Cause Of Early Death Research Articles

86 - Investigating the cause of early death after radical lung radiotherapy

86 - Investigating the cause of early death after radical lung radiotherapy

Long-term Outcome in Severe Left Ventricular Primary Graft Dysfunction Post Cardiac Transplantation Supported by Early Use of Extracorporeal Membrane Oxygenation.

Severe primary graft dysfunction (PGD) is the leading cause of early death following cardiac transplantation. The early use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) may facilitate graft rescue. However, the additional risks of its use are unknown. We retrospectively reviewed the medical records of all adult patients who underwent cardiac transplantation from January 2009 to February 2016 at St Vincent's Hospital, Sydney, to evaluate risk factors for the use of VA-ECMO and related morbidity and long-term survival. One hundred ninety-two transplanted patients were identified, 49 (25%) of whom developed left or biventricular PGD requiring VA-ECMO. The total operation time (median 495 [interquartile range 139.8] versus 412.8 [132] min, P < 0.001), cardiopulmonary bypass time (220 [63] versus 176 [73] min, P < 0.001) and the presence of a previous sternotomy (29 [59%] versus 51 [36%], P = 0.019) were associated with the use of VA-ECMO. One-year survival in the VA-ECMO cohort was 71%. After a median follow-up time of 696 days (interquartile range 1201 d), survival was significantly higher in the non-ECMO group (P = 0.004) but not when conditioned on hospital survival (P = 0.34). Patients with shorter than median ECMO runtime (<108 h) had a similar long-term survival to patients who did not require ECMO (P = 0.559). In the ECMO cohort, multivariable logistic regression revealed baseline creatinine in µmol/L (odds ratio 0.99 [95% confidence interval 0.99-1.00], P = 0.019) and duration of ECMO support in days (odds ratio 0.65 [95% confidence interval 0.44-0.97], P = 0.034) were inversely and independently associated with 1-year survival. Short- and long-term survival of PGD supported with VA-ECMO was better than previously described. Early recovery of PGD on VA-ECMO support negates its negative impact on short- and long-term survival.

Indomethacin for intracranial hypertension secondary to severe traumatic brain injury in adults.

Among people who have suffered a traumatic brain injury, increased intracranial pressure continues to be a major cause of early death; it is estimated that about 11 people per 100 with traumatic brain injury die. Indomethacin (also known as indometacin) is a powerful cerebral vasoconstrictor that can reduce intracranial pressure and, ultimately, restore cerebral perfusion and oxygenation. Thus, indomethacin may improve the recovery of a person with traumatic brain injury. To assess the effects of indomethacin for adults with severe traumatic brain injury. We ran the searches from inception to 23 August 2019. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 8) in the Cochrane Library, Ovid MEDLINE, Ovid Embase, CINAHL Plus (EBSCO), four other databases, and clinical trials registries. We also screened reference lists and conference abstracts, and contacted experts in the field. Our search criteria included randomised controlled trials (RCTs) that compared indomethacin with any control in adults presenting with severe traumatic brain injury associated with elevated intracranial pressure, with no previous decompressive surgery. Two review authors independently decided on the selection of the studies. We followed standard Cochrane methods. We identified no eligible studies for this review, either completed or ongoing. We found no studies, either completed or ongoing, that assessed the effects of indomethacin in controlling intracranial hypertension secondary to severe traumatic brain injury. Thus, we cannot draw any conclusions about the effects of indomethacin on intracranial pressure, mortality rates, quality of life, disability or adverse effects. This absence of evidence should not be interpreted as evidence of no effect for indomethacin in controlling intracranial hypertension secondary to severe traumatic brain injury. It means that we have not identified eligible research for this review.

A Decade of Damage Control Resuscitation: New Transfusion Practice, New Survivors, New Directions.

The aim of this study was to identify the effects of recent innovations in trauma major hemorrhage management on outcome and transfusion practice, and to determine the contemporary timings and patterns of death. The last 10 years have seen a research-led change in hemorrhage management to damage control resuscitation (DCR), focused on the prevention and treatment of trauma-induced coagulopathy. A 10-year retrospective analysis of prospectively collected data of trauma patients who activated the Major Trauma Centre's major hemorrhage protocol (MHP) and received at least 1 unit of red blood cell transfusions (RBC). A total of 1169 trauma patients activated the MHP and received at least 1 unit of RBC, with similar injury and admission physiology characteristics over the decade. Overall mortality declined from 45% in 2008 to 27% in 2017, whereas median RBC transfusion rates dropped from 12 to 4 units (massive transfusion rates from 68% to 24%). The proportion of deaths within 24 hours halved (33%-16%), principally with a fall in mortality between 3 and 24 hours (30%-6%). Survivors are now more likely to be discharged to their own home (57%-73%). Exsanguination is still the principal cause of early deaths, and the mortality associated with massive transfusion remains high (48%). Late deaths are now split between those due to traumatic brain injury (52%) and multiple organ dysfunction (45%). There have been remarkable reductions in mortality after major trauma hemorrhage in recent years. Mortality rates continue to be high and there remain important opportunities for further improvements in these patients.

Cytomegalovirus seropositivity is independently associated with cardiovascular disease in non-dialysis dependent chronic kidney disease.

Cardiovascular disease (CVD) is the leading cause of early death in patients with chronic kidney disease (CKD). Previous work has described an association between Cytomegalovirus (CMV) seropositivity and CVD amongst patients with dialysis dependent end stage renal disease. Whether CMV seropositivity is associated with CVD in non-dialysis dependent CKD has not been established. Investigate whether past CMV infection is associated with prevalent CVD in patients with non-dialysis dependent CKD. A retrospective observational study using the Renal Impairment in Secondary Care cohort, a study evaluating bio-clinical determinants of outcomes in patients with progressive CKD. We assayed cryopreserved serum samples collected at inception for anti-CMV IgG antibodies from 764 patients with stages 2 to 5 CKD (pre-dialysis) and investigated its relationship with prevalent CVD. Median estimated glomerular filtration was 24 ml/min/1.73 m2 (IQR 19-32). Sixty-eight percent of patients were CMV seropositive. CMV seropositivity was associated with older age, non-Caucasian ethnicity, diabetes and higher social deprivation index score. On univariable analysis, CMV seropositivity correlated with higher systolic blood pressure (P = 0.044), prevalent CVD (P < 0.001), ischaemic heart disease (P < 0.001) and cerebrovascular disease (P = 0.022). On multivariable analysis, CMV seropositive patients nearly twice as likely to have CVD compared to seronegative patients [Odds Ratio (OR) = 1.998, CI 1.231-3.242, P = 0.005]. In patients with non-dialysis CKD, CMV seropositivity is independently associated with a higher prevalence of CVD.

Potential causes of early death among admitted newborns in a rural Tanzanian hospital.

BackgroundApproximately 40,000 newborns die each year in Tanzania. Regional differences in outcome are common. Reviewing current local data, as well as defining potential causal pathways leading to death are urgently needed, before targeted interventions can be implementedObjectiveTo describe the clinical characteristics and potential causal pathways contributing to newborn death and determine the presumed causes of newborn mortality within seven days, in a rural hospital setting.MethodsProspective observational study of admitted newborns born October 2014–July 2017. Information about labour/delivery and newborn management/care were recorded on data collection forms. Causes of deaths were predominantly based on clinical diagnosis.Results671 were admitted to a neonatal area. Reasons included prematurity n = 213 (32%), respiratory issues n = 209 (31%), meconium stained amniotic fluid with respiratory issues n = 115 (17%) and observation for < 24 hours n = 97 (14%). Death occurred in 124 infants. Presumed causes were birth asphyxia (BA) n = 59 (48%), prematurity n = 19 (15%), presumed sepsis n = 19 (15%), meconium aspiration syndrome (MAS) n = 13 (10%) and congenital abnormalities n = 14 (11%). More newborns who died versus survivors had oxygen saturation <60% on admission (37/113 vs 32/258; p≤0.001) respectively. Moderate hypothermia on admission was common i.e. deaths 35.1 (34.6–36.0) vs survivors 35.5 (35.0–36.0)°C (p≤0.001). Term newborns who died versus survivors were fourfold more likely to have received positive pressure ventilation after birth i.e. 4.57 (1.22–17.03) (p<0.02).ConclusionIntrapartum-related complications (BA, MAS), prematurity, and presumed sepsis were the leading causes of death. Intrapartum hypoxia, prematurity and attendant complications and presumed sepsis, are major pathways leading to death. Severe hypoxia and hypothermia upon admission are additional contributing factors. Strategies to identify fetuses at risk during labour e.g. improved fetal heart rate monitoring, coupled with timely interventions, and implementation of WHO interventions for preterm newborns, may reduce mortality in this low resource setting.

P903Is left ventricular longitudinal strain a good pronostic factor in friedreich ataxia?

Abstract Introduction Friedreich ataxia (FRDA) is a rare genetic sensory ataxia. The causal mutation is an expanded trinucleotide repeat (GAA) in the frataxin gene. Hypertrophic cardiomyopathy is associated with FRDA and is the major cause of early death before 40 years old. Patients with progressive decline of the left ventricular ejection fraction (LVEF) have the worse prognosis. Speckle tracking echography with 2D longitudinal myocardial strain (GLS) is recognized as a more effective technique than conventional LVEF in detecting subtle changes in LV function. Purpose Evaluate the prognostic value of global longitudinal strain (GLS) in patients with FRDA as compared to LVEF. Methods From 2003 to 2017 consecutive patients with genetically confirmed FRDA were included. Longitudinal strain analysis was retrospectively performed with Tomtec software. News were obtained until April 2018, no patient was lost during follow-up. Results The study included 156 patients (51% male) of 35±12 years (mean ± SD) with an age at disease onset of 17±11 years, age at wheelchair use of 26±10 years, and GAA repeat on the shorter allele of 590±241 pb. The following echocardiographic parameters were studied at baseline: LVEF 64±9%, GLS −19.8±5% (n=141), septal wall thickness (SWT) 11.4±2.5 mm, posterior wall thickness (PWT) 10.4±1.8 mm, LV end diastolic diameter (LVEDD) 44.4±6mm. Correlation between GLS and LVEF was 0.31 (p=0.0002). After a mean follow-up of 7.7±4.0 years, 17 (11%) patients died and the outcome (cardiac arrhythmia, heart failure, stroke or death) concerned 28 (18%) patients. In univariate analysis (Cox model), factors associated with mortality were: GLS (HR: 1.2; 95% CI 1.10–1.32, p=0.0001), LVEF (HR: 0.88; 95% CI 0.85–0.92, p&lt;0.0001), GAA (HR: 1.28; 95% CI 1.11–1.47, p=0.0008), age at onset (HR: 0.84; 95% CI 0.76–0.94, p=0.002), LVMi (HR: 1.02; 95% CI 1.01–1.04, p=0.0078), SWT (HR: 1.18 95% CI 1.01–1.36, p=0.03) and LVEDD (HR: 1.09; 95% CI 1.00–1.19, p=0.04). In multivariate analysis LVEF was the only independent predictor of long-term mortality (HR: 0.93; 95% CI 0.88; 0.99, p=0.02). Similarly GLS was not an independent predictor of the composite outcome in multivariate analysis. Conclusion GLS is a predictor of morbimortality but is not superior to LVEF in FRDA patients. Further prospective studies are mandatory to assess the early predictive value of 2D GLS.

Outcome of a Real-Life Population of Patients With Acute Promyelocytic Leukemia Treated According to the PETHEMA Guidelines: The Polish Adult Leukemia Group (PALG) Experience

BackgroundAcute promyelocytic leukemia (APL) has a favorable prognosis. However, results of randomized studies do not necessarily reflect the outcomes of a real-life population. Patients and MethodsWe analyzed 283 unselected APL patients treated in 20 Polish hospitals between 2005 and 2017. All patients were intended to be treated with PETHEMA (Programa Español para el Tratamiento de las Hemopatías Malignas) protocols based on all-trans retinoic acid plus chemotherapy. ResultsThe probability of overall survival at 4 years was 67%, while event-free survival was 64%. The early death (ED) rate was 20.1% (n = 57), while 3.5% (n = 10) patients died before induction therapy was started. The main causes of ED included hemorrhage (45.6%), infections (17.5%), and differentiation syndrome (14.5%). Of 273 treated patients, 214 (78.4%) experienced hematologic morphologic remission, 2 (0.7%) were found to have resistant disease, 47 (17.2%) could not be evaluated for response because of ED, and in 6 (3.7%) no data concerning the response were available. Multivariate analyses showed that predictors of ED and overall survival were Eastern Cooperative Oncology Group performance status > 2, age > 60 years, and all types of bleeding episodes that occurred before starting therapy, while an additional predictor of event-free survival was high white blood cell count (> 10 109/L). ConclusionED remains a major problem in APL patients, especially in a real-life population. Shortening of the time between the initial contact with a health care professional, and all-trans retinoic acid administration and the use of appropriate supportive care could improve the outcome of unselected APL population, mainly by reducing the ED rate.

Progress in the treatment of disseminated intravascular coagulation in patients with acute promyelocytic leukemia

Acute promyelocytic leukemia(APL)is identified as the M3 subtype of acute myelocytic leukemia(AML). One of its clinical features is severe coagulation dysfunction.Most patients could develop disseminated intravascular coagulation(DIC)resulting vital viscera hemorrhage, which is one of the significant causes of early death in APL patients.Early diagnosis and inductive therapy, dynamic monitoring patients′ coagulation index and correcting the abnormal coagulation could prevent the occurrence or progress of DIC, and then improving the early-term survival rate of APL patients.At present, APL is mainly treated from the treatment of primary disease, anticoagulant antifibrinolytic therapy, and alternative therapy. Key words: Acute promyelocytic leukemia; Disseminated intravascular coagulation; Anticoagulant therapy

Improvement of Early Mortality in Single-Unit Cord Blood Transplantation for Adults During 20 Years: A Retrospective Cohort Study

Background: The major limitation of cord blood transplantation (CBT) for adults remains the delayed hematopoietic recovery and higher incidence of graft failure, which result in a higher risk of early mortality in CBT. Methods: We evaluated early overall survival (OS), non-relapse mortality (NRM), neutrophil engraftment, acute graft-versus-host disease, and cause of early death among 9678 adult patients who received single-unit CBT in Japan between 1998 and 2017. Findings: The probability of OS at 100 days was 61.8%, 64.7%, 71.7%, and 78.9% for the periods 1998 to 2002, 2003 to 2007, 2008 to 2012, and 2013 to 2017, respectively (P<0.001). The cumulative incidences of NRM at 100 days during the same period were 33.2%, 27.6%, 20.8%, and 14.6%, respectively (P<0.001). The cumulative incidences of neutrophil engraftment were also improved during the same period (P<0.001). The most common cause of death within 100 days after CBT was bacterial infection in 1998 to 2002 and primary disease in the latter three time periods. Across the four time periods, the proportions of deaths from bacterial and fungal infection, graft failure, hemorrhage, sinusoidal obstructive syndrome, and organ failure decreased in a stepwise fashion. Landmark analysis of OS and NRM after 100 days showed that OS and NRM did not change over time in the multivariate analysis. Interpretation: Our registry-based data demonstrated a significant improvement of early NRM after CBT for adults over the past 20 years. The landmark analysis suggested that improvement of early mortality could lead to an improvement of long-term OS after CBT. Funding Statement: Japan Agency for Medical Research and Development. Declaration of Interests: The authors declare no competing financial interests. Ethics Approval Statement: This retrospective study complied with the Declaration of Helsinki and was approved by the institutional review board at the Institute of Medical Science, The University of Tokyo, where this study was carried out (30-70-B0128).

A Recurrent Variant in MAGEL2 in Five Siblings with Severe Respiratory Disturbance after Birth

Schaaf-Yang syndrome (SHFYNG) is caused by truncating mutations in the paternal allele of the MAGEL2 gene located in the Prader-Willi syndrome region. We report 5 newborns affected with SHFYNG in one family. Trio exome analysis revealed a heterozygous c.1996dupC frameshift mutation in MAGEL2 inherited from the unaffected father. The phenotypes showed strong resemblance, especially for severe respiratory disturbance requiring mechanical ventilation at birth. After discharge from the hospital, 4 of the patients died of respiratory insufficiency within 1 or 2 weeks after birth, and 1 child died after 110 days of aggravated apnea. Apnea or respiratory failure was the main cause of early death in this family. Respiratory distress is a common manifestation of SHFYNG, especially in patients with c.1996dupC mutations. Hypotonia is a main cause of respiratory disturbance, and we propose another possible cause affecting the respiratory center of the brain.

PF255 INCIDENCE AND RISK FACTORS FOR EARLY DEATH AMONG 2421 APL PATIENTS: THE PETHEMA REGISTRY EXPERIENCE

Background:Differentiating agents (ATRA/ATO) with or without anthracycline‐based chemotherapy have led to significant improvements in APL. We acknowledge that early death remain as the unsolved issue in this disease, especially when we analyse real‐life population cohorts (this cause of failure is underreported in clinical trials/protocols).Aims:To review the incidence or early death in APL in a large real life setting, as well as in patients who were eligible for protocols. To identify patterns of early death and risk factorsMethods:Between 1996 and 2017, consecutive adult and pediatric patients were reported to the PETHEMA registry data‐base (120 Institutions from Spain (PETHEMA), Poland (PALG), The Netherlands (HOVON), Uruguay, Argentina (GATLA), and Colombia). All patients with suspicion of APL had to be reported. Exclusion criteria for LPA96/99/2005 and 2012 PETHEMA trials were: unfit for chemotherapy/ECOG 4; death before starting ATRA; lack of genetic diagnosis, protocol violation; and secondary APL (sAPL). Induction therapy consisted of AIDA schedule (3 days IDA for older patients). Supportive measures defined per protocol. Early death (ED) defined as induction death plus death before starting ATRA.Results:Overall 2421 patients were registered, of whom 1962 (81%) were considered eligible for PETHEMA trial (exclusion because of sAPL (n = 189), unfit or ECOG4 (n = 154), no genetic diagnosis (n = 32) and protocol violation (n = 77)). ED occurred in 352 patients (14.6%) (hemorrhage n = 170, 7%, infection n = 77, 3%, DS n = 46, 2%, Thromboischemic events n = 31, 1.4%, and other/unknown n = 28, 1.3%). The rate of ED was similar among the 4 consecutive protocols (p = .98), with a non‐significant decrease of hemorrhagic death form the LPA96 trial (9%) to the later LPA2012 trial (5%). ED rate was significantly lower among patients included in trial (8.6%) vs non eligible (22.2% among sAPL, 77.9% in unfit/ECOG4, 40.6% among non‐genetic diagnosis), p &lt; .001. In all subsets hemorrhage was the main cause of ED, except sAPL (8% hemorrhagic ED and 8% infectious ED rate). Univariet analysis showed the following risk factors for ED: age&gt;60 yo, male, ECOG&gt;1, sAPL, high‐risk, fever, platelet count &lt;40 x 109/L, circulating blasts &gt;30 x 109/L, M3variant, BCR3, FLT3‐ITD, prolonged PT, prolonged APTT, any bleeding at presentation, thrombosis at presentation, BMI&gt;25, elevated creatinine, uric acid, bilirubin, LDH, GOT&gt;50 UI/L, glucose &gt;150 mg/dL, albumin &lt;3.5 gr/dL, CD34neg, CD56+, and CD2+ (all p &lt; .05). The multivariate analysis, performed in 1854 patients showed that age (RR 1.03 per year), WBC &gt;10x109/L (RR 2.1), ECOG (RR 1.9 per unit), elevated LDH (RR 1.7), elevated creatinine (RR 4.2), circulating blasts (RR 1.009 per 1x109/L), and sAPL (RR 1.7), were independent risk factors for ED. The Figure 1 shows the cause of death by timing since diagnosis date. CNS was the more frequent site of lethal bleeding (72%, vs 24% pulmonary). In addition, we identified specific risk factors according to the main cause of ED. The time from diagnosis to starting ATRA (median 0 day) had no impact on ED rate.Summary/Conclusion:ED rate in this real‐life cohort was 14.6%, higher compared with 8.6% in selected patients for PETHEMA trials. Hemorrhage, but also infection, DS and thrombosis remain challenging issues to solve.image

Predictors of an early death in patients diagnosed with colon cancer: a retrospective case–control study in the UK

ObjectiveDespite considerable improvements, 5-year survival rates for colon cancer in the UK remain poor when compared with other socioeconomically similar countries. Variation in 5-year survival can be partly explained by...

Is left ventricular longitudinal strain a good prognostic factor in Friedreich ataxia?

Friedreich ataxia (FRDA) is a rare genetic ataxia. The causal mutation is an expanded trinucleotide repeat (GAA) in the frataxin gene. Hypertrophic cardiomyopathy in FRDA is the major cause of early death. Patients with progressive decline of the left ventricular ejection fraction (LVEF) have the worst prognosis. The aim of the study was to evaluate the prognostic value of 2D global longitudinal strain (GLS) compared to LVEF in FRDA patients. From 2003 to 2017 consecutive patients with genetically confirmed FRDA were included. GLS was retrospectively performed. News was obtained for all patients until April 2018. The study included 156 patients of 35 ± 12 years (mean ± SD) with an age at disease onset of 17 ± 11 y and GAA repeat on the shorter allele of 590 ± 241 pb. The following echocardiographic parameters were studied: LVEF 64 ± 9%, GLS -19.8 ± 5% ( n = 141), septal wall thickness (SWT) 11.4 ± 2.5 mm, posterior wall thickness (PWT) 10.4 ± 1.8 mm, LV end diastolic diameter (LVEDD) 44.4 ± 6 mm. Correlation between GLS and LVEF was 0.31 ( P = 0.0002). After a mean follow-up of 7.7 ± 4.0 y, 17 (11%) patients died and the outcome (cardiac arrhythmia, heart failure, stroke or death) concerned 28 (18%) patients. In univariate analysis (Cox model), factors associated with mortality were: GLS (HR:1.2;95%CI 1.10–1.32, P = 0.0001), LVEF (HR:0.88;95%CI 0.85–0.92, P < 0.0001), GAA (HR:1.28;95%CI 1.11–1.47, P = 0.0008), age at onset (HR:0.84;95%CI 0.76–0.94, P = 0.002), LVMi (HR:1.02;95%CI 1.01–1.04, P = 0.0078), SWT (HR:1.18%CI 1.01–1.36, P = 0.03) and LVEDD (HR:1.09;95%CI 1.00–1.19, P = 0.04). In multivariate analysis LVEF was the only independent predictor of long-term mortality (HR:0.93;95%CI 0.88;099, P = 0.02). GLS was also an independent predictor of the composite outcome in multivariate analysis. GLS is a predictor of morbimortality but is not superior to LVEF in FRDA patients.

The incidence, associated factors, and predictive nomogram for early death in stage IV colorectal cancer.

The purpose of the present study was to investigate the incidence and associated factors for early death in stage IV colorectal cancer (CRC) and to construct the predictive nomogram. Patients with stage IV CRC, who had been diagnosed between 2010 and 2014 in the Surveillance, Epidemiology, and End Results datasets, were eligible for this retrospective cohort study. The univariable and multivariable logistic regression models were conducted to determine the associated factors for early death (survival time ≤ 3months). The predictive nomogram was constructed and the internal validation was performed. Ten thousand two hundred sixty-three out of 36,461 (28.1%) eligible patients resulted in all causes of early death (25.8% for cancer-specific early death and 2.3% for non-cancer early death). Advanced age, marital status, right colon, poor differentiation, higher N stage, and bone metastasis were positively associated with all causes of early death, cancer-specific early death, and non-cancer early death, while higher T stage, positive carcinoembryonic antigen, and distant metastases (bone, lung, liver, and brain) were only positively associated with all causes of early death and cancer-specific early death. The calibration curve for all causes of early death, cancer-specific early death, and non-cancer early death showed the prediction curve closely approximated at the 45° line and the areas under the curve were 75.7% (95% CI, 74.9-76.4%), 75.9% (95% CI, 75.1-76.6%), and 76.9% (95% CI, 76.3-77.6%), respectively. The nomogram was calibrated to predict all causes of early death development, cancer-specific early death development, and non-cancer early death development. These findings can be utilized in early screening and to tailor targeted treatment regimens for stage IV CRC patients.

Extracorporeal membrane oxygenation as a salvage therapy for patients with severe primary graft dysfunction after heart transplant.

Severe primary graft dysfunction (PGD) is the leading cause of early death after heart transplant. To examine the outcomes of heart transplant recipients who received venoarterial extracorporeal membrane oxygenation (VA-ECMO) for severe PGD. We reviewed electronic health records of adult patients who underwent heart transplant from November 2005 through June 2015. We defined severe PGD according to International Society for Heart and Lung Transplantation consensus statements. Of 1030 heart transplant patients, 31 (3%) had severe PGD and required VA-ECMO. The mean (range) age was 59 (43-69) years. Fifteen patients (48%) underwent prior sternotomy and 10 (32%) received a left ventricular assist device as a bridge to transplant. Severe PGD manifested as failure to wean from cardiopulmonary bypass in 20 patients (65%) and as severe hemodynamic instability in the immediate postoperative period in 10 (32%), including cardiac arrest in 3 (10%). Twenty-five patients (81%) were successfully weaned from VA-ECMO, and 19 (61%) were discharged; the other 12 (39%) died. Although VA-ECMO is a common method for providing mechanical circulatory support to patients with PGD, multicenter studies are needed to assess factors associated with successful outcomes and improved survival of these patients.

Tracking progress on the health status and service delivery outcomes for neonates and children in the Metro West geographic service area of the Cape Metropole, 2010 - 2015

Background. Monitoring the health status of populations of children is one of the building blocks of the health system. The provision of an indicator dashboard with disaggregated data that are collected over time can be used to gauge the performance of the health system, guide the allocation of resources and prioritise health interventions within districts. Objectives. To determine neonatal and child mortality, morbidity and health service outcomes over a 6-year period in the Metro West geographic service area (GSA) of the Cape Town metropole. Methods. A dashboard with key indicators was developed using existing data. Results. From 2010 to 2015, there was a decrease in the perinatal mortality rate from 31.7 to 24.8 per 1 000 deliveries, and the early neonatal and neonatal mortality rates from 7.8 and 8.6 to 7.0 and 8.2 per 1 000 live births, respectively. The main obstetric causes of early neonatal deaths were antepartum haemorrhage (22 - 24%) and unexplained intrauterine death (13 - 16%); the main neonatal causes were immaturity (17 - 34%), congenital abnormalities (23 - 29%) and hypoxia (23 - 26%). Under-five mortality decreased in 2013 from 25 to 22 per 1 000 live births, with the main causes being neonatal conditions (32%), pneumonia (25%), congenital abnormalities (9%), injuries (8%) and diarrhoea (8%). Fifty percent of child deaths were out of hospital, with pneumonia and diarrhoea accounting for more than half of these. There was an improvement in health service coverage rates in 2015: immunisation <1 year old (99%); measles second dose (85%), pneumococcal third dose (100%) and rotavirus second dose (100%); maternal antiretroviral coverage (90%); HIV testing in mothers (93%); HIV DNA polymerase chain reaction testing in babies (97%); and a decrease in HIV transmission (2%). Exclusive breastfeeding coverage rates at 14 weeks, and vitamin A supplementation at 12 - 59 months, were only 30% and 44%, respectively, across the GSA. Conclusion. There was a decrease in perinatal, early neonatal, infant and under-five mortality in Metro West over the 6 years. Further reductions in under-five mortality will require focusing on interventions to reduce neonatal and out-of-hospital deaths across the service delivery platform. Home visits to at-risk mothers and infants by community health workers could prevent out-of-hospital deaths and improve exclusive breastfeeding and vitamin A coverage. This will require increasing the number of community health workers and broadening their scope of practice.

Modern aspects of the pathogenesis, diagnosis and therapy of hemostasis disorders in children with acute leukemias

Patients with oncohematological diseases, both children and adults, face high risks of thrombotic and hemorrhagic complications.About 40 % of pediatric patients with acute lymphoblastic leukemia develop bleedings, and the incidence of thrombosis in this disease ranges from 1 to 36 %. Most thromboses are associated with the use of central venous catheters and the use of L-asparaginase, which leads to a significant reduction in the synthesis of coagulation proteins.Massive hemorrhages account for two-thirds of all causes of early death in pediatric patients with acute myelogenous leukemia (AML). Absolute risks of death due to bleeding and leukostasis range from 1.8 % in the total population of children with AML to 14.3 % in a population with hyperleukocytosis more than 200 × 109 /l. The risk of thrombotic complications in children with AML varies between 3.4–11 %. In patients with AML, complex systemic coagulopathies may occur, such as disseminated intravascular coagulation (DIC), excessive fibrinolysis, or nonspecific proteolysis. This scale is not yet applicable due to the lack of research on its effectiveness in the pediatric population. The laboratory diagnostics of hemostasis is difficult due to the combined nature of thrombotic and hemorrhagic complications: bleeding, thrombosis and even DIC syndrome (combining both hyper- and hypocoagulation phases) can be expected in each specific patient with hemoblastosis. Because of the long-term nature of the treatment and the varying intensity of the various treatment units, the patient’s hemostasis during disease manifestation does not allow one to predict with any certainty the complications on induction or consolidation therapy. Involving all the components of the hemostasis system – vascular, platelet and plasma – into the pathological process makes prediction and diagnosis of thrombohemorrhagic complications impossible with the help of standard hemostatic tests and a general blood test, since these tests are designed to assess the concentrations of individual proteins and the functioning of individual components of the hemostatic system, and does not assess the balance between its procoagulant and anticoagulant components. Global hemostatic tests such as thromboelastography, thrombodynamics and thrombin generation test adequately reflect hypercoagulable conditions and can serve as a basis for the development of a new set of laboratory hemostasis tests.Conflict of interest. F.I. Ataullakhanov is co-founder of HemaCore LLC, which holds several patents and patent applications that are related to the diagnostic use of Thrombodynamics® (Ataullakhanov F.I., international patent applications: PCT/CH2007/000543 filing date 02.11.2007 and РСТ/RU2012/000570 filing date 16.07.2012). None of the other authors has any competing interests to declare.

ExtraCorporeal life support for Cardiac ARrest in patients with post cardiac arrest syndrome: The ECCAR study

Post cardiac arrest shock (PCAS) occurring after resuscitated cardiac arrest (CA) is a main cause of early death. Extracorporeal life support (ECLS) could be useful pending recovery from myocardial failure. To describe our PCAS population, and the factors associated with initiation of ECLS. This analysis included 921 patients admitted to two intensive care units between 2005 and 2014 for CA and PCAS; 43 of these patients had ECLS initiated. Neurological and ECLS-related outcomes were gathered retrospectively. The 43 patients treated with ECLS were predominantly (70%) young males with evidence of myocardial infarction on coronary angiography. ECLS was initiated in patients with severe cardiovascular dysfunction (median left ventricular ejection fraction 15% [interquartile range 10-25%]), a median of 9hours [interquartile range 6-16hours] after the CA. At 1 year, eight patients (19%) had survived without neurological disability. Blood lactate and coronary aetiology were associated with neurological outcomes. Logistic regression conducted using 878 controls with PCAS identified age>62 years, location of CA, use of a high dose of adrenaline (>3mg) and blood lactate and serum creatinine concentrations (>5mmol/L and>109μmol/L, respectively) as risk factors for initiation of ECLS. ECLS, as a salvage therapy for PCAS, could be an acceptable alternative for highly-selected patients.

Causes of death in intermediate-risk patients: The Randomized Surgical Replacement and Transcatheter Aortic Valve Implantation Trial

ObjectivesExamine the causes and timing of death in the Surgical Replacement and Transcatheter Aortic Valve Implantation intermediate-risk randomized trial for transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). MethodsCauses of death were adjudicated by an independent clinical event committee and by post-hoc hierarchical classification. Causes of death were evaluated and characteristics and procedural parameters compared between patients who died and survivors for 3 time periods: early (0-30 days), recovery (31-120 days), and late (121-365 days). ResultsAll-cause mortality at 1 year was 6.5% after TAVR and 6.7% after SAVR. There were no differences in mortality rates between TAVR and SAVR for any of the 3 time periods. Early mortality was primarily due to technical, procedure-related problems in TAVR and due to complications in SAVR. For TAVR and SAVR, most deaths during recovery were caused by complications. Other causes, including comorbid conditions, accounted for most late deaths. ConclusionsMortality rates were similar for patients treated with TAVR or SAVR at any time period including at 1 year. Early cause of death was more commonly technical failure after TAVR and due to complications after SAVR. Recovery phase cause of death was dominated by complications from TAVR and SAVR. Late cause of death appeared to be independent of the procedure in both groups.