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Simultaneous portal vein thrombosis and splenic vein thrombosis in a COVID-19 patient:A case report and review of literature

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World Journal of Clinical Cases 2024年第18期12卷 3561-3566页

作者： Binyamin Ravina Abramowitz Michael Coles Ayse Aytaman Bani Chander-Roland Daniel Anthony DiLeo Department of Gastroenterology and Hepatology SUNY Downstate Health Sciences UniversityBrooklynNY 11203United States Department of Gastroenterology and Hepatology Brooklyn Campus of the Veterans Affairs New York Harbor Healthcare SystemBrooklynNY 11209United States

BACKGROUND It is well-described that the coronavirus disease 2019(COVID-19)infection is associated with an increased risk of thrombotic complications.While there have been many cases of pulmonary emboli and deep vein thrombosis in these patients,reports of COVID-19 associated portal vein thrombosis(PVT)have been uncommon.We present a unique case of concomitant PVT and splenic artery thrombosis in a COVID-19 patient.CASE SUMMARY A 77-year-old-male with no history of liver disease presented with three days of left-sided abdominal pain.One week earlier,the patient was diagnosed with mildly symptomatic COVID-19 and was treated with nirmatrelvir/ritonavir.Physical exam revealed mild right and left lower quadrant tenderness,but was otherwise unremarkable.Significant laboratory findings included white blood cell count 12.5 K/μL,total bilirubin 1.6 mg/dL,aminoaspartate transferase 40 U/L,and alanine aminotransferase 61 U/L.Computed tomography of the abdomen and pelvis revealed acute PVT with thrombus extending from the distal portion of the main portal vein into the right and left branches.Also noted was a thrombus within the distal portion of the splenic artery with resulting splenic infarct.Hypercoagulable workup including prothrombin gene analysis,factor V Leiden,cardiolipin antibody,and JAK2 mutation were all negative.Anticoagulation with enoxaparin was initiated,and the patient’s pain improved.He was discharged on apixaban.CONCLUSION It is quite uncommon for PVT to present simultaneously with an arterial thrombotic occlusion,as in the case of our patient.Unusual thrombotic manifestations are classically linked to hypercoagulable states including malignancy and hereditary and autoimmune disorders.Viral infections such as Epstein-Barr virus,cytomegalovirus,viral hepatitis,and COVID-19 have all been found to increase the risk of splanchnic venous occlusions,including PVT.In our patient,prompt abdominal imaging led to early detection of thrombus,early treatment,and an excellent outcome.This case is unique in that it is

关键词： COVID-19 Thromboembolism Portal vein thrombosis Splenic artery thrombosis Anticoagulation Lovenox Thrombotic complication Case report

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Multimodal comparison of plasma proteins associated with blood-brain barrier impairment in Alzheimer’s disease

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Aging Communications 2024年第1期6卷 1-9页

作者： Elisa Giunti Roberto Collu Joel Reisman Jong Soo Lee Noureddine Melikechi Weiming Xia Geriatric Research Education and Clinical Center Bedford VA Healthcare SystemBedfordMA 01730U.S.A Department of Pharmacology Physiology and BiophysicsBoston University Chobanian&Avedisian School of MedicineBostonMA 02118U.S.A Center for healthcare Organization and Implementation Research Bedford VA Healthcare SystemBedfordMA 01730U.S.A Kennedy College of Science University of Massachusetts LowellLowellMA 01854U.S.A.

Background:Vascular impairment is one of the major contributors to dementia.We aimed to identify blood biomarkers suggestive of potential impairment of the blood-brain barrier(BBB)in subjects with Alzheimer’s disease(AD).Methods:We used administrative data from the VA Informatics and Computing Infrastructure Resource Center to study both inpatients and outpatients with AD.Plasma samples from healthy control and AD individuals were analyzed using enzyme-linked immunosorbent assay and proteomics approaches to identify differentially expressed proteins.Bioinformatic analysis was applied to explore significantly enriched pathways.Results:In the same cohort of patients with AD,we found twice number of subjects with cerebral amyloid angiopathy in the two-year period after the onset of AD,compared to the number of subjects with cerebral amyloid angiopathy in the two-year period prior to AD onset.Different pathways related to BBB,like cell adhesion,extracellular matrix organization and Wnt signaling,were activated and differentially expressed proteins such as ADAM22,PDGFR-α,DKK-4,Neucrin and RSOP-1 were identified.Moreover,matrix metalloproteinase-9,which is implicated in causing degradation of basal lamina and BBB disruption,was significantly increased in the plasma of AD patients.Conclusions:Alteration of proteins found in AD subjects could provide new insights into biomarkers regulating permeability and BBB integrity.

关键词： Alzheimer’s disease blood-brain barrier peripheral biomarkers matrix metalloproteinases cerebral amyloid angiopathy

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Emerging role of microRNAs in lipid metabolism

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Acta Pharmaceutica Sinica B 2015年第2期5卷 145-150页

作者： Zhihong Yang Tyler Cappello Li Wang Department of Physiology and Neurobiology and the Institute for Systems Genomics University of Connecticut veterans affairs connecticut healthcare system Department of Internal Medicine Section of Digestive Diseases Yale University

micro RNAs(mi RNAs or mi Rs) are small non-coding RNAs that are involved in posttranscriptional regulation of their target genes in a sequence-specific manner. Emerging evidence demonstrates that mi RNAs are critical regulators of lipid synthesis, fatty acid oxidation and lipoprotein formation and secretion. Dysregulation of mi RNAs disrupts gene regulatory network, leading to metabolic syndrome and its related diseases. In this review, we introduced epigenetic and transcriptional regulation of mi RNAs expression. We emphasized on several representative mi RNAs that are functionally involved into lipid metabolism, including mi R-33/33 n, mi R122, mi R27a/b, mi R378/378 n, mi R-34 a and mi R-21.Understanding the function of mi RNAs in lipid homeostasis may provide potential therapeutic strategies for fatty liver disease.

关键词： Lipid metabolism microRNAs Nuclear receptors

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Exposure to inorganic arsenic can lead to gut microbe perturbations and hepatocellular carcinoma

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Acta Pharmaceutica Sinica B 2016年第5期6卷 426-429页

作者： Jonathan Choiniere Li Wang Department of Physiology and Neurobiology The Institute for Systems GenomicsUniversity of Connecticut School of Pharmaceutical Sciences Wenzhou Medical University veterans affairs connecticut healthcare system Department of Internal Medicine Section of Digestive DiseasesYale University

Arsenic is a carcinogenic environmental factor found in food and drinking water around the world.The mechanisms in which arsenic alters homeostasis are not fully understood.Over the past few decades,light has been shed on varying mechanisms in which arsenic induces cancer.Such mechanisms include gut microbe perturbations,genotoxic effects,and epigenetic modification.Gut microbe perturbations have been shown to increase the level of pathogen-associated molecular patterns such as lipopolysaccharide(LPS) leading to uncontained inflammation.Increase in inflammation is the major factor in cirrhosis leading to hepatocellular carcinoma.Alterations in gut permeability and metabolites have also been observed as a fallout of arsenic induced gut microbe modification.The guts proximity and interaction through portal flow make the liver susceptible to gut perturbations and ensuing inflammatory responses.Genotoxic and epigenetic dysregulation induced by arsenic and its toxic metabolites present a more direct mechanism that works synergistically with gut microbe perturbations to induce the incidence of cancers.These pathways combined could be some of the main causes of arsenic-induced carcinogenesis.

关键词： Arsenic Microbiome Epigenetics Liver cancer Hepatocellular carcinoma Gut microbiota Lipopolysaccharide

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模拟教学理论框架在心力衰竭高仿真模拟课程中的应用效果研究

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International Journal of Nursing Sciences 2023年第4期10卷 549-554,I0004页

作者： Tricia Nwokocha Nancy Cowan Pinio Yan Cao Holly Wei Satish Mahajan Nursing Scholarship and University School of Nursing Affiliations for veterans affairs Palo Alto healthcare system Palo AltoCAUSA Chabot College CAUSA East Tennessee State University College of Nursing Johnson CityTNUSA Patient Care Service for veterans affairs Palo Alto healthcare system CAUSA

目的探讨基于美国国家护理联盟(National League for Nursing)杰弗里斯(NLN Jeffries)仿真框架的心力衰竭护理高保真仿真教育对职前护理教育的影响。方法在美国萨克拉门托卡林顿学院进行心力衰竭高仿真模拟教学试点项目。23名学生参加... 详细信息

目的探讨基于美国国家护理联盟(National League for Nursing)杰弗里斯(NLN Jeffries)仿真框架的心力衰竭护理高保真仿真教育对职前护理教育的影响。方法在美国萨克拉门托卡林顿学院进行心力衰竭高仿真模拟教学试点项目。23名学生参加了这项研究。本研究采用类实验设计,在教学前后测量学生的自我效能感、满意度和心力衰竭临床知识。结果结果显示,在高仿真模拟教学实施后,学生的自我效能感平均得分(45.39±7.88比38.91±8.35)、满意度(18.70±3.38比15.57±3.38)及心力衰竭临床知识得分(64.09±10.86比54.48±11.19)均明显提高(P<0.001)。该模拟教学设计中包含护士质量安全教育内容、以患者为中心的护理以及急性心力衰竭患者照护的团队合作,对教学效果产生了积极影响。结论基于NLN Jeffries理论框架的心力衰竭高仿真模拟教学提高了学生的知识、满意度、自我效能感及以患者为中心的护理、安全和团队合作意识。护理教育工作者在进行模拟教学计划时应考虑包含5个特性,即目标、解决问题、为学生提供支持、保真度和总结报告,同时结合安全、以患者为中心和团队合作教育,以保障教学效果。

关键词：高仿真模拟教学护理教育护理专业学生满意度自我效能

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Differentiation of human embryonic stem cells derived mesenchymal stem cells into corneal epithelial cells after being seeded on decellularized SMILE-derived lenticules

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International Journal of Ophthalmology(English edition) 2019年第5期12卷 717-724页

作者： Yao Chen Ye-Wei Yin Yang Zhao Xiao-Ying Wu Kelly Young Wei-Tao Song Xiao-Bo Xia Dan Wen Department of Ophthalmology Xiangya HospitalCentral South University Department of veterans affairs Miami VA Healthcare System

AIM: To evaluate the feasibility of mesenchymal stem cells(MSCs) to differentiate into corneal epithelial cells after being seeded on the decellularized small incision lenticule extraction(SMILE)-derived lenticules. METHODS: The fresh lenticules procured from patients undergoing SMILE for the correction of myopia were decellularized. The MSCs were subsequently cultivated on those denuded lenticules. The MSCs without lenticules were used as a control. The proliferation activity of the MSCs after seeding 24 h was quantitatively determined with the Cell Counting Kit-8(CCK-8) assay. Immunofluorescence staining and quantitative reverse transcription polymerase chain reaction(qRT-PCR) were used to assess the marker expression in differentiated MSCs. RESULTS: The data showed that both fresh and decellularized lenticules could significantly promote the proliferation of MSCs, compared to that in control(P=0.02 for fresh lenticules, P=0.001 for decellularize ones, respectively). The MSCs seeded on both lenticules were positive for cytokeratin 3(CK3) staining. The expression of CK3 increased 5-fold in MSCs seeded on fresh lenticules and 18-fold on decellularized ones, compared to that in control. There was a significant difference in the expression of CK3 in MSCs seeded on fresh and decellularized lenticules(P0.05), while the expression of these markers was decreased in MSCs seeded on decellularized ones. CONCLUSION: These results suggest that the decellularized lenticules might be more suitable for MSCs to differentiate into corneal epithelial cells, which offersthe prospect of a novel therapeutic modality of SMILEderived lenticules in regenerative corneal engineering.

关键词： mesenchymal stem cells small incision lenticule extraction lenticules decellularization corneal epithelial cells

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Bilateral diffuse grade 5 radiation pneumonitis after intensity modulated radiation therapy for localized lung cancer

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World Journal of Clinical Oncology 2017年第3期8卷 285-288页

作者： Virginia W Osborn Andrea Leaf Anna Lee Elizabeth Garay Joseph Safdieh David Schwartz David Schreiber veterans affairs New York Harbor healthcare system SUNY Downstate Medical Center

We are reporting a case of fatal radiation pneumonitis that developed six months following chemoradiation for limited stage small cell lung cancer.The patient was a 67-year-old man with a past medical history of Hashimoto's thyroiditis and remote suspicion for CREST,neither of which were active in the years leading up to treatment.He received 6600 cG y delivered in 200 cG y daily fractions via intensity modulated radiation therapy with concurrent cisplatin/etoposide followed by additional chemotherapy with dosereduced cisplatin/etoposide and carboplatin/etoposide and then received prophylactic cranial irradiation.The subsequent months were notable for progressively worsening episodes of respiratory compromise despite administration of prolonged steroids and he ultimately expired.Imaging demonstrated bilateral interstitial and airspace opacities.Autopsy findings were consistent with pneumonitis secondary to chemoradiation as well as lymphangitic spread of small cell carcinoma.The process was diffuse bilaterally although his radiation was delivered focally to the right lung and mediastinum.

关键词： Radiation Pneumonitis Small cell lung cancer Intensity modulated radiation therapy

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Carcinoma of the gastroesophageal junction in Chinese patients

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World Journal of Gastroenterology 2012年第48期18卷 7134-7140页

作者： Qin Huang Department of Pathology Nanjing Drum Tower Hospital Department of Pathology and Laboratory Medicine Veterans Affairs Boston Healthcare System and Harvard Medical School

Carcinoma of the gastroesophageal junction(GEJ) is defined as carcinoma that crosses the GEJ line,irrespective of where the tumor epicenter is located.This group of cancer is rare but controversial.Based on study results from the majority of epidemiologic and clinicopathologic investigations carried out in Western countries,this cancer is believed to arise from Barrett's esophagus(BE) and includes both distal esophageal and proximal gastric carcinomas because of similar characteristics in epidemiology,clinicopathology,and molecular pathobiology in relation to BE.As such,the most recent American Joint Committee on Cancer staging manual requires staging all GEJ carcinomas with the rule for esophageal adenocarcinoma(EA).This mandate has been challenged recently by the data from several studies carried out mainly in Chinese patients.The emerging evidence derivedfrom those studies suggests:(1) both BE and EA are uncommon in the Chinese population;(2) almost all GEJ cancers in Chinese arise in the proximal stomach and show the features of proximal gastric cancer,not those of EA;(3) application of the new cancer staging rule to GEJ cancer of Chinese patients cannot stratify patients' prognosis effectively;and(4) prognostic factors of GEJ cancer in Chinese are similar,but not identical,to those of EA.In conclusion,the recent evidence suggests that GEJ cancer in Chinese shows distinct clinicopathologic characteristics that are different from EA.Further investigations in molecular pathology may help illustrate the underlying pathogenesis mechanisms of this cancer in Chinese patients and better manage patients with this fatal disease.

关键词：中国人群癌症患者食管胃癌交界处分子病理学临床调查

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Impact of COVID-19 on Liver Transplant Activity in the USA: Variation by Etiology and Cirrhosis Complications

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Journal of Clinical and Translational Hepatology 2023年第1期11卷 130-135页

作者： Yong-Fang Kuo Paul Kwo Robert J Wong Ashwani K.Singal Department of Biostatistics University of Texas Medical BranchGalvestonTXUSA Division of Gastroenterology and Hepatology Veterans Affairs Palo Alto Healthcare SystemStanford University School of MedicinePalo AltoCAUSA University of South Dakota Sanford School of MedicineVermillionSDUSA Avera Transplant Institute Sioux FallsSDUSA

Background and Aims:The COVID-19 pandemic has impacted the care of patients with liver disease.We examined impact of COVID-19 on liver transplant(LT)activity in the USA.Methods:LT listings in the United Network for Organ Sharing(UNOS)database(April 2018–May 2021)were analyzed to examine the impact of COVID-19 pandemic on the LT activity based on etiology:hepatitis C virus(HCV),alcohol-associated liver disease(ALD),alcoholic hepatitis(AH),and nonalcoholic steatohepatitis(NASH)complications:hepatocellular carcinoma(HCC)and acute-on-chronic liver failure(ACLF)grade 2 or 3 and Model for End-Stage Liver Disease(MELD)score.Joinpoint regression models assessed time trend changes on a log scale.Results:Of 23,871 recipients(8,995 in the COVID era,April 2018–February 2020),mean age 52 years,62% men,61% Caucasian,32%ALD,15%HCC,30%ACLF grades 2–3,and mean MELD score 20.5,monthly LT changes were a decrease of 3.4%for overall LTs and 22%for HCC after September 2020,and increase of 4.5%for ALD since 11/2020 and 17%since 03/2021 for ACLF grade 2–3.Monthly MELD scores increased by 0.7 and 0.36 after June 2020 for HCV and HCC respectively.Conclusions:The COVID-19 pandemic has impacted LT activity,with a decrease of LTs especially for HCC,and an increase of LTs for ALD and severe ACLF.Strategies are needed to reorganize cirrhosis patients to overcome the aftereffects of COVID-19 pandemic.

关键词： COVID-19 UNOS OLT Region Public policies

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Bile acids and sphingolipids in non-alcoholic fatty liver disease

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Chinese Medical Journal 2022年第10期135卷 1163-1171页

作者： Kaitlyn G.Jackson Grayson W.Way Huiping Zhou Department of Microbiology and Immunology Virginia Commonwealth University School of MedicineRichmondVA 23298USA Center for Clinical and Translational Research Virginia Commonwealth University School of MedicineRichmondVA 23298USA Central Virginia veterans healthcare system RichmondVA 23249USA.

Non-alcoholic fatty liver disease (NAFLD) is one of the fastest-growing diseases, and its global prevalence is estimated to increase >50% by 2030. NAFLD is comorbid with metabolic syndrome, obesity, type 2 diabetes, and insulin resistance. Despite extensive research efforts, there are no pharmacologic or biological therapeutics for the treatment of NAFLD. Bile acids and sphingolipids are well-characterized signaling molecules. Over the last few decades, researchers have uncovered potential mechanisms by which bile acids and sphingolipids regulate hepatic lipid metabolism. Dysregulation of bile acid and sphingolipid metabolism has been linked to steatosis, inflammation, and fibrosis in patients with NAFLD. This clinical observation has been recapitulated in animal models, which are well-accepted by experts in the hepatology field. Recent transcriptomic and lipidomic studies also show that sphingolipids are important players in the pathogenesis of NAFLD. Moreover, the identification of bile acids as activators of sphingolipid-mediated signaling pathways established a novel theory for bile acid and sphingolipid biology. In this review, we summarize the recent advances in the understanding of bile acid and sphingolipid-mediated signaling pathways as potential contributors to NAFLD. A better understanding of the pathologic effects mediated by bile acids and sphingolipids will facilitate the development of new diagnostic and therapeutic strategies for NAFLD.

关键词： Bile acids Sphingolipids Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis

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