Determinant Of Long-term Outcome Research Articles

Cardiovascular rehabilitation - determinants of long-term outcomes

Cardiovascular rehabilitation - determinants of long-term outcomes

Surgery for Active Infective Endocarditis on Mitral Valve: Anatomical, Surgical, and Disease Factors as Long-Term Outcome Modifiers.

Background and Objectives: Determinants of long-term outcomes after surgery for native mitral valve endocarditis have not been thoroughly investigated. The aim of this study was to assess anatomical, disease, and surgical risk factors for long-term mortality and need of reintervention, in patients undergoing mitral valve surgery for active endocarditis. Materials and Methods: Patients who underwent surgery for active native mitral valve endocarditis at three academic centres, between 2000 and 2022, were analysed. The primary outcome was long-term survival. The secondary outcome was the freedom from mitral reoperation. Survival curves were constructed with Kaplan-Meier methodology. Multivariable Cox regression was used to identify demographic, anatomical, disease, and surgical factors associated with late mortality and reoperation. Results: 335 consecutive patients with active mitral endocarditis were analysed. Two hundred and one patients (70.5%) had infection confined to the valve cusp whereas 89 (25.6%) had invasive disease extended to the annulus and surrounding tissues. Preoperative neurological events occurred at the diagnosis in 52 cases. Streptococci were the most common causative organisms followed by Staphylococcus aureus, Coagulase-negative Staphylococcus, and Enterococcus. Valve repair was performed in 108 patients (32.2%). Survival at 5 and 10 years was 70.1% and 59.2%, respectively. Staphylococcus emerged as an independent predictor of late mortality, along with age, chronic obstructive pulmonary disease, and previous cardiac surgery. Survival was considerably reduced in patients with S. aureus compared with those without (log rank p < 0.001). The type of surgery (repair vs. replacement) did not emerge as a risk factor for late mortality and reoperation. Seventeen patients underwent mitral reoperation during the follow-up. The 5- and 10-year freedom from reoperation was 94.7% and 91.8%, respectively. Conclusions: Active mitral valve endocarditis remains a life-threatening disease with impaired survival. While lesion characteristics influenced surgical decision-making and intraoperative management, their impact on long-term survival and freedom from reintervention appears to be moderated by other factors such as infecting pathogens and patient comorbidities.

A Comprehensive Examination of Clinical Characteristics and Determinants of Long-Term Outcomes in Pediatric Cerebral Sinus Venous Thrombosis

BackgroundTo analyze the clinical and neuroimaging features, risk factors, treatment choices, and long-term clinical outcomes in children with cerebral sinus venous thrombosis (CSVT). MethodsThis is a retrospective cohort study of children diagnosed with CSVT between 2002 and 2018 at Texas Children's Hospital. ResultsA total of 183 children (male: 62.3%) with CSVT were included. The average presenting age was 7.7 years (S.D.: 5.6). The mean follow-up duration was 33.7 months (S.D.: 38.6). The most common presenting clinical feature was headache (36.6%). Head and neck infections other than meningitis (36.6%) were the most common risk factors. Prevalent neurological examination findings included motor deficit (21.3%) and altered mental status (AMS, 20.2%). Neuroimaging features included hemorrhagic infarction (19.6%), ischemic infarction (8.2%), and intracranial hemorrhage without infarction (5.5%). The most common site of thrombosis was the superior sagittal sinus (37.2%), with 78.2% of patients demonstrating involvement of multiple sinuses. Treatment of choice was low-molecular-weight heparin in 69.4% of patients. Factors associated with worse clinical outcomes included head and neck infections, malignancy (other than hematologic), cardiac disease, and recent surgery; seizure and dehydration on initial presentation; motor abnormalities and AMS on initial examination; ischemic infarct only; and involvement of vein of Trolard on neuroimaging. Thrombus condition on repeat imaging, receiving any anticoagulant/antithrombotic treatment, treatment duration, or follow-up duration was not associated with severity of long-term outcome. ConclusionsCSVT may lead to unfavorable long-term outcomes in a remarkable portion of pediatric patients. Thus, a high index of suspicion and early and appropriate management of pediatric CSVT is imperative.

UNICORNS: Uveitis in childhood prospective national cohort study protocol.

Background: Childhood uveitis is a rare inflammatory eye disease which is typically chronic, relapsing-remitting in nature, with an uncertain aetiology (idiopathic). Visual loss occurs due to structural damage caused by uncontrolled inflammation. Understanding of the determinants of long term outcome is lacking, including the predictors of therapeutic response or how to define disease control. Aims: To describe disease natural history and outcomes amongst a nationally representative group of children with non-infectious uveitis, describe the impact of disease course on quality of life for both child and family, and identify determinants of adverse visual, structural and developmental outcomes. Methods: UNICORNS is a prospective longitudinal multicentre cohort study of children newly diagnosed with uveitis about whom a core minimum clinical dataset will be collected systematically. Participants and their families will also complete patient-reported outcome measures annually from recruitment. The association of patient (child- and treatment- dependent) characteristics with outcome will be investigated using logistic and ordinal regression models which incorporate adjustment for within-child correspondence between eyes for those with bilateral disease and repeated outcomes measurement. Discussion: Through this population based, prospective longitudinal study of childhood uveitis, we will describe the characteristics of childhood onset disease. Early (1-2 years following diagnosis) outcomes will be described in the first instance, and through the creation of a national inception cohort, longer term studies will be enabled of outcome for affected children and families.

Rescue Paracetamol in Postoperative Pain Management in Extremely Low Birth Weight Neonates Following Abdominal Surgery: A Single Unit Retrospective Study.

BackgroundIntravenous paracetamol added to morphine reduces postoperative morphine consumption in (near)term neonates. However, there are only sparse data on intravenous paracetamol as multimodal strategy in extremely low birth weight (ELBW) neonates.ObjectivesThis study aims to assess the effects of rescue intravenous paracetamol on postoperative pain management (≤48 h postoperatively) in relation to both analgesic efficacy (validated pain assessment, drug consumption, adequate rescue medication) and safety (hypotension and bradycardia). This rescue practice was part of a standardized pain management approach in a single neonatal intensive care unit (NICU).MethodsA single-center retrospective observational study included 20 ELBW neonates, who underwent major abdominal surgery. The primary endpoints of the postoperative study period were pain intensity, over-sedation, time to first rescue analgesic dose, and the effect of paracetamol on opiate consumption. Secondary endpoints were safety parameters (hypotension, bradycardia). And as tertiary endpoints, the determinants of long-term outcome were evaluated (i.e., duration of mechanical ventilation, intraventricular hemorrhage - IVH, periventricular leukomalacia - PVL, postnatal growth restriction, stage of chronic lung disease – CLD or neurodevelopmental outcome according to Bayley-II Scales of Infant Development at 18–24 months).ResultsAll neonates received continuous opioids (sufentanil or morphine) and 13/20 also intravenous paracetamol as rescue pain medication during a 48-h postoperative period. Although opioid consumption was equal in the non-paracetamol and the paracetamol group over 48 h, the non-paracetamol group was characterized by oversedation (COMFORTneo < 9), a higher incidence of severe hypotension, and younger postnatal age (p < 0.05). All long-term outcome findings were similar between both groups.ConclusionsOur study focused on postoperative pain management in ELBW neonates, and showed that intravenous paracetamol seems to be safe. Prospective validation of dosage regimens of analgesic drugs is needed to achieve efficacy goals.

LONG-TERM OUTCOMES AMONG NIGERIAN STROKE SURVIVORS - DATA FROM THE CogFAST-NIGERIA STUDY

<h3>Background</h3> Africa faces a rising burden of stroke with rising incidence and prevalence but little is known about the profile and trajectory of long-term stroke outcomes This study aimed to explore the profile, trajectory and determinants of long-term outcomes up to four years among a cohort of stroke survivors recruited into the CogFAST-Nigeria study. <h3>Methods</h3> The data analysed were collected in a longitudinal study of stroke survivors who were prospectively recruited from the Federal Medical Centre, Abeokuta and University College Hospital, Ibadan Nigeria. Subjects with subarachnoid haemorrhage, neurologic illness, or any systemic disease that could impair cognition were excluded from the study. Cognitive function was assessed using the vascular neuropsychological battery, depression through the Geriatric Depression Scale-short form, and functional dependency through the Barthel Index tool. Baseline enrolment was done three months after stroke (2010 -2011) and the stroke survivors were thereafter followed up for a period of four years (2014-2015). <h3>Results</h3> Of the 253 stroke survivors recruited into the study, the overall mean age was 60.2 (±9.8) <i>years</i>, 62.6% males, and overall mean number of years of formal education was 10.21 (±5.3). The proportion of stroke survivors with cognitive impairment was 53.2% at six months, 56.9%, 58.7%, 60.9 %, and 66.7 % at one, two, three, and four years, respectively, while depression was 39.3 % at three months, 35.2 %, 35.5 %, 26.7 %, and 36.1 % at one, two, three, and four years respectively. At six months after a stroke, the case fatality rate was 7.5 % (95 % C.I = 4.82-11.4), and 24.8 % (95 % C.I = 19.93-30.6), 39.4 % (95 % CI=3.65-45.7), and 45.3 % (95 % CI=39.42-51.6) at 1, 3 and 4 years respectively. Factors associated with mortality at 10% significance level include professional occupation (OR= 0.49; 90% CI=0.27-0.92; p-value=0.063) and those living with spouse/spouse and children (OR=0.57; 90%CI=0.35-0.93 p-value=0.058) while previous stroke was associated with functional dependency (OR=2.17; 95% C.I = 1.19-3.95, p-value 0.011). Older age (>70 yrs) (OR=23.47; 95%C.I=2.71-203.44, p-value=0.004), higher education (OR=0.17 95%C.I=0.04-0.69, p-value=0.013), professional occupation (OR=13.25; 95%C.I=1.04-168.55; p-value=0.046), previous stroke (OR=7.03 95%C.I=1.30-37.96, p-value=0.023), and caregiver burden (OR=3.51; 05% C.I=1.53-8.05, p-value=0.003) were predictors of cognitive impairment among the stroke survivors. <h3>Conclusion</h3> The study findings re-emphasize the importance of educational attainment, secondary stroke prevention and rich social network as a way of improving stroke outcomes.

Long-term outcomes among Nigerian stroke survivors; data from the CogFAST-Nigeria study

Africa faces a rising burden of stroke with rising incidence and prevalence but little is known about the profile and trajectory of long-term outcomes and mortality after stroke. The aim of this study is to explore the trajectory and determinants of long-term outcomes up to four years among a cohort of stroke survivors recruited into the CogFAST-Nigeria study.

Risk factors associated with mechanical ventilation, autonomic nervous dysfunction and physical outcome in Vietnamese adults with tetanus

BackgroundTetanus remains common in many low- and middle-income countries, but as critical care services improve, mortality from tetanus is improving. Nevertheless, patients develop severe syndromes associated with autonomic nervous system disturbance (ANSD) and the requirement for mechanical ventilation (MV). Understanding factors associated with worse outcome in such settings is important to direct interventions. In this study, we investigate risk factors for disease severity and long-term physical outcome in adults with tetanus admitted to a Vietnamese intensive care unit.MethodsClinical and demographic variables were collected prospectively from 180 adults with tetanus. Physical function component scores (PCS), calculated from Short Form Health Survey (SF-36), were assessed in 79 patients at hospital discharge, 3 and 6 months post discharge.ResultsAge, temperature, heart rate, lower peripheral oxygen saturation (SpO2) and shorter time from first symptom to admission were associated with MV (OR 1.03 [ 95% confidence interval (CI) 1.00, 1.05], p = 0.04; OR 2.10 [95% CI 1.03, 4.60], p = 0.04; OR 1.04 [ 95% CI 1.01, 1.07], p = 0.02); OR 0.80 [95% CI 0.66, 0.94], p = 0.02 and OR 0.65 [95% CI 0.52, 0.79, p < 0.001, respectively).Heart rate, SpO2 and time from first symptom to admission were associated with ANSD (OR 1.03 [95% CI 1.01, 1.06], p < 0.01; OR 0.95 [95% CI 0.9, 1.00], p = 0.04 and OR 0.64 [95% CI 0.48, 0.80], p < 0.01, respectively).Median [interquartile range] PCS at hospital discharge, 3 and 6 months were 32.37 [24.95–41.57, 53.0 [41.6–56.3] and 54.8 [51.6–57.3], respectively. Age, female sex, admission systolic blood pressure, admission SpO2, MV, ANSD, midazolam requirement, hospital-acquired infection, pressure ulcer and duration of ICU and hospital stay were associated with reduced 0.25 quantile PCS at 6 months after hospital discharge.ConclusionsMV and ANSD may be suitable endpoints for future research. Risk factors for reduced physical function at 3 months and 6 months post discharge suggest that modifiable features during hospital management are important determinants of long-term outcome.

UNICORNS: Uveitis in childhood prospective national cohort study protocol

Background: Childhood uveitis is a rare inflammatory eye disease which is typically chronic, relapsing-remitting in nature, with an uncertain aetiology (idiopathic). Visual loss occurs due to structural damage caused by uncontrolled inflammation. Understanding of the determinants of long term outcome is lacking, including the predictors of therapeutic response or how to define disease control. Aims: To describe disease natural history and outcomes amongst a nationally representative group of children with non-infectious uveitis, describe the impact of disease course on quality of life for both child and family, and identify determinants of adverse visual, structural and developmental outcomes. Methods: UNICORNS is a prospective longitudinal multicentre cohort study of children newly diagnosed with uveitis about whom a core minimum clinical dataset will be collected systematically. Participants and their families will also complete patient-reported outcome measures annually from recruitment. The association of patient (child- and treatment- dependent) characteristics with outcome will be investigated using logistic and ordinal regression models which incorporate adjustment for within-child correspondence between eyes for those with bilateral disease and repeated outcomes measurement. Discussion: Through this population based, prospective longitudinal study of childhood uveitis, we will describe the characteristics of childhood onset disease. Early (1-2 years following diagnosis) outcomes will be described in the first instance, and through the creation of a national inception cohort, longer term studies will be enabled of outcome for affected children and families.

Food Insecurity and Mortality in American Adults: Results From the NHANES-Linked Mortality Study.

Food insecurity is a significant public health problem in the United States leading to substantial social, economic, and health care-related burdens. While studies continue to estimate the prevalence of food insecurity, the long-term outcomes are not extensively explored. The purpose of this study was to assess the impact of food insecurity on mortality. We analyzed data on adults (≥ 20 years) from the 1999-2010 National Health and Nutrition Examination Survey, with mortality data obtained through 2015. Among the total study participants (n = 25,247), 17.6% reported food insecurity. Food-insecure individuals were more likely to be younger in age, minorities, poorer, with lesser education, obese, smokers, and with diabetes compared to food-secure counterparts. During a 10.2-year follow-up, among the food insecure, 821 individuals died (11%). The hazard ratio (HR) for mortality among the food insecure compared with the food secure, with adjustment for age and gender only, was 1.58; 95% confidence interval [CI: 1.25, 2.01]. The adjusted HRs for all-cause mortality, HR = 1.46, CI [1.23, 1.72], p < .001, and cardiovascular mortality, HR = 1.75, CI [1.19, 2.57], p < .01, were statistically significantly higher among food-insecure individuals, after adjustment for multiple demographic and health risk factors. Individuals who are food-insecure have a significantly higher probability of death from any cause or cardiovascular disease in long-term follow-up. Comprehensive and interdisciplinary approaches to reducing food insecurity-related disparities and health risks should be implemented. Including food insecurity in health risk assessments and addressing food insecurity as a determinant of long-term outcomes may contribute to lower premature death rates.

305Pacemaker therapy after cardiac valve replacement surgery: impact on heart failure hospitalizations

Abstract Background Left ventricular (LV) function is a major determinant of long-term outcomes after valve replacement surgery. Although conventional (right ventricular) pacemaker therapy is life-saving, it may cause heart failure (HF). Aims To determine whether permanent pacemaker implantation (PPI) confers a risk of HF in surgical valve recipients. Methods The primary endpoint of HF hospitalization and the secondary endpoints of total mortality and total mortality / HF hospitalizations were compared in valve recipients with and without PPI. Traditional as well as multi-state, multivariable modelling was used to assess the influence of PPI on clinical outcomes. Results Amongst patients (n = 135,242) undergoing a first aortic (AVR; n = 111,674), mitral (MVR; n = 18,402) valve replacement, or AVR + MVR (n = 5,166) over 14 years in 176 centre, 12,952 (10.6%) had a PPI at any time during follow-up and 5,805 (4.3%) underwent PPI postoperatively. After 3.9 yrs (median, interquartile range: 6.1), heart failure (HF) hospitalizations (HR: 1.47, 95% C.I. 1.36-1.59), total mortality (HR: 1.10, 95% C.I. 1.05-1.16) and total mortality or HF hospitalizations (HR: 1.17, 95% C.I. 1.12-1.22; see figure) were higher in patients with post-operative PPI than in patients without. Multi-state modelling revealed that the transition hazard from PPI at any time to HF hospitalizations was markedly higher (transition hazard rate: 0.29, 95% C.I. 0.24-0.36) than from valve replacement surgery to HF hospitalization. Conclusions After valve replacement surgery, PPI is associated with increased HF hospitalization and total mortality, particularly after dual valve replacements. Abstract Figure.

Correction in article by Galian-Gay et al. “Determinants of long-term outcome of repaired pulmonary valve stenosis”, Rev Esp Cardiol. 2020;73:131-138

Correction in article by Galian-Gay et al. “Determinants of long-term outcome of repaired pulmonary valve stenosis”, Rev Esp Cardiol. 2020;73:131-138

Stimulation of soluble guanylate cyclase improves donor organ function in rat heart transplantation

Heart transplantation remains the definitive therapy of end-stage heart failure. Ischemia-reperfusion injury occurring during transplantation is a primary determinant of long-term outcome of heart transplantation and primary graft insufficiency. Modification of the nitric oxide/soluble guanylate cyclase/cyclic guanosine monophosphate signaling pathway appears to be one of the most promising among the pharmacological interventional options. We aimed at characterizing the cardio-protective effects of the soluble guanylate cyclase stimulator riociguat in a rat model of heterotopic heart transplantation. Donor Lewis rats were treated orally with either riociguat or placebo for two days (n = 9) in each transplanted group and (n = 7) in donor groups. Following explantation, hearts were heterotopically transplanted. After one hour reperfusion, left ventricular pressure-volume relations and coronary blood flow were recorded. Molecular biological measurements and histological examination were also completed. Left ventricular contractility (systolic pressure: 117 ± 13 vs. 48 ± 5 mmHg, p < 0.001; dP/dtmax: 2963 ± 221 vs. 1653 ± 159 mmHg/s, p < 0.001), active relaxation (dP/dtmin: −2014 ± 305 vs. −1063 ± 177 mmHg/s, p = 0.02; all at 120 µl of left ventricular volume), and alteration of coronary blood flow standardized to heart weight (2.55 ± 0.32 vs. 1.67 ± 0.22 ml/min/g, p = 0.03) were markedly increased following preconditioning with riociguat. Myocardial apoptosis markers were also significantly reduced in the riociguat pretreated group as well as the antioxidant markers were elevated. Pharmacological preconditioning with riociguat decreases ischemia-reperfusion injury and improves donor organ function in our animal model of heart transplantation. Therefore, riociguat might be a potential cardioprotective agent.

Long-term outcome changes after mechanical thrombectomy for anterior circulation acute ischemic stroke.

Mechanical thrombectomy (MT) improves early clinical outcome in patients with acute ischemic stroke but insights on determinants of long-term outcome after MT treatment are scarce. Data from stroke patients with anterior circulation large vessel occlusion of a prospective MT registry (01/2014-06/2017) of a large comprehensive stroke center were analyzed regarding clinical outcome between short- (3months) and long-term (12months) assessment reflected by a change of modified Rankin scores (∆mRS). Secondary endpoints included favorable long-term outcome (mRS 0-2). Multi-variable regression analysis was performed to identify determinants of outcome changes and favorable outcome at long term. Of 264 patients included, 42.0% showed a favorable long-term outcome. Longitudinal analysis found that some individuals still improved, but no overall mRS difference between short and long-term follow-up was detected [∆mRS -0.004 (95% CI -0.020; 0.013); p = 0.672]. Right hemispheric stroke [∆mRS 0.286 (0.011; 0.561); p = 0.043] and high NIHSS at discharge [∆mRS, 0.039 (0.004; 0.074); p = 0.029] were associated with a longitudinal mRS decline. Favorable long-term outcome was associated with successful recanalization (p < 0.0001). A significant number of patients with MT experience a favorable long-term outcome. Outcomes remained stable between short- and long-term follow-up, but some individuals may still show improvement beyond short-term rehabilitation. Right hemispheric stroke and clinical stroke severity at hospital discharge may be frail predictors for delayed decline of functional status, whereas successful recanalization remains a positive outcome predictor. Death rarely occurs beyond 3months after MT treatment.

Malnutrition in Cirrhosis and Its Management

The World Health Organization defines malnutrition as a term referring to deficiencies, excesses, or imbalances in a person’s intake or energy and/or nutrients. Malnutrition is a nearly universal complication of end-stage liver disease, with a prevalence of up to 90%. Given their hepatic synthetic dysfunction, patients with cirrhosis are at a particularly high risk for protein-calorie depletion, which has been reported in over half of patients with cirrhosis and worsens with disease severity. Undernutrition is a potent predictor of adverse outcomes in cirrhotic patients, including lower survival rates, hepatic decompensation, longer length of days in the hospital and intensive care unit (ICU), increased number of infection episodes, and higher resource utilization. On the other hand, excess energy intake, or overnutrition, is increasingly being recognized as an important determinant of long-term outcomes in this population, particularly those with nonalcoholic steatohepatitis. Nearly one quarter of patients with cirrhosis are overnourished and up to 72% show excessive daily intake of energy and protein. In this review, we will consider the full spectrum of malnutrition in patients with end-stage liver disease and highlight key areas in need of further investigation. This review contains 4 figures, 4 tables, and 54 references. Key Words: frailty, inflammation, nocturnal feeding, nutritional assessment, nutritional risk, nutritional screening, protein-energy malnutrition, sarcopenia

Malnutrition in Cirrhosis and Its Management

The World Health Organization defines malnutrition as a term referring to deficiencies, excesses, or imbalances in a person’s intake or energy and/or nutrients. Malnutrition is a nearly universal complication of end-stage liver disease, with a prevalence of up to 90%. Given their hepatic synthetic dysfunction, patients with cirrhosis are at a particularly high risk for protein-calorie depletion, which has been reported in over half of patients with cirrhosis and worsens with disease severity. Undernutrition is a potent predictor of adverse outcomes in cirrhotic patients, including lower survival rates, hepatic decompensation, longer length of days in the hospital and intensive care unit (ICU), increased number of infection episodes, and higher resource utilization. On the other hand, excess energy intake, or overnutrition, is increasingly being recognized as an important determinant of long-term outcomes in this population, particularly those with nonalcoholic steatohepatitis. Nearly one quarter of patients with cirrhosis are overnourished and up to 72% show excessive daily intake of energy and protein. In this review, we will consider the full spectrum of malnutrition in patients with end-stage liver disease and highlight key areas in need of further investigation. This review contains 4 figures, 4 tables, and 54 references. Key Words: frailty, inflammation, nocturnal feeding, nutritional assessment, nutritional risk, nutritional screening, protein-energy malnutrition, sarcopenia

A Detailed Overview of Long-Term Outcomes in Severe Traumatic Brain Injury Eight Years Post-injury.

Background and aims: Severe traumatic brain injury is a leading cause of acquired persistent disabilities, and represents an important health and economic burden. However, the determinants of long-term outcome have rarely been systematically studied in a prospective longitudinal study of a homogeneous group of patients suffering exclusively from severe TBIMethods: Prospective observational study of an inception cohort of adult patients with severe traumatic brain injury in the Parisian area (PariS-TBI). Outcome was assessed with face-to-face interview 8 years after Traumatic Brain Injury, focusing on impairments, activity limitations, and participation restriction.Results: Five hundred and four patients were included between 2005 and 2007. At 8-year follow-up, 261 patients were deceased, 128 were lost to follow-up, 22 refused to participate, and 86 were finally evaluated. Age, gender, initial injury severity did not significantly differ between evaluated patients and lost to follow-up, but the latter were more frequently students or unemployed. Mean age was 41.9 (SD 13.6), 79% were male, median initial Glasgow Coma Scale Score was 6. The most frequent somatic complaints concerned balance (47.5%), motricity (31%), and headaches (36%), but these were less frequent than cognitive complaints (Memory 71%, Slowness 68%, Concentration 67%). According to the Hospital Anxiety and Depression Scale (HADS), 25 % had a score >8 for anxiety and 23.7% for depression. According to the Extended Glasgow Outcome Scale, 19.8% remained severely disabled, 46.5% moderately disabled, 33.7% had a good recovery. Older age, longer education duration, lower functional status upon intensive care discharge, and more severe 8-year dysexecutive problems were significantly associated with a lower Extended Glasgow Outcome Scale score in multivariable analysis. At 8 years, 48.7% of patients were employed in a productive job. Of those, 38% declared a salary loss since traumatic brain injury. Unemployment was significantly associated with lower 1-year GOSE score and more severe 8-year dysexecutive problems.Conclusions: These results from an inception cohort study highlight the fact that long-term outcome after severe TBI is determined by a complex combination of injury-related, demographic and neuropsychological factors. Long after the injury, persisting impairments still interfere with social integration, and participation.

The relationship between aortoiliac calcification and long-term outcome in rectal cancer resection.

705 Background: The interaction between host and tumour factors is an important determinant of long-term outcome following rectal cancer resection. At cellular level, hypoxia within the tumour microenvironment stimulates neovascularisation, alters tumour metabolism and is implicated in dissemination and metastases. At host level, restricted blood flow to the tumour may play a role in tumour hypoxia. Significant calcification of the distal aortic and iliac arteries could result in impaired rectal perfusion. We aimed to investigate the relationship between aortoiliac calcification (AC) and long-term outcome following rectal cancer resection. Methods: Patients were identified from a prospectively maintained database. Recurrence and survival data were abstracted. On staging CT images, the sum of calcified quadrants of the distal aorta and iliac arteries at the level of the bifurcation was calculated. ROC analysis was used to identify the optimum threshold for determining significant calcification. Results: Between 2008-2016, 181 patients with available CT scans underwent surgery for rectal cancer. Most were male (60%), aged over 65 (53%) and TNM stage II/III (72%). Median follow-up was 63 months. Significant AC was identified in 44 patients (24%). Recurrence occurred in 42 patients: local in 16 (9%) and systemic in 26 (14%) patients. Recurrence was associated with significant AC (p = 0.017), TNM stage (p = 0.002) and venous invasion (p = 0.006). When considering those with and without significant AC, there were differences in the rates of local (11% vs. 8%) and systemic (25% vs. 11%) recurrence respectively (p = 0.043). On univariate Cox regression analysis, overall survival was related to age (p = 0.012), ASA grade (p = 0.042) and significant AC (p = 0.001). On multivariate analysis, significant AC (p = 0.011) was the only independent predictor of overall survival. Conclusions: The burden of aortoiliac calcification appears to play an important role in influencing long-term outcome following rectal cancer resection, independent of traditional determinants such as TNM stage and ASA grade. While validation is required, further investigation of the mechanism underlying this relationship is warranted.

Long-Term Outcomes of Real-World Korean Patients with Atrial-Fibrillation-Related Stroke and Severely Decreased Ejection Fraction.

Background and PurposeThe clinical implications of echocardiography findings for long-term outcomes in atrial fibrillation (AF)-related stroke patients are unknown.MethodsThis was a substudy of the Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts (K-ATTENTION), which is a multicenter-based cohort comprising prospective stroke registries from 11 tertiary centers. Stroke survivors who underwent two-dimensional transthoracic echocardiography during hospitalization were enrolled. Echocardiography markers included the left-ventricle (LV) ejection fraction (LVEF), the left atrium diameter, and the ratio of the peak transmitral filling velocity to the mean mitral annular velocity during early diastole (E/e′ ratio). LVEF was categorized into normal (≥55%), mildly decreased (>40% and <55%), and severely decreased (≤40%). The E/e′ ratio associated with the LV filling pressure was categorized into normal (<8), borderline (≥8 and <15), and elevated (≥15). Kaplan-Meier and Cox regression analyses were performed for recurrent stroke, major adverse cardiac events, and all-cause death.ResultsThis study finally included 1,947 patients. Over a median follow-up of 1.65 years (interquartile range, 0.42–2.87 years), the rates of recurrent stroke, major adverse cardiac events, and all-cause death were 35.1, 10.8, and 69.6 cases per 1,000 person-years, respectively. Multivariable analyses demonstrated that severely decreased LVEF was associated with a higher risks of major adverse cardiac events [hazard ratio (HR), 3.91; 95% confidence interval (CI), 1.58–9.69] and all-cause death (HR, 1.95; 95% CI, 1.23–3.10). The multivariable fractional polynomial plot indicated that recurrent stroke might be associated with a lower LVEF.ConclusionsSevere LV systolic dysfunction could be a determinant of long-term outcomes in AF-related stroke.

Determinants of Long-Term Outcome in Type 1/like Calreticulin-Mutated Myelofibrosis

Background:Type 1 calreticulin (CALR) variants comprise ~70% of all CALR mutations in primary myelofibrosis (PMF) and form a distinct phenotypic and prognostic disease subset (Leukemia. 2014;28:1568). Determinants of long-term outcome have not, however, been systematically appraised in this population. The current study documents the natural history, molecular correlates, and independent predictors of overall (OS), leukemia-free (LFS), and thrombosis-free (TFS) survival in CALR type 1/like-mutated myelofibrosis.Methods:Patients were recruited from the Mayo Clinic, Rochester, MN, USA. Diagnoses were consistent with World Health Organization (PMF, fibrotic/leukemic transformations) (Blood. 2016;127:2391) and International Working Group for Myeloproliferative Neoplasms Research and Treatment criteria (post-essential thrombocythemia (ET) MF) (Leukemia. 2008;22:437). Laboratory and clinical data were retrospectively abstracted corresponding to time of referral (PMF) or myelofibrotic transformation (post-ET MF). Conventional prognostic scoring was as previously outlined (Blood. 2010;115:1703; J Clin Oncol. 2018;36:1769). Recipients of allogeneic stem cell transplant were censored at the time of transplant. Standard statistical methods were used for all analyses using the JMP® Pro 13.0.0 software package (SAS Institute, Cary, NC, USA).Results:A total of 162 consecutive patients with CALR type 1/like-mutated myelofibrosis were identified: 139 (86%) with PMF and 23 (14%) with post-ET MF with median age 55 years (range 23-85), 62% male. The PMF and post-ET MF cohorts displayed similar phenotypic features with the exception of higher platelet counts (median 443 vs 340 x 109/l; P=0.02) in post-ET MF (Table 1). The most frequent co-existing mutations were ASXL1 (n=47; 37%) and SRSF2 (n=4; 3%), with ASXL1 seen more frequently in PMF (39% vs 11% post-ET MF; P=0.07). Over a median follow-up of 6 years (range 0-25 years), a total of 20 (12%) leukemic transformations and 66 (41%) deaths were recorded, with no significant differences between the PMF and post-ET MF cohorts (P=0.16 and 0.11, respectively). Kaplan-Meier survival estimates revealed comparably favorable median OS in both CALR type 1/like-mutated variants: not yet reached and 13 years in post-ET MF vs PMF, respectively (P=0.7) (Figure 1A).Multivariable analysis disclosed moderate to severe sex-adjusted anemia (P<0.001), ≥2% circulating blasts (P<0.001), very high risk (VHR) karyotype (P<0.001), age >70 years (P=0.006), and constitutional symptoms (P=0.008) to be independent predictors of inferior OS in CALR type 1/like-mutated PMF (Table 2). LFS was significantly shortened in the presence of IDH1 mutations (P=0.01) and platelets <100 x 109/l (P=0.02) while IDH2 mutations (P=0.02), leukocytosis ≥11 x 109/l (P=0.03) and history of arterial thrombosis (P=0.04) were independent predictors of shortened TFS. Importantly, myelofibrosis variant (primary vs post-ET) did not influence survival (P=0.7) or complication rates (P=0.8 for LFS, P=0.09 for TFS) (Table 2).The karyotype- and mutation-enhanced international prognostic scoring system (MIPSS70+ version 2.0), was effective in risk stratifying type 1/like CALR-mutated PMF (P-values 0.01 to <0.0001), with the exception of low vs intermediate (P=0.22) and intermediate vs high risk (P=0.49) (Figure 1C). The detrimental influences of unfavorable/VHR karyotype and ASXL1 mutations were confirmed (Figure 2A-B) while borderline adverse and prognostically neutral effects were seen on OS for U2AF1 (n=116; P=0.05) and SRSF2 (n=120; P=0.98) respectively (Figure 2C-D).Conclusions:The current study documents analogous disease patterns in primary and post-ET CALR type 1/like-mutated MF and provides information on determinants of long-term survival. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.