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Primary sclerosing cholangitis associated colitis: Characterization of clinical, histologic features, and their associations with liver transplantation

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World Journal of Gastroenterology 2020年第28期26卷 4126-4139页

作者： John Aranake-Chrisinger Themistocles Dassopoulos Yan Yan ILKe Nalbantoglu Department of pathology and Immunology Lauren V.Ackerman Laboratory of Surgical PathologyWashington University in St.LouisSchool of MedicineMO 63110United States Baylor Center for IBD Baylor University Medical CenterDallasTX 75246United States Departments of Surgery and Biostatistics Washington University in St.LouisSchool of MedicineMO 63110United States Department of Anatomic pathology Yale University School of MedicineNew HavenCT 06525United States

BACKGROUND Primary sclerosing cholangitis(PSC)associated inflammatory bowel disease(IBD)is a unique form of IBD(PSC-IBD)with distinct clinical and histologic features from ulcerative colitis(UC)and Crohn disease(CD).In patients with PSC and IBD,the severity of the two disease processes may depend on each *** To study the histologic and clinical features of PSC patients with and without *** We assessed specimens from patients with UC(n=28),CD(n=10),PSC and UC(PSC-UC;n=26);PSC and CD(PSC-CD;n=6);and PSC and no IBD(PSC-no IBD;n=4)between years ***-IBD patients were matched to IBD patients without PSC by age and colitis *** data including age,gender,age at IBD and PSC diagnoses,IBD duration,treatment,follow-up,orthotopic liver transplantation(OLT)were *** PSC-UC patients had more isolated right-sided disease(P=0.03),and less active inflammation in left colon,rectum(P=0.03 and P=0.0006),and overall(P=0.0005)compared to *** required less steroids(P=0.01)and fewer colectomies(P=0.03)than UC *** PSC-CD patients had more ileitis and less rectal involvement compared to PSC-UC and *** PSC-CD patients required OLT compared to 38%of PSC-UC(P=0.1).PSC-IBD(PSC-UC and PSCCD)patients with OLT had severe disease in the left colon and rectum(P=0.04).CONCLUSION PSC-UC represents a distinct form of *** different disease phenotype in PSC-IBD patients with OLT may support liver-gut axis interaction,however warrants clinical attention and further research.

关键词： Primary sclerosing cholangitis Inflammatory bowel disease Liver transplantation Inflammation Pathologic features Clinical associations

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Comparative visual analytics for assessing medical records with sequence embedding

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Visual Informatics 2020年第2期4卷 72-85页

作者： Rongchen Guo Takanori Fujiwara Yiran Li Kelly M.Lima Soman Sen Nam K.Tran Kwan-Liu Ma Department of Computer Science Beihang UniversityBeijingChina Department of Computer Science University of CaliforniaDavisUnited States Department of pathology and Laboratory Medicine University of CaliforniaDavisUnited States Department of Surgery University of CaliforniaDavisUnited States

Machine learning for data-driven diagnosis has been actively studied in medicine to provide better *** analysis of a patient cohort similar to a patient under treatment is a key task for clinicians to make decisions with high ***,such analysis is not straightforward due to the characteristics of medical records:high dimensionality,irregularity in time,and *** address this challenge,we introduce a method for similarity calculation of medical *** method employs event and sequence *** we use an autoencoder for the event embedding,we apply its variant with the self-attention mechanism for the sequence ***,in order to better handle the irregularity of data,we enhance the self-attention mechanism with consideration of different time *** have developed a visual analytics system to support comparative studies of patient *** make a comparison of sequences with different lengths easier,our system incorporates a sequence alignment *** its interactive interface,the user can quickly identify patients of interest and conveniently review both the temporal and multivariate aspects of the patient *** demonstrate the effectiveness of our design and system with case studies using a real-world dataset from the neonatal intensive care unit of UC Davis.

关键词： Electronic medical records Event sequence data Autoencoder Self-attention Sequence similarity Visual analytics

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Solid-Tubulocystic carcinoma:A new variant of intrahepatic cholangiocarcinoma

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World Journal of Hepatology 2023年第7期15卷 897-903页

作者： Iván A González Wenyi Luo Xuchen Zhang Department of pathology and Laboratory Medicine Indiana University School of MedicineIN 46202United States Department of pathology Yale University School of MedicineNew HavenCT 06511United States

A new variant of intrahepatic cholangiocarcinoma(iCCA)has been recognized in recent years presenting predominantly as a large hepatic mass in young woman with the characteristic expression of inhibin by *** variant iCCA was originally termed as cholangioblastic variant of iCCA,and subsequently proposed to be renamed as inhibin-positive hepatic carcinoma or solid-tubulocystic variant of iCCA to better reflect its immunohistochemical profile or morphologic *** tumor histologically is composed of small to medium sized cells with scant to moderate amount of eosinophilic cytoplasm heterogeneously organized in solid,tubular,and cystic growth *** tumor cells are positive for biliary markers,inhibin and albumin,and have a novel recurrent gene fusion,NIPBL::*** of this new iCCA variant and its clinicopathologic features will aid in the diagnostic work-up and avoid confusion with other primary and metastatic hepatic neoplasms.

关键词： Cholangiocarcinoma Intrahepatic Solid-tubulocystic Cholangioblastic Inhibin

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Facial amphiphilicity index correlating chemical structures with antimicrobial efficacy

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Bioactive Materials 2023年第2期20卷 519-527页

作者： Leman Buzoglu Kurnaz Yuanyuan Luo Xiaoming Yang Amjed Alabresm Ryan Leighton Rani Kumar JiHyeon Hwang Alan W.Decho Prakash Nagarkatti Mitzi Nagarkatti Chuanbing Tang Department of Chemistry and Biochemistry University of South CarolinaColumbiaSC29208United States Department of pathology Microbiology and ImmunologyUniversity of South CarolinaSchool of MedicineColumbiaSC29209United States Department of Environmental Health Sciences University of South CarolinaColumbiaSC29208United States

Facial amphiphilicity is an extraordinary chemical structure feature of a variety of antimicrobial peptides and *** efforts have been dedicated to small molecular,macromolecular and dendrimer-like systems to mimic this highly preferred structure or conformation,including local facial amphiphilicity and global *** work conceptualizes Facial Amphiphilicity Index(FAI)as a numerical value to quantitatively characterize the measure of chemical compositions and structural features in dictating antimicrobial *** is a ratio of numbers of charges to rings,representing both compositions of hydrophilicity and *** derivatives of multicyclic compounds were evaluated as model systems for testing antimicrobial selectivity against Gram-negative and Gram-positive *** monocyclic and bicyclic compounds are non-antimicrobial regardless of *** efficacy was observed with systems having larger cross-sectional areas including tricyclic abietic acid and tetracyclic bile *** low and high FAIs respectively lead to higher and lower antimicrobial efficacy,in consideration of cytotoxicity,the sweet spot is typically suited with intermediate FAIs for each specific *** can be well explained by the synergistic hydrophobic-hydrophobic and electrostatic interactions with bacterial cell membranes and the difference between bacterial and mammalian cell *** adoption of FAI would pave a new avenue toward the design of next-generation antimicrobial macromolecules and peptides.

关键词： Antimicrobial Facial amphiphilicity Chemical structure Peptide

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Manifestations of gastrointestinal plasmablastic lymphoma: A case series with literature review

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World Journal of Gastroenterology 2014年第33期20卷 11894-11903页

作者： Lynette Luria Johnny Nguyen Jun Zhou Michael Jaglal Jane L Messina Domenico Coppola Lubomir Sokol Ling Zhang Department of pathology University of South Florida Morsani College of Medicine Tampa FL 33612 United States. Department of pathology Wayne State University School of Medicine Detroit MI 48202 United States Department of Malignant Hematology H. Lee Moffitt Cancer Center and Research Institute Tampa FL 33612 United States Department of Surgical pathology H. Lee Moffitt Cancer Center and Research Institute Tampa FL 33612 United States Department of Hematopathology and Laboratory Medicine H. Lee Moffitt Cancer Center and Research Institute Tampa FL 33612 United States

Plasmablastic lymphoma (PBL) rarely occurs in the gastrointestinal (GI) tract with limited studies reported. We reviewed the clinical histories and pathology of four patients with GI PBL at our institute and similar case reports published in peer-reviewed journals. In our first case, a 40 year-old human immunodeficiency virus positive male presented with a hemorrhoid-like sensation, and was diagnosed with PBL via biopsy of a rectal mass. The second case involves a 65 year-old healthy male with bloody diarrhea who was found to have PBL in a resected sigmoid mass. The third patient was a 41 year-old male with a history of Crohn’s disease who presented with abdominal pain, diarrhea, and weight loss. A small intestinal mass (PBL) was removed. The fourth patient was a 65-year-old male who was found PBL after surgical resection of bowel for his florid Crohn’s disease. He later developed secondary acute myeloid leukemia. Clinical outcome was very poor in 3 out of 4 patients as reported in the literature. One patient survived chemotherapy followed by autologous transplant. The prototypical clinical presentation and variations of PBL can help create a more comprehensive differential diagnosis for GI tumors and establish an appropriate therapeutic guideline.

关键词： Plasmablastic lymphoma Undifferentiated carcinoma Non-Hodgkin lymphoma Diverse clinical manifestation and treatment

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Management of pembrolizumab-induced steroid refractory mucositis with infliximab:A case report

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World Journal of Clinical Cases 2020年第18期8卷 4100-4108页

作者： Harry Dang Jiyuan Sun Guoliang Wang Gregory Renner Lester Layfield Jaffar Hilli Department of Medicine University of MissouriColumbiaMO 65212United States Department of Hematology-Oncology University of MissouriColumbiaMO 65212United States Department of pathology University of MissouriColumbiaMO 65212United States Department of Otolaryngology-Head and Neck Surgery University of MissouriColumbiaMO 65212United States

BACKGROUND Pembrolizumab is an anti-programmed death receptor 1(PD-1)that was shown to have a tolerable safety profile with 17%of grade 3-4 drug-related adverse events,notable response rate of 16%with median duration of response of 8 mo,and median overall survival of 8 *** mucositis is a very rare complication with only two cases of grade 4 mucositis reported,and both cases had good response to intravenous methylprednisolone and subsequent oral prednisone *** report the first case of pembrolizumab-induced severe mucositis that was refractory to steroid *** SUMMARY An 80-year-old woman with a past medical history of recurrent right cheek nodular melanoma status post resection and new right lung metastatic melanoma on immunotherapy presented with dysphagia and odynophagia for 2 *** initially received 2 doses of ipilimumab 1 year ago with good outcome,but treatment was discontinued after developing severe diarrhea and *** was then initiated 4 mo after disease *** improvement was noted after 3 ***,after 6 cycles of pembrolizumab,patient developed odynophagia and *** of symptoms was noted after discontinuation of pembrolizumab and initiation of steroids.3 mo later,patient developed pharyngeal swelling with hoarseness and new oxygen requirement due to impending airway obstruction while being on prednisone tapering regimen,finally ended up with intubation and *** analysis of left laryngeal and epiglottis tissue showed granulation tissue with acute on chronic inflammation,negative for malignancy and *** achieved marked improvement after 2 doses of infliximab of 5 mg/kg every 2 wk while continuing on prednisone tapering *** We report the first case of pembrolizumab-induced grade 4 mucositis that had limited recovery with prolonged steroid course but had rapid response with addition of *** patient had recurrent mucositis symp

关键词： Pembrolizumab Infliximab Mucositis Melanoma Immunotherapy Refractory Case report

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An update on the diagnosis of gastroenteropancreatic neuroendocrine neoplasms

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World Journal of Gastroenterology 2022年第10期28卷 1009-1023页

作者： Jiayun M Fang Jay Li Jiaqi Shi Department of pathology&Clinical Labs University of MichiganAnn ArborMI 48109United States Medical Scientist Training Program University of MichiganAnn ArborMI 48109United States

Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)arise from neuroendocrine cells found throughout the gastrointestinal tract and islet cells of the *** incidence and prevalence of GEP-NENs have been increasing each year due to higher awareness,improved diagnostic modalities,and increased incidental detection on cross-sectional imaging and endoscopy for cancer screening and other conditions and ***-NENs are a heterogeneous group of tumors and have a wide range in clinical presentation,histopathologic features,and molecular *** presentation most commonly depends on whether the GEP-NEN secretes an active *** World Health Organization recently updated the classification of GEP-NENs to introduce a distinction between high-grade neuroendocrine tumors and neuroendocrine carcinomas,which can be identified using histology and molecular studies and are more aggressive with a worse prognosis compared to high-grade neuroendocrine *** our understanding of the biology of GEP-NENs has grown,new and improved diagnostic modalities can be developed and ***,we discuss clinical features and updates in diagnosis,including histopathological analysis,biomarkers,molecular techniques,and radiology of *** review established diagnostic tests and discuss promising novel diagnostic tests that are currently in development or require further investigation and validation prior to broad utilization in patient care.

关键词： Neuroendocrine tumor Neuroendocrine carcinoma Gastrointestinal Pancreas pathology Diagnosis

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Mucosal healing and inflammatory bowel disease:Therapeutic implications and new targets

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World Journal of Gastroenterology 2023年第7期29卷 1157-1172页

作者： Megan Lynn Otte Raju Lama Tamang Julia Papapanagiotou Rizwan Ahmad Punita Dhawan Amar B Singh Department of pathology and Microbiology University of Nebraska Medical CenterOmahaNE 68198United States Department of Biochemistry and Molecular Biology University of Nebraska Medical CenterOmahaNE 68198United States

Mucosal healing(MH)is vital in maintaining homeostasis within the gut and protecting against injury and *** factors and signaling pathways contribute in a dynamic and coordinated manner to maintain intestinal homeostasis and mucosal regeneration/***,when intestinal homeostasis becomes chronically disturbed and an inflammatory immune response is constitutively active due to impairment of the intestinal epithelial barrier autoimmune disease results,particularly inflammatory bowel disease(IBD).Many proteins and signaling pathways become dysregulated or impaired during these pathological conditions,with the mechanisms of regulation just beginning to be ***,there remains a relative lack of broadly effective therapeutics that can restore MH due to the complexity of both the disease and healing processes,so tissue damage in the gastrointestinal tract of patients,even those in clinical remission,*** increased understanding of the molecular mechanisms of IBD and MH,tissue damage from autoimmune disease may in the future be ameliorated by developing therapeutics that enhance the body’s own healing *** this review,we introduce the concept of mucosal healing and its relevance in IBD as well as discuss the mechanisms of IBD and potential strategies for altering these processes and inducing MH.

关键词： Inflammation Injury/repair Mucosal healing Mucosal barrier Therapeutics Colitis

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Cardiac resident macrophages: Spatiotemporal distribution, development, physiological functions, and their translational potential on cardiac diseases

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1483-1493页

作者： Jing Jin Yurou Wang Yueqin Liu Subrata Chakrabarti Zhaoliang Su International Genome Center Jiangsu UniversityZhenjiang 212013China Institute for Medical Immunology Jiangsu UniversityZhenjiang 212013China Center Laboratory the Fourth People's Hospital of ZhenjiangZhenjiang 212008China Department of pathology and Laboratory Medicine Western UniversityLondonOntario N6A 5C1Canada

Cardiac resident macrophages (CRMs) are the main population of cardiac immune cells. The role of these cells in regeneration, functional remodeling, and repair after cardiac injury is always the focus of research. However, in recent years, their dynamic changes and contributions in physiological states have a significant attention. CRMs have specific phenotypes and functions in different cardiac chambers or locations of the heart and at different stages. They further show specific differentiation and development processes. The present review will summarize the new progress about the spatiotemporal distribution, potential developmental regulation, and their roles in cardiac development and aging as well as the translational potential of CRMs on cardiac diseases. Of course, the research tools for CRMs, their respective advantages and disadvantages, and key issues on CRMs will further be discussed.

关键词： Cardiac resident macrophages Spatiotemporal distribution Cardiac development Cardiac homeostasis Physiological functions Research tools Clinical translation Transcriptional characteristics

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Diagnosis of alcoholic liver disease

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World Journal of Gastroenterology 2014年第33期20卷 11684-11699页

作者： Cara Torruellas Samuel W French Valentina Medici Division of Gastroenterology and Hepatology Department of Internal Medicine University of California Davis Sacramento CA 95817 United States Department of pathology UCLA/Harbor Medical Center Torrance CA 90502 United States

Alcohol is a hepatotoxin that is commonly consumed worldwide and is associated with a spectrum of liver injury including simple steatosis or fatty liver, alcoholic hepatitis, fibrosis, and cirrhosis. Alcoholic liver disease(ALD) is a general term used to refer to this spectrum of alcohol-related liver injuries. Excessive or harmful alcohol use is ranked as one of the top five risk factors for death and disability globally and results in 2.5 million deaths and 69.4 million annual disability adjusted life years. All patients who present with clinical features of hepatitis or chronic liver disease or who have elevated serum elevated transaminase levels should be screened for an alcohol use disorder. The diagnosis of ALD can generally be made based on history, clinical and laboratory findings. However, the diagnosis of ALD can be clinically challenging as there is no single diagnostic test that confirms the diagnosis and patients may not be forthcoming about their degree of alcohol consumption. In addition, clinical findings may be absent or minimal in early ALD characterized by hepatic steatosis. Typical laboratory findings in ALD include transaminase levels with aspartate aminotransferase greater than alanine aminotransferase as well as increased mean cor-puscular volume, gamma-glutamyltranspeptidase, and IgA to IgG ratio. In unclear cases, the diagnosis can be supported by imaging and liver biopsy. The histological features of ALD can ultimately define the diagnosis according to the typical presence and distribution of hepatic steatosis, inflammation, and Mallory-Denk bodies. Because of the potential reversible nature of ALD with sobriety, regular screening of the general population and early diagnosis are essential.

关键词： Alcoholic liver disease Diagnosis Alcohol screening Histology Mallory-Denk bodies Prognosis

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