Transcriptional reprogramming during human osteoclast differentiation identifies regulators of osteoclast activity

Enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis,which is characterized by increased bone resorption and inadequate bone formation.As novel antiosteoporotic therapeutics are needed,understanding the genetic regulation of human osteoclastogenesis could help identify potential treatment targets.This study aimed to provide an overview of transcriptional reprogramming during human osteoclast differentiation.Osteoclasts were differentiated from CD14+monocytes from eight female donors.RNA sequencing during differentiation revealed 8980 differentially expressed genes grouped into eight temporal patterns conserved across donors.These patterns revealed distinct molecular functions associated with postmenopausal osteoporosis susceptibility genes based on RNA from iliac crest biopsies and bone mineral density SNPs.Network analyses revealed mutual dependencies between temporal expression patterns and provided insight into subtype-specific transcriptional networks.The donor-specific expression patterns revealed genes at the monocyte stage,such as filamin B(FLNB)and oxidized low-density lipoprotein receptor 1(OLR1,encoding LOX-1),that are predictive of the resorptive activity of mature osteoclasts.The expression of differentially expressed G-protein coupled receptors was strong during osteoclast differentiation,and these receptors are associated with bone mineral density SNPs,suggesting that they play a pivotal role in osteoclast differentiation and activity.The regulatory effects of three differentially expressed G-protein coupled receptors were exemplified by in vitro pharmacological modulation of complement 5 A receptor 1(C5AR1),somatostatin receptor 2(SSTR2),and free fatty acid receptor 4(FFAR4/GPR120).Activating C5AR1 enhanced osteoclast formation,while activating SSTR2 decreased the resorptive activity of mature osteoclasts,and activating FFAR4 decreased both the number and resorptive activity of mature osteoclasts.In conclusion,we report the occurrence of transcriptional reprogramming during human osteoclast differentiation and identified SSTR2 and FFAR4 as antiresorptive G-protein coupled receptors and FLNB and LOX-1 as potential molecular markers of osteoclast activity.These data can help future investigations identify molecular regulators of osteoclast differentiation and activity and provide the basis for novel antiosteoporotic targets.

Latent Growth Mixture Modeling to Estimate Differential PTSD Trajectories and Associated Risk Factors in Psychiatric Staff Following Workplace Violence

Background: Workplace violence (WV) towards psychiatric staff has commonly been associated with Posttraumatic Stress Disorder (PTSD). However, prospective studies have shown that not all psychiatric staff who experience workplace violence experience post-traumatic stress. Purpose: We want to examine the longitudinal trajectories of PTSD in this population to identify possible subgroups that might be more at risk. Furthermore, we need to investigate whether certain risk factors of PTSD might identify membership in the subgroups. Method: In a sample of psychiatric staff from 18 psychiatric wards in Denmark who had reported an incident of WV, we used Latent Growth Mixture Modelling (LGMM) and further logistic regression analysis to investigate this. Results: We found three separate PTSD trajectories: a recovering, a delayed-onset, and a moderate-stable trajectory. Higher social support and negative cognitive appraisals about oneself, the world and self-blame predicted membership in the delayed-onset trajectory, while higher social support and lower accept coping predicted membership in the delayed-onset trajectory. Conclusion: Although most psychiatric staff go through a natural recovery, it is important to be aware of and identify staff members who might be struggling long-term. More focus on the factors that might predict these groups should be an important task for psychiatric departments to prevent posttraumatic symptomatology from work.

经支气管超声引导针吸活检在肺癌纵隔分期和胸腔内病变诊断中的应用

既往研究显示,经支气管超声引导针吸活检(endobronchial ultrasound-guided transbronchial needle aspiration, EBUS-TBNA)是一项微创技术,可用于肺癌患者的纵隔分期、胸腔内病变的诊断、不明原因淋巴结肿大的诊断以及非小细胞肺癌(non-small cell lung cancer, NSCLC)新辅助化疗后的纵隔再分期。本综述旨在关注EBUS在NSCLC纵隔分期中的作用,以及EBUS在进一步评估通过常规检查仍诊断未明的胸腔内病变中的应用。总之,就NSCLC患者纵隔分期而言,由于EBUS的诊断敏感性和特异性均较高,其为纵隔镜检查的有效替代,亦可用于疑似胸腔病变的活检,且不会给患者带来任何并发症风险。

我们应该怎样利用新抗凝剂治疗急性肺栓塞?

由于大多数的治疗都增加了出血并发症的风险,因此急性肺栓塞（pulmonary embolism,PE）患者的治疗成为临床医生面临的一大挑战。80%的PE患者具有可识别的诱发因素,

Key players in pancreatic cancer-stroma interaction: cancer-associated fibroblasts, endothelial and inflammatory cells

Pancreatic cancer(PC) is the most aggressive type of common cancers, and in 2014, nearly 40000 patients died from the disease in the United States. Pancreatic ductal adenocarcinoma, which accounts for the majority of PC cases, is characterized by an intense stromal desmoplastic reaction surrounding the cancer cells. Cancer-associated fibroblasts(CAFs) are the main effector cells in the desmoplastic reaction, and pancreatic stellate cells are the most important source of CAFs. However, other important components of the PC stroma are inflammatory cells and endothelial cells. The aim of this review is to describe the complex interplay between PC cells and the cellular and noncellular components of the tumour stroma. Published data have indicated that the desmoplastic stroma protects PC cells against chemotherapy and radiation therapy and that it might promote the proliferation and migration of PC cells. However, in animal studies, experimental depletion of the desmoplastic stroma and CAFs has led to more aggressive cancers. Hence, the precise role of the tumour stroma in PC remains to be elucidated. However, it is likely that a contextdependent therapeutic modification, rather than pure depletion, of the PC stroma holds potential for the development of new treatment strategies for PC patients.

Patients with inflammatory bowel disease have increased risk of autoimmune and inflammatory diseases

AIM To investigate whether immune mediated diseases(IMD) are more frequent in patients with inflammatory bowel disease(IBD).METHODS In this population based registry study,a total of 47325 patients with IBD were alive and registered in the Danish National Patient Registry on December 16,2013. Controls were randomly selected from the Danish Civil Registration System(CRS) and matched for sex,age,and municipality. We used ICD 10 codes to identify the diagnoses of the included patients. The IBD population was divided into three subgroups: Ulcerative colitis(UC),Crohn's disease(CD) and Both the latter referring to those registered with both diagnoses. Subsequently,odds-ratios(OR) and 95%CI were obtained separately for each group and their respective controls. The use of Bonferoni post-test correction adjusted the significance level to P < 0.00125. P-values were estimated using Fisher's exact test.RESULTS There were significantly more women than men in the registry,and a greater percentage of comorbidity in the IBD groups(P < 0.05). Twenty different IMDs were all significantly more frequent in the IBD group. Sixteen were associated with UC versus twelve with CD. In both UC and CD ORs were significantly increased(P < 0.00125) for primary sclerosing cholangitis(PSC),celiac disease,type 1 diabetes(T1D),sarcoidosis,asthma,iridocyclitis,psoriasis,pyoderma gangrenosum,rheumatoid arthritis,and ankylosing spondylitis. Restricted to UC(P < 0.00125) were autoimmune hepatitis,primary biliary cholangitis,Grave's disease,polymyalgia rheumatica,temporal arteritis,and atrophic gastritis. Restricted to CD(P < 0.00125) were psoriatic arthritis and episcleritis. Restricted to women with UC(P < 0.00125) were atrophic gastritis,rheumatoid arthritis,temporal arteritis,and polymyalgia rheumatica. Restricted to women with CD were episcleritis,rheumatoid arthritis,and psoriatic arthritis. The only disease restricted to men(P < 0.00125) was sarcoidosis. CONCLUSION Immune mediated diseases were significantly more frequent in patients with IBD. Our results strengthen the hypothesis that some IMDs and IBD may have overlapping pathogenic pathways.

Endovascular treatment of nonvariceal acute arterial upper gastrointestinal bleeding

Transcatheter arterial embolization as treatment of upper nonvariceal gastrointestinal bleeding is increasingly being used after failed primary endoscopic treatment.The results after embolization have become better and surgery still has a high mortality.Embolization is a safe and effective procedure,but its use is has been limited because of relatively high rates of rebleeding and high mortality,both of which are associated with gastrointestinal bleeding and non-gastrointestinal related mortality causes.Transcatheter arterial embolization is a valuable minimal invasive method in the treatment of early rebleeding and does not involve a high risk of treatment associated complications.A multidisciplinary approach is necessary in the treatment of these patients and should comprise gastroenterologists,interventional radiologists,anaesthesiologists,and surgeons to achieve the best possible results.

Allocation of patients with liver cirrhosis and organ failure to intensive care: Systematic review and a proposal for clinical practice

AIM: To propose an allocation system of patients with liver cirrhosis to intensive care unit(ICU), and developed a decision tool for clinical practice. METHODS: A systematic review of the literature was performed in Pub Med, MEDLINE and EMBASE databases. The search includes studies on hospitalized patients with cirrhosis and organ failure, or acute on chronic liver failure and/or intensive care therapy. RESULTS: The initial search identified 660 potentially relevant articles. Ultimately, five articles were selected; two cohort studies and three reviews were found eligible. The literature on this topic is scarce and no studies specifically address allocation of patients with liver cirrhosis to ICU. Throughout the literature, there is consensus that selection criteria for ICU admission should be developed and validated for this group of patients and multidisciplinary approach is mandatory. Based on current available data we developed an algorithm, to determine if a patient is candidate to intensive care if needed, based on three scoring systems: premorbid Child-Pugh Score, Model of End stage Liver Disease score and the liver specific Sequential Organ Failure Assessment score.CONCLUSION: There are no established systems for allocation of patients with liver cirrhosis to the ICU and no evidence-based recommendations can be made.

Development and predictive validity of the cirrhosis-associated ascites symptom scale: A cohort study of 103 patients

AIM To develop a scale of domains associated with the health-related quality-of-life(HRQOL) in patients with cirrhosis-related ascites.METHODS We initially undertook literature searches and a qualitative study in order to design a cirrhosis-associated ascites symptom(CAS) scale describing symptoms with a potential detrimental impact on health related quality of life(HRQL)(the higher the score, the worse the symptoms). Discriminatory validity was assessed in a validation cohort including cirrhotic patients with(1) tense/severe;(2) moderate/mild; or(3) no ascites(controls). Patients also completed chronic liver disease questionnaire(CLDQ) and the Euro QoL 5-Dimensions 5-Level(EQ-5D-5L) questionnaire evaluating HRQL. The relation between scale scores was analysed using Spearman correlations. RESULTS The final CAS scale included 14 items. The equivalent reliability was high(Chronbach's alpha 0.88). The validation cohort included 103 patients(72% men, mean age 62.4 years). The mean scores for each question in the CAS scale were higher for patients with severe/tense ascites than for mild/moderate ascites and controls. Compared with controls(mean = 9.9 points), the total CAS scale score was higher for severe/tense ascites(mean = 23.8 points) as well as moderate/mild ascites(mean = 18.6 points)(P < 0.001 both groups). We found a strong correlation between the total CAS and CLDQ score(rho = 0.82, P < 0.001) and a moderate correlation between the CAS and the EQ-5D-5L score(0.67, P < 0.001). CONCLUSION The CAS is a valid tool, which reflects HRQOL in patients with ascites.

Dried blood spots,valid screening for viral hepatitis and human immunodeficiency virus in real-life

AIM To detect chronic hepatitis B(CHB),chronic hepatitis C(CHC) and human immunodeficiency virus(HIV) infections in dried blood spot(DBS) and compare these samples to venous blood sampling in real-life.METHODS We included prospective patients with known viral infections from drug treatment centers,a prison and outpatient clinics and included blood donors as negative controls. Five drops of finger capillary blood were spotted on filter paper,and a venous blood sample was obtained. The samples were analyzed for HBs Ag,antiHBc,anti-HBs,anti-HCV,and anti-HIV levels as well as subjected to a combined nucleic acid test(NAT) for HBV DNA,HCV RNA and HIV RNA.RESULTS Samples from 404 subjects were screened(85 CHB,116 CHC,114 HIV and 99 blood donors). DBS had a sensitivity of > 96% and a specificity of > 98% for the detection of all three infections. NAT testing did not improve sensitivity,but correctly classified 95% of the anti-HCV-positive patients with chronic and past infections. Anti-HBc and anti-HBS showed low sensitivity in DBS(68% and 42%).CONCLUSION DBS sampling,combined with an automated analysis system,is a feasible screening method to diagnose chronic viral hepatitis and HIV infections outside of the health care system.

Patient selection and preparation strategies for the use of contrast material in patients with chronic kidney disease

The prevalence of chronic kidney disease and peripheral arterial disease is increasing.Thus,it is increasingly problematic to image these patients as the number of patients needing a vascular examination is increasing accordingly.In high-risk patients with impaired kidney function,intravascular administration of iodinated contrast media can result in contrast-induced acute kidney injury and Gadolinium can induce nephrogenic systemic fibrosis(NSF).It is important to identify these highrisk patients by means of se-creatinine/e glomerular filtration rate.The indication for contrast examination should counterbalance the increased risk.One or more alternative examination methods without contrast media,such as CO 2 angiography,Ultrasound/Doppler examination or magnetic resonance angiography without contrast should be considered,but at the same time,allow for a meaningful outcome of the examination.If contrast is deemed essential,the patient should be well hydrated,the amount of contrast should be restricted,the examination should be focused,metformin and diuretics stopped,and renal function monitored.Sodium bicarbonate and N-acetylcysteine are popular but their efficiency is not evidence-based.There is no evidence that dialysis protects patients with impaired renal function from contrast-induced nephropathy or NSF.

Interventional treatment of pulmonary arteriovenous malformations

Pulmonary arteriovenous malformations(PAVM) are congenital vascular communications in the lungs.They act as right to left shunts so that the blood running through these malformations is not oxygenated or filtered.These patients are typically hypoxaemic with exercise intolerance and are at high risk of paradoxical emboli to the brain and other organs.These malformations are most commonly seen in hereditary haemorrhagic telangiectasia(HHT)(Mb.Osler-Weber-Rendu syndrome).Nowadays,the generally accepted treatment strategy of first choice is embolization of the afferent arteries to the arteriovenous malformations.It is a minimally invasive procedure and at the same time a lung preserving treatment with a very high technical success,high effectiveness and low morbidity and mortality.Embolization prevents cerebral stroke and abscess as well as pulmonary haemorrhage and further raises the functional level.Embolization is a well-established method of treating PAVM,with a significant effect on oxygenation of the blood.Screening for PAVM in patients at risk is recommended,especially in patients with HHT.

Endovascular treatment of aortoiliac aneurysms: From intentional occlusion of the internal iliac artery to branch iliac stent graft

Approximately 20%-40% of patients with abdominal aortic aneurysms can have unilateral or bilateral iliac artery aneurysms and/or ectasia. This influences and compromises the distal sealing zone during endovascular aneurysm repair. There are a few endovascular techniques that are used to treat these types of aneurysms, including intentional occlusion/over-stenting of the internal iliac artery on one or both sides, the "bell-bottom" technique, and the more recent method of using an iliac branch stent graft. In some cases, other options include the "snorkel and sandwich" technique and hybrid interventions. Pelvic ischemia, represented as buttock claudication, has been reported in 16%-55% of cases; this is followed by impotence, which has been described in 10%-17% of cases following internal iliac artery occlusion. The bellbottom technique can be used for a common iliac artery up to 24 mm in diameter given that the largest diameter of the stent graft is 28 mm. There is a paucity of data and evidence regarding the "snorkel and sandwich" technique, which can be used in a few clinical scenarios. The hybrid intervention is comprised of a surgical operation, and is not purely endovascular. The newest branch stent graft technology enables preservation of the anterograde flow of important side branches. Technical success with the newest technique ranges from 85%-96.3%, and in some small series, technical success is 100%. Buttock claudication was reported in up to 4% of patients treated with a branch stent graft at 5-year follow-up. Mid- and short-term follow-up results showed branch patency of up to 88% during the 5-6-year period. Furthermore, branch graft occlusion is a potential complication, and it has been described to occur in 1.2%-11% of cases. Iliac branch stent graft placement represents a further development in endovascular medicine, and it has a high technical success rate without serious complications.

Typing of pancreatic cancer-associated fibroblasts identifies different subpopulations

AIM To determine whether it is possible to identify different immune phenotypic subpopulations of cancer-associated fibroblasts (CAFs) in pancreatic cancer (PC). METHODS We defined four different stromal compartments in surgical specimens with PC: The juxtatumoural, peripheral, lobular and septal stroma. Tissue microarrays were produced containing all pre-defined PC compartments, and the expression of 37 fibroblast (FB) and 8 extracellular matrix (ECM) markers was evaluated by immunohistochemistry, immunofluorescence (IF), double-IF, and/or in situ hybridization. The compartment-specific mean labelling score was determined for each marker using a four-tiered scoring system. DOG1 gene expression was examined byquantitative reverse transcription PCR (qPCR). RESULTS CD10, CD271, cytoglobin, DOG1, miR-21, nestin, and tenascin C exhibited significant differences in expression profiles between the juxtatumoural and peripheral compartments. The expression of CD10, cytoglobin, DOG1, nestin, and miR-21 was moderate/strong in juxtatumoural CAFs (j-CAFs) and barely perceptible/weak in peripheral CAFs (p-CAFs). The upregulation of DOG1 gene expression in PC compared to normal pancreas was verified by qPCR. Tenascin C expression was strong in the juxtatumoural ECM and barely perceptible/weak in the peripheral ECM. CD271 expression was barely perceptible in j-CAFs but moderate in the other compartments. Galectin-1 was stronger expressed in j-CAFs vs septal fibroblasts, PDGFRβ, tissue transglutaminase 2, and hyaluronic acid were stronger expressed in lobular fibroblasts vs p-CAFs, and plectin-1 was stronger expressed in j-CAFs vs l-FBs. The expression of the remaining 33 markers did not differ significantly when related to the quantity of CAFs/FBs or the amount of ECM in the respective compartments.CONCLUSION Different immune phenotypic CAF subpopulations can be identified in PC, using markers such as cytoglobin, CD271, and miR-21. Future studies should determine whether CAF subpopulations have different functional properties.

Aging and menopause reprogram osteoclast precursors for aggressive bone resorption

Women gradually lose bone from the age of〜35 years,but around menopause,the rate of bone loss escalates due to increasing bone resorption and decreasing bone formation levels,rendering these individuals more prone to developing osteoporosis.The increased osteoclast activity has been linked to a reduced estrogen level and other hormonal changes.However,it is unclear whether intrinsic changes in osteoclast precursors around menopause can also explain the increased osteoclast activity.Therefore,we set up a protocol in which CD14f blood monocytes were isolated from 49 female donors(40-66 years old).Cells were differentiated into osteoclasts,and data on differentiation and resorption activity were collected.Using multiple linear regression analyses combining in vitro and in vivo data,we found the following:(1)age and menopausal status correlate with aggressive osteoclastic bone resorption in vitro;(2)the type I procollagen N-terminal propeptide level in vivo inversely correlates with osteoclast resorption activity in vitro;(3)the protein level of mature cathepsin K in osteoclasts in vitro increases with age and menopause;and(4)the promoter of the gene encoding the dendritic cell-specific transmembrane protein is less methylated with age.We conclude that monocytes are"reprogrammed"in vivo,allowing them to"remember"age,the menopausal status,and the bone formation status in vitro,resulting in more aggressive osteoclasts.Our discovery suggests that this may be mediated through DNA methylation.We suggest that this may have clinical implications and could contribute to understanding individual differences in age-and menopause-induced bone loss.

Metabolic programming determines the lineage-differentiation fate of murine bone marrow stromal progenitor cells

Enhanced bone marrow adipogenesis and impaired osteoblastogenesis have been observed in obesity,suggesting that the metabolic microenvironment regulates bone marrow adipocyte and osteoblast progenitor differentiation fate.To determine the molecular mechanisms,we studied two immortalized murine cell lines of adipocyte or osteoblast progenitors(BMSCs^adipo and BMSC^sosteo,respectively)under basal and adipogenic culture conditions.At baseline,BMSCs^adipo,and BMSCs^osteo exhibit a distinct metabolic program evidenced by the presence of specific global gene expression,cellular bioenergetics,and metabolomic signatures that are dependent on insulin signaling and glycolysis in BMSCs^osteo versus oxidative phosphorylation in BMSCs^adipo.To test the flexibility of the metabolic program,we treated BMSCsadipo with parathyroid hormone,S961(an inhibitor of insulin signaling)and oligomycin(an inhibitor of oxidative phosphorylation).The treatment induced significant changes in cellular bioenergetics that were associated with decreased adipocytic differentiation.Similarly,12 weeks of a high-fat diet in mice led to the expansion of adipocyte progenitors,enhanced adipocyte differentiation and insulin signaling in cultured BMSCs.Our data demonstrate that BMSC progenitors possess a distinct metabolic program and are poised to respond to exogenous metabolic cues that regulate their differentiation fate.

Incidental findings at MRI-enterography in patients with suspected or known Crohn's disease

AIM:To determine the frequency and clinical impact of incidental findings detected with magnetic resonance imaging(MRI)-enterography in patients with suspected or known Crohn's disease(CD). METHODS:Incidental findings were defined as unexpected lesions outside the small intestine,not previously known or suspected at the time of referral, and not related to inflammatory bowel disease.Through a systematic review of medical charts we analyzed the clinical impact of incidental findings,and compared the MRI findings with subsequent diagnostic procedures. RESULTS:A total of 283 patients were included in the analysis,and MRI detected active CD in 31%,fistula in 1.4%and abscess in 0.7%.Extra-intestinal findings notrelated to CD were recorded in 72 patients(25%),of which 58 patients(20%)had 74 previously unknown lesions.Important or incompletely characterized findings were detected in 17 patients(6.0%).Incidental findings led to 12 further interventions in 9 patients(3.2%) revealing previously unknown pathological conditions in 5(1.8%).One patient(0.4%)underwent surgery and one patient was diagnosed with a malignant disease. MRI detected incidental colonic lesions in 16 patients of which additional work-up in 4 revealed normal anatomy. Two patients(0.7%)benefitted from the additional examinations,whereas incidental findings led to unnecessary examinations in 9(3.2%). CONCLUSION:In a minority of patients with suspected or known CD,important incidental findings are diagnosed at MRI-enterography.However,a substantial number of patients experience unnecessary morbidity because of additional examinations of benign or normal conditions.

腹腔镜结合腹腔镜超声在肝门部胆管癌治疗中的作用

背景目前影像学已高度发展，但肝门部胆管癌的手术适应症仍是困扰外科医师的难题，多数患者发现时已为晚期，丧失了手术时机。而不必要的腹腔镜检查增加的手术并发症发生率和死亡率更是令肝门部胆管癌极差的预后雪上加霜。目的评价腹腔镜结合腹腔镜超声（LAP／LUS）检查在肝门部胆管癌可切除率评估中的作用。

Pit-and trench-forming osteoclasts:a distinction that matters

Osteoclasts（OCs）seeded on bone slices either drill round pits or dig long trenches.Whereas pits correspond to intermittent resorption,trenches correspond to continuous and faster resorption and require a distinct assembly of the resorption apparatus.It is unknown whether the distinction between pits and trenches has any biological relevance.Using OCs prepared from different blood donors,we found that female OCs achieved increased resorption mainly through pit formation,whereas male OCs did so through trench formation.Trench formation went along with high collagenolytic activity and high cathepsin K（CatK）expression,thereby allowing deeper demineralization.A specific CatK inhibitor abrogated the generation of trenches,while still allowing the generation of pits.OCs obtained from bone marrow were more prone to generate trenches than those obtained from blood.Scanning electron microscopy of bone surfaces eroded in vivo showed trenches and pits of similar size as those made by OCs in culture.We conclude that the distinction between trench-and pit-forming OCs is relevant to the differences among OCs from different skeletal sites,different individuals,including gender,and results from differences in colIagenolytic power.This indicates a biological relevance and highlights the importance of discriminating between pits and trenches when assessing resorption.

Periprocedural complications and one-year outcomes after catheter ablation for treatment of atrial fibrillation in elderly patients:a nationwide Danish cohort study

OBJECTIVES To investigate complications within 30-days following first-time ablation for atrial fibrillation(AF),including a composite of cardiac tamponade,hematoma requiring intervention,stroke or death,in patients≥75 years of age,compared to pa-tients aged 65−74 years.In addition,one-year all-cause mortality and AF relapse were compared.METHODS&RESULTS All patients receiving their first catheter ablation for AF between 2012 and 2016 were identified us-ing Danish nationwide registries.Patients aged 65−74 years served as the reference group for patients≥75 years.Relapse of AF within one year was defined as cardioversion following a three-month blanking period,re-ablation or confirmed relapse within follow-up.The composite complication outcome did not differ between the two age groups,with 39/1554(2.8%)in patients 65−74 years of age,versus 5/199(2.5%)in older patients(adjusted HR=0.94),95%CI:0.37−2.39,P=0.896).Patients≥75 years or older had no increased hazard of death within 30 days after the procedure,with an incidence of 3/1554(0.2%)in younger pa-tients and 2/199(1.0%)in patients≥75 years of age(adjusted HR=4.71,95%CI:0.78−28.40,P=0.091).There was no difference in relapse of AF after one year between age groups(≥75 years adjusted HR=1.00,95%CI:0.78-1.26,P=0.969).CONCLUSION In patients≥75 years of age selected for catheter ablation for AF,the incidence of periprocedural complica-tions,as well as one-year freedom from AF showed no statistical difference,when compared to patients 65−74 years of age.