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Longitudinal gut fungal alterations and potential fungal biomarkers for the progression of primary liver disease

Science China(Life Sciences) 2024年第6期67卷 1183-1198页

作者： Shiman Jiang Lvwan Xu Yanfei Chen Zheyue Shu Longxian Lv Yuxi Zhao Kefan Bi Sisi Yang Qiangqiang Wang Lanjuan Li State Key Laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China division of Hepatobiliary and Pancreatic Surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Liver disease,a major health concern worldwide,is a serious and progressive disorder.Herein,we not only established a mouse model of DEN+CCl4-induced primary liver disease but also collected clinical human samples to investigate longitudinal alterations in the gut mycobiome.As liver disease advanced,gut integrity was disrupted,and the mycobiota was disturbed in the mouse models.The metabolites associated with hepatocellular carcinoma(HCC)differed from those associated with the cirrhotic phase as follows:levels of stercobilin and aflatoxin B1 dialcohol were reduced,while levels of triterpenoids,bafilomycin A1,and DHEA were increased in the HCC group.The abundance of the phylum Chytridiomycota increased as the chronic liver disease progressed and was then replaced by the phylum Ascomycota in HCC.Based on the results from clinical human samples,the genus Candida(Ascomycota)(in humans)and the genus Kazachstania(Ascomycota)(in mice)occupied a dominant position in the HCC group,while other fungi were depleted.The increased abundance of C.albicans and depletion of S.cerevisiae may be hallmarks of the progression of liver cirrhosis to early HCC.Moreover,the administration of C.albicans and S.cerevisiae in the LC-HCC progression could accelerate or retard the progression of HCC.Therefore,gut fungi have the potential to serve as a noninvasive clinical biomarker and even a treatment method.

关键词： gut mycobiome liver disease longitudinal studies hepatocarcinogenesis fungal biomarker

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A retrospective analysis of carbapenem-resistant Acinetobacter baumannii infections in critically ill patients:Experience at a tertiary-care teaching hospital ICU

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Journal of Intensive medicine 2024年第2期4卷 181-186页

作者： Leyla Ferlicolak Neriman Defne Altintas Fugen Yoruk Department of Internal medicine division of Intensive Care Unit Ankara University Faculty of MedicineAnkaraTurkey Department of infectious diseases and Clinical Microbiology Ankara University Faculty of MedicineAnkaraTurkey

Background Acinetobacter baumannii is a clinically significant pathogen with a high incidence of multidrug resistance that is associated with life-threatening nosocomial infections.Here,we aimed to provide an insight into the clinical characteristics and outcomes of a unique group of A.baumannii infections in which the isolates were resistant to carbapenems and most other antibiotic groups in a tertiary-care intensive care unit(ICU).Methods We performed a retrospective observational study in which records of patients hospitalized in the ICU between June 1,2021 and June 1,2023 were reviewed.We checked the clinical,laboratory,and microbiological records of all adult patients who had carbapenem-resistant A.baumannii(CRAB)infections.Prior antibiotic treatments and definitive antibiotic treatments after culture positivity and susceptibility test results were recorded.C-reactive protein(CRP)and procalcitonin levels and leukocyte counts were noted.Length of ICU stay and 30-day mortality were defined as the outcome parameters.Results During the study period,57 patients were diagnosed with CRAB infections.The respiratory tract was the leading infection site(80.7%).In non-survivors,bloodstream infections(21.9%vs.4.0%P=0.05)and colistin-resistant(col-R)CRAB infections(43.8%vs.24.0%,P=0.12)were more common than in survivors,but these parameters were not statistically significant.The length of ICU stay was not different between survivors and non-survivors.Overall,the rate of col-R among CRAB clinical isolates was 35.1%.The 30-day mortality in all patients with CRAB infection was 56.1%.Mortality in col-R CRAB and colistin-susceptible(col-S)CRAB infections was 70.0%and 48.6%,respectively(P=0.12).Prior carbapenem use was 56.1%.Prior colistin use before col-R and col-S CRAB infections was not significant(35.0%vs.27.0%,P=0.53).Conclusions Our study provides real-world data on highly resistant A.baumannii infections and shares the characteristics of infections with such resistant strains.Unfortunately,carbapenem resistance in A.bau

关键词： Mortality Colistin-resi stant Gram-negative bacteria MDR Intensive care unit

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Antimicrobial stewardship and targeted therapies in the changing landscape of maternal sepsis

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Journal of Intensive medicine 2024年第1期4卷 46-61页

作者： Nishel M Shah Esmita Charani Damien Ming Fook-Choe Cheah Mark R Johnson Department of Metabolism Digestion and ReproductionImperial College LondonChelsea and Westminster HospitalLondonUK Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance Imperial College LondonLondonUK division of infectious diseases and hiv medicine Department of MedicineGroote Schuur HospitalUniversity of Cape TownCape TownSouth Africa Department of infectious diseases Imperial College LondonChelsea and Westminster HospitalLondonUK Department of Paediatrics Faculty of MedicineUniversiti Kebangsaan Malaysia Medical CentreKuala LumpurMalaysia

Pregnant and postnatal women are a high-risk population particularly prone to rapid progression to sepsis with significant morbidity and mortality worldwide.Moreover,severe maternal infections can have a serious detrimental impact on neonates with almost 1 million neonatal deaths annually attributed to maternal infection or sepsis.In this review we discuss the susceptibility of pregnant women and their specific physiological and immunological adaptations that contribute to their vulnerability to sepsis,the implications for the neonate,as well as the issues with antimicrobial stewardship and the challenges this poses when attempting to reach a balance between clinical care and urgent treatment.Finally,we review advancements in the development of pregnancy-specific diagnostic and therapeutic approaches and how these can be used to optimize the care of pregnant women and neonates.

关键词： Sepsis Pregnancy Immunology Cardiovascular Personalised medicine Antibiotic stewardship

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The immune response to SARS-CoV-2 in people with hiv

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Cellular & Molecular Immunology 2024年第2期21卷 184-196页

作者： Maxine A.Höft Wendy A.Burgers Catherine Riou Institute of infectious Disease and Molecular medicine University of Cape TownCape TownSouth Africa division of Medical Virology Department of PathologyUniversity of Cape TownCape TownSouth Africa Wellcome Centre for infectious diseases Research in Africa University of Cape TownCape TownSouth Africa

This review examines the intersection of the hiv and SARS-CoV-2 pandemics.People with hiv(PWH)are a heterogeneous group that differ in their degree of immune suppression,immune reconstitution,and viral control.While COVID-19 in those with wellcontrolled hiv infection poses no greater risk than that for hiv-uninfected individuals,people with advanced hiv disease are more vulnerable to poor COVID-19 outcomes.COVID-19 vaccines are effective and well tolerated in the majority of PWH,though reduced vaccine efficacy,breakthrough infections and faster waning of vaccine effectiveness have been demonstrated in PWH.This is likely a result of suboptimal humoral and cellular immune responses after vaccination.People with advanced hiv may also experience prolonged infection that may give rise to new epidemiologically significant variants,but initiation or resumption of antiretroviral therapy(ART)can effectively clear persistent infection.COVID-19 vaccine guidelines reflect these increased risks and recommend prioritization for vaccination and additional booster doses for PWH who are moderately to severely immunocompromised.We recommend continued research and monitoring of PWH with SARS-CoV-2 infection,especially in areas with a high hiv burden.

关键词： SARS-CoV-2 hiv Immune dysfunction Vaccine efficacy Prolonged infection Immunogenicity

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infectious causes of fever of unknown origin in developing countries: An international ID-IRI study

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Journal of Intensive medicine 2024年第1期4卷 94-100页

作者： Hakan Erdem Jaffar AAl-Tawfiq Maha Abid Wissal Ben Yahia George Akafity Manar Ezzelarab Ramadan Fatma Amer Amani El-Kholy Atousa Hakamifard Bilal Ahmad Rahimi Farouq Dayyab Hulya Caskurlu Reham Khedr Muhammad Tahir Lysien Zambrano Mumtaz Ali Khan Aun Raza Nagwa Mostafa El-Sayed Magdalena Baymakova Aysun Yalci Yasemin Cag Umran Elbahr Aamer Ikram Department of infectious diseases&Clinical Microbiology Gulhane School of MedicineTurkish Health Sciences UniversityAnkaraTurkey Specialty Internal medicine and Quality and Patient Safety Department Johns Hopkins Aramco HealthcareDhahranSaudi Arabia division of infectious diseases Indiana University School of MedicineIndianapolisINUSA Department of infectious diseases Farhat Hached University HospitalIbn El Jazzar Medical SchoolUniversity of SousseSousseTunisia Internal medicine Department Farhat Hached University HospitalIbn El Jazzar Medical SchoolUniversity of SousseSousseTunisia Cape Coast Teaching Hospital Cape CoastGhana Medical Parasitology Faculty of MedicineSuez UniversitySuezEgypt Department of Medical Microbiology and Immunology Faculty of MedicineZagazig UniversityZagazigEgypt Department of Clinical Pathology Faculty of MedicineCairo UniversityGizaEgypt Department of infectious diseases School of MedicineIsfahan University of Medical SciencesIsfahanIran Department of infectious diseases Kandahar University Medical FacultyTeaching HospitalKandaharAfghanistan Department of infectious diseases Mohammed Bn Khalifa Bn Salman Alkhalifa Specialist Cardiac CenterAwaliBahrain Department of infectious diseases and Clinical Microbiology Faculty of MedicineIstanbul Medeniyet UniversityIstanbulTurkey Department of Pediatric Oncology National Cancer Institute–Cairo UniversityChildren Cancer Hospital EgyptCairoEgypt Department of medicine Federal General HospitalIslamabadPakistan Institute for Research in Medical Sciences and Right to Health(ICIMEDES) Scientific Research Unit(UIC)Faculty of Medical Sciences(FCM)National Autonomous University of Honduras(UNAH)TegucigalpaHonduras National Institute of Health IslamabadPakistan Shaukat Khanum Memorial Cancer Hospital and Research Center LahorePakistan Medical Parasitology Department Research Institute of OphthalmologyGizaEgypt Department of infectious diseases Military Medical AcademySofiaBulgaria Department of Infecti

Background:Fever of unknown origin(FUO)in developing countries is an important dilemma and further research is needed to elucidate the infectious causes of FUO.Methods:A multi-center study for infectious causes of FUO in lower middle-income countries(LMIC)and lowincome countries(LIC)was conducted between January 1,2018 and January 1,2023.In total,15 participating centers from seven different countries provided the data,which were collected through the infectious diseasesInternational Research Initiative platform.Only adult patients with confirmed infection as the cause of FUO were included in the study.The severity parameters were quick Sequential Organ Failure Assessment(qSOFA)≥2,intensive care unit(ICU)admission,vasopressor use,and invasive mechanical ventilation(IMV).Results:A total of 160 patients with infectious FUO were included in the study.Overall,148(92.5%)patients had community-acquired infections and 12(7.5%)had hospital-acquired infections.The most common infectious syndromes were tuberculosis(TB)(n=27,16.9%),infective endocarditis(n=25,15.6%),malaria(n=21,13.1%),brucellosis(n=15,9.4%),and typhoid fever(n=9,5.6%).Plasmodium falciparum,Mycobacterium tuberculosis,Brucellae,Staphylococcus aureus,Salmonella typhi,and Rickettsiae were the leading infectious agents in this study.A total of 56(35.0%)cases had invasive procedures for diagnosis.The mean qSOFA score was 0.76±0.94{median(interquartile range[IQR]):0(0–1)}.ICU admission(n=26,16.2%),vasopressor use(n=14,8.8%),and IMV(n=10,6.3%)were not rare.Overall,38(23.8%)patients had at least one of the severity parameters.The mortality rate was 15(9.4%),and the mortality was attributable to the infection causing FUO in 12(7.5%)patients.Conclusions:In LMIC and LIC,tuberculosis and cardiac infections were the most severe and the leading infections causing FUO.

关键词： Developing countries Fever of unknown origin Infection

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Relationship between Phenotypic Changes of Dendritic Cell Subsets and the Onset of Plateau Phase during Intermittent Interferon Therapy in Patients with CHB

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Biomedical and Environmental Sciences 2024年第3期37卷 303-314页

作者： YANG Liu WANG Shi Yu JIANG Ting Ting DENG Wen CHANG Min WU Shu Ling CAO Wei Hua LU Yao SHEN Ge LIU Ru Yu GAO Yuan Jiao XU Meng Jiao HU Lei Ping ZHANG Lu XIE Yao LI Ming Hui Department of Hepatology division 2 Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Center for infectious diseases Second Affiliated Hospital of Air Force Medical UniversityXi'an 710038ShaanxiChina Department of Hepatology division 2 Peking University Ditan Teaching HospitalBeijing 100015China

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86.Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer.Results In total,143 patients were enrolled(NH group,n=49;NA group,n=47;P group,n=47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001.Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

关键词： CHB Dendritic Cells Intermittent Interferon Therapy Plateau Phase

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Lecanemab Unveiled:Exploring Alzheimer’s Treatment Advancements,Assessing Strengths,Limitations,and Its Therapeutic Landscape Position

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Biomedical and Environmental Sciences 2024年第4期37卷 428-431页

作者： VICTOR Abiola Adepoju OKECHUKWU Innocent Onyezue SAFAYET Jamil OLALEKAN John Okesanya DON Eliseo Lucero-Prisno Ⅲ Department of hiv and infectious diseases Jhpiegoan affiliate of John Hopkins UniversityAbujaNigeria Department of Prevention and Community Directorate APIN Public Health InitiativesAbujaNigeria Department of Public Health Daffodil International UniversityDhaka-1216Bangladesh Department of Public Health and Maritime Transport University of ThessalyVolosGreece Department of Global Health and Development London School of Hygiene and Tropical MedicineLondonUnited Kingdom

In the ever-evolving landscape of Alzheimer’s treatment,lecanemab(Leqembi)has emerged as a promising drug.Unlike conventional therapies that merely alleviate symptoms,lecanemab is a humanized monoclonal antibody with a distinct focus.It targets protofibrils,insoluble fibrils,amyloid oligomers,and soluble amyloid-beta protofibrils,which are known to be especially damaging to neurons,with high accuracy.

关键词： Alzheimer amyloid Therapeutic

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Prevention of hepatitis B reactivation in patients with hematologic malignancies treated with novel systemic therapies:Who and Why?

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World Journal of Gastroenterology 2024年第5期30卷 509-511页

作者： Matteo Tonnini Clara Solera Horna Luca Ielasi Department of Medical and Surgical Sciences University of BolognaBologna 40138Italy division of Internal medicine Hepatobiliary and Immunoallergic DiseasesIRCCS Azienda Ospedaliero-Universitaria di BolognaBologna 40138Italy infectious Disease Unit Azienda USL-IRCCS di Reggio EmiliaReggio Emilia 42123Italy Department of Internal medicine Ospedale degli Infermi di FaenzaFaenza 48018Italy

The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis with nucleo(t)side analogue is given according to the risk of HBV reactivation of the prescribed therapy.Though the advent of new drugs is occurring in all the field of medicine,in the setting of hematologic malignancies the last few years have been characterized by several drug classes and innovative cellular treatment.As novel therapies,there are few data about the rate of HBV reactivation and the decision of starting or not an antiviral prophylaxis could be challenging.Moreover,patients are often treated with a combination of different drugs,so evaluating the actual role of these new therapies in increasing the risk of HBV reactivation is difficult.First results are now available,but further studies are still needed.Patients with chronic HBV infection[hepatitis B surface antigen(HBsAg)positive]are reasonably all treated.Past/resolved HBV patients(HBsAg negative)are the actual area of uncertainty where it could be difficult choosing between prophylaxis and pre-emptive strategy.

关键词： Hepatitis B reactivation Hepatitis B virus Antiviral prophylaxis Hematologic malignancies Chimeric antigens receptor-T cell therapy Immune checkpoint inhibitors

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No Incidence of Liver Cancer Was Observed in A Retrospective Studyof Patients with Aristolochic Acid Nephropathy

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Chinese Journal of Integrative medicine 2024年第2期30卷 99-106页

作者： SU Tao FANG Zhi-e GUO Yu-ming WANG Chun-yu WANG Jia-bo JI Dong BAI Zhao-fang YANG Li XiAO Xiao-he Renal division Department of MedicinePeking University First HospitalBeijing(100034)China Department of Pharmacy Chongqing Hospital of Traditional Chinese MedicineChongqing(400021)China Department of Hepatology Fifth Medical Center of Chinese PLA General HospitalBeijing(100039)China China Military Institute of Chinese Materia Fifth Medical Center of Chinese PLA General HospitalBeijing(100039)China Phase I Clinical Trials Unit Department of Medicine for Infectious DiseasesFifth Medical Center of Chinese PLA General HospitalBeijing(100039)China Department of Pharmacy Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan(250000)China National Key Laboratory of Kidney diseases Beijing(100039)China

Objective:To assess the risk of aristolochic acid(AA)-associated cancer in patients with AA nephropathy(AAN).Methods:A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014.Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer.The primary endpoint was the incidence of liver cancer,and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014.Results:A total of 337 patients diagnosed with AAN were included in this study.From the initiation of taking AA to the termination of follow-up,39 patients were diagnosed with cancer.No cases of liver cancer were observed throughout the entire follow-up period,with urinary cancer being the predominant type(34/39,87.17%).Logistic regression analysis showed that age,follow-up period,and diabetes were potential risk factors,however,the dosage of the drug was not significantly associated with urinary cancer.Conclusions:No cases of liver cancer were observed at the end of follow-up.However,a high prevalence of urinary cancer was observed in AAN patients.Establishing a direct causality between AA and HCC is challenging.

关键词： aristolochic acid hepatocellular carcinoma urinary cancer drug safety retrospective study

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Nuclear receptor coactivator 6 is a critical regulator of NLRP3 inflammasome activation and gouty arthritis

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Cellular & Molecular Immunology 2024年第3期21卷 227-244页

作者： Kang-Gu Lee Bong-Ki Hong Saseong Lee Naeun Lee Seung-Whan Kim Donghyun Kim Wan-Uk Kim Center for Integrative Rheumatoid Transcriptomics and Dynamics The Catholic University of KoreaSeoul 06591Republic of Korea Department of Biomedicine&Health Sciences The Catholic University of KoreaSeoul 06591Republic of Korea Department of Pharmacology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505Republic of Korea Bio-Medical Institute of Technology University of UlsanSeoul 05505Republic of Korea Department of Microbiology and Immunology Seoul National University College of MedicineSeoul 03080Republic of Korea Institute of infectious diseases Seoul National University College of MedicineSeoul 03080Republic of Korea division of Rheumatology Department of Internal MedicineThe Catholic University of KoreaSeoul 06591Republic of Korea

Transcriptional coactivators regulate the rate of gene expression in the nucleus.Nuclear receptor coactivator 6(NCOA6),a coactivator,has been implicated in embryonic development,metabolism,and cancer pathogenesis,but its role in innate immunity and inflammatory diseases remains unclear.Here,we demonstrated that NCOA6 was expressed in monocytes and macrophages and that its level was increased under proinflammatory conditions.Unexpectedly,nuclear NCOA6 was found to translocate to the cytoplasm in activated monocytes and then become incorporated into the inflammasome with NLRP3 and ASC,forming cytoplasmic specks.Mechanistically,NCOA6 associated with the ATP hydrolysis motifs in the NACHT domain of NLRP3,promoting the oligomerization of NLRP3 and ASC and thereby instigating the production of IL-1βand active caspase-1.Of note,Ncoa6 deficiency markedly inhibited NLRP3 hyperactivation caused by the Nlrp3^(R258W) gain-of-function mutation in macrophages.Genetic ablation of Ncoa6 substantially attenuated the severity of two NLRP3-dependent diseases,folic-induced acute tubular necrosis and crystal-induced arthritis,in mice.Consistent with these findings,NCOA6 was highly expressed in macrophages derived from gout patients,and NCOA6-positive macrophages were significantly enriched in gout macrophages according to the transcriptome profiling results.Conclusively,NCOA6 is a critical regulator of NLRP3 inflammasome activation and is therefore a promising target for NLRP3-dependent diseases,including gout.

关键词： Nuclear receptor coactivator 6 Nuclear-to-cytoplasmic translocation NLRP3 inflammasome NACHT domain Gouty arthritis

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