Purpose
MYCN
onco-gene amplification in neuroblastoma confers patients to the high-risk disease category for which prognosis is poor and more aggressive multimodal treatment is indicated. This ...retrospective study leverages machine learning techniques to develop a computed tomography (CT)–based model incorporating semantic and non-semantic features for non-invasive prediction of
MYCN
amplification status in pediatric neuroblastoma.
Methods
From 2009 to 2020, 54 pediatric patients treated for neuroblastoma at a specialized children’s hospital with pre-treatment contrast-enhanced CT and
MYCN
status were identified (training cohort,
n
= 44; testing cohort,
n
= 10). Six morphologic features and 107 quantitative gray-level texture radiomics features extracted from manually drawn volume-of-interest were analyzed. Following feature selection and class balancing, the final predictive model was developed with eXtreme Gradient Boosting (XGBoost) algorithm. Accumulated local effects (ALE) plots were used to explore main effects of the predictive features. Tumor texture maps were also generated for visualization of radiomics features.
Results
One morphologic and 2 radiomics features were selected for model building. The XGBoost model from the training cohort yielded an area under the receiver operating characteristics curve (AUC-ROC) of 0.930 (95%
CI
, 0.85–1.00), optimized F1-score of 0.878, and Matthews correlation coefficient (MCC) of 0.773. Evaluation on the testing cohort returned AUC-ROC of 0.880 (95%
CI
, 0.64–1.00), optimized F1-score of 0.933, and MCC of 0.764. ALE plots and texture maps showed higher “GreyLevelNonUniformity” values, lower “Strength” values, and higher number of image-defined risk factors contribute to higher predicted probability of
MYCN
amplification.
Conclusion
The machine learning model reliably classified
MYCN
amplification in pediatric neuroblastoma and shows potential as a surrogate imaging biomarker.
The effect of employing severity scores to identify severe community-acquired pneumonia (SCAP) cases for early aggressive resuscitation is unknown. Optimising pre-intensive care unit (ICU) care may ...improve outcomes in patients at risk of SCAP. We conducted a before-and-after study of patients classified into control and intervention groups (January 2004 to December 2007 and January 2008 to December 2010, respectively). Our intervention was two-pronged, using the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) minor criteria to identify SCAP for aggressive emergency department resuscitation. Patients with SCAP, defined as those with three or more IDSA/ATS minor criteria, were targeted. Differences in mortality, triage and compliance with emergency department resuscitation were compared between the groups. The hospital mortality rate was lower in the intervention versus the control group (5.7% versus 23.8%, p<0.001). On multivariate analysis, the intervention group was associated with lower mortality (OR 0.24, 95% CI 0.09-0.67). ICU admission rates decreased from 52.9% to 38.6% (p=0.008) and inappropriately delayed ICU admissions decreased from 32.0% to 14.8% (p<0.001). There was increased compliance with the aggressive resuscitation protocol after the intervention. A combined intervention, using a pneumonia score to identify those at risk of SCAP early and an aggressive pre-ICU resuscitation protocol may reduce mortality and ICU admissions.
Connective tissue diseases of the skin are characterized by excessive collagen deposition in the skin and internal organs. Fibroblasts play a pivotal role in the clinical presentation of these ...conditions. Nuclear receptor peroxisome-proliferator activated receptors (PPARs) are therapeutic targets for dermal fibrosis, but the contribution of the different PPAR subtypes are poorly understood. Particularly, the role of fibroblast PPARβ/δ in dermal fibrosis has not been elucidated. Thus, we generated a mouse strain with selective deletion of PPARβ/δ in the fibroblast (FSPCre-
) and interrogated its epidermal and dermal transcriptome profiles. We uncovered a downregulated gene, leucine-rich alpha-2-glycoprotein-1 (
), of previously unknown function in skin development and architecture. Our findings suggest that the regulation of
by PPARβ/δ in fibroblasts is an important signaling conduit integrating PPARβ/δ and TGFβ1-signaling networks in skin health and disease. Thus, the FSPCre-
mouse model could serve as a novel tool in the current gunnery of animal models to better understand dermal fibrosis.
Background. Data on long-term outcomes of elderly (≥65 years) patients in ICU are sparse. Materials and Methods. Adult patients ( n = 1563 , 45.4% elderly) admitted over 28 months were analyzed by ...competing risks regression model to determine independent factors related to in-hospital and long-term mortality. Results. 414 (26.5%) and 337 (21.6%) patients died in-hospital and during the 52 months following discharge, respectively; the elderly group had higher mortality during both periods. After discharge, elderly patients had 2.3 times higher mortality compared to the general population of the same age-group. In-hospital mortality was independently associated with mechanical ventilation (subdistribution hazard ratio (SHR) 2.74), vasopressors (SHR 2.56), neurological disease (SHR 1.77), and Mortality Prediction Model II score (SHR 1.01) regardless of age and with malignancy (SHR, hematological 3.65, nonhematological 3.4) and prior renal replacement therapy (RRT, SHR 2.21) only in the elderly. Long-term mortality was associated with low hemoglobin concentration (SHR 0.94), airway disease (SHR 2.23), and malignancy (SHR hematological 1.11, nonhematological 2.31) regardless of age and with comorbidities especially among the nonelderly. Conclusions. Following discharge, elderly ICU patients have higher mortality compared to the nonelderly and general population. In the elderly group, prior RRT and malignancy contribute additionally to in-hospital mortality risk. In the long-term, comorbidities (age-related), anemia, airway disease, and malignancy were significantly associated with mortality.
It is well established that Ly6C
monocytes develop from common monocyte progenitors (cMoPs) and reside in the bone marrow (BM) until they are mobilized into the circulation. In our study, we found ...that BM Ly6C
monocytes are not a homogenous population, as current data would suggest. Using computational analysis approaches to interpret multidimensional datasets, we demonstrate that BM Ly6C
monocytes consist of two distinct subpopulations (CXCR4
and CXCR4
subpopulations) in both mice and humans. Transcriptome studies and in vivo assays revealed functional differences between the two subpopulations. Notably, the CXCR4
subset proliferates and is immobilized in the BM for the replenishment of functionally mature CXCR4
monocytes. We propose that the CXCR4
subset represents a transitional premonocyte population, and that this sequential step of maturation from cMoPs serves to maintain a stable pool of BM monocytes. Additionally, reduced CXCR4 expression on monocytes, upon their exit into the circulation, does not reflect its diminished role in monocyte biology. Specifically, CXCR4 regulates monocyte peripheral cellular activities by governing their circadian oscillations and pulmonary margination, which contributes toward lung injury and sepsis mortality. Together, our study demonstrates the multifaceted role of CXCR4 in defining BM monocyte heterogeneity and in regulating their function in peripheral tissues.
The presence of trigger factors may help to distinguish asthma from chronic obstructive pulmonary disease (COPD). Knowing and avoiding trigger factors for both asthma and COPD can facilitate the ...design of comprehensive management programmes that can aid disease control. This study aimed to describe the relative frequency and range of various trigger factors in asthma and COPD.
We conducted a telephone-based survey involving asthma and COPD patients on follow-up at a university hospital in Singapore.
A total of 779 asthma patients and 129 COPD patients participated in this study. Among these patients, 93.8% of those with asthma and 42.6% of those with COPD had trigger factors (p < 0.001). The median number of trigger factors was greater among asthma patients than among those with COPD (3 vs. 0, p < 0.001). Trigger factors found to be significantly more prevalent among asthma patients compared to those with COPD include tobacco smoke, alcohol, upper respiratory tract infections, incense smoke, perfume, laughter, a dusty environment, air-conditioning, heavy rain, heavy traffic fumes, citrus fruits, gastro-oesophageal reflux, household pets, flowers/pollen, medications and psychological triggers. Trigger factors that were not previously described, such as bathing, fatigue, insufficient sleep, crowded places and overeating, were also reported.
Trigger factors, although found in both groups of patients, were more common among asthma patients. Knowledge of these trigger factors may be useful in distinguishing between the two diseases and optimising disease management.
High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We ...estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010.
We used data for exposure to risk factors by country, age group, and sex from pooled analyses of population-based health surveys. We obtained relative risks for the effects of risk factors on cause-specific mortality from meta-analyses of large prospective studies. We calculated the population attributable fractions for each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the effects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specific population attributable fractions by the number of disease-specific deaths. We obtained cause-specific mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the final estimates.
In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10·8 million deaths, 95% CI 10·1–11·5) of deaths from these diseases in 2010 were attributable to the combined effect of these four metabolic risk factors, compared with 67% (7·1 million deaths, 6·6–7·6) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined effects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain.
The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing effect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the global response to non-communicable diseases.
UK Medical Research Council, US National Institutes of Health.
Data for trends in blood pressure are needed to understand the effects of its dietary, lifestyle, and pharmacological determinants; set intervention priorities; and evaluate national programmes. ...However, few worldwide analyses of trends in blood pressure have been done. We estimated worldwide trends in population mean systolic blood pressure (SBP). We estimated trends and their uncertainties in mean SBP for adults 25 years and older in 199 countries and territories. We obtained data from published and unpublished health examination surveys and epidemiological studies (786 country-years and 5.4 million participants). For each sex, we used a Bayesian hierarchical model to estimate mean SBP by age, country, and year, accounting for whether a study was nationally representative. In 2008, age-standardised mean SBP worldwide was 128.1 mm Hg (95% uncertainty interval 126.7-129.4) in men and 124.4 mm Hg (123.0-125.9) in women. Globally, between 1980 and 2008, SBP decreased by 0.8 mm Hg per decade (-0.4 to 2.2, posterior probability of being a true decline=0.90) in men and 1.0 mm Hg per decade (-0.3 to 2.3, posterior probability=0.93) in women. Female SBP decreased by 3.5 mm Hg or more per decade in western Europe and Australasia (posterior probabilities ≥0.999). Male SBP fell most in high-income North America, by 2.8 mm Hg per decade (1.3-4.5, posterior probability >0.999), followed by Australasia and western Europe where it decreased by more than 2.0 mm Hg per decade (posterior probabilities >0.98). SBP rose in Oceania, east Africa, and south and southeast Asia for both sexes, and in west Africa for women, with the increases ranging 0.8-1.6 mm Hg per decade in men (posterior probabilities 0.72-0.91) and 1.0-2.7 mm Hg per decade for women (posterior probabilities 0.75-0.98). Female SBP was highest in some east and west African countries, with means of 135 mm Hg or greater. Male SBP was highest in Baltic and east and west African countries, where mean SBP reached 138 mm Hg or more. Men and women in western Europe had the highest SBP in high-income regions. On average, global population SBP decreased slightly since 1980, but trends varied significantly across regions and countries. SBP is currently highest in low-income and middle-income countries. Effective population-based and personal interventions should be targeted towards low-income and middle-income countries. Bill & Melinda Gates Foundation and WHO.
PDF
