Large International Multicenter Study Research Articles

Bartonella species bacteremia in association with adult psychosis.

The potential role of pathogens, particularly vector-transmitted infectious agents, as a cause of psychosis has not been intensively investigated. We have reported a potential link between Bartonella spp. bacteremia and neuropsychiatric symptoms, including pediatric acute onset neuropsychiatric syndrome and schizophrenia. The purpose of this study was to further assess whether Bartonella spp. exposure or infection are associated with psychosis. In a blinded manner, we assessed the presence of anti-Bartonella antibodies by indirect immunofluorescence assays (IFA), and infection by amplification of bacterial DNA from blood by quantitative polymerase chain reaction (qPCR), digital PCR (dPCR), and droplet digital PCR (ddPCR) in 116 participants. Participants were categorized into one of five groups: 1) controls unaffected by psychosis (n = 29); 2) prodromal participants (n = 16); 3) children or adolescents with psychosis (n = 7); 4) adults with psychosis (n = 44); and 5) relatives of a participant with psychosis (n = 20). There was no significant difference in Bartonella spp. IFA seroreactivity between adults with psychosis and adult controls unaffected by psychosis. There was a higher proportion of adults with psychosis who had Bartonella spp. DNA in the bloodstream (43.2%) compared to adult controls unaffected by psychosis (14.3%, p = 0.021). The Bartonella species was determined for 18 of the 31 bacteremic participants, including infection or co-infection with Bartonella henselae (11/18), Bartonella vinsonii subsp. berkhoffii (6/18), Bartonella quintana (2/18), Bartonella alsatica (1/18), and Bartonella rochalimae (1/18). In conjunction with other recent research, the results of this study provide justification for a large national or international multi-center study to determine if Bartonella spp. bacteremia is more prevalent in adults with psychosis compared to adults unaffected by psychosis. Expanding the investigation to include a range of vector-borne and other microbial infections with potential CNS effects would enhance knowledge on the relationship between psychosis and infection.

#723 The impact of kidney function on arterial stiffness in COVID-19 survivors: an analysis from CARTESIAN Study

Abstract Background and Aims SARS-CoV-2 pandemic has been linked to an increased incidence of cardiovascular events, potentially due to accelerated vascular aging [1]. Conversely, impaired kidney function is known to contribute to the pathogenesis of heightened arterial stiffness, independent of traditional cardiovascular risk factors [2]. This study aimed to assess the impact of COVID-19 on arterial stiffness among a cohort of survivors of the first pandemic wave, with varying degrees of infection severity. The assessment was conducted at 6 ± 3 (T1) and 12 ± 3 months (T2) post-infection, with the population stratified based on kidney function. Method the CARTESIAN study, a large international multicenter cohort study, was designed to assess the long-term effects of COVID-19 on vascular aging. A total of 938 subjects were stratified into three groups based on their estimated glomerular filtration rate (eGFR) percentiles using the CKD-EPI_2021 equation: 1) >75th percentile, 2) 75th-25th percentile, and 3) <25th percentile, respectively. The same population was further categorized based on the severity of COVID-19 into three groups: 1) patients who were not hospitalized (No-Hosp), 2) subjects requiring hospitalization in a medical unit (Hosp), or 3) those in an intensive care unit (ICU). Arterial stiffness was evaluated using carotid-femoral pulse wave velocity (cf-PWV). A hierarchical repeated measures mixed model analysis was conducted to compare cf-PWV across these groups (>75th, 75th-25th, and <25th groups, respectively). Results in the cross-section analysis (T1) <25th group exhibited higher age, increased cardiovascular risk factors, and higher prevalence of severe COVID-19 compared to the >75th group. Using hierarchical linear modeling, the <25th exhibited higher cf-PWV than the >75th group, even after adjusting for both all the random and fixed variables, included the three COVID-19 group (+0.51 m/s, p = 0.013). In longitudinal analysis, globally, no substantial changes were found in the cf-PWV between T1 and T2, remained significantly higher in the <25th group compared to the >75th group (p = 0.003), in a linear mixed model adjusted for all the random and fixed variables. Interestingly, a significant interaction between eGFR groups* COVID-19 groups was found in repeated measures analysis (p = 0.039). In particular, within ICU group, we found a significant increase of cf-PWV between 6- and 12-months in <25th group, from 8.64 [7.59-9.31] to 9.41 [8.89-10.41] m/s, p = 0.021) (Fig. 1). Conclusion the findings suggest that individuals with both lower eGFR and a history of severe COVID-19 may be at a heightened risk of accelerated arterial aging. Understanding these dynamics is crucial for targeted interventions to mitigate long-term cardiovascular consequences in COVID-19 survivors with kidney disease.

As simple as it sounds? The treatment of simple bone cysts in the proximal femur in children and adolescents: Retrospective multicenter EPOS study of 74 patients.

Simple bone cysts are among the most prevalent benign cystic tumor-like lesions in children. Proximal femoral simple bone cysts may require specific treatment because of increased fracture risk. With limited literature available on this specific localization, consensus regarding optimal treatment is lacking. We present a large international multicenter retrospective cohort study on proximal femoral simple bone cysts. All consecutive pediatric patients with proximal femoral simple bone cyst from 10 tertiary referral centers for musculoskeletal oncology were included (2000-2021). Demographics, primary treatment, complications, and re-operations were evaluated. Primary outcomes were time until full weight-bearing and failure-free survival. Overall, 74 simple bone cyst patients were included (median age 9 years (range = 2-16), 56 (76%) male). Median follow-up was 2.9 years (range = 0.5-21). Index procedure was watchful waiting (n = 6), percutaneous procedure (n = 12), open procedure (n = 50), or osteosynthesis alone (n = 6). Median time until full weight-bearing was 8 weeks (95% confidence interval = 0.1-15.9) for watchful waiting, 9.5 (95% confidence interval = 3.7-15.3) for percutaneous procedure, 11 (95% confidence interval = -0.7 to 13.7) for open procedure, and 6.5 (95% confidence interval = 5.9-16.1) for osteosynthesis alone (p = 0.58). Failure rates were 33%, 58%, 29%, and 0%, respectively (p = 0.069). Overall failure-free survival at 1, 2, and 5 years was 77.8% (95% confidence interval = 68.2-87.4), 69.5% (95% confidence interval = 58.5-80.5), and 62.0% (95% confidence interval = 47.9-76.1), respectively. A preferred treatment for proximal femoral simple bone cysts remains unclear, with comparable failure rates and times until full weight-bearing. Watchful waiting may be successful in certain cases. If not feasible, osteosynthesis alone can be considered. Treatment goals should be cyst control, minimizing complications and swift return to normal activities. Therefore, an individualized balance should be made between undertreatment, with potentially higher complication risks versus overtreatment, resulting in possible larger interventions and accompanying complications. Level IV, retrospective multicentre study.

Robotic versus laparoscopic liver resection for huge (≥10 cm) liver tumors: an international multicenter propensity-score matched cohort study of 799 cases.

The use of laparoscopic (LLR) and robotic liver resections (RLR) has been safely performed in many institutions for liver tumours. A large scale international multicenter study would provide stronger evidence and insight into application of these techniques for huge liver tumours ≥10 cm. This was a retrospective review of 971 patients who underwent LLR and RLR for huge (≥10 cm) tumors at 42 international centers between 2002-2020. One hundred RLR and 699 LLR which met study criteria were included. The comparison between the 2 approaches for patients with huge tumors were performed using 1:3 propensity-score matching (PSM) (73 vs. 219). Before PSM, LLR was associated with significantly increased frequency of previous abdominal surgery, malignant pathology, liver cirrhosis and increased median blood. After PSM, RLR and LLR was associated with no significant difference in key perioperative outcomes including media operation time (242 vs. 290 min, P=0.286), transfusion rate rate (19.2% vs. 16.9%, P=0.652), median blood loss (200 vs. 300 mL, P=0.694), open conversion rate (8.2% vs. 11.0%, P=0.519), morbidity (28.8% vs. 21.9%, P=0.221), major morbidity (4.1% vs. 9.6%, P=0.152), mortality and postoperative length of stay (6 vs. 6 days, P=0.435). RLR and LLR can be performed safely for selected patients with huge liver tumours with excellent outcomes. There was no significant difference in perioperative outcomes after RLR or LLR.

Clinical and genetic correlates of mitral valve pathology in patients with heritable thoracic aortic disease: results from the montalcino aortic consortium

Abstract Background Mitral valve (MV) pathology, including prolapse and regurgitation, is a well-known cardiovascular manifestation associated with the genes that predispose to Heritable Thoracic Aortic Disease (HTAD). The extent to which there are differences in prevalence, presentation and severity of MV pathology as a function of the underlying genetic cause has not been investigated in detail. Purpose Assess the prevalence, presenting features and outcome of mitral valve pathology according to the underlying genetic defect in patients with HTAD. Study design We leveraged clinical and genetic data of a large international multicenter retrospective cohort study. Probands and relatives with a validated (likely) pathogenic (LP/P) variant in 8 HTAD genes were included. Genes were categorized in 2 groups: Group 1 encoding for components of the TGFβ pathway (TGFBR1, TGFBR2, SMAD3 and TGFB2) and Group 2 encoding for proteins involved in vascular smooth muscle cell contraction (VSMC) (ACTA2, MYLK, PRKG1, MYH11). Comparison between these groups was performed. MV pathology was defined as at least moderate MV regurgitation, MV prolapse and past MV surgeries. Results A total of 459 patients. 68.8% of the patients carried a variant in one of the Group 1 genes and 31.2% had a Group 2 gene variant. 52 patients (11.3%) presented MV pathology. Significant differences in MV status according to the gene group were present: 15.5% of the patients in group 1 presented MV disease, versus 2.1% in group 2, (p<0.001). Within Group 1, LP/P variants in SMAD3 were most common (32.7%), followed by TGFBR2 (25.0%) and TGFB2 (23.1%) (p=0.006). The remaining 5.8% of MV pathology cases were patients carrying ACTA2 variants. No MV pathology was found in MYLK, PRKG1 and MYH11 variant carriers. Compared to patients without MV pathology, patients with MV pathology more often underwent aortic aneurysm repair (34.6% vs 15.5%, p<0.001). To the contrary, aortic dissection/rupture occurred less frequently in patients with MV pathology (7.7% vs 26.8%, p<0.001). No differences were observed for prevalence of congenital heart defects, left ventricular dilatation, arrhythmic events or heart failure. Conclusion Patients with HTAD carrying LP/P variants in genes encoding TGFβ components present more frequently with MV pathology than patients carrying variants in genes encoding proteins involved in VSMC contraction. In the latter group, only patients carrying ACTA2 variants presented MV pathology. Patients with MV pathology are more likely to undergo aortic aneurysm repair and present less frequently with aortic dissection/rupture. Whether the presence of MV pathology accelerates the diagnosis and hence leads to a more aggressive management/stricter surveillance in these patients and/or whether biological differences between these genetic entities explain these differences requires further study. These data provide tools for developing improved, gene-tailored management of patients with HTAD. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Baillet Latour FoundationFunds for Scientific Research Flanders

Differences in Prognostic Value of Myocardial Perfusion Single-Photon Emission Computed Tomography Using High-Efficiency Solid-State Detector Between Men and Women in a Large International Multicenter Study.

Semiquantitative assessment of stress myocardial perfusion defect has been shown to have greater prognostic value for prediction of major adverse cardiac events (MACE) in women compared with men in single-center studies with conventional single-photon emission computed tomography (SPECT) cameras. We evaluated sex-specific difference in the prognostic value of automated quantification of ischemic total perfusion defect (ITPD) and the interaction between sex and ITPD using high-efficiency SPECT cameras with solid-state detectors in an international multicenter imaging registry (REFINE SPECT [Registry of Fast Myocardial Perfusion Imaging With Next-Generation SPECT]). Rest and exercise or pharmacological stress SPECT myocardial perfusion imaging were performed in 17 833 patients from 5 centers. MACE was defined as the first occurrence of death or myocardial infarction. Total perfusion defect (TPD) at rest, stress, and ejection fraction were quantified automatically by software. ITPD was given by stressTPD-restTPD. Cox proportional hazards model was used to evaluate the association between ITPD versus MACE-free survival and expressed as a hazard ratio. In 10614 men and 7219 women, with a median follow-up of 4.75 years (interquartile range, 3.7-6.1), there were 1709 MACE. In a multivariable Cox model, after adjusting for revascularization and other confounding variables, ITPD was associated with MACE (hazard ratio, 1.08 [95% CI, 1.05-1.1]; P<0.001). There was an interaction between ITPD and sex (P<0.001); predicted survival for ITPD<5% was worse among men compared to women, whereas survival among women was worse than men for ITPD≥5%, P<0.001. In the international, multicenter REFINE SPECT registry, moderate and severe ischemia as quantified by ITPD from high-efficiency SPECT is associated with a worse prognosis in women compared with men.

Mortality and pulmonary complications in emergency general surgery patients with COVID-19: A large international multicenter study.

The outcomes of emergency general surgery (EGS) patients with concomitant COVID-19 infection remain unknown. With a multicenter study in 361 hospitals from 52 countries, we sought to study the mortality and pulmonary complications of COVID-19 patients undergoing EGS. All patients 17 years or older and diagnosed preoperatively with COVID-19 between February and July 2020 were included. Emergency general surgery was defined as the urgent/emergent performance of appendectomy, cholecystectomy, or laparotomy. The main outcomes were 30-day mortality and 30-day pulmonary complications (a composite of acute respiratory distress syndrome, unexpected mechanical ventilation, or pneumonia). Planned subgroup analyses were performed based on presence of preoperative COVID-related respiratory findings (e.g., cough, dyspnea, need for oxygen therapy, chest radiology abnormality). A total of 1,045 patients were included, of which 40.1% were female and 50.0% were older than 50 years; 461 (44.1%), 145 (13.9%), and 439 (42.0%) underwent appendectomy, cholecystectomy, and laparotomy, respectively. The overall mortality rate was 15.1% (158 of 1,045 patients), and the overall pulmonary complication rate was 32.9% (344 of 1,045 patients); in the subgroup of laparotomy patients, the rates were 30.6% (134 of 438 patients) and 59.2% (260 of 439 patients), respectively. Subgroup analyses found mortality and pulmonary complication risk to be especially increased in patients with preoperative respiratory findings. COVID-19 patients undergoing EGS have significantly high rates of mortality and pulmonary complications, but the risk is most pronounced in those with preoperative respiratory findings. Prognostic and Epidemiologic; Level IV.

Impact of Dose Reduction Strategies on Image Quality of Coronary CTA in Real-World Clinical Practice: A Subanalysis of PROTECTION VI Registry Data.

BACKGROUND. Dose reduction strategies for coronary CTA (CCTA) have been underused in clinical practice given concern that the strategies may lower image quality. OBJECTIVE. The purpose of this study was to explore associations between dose reduction strategies and CCTA image quality in real-world clinical practice. METHODS. This subanalysis of the international Prospective Multicenter Registry on Radiation Dose Estimates of Cardiac CT Angiography in Daily Practice in 2017 (PROTECTION VI) study included 3725 patients (2109 men, 1616 women; median age, 59 years) who underwent CCTA for coronary artery evaluation performed at 55 sites in 32 countries. CCTA image sets were reviewed at a core laboratory. A range of patient and scan characteristics, including use of three dose reduction strategies (prospective ECG triggering, low tube potential, and iterative image reconstruction) and image dose, were recorded. A single core laboratory member reviewed all examinations for quantitative image quality measures, including signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), and reviewed 50% of examinations to assign a qualitative CCTA image quality score and a semiquantitative coronary calcification measure. Multivariable logistic regression models were used to identify predictors of image quality. A second core laboratory member repeated quantitative measures for 100 examinations and the qualitative measure for 383 (approximately 20%) examinations to assess interreader agreement. RESULTS. Independent predictors (p < .05) of SNR were female sex (effect size, 2.70), lower body mass index (0.38 per 1-unit decrease), stable sinus rhythm (1.71), and scanner manufacturer (variable effect across manufacturers). These factors were also the only independent predictors of CNR. Independent predictors (p < .05) of CCTA image quality were heart rate (0.17 per 10 beats/min reduction) and coronary calcification (0.15 per coronary calcification grade). None of the three dose-saving strategies or dose-length product was an independent predictor of any image quality measure. Interreader agreement analysis showed intraclass correlation coefficients of 0.874 for SNR and 0.891 for CNR and a kappa value of 0.812 for the qualitative score. CONCLUSION. This large international multicenter study shows that three dose reduction strategies were not associated with decreased CCTA image quality. CLINICAL IMPACT. The dose reduction strategies should be routinely implemented in clinical CCTA.

Drainage of pancreatic fluid collections using a lumen-apposing metal stent with an electrocautery-enhanced delivery system.

Our aim was to evaluate the efficacy and safety of a lumen-apposing metal stent with an electrocautery-enhanced delivery system (EDS-LAMS) for endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFCs) in regular clinical practice. A retrospective and subsequent prospective analysis was undertaken of all patients who underwent EUS-guided drainage of their PFCs using the EDS-LAMS at 17 tertiary therapeutic endoscopy centers. Two hundred eight cases of EDS-LAMS deployment were attempted in 202 patients (mean age 52.9years) at time of evaluation. Ninety-seven patients had pancreatic pseudocysts (PPs), 75 walled-off pancreatic necrosis (WOPN), 10 acute peripancreatic fluid collections (APFCs), 6 acute necrotic collections (ANCs), and 14 postoperative collections (POCs). Procedural technical success was achieved in 202/208 cases (97.1%). Maldeployment occurred in 7/208 cases (3.4%). Clinical success was achieved in 142/160 (88.8%) patients (PP 90%, WOPN 85.2%, APFC 100%, ANC 75%, POC 100%). Delayed adverse events included stent migration in 15/202 (7.4%), stent occlusion and infection in 16/202 (7.9%), major bleeding in 4/202 (2%), and buried EDS-LAMS in 2/202 (1%). PFC recurrence occurred in 13/142 (9.2%) patients; 9/202 (4.5%) required surgical or radiological intervention for PFC management after EDS-LAMS insertion. This large international multicenter study evaluating the EDS-LAMS for drainage of PFCs in routine clinical practice suggests that the EDS-LAMS are safe and effective for drainage of all types of PFCs; however, further endoscopic therapy is often required for WOPN. Major bleeding was a rare complication in our cohort.

Evaluation of the association of heterozygous germline variants in NTHL1 with breast cancer predisposition: an international multi-center study of 47,180 subjects

Bi-allelic loss-of-function (LoF) variants in the base excision repair (BER) gene NTHL1 cause a high-risk hereditary multi-tumor syndrome that includes breast cancer, but the contribution of heterozygous variants to hereditary breast cancer is unknown. An analysis of 4985 women with breast cancer, enriched for familial features, and 4786 cancer-free women revealed significant enrichment for NTHL1 LoF variants. Immunohistochemistry confirmed reduced NTHL1 expression in tumors from heterozygous carriers but the NTHL1 bi-allelic loss characteristic mutational signature (SBS 30) was not present. The analysis was extended to 27,421 breast cancer cases and 19,759 controls from 10 international studies revealing 138 cases and 93 controls with a heterozygous LoF variant (OR 1.06, 95% CI: 0.82–1.39) and 316 cases and 179 controls with a missense variant (OR 1.31, 95% CI: 1.09–1.57). Missense variants selected for deleterious features by a number of in silico bioinformatic prediction tools or located within the endonuclease III functional domain showed a stronger association with breast cancer. Somatic sequencing of breast cancers from carriers indicated that the risk associated with NTHL1 appears to operate through haploinsufficiency, consistent with other described low-penetrance breast cancer genes. Data from this very large international multicenter study suggests that heterozygous pathogenic germline coding variants in NTHL1 may be associated with low- to moderate- increased risk of breast cancer.

Oncological outcome after minimally-invasive or open pancreatoduodenectomy for pancreatic cancer: an international propensity-score matched study

Introduction: Minimally-invasive pancreatoduodenectomy (MIPD) has been suggested as an alternative to open pancreatoduodenectomy (OPD). However, large international multicenter studies comparing oncological outcome after MIPD and OPD for pancreatic cancer are lacking.

Validation of the Canadian syncope risk score in a large prospective international multicenter study

Abstract Background Management and risk stratification of patients with syncope in the emergency department (ED) is often challenging. In an effort to support ED physicians in disposition decisions, the Canadian Syncope Risk Score (CSRS) was developed to predict 30-day serious outcomes. Methods The CSRS was developed in a Canadian multicenter study and contains nine predictors: predisposition to vasovagal syncope, heart disease, systolic pressure &amp;lt;90 or &amp;gt;180mmHg in the ED, troponin level &amp;gt;99th percentile, abnormal QRS axis, QRS duration &amp;gt;130ms, QTc interval &amp;gt;480ms and an ED diagnosis of vasovagal or cardiac syncope. Patients can achieve a CSRS score between −3 and +11 points. We validated the CSRS in a large prospective international multicenter study recruiting patients 40 years or older presenting to the ED with a syncopal event within the last 12 hours. Recruitment centers contained smaller provincial hospitals, as well as big University Hospitals in eight countries on three continents. Primary outcome measure were 30-day serious arrhythmic and non-arrhythmic adverse events, as defined by the authors of the original score. Results 1581 patients were eligible for this analysis. The population in this validation cohort was older (mean age 68 vs 54 years) and had a considerably higher rate of serious outcomes compared to the derivation cohort (n=186 (11.8%) vs n=147 (3.6%)). The area under the receiver operating characteristic curve (AUC) for the CSRS was 0.88 (95% confidence interval (CI) 0.86–0.91) and significantly higher compared to the validated OESIL score (AUC 0.75, 95% CI 0.71–0.78, p&amp;lt;0.001). Calibration curve analysis showed an underestimation of risk in patients with a low CSRS and an overestimation in patients with a high CSRS. The rate of observed serious outcomes within 30d increased from 0.8% in the very low risk group (CSRS equal to or below −2) to 48% in the (very) high risk group (CSRS equal to or above 4, Hazard ratio 79.4, 95% CI 11.1–570.9). A Kaplan-Meier plot was used to visualize rates of serious outcomes in three different risk groups (Figure). Conclusion This is the first validation of the Canadian Syncope Risk Score in a large international syncope cohort. The prognostic discrimination of the CSRS for 30-day serious outcomes was very good in our validation cohort and comparable to that of the Canadian derivation study. Despite suboptimal calibration, prognostic analysis showed a high rate of serious outcomes in the CSRS (very) high risk group and a low rate of serious outcomes in the very low risk group. Allowing the clinical judgement of the ED physician in the form of suspected syncope etiology to be a part of the score seems to largely contribute to the high performance of the CSRS. Additional validation studies might be needed to further increase the accuracy of the CSRS in different patient populations with a different incidence of outcomes in settings outside of Canada. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation; Swiss Heart Foundation

Validation of the FAINT risk score in a large prospective international multicenter study

Abstract Background Risk stratification of older patients presenting to the Emergency Department (ED) with syncope remains an unmet clinical need. The FAINT Score was derived in a large American cohort in an attempt to predict 30-day serious cardiac outcomes in patients &amp;gt;60y.o. While a FAINT score of 0 showed high sensitivity to exclude death and serious outcomes at 30 days in the derivation cohort, it remains unvalidated. Methods We validated the FAINT score (History of heart failure, history of arrhythmia, initial ECG result abnormal, elevate NT-proBNP, elevated hs-troponin T) in a large prospective international multicenter study recruiting patients 40 years presenting to the ED with syncope within the last 12 hours in eight countries on three continents. Main outcome measure was 30-day serious cardiac events or mortality. We assessed the performance and calibration of the FAINT score for validation and compared it to the OESIL score (Age &amp;gt;64y, cardiovascular disease history, syncope without prodromes, abnormal ECG). Results 1885 patients were eligible for this validation analysis. 169 (8.9%) patients experienced 30-day serious adverse events. A FAINT score of 0 was present for 378 patients (20% of the cohort) and allowed for a sensitivity of 0.97 to rule out adverse events and death at 30-days. A FAINT score of 0 or 1 was present for 626 patients (33% of the cohort) and allowed for a sensitivity of 0.92. The area under the receiver operating characteristic curve (AUC) for the FAINT score was 0.75 (95%, Confidence Interval (CI) 0.72–0.79), which was comparable to the performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) or high-sensitivity Troponin T (hs-cTnT) alone, which are two biomarkers used in the FAINT score. The score did not outperform the OESIL score. A calibration curve showed that the score was extremely well calibrated for low-risk patients. Conclusion This is the first validation of the FAINT score in a large international syncope cohort. The safety of a FAINT score of 0 or 1 was good and comparable to the results obtained in the derivation cohort. While the score is suitable to highlight low-risk patients and calibrates well in an external cohort, its discrimination for higher risk patients is not better than biomarkers alone or an older, less complex risk score. Figure 1. Area under the Receiver Operating Curve (ROC) for the FAINT score and for NT-proBNP and hs-cTnT as continuous markers as well as for the OESIL score. CI = Confidence Interval. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): University Hospital Basel, Switzerland

Incidence, characteristics, determinants and prognostic impact of recurrent syncope

Abstract Background The incidence, characteristics, determinants, and prognostic impact of recurrent syncope are largely unknown, causing uncertainty for both patients and physicians. Methods We characterized recurrent syncope including sex-specific aspects and its impact on death and major adverse cardiovascular events (MACE) in a large prospective international multicenter study enrolling patients ≥40 years presenting with syncope to the emergency department (ED). Syncope etiology was centrally adjudicated by two independent and blinded cardiologists using all information becoming available during syncope work-up and 12-month follow-up. MACE were defined as a composite of all-cause death, acute myocardial infarction, surgical or percutaneous coronary intervention, life-threatening arrhythmia including cardiac arrest, pacemaker or implantable cardioverter defibrillator implantation, valve intervention, heart-failure, gastrointestinal bleeding or other bleeding requiring transfusion, intracranial hemorrhage, ischemic stroke or transient ischemic attack, sepsis and pulmonary embolism. Results Incidence of recurrent syncope among 1790 patients was 20% (95%-confidence interval (CI) 18% to 22%) within 24 months. Patients with an adjudicated final diagnosis of cardiac syncope (hazard ratio (HR) 1.50, 95%-CI 1.11 to 2.01) or syncope of unknown etiology even after central adjudication (HR 2.11, 95%-CI 1.54 to 2.89) had an increased risk for syncope recurrence (Figure). LASSO regression fit on all patient information available early in the ED identified more than three previous episodes of syncope as the only independent predictor for recurrent syncope (HR 2.13, 95%-CI 1.64 to 2.75). Recurrent syncope within the first 12 months after the index event carried an increased risk for all-cause death (HR 1.59, 95%-CI 1.06 to 2.38) and MACE (HR 2.24, 95%-CI 1.67 to 3.01), whereas recurrences after 12 months did not have a significant impact on outcome measures. Conclusion Recurrence rates of syncope are substantial and vary depending on syncope etiology. There seem to be no reliable patient characteristics available early on the ED that allow for the prediction of recurrent syncope with only a history of more than three previous syncope being associated with a higher risk for future recurrences. Importantly, recurrent syncope within the first 12 months carries an increased risk for death and MACE. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation, Swiss Heart Foundation

Application of the ESC and AHA guidelines for admission of syncope patients presenting to the ED

Abstract Background Syncope in the ED is linked with high diagnostic and prognostic uncertainty, leading to an extremely high rate of admissions. These often inappropriate admissions are costly and expose patients to unnecessary testing. The recent ESC and AHA guidelines aim at reducing these admissions by stratifying patients in high- and low-risk groups. Methods The BASEL IX Syncope study is a large prospective international multicenter study recruiting patients 40 years presenting to the ED with syncope within the last 12 hours in eight countries on three continents. Cardiac syncope was centrally adjudicated by two physicians using all data collected up to 1-y follow-up. We classified patients as requiring admission or being judged safe for discharge according to the ESC and AHA guidelines criteria and compared these with the physician's decision regarding hospitalization. We assessed the consequence of these decisions on 30-day serious cardiac events and mortality. We validated our findings in a large American cohort recruiting syncope patients &amp;gt;60 years in 11 EDs. Results 1977 patients were eligible for this analysis. 215 (10.8%) experienced 30-day Major Adverse Cardiovascular Events (MACE). The ESC and AHA guidelines would have admitted a largely different number of patients (75.9% vs 29.6%) and provided different safety regarding adverse events and death at 30 days (Figure). The validation in the US cohort provided similar results, however US ED physicians decided to admit more patients (84%) as compared with the international derivation cohort (46.6%). Conclusion The AHA and ESC syncope guidelines recommend admission based on very different criteria and for a largely different number of patients. While the most recent ESC guidelines were written with the aim to limit the number of patients admitted, they still classify a large majority of an ED syncope cohort as high risk and warranting admission. The large discrepancy between the two guidelines is based on the criteria used for the classification: While the ESC guidelines consider risk factors, previous cardiac history, physical examination and ECG criteria, the AHA guidelines focus on serious conditions previously known or diagnosed in the ED. Figure: Percentage of the overall cohort admitted (green) or discharged (red) according to the AHA and ESC guidelines and to the decision of the physician in the BASEL-IX cohort. Patients experiencing a cardiac syncope, a 30-day MACE or death are represented for both the discharged and admitted groups. Figure 1 Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): University hospital Basel

Differences in responses to English and Korean versions of the Caregiver Priorities & Child Health Index of Life with Disabilities (CPCHILD)

BackgroundThe purpose of this study was to identify differences in caregiver responses to Korean-language and English-language versions of the Caregiver Priorities & Child Health Index of Life with Disabilities (CPCHILD) questionnaire.MethodsPatient data were acquired from the Cerebral Palsy Hip Outcomes Project database, which was established to run a large international multicenter prospective cohort study of the outcomes of hip interventions in cerebral palsy. Thirty-three children whose caregivers had completed the Korean version of CPCHILD were matched by propensity scoring with 33 children whose parents completed the English version. Matching was performed on the basis of 12 covariates: age, gender, gross motor function classification system level, migration percentage of right and hip, seizure status, feeding method, tracheostomy status, pelvic obliquity, spinal deformity, parental report of hip pain and contracture interfering with care.ResultsThere were no significant differences in CPCHILD scores for section 4 (Communication and Social Interaction), and section 5 (Health) between two groups. Korean-language CPCHILD scores were significantly lower than English-language CPCHILD scores for section 1 (Personal Care/Activities of Daily Living), section 2 (Positioning, Transferring and Mobility), section 3 (Comfort and Emotions) and section 6 (Overall Quality of Life) as well as in terms of total score.ConclusionsCultural influences, and the community or social environment may impact the caregivers’ perception of the health-related quality of life of their children. Therefore, physicians should consider these differences when interpreting the study outcomes across different countries.

Mechanical Ventilation for Acute Respiratory Distress Syndrome during Extracorporeal Life Support. Research and Practice.

Ventilator-induced lung injury remains a key contributor to the morbidity and mortality of acute respiratory distress syndrome (ARDS). Efforts to minimize this injury are typically limited by the need to preserve adequate gas exchange. In the most severe forms of the syndrome, extracorporeal life support is increasingly being deployed for severe hypoxemia or hypercapnic acidosis refractory to conventional ventilator management strategies. Data from a recent randomized controlled trial, a post hoc analysis of that trial, a meta-analysis, and a large international multicenter observational study suggest that extracorporeal life support, when combined with lower Vt and airway pressures than the current standard of care, may improve outcomes compared with conventional management in patients with the most severe forms of ARDS. These findings raise important questions not only about the optimal ventilation strategies for patients receiving extracorporeal support but also regarding how various mechanisms of lung injury in ARDS may potentially be mitigated by ultra-lung-protective ventilation strategies when gas exchange is sufficiently managed with the extracorporeal circuit. Additional studies are needed to more precisely delineate the best strategies for optimizing invasive mechanical ventilation in this patient population.

Long-term exposure to outdoor and household air pollution and blood pressure in the Prospective Urban and Rural Epidemiological (PURE) study

Exposure to air pollution has been linked to elevated blood pressure (BP) and hypertension, but most research has focused on short-term (hours, days, or months) exposures at relatively low concentrations. We examined the associations between long-term (3-year average) concentrations of outdoor PM2.5 and household air pollution (HAP) from cooking with solid fuels with BP and hypertension in the Prospective Urban and Rural Epidemiology (PURE) study. Outdoor PM2.5 exposures were estimated at year of enrollment for 137,809 adults aged 35–70 years from 640 urban and rural communities in 21 countries using satellite and ground-based methods. Primary use of solid fuel for cooking was used as an indicator of HAP exposure, with analyses restricted to rural participants (n = 43,313) in 27 study centers in 10 countries. BP was measured following a standardized procedure and associations with air pollution examined with mixed-effect regression models, after adjustment for a comprehensive set of potential confounding factors. Baseline outdoor PM2.5 exposure ranged from 3 to 97 μg/m3 across study communities and was associated with an increased odds ratio (OR) of 1.04 (95% CI: 1.01, 1.07) for hypertension, per 10 μg/m3 increase in concentration. This association demonstrated non-linearity and was strongest for the fourth (PM2.5 > 62 μg/m3) compared to the first (PM2.5 < 14 μg/m3) quartiles (OR = 1.36, 95% CI: 1.10, 1.69). Similar non-linear patterns were observed for systolic BP (β = 2.15 mmHg, 95% CI: −0.59, 4.89) and diastolic BP (β = 1.35, 95% CI: −0.20, 2.89), while there was no overall increase in ORs across the full exposure distribution. Individuals who used solid fuels for cooking had lower BP measures compared to clean fuel users (e.g. 34% of solid fuels users compared to 42% of clean fuel users had hypertension), and even in fully adjusted models had slightly decreased odds of hypertension (OR = 0.93; 95% CI: 0.88, 0.99) and reductions in systolic (−0.51 mmHg; 95% CI: −0.99, −0.03) and diastolic (−0.46 mmHg; 95% CI: −0.75, −0.18) BP. In this large international multi-center study, chronic exposures to outdoor PM2.5 was associated with increased BP and hypertension while there were small inverse associations with HAP.

2409ALERT-CS - Development of an ECG-based cardiac syncope risk calculator

Abstract Background Syncope is a common symptom with rising incidence, often leading to emergency department (ED) visits. Early determination of diagnosis is often difficult in patients with syncope and there is an unmet clinical need for tools that can support physicians in their decision making. We hypothesized that an electrocardiogram (ECG)-based cardiac syncope risk calculator might create a simple and attractive clinical decision tool for the diagnosis and risk stratification of patients with syncope. Methods Based on a large prospective diagnostic international multicenter study enrolling patients who presented to the ED with syncope, we derived a cardiac syncope risk calculator by penalized stepwise backward-selection and multivariable logistic regression utilizing predefined ECG criteria. Primary diagnostic endpoint was cardiac syncope, as adjudicated by two independent physicians taking into account all available information including cardiac work-up and 12-month follow-up. Major adverse cardiac events (MACE) including life-threatening arrhythmias, myocardial infarction, pulmonary embolism, stroke, transient ischemic attack, valvular surgery, and death within 30 days were the prognostic endpoint. Results Median age in our cohort was 71 years and 40% of patients were women. Of all 2007 patients enrolled, 1696 patients were eligible for the prognostic analysis and 1550 patients were eligible for the diagnostic analysis. We identified seven ECG criteria (rhythm, heart rate, corrected QT-interval, ST-segment depression, atrioventricular-block, bundle-branch-block and ventricular extrasystole/non-sustained ventricular tachycardia) as significant predictors for cardiac syncope and combined them into the bAseL Ecg Risk calculaTor for Cardiac Syncope (ALERT-CS). Diagnostic accuracy for cardiac syncope, as quantified by the area under the receiver operating characteristic curve (AUC), was high (AUC 0.80, 95%-confidence interval (CI) 0.77 to 0.83), and significantly higher compared to that of the EGSYS score (AUC 0.73, 95%-CI 0.70 to 0.76, p&lt;0.001). Prognostic verification of the ALERT-CS to predict 30-day overall MACE showed similar accuracy (AUC 0.75, 95%-CI 0.71 to 0.79). Comparison of diagnostic discrimination Conclusion Combining seven ECG criteria within a simple risk calculator for cardiac syncope may aid physicians in the diagnosis and risk stratification of patients presenting to the ED with syncope. Acknowledgement/Funding Swiss National Science Foundation, Swiss Heart Foundation, Cardiovascular Research Foundation Basel, University Basel

Lumen apposing metal stents are superior to plastic stents in pancreatic walled-off necrosis: a large international multicenter study.

Background and study aims The use of lumen apposing metal stents (LAMS) during EUS-guided transmural drainage (EUS-TD) of pancreatic walled-off necrosis (WON) has gained popularity. Data supporting their use in WON over plastic stents (PS), however, remain scarce. The aim of this study was to compare the clinical efficacy of LAMS (Axios, Boston Scientific) with PS in WON. Patients and methods This was a multicenter, retrospective study involving 14 centers. Consecutive patients who underwent EUS-TD of WON (2012 – 2016) were included. The primary end point was clinical success defined as WON size ≤ 3 cm within a 6-month period without need for percutaneous drainage (PCD) or surgery. Results A total of 189 patients (mean age 55.2 ± 15.6 years, 34.9 % female) were included (102 LAMS and 87 PS). Technical success rates were similar: 100 % in LAMS and 98.9 % in PS ( P = 0.28). Clinical success was attained in 80.4 % of LAMS and 57.5 % of PS ( P = 0.001). Rate of PCD was similar (13.7 % LAMS vs. 16.3 % PS, P = 0.62), while PS was associated with a greater need for surgery (16.1 % PS vs. 5.6 % LAMS, P = 0.02). Adverse events (AEs) were observed in 9.8 % of LAMS and 10.3 % of PS ( P = 0.90) and were rated as severe in 2.0 % and 6.9 %, respectively ( P = 0.93). After excluding patients with < 6 months follow-up, the rate of WON recurrence following initial clinical success was greater with PS (22.9 % PS vs. 5.6 % LAMS, P = 0.04). Conclusions When compared to PS, LAMS in WON is associated with higher clinical success, shorter procedure time, lower need for surgery, and lower rate of recurrence.