European Journal of Clinical Investigation最新文献

{"title":"Single versus dual antiplatelet therapy following percutaneous left atrial appendage closure—A systematic review and meta-analysis","authors":"Saverio Continisio,&nbsp;Carolina Montonati,&nbsp;Filippo Angelini,&nbsp;Pier Paolo Bocchino,&nbsp;Carla Carbonaro,&nbsp;Federico Giacobbe,&nbsp;Veronica Dusi,&nbsp;Ovidio De Filippo,&nbsp;Alfonso Ielasi,&nbsp;Giuseppe Giannino,&nbsp;Emiliano Boldi,&nbsp;Tommaso Fabris,&nbsp;Fabrizio D'Ascenzo,&nbsp;Gaetano Maria De Ferrari,&nbsp;Giuseppe Tarantini","doi":"10.1111/eci.14209","DOIUrl":"10.1111/eci.14209","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In the last few years, percutaneous LAA occlusion (LAAO) has become a plausible alternative in atrial fibrillation (AF) patients with contraindications to anticoagulation therapy. Nevertheless, the optimal antiplatelet strategy following percutaneous LAAO remains to be defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Studies comparing single antiplatelet therapy (SAPT) versus dual antiplatelet therapy (DAPT) following LAAO were systematically searched and screened. The outcomes of interest were ischemic stroke, device-related thrombus (DRT) and major bleeding. A random-effect meta-analysis was performed comparing outcomes in both groups. The moderator effect of baseline characteristics on outcomes was evaluated by univariate meta-regression analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sixteen observational studies with 3255 patients treated with antiplatelet therapy (SAPT, <i>n</i> = 1033; DAPT, <i>n</i> = 2222) after LAAO were included. Mean age was 74.5 ± 8.3 years, mean CHA₂DS₂-VASc and HAS-BLED scores were 4.3 ± 1.5 and 3.2 ± 1.0, respectively. At a weighted mean follow-up of 12.7 months, the occurrence of stroke (RR 1.33; 95% CI 0.64–2.77; <i>p</i> =.44), DRT (RR 1.52; 95% CI 0.90–2.58; <i>p</i> =.12), and the composite of stroke and DRT (RR 1.26; 95% CI 0.67–2.37; <i>p</i> =.47) did not differ significantly between SAPT and DAPT groups. The rate of major bleedings was also not different between groups (RR 1.41; 95% CI 0.64–3.12; <i>p</i> =.39).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Among AF patients at high bleeding risk undergoing percutaneous LAAO, a post-procedural minimalistic antiplatelet strategy with SAPT did not significantly differ from DAPT regimens regarding the rate of stroke, DRT and major bleeding.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140588881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of anaemia and iron deficiency in heart failure with mildly reduced ejection fraction","authors":"Tobias Schupp,&nbsp;Kathrin Weidner,&nbsp;Marielen Reinhardt,&nbsp;Noah Abel,&nbsp;Alexander Schmitt,&nbsp;Felix Lau,&nbsp;Maximilian Kittel,&nbsp;Thomas Bertsch,&nbsp;Christel Weiß,&nbsp;Michael Behnes,&nbsp;Ibrahim Akin","doi":"10.1111/eci.14205","DOIUrl":"10.1111/eci.14205","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The present study aims to clarify the prevalence and prognostic impact of anaemia and iron deficiency in patients with heart failure with mildly reduced ejection fraction (HFmrEF).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The prognostic impact of anaemia and iron deficiency in HFmrEF has not yet been clarified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Consecutive patients with HFmrEF were retrospectively included at one institution from 2016 to 2022. Patients with anaemia (i.e. haemoglobin &lt;13 g/dL in males and &lt; 12 g/dL in females) were compared to patients without, respectively patients with or without iron deficiency. The primary endpoint was all-cause mortality at 30 months (median follow-up), secondary endpoints comprised HF-related rehospitalisation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Two thousand one hundred and fifty four patients with HFmrEF with a median haemoglobin level of 12.2 g/dL were included. Anaemia was present in 52% of patients with HFmrEF and associated with a higher risk of all-cause mortality (44% vs. 18%; HR = 3.021; 95% CI 2.552–3.576; <i>p</i> =.001) and HF-related rehospitalisation (18% vs. 8%; HR = 2.351; 95% CI 1.819–3.040; <i>p</i> =.001) at 30 months, which was confirmed after multivariable adjustment. Although iron status was infrequently assessed in anaemics with HFmrEF (27%), the presence of iron deficiency was associated with higher risk of rehospitalisation for worsening HF (25% vs. 15%; HR = 1.746; 95% CI 1.024–2.976; <i>p</i> =.038), but not all-cause mortality (<i>p</i> =.279) at 30 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Anaemia and iron deficiency are very common in atleast half of patients with HFmrEF and independently associated with adverse long-term prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140588869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated circulating BMP9 aggravates pulmonary angiogenesis in hepatopulmonary syndrome rats through ALK1-Endoglin-Smad1/5/9 signalling","authors":"Chunyong Yang,&nbsp;Mei Sun,&nbsp;Yihui Yang,&nbsp;Yan Han,&nbsp;Xiulin Wu,&nbsp;Xianfeng Wu,&nbsp;Huilin Cao,&nbsp;Lin Chen,&nbsp;Yuhao Lei,&nbsp;Xiaoyan Hu,&nbsp;Yang Chen,&nbsp;Ziyang Zeng,&nbsp;Junhong Li,&nbsp;Xin Shu,&nbsp;Zhiyong Yang,&nbsp;Kaizhi Lu,&nbsp;Yujie Li,&nbsp;Xiaobo Wang,&nbsp;Bin Yi","doi":"10.1111/eci.14212","DOIUrl":"10.1111/eci.14212","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bone morphogenetic protein 9 (BMP9) is a hepatokine that plays a pivotal role in the progression of liver diseases. Moreover, an increasing number of studies have shown that BMP9 is associated with hepatopulmonary syndrome (HPS), but its role in HPS is unclear. Here, we evaluated the influence of CBDL on BMP9 expression and investigated potential mechanisms of BMP9 signalling in HPS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We profiled the circulating BMP9 levels in common bile duct ligation-induced HPS rat model, and then investigated the effects and mechanisms of HPS rat serum on pulmonary vascular endothelial dysfunction in rat model, as well as in primarily cultured rat pulmonary microvascular endothelial cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our data revealed that circulating BMP9 levels were significantly increased in the HPS rats compared to control group. Besides, the elevated BMP9 in HPS rat serum was not only crucial for promoting endothelial cell proliferation and tube formation through the activin receptor-like kinase1 (ALK1)-Endoglin-Smad1/5/9 pathway, but also important for accumulation of monocytes. Treatments with ALK1-Fc or silencing ALK1 expression to inhibit the BMP9 signalling pathway effectively eliminated these effects. In agreement with these observations, increased circulating BMP9 was associated with an increase in lung vessel density and accumulation of pro-angiogenic monocytes in the microvasculature in HPS rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study provided evidence that elevated circulating BMP9, secreted from the liver, promote pulmonary angiogenesis in HPS rats via ALK1-Endoglin-Smad1/5/9 pathway. In addition, BMP9-regulated pathways are also involved in accumulation of pro-angiogenic monocytes in the pulmonary microvasculature in HPS rats.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140588969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The fate and role of the pericytes in myocardial diseases","authors":"Nikolaos G. Frangogiannis","doi":"10.1111/eci.14204","DOIUrl":"10.1111/eci.14204","url":null,"abstract":"<p>The adult mammalian heart contains a large population of pericytes that play important roles in homeostasis and disease. In the normal heart, pericytes regulate microvascular permeability and flow. Myocardial diseases are associated with marked alterations in pericyte phenotype and function. This review manuscript discusses the role of pericytes in cardiac homeostasis and disease. Following myocardial infarction (MI), cardiac pericytes participate in all phases of cardiac repair. During the inflammatory phase, pericytes may secrete cytokines and chemokines and may regulate leukocyte trafficking, through formation of intercellular gaps that serve as exit points for inflammatory cells. Moreover, pericyte contraction induces microvascular constriction, contributing to the pathogenesis of ‘no-reflow’ in ischemia and reperfusion. During the proliferative phase, pericytes are activated by growth factors, such as transforming growth factor (TGF)-β and contribute to fibrosis, predominantly through secretion of fibrogenic mediators. A fraction of pericytes acquires fibroblast identity but contributes only to a small percentage of infarct fibroblasts and myofibroblasts. As the scar matures, pericytes form a coat around infarct neovessels, promoting stabilization of the vasculature. Pericytes may also be involved in the pathogenesis of chronic heart failure, by regulating inflammation, fibrosis, angiogenesis and myocardial perfusion. Pericytes are also important targets of viral infections (such as SARS-CoV2) and may be implicated in the pathogenesis of cardiac complications of COVID19. Considering their role in myocardial inflammation, fibrosis and angiogenesis, pericytes may be promising therapeutic targets in myocardial disease.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140588970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mineralocorticoid receptor antagonists in kidney transplantation","authors":"Mehmet Kanbay,&nbsp;Sidar Copur,&nbsp;Berk Mizrak,&nbsp;Francesca Mallamaci,&nbsp;Carmine Zoccali","doi":"10.1111/eci.14206","DOIUrl":"10.1111/eci.14206","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The fundamental role of the renin–angiotensin–aldosterone system in the pathophysiology of chronic kidney disease, congestive heart failure, hypertension and proteinuria is well established in pre-clinical and clinical studies. Mineralocorticoid receptor antagonists are among the primary options for renin–angiotensin–aldosterone system blockage, along with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this narrative review, we aim to evaluate the efficiency and safety of mineralocorticoid receptor antagonists in kidney transplant recipients, including the potential underlying pathophysiology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The efficiency and safety of mineralocorticoid receptor antagonists in managing chronic kidney disease and proteinuria, either non-nephrotic or nephrotic range, have been demonstrated among nontransplanted patients, though studies investigating the role of mineralocorticoid receptor antagonists among kidney transplant recipients are scarce. Nevertheless, promising results have been reported in pre-clinical and clinical studies among kidney transplant recipients regarding the role of mineralocorticoid receptor antagonists in terms of ischaemia–reperfusion injury, proteinuria, or calcineurin inhibitor-mediated nephrotoxicity without considerable adverse events such as hypotension, hyperkalaemia or worsening renal functions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Even though initial results regarding the role of mineralocorticoid receptor antagonist therapy for kidney transplant recipients are promising, there is clear need for large-scale randomized clinical trials with long-term follow-up data.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140588961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic significance of echocardiographic deformation imaging in adult congenital heart disease","authors":"Philippe J. van Rosendael,&nbsp;Karim Taha,&nbsp;Marco Guglielmo,&nbsp;Arco J. Teske,&nbsp;Pim van der Harst,&nbsp;Gertjan Sieswerda,&nbsp;Maarten J. Cramer,&nbsp;Heleen B. van der Zwaan","doi":"10.1111/eci.14200","DOIUrl":"10.1111/eci.14200","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Due to medical and surgical advancements, the population of adult patients with congenital heart disease (ACHD) is growing. Despite successful therapy, ACHD patients face structural sequalae, placing them at increased risk for heart failure and arrhythmias. Left and right ventricular function are important predictors for adverse clinical outcomes. In acquired heart disease it has been shown that echocardiographic deformation imaging is of superior prognostic value as compared to conventional parameters as ejection fraction. However, in adult congenital heart disease, the clinical significance of deformation imaging has not been systematically assessed and remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>According to the Preferred Reporting Items for Systematic Reviews checklist, this systematic review included studies that reported on the prognostic value of echocardiographic left and/or right ventricular strain by 2-dimensional speckle tracking for hard clinical end-points (death, heart failure hospitalization, arrhythmias) in the most frequent forms of adult congenital heart disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 19 contemporary studies were included. Current data shows that left ventricular and right ventricular global longitudinal strain (GLS) predict heart failure, transplantation, ventricular arrhythmias and mortality in patients with Ebstein's disease and tetralogy of Fallot, and that GLS of the systemic right ventricle predicts heart failure and mortality in patients post atrial switch operation or with a congenitally corrected transposition of the great arteries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Deformation imaging can potentially impact the clinical decision making in ACHD patients. Further studies are needed to establish disease-specific reference strain values and ranges of impaired strain that would indicate the need for medical or structural intervention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14200","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-type specific molecular expression levels by restricted-dimensional cytometry","authors":"David Kaplan,&nbsp;Hillard M. Lazarus,&nbsp;Eric Christian","doi":"10.1111/eci.14207","DOIUrl":"10.1111/eci.14207","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cytometric analysis has been commonly used to delineate distinct cell subpopulations among peripheral blood mononuclear cells by the differential expression of surface receptors. This capability has reached its apogee with high-dimensional approaches such as mass cytometry and spectral cytometry that include simultaneous assessment of 20–50 analytes. Unfortunately, this approach also engenders significant complexity with analytical and interpretational pitfalls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we demonstrate a complementary approach with restricted-dimensionality to assess cell-type specific intracellular molecular expression levels at exceptional levels of precision. The expression of five analytes was individually assessed in four mononuclear cell-types from peripheral blood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Distinctions in expression levels were seen between cell-types and between samples from different donor groups. Mononuclear cell-type specific molecular expression levels distinguished pregnant from nonpregnant women and G-CSF-treated from untreated persons. Additionally, the precision of our analysis was sufficient to quantify a novel relationship between two molecules—Rel A and translocator protein—by correlational analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Restricted-dimensional cytometry can provide a complementary approach to define characteristics of cell-type specific intracellular protein and phosphoantigen expression in mononuclear cells.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14207","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long noncoding RNA ANRIL alleviates hypoxia-induced pulmonary microvascular endothelial cell damage","authors":"Yijin Qi,&nbsp;Mingyue Chen,&nbsp;Tianyi Zhang,&nbsp;Beibei Zhao,&nbsp;Tianbo Jin,&nbsp;Dongya Yuan","doi":"10.1111/eci.14202","DOIUrl":"10.1111/eci.14202","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>High-altitude pulmonary oedema (HAPE) is a form of noncardiogenic pulmonary oedema. Studies have found that long noncoding RNA (lncRNA) plays an important role in HAPE. ANRIL is significant in pulmonary illnesses, which implies that alterations in ANRIL expression levels may be involved in the beginning and development of HAPE. However, the specific mechanism is indistinct. The present study is meant to explore the effect and mechanism of ANRIL on hypoxic-induced injury of pulmonary microvascular endothelial cells (PMEVCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In the hypoxic model of PMVECs, overexpression of ANRIL or knockdown of miR-181c-5p was performed to assess cell proliferation, apoptosis, and migration. Furthermore, the levels of apoptosis-related proteins, inflammatory factors, and vascular active factors were also measured.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results showed that, after 24 h of hypoxia, PMVECs proliferation and migration were suppressed in comparison to the control group, along with an increase in apoptosis, a decrease in the expression of ANRIL, and an increase in the expression of miR-181c-5p (all <i>p</i> &lt; .05). The damage caused by hypoxia in PMVECs can be lessened by overexpressing ANRIL, which also inhibits the production of TNF-α, iNOS, and VEGF as well as BAX and cleaved caspase-3 (all <i>p</i> &lt; .05). Further experimental results showed that overexpression of ANRIL and knockdown of miR-181c-5p had the same protection against hypoxic injury in PMVECs (all <i>p</i> &lt; .05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study suggests that ANRIL may prevent hypoxia injury to PMVECs in HAPE through the negative regulation of miR-181c-5p.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140326501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR T therapy from haematological malignancies to aging-related diseases: An ever-expanding universe","authors":"Davide Ramoni,&nbsp;Fabrizio Montecucco,&nbsp;Federico Carbone","doi":"10.1111/eci.14203","DOIUrl":"10.1111/eci.14203","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Short but impactful, the two-decade story of gene editing allowed a significant breakthrough in the treatment of haematological malignancies. However, despite different generations of chimeric antigen receptor T (CAR T), such a successful therapy has not yet been replicated in solid tumours and non-oncological diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This narrative review discusses how CAR T therapy still faces challenges in overcoming the complexity of the solid tumour microenvironment and the concerns that its long-term activity raises about potential unknown and unpredictable consequences in non-oncological diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the most recent studies, the senolytic potential of CAR T is becoming an exciting field of research. Still, experimental but promising results indeed indicate the clearance of senescent cells as an effective strategy to improve exercise capacity and metabolic dysfunction in physiological ageing, with long-term therapeutic and preventive effects. However, an effective expansion of a CAR T population requires a lympho-depleting chemotherapy prior to infusion. While this procedure sounds reasonable for rescue therapy of oncological diseases, it poses genotoxic risks that may not be justified for non-malignant diseases. Those represent the leading gaps for applying CAR T therapy in non-oncological diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>More is expected from current studies on the other classes of CAR cells now under investigation. Engineering NK cells and macrophages are candidates to improve cytotoxic and immunomodulating properties, potentially able to broaden application in solid tumours and non-oncological diseases. Finally, engineering autologous T cells in old individuals may generate biologically deteriorated CAR T clones with impaired function and unpredictable effects on cytokine release.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14203","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myosteatosis predicts postoperative complications and long-term survival in robotic gastrectomy for gastric cancer: A propensity score analysis","authors":"Pingan Ding,&nbsp;Jiaxiang Wu,&nbsp;Haotian Wu,&nbsp;Tongkun Li,&nbsp;Jiaxuan Yang,&nbsp;Li Yang,&nbsp;Honghai Guo,&nbsp;Yuan Tian,&nbsp;Peigang Yang,&nbsp;Lingjiao Meng,&nbsp;Qun Zhao","doi":"10.1111/eci.14201","DOIUrl":"10.1111/eci.14201","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Robotic gastrectomy is increasingly utilized for gastric cancer, but high morbidity remains a concern. Myosteatosis or low skeletal muscle density reflecting fatty infiltration, associates with complications after other cancer surgeries but has not been evaluated for robotic gastrectomy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study analysed 381 patients undergoing robotic gastrectomy for gastric cancer from September 2019 to October 2022. Myosteatosis was quantified on preoperative computed tomography (CT) images at lumbar 3 (L3). Propensity score matching addressed potential confounding between myosteatosis and non-myosteatosis groups. Outcomes were postoperative complications, 30 days mortality, 30 days readmissions and survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Myosteatosis was present in 33.6% of patients. Myosteatosis associated with increased overall (47.7% vs. 26.5%, <i>p</i> &lt; 0.001) and severe complications (12.4% vs. 4.9%, <i>p</i> &lt; 0.001). After matching, myosteatosis remained associated with increased overall complications, major complications, intensive care unit (ICU) transfer and readmission (all <i>p</i> &lt; 0.05). Myosteatosis independently predicted overall [odds ratio (OR) = 2.86, 95% confidence interval (CI): 1.57–5.20, <i>p</i> = 0.001] and severe complications (OR = 4.81, 95% CI: 1.51–15.27, <i>p</i> = 0.008). Myosteatosis also associated with reduced overall (85.0% vs. 93.2%, <i>p</i> = 0.015) and disease-free survival (80.3% vs. 88.4%, <i>p=</i>0.029). On multivariate analysis, myosteatosis independently predicted poorer survival [hazard ratio (HR) = 2.83, 95% CI: 1.32–6.08, <i>p=</i>0.012] and disease-free survival (HR = 1.83, 95% CI: 1.01–3.30, <i>p=</i>0.032).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Preoperative CT-defined myosteatosis independently predicts increased postoperative complications and reduced long-term survival after robotic gastrectomy for gastric cancer. Assessing myosteatosis on staging CT could optimize preoperative risk stratification.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140293222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}