity in pediatric EoE patients.

Corticosteroid-associated osteonecrosis of the femoral head in an 87-year-old patient following treatment for COVID-19-associated pneumonia: A case report.

Coronavirus disease 2019 is known to cause severe acute respiratory syndrome, and serious cases need to be treated with corticosteroids. Herein, we report an 87-year-old woman who developed bilateral osteonecrosis of the femoral head after corticosteroid treatment for coronavirus disease 2019-related pneumonia. Sixteen months after treatment, she developed right hip pain without any evidence of trauma. A diagnosis of bilateral osteonecrosis of the femoral head was made based on sclerotic bands on plain radiographs and low-signal bands on T1-weighted magnetic resonance images. The patient underwent right total hip arthroplasty 4 months after symptom onset. Histological examination of the resected femoral head revealed pathological evidence of osteonecrosis. The postoperative course was good, and the patient can now walk unassisted. To the best of our knowledge, this is the first report of histologically proven osteonecrosis after corticosteroid therapy for coronavirus disease 2019-related disease.

An artificial intelligence-driven scoring system to measure histological disease activity in ulcerative colitis.

BACKGROUND AND AIMS: Assessment and scoring of histological images in Ulcerative colitis (UC) is prone to inter- and intra-observer variability. This study aimed to investigate whether an artificial intelligence (AI) system developed using image processing and machine learning algorithms could measure histological disease activity based on the Nancy index. METHODS: A total of 200 histological images of patients with UC were used in this study. A novel AI algorithm was developed using state-of-the-art image processing and machine learning algorithms based on deep learning and feature extraction. The cell regions of each image, followed by the Nancy index, were manually annotated and measured independently by four histopathologists. Manual and AI-automated measurements of the Nancy index score were conducted and assessed using the intraclass correlation coefficient (ICC). RESULTS: The 200-image dataset was divided into two groups (80% was used for training and 20% for testing). Intraclass correlation coefficient statistical analyses were performed to evaluate the AI tool and used as a reference to calculate the accuracy. The average ICC among the histopathologists was 89.3 and the average ICC between histopathologists and the AI tool was 87.2. The AI tool was found to be highly correlated with histopathologists. CONCLUSIONS: The high correlation of performance of the AI method suggests promising potential for inflammatory bowel disease clinical applications. A standardized automated histological AI-driven scoring system can potentially be used in daily inflammatory bowel disease practice to reduce training needs and resource use, eliminate the subjectivity of the pathologists, and assess disease severity for treatment decisions.

Capsular attachment on the anterosuperior femoral head-neck junction: A hypothesis about femoroacetabular impingement.

Femoroacetabular impingement (FAI), characterized by a pathological contact between the proximal femur and acetabulum, is a common precursor of hip osteoarthritis. Cam morphology is a bony prominence that causes FAI and frequently forms on the anterosuperior femoral head-neck junction. Despite anatomical consensus regarding the femoral head-neck junction as a boundary area covered by the articular cartilage and joint capsule, it remains unclear whether the joint capsule is continuous with the anterosuperior articular cartilage. For the anatomical consideration of cam morphology formation, this study aimed to investigate the histological characteristics of the capsular attachment on the anterosuperior femoral head-neck junction, particularly focusing on the presence or absence of continuity of the joint capsule to the articular cartilage. A total of 21 anterosuperior regions (seven hips each for the 12:00, 1:30, and 3:00 positions) from seven hips (three males and four females; mean age at death, 68.7 years) were histologically analyzed in this study for quantitative evaluation of the capsular thickness using histological sections stained with Masson's trichrome, as well as qualitative evaluation of the capsular attachment. The present study showed that the joint capsule, which folded proximally to the femoral head-neck junction from the recess, exhibited a blend of the fibrous and synovial regions. Notably, it not only continued with the superficial layer of the articular cartilage, but also attached to the articular cartilage via the fibrocartilage. This continuous region was relatively fibrous with dense connective tissue running in the longitudinal direction. The capsular thickness at the recess point (mean, 1.7 ± 0.9 mm) and those at the distal end of the articular cartilage (0.35 ± 0.16 mm) were significantly greater than the control value for the most superficial layer thickness of the articular cartilage (0.019 ± 0.003 mm) (Dunnett's T3, both p-value <0.001). Based on the fibrous continuity between the joint capsule and articular cartilage and its thickness, this study suggests the anatomical possibility that some mechanical stress can be transmitted from the joint capsule to the articular cartilage at the frequent sites of cam morphology.

Assessment of dental pulp response to carries via MR T2mapping and histological analysis.

OBJECTIVES: The aim of our study was to assess the correlation between T2 relaxation times and their variability with the histopathological results of the same teeth in relation to caries progression. MATERIALS AND METHODS: 52 extracted permanent premolars were included in the study. Prior to extractions, patients underwent magnetic resonance imaging (MRI) scanning and teeth were evaluated using ICDAS classification. Pulps of extracted teeth were histologically analysed. RESULTS: MRI T2 relaxation times (ms) were 111,9 ± 11.2 for ICDAS 0, 132.3 ± 18.5* for ICDAS 1, 124.6 ± 14.8 for ICDAS 2 and 112. 6 ± 18.2 for ICDAS 3 group (p = 0,013). A positive correlation was observed between MRI T2 relaxation times and macrophage and T lymphocyte density in healthy teeth. There was a positive correlation between vascular density and T2 relaxation times of dental pulp in teeth with ICDAS score 1. A negative correlation was found between T2 relaxation times and macrophage density. There was a positive correlation between T2 relaxation time variability and macrophage and T lymphocyte density in teeth with ICDAS score 2. In teeth with ICDAS score 3, a positive correlation between T2 relaxation times and T2 relaxation time variability and lymphocyte B density was found. CONCLUSION: The results of our study confirm the applicability of MRI in evaluation of the true condition of the pulp tissue. CLINICAL RELEVANCE: With the high correlation to histological validation, MRI method serves as a promising imaging implement in the field of general dentistry and endodontics.

[Research progress on pseudocirrhosis].

Presently, pseudocirrhosis occurs in most patients with liver metastases from malignant tumors and can exhibit clinical manifestations related to portal hypertension, such as edema, ascites, and gastrointestinal bleeding. Imaging features include malignant tumor liver metastasis, the appearance of nodules accompanied with or without hepatic contour, segmental liver volume reduction, and caudate lobe enlargement. Histology shows the typical pathological manifestations of liver cirrhosis, such as diffuse tumor cell infiltration, fibrosis around the infiltrating lesion, hepatic sinus vascular thrombosis, nodular hyperplasia, non-accompanied bridging necrosis, bridging fibrosis, and pseudolobule formation. The possible pathogenesis of pseudocirrhosis is tumor cell infiltration and toxic reactions of tumor cells and liver cells to chemotherapy. The presence of pseudocirrhosis in patients diagnosed with malignant tumors is one of the challenges affecting their survival cycle and shortening the median survival time. The relationship between its onset, tumor type and metastasis, and the use of chemotherapy drugs is still unclear. The atypical clinical manifestations and imaging characteristics bring about great challenges for clinicians and patients. Thus, based on the existing case reports, observational studies, and meta-analysis results, this article reviews the research progress on the prevalence, etiology, pathogenesis, diagnosis, treatment, and prognosis of pseudocirrhosis.

Research Note: Prospects for early detection of breast muscle myopathies by automated image analysis.

White Striping (WS), Wooden Breast (WB), and Spaghetti Meat (SM) are documented breast muscle myopathies (BMM) affecting broiler chickens' product quality, profitability and welfare. This study evaluated the efficacy of our newly developed deep learning-based automated image analysis tool for early detection of morphometric parameters related to BMM in broiler chickens. Male chicks were utilized, and muscle samples were collected on d 14 of rearing. Histological procedures, including microscopic scoring, blood vessel count, and collagen quantification, were conducted. A previous study demonstrated our automated image analysis as a reliable tool for evaluating myofiber size, conforming with manual histological measurements. A threshold for BMM detection was established by normalizing and consolidating myofiber diameter and area into a unified metric based on automated measurements, also termed as "relative myofiber size value." Results show that severe myopathy broilers consistently exhibited lower relative myofiber size values, effectively detecting myopathy severity. Our study, aimed as proof of concept, underscores the potential of our automated image analysis tool as an early detection method for BMM.

Evaluation of histological variants of upper tract urothelial carcinoma as prognostic factor after radical nephroureterectomy.

PURPOSE: To evaluate the impact of variant histology on patients with upper tract urothelial carcinoma (UTUC) survival outcomes. MATERIALS AND METHODS: A total of 519 patients underwent radical nephroureterectomy without neoadjuvant therapy for UTUC at a single institution between May 2003 and December 2019. Multivariate Cox regression analysis evaluated the impact of variant histology on progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: Among 84 patients (16.2%) with variant histology, the most frequent variant type was squamous cell differentiation (64.3%), followed by glandular differentiation (25.0%) and sarcomatoid variant (2.4%). They showed pathologically advanced T stage (for ≥ T3, 59.5% vs 33.3%, p < 0.001), higher tumor grade (96.4% vs 85.7%, p = 0.025), and higher rates of lymph node metastasis (17.9% vs 7.8%, p = 0.015), angiolymphatic invasion (41.7% vs 25.7%, p = 0.003), tumor necrosis (57.1% vs 29.0%, p < 0.001) and positive surgical margin (13.1% vs 5.7%, p = 0.015). On multivariate Cox regression analyses, variant histology was significantly associated with worse PFS (hazard ratio [HR] 2.23; 95% confidence interval [CI] 1.55-3.21; p < 0.001), CSS (HR 2.67; 95% CI 1.35-5.30; p = 0.005) and OS (HR 2.22; 95% CI 1.27-3.88; p = 0.005). In subgroup analysis, no significant survival gains of adjuvant chemotherapy occurred in patients with variant histology. CONCLUSIONS: Variant histology was associated with adverse pathologic features and poor survival outcomes. Our results suggest that patients with variant histology may require a close follow-up schedule and novel adjuvant therapy other than chemotherapy postoperatively.

Flipped online teaching of histology and embryology with design thinking: design, practice and reflection.

BACKGROUND: Flexible hybrid teaching has become the new normal of basic medical education in the postepidemic era. Identifying ways to improve the quality of curriculum teaching and achieve high-level talent training is a complex problem that urgently needs to be solved. Over the course of the past several semesters, the research team has integrated design thinking (DT) into undergraduate teaching to identify, redesign and solve complex problems in achieving curriculum teaching and professional talent training objectives. METHODS: This study is an observational research. A total of 156 undergraduate stomatology students from Jining Medical University in 2021 were selected to participate in two rounds of online flipped teaching using the design thinking EDIPT (empathy, definition, idea, prototype, and test) method. This approach was applied specifically to the chapters on the respiratory system and female reproductive system. Data collection included student questionnaires, teacher-student interviews, and exam scores. GraphPad Prism software was used for data analysis, and the statistical method was conducted by multiple or unpaired t test. RESULTS: According to the questionnaire results, the flipped classroom teaching design developed using design thinking methods received strong support from the majority of students, with nearly 80% of students providing feedback that they developed multiple abilities during the study process. The interview results indicated that teachers generally believed that using design thinking methods to understand students' real needs, define teaching problems, and devise instructional design solutions, along with testing and promptly adjusting the effectiveness through teaching practices, played a highly positive role in improving teaching and student learning outcomes. A comparison of exam scores showed a significant improvement in the exam scores of the class of 2021 stomatology students in the flipped teaching chapters compared to the class of 2020 stomatology students, and this difference was statistically significant. However, due to the limitation of the experimental chapter scope, there was no significant difference in the overall course grades. CONCLUSION: The study explores the application of design thinking in histology and embryology teaching, revealing its positive impact on innovative teaching strategies and students' learning experience in medical education. Online flipped teaching, developed through design thinking, proves to be an effective and flexible method that enhances student engagement and fosters autonomous learning abilities.

Validation of NIAAAm-CRP criteria to predict alcohol-associated steatohepatitis on liver histology.

Background & Aims: In clinical practice, the diagnosis of alcohol-associated hepatitis (AH) is mostly based on non-invasive criteria, which were defined at a consensus conference by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). These criteria were recently modified by adding C-reactive protein (CRP) and termed NIAAAm-CRP criteria, which showed superior diagnostic accuracy for presence of alcohol-associated steatohepatitis (ASH) on liver histology. The aim of our study was to validate the diagnostic accuracy of both original NIAAA criteria and NIAAAm-CRP criteria for presence of ASH on liver histology in an independent cohort. Methods: Data from a large multinational cohort of 445 patients with alcohol-associated liver disease (ALD) that served to establish a novel grading and staging system of alcohol-associated liver disease were analyzed retrospectively. Diagnosis of ASH was based on presence of hepatocyte ballooning plus lobular neutrophil infiltration and established in virtual consensus meetings of multiple expert liver pathologists. Results: Complete data including CRP values were available in 346 patients. Overall diagnostic accuracy for prediction of ASH was 73% for NIAAA criteria and 77% for NIAAAm-CRP criteria. In a subgroup with suspected severe AH (MELD >20, n = 123), overall diagnostic accuracy for prediction of ASH was 69% for NIAAA criteria and 74% for NIAAAm-CRP criteria. Conclusion: Our findings confirm recent data on suboptimal diagnostic accuracy of original NIAAA criteria and validate slightly better but still suboptimal performance of NIAAAm-CRP criteria for presence of ASH. Impact and Implications: Alcohol-associated steatohepatitis (ASH) is diagnosed on liver histology but liver biopsy is not always feasible. Non-invasive diagnosis based on clinical findings has been proposed using the National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria and recently improved using NIAAAm-CRP criteria. Our findings validate slightly better but still suboptimal performance of NIAAAm-CRP criteria for the presence of histological ASH. Clinical trials of novel drugs should focus on histologically proven ASH.

Precirrhotic Primary Biliary Cholangitis with Portal Hypertension: Bile Duct Injury Correlate.

Background/Aims: : The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH. Methods: : This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients. Results: : Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH. Conclusions: : Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

Histopathological findings of failed blebs after microinvasive bleb surgery with the XEN Gel Stent and Preserflo MicroShunt.

PURPOSE: The success of XEN Gel Stent (XEN) and Preserflo MicroShunt (Preserflo) implantation depends mainly on the development of bleb fibrosis. This study aimed to describe the histological findings of bleb fibrosis after XEN and Preserflo surgery. METHODS: This retrospective study included patients with different types of glaucoma who underwent revision surgery after XEN or Preserflo implantation. The available clinical information and histological samples of removed fibrotic tissue were analyzed. RESULTS: Thirty-six patients were included. Revision surgery was performed at a median of 195 (range = 31-1264) days after primary surgery. The mean intraocular pressure changed from 29.1 (± 10.3) mmHg at baseline to 18.3 (± 8.7) mmHg (- 37%; p < 0.0001) and 16.2 (± 4.2) mmHg (- 45%; p < 0.0001) after 6 and 12 months, respectively. Histological analysis revealed an increase in activated fibroblasts and macrophages in all specimens and a parallel orientation of fibroblasts in a minor part of the probe in 60% of the specimens. No pronounced inflammatory reaction in the form of lymphocytic or granulocytic infiltration was observed. The comparison of specimens from uveitic glaucoma and primary open-angle glaucoma patients revealed no significant differences. CONCLUSIONS: The histological analysis of fibrotic blebs from the XEN and Preserflo implants did not show any pronounced immune or foreign-body reaction and revealed a similar histological pattern of failed blebs after trabeculectomy.

Local, Quantitative Morphometry of Fibroproliferative Lung Injury Using Laminin.

Investigations into the mechanisms of injury and repair in fibroproliferative disease require consideration of the spatial heterogeneity inherent in the disease. Most scoring of fibrotic remodeling in preclinical animal models rely on the modified Ashcroft score, which is a semi-quantitative scoring rubric of macroscopic resolution. The obvious limitations inherent in manual pathohistological grading have generated an unmet need for unbiased, repeatable scoring of fibroproliferative burden in tissue. Using computer vision approaches on immunofluorescent imaging of the extracellular matrix (ECM) component laminin, we generate a robust and repeatable quantitative remodeling scorer (QRS). In the bleomycin lung injury model, QRS shows agreement with modified Ashcroft scoring with a significant Spearman coefficient r=0.768. This antibody-based approach is easily integrated into larger multiplex immunofluorescent experiments, which we demonstrate by testing the spatial apposition of tertiary lymphoid structures (TLS) to fibroproliferative tissue. The tool reported in this manuscript is available as a standalone application which is usable without programming knowledge.