PET metabolic tumor volume as a new prognostic factor in childhood rhabdomyosarcoma

Purpose Childhood RMS is a rare malignant disease in which evaluation of tumour spread at diagnosis is essential for therapeutic management. F-18 FDG-PET imaging is currently used for initial RMS disease staging. Materials and methods This multicentre retrospective study in six French university hospitals was designed to analyse the prognostic accuracy of MTV at diagnosis for patients with RMS between 1 January 2007 and 31 October 2017, for overall (OS) and progression-free survival (PFS). MTV was defined as the sum of the primitive tumour and the largest metastasis, where relevant, with a 40% threshold of the primary tumour SUVmax. Additional aims were to define the prognostic value of SUVmax, SUVpeak, and bone lysis at diagnosis. Results Participants were 101 patients with a median age of 7.4 years (IQR [4.0-12.5], 62 boys), with localized disease (35 cases), regional nodal spread (43 cases), or distant metastases (23). 44 patients had alveolar subtypes. In a univariate analysis, a MTV greater than 200 cm3 was associated with OS (HR = 3.47 [1.79;6.74], p<0.001) and PFS (HR = 3.03 [1.51;6.07], p = 0.002). SUVmax, SUVpeak, and bone lysis also influenced OS (respectively p = 0.005, p = 0.004 and p = 0.007) and PFS (p = 0.029, p = 0.019 and p = 0.015). In a multivariate analysis, a MTV greater than 200 cm3 was associated with OS (HR = 2.642 [1.272;5.486], p = 0.009) and PFS (HR = 2.707 [1.322;5.547], p = 0.006) after adjustment for confounding factors, including SUVmax, SUVpeak, and bone lysis. Conclusion A metabolic tumor volume greater than 200 cm3, SUVmax, SUVpeak, and bone lysis in the pre-treatment assessment were unfavourable for outcome.

Non-linear and Interaction Analyses of Biomarkers for Organ Dysfunctions as Predictive Markers for Sepsis: A Nationwide Retrospective Study

The Sequential Organ Failure Assessment (SOFA) score is predominantly used to assess the severity of organ dysfunction in sepsis. However, differences in prognostic value between SOFA subscores have not been sufficiently evaluated. This retrospective observational study used a large-scale database containing about 30 million patients. Among them, we included 38,869 adult patients with sepsis from 2006 to 2019. The cardiovascular and neurological subscores were calculated by a modified method. Associations between the biomarkers of the SOFA components and mortality were examined using restricted cubic spline analyses, which showed that an increase in the total modified SOFA score was linearly associated with increased mortality. However, the prognostic association of subscores varied widely: platelet count showed a J-shaped association, creatinine showed an inverted J-shaped association, and bilirubin showed only a weak association. We also evaluated interaction effects on mortality between an increase of one subscore and another. The joint odds ratios on mortality of two modified SOFA subscores were synergistically increased compared to the sum of the single odds ratios, especially in cardiovascular-neurological, coagulation-hepatic, and renal-hepatic combinations. In conclusion, total modified SOFA score was associated with increased mortality despite the varied prognostic associations of the subscores, possibly because interactions between subscores synergistically enhanced prognostic accuracy.

Significance of the Modified NUTRIC Score for Predicting Clinical Outcomes in Patients with Severe Community-Acquired Pneumonia

Nutritional status could affect clinical outcomes in critical patients. We aimed to determine the prognostic accuracy of the modified Nutrition Risk in Critically Ill (mNUTRIC) score for hospital mortality and treatment outcomes in patients with severe community-acquired pneumonia (SCAP) compared to other clinical prediction rules. We enrolled SCAP patients in a multi-center setting retrospectively. The mNUTRIC score and clinical prediction rules for pneumonia, as well as clinical factors, were calculated and recorded. Clinical outcomes, including mortality status and treatment outcome, were assessed after the patient was discharged. We used the receiver operating characteristic (ROC) curve method and multivariate logistic regression analysis to determine the prognostic accuracy of the mNUTRIC score for predicting clinical outcomes compared to clinical prediction rules, while 815 SCAP patients were enrolled. ROC curve analysis showed that the mNUTRIC score was the most effective at predicting each clinical outcome and had the highest area under the ROC curve value. The cut-off value for predicting clinical outcomes was 5.5. By multivariate logistic regression analysis, the mNUTRIC score was also an independent predictor of both clinical outcomes in SCAP patients. We concluded that the mNUTRIC score is a better prognostic factor for predicting clinical outcomes in SCAP patients compared to other clinical prediction rules.

Role of Clinical Characteristics and Biomarkers at Admission to Predict One-Year Mortality in Elderly Patients with Pneumonia

Background: A hospitalization for community-acquired pneumonia results in a decrease in long-term survival in elderly patients. We assessed biomarkers at admission to predict one-year mortality in a cohort of elderly patients with pneumonia. Methods: A prospective observational study included patients >65 years hospitalized with pneumonia. Assessment of PSI, CURB-65, and biomarkers (C-reactive protein (CRP), procalcitonin (PCT), NT-pro-B-type natriuretic peptide (NT-proBNP), interleukin (IL)-6 and -8, tumor necrosis factor alpha (TNF-α), serum amyloid A (SAA), neopterin (NP), myeloperoxidase (MPO), anti-apolipoprotein A-1 IgG (anti-apoA-1), and anti-phosphorylcholine IgM (anti-PC IgM)) was used to calculate prognostic values for one-year mortality using ROC curve analyses. Post hoc optimal cutoffs with corresponding sensitivity (SE) and specificity (SP) were determined using the Youden index. Results: A total of 133 patients were included (median age 83 years [IQR: 78–89]). Age, dementia, BMI, NT-proBNP (AUROC 0.65 (95% CI: 0.55–0.77)), and IL-8 (AUROC 0.66 (95% CI: 0.56–0.75)) were significantly associated with mortality, with NT-proBNP (HR 1.01 (95% CI 1.00–1.02) and BMI (HR 0.92 (95% CI 0.85–1.000) being independent of age, gender, comorbidities, and PSI with Cox regression. At the cutoff value of 2200 ng/L, NT-proBNP had 67% sensitivity and 70% specificity. PSI and CURB-65 were not associated with mortality. Conclusions: NT-proBNP levels upon admission and BMI displayed the highest prognostic accuracy for one-year mortality and may help clinicians to identify patients with poor long-term prognosis.

Posterior National Institutes of Health Stroke Scale Improves Prognostic Accuracy in Posterior Circulation Stroke

Background and Purpose: The National Institutes of Health Stroke Scale (NIHSS) underestimates clinical severity in posterior circulation stroke and patients presenting with low NIHSS may be considered ineligible for reperfusion therapies. This study aimed to develop a modified version of the NIHSS, the Posterior NIHSS (POST-NIHSS), to improve NIHSS prognostic accuracy for posterior circulation stroke patients with mild-moderate symptoms. Methods: Clinical data of consecutive posterior circulation stroke patients with mild-moderate symptoms (NIHSS <10), who were conservatively managed, were retrospectively analyzed from the Basilar Artery Treatment and Management registry. Clinical features were assessed within 24 hours of symptom onset; dysphagia was assessed by a speech therapist within 48 hours of symptom onset. Random forest classification algorithm and constrained optimization were used to develop the POST-NIHSS in the derivation cohort. The POST-NIHSS was then validated in a prospective cohort. Poor outcome was defined as modified Rankin Scale score ≥3 at 3 months. Results: We included 202 patients (mean [SD] age 63 [14] years, median NIHSS 3 [interquartile range, 1–5]) in the derivation cohort and 65 patients (mean [SD] age 63 [16] years, median NIHSS 2 [interquartile range, 1–4]) in the validation cohort. In the derivation cohort, age, NIHSS, abnormal cough, dysphagia and gait/truncal ataxia were ranked as the most important predictors of functional outcome. POST-NIHSS was calculated by adding 5 points for abnormal cough, 4 points for dysphagia, and 3 points for gait/truncal ataxia to the baseline NIHSS. In receiver operating characteristic analysis adjusted for age, POST-NIHSS area under receiver operating characteristic curve was 0.80 (95% CI, 0.73–0.87) versus NIHSS area under receiver operating characteristic curve, 0.73 (95% CI, 0.64–0.83), P =0.03. In the validation cohort, POST-NIHSS area under receiver operating characteristic curve was 0.82 (95% CI, 0.69–0.94) versus NIHSS area under receiver operating characteristic curve 0.73 (95% CI, 0.58–0.87), P =0.04. Conclusions: POST-NIHSS showed higher prognostic accuracy than NIHSS and may be useful to identify posterior circulation stroke patients with NIHSS <10 at higher risk of poor outcome.

Association between neutrophil to lymphocyte ratio and mortality among community acquired pneumonia patients: a meta-analysis

The neutrophil to lymphocyte ratio (NLR)is an emerging biomarker used in the prognosis of many conditions. We aimed to conduct a meta-analysis to assess the prognostic accuracy of the NLR in determining mortality in patients with Community acquired pneumonia (CAP). The Pubmed, EBSCO, and Scopus databases were searched to find all relevant articles. 10 articles with 5220 patients were included. The pooled area under the curve (AUC) of NLR admission levels to predict 30-Day mortality of CAP patients was 0.706; 95% CI (0.631 to 0.781), while the pooled AUC of NLR levels taken at 3-5 days was 0.882; 95% CI (0.818 to 0.945). Meta analysis also showed a significant difference in the NLR between the Survivors and 30-Day non-survivors. This difference was greater when NLR levels were taken at 3-5 days; Standardized mean difference (SMD) = 1.646; 95% CI (0.451 to 2.840) compared to NLR levels at admission SMD = 1.139; 95% CI (0.514 to 1.764). These results show that the NLR has potential to be incorporated in the routine assessment and stratification of CAP patients, especially in the early-stage evolution (3-5 days), keeping in mind the availability and cost effectiveness of this test.

Deep-Learning Approach to Predict Survival Outcomes Using Wearable Actigraphy Device Among End-Stage Cancer Patients

Survival prediction is highly valued in end-of-life care clinical practice, and patient performance status evaluation stands as a predominant component in survival prognostication. While current performance status evaluation tools are limited to their subjective nature, the advent of wearable technology enables continual recordings of patients' activity and has the potential to measure performance status objectively. We hypothesize that wristband actigraphy monitoring devices can predict in-hospital death of end-stage cancer patients during the time of their hospital admissions. The objective of this study was to train and validate a long short-term memory (LSTM) deep-learning prediction model based on activity data of wearable actigraphy devices. The study recruited 60 end-stage cancer patients in a hospice care unit, with 28 deaths and 32 discharged in stable condition at the end of their hospital stay. The standard Karnofsky Performance Status score had an overall prognostic accuracy of 0.83. The LSTM prediction model based on patients' continual actigraphy monitoring had an overall prognostic accuracy of 0.83. Furthermore, the model performance improved with longer input data length up to 48 h. In conclusion, our research suggests the potential feasibility of wristband actigraphy to predict end-of-life admission outcomes in palliative care for end-stage cancer patients.Clinical Trial Registration: The study protocol was registered on ClinicalTrials.gov (ID: NCT04883879).

Prognostic Accuracy of the qSOFA Score for In-Hospital Mortality in Elderly Patients with Obstructive Acute Pyelonephritis: A Multi-Institutional Study

Prognostic accuracy of the quick sequential organ failure assessment (qSOFA) score for mortality may be limited in elderly patients. Using our multi-institutional database, we classified obstructive acute pyelonephritis (OAPN) patients into young and elderly groups, and evaluated predictive performance of the qSOFA score for in-hospital mortality. qSOFA score ≥ 2 was an independent predictor for in-hospital mortality, as was higher age, and Charlson comorbidity index (CCI) ≥ 2. In young patients, the area under the curve (AUC) of the qSOFA score for in-hospital mortality was 0.85, whereas it was 0.61 in elderly patients. The sensitivity and specificity of qSOFA score ≥ 2 for in-hospital mortality was 80% and 80% in young patients, and 50% and 68% in elderly patients, respectively. For elderly patients, we developed the CCI-incorporated qSOFA score, which showed higher prognostic accuracy compared with the qSOFA score (AUC, 0.66 vs. 0.61, p < 0.001). Therefore, the prognostic accuracy of the qSOFA score for in-hospital mortality was high in young OAPN patients, but modest in elderly patients. Although it can work as a screening tool to determine therapeutic management in young patients, for elderly patients, the presence of comorbidities should be considered at the initial assessment.

Integration of Tumor Heterogeneity for Recurrence Prediction in Patients with Esophageal Squamous Cell Cancer

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest malignancies in China. The prognostic value of mutations, especially those in minor tumor clones, has not been systematically investigated. We conducted targeted deep sequencing to analyze the mutation status and the cancer cell fraction (CCF) of mutations in 201 ESCC patients. Our analysis showed that the prognostic effect of mutations was relevant to the CCF, and it should be considered in prognosis prediction. EP300 was a promising biomarker for overall survival, impairing prognosis in a CCF dose-dependent manner. We constructed a CCF-based predictor using a smooth clipped absolute deviation Cox model in the training set of 143 patients. The 3-year disease-free survival rates were 6.3% (95% CI: 1.6–23.9%), 29.8% (20.9–42.6%) and 70.5% (56.6–87.7%) in high-, intermediate- and low-risk patients, respectively, in the training set. The prognostic accuracy was verified in a validation set of 58 patients and the TCGA-ESCC cohort. The eight-gene model predicted prognosis independent of clinicopathological factors and the combination of our model and pathological staging markedly improved the prognostic accuracy of pathological staging alone. Our study describes a novel recurrence predictor for ESCC patients and provides a new perspective for the clinical translation of genomic findings.

Prognostic accuracy of antenatal Doppler ultrasound for adverse perinatal outcomes in low-income and middle-income countries: a systematic review

ObjectivesThis systematic review examined available literature on the prognostic accuracy of Doppler ultrasound for adverse perinatal outcomes in low/middle-income countries (LMIC).DesignWe searched PubMed, Embase, Cochrane Library and Scopus from inception to April 2020.SettingObservational or interventional studies from LMICs.ParticipantsSingleton pregnancies of any risk profile.InterventionsUmbilical artery (UA), middle cerebral artery (MCA), cerebroplacental ratio (CPR), uterine artery (UtA), fetal descending aorta (FDA), ductus venosus, umbilical vein and inferior vena cava.Primary and secondary outcome measuresPerinatal death, stillbirth, neonatal death, expedited delivery for fetal distress, meconium-stained amniotic fluid, low birth weight, fetal growth restriction, admission to neonatal intensive care unit, neonatal acidosis, Apgar scores, preterm birth, fetal anaemia, respiratory distress syndrome, length of hospital stay, birth asphyxia and composite adverse perinatal outcomes (CAPO).ResultsWe identified 2825 records, and 30 (including 4977 women) from Africa (40.0%, n=12), Asia (56.7%, n=17) and South America (3.3%, n=01) were included. Many individual studies reported associations and promising predictive values of UA Doppler for various adverse perinatal outcomes mostly in high-risk pregnancies, and moderate to high predictive values of MCA, CPR and UtA Dopplers for CAPO. A few studies suggested that the MCA and FDA may be potent predictors of fetal anaemia. No randomised clinical trial (RCT) was found. Most studies were of suboptimal quality, poorly powered and characterised by wide variations in outcome classifications, the timing for the Doppler tests and study populations.ConclusionLocal evidence to guide how antenatal Doppler ultrasound should be used in LMIC is lacking. Well-designed studies, preferably RCTs, are required. Standardisation of practice and classification of perinatal outcomes across countries, following the international standards, is imperative.PROSPERO registration numberCRD42019128546