Risk Factors For Early Death Research Articles

Efficacy of Balloon Blowing Exercise on Peak Expiratory Flow Rate in Young Adult Smokers.

BackgroundSmoking cigarettes which progressively impairs the lung functions is a leading risk factor for early death and disability worldwide. Alternate use of the tobacco products along with some exercise practicing behaviour help to prevent the impairment of lung function because most smokers fail to cease smoking. The objective of this research was to find out the effectiveness of the balloon blowing exercise among the young adult smokers using the peak expiratory flow meter.MethodsA quasi- experimental study in which 100 male participants were included according to inclusion and exclusion criteria. Pre-test and Post-test was taken using Peak expiratory flow meter, after intervention is provided.ResultsThe mean appraise of the Group A pre-test was 287.1 and the post-test was 283.2, and the mean appraise of the Group B pre-test was 279.7 and the post-test was 367.2. The significant appraise was .581 for Group A and .000 for the Group B since the p < 0.05. The study shows the significant result as the p appraise is less than 0.05.ConclusionThis study concludes that there was a significant increase in the peak expiratory flow rate in the post test of Group B.

Suboptimal baseline mental health associated with 4-month premature all-cause mortality: Findings from 18 years of follow-up of the Canadian National Population Health Survey

ObjectiveTo investigate: 1) whether baseline non-flourishing mental health is associated with a higher probability of all-cause mortality over 18-year follow-up after controlling for many risk factors for premature mortality; and 2) what other factors, independent of mental health status, are associated with all-cause mortality after adjustment for known risk factors. MethodsData were derived from waves 1 and 9 (1994/1995; 2010/2011) of the Canadian National Population Health Survey. An analytic sample of 12,424 participants 18 years and above was selected. Baseline information on flourishing and predictors of all-cause mortality was from wave 1 and mortality data was ascertained by the Canadian Vital Statistics-Death Database in wave 9. Mean time to all-cause mortality was estimated using Kaplan-Meir procedure. Cox proportional hazards models were used to assess the association of baseline non-flourishing mental health and potential predictors with time to all-cause mortality. ResultsAbout one in five participants was classified as non-flourishing at baseline. At the end of the study period 2317 deaths were observed. Baseline non-flourishing mental health was associated with a 19% higher probability of all-cause mortality during 18-year follow-up (HR = 1.19; 95% CI 1.08–1.32), corresponding to a 4.7-month shorter survival time. After controlling for baseline chronic health conditions, past-year depression, sociodemographics, health behaviors, social support, pain and functioning, baseline non-flourishing mental health status was associated with a 14% higher probability of death (HR = 1.14; 95% CI 1.02–1.27). ConclusionsSuboptimal mental health is associated with premature mortality even after accounting for many risk factors for early death. Future research should explore the physiological pathways through which non-flourishing influences mortality.

Early Death Incidence and Prediction in Stage IV Breast Cancer.

BackgroundThe early death of patients is a global cancer issue. We aimed to identify the risk factors for early death in stage IV breast cancer. Predictive nomograms for early death evaluation were generated based on the risk factors.Material/MethodsBased on the Surveillance, Epidemiology, and End Results (SEER) database, patients diagnosed with IV breast cancer were selected. The risk factors for early death (survival time ≤1 year) were identified using logistic regression model analysis. Predictive nomograms were constructed and internal validation was performed.ResultsA total of 5998 (32.6%) breast cancer patients were diagnosed as early death in the construction cohort. Age older than 50 years, unmarried status, black race, uninsured status, triple-negative type, grade (II and III), tumor size >5 cm, and metastasis to lung, liver, and brain were risk factors for total early death, while Luminal B subtype, N1 stage, and surgical interventions were associated with lower risk of early death. As for cancer-specific and non-cancer-specific early death, several factors were not consistent between the 2 groups. Nomograms for all-cause, cancer-specific, and non-cancer-specific early death were constructed. The calibration curve showed satisfactory agreement. The areas under the ROC curve (AUC) were 78.3% (95% CI: 77.7–78.9%), 75.8% (75.1–76.4%), and 72.3% (71.6–72.9%), respectively. In the validation cohort, a total of 689 (19.3%) patients were diagnosed as early death and the calibration curve showed satisfactory agreement. The AUCs of the all-cause, cancer-specific, and non-cancer-specific early death prediction were 74.0% (95% CI: 72.5–75.4%), 73.5% (72.0–74.9%), and 68.6% (67.0–70.1%), respectively.ConclusionsNomograms were generated to predict early death, with good calibration and discrimination. The predictive model can provide a reference for identifying cases with high risk of early death among stage IV breast cancer patients and play an auxiliary role in guiding individual treatment.

Association between age at disease onset of anti-neutrophil cytoplasmic antibody-associated vasculitis and clinical presentation and short-term outcomes.

ANCA-associated vasculitis (AAV) can affect all age groups. We aimed to show that differences in disease presentation and 6 month outcome between younger- and older-onset patients are still incompletely understood. We included patients enrolled in the Diagnostic and Classification Criteria for Primary Systemic Vasculitis (DCVAS) study between October 2010 and January 2017 with a diagnosis of AAV. We divided the population according to age at diagnosis: <65 years or ≥65 years. We adjusted associations for the type of AAV and the type of ANCA (anti-MPO, anti-PR3 or negative). A total of 1338 patients with AAV were included: 66% had disease onset at <65 years of age [female 50%; mean age 48.4 years (s.d. 12.6)] and 34% had disease onset at ≥65 years [female 54%; mean age 73.6 years (s.d. 6)]. ANCA (MPO) positivity was more frequent in the older group (48% vs 27%; P = 0.001). Younger patients had higher rates of musculoskeletal, cutaneous and ENT manifestations compared with older patients. Systemic, neurologic,cardiovascular involvement and worsening renal function were more frequent in the older-onset group. Damage accrual, measured with the Vasculitis Damage Index (VDI), was significantly higher in older patients, 12% of whom had a 6 month VDI ≥5, compared with 7% of younger patients (P = 0.01). Older age was an independent risk factor for early death within 6 months from diagnosis [hazard ratio 2.06 (95% CI 1.07, 3.97); P = 0.03]. Within 6 months of diagnosis of AAV, patients >65 years of age display a different pattern of organ involvement and an increased risk of significant damage and mortality compared with younger patients.

Surgery for Bentall endocarditis: short- and midterm outcomes from a multicentre registry.

Endocarditis after the Bentall procedure is a severe disease often complicated by a pseudoaneurysm or mediastinitis. Reoperation is challenging but conservative therapy is not effective. The aim of this study was to assess short- and midterm outcomes of patients reoperated on for Bentall-related endocarditis. Seventy-three patients with Bentall procedure-related endocarditis were recorded in the Italian registry. The mean age was 57 ± 14 years and 92% were men; preoperative comorbidities included hypertension (45%), diabetes (12%) and renal failure (11%). The logistic EuroSCORE was 25%; the EuroSCORE II was 8%. Preoperatively, 12% of the patients were in septic shock; left ventricular-aortic discontinuity was present in 63% and mitral valve involvement occurred in 12%. The most common pathogens were Staphylococcus aureus (22%) and Streptococci (14%). Reoperations after a median interval of 30 months (1-221 months) included a repeat Bentall with a bioconduit (41%), a composite mechanical (33%) or biological valved conduit (19%) and a homograft (6%). In 1 patient, a heart transplant was required (1%); in 12%, a mitral valve procedure was needed. The hospital mortality rate was 15%. The postoperative course was complicated by renal failure (19%), major bleeding (14%), pulmonary failure (14%), sepsis (11%) and multiorgan failure (8%). At multivariate analysis, urgent surgery was a risk factor for early death [hazard ratio 20.5 (1.9-219)]. Survival at 5 and 8 years was 75 ± 6% and 71 ± 7%, with 3 cases of endocarditis relapse. Surgery is effective in treating endocarditis following the Bentall procedure although it is associated with high perioperative mortality and morbidity rates. Endocarditis relapse seems to be uncommon.

An effective early death scoring system for predicting early death risk in de novo acute promyelocytic leukemia

The Sanz risk, which was originally used to predict the risk of acute promyelocytic leukemia (APL) relapse, is a recognized method to predict the prognosis of APL. About 570 de novo APL patients admitted to our center were randomly divided into a training cohort (N = 344) and validation cohort (N = 226). Multivariate analysis of training cohort demonstrated that age >52 (OR = 5.170, p = .002), white blood cell count >10 × 109/L (OR = 9.062, p < .001), PLT count ≤10 × 109/L (OR = 4.254, p < .001), and LDH level >500 U/L (OR= 3.002, p = .046) were independent risk factors for early death. A risk score (age >52: 1.5 points; WBC >10 × 109/L: 2 points; PLT ≤10 × 109/L: 1 point; LDH >500 U/L: 1 point) was used to predict early death risk. The model shows a better predictive power of early death in training cohort and validation cohort compared with Sanz risk stratification.

Surgical Management of Heterotaxy Syndrome: Current Challenges and Opportunities.

Heterotaxy syndrome presents a unique challenge in surgical management, even in the current era. We hypothesized that certain anatomic subsets merit novel strategies. We analyzed morphologic details, surgeries, comorbidities, subsequent admissions, and survival using Kaplan-Meier methods and multivariable risk models from a single-institution experience of 103 consecutive patients with heterotaxy who underwent cardiac surgery between January 1, 1990, and May 31, 2016. Of the 103 patients (50 males and 53 females), 31 had left atrial isomerism, 64 had right atrial isomerism (RAI), and 8 patients' isomerism was indeterminate (IND), with first cardiac operation at a mean 1.0 year (standard deviation ±3.0 years) of age. Kaplan-Meier overall survival estimate was 83.1% at six months, 77.8% at one year, 65.9% at five years, and 52.1% at ten years. Survival was particularly low among RAI following repair of total anomalous pulmonary venous connection (TAPVC) at first operation, with one- and five-year survival of 57% and 46%, respectively. By multivariable analysis, the only risk factor for death during the early phase (hazard model) was repair of TAPVC at the first cardiac operation (hazard ratio [HR]: 4.4, P = .01), and risk factors during the longer term constant phase were atrioventricular valve (AVV) regurgitation (HR: 4.2, P < .01), male gender (HR: 3.7, P < .01), and two-ventricle repair (HR: 3.0, P = .02). Patients with heterotaxy undergoing the Fontan procedure had excellent subsequent survival (85% at ten years). This analysis of over 100 patients with heterotaxy identified TAPVC requiring initial repair as the major risk factor for early death and important AVV regurgitation as the major risk factor in the longer term. Survival with RAI and early repair of TAPVC were poor, with one-year mortality exceeding 40%. Patients with single ventricle completing the Fontan operation enjoyed outstanding ten-year survival (85%). Initial management of RAI requiring early repair of TAPVC remains challenging. For this high-risk subset, alternative strategies such as early referral for cardiac transplantation evaluation warrant consideration.

Cardiorespiratory Fitness Is Associated With Early Death Among Healthy Young and Middle-Aged Baby Boomers and Generation Xers

BackgroundIncreased mortality associated with low cardiorespiratory fitness has shown to take effect during late adulthood in previous generations. A recent rise in early death was observed in the United States. We investigated the impact of low cardiorespiratory fitness during young and middle adulthood on premature death in healthy adults from recent generations. MethodsA prospective cohort study of a nationally representative sample of US Baby Boomers and Generation Xers (born 1945-1980). Between 1999 and 2004, 3242 adults ages 20 to 49 years (weighted N = 59,888,450; mean age, 33.8 ± 0.2 years) underwent submaximal treadmill exercise test in the National Health and Nutrition Examination Survey study. Weighted Cox proportional hazards regression were used to evaluate the association of cardiorespiratory fitness with premature death at 65 years or younger. ResultsDuring a mean follow-up of 13.8 years, 104 deaths (weighted deaths N =1,326,808) occurred. Low cardiorespiratory fitness was associated with an increased risk of premature death as a result of all-cause (hazard ratio [HR], low vs high: 2.26; 95% confidence interval [CI], 1.10 to 4.64, P for trend = 0.036) and cancer mortality (HR low vs moderate/high: 6.53; 95% CI, 2.38 to 17.9). Further, this association was stronger in adults ages 35 to 49 years at baseline (HR, 4.17 [95% CI, 1.19 to 9.11]). ConclusionWe observed an inverse association between cardiorespiratory fitness during middle adulthood and premature death, which was not detected in preceding generations. These findings suggested that low cardiorespiratory fitness might be emerging as a new risk factor for early death among US Baby Boomers and Generation Xers.

Combined Ischemic Preconditioning and Resveratrol Improved Bloodbrain Barrier Breakdown via Hippo/YAP/TAZ Signaling Pathway.

Transient Ischemia/Reperfusion (I/R) is the main reason for brain injury and results in disruption of the Blood-Brain Barrier (BBB). It had been reported that BBB injury is one of the main risk factors for early death in patients with cerebral ischemia. Numerous investigations focus on the study of BBB injury which have been carried out. The objective of this study was to investigate the treatment function of the activation of the Hippo/Yes-Associated Protein (YAP) signaling pathway by combined Ischemic Preconditioning (IPC) and resveratrol (RES) before brain Ischemia/Reperfusion (BI/R) improves Blood-Brain Barrier (BBB) disruption in rats. Sprague-Dawley (SD) rats were pretreated with 20 mg/kg RES and IPC and then subjected to 2 h of ischemia and 22 h of reperfusion. The cerebral tissues were collected; the cerebral infarct volume was determined; the Evans Blue (EB) level, the brain Water Content (BWC), and apoptosis were assessed; and the expressions of YAP and TAZ were investigated in cerebral tissues. Both IPC and RES preconditioning reduced the cerebral infarct size, improved BBB permeability, lessened apoptosis, and upregulated expressions of YAP and transcriptional co-activator with PDZ-binding motif (TAZ) compared to the Ischemia/Reperfusion (I/R) group, while combined IPC and RES significantly enhanced this action. combined ischemic preconditioning and resveratrol improved blood-brain barrier breakdown via Hippo/YAP/TAZ signaling pathway.

Risk factors for early death among ovarian cancer patients: a nationwide cohort study.

ObjectiveTo characterize ovarian cancer patients who die within 6 months of diagnosis and to identify prognostic factors for these early deaths.MethodsA nationwide cohort study covering ovarian cancer in Denmark in 2005–2016. Tumor and patient characteristics including comorbidity and socioeconomic factors were obtained from the comprehensive Danish national registers.ResultsA total of 5,570 patients were included in the study. Three months after ovarian cancer diagnosis 456 (8.2%) had died and 664 (11.9%) died within 6 months of diagnosis. Adjusted for age and comorbidity, patients who died early were admitted to hospital significantly more often in a 6-month period before the diagnosis (odds ratio [OR]=1.61 [1.29–2.00], and OR=1.47 [1.21–1.78]), for patients who died within 3 and 6 months respectively). Low educational level (OR=2.11), low income (OR=2.50) and singlehood (OR=1.90) were factors significantly associated with higher risk of early death. The discriminative ability of risk factors in identifying early death was assessed by cross-validated area under the receiver operating characteristic curve (AUC). The AUC was found to be 0.91 (0.88–0.93) and 0.90 (0.87–0.92) for death within 3 and 6 months, respectively.ConclusionsDespite several admissions to hospital, the ovarian cancer diagnosis is delayed for a subgroup of patients, who end up dying early, probably due to physical deterioration in the ineffective waiting time. Up to 90% of high-risk patients might be identified significantly earlier to improve the prognosis. The admittance of the patients having risk symptoms should include fast track investigation for ovarian cancer.

Analisis Nilai Indeks Trombosit Dan Rasio Trombosit Limfosit Sebagai Penanda Inflamasi Glomerulus Pada Penderita Hipertensi Berbagai Derajat

AbstractBackground : Hypertension is a major risk factor for early death and cardiovascular disease (CVD), which causes at least 1.1 million deaths per year in the world. Hypertension is also called The Silent Killer because it is often found without symptoms, which if left untreated and treated will cause complications such as stroke, heart and blood vessel disease, kidney disorders and others which can ultimately lead to disability or death. Endothelial dysfunction indirectly affects platelet dysfunction which can be assessed based on platelet index and platelet lymphocyte ratio. 2,6,7Method :170 Patients with hypertension are grouped into hypertensive stage groups 1, 2 and 3. Platelet index (MPV, PDW and PCT) and lymphocyte platelet ratio are calculated based on the results of routine blood tests. Data distribution was tested by Kolmogrov-Smirnov and analyzed with the corresponding data test.Results:Platelet index namely MPV in hypertensive patients was significantly different in each degree of hypertension, grade 1 (8.92 ± 1.23), degree 2 (8.99 ± 1.63) and degree 3 (11.2 ± 4.29) with a p value = 0.003. There is a weak correlation between MPV and serum creatinine ureum levels. However, PDW and RTL values only correlate with creatinine.Conclusion:There are differences in the value of MPV in patients with hypertension of various degrees. There is a correlation between the values of MPV, PDW and RTL and creatinine which indicate inflammation of the glomerulus.

Prognostic differences among patients with idiopathic interstitial pneumonias with acute exacerbation of varying pathogenesis: a retrospective study

BackgroundAcute exacerbation of chronic fibrosing idiopathic interstitial pneumonias (AE-IIPs) is associated with a high mortality rate. In 2016, an international working group proposed a revised diagnostic criteria for AE-IIPs, suggesting that it be classified as idiopathic or triggered. Many factors are known to trigger AE-IIPs, including surgery, infection, and drugs. However, it is unknown which AE-IIPs triggers have a worse prognosis. We aimed to investigate the prognosis of patients with various clinical types of AE-IIPs, particularly infection-triggered, non-infection triggered, and idiopathic AE-IIPs.MethodsWe retrospectively collected data from 128 chronic fibrosing IIPs (CF-IIPs) patients who were hospitalized by respiratory failure between April 2009 and March 2019 at Juntendo University Hospital. Among these patients, we evaluated 79 patients who developed AE-IIPs and 21 who developed pneumonia superimposed on CF-IIPs. Patients with AE-IIPs were classified into three types: idiopathic, infection-triggered, and non-infection-triggered AE-IIPs. We analyzed differences in patient characteristics, examination findings; level of serum markers, results of pulmonary function, and radiological findings, prior treatment for baseline CF-IIPs, and prognosis. We then evaluated the risk factor for early death (death within 30 days from the onset of AE-IIPs) associated with AE-IIPs.ResultsAmong the patients who developed AE-IIPs, 34 were characterized as having idiopathic, 25 were characterized as having infection-triggered, and 20 were categorized as having non-infection-triggered AE-IIPs. Survival time for pneumonia superimposed on IIPs was significantly longer than that for any AE-IIPs. Survival time for bacterial pneumonia superimposed on CF-IIPs was significantly longer than that for AE-IIPs (for each idiopathic and all triggered IIPs). Thereafter, survival time for infection-triggered was significantly longer than for idiopathic or non-infection-triggered AE-IIPs. The mortality rate was significantly lower in infection-triggered AE-IIPs than in other types of AE-IIPs. Furthermore, the incidence of infection-triggered AE-IIPs in winter was significantly higher than that in other seasons. Moreover, the clinical AE-IIPs types and radiological findings at AE-IIP onset were significant risk factors for AE-IIPs-induced early death.ConclusionsOur findings suggest that patients with infection-triggered AE-IIPs can expect a better prognosis than can patients with other clinical types of AE-IIPs.

Low overall mortality during 10 years of bariatric surgery: nationwide study on 63,469 procedures from the Scandinavian Obesity Registry.

Bariatric surgery results in an improvement in quality of life, co-morbid diseases, and an increased life expectancy. However, to obtain these benefits perioperative mortality rates need to be low. Evaluate 90-day and 1-year mortality after bariatric surgery in Sweden from 2008 to2017. National quality register. Data on applicable patients from the Scandinavian Obesity Surgery Registry, including 63,469 patients (85.1% gastric bypass, 12.5% sleeve gastrectomy, .8% duodenal switch, .5% minor revisions, and 1.1% other procedures), were retrieved and matched to the Cause of Death registry. During the 10-year period, 36 patients died within 90 days, resulting in a .06% overall mortality. The 1-year mortality rate was .19% (n = 111). Both mortality rates decreased over the study period. In a multivariate analysis, depression (odds ratio [OR] 2.38, [95% confidence interval 1.48-3.84]), leakage (OR 9.32 [4.85-17.94]), and thromboembolic events (OR 7.60 [1.63-35.37]) increased mortality risks at both 90 days and 1 year, whereas age (OR 1.03 [1.01-1.06] per increased year of age) and abdominal circumference (OR 1.03 [1.01-1.05] per cm) were also associated with increased mortality at 1 year. The predictive value of the Obesity Surgery Mortality Risk Score was confirmed. The low 90-day and 1-year mortality, .06% and .19%, respectively, demonstrates that bariatric surgery in Sweden is safe. The use of antidepressants and 2 serious postoperative complications were the most significant risk factors for early deaths, while increased age and preoperative abdominal circumference also contributed at 1 year.

Early mortality after diagnosis of cancer of the head and neck - A population-based nationwide study.

Cancers of the head and neck have a high mortality rate, and roughly 10% of the patients die within six months of diagnosis. To our knowledge little has been written about this group. We wished to identify risk factors for early death, to predict and monitor patients at risk better and, if possible, avoid unjustified major treatment. This population-based nationwide study from the Swedish Head and Neck Cancer Register (SweHNCR) included data from 2008-2015 and 9733 patients at potential risk of early death. A total of 925 (9.5%) patients died within six months. For every year older the patients became, the risk of early death increased by 2.3% (p<0.001). The relative risk of death was 3.37 times higher (237%) for patients with WHO score 1 compared with WHO score 0. A primary tumour in the hypopharynx correlated with a 24% increased risk over the oral cavity (p<0.024). Patients with stage IV disease had a 3.7 times greater risk of early death than those with stage I (p<0.001). As expected, a 12 times increased risk of early death was noted in the palliative treatment group, compared to the curative group. Limitations to this study were that the actual cause of death was not recorded in the SweHNCR, and that socioeconomic factors, alcohol consumption, smoking habits, and HPV status, were not reported in SweHNCR until 2015. However, the fact that this is a population-based nationwide study including 9733 patients compensates for some of these limitations. Identification of patients at increased risk of early death shows that older patients with advanced disease, increased WHO score, primary tumour in the hypopharynx, and those given palliative treatment, are more likely than the others to die from head and neck cancer within six months of diagnosis.

Prediction of complication related death after radical cystectomy for bladder cancer with machine learning methodology

Purpose: To create a pre-operatively usable tool to identify patients at high risk of early death (within 90 days post-operatively) after radical cystectomy and to assess potential risk factors for post-operative and surgery related mortality.Materials and methods: Material consists of 1099 consecutive radical cystectomy (RC) patients operated at 16 different hospitals in Finland 2005–2014. Machine learning methodology was utilized. For model building and testing, the data was randomly divided into training data (n = 733, 66.7%) and independent testing data (n = 366, 33.3%). To predict the risk of early death after RC from baseline variables, a binary classifier was constructed using logistic regression with lasso regularization. Finally, a user-friendly risk table was constructed for practical use.Results: The model resulted in an area under the receiver operating characteristic curve (AUROC) of 0.73 (95% CI = 0.59–0.87). The strongest risk factors were: American Society of Anesthesiologists physical status classification (ASA), congestive heart failure (CHF), age adjusted Charlson comorbidity index (ACCI) and chronic pulmonary disease.Conclusion: This study with a novel methodological approach adds CHF and chronic pulmonary disease to previously known independent prognostic risk factors for early death after RC. Importantly, the risk prediction tool uses purely pre-operative data and can be used before surgery.

Prevalence of Smoking among Medical Students in Kathmandu, Nepal

Smoking is a leading risk factor for early death and disability worldwide. Medical students and physicians are the ideal persons to educate patients about hazards of smoking. Today’s medical students will play a prominent role in future to prevent and control tobacco use. Still, the problem of smoking among the medical students is common worldwide but the pattern and extent of the problem varies from place to place. Aim of this study was to find out prevalence of smoking among medical students, factors contributing to their smoking habits, their exposure to passive smoking and to know about their knowledge about smoking related health problems. This is a cross sectional study, conducted among all first and second year MBBS students during July-September 2018. Self administered questionnaire were given to all the participants and collected after it was filled up. One hundred seventy four students participated in the study. Prevalence of smoking was 5.2% and all the students who smoked were male. The most important cause for initiation of smoking was peer pressure (56%). The average cigarettes smoked was seven sticks per day. Though 80% students knew about hazards of passive smoking, almost half of them were exposed to passive smoking. In our study we found that most of the students do not counsel their patients regarding hazards of smoking and only few participants were found to advise and encourage their patients to quit smoking.

Effects of Clinical Characteristics, Laboratory Parameters and Treatment Regimens on Prognosis of Patients with Multiple Myeloma

To study the effects of clinicopathological features, laboratory parameters and treatment regimens on the prognosis of patients with multiple myeloma. The clinical data of 97 patients with multiple myeloma treated with chemotherapy in Department of Hematology, the 1st Hospital of Hainan Medical College were analyzed retrospectively. The clinicopathological features (age, sex, severe anemia, light chain type, hypoproteinemia, paraplegia, renal injury, amyloidosis, complex karyotype, bone disease classification, Eastern Cooperative Oncology Group (ECOG) physical status score, complete remission, etc.), laboratory parameters (C-reactive protein, lactate dehydrogenase, blood calcium, serum β2 microglobulin, etc.), and treatment schemes (thalidomide maintenance treatment) were recorded. The patients were followed up for 1-60 months, and their total survival time were recorded. A single factor and multiple factors were used to analyze the factors affecting the total and early mortality of the patients. The survival curves were plotted by the Kaplan-Meier method and the survival analysis was carried out by Log-rank test. Among 97 patients, 29 cases (29.90%) achieved complete remission, and 56 cases (57.73%) achineved partial remission. The total effective rate was 87.63% (85/97). At the end of the follow-up, 19 cases (19.59%) died, and 1, 3 and 5 year survival rates were 80.41%, 71.13% and 37.11% respectively. The median overall survival time was 29 (1-60) months. The results of single factor analysis showed that age, hypoproteinemia, severe anemia, paraplegia, renal injury, amyloidosis, complex karyotype, complete remission and thalidomide maintenance therapy were the factors affecting the prognosis of the patients (all P＜0.05). Further multiple factor Logistic regression analysis showed that age and hypoproteinemia, severe anemia, paraplegia, amyloidosis, complex karyotype and thalidomide maintenance treatment were factors affecting the prognosis (P＜0.05). Of the 97 patients, 8 cases died early. The results of single factor analysis showed that amyloidosis and severe anemia were risk factors for early death (all P＜0.05), and further multivariate Logistic regression analysis showed that amyloidosis was an independent risk factor for early death (P＜0.05). There are many adverse factors affecting the prognosis of patients with multiple myeloma, such as age, hypoproteinemia, severe anemia, paraplegia, amyloidosis, complex karyotype and so on. The risk of early death in the patients with amyloidosis is higher, and salidomide maintenance therapy can help to prolong the life span of the patient.

A 30-Year Prospective Follow-Up Study Reveals Risk Factors for Early Death in Cartilage-Hair Hypoplasia.

Cartilage-hair hypoplasia (CHH) is a skeletal dysplasia with combined immunodeficiency, variable clinical course and increased risk of malignancy. Management of CHH is complicated by a paucity of long-term follow-up data, as well as knowledge on prognostic factors. We assessed clinical course and risk factors for mortality in a prospective cohort study of 80 patients with CHH recruited in 1985–1991 and followed up until 2016. For all patients we collected additional health information from health records and from the national Medical Databases and Cause-of-death Registry. The primary outcome was immunodeficiency-related death, including death from infections, lung disease and malignancy. Standardized mortality ratios (SMRs) were calculated using national mortality rates as reference. Half of the patients (57%, n = 46) manifested no symptoms of immunodeficiency during follow-up while 19% (n = 15) and 24% (n = 19) demonstrated symptoms of humoral or combined immunodeficiency, including six cases of adult-onset immunodeficiency. In a significant proportion of patients (17/79, 22%), clinical features of immunodeficiency progressed over time. Of the 15 patients with non-skin cancer, eight had no preceding clinical symptoms of immunodeficiency. Altogether 20 patients had deceased (SMR = 7.0, 95%CI = 4.3–11); most commonly from malignancy (n = 7, SMR = 10, 95%CI = 4.1–21) and lung disease (n = 4, SMR = 46, 95%CI = 9.5–130). Mortality associated with birth length below −4 standard deviation (compared to normal, SMR/SMR ratio = 5.4, 95%CI = 1.5–20), symptoms of combined immunodeficiency (compared to asymptomatic, SMR/SMR ratio = 3.9, 95%CI = 1.3–11), Hirschsprung disease (odds ratio (OR) 7.2, 95%CI = 1.04–55), pneumonia in the first year of life or recurrently in adulthood (OR = 7.6/19, 95%CI = 1.3–43/2.6–140) and autoimmunity in adulthood (OR = 39, 95%CI = 3.5–430). In conclusion, patients with CHH may develop adult-onset immunodeficiency or malignancy without preceding clinical symptoms of immune defect, warranting careful follow-up. Variable disease course and risk factors for mortality should be acknowledged.

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

PF677 DNA HYPERMETHYLATION EMERGES AS THE STRONGEST PREDICTOR FOR POOR OUTCOME AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN JUVENILE MYELOMONOCYTIC LEUKEMIA (JMML)

Background: JMML is a childhood hematopoietic malignancy characterized by hyperactive RAS signaling. For most patients early allogeneic hematopoietic stem cell transplantation (HSCT) is the therapy of choice. Risk factors for early death and relapse following HSCT are represented by age ≥ 2 yrs, low platelet count and HbF elevated for age. Most recently, genome-wide DNA methylation profiles (Lipka, Nat Comm 2017) identified distinct methylation signatures predictive for outcome. Aims: This study evaluates the clinical significance of these epigenetic changes in a large cohort of uniformly transplanted children registered to the European Working Group of MDS in Childhood (EWOG-MDS). Methods: We analyzed the outcome of 153 children with JMML (96 males, 57 females; median age at HSCT 2.7 yrs [0.3–11.5]) given a HSCT after a preparative regimen consisting of busulfan, cyclophosphamide, and melphalan. Results: Thirty-seven patients (pts) were transplanted from an HLA-identical sibling donor (MSD) and 116 from a matched unrelated donor (UD). Stem cell source was bone marrow (n = 122) or peripheral blood (n = 31). GVHD prophylaxis was CSA only in 25 (68%) MSD procedures, CSA/MTX/ATG was administered in 88 (76%) of UD-HSCT recipients. All but 9 pts engrafted. The cumulative incidence of grades II-IV acute GVHD was 44% (37–52). Thirty-three of the 133 pts at risk developed chronic GVHD, which was limited in 20 and extensive in 13 pts. With a median follow-up of 3.7 years (0.1–17.5), the 5-year leukemia-free survival (LFS) was 61% (53–69), while the cumulative incidence of non-relapse mortality (NRM) and relapse (CIR) were 13% (8–20) and 26% (20–35), respectively. There was no difference in outcome between MSD and UD-HSCT recipients. Of the 153 pts, 76 had a somatic PTPN11 mutation, 21 had neurofibromatosis type 1, 22 belonged to the NRAS- and 18 to the KRAS-mutated subgroup, while RAS pathway alterations were absent in 16 pts (“all negative”). 5-year CIR was higher in PTPN11-mutated JMML (35%) compared to that of the NF1 (24%), NRAS (23%), KRAS (11%) or all negative subtypes (14%). Methylation status was high (HM), intermediate (IM) or low (LM) in 61, 52 or 40 pts, respectively. 5-year LFS and CIR of pts of the LM class was similar to that noted in the IM class with 76% vs 69%, and 8% vs 13%, respectively. In contrast, children of the HM class had a significantly inferior LFS (44%, 31–57, p < 0.01) due to a high CIR (50%, 38–65, p < 0.01). NRM in the 3 methylation groups (LM 16%, IM 19%, HM 6%) did not differ. There was a clear correlation between methylation class and molecular genetic subtype: PTPN11-mutated JMML was less common in the LM class and the proportion of KRAS-mutated pts was highest in the LM class. Also, patients in the HM class had a higher median age at HSCT (3.8 yrs) than pts in the IM (2.1 yrs) or LM class (1.1 yrs). Multivariate analysis identified methylation class (HM vs IM: RR 5.3 [1.8–15.3], HM vs LM RR 7.6 [1.6 – 37.3]) as the only independent variable predicting relapse when analyzed with age at HSCT, platelet count and molecular genetic type (PTPN11-mutated vs others). Summary/Conclusion: Patient outcome in genome-wide methylation classes nicely recapitulated earlier data applying a DNA methylation score of candidate gene regions (Olk-Batz, Blood 2011). Thus, DNA methylation classifiers are exceptionally consistent allowing prospective assignment of DNA methylation categories for molecularly-driven risk stratification. Future research needs to be directed at better understanding the mechanistic link of epigenetic dysregulation and resistance to treatment.