Estimating Neurologic Prognosis in Children: High Stakes, Poor Data.
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ABSTRACT:
SUBMITTER: Lemmon ME
PROVIDER: S-EPMC7472892 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Prognosis can no longer be relegated behind diagnosis and therapy in high-quality neurologic care. High-stakes decisions that patients (or their surrogates) make often rest upon perceptions and beliefs about prognosis, many of which are poorly informed. The new science of prognostication--the estimating and communication "what to expect"--is in its infancy and the evidence base to support "best practices" is lacking. We propose a framework for formulating a prediction and communicating "what to expect" with patients, families, and surrogates in the context of common neurologic illnesses. Because neurologic disease affects function as much as survival, we specifically address 2 important prognostic questions: "How long?" and "How well?" We provide a summary of prognostic information and highlight key points when tailoring a prognosis for common neurologic diseases. We discuss the challenges of managing prognostic uncertainty, balancing hope and realism, and ways to effectively engage surrogate decision-makers. We also describe what is known about the nocebo effects and the self-fulfilling prophecy when communicating prognoses. There is an urgent need to establish research and educational priorities to build a credible evidence base to support best practices, improve communication skills, and optimize decision-making. Confronting the challenges of prognosis is necessary to fulfill the promise of delivering high-quality, patient-centered care.
| S-EPMC3589298 | biostudies-literature
Project description:Although intracerebral hemorrhage (ICH) volume and location are important predictors of outcome in adults, few data exist in children.A consecutive cohort of children, including full-term newborns to those younger than 18 years of age with nontraumatic, acute ICH and head CT available for analysis were studied. Clinical information was abstracted via chart review. Hemorrhage volume was expressed as percentage of total brain volume (TBV) with large hemorrhage defined as >or=4% of TBV. Hemorrhages were manually traced on each head CT slice and volumes were calculated by multiplying by slice thickness. Location was classified as supratentorial or infratentorial. Logistic regression was used to identify predictors of poor neurological outcome, defined as a Glasgow outcome scale <or=2 (death or persistent vegetative state).Thirty children were included, median age 6 years. Median ICH volume was 20.4 cm(3) and median ICH size as a percentage of TBV was 1.9%. Only 4 of 22 children with ICH <4% of TBV had poor outcomes, vs 5 of 8 children with ICH >or=4% of TBV (P=0.03). In multivariate analysis, hemorrhage >or=4% of TBV (OR, 22.5; 95% CI, 1.4-354; P=0.03) independently predicted poor outcome 30 days after ICH. In this small sample, infratentorial hemorrhage location and the presence of intraventricular hemorrhage did not predict poor outcome.ICH volume predicts neurological outcome at 30 days in children, with worst outcome when hemorrhage is >or=4% of TBV. Location and ICH etiology may also be important. These findings identify children with ICH who are candidates for aggressive management and may influence counseling regarding prognosis.
| S-EPMC2830068 | biostudies-other
Project description:To measure the frequency of withdrawal of life-sustaining therapy for perceived poor neurologic prognosis among decedents in hospitals of different sizes and teaching statuses.DesignWe performed a multicenter, retrospective cohort study.SettingFour large teaching hospitals, four affiliated small teaching hospitals, and nine affiliated nonteaching hospitals in the United States.PatientsWe included a sample of all adult inpatient decedents between August 2017 and August 2019.Measurements and main resultsWe reviewed inpatient notes and categorized the immediately preceding circumstances as withdrawal of life-sustaining therapy for perceived poor neurologic prognosis, withdrawal of life-sustaining therapy for nonneurologic reasons, limitations or withholding of life support or resuscitation, cardiac death despite full treatment, or brain death. Of 2,100 patients, median age was 71 years (interquartile range, 60-81 yr), median hospital length of stay was 5 days (interquartile range, 2-11 d), and 1,326 (63%) were treated at four large teaching hospitals. Withdrawal of life-sustaining therapy for perceived poor neurologic prognosis occurred in 516 patients (25%) and was the sole contributing factor to death in 331 (15%). Withdrawal of life-sustaining therapy for perceived poor neurologic prognosis was common in all hospitals: 30% of deaths at large teaching hospitals, 19% of deaths in small teaching hospitals, and 15% of deaths at nonteaching hospitals. Withdrawal of life-sustaining therapy for perceived poor neurologic prognosis happened frequently across all hospital units. Withdrawal of life-sustaining therapy for perceived poor neurologic prognosis contributed to one in 12 deaths in patients without a primary neurologic diagnosis. After accounting for patient and hospital characteristics, significant between-hospital variability in the odds of withdrawal of life-sustaining therapy for perceived poor neurologic prognosis persisted.ConclusionsA quarter of inpatient deaths in this cohort occurred after withdrawal of life-sustaining therapy for perceived poor neurologic prognosis. The rate of withdrawal of life-sustaining therapy for perceived poor neurologic prognosis occurred commonly in all type of hospital settings. We observed significant unexplained variation in the odds of withdrawal of life-sustaining therapy for perceived poor neurologic prognosis across participating hospitals.
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Project description:Adults report more willingness to help siblings over close friends when the stakes are extremely high, such as when deciding whether to donate a kidney or risk injury to rescue someone in peril. When dividing plentiful, low-value resources, in contrast, children expect people to share equally with friends and siblings. Even when distributing limited resources-one instead of many-and distributing to their own social partners rather than fictional characters, children share more with kin and friends than with strangers but do not favor kin over friends until 5.5 years of age. However, no study has tested whether children would preferentially benefit kin if the rewards require that children incur a higher personal cost of their own time and effort. In the present experiment, therefore, we asked if children would work harder for kin over non-kin when playing a challenging geometry game that allowed them to earn rewards for others. We found that 4.5-year-old children calibrated their time and effort in the game differently according to who received the rewards-they played for more trials and answered more trials correctly for kin over non-kin, but 5.5-year-old children did not. The older children may have found the task easier and less costly or may have different social experiences affecting their efforts to benefit others. Nonetheless, 4.5-year-old children's social decisions favored kin as recipients of their generosity.
| S-EPMC6095549 | biostudies-literature
Project description:Using an incentivized experiment with statistical power, this paper explores the role of stakes in charitable giving of lottery prizes, where subjects commit to donate a fraction of the prize before they learn the outcome of the lottery. We study three stake levels: 5€ (n = 177), 100€ (n = 168), and 1,000€ (n = 171). Although the donations increase in absolute terms as the stakes increase, subjects decrease the donated fraction of the pie. However, people still share roughly 20% of 1,000€, an amount as high as the average monthly salary of people at the age of our subjects. The number of people sharing 50% of the pie is remarkably stable across stakes, but donating the the whole pie-the modal behavior in charity-donation experiments-disappears with stakes. Such hyper-altruistic behavior thus seems to be an artifact of the stakes typically employed in economic and psychological experiments. Our findings point out that sharing with others is a prevalent human feature, but stakes are an important determinant of sharing. Policies promoted via prosocial frames (e.g., stressing the effects of mask-wearing or social distancing on others during the Covid-19 pandemic or environmentally-friendly behaviors on future generations) may thus be miscalibrated if they disregard the stakes at play.
| S-EPMC8386826 | biostudies-literature
Project description:TRPS1 is aberrantly expressed in a variety of tumors, including breast, prostate, and gastric cancers, and is strongly associated with tumorigenesis or prognosis. However, the role of TRPS1 in high grade serous ovarian carcinoma (HGSC) is unknown. We investigated the relationship between TRPS1 expression and clinicopathology in HGSC patients. The tumor-related regulatory mechanisms of TRPS1 was explored through in vivo and vitro experiments. The results showed that TRPS1 was highly expressed in HGSC compared to normal tissues. It was also linked to the cell proliferation index Ki67 and poor prognosis. In vivo experiments showed that knockdown of TRPS1 could inhibit tumor growth. In vitro experiments, knockdown of TRPS1 inhibited the proliferation of ovarian cancer cells. TRPS1 exerted its regulatory role as a transcription factor, binding to the PSAT1 promoter and promoting the expression of PSAT1 gene. Meanwhile, PSAT1 was positively correlated with CCND1 expression. These results suggest that TRPS1 affects HGSC proliferation and cell cycle by regulating PSAT1 and thus CCND1 expression.
2023-12-11 | GSE249935 | GEO
Project description:DHCR7 is a rate-limiting enzyme in cholesterol synthesis. The expression pattern and prognostic value of DHCR7 in cervical cancer are unknown. We investigated the relationship between DHCR7 expression and clinicopathological features of cervical cancer patients. The dataset was acquired from TCGA database. The Wilcoxon rank sum test was used to explore DHCR7 expression level in cervical cancer. The Kruskal-Wallis test and the logistic regression were performed to estimate the association between the DHCR7 and clinical features. The Kaplan-Meier and Cox regression analyses were used to evaluate factors that affect cervical cancer prognosis. GSEA was used to screen the DHCR7-related pathways. We found that DHCR7 was increased in cervical cancer samples and increased DHCR7 was correlated with advanced T stage, lymph node invasion, and clinical stage (P < 0.05). Patients with elevated DHCR7 levels had poorer overall survival (P = 0.021), progression-free interval (P = 0.002), and disease-specific survival (P = 0.005). Cox analysis revealed that DHCR7 was an independent prognostic factor in cervical cancer (P = 0.005). WNT activated receptor activity, G2/M checkpoint, mTORC1 signaling, KRAS signaling, regulation of cholesterol biosynthetic, FGF signaling, T-cell receptor signaling, JAK/STAT signaling cascade T cell activation, and macrophage migration were enriched in high DHCR7 phenotype. Our data also showed that DHCR7 moderately correlates with T-cell infiltration, including CD8+ T-cells. Conclusion. Increased DHCR7 expression is associated with poor survival in cervical cancer.
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Project description:Human RING-finger protein 40 (RNF40) is reported as an E3 ligase of H2B ubiquitination. RNF40 needs to couple with its homolog RNF20 to format a complex to regulate DNA double strand break (DSB) response and chromatin stability. Deficient expression of RNF40 might cause incorrect DNA repair and contribute to genomic instability, leading to an abnormal transcriptional program. Incorrect DSB repair and aberrant gene transcription play important roles in tumorigenesis. The role in primary hepatocellular carcinoma (HCC), however, remains unclear. In this study, we selected 103 cases of HCC for immunohistochemistry to explore the role of RNF40 in HCC. The relationship between RNF40 expression and clinicopathological features of HCC was evaluated. RNF40 was mainly localized in the nucleus, where the percentage of low and high staining of RNF40 in tumor tissues was 50.4% (53/103) and 49.6% (50/103), respectively. By contrast, in para-normal tissues the percentage was 92.2% (95/103) and 7.8% (8/103) respectively. Expression of RNF40 in tumor tissues was significantly higher than that in para-normal tissues (P>0.01). Expression of RNF40 had significant association with AFP and TNM tumor stage (both P>0.01). However, age, gender, Hepatitis B Virus infection, liver cirrhosis, tumor size, tumor number, differential stage, and tumor thrombosis were not associated with RNF40 expression. Meanwhile, HCC patients with high expression of RNF40 had lower 5 year overall survival rates and disease-free survival rates (P>0.05). RNF40 is, potentially, an independent prognostic factor for survival in HCC.
| S-EPMC6958262 | biostudies-literature
Project description:Background: PYGL has been reported as a glycogen degradation-related gene, which is up-regulated in many tumors. This study was designed to investigate the predictive value of high PYGL expression in patients with gliomas through bioinformatics analysis of the gene transcriptome and the single-cell sequencing data. Methods: The gene transcriptome data of 595 glioma patients from the TCGA database and the single-cell RNA sequencing data of 7,930 GBM cells from the GEO database were included in the study. Differential analysis was used to find the distribution of expression of PYGL in different groups of glioma patients. OS analysis was used to assess the influence of the high expression of PYGL on the prognosis of patients. The reliability of its prediction was evaluated by the AUC of ROC and the C-index. The GSEA be used to reveal potential mechanisms. The single-cell analysis was used to observe the high expression of PYGL in different cell groups to further analyze the mechanism of its prediction. Results: Differential analysis identified the expression level of PYGL is positively associated with glioma malignancy. OS analysis and Cox regression analyses showed high expression of PYGL was an independent factor for poor prognosis of gliomas (p < 0.05). The AUC values were 0.838 (1-year ROC), 0.864 (3-year ROC) and 0.833 (5-year ROC). The C index was 0.81. The GSEA showed that gene sets related to MTORC1 signaling, glycolysis, hypoxia, PI3K/AKT/mTOR signaling, KRAS signaling up and angiogenesis were differentially enriched in the high PYGL expression phenotype. The single-cell sequencing data analysis showed TAMs and malignant cells in GBM tissues expressed a high level of PYGL. Conclusion: The high expression of PYGL is an independent predictor of poor prognosis in patients with glioma.
| S-EPMC8225935 | biostudies-literature
Project description:Apelin (APLN) is an endogenous ligand of the G protein-coupled receptor APJ (APLNR). APLN/APLNR system was involved in a variety of pathological and physiological functions, such as tumorigenesis and development. However, its prognostic roles in patients with central nervous system (CNS) cancers remain unknown. The present study was designed to explore the expression profile, prognostic significance, and interaction network of APLN/APLNR by integrating data from Oncomine, GEPIA, LOGpc, STRING, GeneMANIA, and immunohistochemical staining. The results demonstrated that APLN and APLNR mRNA expression were significantly increased in CNS cancers, including both low-grade glioma (LGG) and glioblastoma (GBM), when compared with normal CNS tissues. The high APLN, but not APLNR, expression was significantly correlated with overall survival (OS), recurrence free survival (RFS), and progression free survival (PFS) of LGG patients. However, neither APLN nor APLNR expression was significantly related to prognostic value in terms of OS, disease free interval (DFI), disease specific survival (DSS), or progression free interval (PFI) for GBM patients. Additionally, immunohistochemistry staining confirmed the increased APLN expression in tissues of LGG patients with grade II than grade I. These results showed that an elevated APLN level could predict poor OS, RFS, and PFS for LGG patients, and it could be a promising prognostic biomarker for LGG.
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