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Comorbidities,clinical characteristics and outcomes of COVID‑19 in pediatric patients in a tertiary medical center in the Netherlands

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World Journal of Pediatrics 2022年第8期18卷 558-563页

作者： Amrita Biharie Maya WKeuning Katja CWolthers Dasja Pajkrt Department of Pediatric Infectious Diseases Rheumatology and ImmunologyAmsterdam University Medical Centers Location Academic Medical CenterUniversity of AmsterdamMeibergdreef 91105 AZ AmsterdamNetherlands Department of Medical Microbiology Amsterdam University Medical Centers Location Academic Medical CenterUniversity of AmsterdamAmsterdamNetherlands

Having pre-existing comorbidities is described as a risk factor for more severe disease in adult corona virus disease 2019(COVID-19)and in infections with SARS-CoV-1 and MERS-CoV[1].In adult SARS-CoV-2 infections,patients with pre-existing underlying comorbidities,such as chronic obstructive pulmonary disease,cardiovascular disease,diabetes and obesity,are more likely to have severe disease compared to healthy adults[2].An inconsistency is seen in current fndings on the association with comorbidities and pediatric COVID-19 *** important limitation in currently available studies is limited data:severe disease is rare in children compared to adults,and most studies describe COVID-19 severity merely by reporting intensive care unit(ICU)admission or mortality rates instead of detailed data on clinical presentation and outcomes.

关键词： morbid pediatric patients

CXCR5^(+)PD-1^(++)CD4^(+)T cells colonize infant intestines early in life and promote B cell maturation

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Cellular & Molecular immunology 2023年第2期20卷 201-213页

作者： Ana Jordan-Paiz Glòria Martrus Fenja L.Steinert Max Kaufmann Adrian F.Sagebiel Renée R.C.E.Schreurs Anne Rechtien Martin E.Baumdick Johannes M.Jung Kimberly J.Möller Lucy Wegner Cordula Grüttner Laura Richert Roland Thünauer Jennifer Schroeder-Schwarz Johannes Bvan Goudoever Teunis B.H.Geijtenbeek Marcus Altfeld Steven T.Pals Daniel Perez Paul L.Klarenbeek Christian Tomuschat Guido Sauter Ingo Königs Udo Schumacher Manuel A.Friese Nathaniel Melling Konrad Reinshagen Madeleine J.Bunders Department of Virus immunology Leibniz Institute of VirologyHamburg20251Germany University Medical center Hamburg-Eppendorf Hamburg20246Germany Institute of Neuroimmunology and Multiple Sclerosis Center for Molecular Neurobiology HamburgUniversity Medical Center Hamburg-EppendorfHamburg20251Germany Department of General Visceral and Thoracic SurgeryUniversity Medical Center Hamburg-EppendorfHamburg20246Germany Department of Experimental immunology Amsterdam Infection&Immunity InstituteAmsterdam University Medical CenterUniversity of AmsterdamAmsterdam1105 AZThe Netherlands Department of Pediatrics Emma Children’s HospitalAmsterdam University Medical CenterUniversity of Amsterdam and Vrije Universiteit AmsterdamAmsterdam1105 AZThe Netherlands I.Department of Medicine University Medical Center Hamburg-EppendorfHamburg20246Germany Partner Site Hamburg-Lübeck-Borstel-Riems German Center for Infection Research(DZIF)Hamburg20246Germany University of Bordeaux Institut National de la Santéet de la Recherche MédicaleBordeaux Population Health Research Center UMR1219 and INRIA SISTM TeamBordeaux33000France Institute of Anatomy and Experimental Morphology University Medical Center Hamburg-EppendorfHamburg20246Germany Department of Pathology Amsterdam University Medical CenterUniversity of AmsterdamAmsterdam1105 AZThe Netherlands Department of rheumatology and Clinical immunology and Department of Experimental immunology Amsterdam Infection&Immunity InstituteAmsterdam University Medical CenterUniversity of AmsterdamAmsterdam1007 MBThe Netherlands amsterdam rheumatology&immunology center Amsterdam University Medical CenterUniversity of AmsterdamAmsterdam1105 AZThe Netherlands Department of Pediatric Surgery University Medical Center Hamburg-EppendorfHamburg20246Germany Institute of Pathology University Medical Center Hamburg-EppendorfHamburg20246Germany Department of Pediatric Surgery Altona Children’s HospitalHamburg22763Germany III.Department of Medicine University M

Gastrointestinal infections are a major cause for serious clinical complications in *** induction of antibody responses by B cells is critical for protective immunity against infections and requires CXCR5+PD-1++CD4+T cells(TFH cells).We investigated the ontogeny of CXCR5+PD-1++CD4+T cells in human *** CXCR5+PD-1++CD4+T cells were absent in fetal intestines,CXCR5+PD-1++CD4+T cells increased after birth and were abundant in infant intestines,resulting in significant higher numbers compared to *** findings were supported by scRNAseq analyses,showing increased frequencies of CD4+T cells with a TFH gene signature in infant intestines compared to ***-cultures of autologous infant intestinal CXCR5+PD-1+/−CD4+T cells with B cells further demonstrated that infant intestinal TFH cells were able to effectively promote class switching and antibody production by B *** together,we demonstrate that functional TFH cells are numerous in infant intestines,making them a promising target for oral pediatric vaccine strategies.

关键词： TFH cells B cells Antibodies Intestine Pediatrics

How to overcome ATP-binding cassette drug efflux transporter-mediated drug resistance?

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Cancer Drug Resistance 2018年第1期1卷 6-29页

作者： Adrian C.Jaramillo Farah Al Saig Jacqueline Cloos Gerrit Jansen Godefridus J.Peters Department of Hematology VU University Medical CenterCancer Center AmsterdamAmsterdam 1007 MBThe Netherlands Department of Medical Oncology VU University Medical CenterCancer Center AmsterdamAmsterdam 1007 MBThe Netherlands amsterdam rheumatology and immunology center VU University Medical CenterAmsterdam 1007 MBThe Netherlands

P-glycoprotein(ABCB1),multidrug resistance protein-1(ABCC1)and breast cancer resistance protein(ABCG2)belong to the ATP-binding cassette(ABC)superfamily of proteins that play an important physiological role in protection of the body from toxic xenobiotics and endogenous *** this,these transporters determine the toxicity profile of many drugs,and confer multidrug resistance(MDR)in cancer cells associated with a poor treatment outcome of cancer *** has long been hypothesized that inhibition of ABC drug efflux transporters will increase drug accumulation and thereby overcome MDR,but until now no approved inhibitor of these transporters is available in the *** this review we present molecular strategies to overcome this type of drug resistance and discuss for each of these strategies their promising value or indicate underlying reasons for their limited success.

关键词： Breast cancer resistance protein ATP-binding cassette transporters multidrug resistance multidrug resistance protein

Staying home or leaving for a party:tissue-dependent choices of tissue-resident memory T cells

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Cellular & Molecular immunology 2022年第6期19卷 651-652页

作者： Klaas P.J.M.van Gisbergen Joke M.M.den Haan Department of Hematopoiesis Sanquin Research and Landsteiner LaboratoryAmsterdam UMCUniversity of Amsterdam1066CXAmsterdamThe Netherlands Department of Molecular Cell Biology and immunology Cancer Center AmsterdamAmsterdam Institute for Infection and ImmunityAmsterdam UMCVrije Universiteit AmsterdamAmsterdamThe Netherlands

CD8+T cells differentiate into different types of memory T cells after priming in the lymphoid *** memory T cells selectively express lymph node homing markers and recirculate between the blood and the secondary lymphoid *** memory T cells lack lymph node homing capacity,mainly circulate in the blood,and may enter peripheral *** third subset consists of tissue-resident memory T(Trm)cells that express CD69 and adhesion molecules such as CD11a,CD103,and CD49a that prevent tissue egress.

关键词： organs lymphoid CD69

Statins markedly potentiate aminopeptidase inhibitor activity against(drug-resistant)human acute myeloid leukemia cells

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Cancer Drug Resistance 2023年第3期6卷 430-446页

作者： Gerrit Jansen Marjon Al Yehuda G.Assaraf Sarah Kammerer Johan van Meerloo Gert J.Ossenkoppele Jacqueline Cloos Godefridus J.Peters Department of rheumatology and Clinical immunology Amsterdam Rheumatology and immunology CenterAmsterdam University Medical Centerlocation VUmcAmsterdam 1081 HVThe Netherlands The Fred Wyszkowsky Cancer Research Laboratory Faculty of BiologyThe Technion-Israel Institute of TechnologyHaifa 3200003Israel Department of Medical Oncology Amsterdam University Medical Centerlocation VUmcAmsterdam 1081 HVThe Netherlands Institute of Biotechnology Molecular Cell BiologyBrandenburg University of Technology Cottbus-SenftenbergSenftenberg 01968Germany Department of Hematology Amsterdam University Medical Centerlocation VUmcAmsterdam 1081 HVThe Netherlands Department of Biochemistry Medical University of GdanskGdansk 80-210Poland

Aim: This study aimed to decipher the molecular mechanism underlying the synergistic effect of inhibitors of the mevalonate-cholesterol pathway (i.e., statins) and aminopeptidase inhibitors (APis) on APi-sensitive and -resistant acute myeloid leukemia (AML) ***: U937 cells and their sublines with low and high levels of acquired resistance to (6S)-[(R)-2-((S)-Hydroxy-hydroxycarbamoyl-methoxy-methyl)-4-methyl-pentanoylamino]-3,3 dimethyl-butyric acid cyclopentyl ester (CHR2863), an APi prodrug, served as main AML cell line models. Drug combination effects were assessed with CHR2863 and in vitro non-toxic concentrations of various statins upon cell growth inhibition, cell cycle effects, and apoptosis induction. Mechanistic studies involved analysis of Rheb prenylation required for mTOR ***: A strong synergy of CHR2863 with the statins simvastatin, fluvastatin, lovastatin, and pravastatin was demonstrated in U937 cells and two CHR2863-resistant sublines. This potent synergy between simvastatin and CHR2863 was also observed with a series of other human AML cell lines (e.g., THP1, MV4-11, and KG1), but not with acute lymphocytic leukemia or multiple solid tumor cell lines. This synergistic activity was: (i) specific for APis (e.g., CHR2863 and Bestatin), rather than for other cytotoxic agents;and (ii) corroborated by enhanced induction of apoptosis and cell cycle arrest which increased the sub-G1 fraction. Consistently, statin potentiation of CHR2863 activity was abrogated by co-administration of mevalonate and/or farnesyl pyrophosphate, suggesting the involvement of protein prenylation;this was experimentally confirmed by impaired Rheb prenylation by ***: These novel findings suggest that the combined inhibitory effect of impaired Rheb prenylation and CHR2863-dependent mTOR inhibition instigates a potent synergistic inhibition of statins and APis on human AML cells.

关键词： Aminopeptidase statins mevalonate pathway carboxyl esterase Rheb mTOR

Thrombin-mediated vasculogenic mimicry:important lessons to improve anticoagulant therapy of selected cancer patients

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Signal Transduction and Targeted Therapy 2020年第1期5卷 319-320页

作者： C.Arnold Spek amsterdam UMC University of AmsterdamCenter of Experimental and Molecular MedicineAmsterdamThe Netherlands amsterdam UMC University of AmsterdamCancer Center AmsterdamAmsterdamNetherlands

In a recent study published in Signal Transduction and Targeted Therapy,*** and colleagues1 identify thrombin as a novel mediator of vasculogenic mimicry in non-small-cell lung cancer(NSCLC).This provides important mechanistic insight by which coagulation(factors)may drive tumor progression and several lessons to improve anticoagulant therapy of cancer patients can be learned from the paper.

关键词： patients cancer lung

Experience of Patients Undergoing Mini-Arthroscopy Compared to MRI in the Earliest Phases of Arthritis

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International Journal of Clinical Medicine 2013年第12期4卷 1-5页

作者： Maria J. H. de Hair Marleen G. H. van de Sande Mario Maas Danielle M. Gerlag Paul P. Tak Department of Clinical immunology and rheumatology Aca-demic Medical Center University of Amsterdam Amsterdam The Netherlands Department of Radiology Academic Medical Center University of Amsterdam Amsterdam The Netherlands

Objective: To evaluate the expectations and experience of patients undergoing mini-arthroscopy compared to contrast enhanced MRI for research purposes. Methods: Seventeen patients with early, active arthritis (Group A) and 21 autoantibody-positive individuals without any evidence of arthritis upon physical examination (Group B) were included. All subjects underwent both contrast enhanced MRI and synovial biopsy sampling by mini-arthroscopy of the same joint within one week. At inclusion and after both procedures, subjects filled in questionnaires with items about expectations and experience with regard to the procedures. Results: Before procedures, subjects in group B had a higher fear of and reluctance to undergo mini-arthroscopy compared to MRI (p < 0.0001 and p = 0.001, respectively). Before procedures, 42% of the subjects preferred MRI, 11% of the subjects preferred mini-arthroscopy and 47% had no preference for either procedure. After both procedures, subjects preferences changed to 39% for MRI, 32% for mini-arthroscopy and 29% for no preference for one or the other procedure. When comparing Group A with Group B, there were no significant differences in preference before and after the procedures. Conclusion: Synovial biopsy sampling by mini-arthroscopy for analysis of synovial inflammation is a well-experienced procedure when compared to contrast enhanced MRI. These results support the use of mini-arthroscopy in a research setting from a patient perspective.

关键词： Arthritis Rheumatoid Synovium Arthroscopy MRI

Clinical outcomes of patients with duodenal adenocarcinoma and intestinal-type papilla of Vater adenocarcinoma

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World Journal of Gastrointestinal Oncology 2020年第3期12卷 347-357页

作者： Laura L Meijer Marin Strijker Jacob K de Bakker Jurgen GJ Toennaer Barbara M Zonderhuis Hans J van der Vliet Hanneke Wilmink Joanne Verheij Freek Daams Olivier R Busch Nicole CT van Grieken Marc G Besselink Geert Kazemier Department of Surgery Cancer Center AmsterdamAmsterdam UMCVU University AmsterdamAmsterdamNoord-Holland 1081HVThe Netherlands Department of Surgery Cancer Center AmsterdamAmsterdam UMCUniversity of AmsterdamAmsterdamNoord-Holland 1105AZThe Netherlands Department of Medical Oncology Cancer Center AmsterdamAmsterdam UMCVU University AmsterdamAmsterdamNoord-Holland 1081HVThe Netherlands Department of Medical Oncology Cancer Center AmsterdamAmsterdam UMCUniversity of Amsterdam AmsterdamNoord-Holland 1105AZThe Netherlands Department of Pathology Cancer Center AmsterdamAmsterdam UMCUniversity of Amsterdam AmsterdamNoord-Holland 1105AZThe Netherlands Department of Pathology Cancer Center AmsterdamAmsterdam UMCVU University Amsterdam Noord-Holland 1081HVThe Netherlands

BACKGROUND Duodenal adenocarcinoma(DA)and intestinal-type papilla of Vater adenocarcinoma(it-PVA)are rare malignancies of the gastrointestinal *** therapeutic options are translated nowadays from treatment strategies for patients with colorectal cancer due to histopathological *** To retrospectively investigate the clinical outcome of patients with DA and *** All patients with DA and it-PVA diagnosed between 2000 and 2017 were included at two academic centers in the *** patients with histopathologically-confirmed DA or it-PVA were eligible for *** outcome was compared between DA and it-PVA per disease *** the subgroup of stage IV disease,survival after local treatment of oligometastases was compared with systemic therapy or supportive *** In total,155 patients with DA and it-PVA were *** with it-PVA more often presented with stage I disease,while DA was more often diagnosed at stage IV(P<0.001).Of all patients,79%were treated with curative *** median survival was 39 mo,and no difference in survival was found for patients with DA and it-PVA after stratification for disease ***(23%)of 31 patients with synchronous stage IV disease underwent resection of the primary tumor,combined with local treatment of *** treatment of metastases was associated with an overall survival of 37 mo,compared to 14 and 6 mo for systemic therapy and supportive care,*** Survival of patients with DA and it-PVA is comparable per disease *** results suggest a potential benefit for local treatment strategies in selected patients with oligometastases,although additional prospective studies are needed.

关键词： Duodenal adenocarcinoma Papilla of Vater adenocarcinoma Clinical outcomes Local treatment Metastases Survival

Surgery in (pre)malignant celiac disease

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World Journal of Gastroenterology 2015年第43期21卷 12403-12409页

作者： Jolanda MW van de Water Petula Nijeboer Laura R de Baaij Jessy Zegers Gerd Bouma Otto J Visser Donald L van der Peet Chris JJ Mulder Wilhelmus JHJ Meijerink Department of Gastroenterology and Hepatology Coeliac Center AmsterdamVU University Medical Center Department of Haematology Coeliac Center AmsterdamVU University Medical Center Department of Surgery Coeliac center amsterdam VU University Medical Center

AIM: To report the outcome of surgery in patients with(pre)malignant conditions of celiac disease(CD) and the impact on ***: A total of 40 patients with(pre)malignant conditions of CD,ulcerative jejunitis(n = 5) and enteropathy associated T-cell lymphoma(EATL)(n = 35),who underwent surgery between 2002 and 2013 were retrospectively evaluated. Data on indications,operative procedure,post-operative morbidity and mortali ty,adjuvant therapy and overal l survival(OS) were collected. Eleven patients with EATL who underwent chemotherapy without resection were included as a control group for survival analysis. Patients were followed-up every three months during the first year and at 6-mo intervals ***: Mean age at resection was 62 years. The majority of patients(63%) underwent elective laparotomy. Functional stenosis(n = 1 3) and perforation(n = 12) were the major indications for surgery. In 70% of patients radical resection wasperformed. Early postoperative complications,mainly due to leakage or sepsis,occurred in 14/40(35%) of patients. Eight patients required reoperation. More patients who underwent resection in the acute setting(n = 3,20%) died compared to patients treated in the elective setting. With a median follow-up of 20 mo,seven patients(18%) required reoperation due to long-term complications. Significantly more patients who underwent acute surgery could not be treated with adjuvant chemotherapy. Patients who first underwent surgical resection showed significantly better OS than patients who received chemotherapy without ***: Although the complication rate is high,the preferred first step of treatment in(pre)malignant CD consists of local resection as early as possible to improve survival.

关键词： Enteropathy associated T-cell lymphoma Ulcerative