Crosstalk between Oxidative Stress and Inflammatory Liver Injury in the Pathogenesis of Alcoholic Liver Disease

Alcoholic liver disease (ALD) is characterized by the injury, inflammation, and scarring in the liver owing to excessive alcohol consumption. Currently, ALD is a leading cause for liver transplantation. Therefore, extensive studies (in vitro, in experimental ALD models and in humans) are needed to elucidate pathological features and pathogenic mechanisms underlying ALD. Notably, oxidative changes in the liver have been recognized as a signature trait of ALD. Progression of ALD is linked to the generation of highly reactive free radicals by reactions involving ethanol and its metabolites. Furthermore, hepatic oxidative stress promotes tissue injury and, in turn, stimulates inflammatory responses in the liver, forming a pathological loop that promotes the progression of ALD. Accordingly, accumulating further knowledge on the relationship between oxidative stress and inflammation may help establish a viable therapeutic approach for treating ALD.

Clinical and Pathological Features of Immune-Mediated Necrotising Myopathies in a Single-Centre Muscle Biopsy Cohort

Objective Immune-mediated necrotising myopathy (IMNM) is a recently entitled novel subset of idiopathic inflammatory myopathies (IIM) characterized by significant elevated creatine kinase (CK) level, muscle weakness and predominant muscle fibre necrosis in muscle biopsy. This study aimed to investigate the clinical and pathological characteristics of patients with IMNM in our single-centre muscle biopsy cohort. Methods A total of 860 patients who had muscle biopsy reports in our centre from May 2008 to December 2017 were enrolled in this study. IMNM was diagnosed in according with 2018 European Neuromuscular Centre (ENMC) clinicopathological diagnostic criteria for IMNM. Results The muscle biopsy cohort consisted of 531 patients with IIM (61.7%), 253 patients with non-IIM (29.4%), and 76 undiagnosed patients (8.8%). Among IIM patients, polymyositis (PM), dermatomyositis(DM), amyopathic dermatomyositis, juvenile DM, and inclusion body myositis were 182(21.2%), 236(27.4%), 83(9.7%), 18(2.1%) and 3(0.3%), respectively. In PM subgroup, 59 patients met serological and pathological characteristics of IMNM according to 2018 ENMC criteria including 29 anti-SRP-positive patients,10 anti-HMGCR-positive patients and 20 MSA-negative patients. Limb girdle muscular dystrophy (LGMD) 2B and lipid storage myopathy (LSM) were 29 and 16 respectively, which present similar manifestations of IMNM with elevated CK levels and muscle weakness among non-IIM group. IMNM patients had older age of onset (mean: 42.25 vs 21.66 and 24.56, p<0.0001), shorter duration of diseases (mean: 22.56 vs 66.69 and 48.94, p<0.0001) and more frequent of dysphagia (33.9% vs 3.4% and 6.3%, p<0.0001) compare to patients with LGMD 2B and LSM. Muscle biopsy from IMNM patients showed frequent muscle fibre necrosis (96.6% vs 72.4% and 56.3%, p<0.0001), overexpression of MHC-I on sarcolemma (81.4% vs 37.9% and 12.9%, p<0.0001) and CD4+ T cell endomysial infiltration (89.9% vs 53.6% and 50%, p<0.0001) compared with LGMD 2B and LSM patients. Conclusions It is easy to distinguish IMNM from other subtype of IIM according to clinical symptoms and MSAs profiles. However, distinguishing IMNM from disorders clinically similar non-IIM need to combine with clinical, serological and pathological features.

Analysis of Clinical Characteristics, Radiological Predictors, Pathological Features, and Perioperative Outcomes Associated with Perinephric Fat Adhesion Degree

Background. To assess the clinical characteristics, radiological predictors, and pathological features of perinephric fat adhesion degree (PFAD) graded based on fixed criteria and to determine the impact of adherent perinephric fat (APF) on retroperitoneal laparoscopic partial nephrectomy (RLPN) outcomes. Methods. 84 patients undergoing RLPN were included and graded into 4 groups based on PFAD. Univariate and multivariate analyses were performed for clinical characteristics and radiological predictors of PFAD. Perioperative data were compared between APF groups and non-APF groups. Masson staining determined collagen fibers. Immunohistochemistry detected CD45 immune cells and CD34 vessels. Results. 20, 28, 18, and 18 patients were graded as normal perinephric fat (NPF), mild adherent perinephric fat (MiPF), moderate adherent perinephric fat (MoPF), and severe adherent perinephric fat (SPF), respectively. Multivariate analysis revealed that gender ( p < 0.001), age ( p = 0.003), and hypertension ( p = 0.006) were significant clinical risk factors of PFAD, while radiological predictors included perinephric stranding ( p = 0.001), posterior perinephric fat thickness ( p = 0.009), and perinephric fat density ( p = 0.02). APF was associated with drain output ( p = 0.012) and accompanied by immune cells gathering in renal cortex near thickened renal capsule with many vessels. Conclusions. Clinical characteristics and radiological predictors can evaluate PFAD and may assist to guide preoperative surgical option. Pathological features of APF reflect decapsulation and bleeding during kidney mobilization at RLPN.

Demographic, clinico-pathological features and management pattern of primary bone tumors in a tertiary care hospital of South India

<p><strong>Background</strong>: Primary bone tumors are very rare tumors. The true incidence of bone tumors is not well established and is under reported due to rarity and lack of accurate registries. Hence it is essential to study about the demographic, clinico-pathological features and the pattern of surgical management of bone tumors. The aim of this study is to analyze the demographic and clinico-pathological features of primary bone tumors that were managed by surgery.</p><p><strong>Methods</strong>: A retrospective analysis of all patients with primary bone tumor who were treated by surgery from 2012 to 2019 was done. The age, sex distribution, histopathology, location of the tumor and surgical procedure done were analyzed.</p><p><strong>Results</strong>: Among 103 patients analyzed, 66 (64%) were men and 37 (36%) were women. Primary bone tumors most commonly presented in 11 to 20 years of age with 35 (33.9%) patients occurring in this age group. Osteosarcoma was the most common primary bone tumor and it occurred in 49 (47.6%) patients, out of which 34 (69.3%) patients were below 20 years of age. Giant cell tumor was the most common benign bone tumor and it occurred in 22 patients, out of which nine (40.9%) patients were of age 21 to 30 years. Distal femur was the most common site with 39 (37.9%) patients. The limb preservation rate for malignant appendicular bone tumors was 69.0%.</p><p><strong>Conclusions</strong>: The diagnosis of bone tumor depends not only on histopathological features but also needs correlation with age, clinical features, tumor location and radiological features for confirmation of diagnosis.</p>

Nomograms Combining Ultrasonic Features With Clinical and Pathological Features for Estimation of Delphian Lymph Node Metastasis Risk in Papillary Thyroid Carcinoma

BackgroundThis work explores the clinical significance of Delphian lymph nodes (DLN) in thyroid papillary carcinoma (PTC). At the same time, a nomogram is constructed based on clinical, pathological, and ultrasonic (US) features to evaluate the possibility of DLN metastasis (DLNM) in PTC patients. This is the first study to predict DLNM using US characteristics.MethodsA total of 485 patients, surgically diagnosed with PTC between February 2017 and June 2021, all of whom underwent thyroidectomy, were included in the study. Using the clinical, pathological, and US information of patients, the related factors of DLNM were retrospectively analyzed. The risk factors associated with DLNM were identified through univariate and multivariate analyses. According to clinical + pathology, clinical + US, and clinical + US + pathology, the predictive nomogram for DLNM was established and validated.ResultsOf the 485 patients with DLN, 98 (20.2%) exhibited DLNM. The DLNM positive group had higher positive rates of central lymph node metastasis (CLNM), lateral lymph node metastasis (LLNM), and T3b–T4b thyroid tumors than the negative rates. The number of CLNM and LLNM lymph nodes in the DLNM+ group was higher as compared to that in the DLNM- group. Multivariate analysis demonstrated that the common independent risk factors of the three prediction models were male, bilaterality, and located in the isthmus. Age ≥45 years, located in the lower pole, and nodural goiter were protective factors. In addition, the independent risk factors were classified as follows: (I) P-extrathyroidal extension (ETE) and CLNM based on clinical + pathological characteristics; (II) US-ETE and US-CLNM based on clinical + US characteristics; and (III) US-ETE and CLNM based on clinical +US + pathological features. Better diagnostic efficacy was reported with clinical + pathology + US diagnostic model than that of clinical + pathology diagnostic model (AUC 0.872 vs. 0.821, p = 0.039). However, there was no significant difference between clinical + pathology + US diagnostic model and clinical + US diagnostic model (AUC 0.872 vs. 0.821, p = 0.724).ConclusionsThis study found that DLNM may be a sign that PTC is more invasive and has extensive lymph node metastasis. By exploring the clinical, pathology, and US characteristics of PTC progression to DLNM, three prediction nomograms, established according to different combinations of features, can be used in different situations to evaluate the transfer risk of DLN.