Early Death
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2021 ◽  
Tingting Zhang ◽  
Liancheng Zhu

Abstract Background: Ovarian cancer is a common gynecological malignant tumor. Poor prognosis is strongly associated with early death, but there is no effective tool to predict this. This study aimed to construct a nomogram for predicting cancer-specific early death in ovarian cancer patients.Methods: Our study used data from the Surveillance, Epidemiology, and End Results (SEER) database of ovarian cancer patients registered from 1988 to 2016. Important independent prognostic factors were determined by univariate and multivariate logistic regression and LASSO Cox regression. Several risk factors were considered in constructing the nomogram. Nomogram discrimination and calibration were evaluated using C-index, internal validation, and receiver operating characteristic (ROC) curves.Results: A total of 4769 patients were included. Patients were assigned to the training set (n = 3340; 70%) and validation set (n = 1429; 30%). Based on the training set, eight variables were shown to be significant factors for early death and were incorporated in the nomogram: AJCC (American Joint Committee on Cancer) stage, residual lesion size, chemotherapy, serum CA125 level, tumor size, number of lymph nodes examined, surgery of primary site, and age. The C-indices and ROC curves showed that the nomogram had better predictive ability than the AJCC staging system and good clinical practicability. Internal validation based on validation set showed good consistency between predicted and observed values for early death. Conclusions: Compared with predictions made using AJCC stage or residual lesion size, the nomogram was able to provide more robust predictions for early death in ovarian cancer patients.

2021 ◽  
Vol 11 ◽  
Zhong Zhang ◽  
Juan Pu ◽  
Haijun Zhang

BackgroundPancreatic adenocarcinoma (PCa) is a highly aggressive malignancy with high risk of early death (survival time ≤3 months). The present study aimed to identify associated risk factors and develop a simple-to-use nomogram to predict early death in metastatic PCa patients.MethodsPatients diagnosed with metastatic PCa between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were collected for model construction and internal validation. An independent data set was obtained from China for external validation. Independent risk variables contributed to early death were identified by logistic regression models, which were then used to construct a nomogram. Internal and external validation was performed to evaluate the nomogram using calibration curves and the receiver operating characteristic curves.ResultsA total of 19,464 patients in the SEER cohort and 67 patients in the Chinese cohort were included. Patients from the SEER database were randomly divided into the training cohort (n = 13,040) and internal validation cohort (n = 6,424). Patients in the Chinese cohort were selected for the external validation cohort. Overall, 10,484 patients experienced early death in the SEER cohort and 35 in the Chinese cohort. A reliable nomogram was constructed on the basis of 11 significant risk factors. Internal validation and external validation of the nomogram showed high accuracy in predicting early death. Decision curve analysis demonstrated that this predictive nomogram had excellent and potential clinical applicability.ConclusionThe nomogram provided a simple-to-use tool to distinguish early death in patients with metastatic PCa, assisting clinicians in implementing individualized treatment regimens.

2021 ◽  
Vol 50 (Supplement_1) ◽  
Saber Dini ◽  
Nicholas Douglas ◽  
Jeanne Rini Poespoprodjo ◽  
Enny Kenangalem ◽  
Paulus Sugiarto ◽  

Abstract Background Inadequate prevention and treatment of malaria can lead to reinfections and recurrent episodes, and for vivax malaria, further recurrences from the dormant liver stage. This study quantified the impact of recurrent malaria episodes on morbidity and mortality. Methods Routinely collected data were available from 68,381 malaria patients presenting to the primary referral hospital in Papua, Indonesia. A multi-state modelling framework, with Cox regression for transition rates, was employed to determine the risks of re-presentation to hospital, receiving in-patient treatment, and early (≤14 days post treatment)/late death following multiple malaria episodes. Results The risk of re-presentation to hospital increased from 34.7% (95%CI: 34.4%–35.1%) at first episode to 58.6% (57.5%–59.6%) following the third episode. Infection with vivax malaria increased the rate of re-presentation to hospital by 1.48-fold (Hazard Ratio 1.48; 95%CI 1.44–1.51) and late hospital in-patient admission by 1.17-fold (1.11–1.22), compared to falciparum. Falciparum malaria caused a higher overall rate of early death (1.54 (1.25–1.92)), however, after multiple episodes, there was a trend towards a greater rate of early death for vivax infection (1.91 (0.73–4.97)). Conclusions Recurrent episodes of malaria can cause substantial morbidity and mortality, highlighting the importance of prevention and effective treatments for both falciparum and vivax malaria. Key messages To achieve elimination of malaria in South-East Asia, where prevalence of vivax malaria is high, we must prioritise the radical cure of vivax to eliminate the liver-stage of this species that causes relapses of infection.

2021 ◽  
Yu Xie ◽  
Changzhi Huang ◽  
Xingchen Zhu ◽  
Jiayu Wang ◽  
Xikang Fan ◽  

Abstract Background: Insulin-like growth factor 1 (IGF-1) is an important growth factor modulating development, homeostasis, and aging. However, whether and how circulating IGF-1 concentrations influence early death risk in the general population remains largely unknown. Methods: We included 380,997 participants who had serum IGF-1 measurement and no history of cancer, cardiovascular disease (CVD) or diabetes at baseline from UK Biobank, a prospective cohort study initiated in 2006-2010. Restricted cubic splines and Cox proportional hazards regression models were used to assess the association between baseline IGF-1 concentrations and all-cause and cause-specific mortality. Results: Over a median follow-up of 8.8 years, 10,753 of the participants died, including 6110 from cancer and 1949 from CVD. Dose-response analysis showed a U-shaped relationship between IGF-1 levels and mortality. Compared to the fifth decile of IGF-1, the lowest decile was associated with 39% (95% CI: 29%-50%), 20% (95% CI: 8%-34%), and 39% (95% CI: 14%-68%) higher risk of all-cause, cancer, and CVD mortality, respectively, while the highest decile was associated with 17% (95% CI: 7%-28%) and 38% (95% CI: 11%-71%) higher risk of all-cause and CVD mortality, respectively. The results remained stable in detailed stratified and sensitivity analyses. Conclusions: Our findings indicate that both low and high concentrations of serum IGF-1 are associated with increased risk of mortality in the general population. Our study provides a basis for future interrogation of underlying mechanisms of IGF-1 in early death occurrence and possible implications for mitigating the risk.

2021 ◽  
Sina Al-Kershi ◽  
Richard Golnik ◽  
Marius Flasinski ◽  
Katharina Waack ◽  
Mareike Rasche ◽  

AbstractChildren with Down syndrome are at a high risk of developing transient abnormal myelopoiesis (TAM; synonym: TMD) or myeloid leukemia (ML-DS). While most patients with TAM are asymptomatic and go into spontaneous remission without a need for therapy, around 20% of patients die within the first six months due to TAM-related complications. Another 20–30% of patients progress from TAM to ML-DS. ML-DS patients are particularly vulnerable to therapy-associated toxicity, but the prognosis of relapsed ML-DS is extremely poor – thus, ML-DS therapy schemata must strive for a balance between appropriate efficacy (to avoid relapses) and treatment-related toxicity. This guideline presents diagnostic and therapeutic strategies for TAM and ML-DS based on the experience and results of previous clinical studies from the BFM working group, which have helped reduce the risk of early death in symptomatic TAM patients using low-dose cytarabine, and which have achieved excellent cure rates for ML-DS using intensity-reduced treatment protocols.

2021 ◽  
Vol 12 ◽  
Qingyu Xu ◽  
Shujiao He ◽  
Li Yu

BackgroundPrevious trials demonstrated evidence involving the total effects of gemtuzumab ozogamicin (GO), an anti-CD33 humanized antibody, on treating acute myeloid leukemia (AML). In this updated systematic review, meta-analysis, and network meta-analysis (NMA), we aimed to comprehensively explore the clinical benefits and safety of GO in various subtypes of AML.MethodsPubMed, Embase, Cochrane, and Chinese databases were filtered to search randomized controlled trials (RCTs) and retrospective cohort studies that compared clinical efficiency and toxicity of GO with non-GO groups in AML. Random-effects models were used to calculate pooled effect sizes and 95% confidence intervals (CIs). Relative risk (RR) was used for estimating complete remission (CR), early death, and toxicity. Hazard risk (HR) was accomplished to evaluate survival.ResultsFifteen RCTs and 15 retrospective cohort studies were identified (GO: 4,768; Control: 6,466). GO tended to improve CR (RR 0.95, p = 0.084), followed by significantly improved survival (overall survival: HR 0.86, p = 0.003; event-free survival: HR 0.86, p = 0.015; relapse-free survival: HR 0.83, p = 0.001; cumulative incidence of relapse: HR 0.82, p < 0.001). GO benefits of CR and survival were evident in favorable- and intermediate-risk karyotypes (p ≤ 0.023). GO advantages were also associated with nucleophosmin 1 mutations (p ≤ 0.04), wild-type FMS-like tyrosine kinase 3 internal tandem duplication gene (p ≤ 0.03), age of <70 years (p < 0.05), de novo AML (p ≤ 0.017), and CD33(+) (p ≤ 0.021). Both adding GO into induction therapy (p ≤ 0.011) and a lower (<6 mg/m2) dose of GO (p ≤ 0.03) enhanced survival. Prognosis of combined regimens with GO was heterogeneous in both meta-analysis and NMA, with several binding strategies showing improved prognosis. Additionally, GO was related to increased risk of early death at a higher dose (≥6 mg/m2) (RR 2.01, p = 0.005), hepatic-related adverse effects (RR 1.29, p = 0.02), and a tendency of higher risk for hepatic veno-occlusive disease or sinusoidal obstruction syndrome (RR 1.56, p = 0.072).ConclusionsThese data indicated therapeutic benefits and safety of GO in AML, especially in some subtypes, for which further head-to-head RCTs are warranted.Systematic Review Registration[PROSPERO: https://www.crd.york.ac.uk/prospero/], identifier [CRD42020158540].

Benjamin Chatel ◽  
Sylvie Ducreux ◽  
Zeina Harhous ◽  
Nadia Bendridi ◽  
Isabelle Varlet ◽  

Mitochondrial diseases are genetic disorders leading to an impaired mitochondrial function and resulting in exercise intolerance and muscle weakness. In patients, muscle fatigue due to defects in mitochondrial oxidative capacities commonly precedes muscle weakness. In mice, the fast-twitch skeletal muscle-specific Tfam deletion (Tfam KO) leads to deficit in the respiratory chain activity, severe muscle weakness and early death. Here, we performed a time-course study of mitochondrial and muscular dysfunctions in 11 and 14 weeks Tfam KO mice, i.e., before and when mice are about to enter the terminal stage, respectively. While force in the unfatigued state was reduced in Tfam KO mice as compared to control littermates (WT) only at 14 weeks, during repeated submaximal contractions fatigue was faster at both ages. During fatiguing stimulation, total phosphocreatine breakdown was larger in Tfam KO muscle than in WT muscle at both ages whereas phosphocreatine consumption was faster only at 14 weeks. In conclusion, the Tfam KO mouse model represents a reliable model of lethal mitochondrial myopathy where impaired mitochondrial energy production and premature fatigue occur before muscle weakness and early death.

2021 ◽  
Cheng Shi ◽  
Coleen T Murphy

The reproductive system regulates the aging of the soma through competing anti- and pro-aging signals. Germline removal extends somatic lifespan through conserved pathways including Insulin, mTOR, and steroid signaling, while germline hyperactivity cuts lifespan short through mechanisms that remain elusive. Here, we show that mating-induced germline hyperactivity leads to the dramatic downregulation of piRNAs, which in turn releases silencing of their targets, including the Hedgehog-like ligand encoding genes wrt-1 and wrt-10, ultimately causing somatic collapse and early death. Germline-produced Hedgehog signals require PTR-6 and PTR-16 receptors for mating-induced body shrinking and lifespan shortening. Our results reveal an unconventional role of the piRNA pathway in transcriptional regulation of Hedgehog signaling, as well as a new role of Hedgehog signaling in the regulation of longevity and somatic maintenance. Our data suggest that Hedgehog signaling is controlled by the tunable piRNA pathway to encode the previously unknown germline-to-soma pro-aging signal. Mating-induced downregulation of piRNAs in the germline and subsequent signaling to the soma via the Hedgehog pathway enables the animal to tune its somatic resource allocation in response to germline needs to optimize reproductive timing and survival.

CJC Open ◽  
2021 ◽  
Steven C. Greenway ◽  
Deborah Fruitman ◽  
Raechel Ferrier ◽  
Cathleen Huculak ◽  
Julien Marcadier ◽  

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