Immunohistochemical analysis of von Willebrand factor expression in myocardial tissues from autopsies of patients with ischemic heart disease

von Willebrand factor (VWF) plays a crucial role in hemostasis and thrombosis. VWF is involved in platelet attachment to the subendothelium, serving as a carrier protein for coagulation factor VIII. In this study, myocardial tissues from deceased patients with ischemic heart disease and a mouse model of acute myocardial infarction were subjected to immunohistochemistry to determine VWF expression. We examined 28 neutral formalin-fixed, paraffin-embedded myocardial tissue samples obtained from the autopsies of patients who were diagnosed with ischemic heart disease within 48 h postmortem. Most myocardial cells were negative for VWF, although some cells showed nonspecific positivity. Elevated VWF expression was observed around myocardial cells undergoing remodeling, suggesting that endothelial proliferation occurred at these sites. In contrast, completely fibrotic myocardial foci did not show upregulated VWF expression. Positivity in fibrin deposition and hemorrhagic sites was observed. The same VWF expression characteristics as those observed in the human samples were observed in the mouse model. VWF immunostaining as an endothelial marker may be a useful supplementation to conventional staining techniques that are currently used in the diagnosis of ischemic heart disease in terms of examining the timing of myocardial remodeling in detail and highlighting the remodeling process.     

下一代诊断病理学

随着人类基因组测序、生物大数据信息分析、分子病理检测和人工智能辅助病理诊断等技术进步及其应用, 临床医学发展迈向精准诊疗时代。这一时代背景下, 传统诊断病理学迎来前所未有的历史机遇, 正在向"下一代诊断病理学(next-generation diagnostic pathology)"迈进。下一代诊断病理学以病理形态和临床信息为诊断基础, 以分子检测与生物信息分析、智慧制样与流程质控、智能诊断与远程会诊、病灶活体可视化与"无创"病理诊断等创新前沿交叉技术为主要特征, 以多组学和跨尺度整合诊断为病理报告内容, 实现对疾病的"最后诊断", 并预测疾病演进和结局、建议治疗方案和评估治疗反应, 形成新的疾病诊断"金标准"。未来, 需要激发病理学科创新活力, 加快下一代诊断病理学成熟和应用, 重塑病理学科理论和技术体系, 发挥诊断病理学在疾病"防、诊、治、养"等过程中的重要作用, 促进临床医学进一步发展, 服务健康中国战略。     

The 2021 WHO Classification of Lung Tumors: Impact of Advances Since 2015

The 2021 WHO Classification of Thoracic Tumours was published earlier this year, with classification of lung tumors being one of the chapters. The principles remain those of using morphology first, supported by immunohistochemistry, and then molecular techniques. In 2015, there was particular emphasis on using immunohistochemistry to make classification more accurate. In 2021, there is greater emphasis throughout the book on advances in molecular pathology across all tumor types. Major features within this edition are (1) broader emphasis on genetic testing than in the 2015 WHO Classification; (2) a section entirely dedicated to the classification of small diagnostic samples; (3) continued recommendation to document percentages of histologic patterns in invasive nonmucinous adenocarcinomas, with utilization of these features to apply a formal grading system, and using only invasive size for T-factor size determination in part lepidic nonmucinous lung adenocarcinomas as recommended by the eighth edition TNM classification; (4) recognition of spread through airspaces as a histologic feature with prognostic significance; (5) moving lymphoepithelial carcinoma to squamous cell carcinomas; (6) update on evolving concepts in lung neuroendocrine neoplasm classification; (7) recognition of bronchiolar adenoma/ciliated muconodular papillary tumor as a new entity within the adenoma subgroup; (8) recognition of thoracic SMARCA4-deficient undifferentiated tumor; and (9) inclusion of essential and desirable diagnostic criteria for each tumor.     

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project

IntroductionLarge variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways.MethodsGenome Research at Fundacio ACE ([email protected]) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, [email protected] series were meta-analyzed with additional genome-wide association study data sets.ResultsWe classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444.DiscussionThe regulation of vasculature is a prominent causal component of probable AD. [email protected] meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series.     

Subtyping of intraductal papillary mucinous neoplasms – pitfalls of MUC1 immunohistochemistry

Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions of pancreatic ductal adenocarcinoma (PDAC). Current edition of WHO Classification of Tumors of the Digestive System recognizes four different subtypes (gastric, intestinal, pancreatobiliary, and oncocytic) and recommends analysis of mucin expression (MUC1, MUC2, MUC5AC, MUC6) as well as evaluation of architectural and cell differentiation patterns for correct classification. However, there is no consensus on MUC1 expression of IPMN‐lesions in the literature. Current recommendations are based on studies where antibodies against the core MUC1 protein or sialylated MUC1 (tumor associated MUC1), not the fully glycosylated MUC1 were used. We have recently reported that MUC1 is strongly expressed in both gastric and intestinal types IPMN specimens from the cystic wall, obtained by endoscopic ultrasound guided microbiopsy procedure. We have used a commercial MUC1 antibody, validated and recommended for diagnostic use, which recognizes fully glycosylated MUC1. Based on the above, we propose a revision of the WHO Classification, specifying that antibodies against tumor associated MUC1 should be used for IPMN subtyping.     

Heart rupture as an acute complication of cocaine abuse: A case report

The purpose of this study is to show a very rare complication of acute cocaine poisoning, namely heart rupture. In the present case report, acute cocaine intoxication caused massive myocardial infarction, resulting in heart rupture and cardiac tamponade. A crime scene investigation found a dead body on the street in a drug dealing district. Examination of the body showed no external injuries. A thorough autopsy was performed showing massive cardiac tamponade with 510 ml of blood within the pericardium and full-thickness tissue lesion at the posterior wall of the left ventricle of 3.5 × 3 cm. Histological examination in hematoxylin and eosin was performed and confirmed the interruption of the posterior wall of the left ventricle with the presence of blood. In fact, although the correlation between cocaine and myocardial damage is well established, the relationship between heart rupture and acute cocaine intoxication is an extremely rare event. Moreover, since there are, to date, few reports of similar deaths, our report provides useful information regarding sudden death in a cocaine abuser. It is, therefore, of crucial importance to report this case to the scientific community.     

Understanding How Newly Implemented Rehabilitation Best Practices Are Sustained: A Realist Review

ObjectiveWe conducted a realist review to understand how (mechanism) and in what circumstances (context) evidence-based practices are sustained in rehabilitation (outcome).Data SourcesMEDLINE, Embase, reference lists, and targeted websites.Study SelectionTwo independent reviewers calibrated study selection; then 1 reviewer screened all titles and abstracts, while the second reviewer screened a random 20%. We repeated this process for full texts. We included 115 documents representing 61 implementation projects (8.9% of identified documents). Included documents described implementation projects in which physical therapists, occupational therapists, and/or speech-language pathologists were the target users of an evidence-based practice.Data ExtractionTwo reviewers repeated the independent process described in study selection to extract basic study and sustainability characteristics as well as context, mechanism, outcome, and strategy text.Data SynthesisUsing basic numerical analyses, we found that only 54% of evidence-based practices in rehabilitation are sustained. Furthermore, while authors who reported sustainability planning sustained the practice 94% of the time, sustainability planning in rehabilitation is rare (only reported 26% of the time). Extracted text was synthesized using the realist technique of inductive and deductive retroduction in which context, mechanism, outcome, and strategy text are combined into narrative explanations of how sustainability works. To inform these explanations, we applied normalization process theory and the theory of planned behavior. Collectively, the 52 identified narratives provide evidence for 3 patterns: (1) implementation and sustainability phases are interconnected, (2) continued use of the evidence-based practice can be interpreted as the ultimate sustainability outcome, and (3) intermediate sustainability outcomes (ie, fit/alignment, financial support, benefits, expertise) can become contextual features influencing other sustainability outcomes.ConclusionsImplementation teams can use the narrative explanations generated in this review to optimize sustainability planning. This can sustain practice changes and improve quality of care and patient outcomes. Future research should seek to iteratively refine the proposed narrative explanations.