Occurrence Of Death Research Articles

Umbilical Cord Blood IgA Levels and Bacterial Profile in Preterm Neonates Born with Maternal Risk Factors for Early-Onset Neonatal Sepsis.

To investigate the IgA levels and bacterial profile in umbilical cord blood (UCB) samples of mothers with risk factors compared to those without risk factors; and to understand the link between UCB culture positivity and neonatal outcomes [early-onset sepsis (EOS) or death within 7 d of life]. This is a pilot prospective case-control study. Mothers with preterm deliveries (gestational age <34 wk) were enrolled in two groups- Cases: Those with antenatal risk factors (prolonged duration of rupture of membranes of ≥24h or chorioamnionitis) and controls: Those without these two risk factors. Serum IgA levels was assayed and microbiological culture was tested in UCB samples. 16S sequencing to determine the UCB microbiome was performed in a subset of samples (n = 15). Neonates were followed-up for the occurrence of EOS or death until 7 d of life. Forty-nine mothers as cases and 50 mothers as controls were consecutively enrolled. No significant difference was observed in the IgA levels (60.5 vs. 58.1mg/L; p = 0.71), neonatal blood culture positivity (4.1% vs. 8.0%; p = 0.41) and UCB culture positivity (30.6% vs. 26.0%; p = 0.61) in the two groups.No difference was observed between the groups in occurrence of EOS or death within 7 d of life. Proteobacteria, Firmicutes and Actinobacteria were the most abundant phyla. Serratia, Bifidobacterium, Collinsella, Meganomas and Blautia being the most common genera. Cord blood IgA concentration could not differentiate the neonates at-risk of infection due to its presence in both the groups.

A Pilot Study Omitting Radiation in the Treatment of Children with Newly Diagnosed Wnt-Activated Medulloblastoma.

Treatment of wingless (WNT)-activated medulloblastoma (WNT+MB) with surgery, irradiation (XRT), and chemotherapy results in excellent outcomes. We studied the efficacy of therapy de-intensification by omitting XRT entirely in children with WNT+MB. Tumors were molecularly screened to confirm the diagnosis of WNT+MB. Eligible children were treated within 31 days following surgery with nine cycles of adjuvant chemotherapy per ACNS0331. No XRT was planned. The primary endpoint was the occurrence of relapse, progression, or death in the absence of XRT within the first two years after study enrollment. Four events in the first 10 evaluable patients would result in early study closure. Fourteen children were prescreened, and nine met the protocol definition of WNT+MB. Six of the nine eligible patients consented to protocol therapy, and five completed planned protocol therapy. The first two children enrolled relapsed shortly after therapy completion with local and leptomeningeal recurrences. The study was closed early due to safety concerns. Both children are surviving after XRT and additional chemotherapy. A third child relapsed at completion of therapy but died of progressive disease 35 months from diagnosis. Two children finished treatment but immediately received post-treatment XRT to guard against early relapse. The final child's treatment was aborted in favor of a high-dose therapy/stem cell rescue approach. Although OS at 5 years is 83%, no child received only planned protocol therapy, with all receiving eventual XRT and/or alternative therapy. Radiotherapy is required to effectively treat children with WNT-altered medulloblastoma. See related commentary by Gottardo and Gajjar, p. 4996.

Ferroptosis-Like Death in Microorganisms: A Novel Programmed Cell Death Following Lipid Peroxidation.

Ferroptosis is a new kind of programmed cell death of which occurrence in microorganisms is not clearly verified. The elevated level of reactive oxygen species (ROS) influences cellular metabolisms through highly reactive hydroxyl radical formation under the iron-dependent Fenton reaction. Iron contributes to ROS production and acts as a cofactor for lipoxygenase to catalyze poly unsaturated fatty acid (PUFA) oxidation, exerting oxidative damage in cells. While ferroptosis is known to take place only in mammalian cells, recent studies discovered the possible ferroptosis-like death in few specific microorganisms. Capacity of integrating PUFA into intracellular membrane phospholipid has been considered as a key factor in bacterial or fungal ferroptosis-like death. Vibrio species in bacteria and Saccharomyces cerevisiae in fungi exhibited certain characteristics. Therefore, this review focus on introducing the occurrence of ferroptosis-like death in microorganisms and investigating the mode of action underlying the cells based on contribution of lipid peroxidation and iron-dependent reaction.

Whole-transcriptome analysis reveals virulence-specific pathogen-host interactions at the placenta in bovine neosporosis.

Research on bovine neosporosis has achieved relevant milestones, but the mechanisms underlying the occurrence of foetal death or protection against foetal death remain unclear. In a recent study, placentas from heifers challenged with the high-virulence isolate Nc-Spain7 exhibited focal necrosis and inflammatory infiltrates as soon as 10 days post-infection (dpi), although parasite detection was minimal. These lesions were more frequent at 20 dpi, coinciding with higher rates of parasite detection and the occurrence of foetal death in some animals. In contrast, such lesions were not observed in placentas from animals infected with the low-virulence isolate Nc-Spain1H, where the parasite was detected only in placenta from one animal at 20 dpi. This work aimed to study which mechanisms are triggered in the placentas (caruncles and cotyledons) of these pregnant heifers at early stages of infection (10 and 20 dpi) through whole-transcriptome analysis. In caruncles, infection with the high-virulence isolate provoked a strong proinflammatory response at 10 dpi. This effect was not observed in heifers infected with the low-virulence isolate, where IL-6/JAK/STAT3 signalling and TNF-alpha signalling via NF-κB pathways were down-regulated. Interestingly, the expression of E2F target genes, related to restraining the inflammatory response, was higher in these animals. At 20 dpi, more pronounced proinflammatory gene signatures were detectable in heifers infected with the high-virulence isolate, being more intense in heifers carrying dead fetuses. However, the low-virulence isolate continued without activating the proinflammatory response. In cotyledons, the response to infection with the high-virulence isolate was similar to that observed in caruncles; however, the low-virulence isolate induced mild proinflammatory signals at 20 dpi. Finally, a deconvolutional analysis of gene signatures from both placentome tissues revealed a markedly higher fraction of activated natural killers, M1 macrophages and CD8+ T cells for the high-virulence isolate. Therefore, our transcriptomic analysis supports the hypothesis that an intense immune response probably triggered by parasite multiplication could be a key contributor to abortion. Further studies are required to determine the parasite effectors that govern the distinct interactions of high- and low-virulence isolates with the host, which could help elucidate the molecular processes underlying the pathogenesis of neosporosis in cattle.

Heart Rate Recovery as a Predictor of Long-Term Adverse Events after Negative Exercise Testing in Patients with Chest Pain and Pre-Test Probability of Coronary Artery Disease from 15% to 65.

The prognosis of patients with chest pain after a negative exercise test is good, but some adverse events occur in this low-risk group. The aim of our study was to identify predictors of long-term adverse events after a negative exercise test in patients with chest pain and a lower intermediate (15-65%) pre-test probability of coronary artery disease (CAD) and to assess the prognostic value of exercise electrocardiography and exercise stress echocardiography in this group of patients. We identified from our stress test laboratory database 862 patients with chest pain without previously known CAD and with a pre-test probability of CAD ranging from 15 to 65% (mean 41 ± 14%) who underwent exercise testing. Patients were followed for the occurrence of death, non-fatal myocardial infarction (MI) and clinically guided revascularization. During the median follow-up of 94 months, 87 patients (10.1%) had an adverse event (AE). A total of 30 patients died (3.5%), 23 patients suffered non-fatal MI (2.7%) and 34 patients (3.9%) had clinically guided revascularization (20 patients percutaneous and 14 patients surgical revascularizations). Male gender, age, the presence of diabetes and a slow heart rate recovery (HRR) in the first minute after exercise were independently related to the occurrence of AEs. Adverse events occurred in 10.3% of patients who were tested by exercise stress echocardiography and in 10.0% of those who underwent stress electrocardiography (p = 0.888). The risk of AEs after negative exercise testing in patients with a pre-test probability of CAD of 15-65% is low. Male patients with a history of diabetes and slow HRR in the first minute after exercise have an increased risk of an adverse outcome.

The Effect of Age-Threshold on COVID-19 Patients Cure Rate: A Historical Cohort Study

Background: The COVID-19 pandemic had caused unexpected strain on healthcare systems in most countries in 2020. Although different survival models were used in clinical decision-making for COVID-19 patients, the effect of different risk factors in patients has not been identified clearly. Elderly patients, especially with comorbidities, were introduced as the most susceptible group at the risk of death. This study aimed to determine the threshold of age that influences chronic diseases and other factors that increase the cure rate of COVID-19 patients. Methods: This observational study was conducted at Shahid Sadoughi hospital in Yazd, Iran. All participants were older than 18 years old with confirmed COVID-19 and completed the day-30 and day-180 follow-ups. The Bayesian method was used through the cure rate models, practical models in survival with a single change-point to detect the threshold of age, illustrating each risk factor’s effect on the cure rate of patients. Results: The analysis included 901 confirmed COVID-19 cases with a mean age of 54.93±17.37 years. From all, 58.7% (n=529) were men and 9.9% (n=83) death occurrences were recorded. Sixty-five years of age was estimated as the effective changepoint that could change the cure rate of patients at the end of the follow-up times. Conclusion: The cure rate at any time during 30 and 180 follow-up days was noticeably higher in COVID-19 patients younger than 65 years who had cancer.

Myocarditis during SARS-CoV-2 Infection: A Series of 15 Cases

COVID-19 is a global health problem responsible for significant morbidity and mortality and a major socioeconomic impact. While the major manifestation is respirator with a risk of acute respiratory distress syndrome, several extrapulmonary aspects, particularly cardiovascular, have emerged over time.&#x0D; The aim of this work is to study the clinical, biological, radiological, therapeutic, and evolutionary characteristics of acute myocarditis associated with SARS-CoV-2 infection in comparison to data from the literature.&#x0D; This is a prospective cohort study conducted at the Ibn Sina University Hospital in Rabat over a period of 9 months (from January 1, 2021, to September 30, 2021) and included patients hospitalized in different departments managing COVID-19 and diagnosed with acute myocarditis confirmed by cardiac MRI.&#x0D; Fifteen patients were included during the study period. The average age of patients was 40 years old with a slight male predominance (sex ratio M/F-1.14). The average time between the onset of COVID-19 infection and the appearance of myocarditis symptoms was 17 days. The symptoms were mainly dominated by chest pain (40% of cases), unexplained cardiogenic shock (40% of cases), and palpitations (20% of cases). ECG revealed diffuse repolarization abnormalities in more than half of the cases (53%) and supraventricular tachycardia (27%). The inflammatory markers were significantly disturbed (CRP = 102 +/-47.30 mg/L and ferritin - 510 +/-336.45 ng/mL). Troponin I was elevated with myocarditis kinetics in all patients. Cardiac MRI showed T2 hypersignal corresponding to edema with early and late subepicardial enhancement, mainly located at the level of the left ventricular lateral wall.&#x0D; The evolution was marked by the occurrence of death in 5 patients (33.33%) in the days following hospitalization for cardiogenic shock and dilated cardiomyopathy in only one case (6.67%). It was favourable for the rest of the patients (60%).&#x0D; The results of this study have highlighted several characteristics of myocarditis associated with SARS-CoV-2. Firstly, there is a delayed interval between virus infection and the onset of cardiac symptoms. Additionally, the kinetics of myocardial injury markers are distinct, and there is significant disruption of inflammatory markers at the time of diagnosis. Moreover, fulminant forms of myocarditis are associated with a reserved prognosis and high mortality.&#x0D; Furthermore, the study emphasizes the crucial importance of cardiac MRI availability for confirming the diagnosis in the absence of histological evidence from endomyocardial biopsy.

Arrhythmias and Clinical Outcomes in a Swiss Multicenter Cohort of Patients With Dextro-Transposition of the Great Arteries and Atrial Switch.

Background Data on the incidence of arrhythmias, associated cardiac interventions, and outcome in patients with dextro-transposition of the great arteries and atrial switch are scarce. Methods and Results In this multicenter analysis, we included adult patients with dextro-transposition of the great arteries and atrial switch regularly followed up at 3 Swiss tertiary care hospitals. The primary outcome was a composite of left ventricular assist device, heart transplantation, and death. The secondary outcome was occurrence of ventricular tachycardia, ventricular fibrillation, or sudden cardiac death. We identified 207 patients (34% women; median age at last follow-up, 35 years) with dextro-transposition of the great arteries and atrial switch. Arrhythmias occurred in 97 patients (47%) at a median age of 22 years. A pacemaker or an implantable cardioverter-defibrillator was implanted in 39 (19%) and 13 (6%) patients, respectively, and 33 (16%) patients underwent a total of 51 ablation procedures to target 60 intra-atrial re-entry tachycardias, 4 atrioventricular nodal re-entry tachycardias, and 1 atrial fibrillation. The primary outcome occurred in 21 patients (10%), and the secondary outcome occurred in 18 patients (9%); both were more common in patients with concomitant ventricular septum defect than in those without (hazard ratio [HR], 3.06 [95% CI, 1.29-7.27], P=0.011; and HR, 3.62 [95% CI, 1.43-9.18], P=0.007, respectively). Conclusions In patients with dextro-transposition of the great arteries and atrial switch reaching adulthood, arrhythmias occur in almost half of patients, and associated rhythm interventions are frequent. One-tenth of those patients do not survive until the age of 35 years free from left ventricular assist device or heart transplantation, and the outcome is worse in patients with concomitant ventricular septum defect.

Left atrioventricular coupling index assessed using cardiac CT as a prognostic marker of cardiovascular death

PurposeThe purpose of this study was to investigate the prognostic value of left atrioventricular coupling index (LACI) assessed by cardiac computed tomography (CT), to predict cardiovascular death in consecutive patients referred for cardiac CT with coronary analysis. Materials and methodsBetween 2010 and 2020, we conducted a single-centre study with all consecutive patients without known cardiovascular disease referred for cardiac CT. LACI was defined as the ratio of left atrial to left ventricle end-diastolic volumes. The primary outcome was cardiovascular death. Cox regressions were used to evaluate the association between LACI and primary outcome after adjustment for traditional risk factors and cardiac CT angiography findings. ResultsIn 1,444 patients (mean age, 70 ± 12 [standard deviation] years; 43% men), 67 (4.3%) patients experienced cardiovascular death after a median follow-up of 6.8 (Q1, Q3: 5.9, 9.1) years. After adjustment, LACI was positively associated with the occurrence of cardiovascular death (adjusted hazard ratio [HR], 1.07 [95% CI: 1.05–1.09] per 1% increment; P < 0.001), and all-cause death (adjusted HR, 1.05 [95% CI: 1.03–1.07] per 1% increment; P <0.001). After adjustment, a LACI ≥ 25% showed the best improvement in model discrimination and reclassification for predicting cardiovascular death above traditional risk factors and cardiac CT findings (C-statistic improvement: 0.27; Nnet reclassification improvement = 0.826; Integrative discrimination index =0.209, all P < 0.001; likelihood-ratio-test, P < 0.001). ConclusionLACI measured by cardiac CT is independently associated with cardiovascular death and all-cause death in patients without known cardiovascular disease referred for cardiac CT, with an incremental prognostic value over traditional risk factors and cardiac CT findings.

Skin‐Adherent Elastomer‐Hydrogel Patch for Continuous 12‐Lead Cardiac Ambulatory Monitoring during Physical Activities

AbstractContinuous electrocardiography (ECG) monitoring is a necessity to prevent the sudden occurrence of cardiac events and premature death. Wearable bioelectronics provides the opportunity to realize noninvasive 12‐lead ambulatory monitoring for cardiovascular disease (CVD) detection and diagnosis. This work introduces a 12‐lead ECG patch that eliminates the issues associated with compliance, skin damage, and user‐discomfort encountered in conventional ECG sensors. The patch is safe, stretchable, and skin‐adherent with an adaptable design that allows for user‐friendly ECG monitoring. These can be attributed to the unique 3‐bridge patch structure, embedded liquid metal circuitry, and the wet‐adhesive polyacrylamide‐polydopamine‐tannic acid (PAM‐PDA‐TA) hydrogel. The hydrogel displays improved wet adhesiveness and biosafety for long‐term usage on deforming skin. The patch can acquire clean and consistent ECG signals with a higher signal‐to‐noise (SNR) ratio compared to commercial electrodes during both static and dynamic monitoring. The outstanding performance of the patch ascertains its potential for daily continuous ECG monitoring and remote diagnosis.

Additional prognostic value of fully-automatic Global Longitudinal Strain using machine learning

Abstract Funding Acknowledgements Type of funding sources: None. Background Several studies described the independent prognostic value of left ventricular global longitudinal strain (GLS) using cardiovascular magnetic resonance (CMR) to predict cardiovascular events. However, the potential interest of GLS using a fully automatic method assessed at rest during a stress CMR exam was not well established. Aim To assess the prognostic value of GLS to predict all-cause death using a fully automatic machine learning algorithm without human correction in consecutive patients referred for stress CMR. Methods Between 2016 and 2018, all consecutive patients referred for stress CMR were included and followed for the occurrence of all-cause death. A fully automatic machine learning algorithm was trained and validated unseen CMR studies (MAGNETOM Aera and Skyra, Siemens Healthcare, Erlangen, Germany) to assess the GLS from long-axis cine images acquired at rest. The algorithm combines multiple deep learning networks for detection and segmentation with an active contours approach. Cox regressions were performed to determine the prognostic value of GLS. Results Among 9,883 consecutive patients who underwent stress CMR between 2016 and 2018 retrospectively included, the automatic GLS was successfully computed in 9,638 (97.5%) patients (67% male, mean age 66±12 years). A total of 510 (5.3%) deaths were observed during a median (IQR) follow-up period of 4.5 (3.7–5.2) years. GLS, the presence of inducible ischemia and late gadolinium enhancement (LGE) were significantly associated with the occurrence of death (hazard ratio, HR: 1.22 [95% CI, 1.17–1.26]; HR: 2.23 [95% CI, 1.61–3.10]; and HR: 2.04 [95% CI, 1.41–2.95], respectively, all p&amp;lt;0.001). After adjustment for traditional risk factors, inducible ischemia and LGE, GLS was an independent predictor of a higher incidence of death (adjusted HR: 1.14 [95% CI, 1.08–1.20]). Automatic GLS showed an incremental prognostic value to predict death compared to traditional risk factors, inducible ischemia and LGE (C-statistic improvement: 0.05; NRI=0.146; IDI=0.244; all p&amp;lt;0.001). Conclusions Automatic GLS measured at rest has an incremental prognostic value to predict all-cause death above traditional risk factors, and other stress CMR parameters.

Incremental prognostic value of fully-automatic LVEF by stress CMR using machine learning

Abstract Funding Acknowledgements Type of funding sources: None. Background Although some recent reports showed that fully automated artificial intelligence (AI)-based left ventricular ejection fraction (LVEF) measured at stress has good performance, its prognostic value during a stress CMR exam to predict outcomes is not well established. Aim To determine in patients undergoing stress CMR whether fully automated AI-based LVEF (LVEF-AI) measured at stress can provide incremental prognostic value to predict death. Methods Between 2016 and 2018, we conducted a longitudinal study including all consecutive patients referred for vasodilator stress CMR. LVEF-AI was assessed using AI-algorithm combines multiple deep learning networks for LV segmentation. The primary outcome was all-cause death defined by the French National Registry of Death. Cox regression was used to evaluate the association of stress LVEF-AI with death after adjustment for traditional risk factors. Results In 9,712 patients (66±15 years, 67% men), there was an excellent correlation between stress LVEF-AI measurement and LVEF measured by expert (LVEF-expert) (r=0.94, p&amp;lt;0.001). Using Bland–Altman analysis, we found that the difference between the mean LVEF-expert and the LVEF-AI group was −0.1% (−0.066–0.067), that was not statistically significant (p = 0.46). Stress LVEF-AI was associated with death (median [IQR] follow-up 4.5 [3.7–5.2] years) before and after adjustment for risk factors (adjusted hazard ratio [HR], 0.84 [95% CI, 0.82–0.87] per 5% increment, p&amp;lt;0.001). Stress LVEF-AI had similar significant association with death occurrence compared with LVEF-expert. After adjustment, a lower stress LVEF-AI showed the greatest improvement in model discrimination and reclassification over and above traditional risk factors and stress CMR findings (C-statistic improvement: 0.11; NRI=0.250; IDI=0.049, all p&amp;lt;0.001; LR-test p&amp;lt;0.001), with a superior additional prognostic value than the LVEF-AI measured at rest. Conclusion AI-based fully automated LVEF measured at stress is independently associated with the occurrence of death in patients undergoing stress CMR, with an additional prognostic value above traditional risk factors, inducible ischemia and LGE.

Safety and incremental prognostic value of stress CMR in patients with known chronic kidney disease

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiovascular disease (CVD) is the main cause of mortality in patients with chronic kidney disease (CKD). Although several studies have demonstrated the consistently high prognostic value of stress cardiovascular magnetic resonance (CMR), its prognostic value in patients with CKD is not well established. We aimed to assess the safety and the incremental prognostic value of vasodilator stress perfusion CMR in consecutive symptomatic patients with known CKD. Methods Between 2008 and 2021, we conducted a bi-center longitudinal study with all consecutive symptomatic patients with known CKD, defined by estimated glomerular filtration rate (eGFR) between 30 and 60 ml/min/1.73 m2, referred for vasodilator stress CMR. All patients with eGFR &amp;lt;30 ml/min/1.73 m² (n=62) were excluded due the risk of nephrogenic systemic fibrosis. All patients were followed for the occurrence of major adverse cardiovascular events (MACE) defined as cardiac death or recurrent nonfatal myocardial infarction (MI). Cox regressions were used to determine the prognostic value of stress CMR parameters. Results Of 825 patients with known CKD (71.4±8.8 years, 70% men), 769 (93%) completed the CMR protocol, and among those 702 (91%) completed the follow-up (median follow-up 6.4 (4.0–8.2) years). Stress CMR was well tolerated without occurrence of death or severe adverse event related to the injection of gadolinium or nephrogenic systemic fibrosis case. The presence of inducible ischemia was associated with the occurrence of MACE (hazard ratio [HR] 12.50; 95% confidence interval [CI]: 7.50–20.8; p&amp;lt;0.001). In multivariable analysis, ischemia and late gadolinium enhancement were independent predictors of MACE (HR 15.5; 95% CI: 7.72 to 30.9; and HR:4.67 [95%CI: 2.83–7.68]; respectively, both p&amp;lt;0.001). After adjustment, stress CMR findings showed the best improvement in model discrimination and reclassification above traditional risk factors (C-statistic improvement: 0.13; NRI=0.477; IDI=0.049). Conclusions In patients with known CKD, stress CMR is safe and its findings have an incremental prognostic value to predict MACE over traditional risk factors.

Machine learning model including left ventricular strain analysis for sudden cardiac death prediction in hypertrophic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Background The excess mortality in hypertrophic cardiomyopathy (HCM) patients is mainly attributed to the occurrence of sudden cardiac death (SCD). The prediction of ventricular arrhythmias remains challenging and could be improved. Purpose This study evaluated the added predictive value of a machine learning-based model combining clinical and conventional imaging parameters with information from left ventricular strain analysis to predict SCD in patients with HCM. Methods A total of 434 HCM patients (65% men, mean age 56 years) were retrospectively included from two referral centers from two different countries and followed longitudinally (mean duration 6 years). Strain parameters were automatically extracted from the left ventricle longitudinal strain segmental curves of each patient and included in a Ridge Regression model alongside conventional clinical and imaging data. The composite endpoint included sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator therapy, aborted cardiac arrest, or sudden cardiac death. Results 34 patients (7.8%) met the endpoint with an incidence of ventricular arrhythmias of 0.9%/years. Among the 18 most discriminating parameters, 7 were derived from left ventricle longitudinal strain segmental curves analysis (figure 1). After n=200 rounds of cross-validation, the final model showed superior predictive performance compared to conventional models with a mean area under the curve (AUC) of 0.83 ± 0.8 compared with an AUC of 0.56 and 0.61 for the 2014 ESC risk score and the 2020 AHA/ACC model, respectively. Conclusion A machine learning model including automatically extracted left ventricular strain-derived parameters was superior in the prediction of sustained ventricular arrhythmias and SCD in patients with HCM compared to existing models. A machine learning model including left ventricle longitudinal strain analysis could improve SCD risk stratification in HCM patients.

تأثيرات مضاد الهستامين الدايفنهايدرامين في السمّية الحادة لمبيدات الحشرات الفوسفورية العضوية والكارباميتية لمختلف الدراسات على الحيوانات: تحليل ميتا

الملخص لمضاد الهستامين-1 الدايفنهايدرامين صفات مواجهة المستقبلات الكولينية المسكرينية، مما يؤهله لأن يعمل مضاداً لتأثيرات مبيدات الحشرات الفوسفورية العضوية والكارباميتية المثبّطة لإنزيم الكولين إستيريز في الإنسان والحيوان. وفي ضوء المنشورات العلمية العديدة التي تُبين الفائدة النوعية للدايفنهايدرامين في علاج التسمم بهذه المبيدات، مع بعض الاختلاف في فاعلية الدواء الترياقي أو العلاجي، تهدف هذه المراجعة إلى حصر الدراسات التي تناولت تأثيرات الدايفنهايدرامين في السمّية الحادة للمبيدات، وعرض تحليل ميتا لبيان الدلالة الإحصائية من هذا الدواء الذي يُحسب مضاداً نوعياً إضافياً مع الترياق الأساس الأتروبين. استخدمنا طريقة بريسما بحسب عناصر التقارير المفضلة للمراجعات المنهجية، وتحليل ميتا لمؤشرات التسمم بالمبيدات الحشرية في الحيوانات التي شملت على حدوث الموت وعلامات التسمم ومرتبة التسمم. وجرى حصر الدراسات وبياناتها من قواعد المعلومات التي تُفهرِس المنشورات العلمية، فضلاً عن الفحص اليدوي للمنشورات من الجامعات. وفي تحليل ميتا، استخدمنا برنامج محلل ميتا الحر لمجموعتين، والذي شمل رسم الغابة وحجم التأثير وهو الخطورة النسبية، وتحليل التباين، فضلاً عن تحليل حجب مجموعة واحدة. كما طبَّقنا برنامج (Meta-Essentials) لرسم مخطط القمع الذي يشمل حجم التأثير والخطأ القياسي، واختبار إيغر لتقييم أيّ تحيز نشر ذي دلالة إحصائية، مع تحليل التقليم والملء للدراسات المفقودة. بلغ عدد الدراسات المختارة 13، واحتوت على 16 تقريراً مختلفاً لمؤشرات التسمم بالمبيدات وتأثير الدايفنهايدرامين فيها. وأظهرت نتائج تحليل ميتا لكل مؤشر من مؤشرات التسمم أن الدايفنهايدرامين قلّل معنوياً من الخطورة النسبية للمبيدات الفوسفورية العضوية أو الكارباميتية، حيث بلغت هذه النسبة مع 95% فاصل الثقة 0.375 (0.261، 0.54) لموت الحيوانات، و0.399 (0.283، 0.563) لعلامات التسمم، و0.466 (0.363، 0.597) لمرتبة التسمم. وتباينت النسب المئوية لأوزان التقارير الواردة في الدراسات ما بين 1.713 و20.245% لتحليل الموت، وبين 1.612 و23.062% لعلامات التسمم، وبين 4.566 و13% لمرتبة التسمم. وبيَّن تحليل حجب مجموعة واحدة عدم تأثر حجم التأثير لمؤشرات التسمم، إذ كانت القيم قريبة من حجم التأثير عند حذف قيمة أيّ تقرير من تقارير الدراسات المشمولة في التحليل. وقد ظهر اختلاف معنوي ذو دلالة إحصائية في تحليل التباين لبيانات مرتبة التسمم، في حين لم يكن التباين معنوياً لبيانات الموت وعلامات التسمم. وفي مخطط القمع، ظهر تحيّز النشر وبيَّن تحليل التقليم والملء احتمال وجود دراسات مفقودة. نستنتج من هذه المراجعة وتحليل ميتا أن للدايفنهايدرامين خاصية مضادة للتسمم بالمبيدات الحشرية المثبّطة لإنزيم الكولين إستيريز والتقليل من خطورتها النسبية ضمن مؤشرات التسمم، مع التأكيد أنه ليس بديلاً من الترياق الأساس الأتروبين.

#6035 PREDICTORS OF MORTALITY IN ANCA-ASSOCIATED VASCULITIS: WHAT IS THE ROLE OF SERUM BIOMARKERS?

Abstract Background and Aims ANCA-Associated vasculitis (AAV) is an autoimmune disease with necrotizing inflammation of small vessels as the main manifestation. AAV is a severe disease with high level of mortality. Severity markers are needed to better tailor treatment. ANCA titers have not always been correlated with disease severity and mortality. Other inflammation markers have also been used such as C3 and C-reactive protein (CRP). The aim of this study is to correlate ANCA titers, C3 and CPR values ​​with mortality in patients with renal vasculitis. Method We retrospectively analyzed all adult patients between June 2006 and December 2022 with a renal AAV in the nephrology department of São Bernardo Hospital. Demographic, clinical and laboratory findings of all patients were recorded. ANCA titers at the time of diagnosis (ANCAd), remission (ANCArm), relapse (ANCArl) and last follow-up (ANCAf) dates were registered. C3 levels were measured at diagnosis (dC3) and at the last follow-up (fC3) dates. CRP was measured at diagnosis (CRPd), remission (CRPrm) and last follow-up (CRPf). ANCA titers was analysed as continuous and categorical variables. C3 and CRP were used as continuous variables. We analyse the association between ANCA titers, C3, CPR values and mortality with univariate analysis. Multivariable adjusted cox regression analysis was performed for assessing predictive variables associated with mortality. Results We included 58 AAV patients with kidney involvement, with mean age of 69±10 years old, 54.4% were male (n = 31), 82.7% (n = 48) MPO-ANCA+, 12.1% (n = 7) PR3-ANCA+ and 5.2% (n = 3) seronegative. Median follow-up was 32.2 months. 20 (34.5%) patients died. At admission, categorization by ANCA titer revealed 5.2% (3) 0-19 UI/mL, 10.3% (6) 20-39, 8.6% (5) 40-59, 17.2% (10) 60-99, 8.6% (5) 100-134 and 38% &amp;gt;134 (22). C3 median was 109 UI/L at admission, 96.5 UI/L at last follow-up, CPR median was 7.9 mg/dL at admission, 2.4 mg/dL at last follow-up. Univariate analysis did not reveal a difference between patients who survived and those who died, in relation to ANCAd (p = 0.221), ANCArm (p = 0.346), ANCArl (p = 0.180) and ANCAf (p = 0.072). However, it did show that dC3 where significantly lower in those patients who died (p = 0.023) and CRPf higher (p = 0.012), but not for fC3 (p = 0.372), CRPd (p = 0.408) and CRPrm (p = 0.384). Used as categorical variable, ANCAd did not correlate to patients’ death occurrence (p = 0.788). In multivariate analysis including age, gender, dC3 and CRPf, only CRPf was almost significantly (p = 0,06, model p = 0,05). In univariate cox regression analysis to evaluate factors related to survival, none where statistic significant to predict dead – ANCA d (p = 0,349), ANCAf (p = 0.136), dC3 (p = 0.082) and CRPf (p = 0.066). In multivariate cox regression analysis, including age (p = 0.039), gender (p = 0.658), dC3 (p = 0.227) and CRPf (p = 0.639), none factor predict dead (model p = 0,08). Conclusion In our cohort of patients with AAV, we did not found a serologic marker to predict dead. However, it appears to have a relationship with low serum C3 levels at the time of diagnosis. We also found that could be a relationship with CRP at the last follow-up, but that could be a bias due to higher levels in those how died from infection causes. The diagnostic value of the PR3- and MPO ANCA test is well established, however the relationship between mortality and titer levels in the various stages of the disease is not well established. In our study, there was no association between them. Further research should determine whether C3 levels and CPR are indeed an independent predictor of AAV outcome.

#3647 RELATIONSHIP BETWEEN MONOCYTE-LYMPHOCYTE RATIO AND RENAL OUTCOMES IN PATIENTS WITH TYPE 2 DIABETES

Abstract Background and Aims Acute kidney injury (AKI) is a common complication of hospitalized adults with increased risk of chronic kidney disease and end-stage kidney disease. Sepsis is the most common reason of AKI in patients admitted in intensive care unit(ICU) with the incidence over 50%. Soluble urokinase-type plasminogen activator receptor (suPAR) is an important immune mediator involved in kidney injury. Numerous studies have shown that the suPAR is associated with a variety of kidney diseases.However, it remains unknown on the diagnosis and prognosis value of suPAR in sepsis-associated acute kidney injury (S-AKI). Hence,this study aimed to explore the diagnostic value for the prediction of S-AKI courses and 28-day death. Method In this prospective study, adult patients with sepsis admitted to the ICU of Henan people's Hospital from December 2020 to February 2022 were enrolled. Plasma suPAR levels at 0, 12,24 and 48 hours after admission to ICU were measured by enzyme-linked immunosorbent assay. We assessed the development of S-AKI as the primary outcome and the occurrence of death within 28 days in patients who had S-AKI as a secondary outcome. The prediction of the suPAR level on S-AKI and death was tested using receiver operating characteristic curve (ROC) analysis, by calculating the area under the curve (AUC), and 95% confidence interval (CI). Results Of the 182 sepsis patients, 66 (36.3%) developed AKI during hospitalization, of whom 31 (46.9%) died. At 12,24 and 48 hours after admission to ICU, the plasma suPAR level was significantly higher in patients with S-AKI than in patients without AKI (P&amp;lt;0.05). (Fig. 1) In sepsis patients dead with 28 days after admission in ICU, the plasma suPAR level was significantly higher at 0 and 48 hours after admission in ICU compared to the survival patients(P&amp;lt;0.05). (Fig. 1) Diagnostic performance of plasma suPAR level improved over time with the highest area under the receiver operating characteristic curve of 0.701 (95% CI, 0.623∼0.779) 24 hours after study inclusion. Additionally, plasma suPAR levels at 0h have the highest area under the receiver operating characteristic curve of 0.647 (95% CI, 0.512∼0.782) in predicting 28-day death. The best discrimination ability for the S-AKI was achieved for suPAR 24 hours after inclusion by applying a cutoff value of greater than or equal to 6.31 ng/ml (sensitivity 62.1, specificity 71.6). The suPAR at 0h after inclusion performed best in discriminating 28-day death by using a cutoff value of greater than or equal to 4.57 ng/mL (sensitivity 87.1, specificity 51.4).(Table 1) Conclusion Plasma suPAR level can be a potential biomarker for early diagnosis of S-AKI and has a certain clinical value in predicting the short-term death of S-AKI. However, further clinical studies with larger sample size is needed.

#6279 ESKD TREATMENTS: A DIFFICULT CHOICE TO ELDERLY PATIENTS?

Abstract Background and Aims End stage kidney disease (ESKD) treatment choice may be very difficult mainly for elderly patients. Dialysis can be burdensome for the frail patients, offering more aggressive procedures and less quality of life. Conservative Care (CC) may shorten life in a fit patient. This study aimed to describe our elderly patients' choices when it comes to CKD treatment options and reflect about them. Method We designed a single center retrospective observational, cross-sectional study regarding patients (pts) over 80 years old (yo) who attend the appointment of ESKD treatment modalities between July 2015 and and December 2021, since a Conservative Care Program is available in our hospital. Results During these 6,5 years, 113 pts over 80 yo were attended. Mean age was 85 yo (range 80–103). 66% were male and mean charlson comorbidity index (CMI) was 7 (sd ± 1,2). Mean seric creatinine was 3,69 mg/dl (sd 0,99; range 1,8-7,0). Mean estimated glomerular filtration rate was 17,41 (sd ±4,12) and 14,64 (sd ± 7,6) ml/min per 1.73 m2 when calculated with BIS1 and CKD-EPI equation, respectively. Two patients were already on a regular program of dialysis. Regarding CKD etiology, 31,9% was from multifactorial origin, 27,4% was from undetermined origin, 10,6% was hypertensive, 8% was diabetic, 6,2% was from chronic pyelonephritis and 9,7% was in the context of cardiorenal syndrome. Regarding treatment options, 54% chose hemodialysis, 38,9% chose conservative care (CC), 2,7% chose peritoneal dialysis and 2,7% refused any treatment. We also observed a significant increase in the CC during these 6.5 years of study. Of those who chose hemodialysis, 22,95% (n = 14) died before starting on a regular program of dialysis, 62,3% (n = 38) actually started on a regular program and 14,75% (n = 9) still maintain follow-up in nephrology appointment. Regarding those who died before starting on dialysis treatment, the mean time between choosing dialysis and death was 1,36 years (range 115 days to 5,46 years, median 1,36 years), and between starting on a regular program and death was 1,38 year (range 11 days to 4,9 years). The main cause of death was unknown (66%) (by lack of data), followed by infectious cause (26,6%). Considering those who chose CC, 31,8% (n = 14) died before starting the regular follow up, 54,5% (n = 24) are on a regular program of follow up, and 4,5% (n = 2) lately decided for dialysis. Regarding those who died before CC, the mean time between choosing it and death was approximately 1 year (range 29 days to 3,4 years), and between starting on a regular follow up and death was 0,68 years (range 14 days to 1,7 years). We didn’t find any statistical significance between CMI and the ESRD modality chosen (p = 0.709) or the occurrence of death (p = 0,496). Conclusion Even considering the poor prognosis and the high mortality rate, the majority of patients over 80 years old still chose dialysis over conservative kidney treatment. In our cohort, there was no survival benefit from those who choose dialysis instead of CC. CC should be offered as an alternative treatment to all the patients who may not benefit from dialysis. It is important to find tools who help us to guide patients in the best suitable choice in regard to ESKD treatments.

#3644 CLINICAL VALUE OF SOLUBLE UROKINASE-TYPE PLASMINOGEN ACTIVATOR RECEPTOR IN DIAGNOSIS AND PROGNOSIS OF SEPSIS-ASSOCIATED ACUTE KIDNEY INJURY

Abstract Background and Aims Acute kidney injury (AKI) is a common complication of hospitalized adults with increased risk of chronic kidney disease and end-stage kidney disease. Sepsis is the most common reason of AKI in patients admitted in intensive care unit(ICU) with the incidence over 50%. Soluble urokinase-type plasminogen activator receptor (suPAR) is an important immune mediator involved in kidney injury. Numerous studies have shown that the suPAR is associated with a variety of kidney diseases.However, it remains unknown on the diagnosis and prognosis value of suPAR in sepsis-associated acute kidney injury (S-AKI). Hence,this study aimed to explore the diagnostic value for the prediction of S-AKI courses and 28-day death. Method In this prospective study, adult patients with sepsis admitted to the ICU of Henan people's Hospital from December 2020 to February 2022 were enrolled. Plasma suPAR levels at 0, 12,24 and 48 hours after admission to ICU were measured by enzyme-linked immunosorbent assay. We assessed the development of S-AKI as the primary outcome and the occurrence of death within 28 days in patients who had S-AKI as a secondary outcome. The prediction of the suPAR level on S-AKI and death was tested using receiver operating characteristic curve (ROC) analysis, by calculating the area under the curve (AUC), and 95% confidence interval (CI). Results Of the 182 sepsis patients, 66 (36.3%) developed AKI during hospitalization, of whom 31 (46.9%) died. At 12,24 and 48 hours after admission to ICU, the plasma suPAR level was significantly higher in patients with S-AKI than in patients without AKI (P&amp;lt;0.05). (Figue 1) In sepsis patients dead with 28 days after admission in ICU, the plasma suPAR level was significantly higher at 0 and 48 hours after admission in ICU compared to the survival patients(P&amp;lt;0.05). (Figue 1) Diagnostic performance of plasma suPAR level improved over time with the highest area under the receiver operating characteristic curve of 0.701 (95% CI, 0.623∼0.779) 24 hours after study inclusion. Additionally, plasma suPAR levels at 0h have the highest area under the receiver operating characteristic curve of 0.647 (95% CI, 0.512∼0.782) in predicting 28-day death. The best discrimination ability for the S-AKI was achieved for suPAR 24 hours after inclusion by applying a cutoff value of greater than or equal to 6.31 ng/ml (sensitivity 62.1, specificity 71.6). The suPAR at 0h after inclusion performed best in discriminating 28-day death by using a cutoff value of greater than or equal to 4.57 ng/mL (sensitivity 87.1, specificity 51.4). (Table 1) Conclusion Plasma suPAR level can be a potential biomarker for early diagnosis of S-AKI and has a certain clinical value in predicting the short-term death of S-AKI. However, further clinical studies with larger sample size is needed.

#2599 LONG-TERM LONGITUDINAL CHANGES OF PULSE WAVE VELOCITY AND THEIR ASSOCIATION TO CARDIOVASCULAR RISK FACTORS IN MAINTENANCE HEMODIALYSIS PATIENTS

Abstract Background and Aims The incidence of end-stage renal disease (ESRD) is increasing worldwide. The mortality rate in this patient cohort remains unacceptably high. The WHO estimates ESRD as one of the ten global causes of premature death. Approximately half of all death cases are due to cardiovascular complications. A main cardiovascular risk factor is enhanced arterial stiffness. The measurement of pulse wave velocity (PWV) for evaluation of progressive atherosclerosis is known to be an independent risk predictor for cardiovascular and all-cause mortality in chronic dialysis patients. Method The study cohort contains patients from the “Risk stratification in end-stage renal disease - the ISAR study”, a multicenter prospective longitudinal observatory cohort study. A total of 105 patients on maintenance hemodialysis were examined and followed-up for up to 72 months. Pulse wave velocity was obtained by the Mobil-O-Graph 24h PWA Monitor device at baseline and follow-up. We assessed the PWV change over time and correlated PWV with known cardiovascular risk factors using Pearson correlation coefficient adjusting for age. Longitudinal changes were examined using t-tests for paired and independent samples. Results Patients had a median age of 61,2 years (IQR 23,2), 36 (34%) were female. Median baseline dialysis vintage was 105 months (IQR 71), and median adapted Charlson Comorbidity Index 2 (IQR 3). During a median follow-up of 74,1 months there was a significant increase in PWV from baseline (9,25 m/s) to 6YFU (10,18 m/s, p = &amp;lt;0,001), a delta-PWV of 0,92 m/s, appropriate to a yearly change of 0,15 m/s. Patients with hypertension had a significant higher PWV (10,47 m/s) than those with normal blood pressure (8,91 m/s, p = 0,034). The Pearson correlation coefficient analysis showed after adjustment for age a significant correlation between blood pressure and both 6YFU-PWV (systolic r = 0,89 diastolic r = 0,62, p = &amp;lt;0,001) and delta-PWV (systolic r = 0,71 diastolic 0,48, p = &amp;lt;0,001). Additionally, after adjustment for age delta-PWV correlated with LDL-cholesterol (r = 0,27, p = 0,023). Neither 6YFU-PWV nor delta-PWV showed significant associations to other traditional cardiovascular risk factors such as diabetes, high cholesterol or obesity. Conclusion In this cohort, we found a longitudinal increase of pulse wave velocity over 6 years. However, the average change in PWV per year was significantly lower in our cohort compared to other studies with a shorter observation period. A main reason might be the long follow-up time, with the occurrence of several deaths in the primary cohort of the ISAR-Study before reaching the follow-up point and therefore including more younger and possibly healthier patients. Nevertheless, in this cohort blood pressure in contrast to diabetes, high cholesterol or obesity was a primary factor in the change of PWV. The reasons for the deceleration of cardiovascular and mortality risk after a long term in this sub cohort remains unclear and requires further investigation.