Strong Predictor Of Death Research Articles

Neutrophil-to-lymphocyte ratio as a prognostic indicator of mortality in Polycythemia Vera: insights from a prospective cohort analysis

We analyzed the neutrophil-to-lymphocyte ratio (NLR) in 1508 patients with PV and found that those with an NLR ≥ 5 were generally older, had a longer disease history, and had higher cardiovascular risk factors, more arterial thrombosis, and more aggressive blood counts, indicating a more proliferative disease. NLR was an accurate predictor of mortality, with patients with NLR ≥ 5 having significantly worse overall survival and more than twice the mortality rate compared to those with NLR < 5. Multivariable models confirmed that increasing age, previous venous thrombosis and NLR ≥ 5 were strong predictors of death, further influenced by cardiovascular risk factors. We examined the interaction between NLR and the number of cardiovascular risk factors and found a progressive trend of increased mortality risk for NLR values ≥ 5 in addition to the presence of more than one risk factor. In conclusion, patients with NLR ≥ 5 require careful monitoring and management of cardiovascular risk factors because they increase mortality when associated with progressive levels of NLR.

The Incidence, Aetiology and Clinical Course of Serious Infections Complicating Biological and Targeted Synthetic Disease-Modifying Antirheumatic Drug Therapy in Patients with Rheumatoid Arthritis in Tropical Australia

Introduction: Patients receiving biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) for rheumatological conditions are at an increased risk of serious, potentially life-threatening, infection. However, the incidence, aetiology, and clinical course of serious infection in patients receiving b/tsDMARDs in tropical settings are incompletely defined. Methods: We retrospectively reviewed all patients with rheumatoid arthritis receiving b/tsDMARDs between October 2012 and October 2021, at Cairns Hospital in tropical Australia. The incidence, aetiology, and clinical course of serious infections (those requiring admission to hospital or parenteral antibiotics) were determined. Results: 310 patients had 1468 patient years of b/tsDMARD therapy during the study period; 74/310 (24%) had 147 serious infections translating to an overall risk of 10.0 episodes of serious infection per 100 patient years. The respiratory tract (50/147, 34%) and skin (37/147, 25%) were the most frequently affected sites. A pathogen was identified in 59/147 (40%) episodes and was most commonly Staphylococcus aureus (24/147, 16%). Only 2/147 (1%) were confirmed “tropical infections”: 1 case of Burkholderia pseudomallei and 1 case of mixed B. pseudomallei and community-acquired Acinetobacter baumannii infection. Overall, 13/147 (9%) episodes of serious infection required Intensive Care Unit admission (0.9 per 100-patient years of b/tsDMARD therapy) and 4/147 (3%) died from their infection (0.3 per 100-patient years of b/tsDMARD therapy). The burden of comorbidity and co-administration of prednisone were the strongest predictors of death or a requirement for ICU admission. Conclusions: The risk of serious infection in patients taking b/tsDMARDs in tropical Australia is higher than in temperate settings, but this is not explained by an increased incidence of traditional tropical pathogens.

Long term follow up in pulmonary embolism: can right ventricular strain echocardiographic imaging contribute to refine risk stratification?

Abstract Background In pulmonary embolism (PE), the usual evaluation of early risk of death includes clinical, biological and two-dimensional right ventricular (RV) echocardiographic (TTE) parameters. Purpose We hypothesized that myocardial strain analysis could contribute to risk of death prediction at long term follow up. Methods We retrospectively analyzed 477 patients hospitalized for acute EP. Usual parameters used to define RV dysfunction were evaluated using TTE (RV dilatation, systolic pulmonary arterial pressure, TAPSE, S’, Fractionnal Area Change (FAC), end diastolic RV diameter and right atrial, RA, area). In addition, we evaluated, left ventricle (LV) longitudinal, left atrial (LA), RA and RV free wall strains. Patients without history of cancer (n=419) were analyzed on the primary outcome of death at long term follow up. Results Mean of age was 63.7 ± 17.2 years and 227 (47.6) patients were male. The main clinical and echocardiographic characteristics are displayed in the Table 1. During a mean follow-up was 45.0 ± 16.6 months, the primary outcome occurred in 56 patients. In multivariable analysis, systolic pulmonary arterial pressure, indexed right atrial and left atrial volumes, right ventricle free wall strain, right ventricle global longitudinal strain were the only predictors of death (Table 2). Conclusion Atrial volumes and RV strain appeared as strong predictors of death in PE at long term follow up. Right ventricle myocardial strain analysis should be evaluated in each patient hospitalized for PE.

What Important Information Does Transesophageal Echocardiography Provide When Performed before Transvenous Lead Extraction?

Background: Transesophageal echocardiography (TEE) is mandatory before transvenous lead extraction (TLE), but its usefulness remains underestimated. This study aims to describe the broad range of TEE findings in TLE candidates, as well as their influence on procedure complexity, major complications (MCs) and long-term survival. Methods: Preoperative TEE was performed in 1191 patients undergoing TLE. Results: Lead thickening (OR = 1.536; p = 0.007), lead adhesion to heart structures (OR = 2.531; p < 0.001) and abnormally long lead loops (OR = 1.632; p = 0.006) increased the complexity of TLE. Vegetation-like masses on the lead (OR = 4.080; p = 0.44), lead thickening (OR = 2.389; p = 0.049) and lead adhesion to heart structures (OR = 6.341; p < 0.001) increased the rate of MCs. The presence of vegetations (HR = 7.254; p < 0.001) was the strongest predictor of death during a 1-year follow-up period. Conclusions: TEE before TLE provides a lot of important information for the operator. Apart from the visualization of possible vegetations, it can also detect various forms of lead-related scar tissue. Build-up of scar tissue and the presence of long lead loops are associated with increased complexity of the procedure and risk of MCs. Preoperative TEE performed outside the operating room may have an impact on the clinical decision-making process, such as transferring potentially more difficult patients to a more experienced center or having the procedure performed by the most experienced operator. Moreover, the presence of masses or vegetations on the leads significantly increases 1-year and all-cause mortality.

The impact of hyperkalemia on ICU admission and mortality: a retrospective study of Chinese emergency department data

ObjectiveThis study assesses the influence of hyperkalemia on both disease severity and the risk of mortality among patients admitted to the emergency room.MethodsThis retrospective observational study utilized data from the Chinese Emergency Triage Assessment and Treatment database (CETAT, version 2.0), which was designed to evaluate and optimize management strategies for emergency room (ER) patients. Patients were systematically categorized based on serum potassium levels. Relationships between serum potassium levels, risk of mortality, and the severity of illness were then analyzed using multifactorial logistic regression and through Receiver Operating Characteristic (ROC) analysis. The effectiveness of various treatments at lowering potassium levels was also investigated.Results12,799 emergency patients were enrolled, of whom 20.1% (n = 2,577) were hypokalemic and 2.98% (n = 381) were hyperkalemic. Among hyperkalemic patients, the leading reasons for visiting the ER were altered consciousness 23.88% (n = 91), cardiovascular symptoms 22.31% (n = 85), and gastrointestinal symptoms 20.47% (n = 78). Comparative analysis with patients exhibiting normal potassium levels revealed hyperkalemia as an independent factor associated with mortality in the ER. Mortality risk appears to positively correlate with increasing potassium levels, reaching peaks when blood potassium levels ranged between 6.5 and 7.0. Hyperkalemia emerged as a strong predictor of death in the ER, with an Area Under the Curve (AUC) of 0.89. The most frequently prescribed treatment for hyperkalemia patients was diuretics (57.32%, n = 188), followed by intravenous sodium bicarbonate (50.91%, n = 167), IV calcium (37.2%, n = 122), insulin combined with high glucose (27.74%, n = 91), and Continuous Renal Replacement Therapy (CRRT) for 19.82% (n = 65). Among these, CRRT appeared to be the most efficacious at reducing potassium levels. Diuretics appeared relatively ineffective, while high-glucose insulin, sodium bicarbonate, and calcium preparations having no significant effect on the rate of potassium decline.ConclusionHyperkalemia is common in emergency situations, especially among patients with altered consciousness. There is a strong positive correlation between the severity of hyperkalemia and mortality risk. CRRT appears to be the most effective potassium reducting strategy, while the use of diuretics should be approached with caution.

INDIPENDENT PROGNOSTIC VALUE OF SOLUBLE–SUPRESSION OF TUMORIGENICITY (S–ST2) IN PATIENTS AFFECTED BY PULMONARY HYPERTENSION

Abstract Introduction According to ESC 2022 guidelines, pulmonary hypertension (PH) is a hemodynamic condition characterized by mean pulmonary arterial pressure&amp;gt;20 mmHg. Pulmonary arterial hypertension (PAH) represents 5% of the PH, with an unfavorable prognosis primarily because of late diagnosis and treatment. In PAH, it is important to evaluate the individual patient mortality risk through a multiparametric approach: a three–layer model at diagnosis and a four–layer model based on WHO–FC, 6MWD and NT–proBNP at follow up, which allows better discrimination within the intermediate risk group helping therapeutic decision making. The only biomarker included in risk stratification is NT–proBNP; however, in previous studies soluble–Supression of Tumorigenicity 2(s–ST2), a marker of myocardial stress, resulted a strong predictor of death in heart failure and acute coronary syndromes. Aim The aim of this study is to analyze the prognostic value of s–ST2 in patients with pulmonary hypertension. Methods This is a prospective study conducted on 45 PH patients (75% PAH), which were followed for survival. They underwent echocardiography, venous sampling to measure s–ST2 levels, right heart catheterization. All the patients were followed for survival. Results During an average 18–month follow–up, 17 patients died, 76% of whom had pulmonary arterial hypertension (PAH). They showed significantly higher values of s–ST2. sST2&amp;gt;78 ng/ml represents a numerical value with the highest association with mortality in our study population: at 6–12 months the patients with sST2&amp;gt;78 ng/ml showed statistically significant early higher mortality in comparison with sST2 &amp;lt;78 ng/ml patients (Fig. 1). At multivariate analysis s–ST2&amp;gt;78 ng/ml is confirmed to be a statistically significant predictor of mortality, regardless of WHO functional class III–IV, PAPs and NT–proBNP. Furthermore, s–ST2 appears a better early mortality predictor than NT–proBNP, at the limit of statistical significance (Fig. 2). Conclusions In a population of patients with pulmonary hypertension (predominantly PAH) we define a numerical value of sST2&amp;gt;78 ng/ml, which is a prognostic discriminator, independent and incremental to NT–proBNP at short–term follow–up. It allows the clinician the appropriate planning of therapeutic strategies in a condition in which the earliness of therapy affects prognosis.

Impact of the 2022 pulmonary hypertension definition on haemodynamic classification and mortality in patients with aortic stenosis undergoing valve replacement.

With the 2022 pulmonary hypertension (PH) definition, the mean pulmonary artery pressure (mPAP) threshold for any PH was lowered from ≥25 to >20 mmHg, and the pulmonary vascular resistance (PVR) value to differentiate between isolated post-capillary PH (IpcPH) and combined pre- and post-capillary PH (CpcPH) was reduced from >3 Wood units (WU) to >2 WU. We assessed the impact of this change in the PH definition in aortic stenosis (AS) patients undergoing aortic valve replacement (AVR). Severe AS patients (n = 503) undergoing pre-AVR cardiac heart catheterization were classified according to both the 2015 and 2022 definitions. The post-AVR mortality [median follow-up 1348 (interquartile range 948-1885) days] was assessed. According to the 2015 definition, 219 (44% of the entire population) patients had PH: 63 (29%) CpcPH, 125 (57%) IpcPH, and 31 (14%) pre-capillary PH. According to the 2022 definition, 321 (+47%) patients were diagnosed with PH, and 156 patients (31%) were re-classified: 26 patients from no PH to IpcPH, 38 from no PH to pre-capillary PH, 38 from no PH to unclassified PH, 4 from pre-capillary PH to unclassified PH, and 50 from IpcPH to CpcPH (CpcPH: +79%). With both definitions, only the CpcPH patients displayed increased mortality (hazard ratios ≈ 4). Among the PH-defining haemodynamic components, PVR was the strongest predictor of death. In severe AS, the application of the 2022 PH definition results in a substantially higher number of patients with any PH as well as CpcPH. With either definition, CpcPH patients have a significantly increased post-AVR mortality.

Cardiogenic shock and chronic kidney disease: Dangerous liaisons

BackgroundChronic kidney disease (CKD) is one of the leading causes of death worldwide, closely interrelated with cardiovascular diseases, ultimately leading to the failure of both organs – the so-called “cardiorenal syndrome”. Despite this burden, data related to cardiogenic shock outcomes in CKD patients are scarce. MethodsFRENSHOCK (NCT02703038) was a prospective registry involving 772 patients with cardiogenic shock from 49 centres. One-year outcomes (rehospitalization, death, heart transplantation, ventricular assist device) were analysed according to history of CKD at admission and were adjusted on independent predictive factors. ResultsCKD was present in 164 of 771 patients (21.3%) with cardiogenic shock; these patients were older (72.7 vs. 63.9years) and had more comorbidities than those without CKD. CKD was associated with a higher rate of all-cause mortality at 1month (36.6% vs. 23.2%; hazard ratio 1.39, 95% confidence interval 1.01–1.9; P=0.04) and 1year (62.8% vs. 40.5%, hazard ratio 1.39, 95% confidence interval 1.09–1.77; P<0.01). Patients with CKD were less likely to be treated with norepinephrine/epinephrine or undergo invasive ventilation or receive mechanical circulatory support, but were more likely to receive renal replacement therapy (RRT). RRT was associated with a higher risk of all-cause death at 1month and 1year regardless of baseline CKD status. ConclusionsCardiogenic shock and CKD are frequent “cross-talking” conditions with limited therapeutic options, resulting in higher rates of death at 1month and 1year. RRT is a strong predictor of death, regardless of preexisting CKD. Multidisciplinary teams involving cardiac and kidney physicians are required to provide integrated care for patients with failure of both organs.

Incremental prognostic value of functional impairment assessed by 6-min walking test for the prediction of mortality in heart failure

Natriuretic peptides (NP) are recognized as the most powerful predictors of adverse outcomes in heart failure (HF). We hypothesized that a measure of functional limitation, as assessed by 6-min walking test (6MWT), would improve the accuracy of a prognostic model incorporating a NP. This was a multicenter observational retrospective study. We studied the prognostic value of severe functional impairment (SFI), defined as the inability to perform a 6MWT or a distance walked during a 6MWT < 300 m, in 1696 patients with HF admitted to cardiac rehabilitation. The primary outcome was 1-year all-cause mortality. After adjusting for the baseline multivariable risk model—including age, sex, systolic blood pressure, anemia, renal dysfunction, sodium level, and NT-proBNP—or for the MAGGIC score, SFI had an odds ratio of 2.58 (95% CI 1.72–3.88; p < 0.001) and 3.12 (95% CI 2.16–4.52; p < 0.001), respectively. Adding SFI to the baseline risk model or the MAGGIC score yielded a significant improvement in discrimination and risk classification. Our data suggest that a simple, 6MWT-derived measure of SFI is a strong predictor of death and provide incremental prognostic information over well-established risk markers in HF, including NP, and the MAGGIC score.

Fatal Road Traffic Accidents and Associated Factors in North Shewa Zone, Central Ethiopia: A Cross-Sectional Study.

Road traffic accidents (RTAs) are among the top three global causes of death among people aged 15 to 44 years. More importantly, it is the main cause of death and permanent disability among young people aged 15 to 29 years. This study aimed to assess the magnitude of fatal traffic accidents and the factors associated with them in the North Shewa Zone, Central Ethiopia, from 2013 to 2018. An institution-based cross-sectional study was conducted in all registered RTAs from July 2013 to June 2018 that had full documentation. The data extraction tool was developed based on the daily RTA registration book format that was utilized. Data was entered into Epi-data version 3.1 and then exported to SPSS version 21 for analysis. Logistic regression analysis was used to assess the relationship between the factors and the fatality of RTA. P-values less than 0.05 were reported as statistically significant. Among 846 RTAs studied, 351 (41.5%) were found fatal, while 495 (58.5%) caused non-fatal injuries. Failure to give priority to pedestrians was 2.8 times (AOR = 2.8, 95% CI: 1.3, 5.9) more likely to cause fatal RTAs than drivers who failed to maintain distance between vehicles. Pedestrians were 2.7 times (AOR = 2.7, 95% CI: 1.1, 6.7) more likely to die in RTAs than drivers. The fatality of RTA was high. Failure to give priority to pedestrians and being a pedestrian were strong predictors of death. The North Shewa Zone Traffic Police Department and police officers should focus on enforcing traffic safety laws.

Prognostic impact of the extent, location, and pattern of late gadolinium enhancement in dilated cardiomyopathy

Abstract Background Several studies have shown that the presence and extent of late gadolinium enhancement (LGE) defined by cardiac magnetic resonance imaging (CMR) are strong prognosticators of death in patients with dilated cardiomyopathy (DCM). The interest of LGE location and pattern to improve risk stratification is not well established. Purpose To assess the incremental prognostic value of LGE extent, location and pattern for predicting all-cause death over traditional risk factors in DCM patients. Methods Between 2008 and 2021, we conducted a bi-centre longitudinal study including all consecutive DCM patients referred for CMR. DCM was confirmed excluding patients with ischemic heart disease, history of acute myocarditis, hypertrophic cardiomyopathy, and infiltrative disease. The outcome was all-cause death using the electronic French National Registry of Death. The prognostic value of LGE parameters was assessed using Cox analyses after adjustment for traditional prognostic factors: LGE presence, extent (number of segments), pattern (midwall or subepicardial), location and multiple areas. The incremental prognostic value of these LGE parameters was assessed using C-statistic increment, the continuous net reclassification improvement (NRI), the integrative discrimination index (IDI) and the global Chi-2. Results In 2,752 DCM patients (52±8 years, 56% male), 408 (15%) died after a median (IQR) follow-up of 9.2 (6.8-11.5) years. A total of 737 (27%) patients had LGE, including 664 (90%) LGE mid-wall and 73 (10%) LGE sub-epicardial. In the whole cohort (n=2,752), the LGE presence and extent were strong predictors of death (HR: 2.42 [95% CI: 1.67-3.51] and HR: 1.78 [95% CI: 1.64-1.93]; both p&amp;lt;0.001). In the subgroup of patients with LGE (n=737), the LGE multiple area was an independent predictor of death (HR: 5.12 with 95% CI: 3.53-7.41; p&amp;lt;0.001). The LGE pattern wasn't associated with death (subepicardial: HR: 0.88; 95% CI: 0.56-1.39, p=0.58). The location in both septal and free-wall was strongly associated with death compared to septal LGE only (HR: 10.1; 95% CI: 7.53-13.6; p&amp;lt;0.001), itself more at risk of death than free-wall LGE only (HR: 3.12; 95% CI: 2.03-4.78; p&amp;lt;0.001). In the 537 patients with LGE single area, LGE in septal segments was a strong prognostic marker (HR: 17.0; 95% CI: 5.88-49.4; p&amp;lt;0.001) compared to other locations (inferior: HR: 10.3; 95% CI: 3.45-30.5; p&amp;lt;0.001; lateral: HR: 6.13; 95% CI: 1.95-19.2; p&amp;lt;0.01; reference=anterior). A model combining the LGE extent, location and multiple area showed the best improvement in model discrimination and reclassification above traditional risk factors (C-statistic improvement: 0.19; NRI=11.8%; IDI=2.2%, all p&amp;lt;0.001). Conclusion In a large cohort of DCM patients, the LGE extent, location, and multiple area were independent prognosticators of death. A model combining these LGE findings had an incremental prognostic value over traditional prognostic factors to predict all-cause death.Incremental prognostic value of LGEHazard ratios regarding LGE segments

Use of machine learning to predict mortality in patients with type 2 diabetes mellitus, according to socioeconomic status

Abstract Introduction Patients with Type 2 diabetes mellitus (T2DM) are at increased risk of developing cardiovascular disease (CVD) that adversely affects prognosis. Socioeconomic deprivation may be associated with lifestyle choices that contribute to adverse outcomes. The influence of social deprivation on the prognosis of T2DM is rarely investigated in large cohorts. Therefore, we assessed the associations between socioeconomic status and survival in patients with T2DM by applying conventional statistical methods and state-of-the-art, machine learning (ML) models. Methods We obtained routinely collected, linked administrative data for individuals with T2DM aged &amp;gt;50 years from the National Health Service (NHS) Scotland, including demographic data, laboratory measurements, prescriptions, death records and primary and secondary care diagnostic codes. We developed a random survival forest model for predicting all-cause mortality, overall and for each quintile of socioeconomic status using the Scottish Index of Multiple Deprivation (SIMD), which is based on postcodes that reflect a combination of income, employment, local crime rates, education, housing and health. We used Cox proportional hazards models to investigate the risk between the most and least deprived quintiles. Subsequently, we applied Shapely Additive Explanations (SHAP), a state-of-the-art ML interpretability method, to identify key prognostic factors that influence the survival probability prediction score for each sub-group. Results 30,495 people had a newly recorded diagnosis of T2DM between 2009-2019, of whom 4,300 died within 10 years. Table 1 shows the c-index (global assessment of model discrimination) and time-brier score (measure of calibration for time-dependent probability prediction) for the whole cohort and for each SIMD quintile: use of loop diuretics, older age, lower serum concentrations of albumin and alanine transaminase (ALT) and estimated glomerular function rate (eGFR) were strong predictors of death for all quintiles. Prevalence of chronic obstructive pulmonary disease (COPD) was strongly associated with mortality for the most deprived quintile (Q1, whilst strokes were strongly associated with mortality for the most affluent (Q5). A history of heart failure, in addition to use of loop diuretics, predicted a higher risk, in 3 of the 5 quintiles. Overall Q1 had a 36% higher mortality than Q5 (HR: adjusted for age and sex 1.36 [95% CI 1.24 – 1.50 (&amp;lt;0.005)]). Conclusion Greater socioeconomic deprivation is associated with a worse prognosis in patients with T2DM. Results of commonly measured blood tests, allied to readily available patient characteristics (including heart failure and use of loop diuretics) predict mortality risks across all deprivation groups for people with T2DM.Table:Predictors of Mortality in T2DM

Residual or recurrent mitral regurgitation predicts mortality following transcatheter edge-to-edge mitral valve repair

ObjectiveAlthough regurgitant mitral valves can be repaired through surgical or transcatheter approaches, contemporary comparative outcomes are limited with the impact of residual and recurrent mitral regurgitation (MR) on clinical outcomes being poorly defined. We hypothesized that moderate (2+) or greater residual or recurrent (RR) MR—regardless of type of repair—predicts worse clinical outcomes. MethodsOur institutional experience of 660 consecutive patients undergoing mitral valve repair (2015-2021) consisting of 393 surgical mitral valve repair (SMVr) and 267 transcatheter edge-to-edge mitral valve repair (TEER) was studied. The echocardiographic impact of RRMR (2+) following both SMVr and TEER on death and reintervention was evaluated. ResultsPatients averaged 67.8 ± 14.2 years (SMVr = 63.8 ± 13.3 vs 73.6 ± 13.6, P < .0001) and 62.1% were male. Baseline clinical and demographic data were vastly different between the 2 groups. Residual or recurrent 2+ or greater MR developed in 25% (n = 68) of patients who received TEER compared with 6% (n = 25) of SMVr (P < .0001). Reintervention (9.3% vs 2.4%, P = .002) and death (37.9% vs 10.4%, P < .0001) rates at 3-years were greater among the TEER group versus SMVr group. Given the heterogeneity in baseline characteristics and difference in survival, each cohort was analyzed separately, stratified by RRMR, using multivariable modeling to identify predictors of repeat reintervention and death. There were too few events of RRMR in the SMVr cohort for evaluation. For the TEER subgroups, we observed greater long-term mortality, but not reintervention among those with RRMR., Hypertension was the strongest predictor of death and obesity was for reintervention. ConclusionsPatients undergoing SMVr and TEER are vastly different with respect to baseline patient characteristics and clinical outcomes, with patients who undergo TEER being much greater risk with poorer prognosis. Moderate or greater RRMR predicted worse long-term survival but not reintervention among patients who received TEER. Given the difference in survival among patients with RRMR following TEER, care must be taken to ensure that patients entering clinical trials and receiving TEER should have a high probability of achieving mild or less MR as seen in contemporary surgical results.

Revisiting anti-Hu paraneoplastic autoimmunity: phenotypic characterization and cancer diagnosis.

Anti-Hu are the most frequent antibodies in paraneoplastic neurological syndromes, mainly associated with an often limited stage small cell lung cancer. The clinical presentation is pleomorphic, frequently multifocal. Although the predominant phenotypes are well characterized, how different neurological syndromes associate is unclear. Likewise, no specific study assessed the performance of new-generation CT and PET scanners for cancer screening in these patients. Herein, we aimed to describe the clinical pattern and cancer screening in a retrospective cohort of 466 patients with anti-Hu autoimmunity from the French Reference Centre on Paraneoplastic Neurological Syndromes registry. Clinical presentation, cancer screening and diagnosis were analysed. Among the 466 patients, 220 (54%) had multifocal neurological involvement. A hierarchical cluster analysis grouped the patients into (i) mainly limbic encephalitis, (ii) predominantly peripheral neuropathy and (iii) broad involvement of the nervous system (mixed group). Compared with limbic encephalitis and mixed groups, patients in the neuropathy group more frequently had a chronic onset of symptoms (29 versus 13 and 17%), elevated CSF proteins (83 versus 47 and 67%) and died from cancer progression (67 versus 15 and 28%; all P < 0.05). No significant difference in overall survival was observed between groups. Dysautonomia and brainstem signs were associated with a higher risk of death from the neurological cause; cancer diagnosis was the main predictor of all-cause death, especially when diagnosed within 2 years from clinical onset (all P < 0.05). Three hundred and forty-nine (75%) patients had cancer: in 295 (84%) neurological symptoms preceded tumour diagnosis, being lung cancer in 262 (89%), thereof small cell lung cancer in 227 (87%). First CT scan revealed lung cancer in 205/241 (85%), and PET scan shortened the interval to diagnosis when the initial CT scan was negative [7 months (1-66) in 27 patients versus 14 months (2-45) in 6; P < 0.001]. Although cancer diagnosis mostly occurred within 2 years from clinical onset, 13/295 (4%) patients exceeded that threshold. Conversely, 33 patients (7%) were 'cancer-free' after 2 years of follow-up. However, 13/33 (39%) had initial suspicious imaging findings that spontaneously regressed. In conclusion, although anti-Hu autoimmunity clinical presentation is mostly multifocal, we observed patients with a predominant limbic syndrome or isolated sensory neuropathy. Early implementation of PET scan shortens the interval to cancer diagnosis, which was the strongest predictor of death, especially if diagnosed ≤2 years from clinical onset. As cancer was diagnosed >2 years after clinical onset in few patients, screening should be extended up to 5 years. In addition, tumour regression was suspected in a substantial proportion of 'cancer-free' patients.

Metabolic PET/CT analysis of aggressive Non-Hodgkin lymphoma prior to Axicabtagene Ciloleucel CAR-T infusion: predictors of progressive disease, survival, and toxicity

PET/CT is used to evaluate relapsed/refractory non-Hodgkin lymphoma (NHL) prior to chimeric antigen receptor T-cell (CAR-T) infusion at two time points: pre-leukapheresis (pre-leuk) and pre-lymphodepletion chemotherapy (pre-LD). We hypothesized that changes in PET/CT between these time points predict outcomes after CAR-T. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and other metrics were calculated from pre-leuk and pre-LD PET/CT scans in patients with NHL who received axicabtagene ciloleucel, and assessed for association with outcomes. Sixty-nine patients were analyzed. While single time point PET/CT characteristics were not associated with risk of PD or death, increases from pre-leuk to pre-LD in parenchymal MTV, nodal MTV, TLG of the largest lesion, and total number of lesions were associated with increased risk of death (p < 0.05 for all). LASSO analysis identified increasing extranodal MTV and increasing TLG of the largest lesion as strong predictors of death (AUC 0.74). Greater pre-LD total MTV was associated with higher risk of grade 3+ immune effector cell-associated neurotoxicity syndrome (ICANS) (p = 0.042). Increasing metabolic disease burden during CAR-T manufacturing is associated with increased risk of progression and death. A two variable risk score stratifies prognosis prior to CAR-T infusion and may inform risk-adapted strategies.

#3805 A FEASIBILITY STUDY EXPLORING THE IMPACT OF A LOW ADVANCED GLYCATION END-PRODUCT DIET ON SKIN AUTOFLUORESCENCE IN KIDNEY TRANSPLANT RECIPIENTS

Abstract Background and Aims Advanced glycation end-products (AGEs) are uremic toxins that result from hyperglycaemia and oxidative stress. AGEs are also formed in food, especially during cooking using dry-heat methods. AGE accumulation can be measured by skin autofluorescence (SAF) and increased SAF is a strong predictor of death and graft loss in kidney transplant recipients (KTR). Previous studies have reported that reduction of dietary AGE intake is associated with a decrease in circulating AGE levels, suggesting that a low-AGE diet may also be associated with a decrease in SAF. The aim of this feasibility study was to investigate whether a low-AGE diet leads to a reduction in SAF levels in KTR. Methods Thirty-eight KTR were randomly allocated to a usual diet (control group, n = 19) or a low-AGE diet (intervention group, n = 19) and then followed-up for 6 months. The intervention group was provided with detailed written advice and counselling on how to choose foods low in AGEs, and to use high-water content cooking methods (stewing, steaming, boiling, poaching), instead of dry-heat methods (frying, grilling, roasting). The goal was to reduce dietary AGE intake to &amp;lt;8000 kilounits/day (kU/day). SAF was measured at baseline, 3 and 6 months. Rate of change in SAF (i.e., SAF trend) was calculated using the SLOPE function in Microsoft Excel. Dietary AGE intake, biochemistry and nutritional assessments were performed at baseline and 6 months. Results Mean age of the whole cohort was 56±11 years. Mean SAF was high at 2.9±0.7 arbitrary units (AU) compared to the reference value of 2.1±0.4 AU. Transplant vintage ranged from 42 to 126 (median 88) months. The majority of the participants were male (71%) and of white ethnicity (84%). Prevalence of diabetes, hypertension and heart disease was 16%, 53%, and 10%, respectively. Median dietary AGE intake was high at 18558 (15164 to 25341) kU/day. There were no significant differences between the intervention and control groups at baseline in SAF, dietary AGE intake, estimated glomerular filtration rate (eGFR), demographics, and clinical, biochemical and nutritional characteristics. Baseline SAF was negatively associated with eGFR (r = −0.387; p = 0.02), energy intake (r = −0.464; p = 0.003) and fat intake (r = −0.438; p = 0.006). Seventeen participants in the control group and 13 participants in the intervention group completed 6 months of follow-up (Fig. 1). Adherence to the low-AGE diet was moderate (69%). Dietary AGE intake decreased significantly in the intervention group but remained high in the control group. Body weight, energy, and fat intake decreased in the intervention group but there was no significant change in SAF (Table 1). The mean SAF trend observed was a decrease of 0.45±1.19 and 0.22±0.75 AU/year in the intervention and control groups, respectively (p = 0.7 for comparison between groups). Conclusion In this feasibility study, we observed a high drop-out rate in the intervention group, which may explain our finding that reduction in dietary AGE intake did not seem to have any significant effect in decreasing SAF levels. This highlights the need for a larger trial to determine the effect of dietary AGE restriction on SAF levels in KTR.

Prevalence of anemia and associated All-Cause mortality among adults with Diabetes: The role of chronic kidney disease

AimsAmong adults with diabetes in the United States, we evaluated anemia prevalence by CKD status as well as the role of CKD and anemia, as potential risk factors for all-cause mortality. MethodsIn a retrospective cohort study, we included 6,718 adult participants with prevalent diabetes from the 2003-March 2020 National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of the non-institutionalized civilian population in the United States. Cox regression models evaluated the role of anemia and CKD, alone or combined, as predictors of all-cause mortality. ResultsAnemia prevalence among adults with diabetes and CKD was 20%. Having anemia or CKD alone, compared with having neither condition, was significantly associated with all-cause mortality (anemia: HR = 2.10 [1.49–2.96], CKD: HR = 2.24 [1.90–2.64]). Having both conditions conferred a greater potential risk (HR = 3.41 [2.75–4.23]). ConclusionsApproximately one-quarter of the adult US population with diabetes and CKD also has anemia. The presence of anemia, with or without CKD, is associated with a two- to threefold increased risk of death by compared with adults who have neither condition, suggesting that anemia may be a strong predictor of death among adults with diabetes.

Usefulness of the Klotho protein, FGF-23 and GDF-15 in assessment of the new onset Acute Heart Failure

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): This work was supported by a grant from the Institute of Medical Sciences, University of Opole, Poland. Background Acute heart failure (AHF) is a life-threatening multifaceted clinical condition requiring intensive and expensive treatment. Earlier studies highlighted the difference in characteristics and prognosis of new onset AHF (NO- AHF) and acute decompensated heart failure (ADHF). Protein Klotho and FGF23 could be attractive tools in the evaluation of patients with AHF. GDF-15 is a recognized marker of the risk of death and complications, including bleeding in many cardiovascular diseases. Aim The aim of the study was to compare selected biomarkers (Protein Klotho, FGF-23, GDF-15) with clinical characteristics and 12-month outcomes of patients with NO-AHF and ADHF. Methods As part of the prospective Acute Heart Failure Registry (OP-AHF), data from 112 patients hospitalized in Intensive Cardiac Care Unit (ICCU) were collected from June 2019. Inclusion criteria were: hospitalization for AHF and the use of at least one of: intravenous diuretics, catecholamines or mechanical circulatory support. Blood samples were collected on admission, at discharge as well as at the 30-day. Patients were than follow-up for one year. Results Patients with NO-AHF constituted 46% of the study group (52 out of 112) and compared to patients with ADHF they were more often aged under 65 years (44% vs. 30%, p=0.12), better educated (25% vs. 8%, p=0.03), less frequently with diabetes (31% vs. 43%, p=0.17), hypertension (58% vs. 83%, p=0.03), and prior myocardial infarction (19% vs. 45%, p=0.004). In both groups there were more men (69% vs. 80%,p=0.19) and ischemic etiology of heart failure were more frequent (33% vs. 51%, p=0.42) in NO-AHF and ADHF, respectively. Left ventricular ejection fraction (LVEF) was insignificantly higher in patients with NO-AHF on admission (30% vs. 26%, p=0.6) and at discharge (35% vs. 30%, p=0.27).Only patient with NO-AHF improved LVEF at the 12- month follow–up (50% vs. 35%, p=0,003).It was no signifcant differences between median value of Klotho protein in both groups at admission, discharge and 30–day follow up visit. We observed significant reduction in FGF-23 and GDF-16 at tree time points (Table 1). 12-month mortality in patients with NO-AHF was insignificantly lower (17% vs. 28% in ADHF HR=1,7 (95% Cl=0.25-1.18)),also after correction for age, sex and ,LVEF- 20% vs. 25%, respectively, p=0.58; HR=1,26 (0.3-1.8). In the Cox multivariate model, the risk of death was presented as hazard ratio (HR) and was highest for GDF-15 in both groups (Table2). Conclusion Patients with the NO- AHF have different clinical profile than patients with acute decompensated heart failure with a tendency to lower 12-month mortality. There were no significant differences in the median value of Klotho protein in both groups. Reduction of the FGF-23 during hospitalization can serve as a marker of AHF compensation, thus FGF-23 could be a valuable tool for assessing response to treatment. GDF-15 seems to be the strongest predictor of death in both groups of AHF.

Cardiac magnetic resonance-feature tracking technique can assess cardiac function and prognosis in patients with myocardial amyloidosis

To quantitatively assess cardiac functions in patients with cardiac amyloidosis (CA) and hypertrophic cardiomyopathy (HCM) using cardiac magnetic resonance-feature tracking (CMR-FT) technique and evaluate the prognostic value of CMR-FT in patients with CA. We retrospectively collected the data from 31 CA patients with systemic amyloidosis confirmed by Congo red staining and serum immunohistochemistry after extracardiac tissue biopsy undergoing CMR at our hospital from March, 2013 to June, 2021.Thirty-one age and gender matched patients with asymmetric left ventricular wall hypertrophy and 31 healthy individuals without organic or functional heart disease served as the controls.Radial, circumferential and longitudinal strains and strain rates of the left ventricle at the global level and in each myocardial segment (basal, middle and apical) were obtained with CMR-FT technique and compared among the 3 groups.The predictive value of myocardial strains and strain rates for all-cause mortality in CA patients was analyzed using a stepwise COX regression model. The left ventricular volume, myocardial mass, ejection fraction and cardiac output differed significantly among the groups (P < 0.05).Except for apical longitudinal strain, the global and segmental strains were all significantly lower in CA group than in HCM group (P < 0.05).The global and segmental strains were all significantly lower in CA group than in the healthy individuals (P < 0.05).The basal strain rates in the 3 directions were significantly lower in CA group than in the healthy individuals (P < 0.05), but the difference in apical strain rates was not statistically significant between the two groups.Multivariate stepwise COX analysis showed that troponin T (HR=1.05, 95%CI: 1.01-1.10, P=0.017) and middle peak diastolic circumferential strain rate (HR=6.87, 95%CI: 1.52-31.06, P=0.012) were strong predictors of death in CA patients. Strain and strain rate parameters derived from CMR-FT based on cine sequences are new noninvasive imaging markers for assessing cardiac impairment in CA and cardiac function changes in HCM, and provide independent predictive information for all-cause mortality in CA patients.

Congenital diaphragmatic hernia survival in an English regional ECMO center

IntroductionCongenital diaphragmatic hernia (CDH) remains a cause of neonatal death. Our aims are to describe contemporary rates of survival and the variables associated with this outcome, contrasting these with our...