Validation of a modified bedside Pediatric Early Warning System score for detection of clinical deterioration in hospitalized pediatric oncology patients: A prospective cohort study

alexandrossfakianakis shared this article with you from Inoreader Validation of a modified bedside Pediatric Early Warning System score for detection of clinical deterioration in hospitalized pediatric oncology patients: A prospective cohort study via Pediatric Blood & Cancer Abstract Background Hospitalized pediatric oncology patients are at risk of severe clinical deterioration. Yet Pediatric Early Warning System (PEWS) scores have not been prospectively validated in these patients. We aimed to determine the predictive performance of the modified BedsidePEWS score for unplanned pediatric intensive care unit (PICU) admission and cardiopulmonary resuscitation (CPR) in this patient population. Methods We performed a prospective cohort study in an 80-bed pediatric oncology hospital in the Netherlands, where care has been nationally centralized. All hospitalized pediatric oncology patients aged 0–18 years were eligible for inclusion. A Cox proportional hazard model was estimated to study the association between BedsidePEWS score and unplanned PICU admissions or CPR. The predictive performance of the model was internally validated by bootstrapping. Results A total of 1137 patients were included. During the study, 103 patients experienced 127 unplanned PICU admissions and three CPRs. The hazard ratio for unplanned PICU admission or CPR was 1.65 (95% confidence interval [CI]: 1.59–1.72) for each point increase in the modified BedsidePEWS score. The discriminative ability was moderate (D-index close to 0 and a C-index of 0.83 [95% CI: 0.79–0.90]). Positive and negative predictive values of modified BedsidePEWS score at the widely used cutoff of 8, at which escalation of care is required, were 1.4% and 99.9%, respectively. Conclusion The modified BedsidePEWS score is significantly associated with requirement of PICU transfer or CPR. In pediatric oncology patients, this PEWS score may aid in clinical decision-making for timing of PICU transfer. View on Web

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Selenium ameliorates inflammation by decreasing autophagic flux and mitogen‐activated protein kinase signalling on experimentally induced rat periapical lesions

alexandrossfakianakis shared this article with you from Inoreader Selenium ameliorates inflammation by decreasing autophagic flux and mitogen‐activated protein kinase signalling on experimentally induced rat periapical lesions via International Endodontic Journal Abstract AIM To reveal the molecular mechanisms that targets mitogen-activated protein kinase (MAPK) signalling and the autophagic flux and to investigate the possible effects of the systemic administration of selenium (Se) on experimentally induced rat periapical lesions. METHODOLOGY Thirty adult Sprague Dawley rats were divided equally into negative control, positive control and Se groups. In the positive control and Se groups, the pulp chambers of their mandibular first molars were exposed to the oral environment to induce periapical lesions The Se group received daily intraperitoneal injections of Se at a dose of 0.1 mg kg−1. After 28 days, the amount of bone destruction; severity of inflammation; penetration of microorganisms along the root canal; collagen degradation in periodontal ligament; interleukin (IL)-6, hypoxia-inducible factor-1 (HIF-1), cyclooxygenase-2 (COX-2) and caspase-3 expression; autophagic flux; and p38 MAPK signalling were evaluated using radiographic, histopathological, Gram staining, picrosirius red stain, immunohistochemical, quantitative real-time polymerase chain (qRT–PCR) and western blot methods, respectively. The data was analysed through the Kruskal–Wallis and Dunnett's tests (p<0.05). RESULTS The area of radiographic periapical bone loss, histopathological scores, the area of periapical bone loss and the scores for the bacteria localisation, the intensity of immunohistochemical staining for IL-6, HIF-1, COX-2 and caspase-3 in the Se group was significantly less than those of the positive control group (p<0.01). The mRNA expression levels of Beclin-1, Atg3, Atg5, Atg7, and Atg16L1 were lower in the Se group than in the positive control group (p<0.01). The protein expressions of Beclin-1, Atg5 and LC3-II, the phosphorylation ratio of the p38 MAPK and the ratios of LC3II/LC3I were significantly higher (p<0.05) in the positive control and Se groups. On the other hand, the expression of the p62/SQSTM1 protein was significantly lower (p < 0.05) in the positive control and Se groups than in the negative control group. CONCLUSION The induction of periapical lesions in rats increased autophagic flux and activated p38 MAPK signal transduction processes. Se suppressed the inflammatory process, reduced bone destruction and both the autophagic flux and p38 MAPK activation. View on Web

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COVID-19 Vaccination and the Timing of Surgery Following COVID-19 Infection

alexandrossfakianakis shared this article with you from Inoreader COVID-19 Vaccination and the Timing of Surgery Following COVID-19 Infection via Annals of Surgery - Most Popular Articles Objective: To evaluate whether COVID-19 vaccination status or mode of anesthesia modified the temporal harms associated with surgery following coronavirus disease-2019 (COVID-19) infection. Background: Surgery shortly after COVID-19 infection is associated with higher rates of complications, leading to recommendations to delay surgery following COVID-19 infection when possible. However, prior studies were based on populations with low or no prevalence of vaccination. Methods: A retrospective cohort study of patients who underwent scheduled surgery in a health system from January 1, 2018 to February 28, 2022 (N=228,913) was performed. Patients were grouped by time of surgery relative to COVID-19 test positivity: 0 to 4 weeks after COVID-19 ("early post-COVID-19"), 4 to 8 weeks after COVID-19 ("mid post-COVID-19"), >8 weeks after COVID-19 ("late post-COVID-19"), surgery at least 30 days before subsequent COVID-19 ("pre-COVID-19"), and surgery with no prior or subsequent test positivity for COVID-19. Results: Among patients who were not fully vaccinated at the time of COVID-19 infection, the adjusted rate of perioperative complications for the early post-COVID-19 group was significantly higher than for the pre-COVID-19 group (relative risk: 1.55; P=0.05). No significantly higher risk was identified between these groups for patients who were fully vaccinated (0.66; P=1.00), or for patients who were not fully vaccinated and underwent surgery without general anesthesia (0.52; P=0.83). Conclusions: Surgery shortly following COVID-19 infection was not associated with higher risks among fully vaccinated patients or among patients who underwent surgery without general anesthesia. Further research will be valuable to understand additional factors that modify perioperative risks associated with prior COVID-19 infection. View on Web

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Accessibility of Level III trauma centers for underserved populations: A cross-sectional study

alexandrossfakianakis shared this article with you from Inoreader Accessibility of Level III trauma centers for underserved populations: A cross-sectional study via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND By providing definitive care for many, and rapid assessment, resuscitation, stabilization, and transfer to Level I/II centers when needed, Level III trauma centers can augment capacity in high resource regions and extend the geographic reach to lower resource regions. We sought to (1) characterize populations served principally by Level III trauma centers, (2) estimate differences in time to care by trauma center level, and (3) update national estimates of trauma center access. METHODS In a cross-sectional study (United States, 2019), we estimated travel time from census block groups to the nearest Level I/II trauma center and nearest Level III trauma center. Block groups were categorized based on the level of care accessible within 60 minutes, then distributions of population characteristics and differences in time to care were estimated. RESULTS An estimated 22.8% of the US population (N = 76,119,228) lacked access to any level of trauma center care within 60 minutes, and 8.8% (N = 29,422,523) were principally served by Level III centers. Black and American Indian/Alaska Native (AIAN) populations were disproportionately represented among those principally served by Level III centers (39.1% and 12.2%, respectively). White and AIAN populations were disproportionately represented among those without access to any trauma center care (26.2% and 40.8%, respectively). Time to Level III care was shorter than Level I/II for 27.9% of the population, with a mean reduction in time to care of 28.9 minutes (SD = 31.4). CONCLUSION Level III trauma centers are a potential source of trauma care for underserved populations. While Black and AIAN disproportionately rely on Level III centers for care, most with access to Level III centers also have access to Level I/II centers. The proportion of the US population with timely access to trauma care has not improved since 2010. LEVEL OF EVIDENCE Prognostic/Epidemiological; Level IV. View on Web

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A Gene Expression Signature to Select Hepatocellular Carcinoma Patients for Liver Transplantation

alexandrossfakianakis shared this article with you from Inoreader A Gene Expression Signature to Select Hepatocellular Carcinoma Patients for Liver Transplantation via Annals of Surgery - Most Popular Articles Objective: To propose a new decision algorithm combining biomarkers measured in a tumor biopsy with clinical variables, to predict recurrence after liver transplantation (LT). Background: Liver cancer is one of the most frequent causes of cancer-related mortality. LT is the best treatment for hepatocellular carcinoma (HCC) patients but the scarcity of organs makes patient selection a critical step. In addition, clinical criteria widely applied in patient eligibility decisions miss potentially curable patients while selecting patients that relapse after transplantation. Methods: A literature systematic review singled out candidate biomarkers whose RNA levels were assessed by quantitative PCR in tumor tissue from 138 HCC patients submitted to LT (>5 years follow up, 32% beyond Milan criteria). The resulting 4 gene signature was combined with clinical variables to develop a decision algorithm using machine learning approaches. The method was named HepatoPredict. Results: HepatoPredict identifies 99% disease-free patients (>5 year) from a retrospective cohort, including many outside clinical criteria (16%–24%), thus reducing the false negative rate. This increased sensitivity is accompanied by an increased positive predictive value (88.5%–94.4%) without any loss of long-term overall survival or recurrence rates for patients deemed eligible by HepatoPredict; those deemed ineligible display marked reduction of survival and increased recurrence in the short and long term. Conclusions: HepatoPredict outperforms conventional clinical-pathologic selection criteria (Milan, UCSF), providing superior prognostic information. Accurately identifying which patients most likely benefit from LT enables an objective stratification of waiting lists and information-based allocation of optimal versus suboptimal organs. View on Web

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Sirtuin 1 deletion increases inflammation and mortality in sepsis

alexandrossfakianakis shared this article with you from Inoreader Sirtuin 1 deletion increases inflammation and mortality in sepsis via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND Sepsis is a hyperinflammatory response to infection that can lead to multiorgan failure and eventually death. Often, the onset of multiorgan failure is heralded by renal dysfunction. Sirtuin 1 (SIRT1) promotes cellular stress resilience by inhibiting inflammation and promoting mitochondrial function. We hypothesize that SIRT1 plays an important role in limiting the inflammatory responses that drive organ failure in sepsis, predominantly via expression in myeloid cells. METHODS We performed cecal ligation and puncture (CLP) on whole body SIRT1 knockout (S1KO) and myeloid cell–specific S1KO (S1KO-LysMCre) mice on a C57BL/6J background. Serum interleukin (IL)-6 was quantified by enzyme-linked immunosorbent assay. Renal mitochondrial complex activity was measured using Oxygraph-2k (Oroboros Instruments, Innsbruck, Austria). Blood urea nitrogen (BUN) was measured from serum. Survival was monitored for up to 5 days. RESULTS Following CLP, S1KO mice had decreased renal mitochondrial complex I–dependent respiratory capacity (241.7 vs. 418.3 mmolO2/mg/min, p = 0.018) and renal mitochondrial complex II–dependent respiratory capacity (932.3 vs. 1,178.4, p = 0.027), as well as reduced rates of fatty acid oxidation (187.3 vs. 250.3, p = 0.022). Sirtuin 1 knockout mice also had increased BUN (48.0 mg/dL vs. 16.0 mg/dL, p = 0.049). Interleukin-6 levels were elevated in S1KO mice (96.5 ng/mL vs. 45.6 ng/mL, p = 0.028) and S1KO-LysMCre mice (35.8 ng/mL vs. 24.5 ng/mL, p = 0.033) compared with controls 12 hours after surgery. Five-day survival in S1KO (33.3% vs. 83.3%, p = 0.025) and S1KO-LysMCre (60% vs. 100%, p = 0.049) mice was decreased compared with controls. CONCLUSION Sirtuin 1 deletion increases systemic inflammation in sepsis. Renal mitochondrial dysfunction, kidney injury, and mortality following CLP were all exacerbated by SIRT1 deletion. Similar effects on inflammation and survival were seen following myeloid cell–specific SIRT1 deletion, indicating that SIRT1 activity in myeloid cells may be a significant contributor for the protective effects of SIRT1 in sepsis. View on Web

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Integrating traffic safety data with area deprivation index: A method to better understand the causes of pediatric pedestrian versus automobile collisions

alexandrossfakianakis shared this article with you from Inoreader Integrating traffic safety data with area deprivation index: A method to better understand the causes of pediatric pedestrian versus automobile collisions via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND The purpose of this study was to identify clinical and traffic factors that influence pediatric pedestrian versus automobile collisions (P-ACs) with an emphasis on health care disparities. METHODS A retrospective review was performed of pediatric (18 years or younger) P-ACs treated at a Level I pediatric trauma center from 2008 to 2018. Demographic, clinical, and traffic scene data were analyzed. Area deprivation index (ADI) was used to measure neighborhood socioeconomic disadvantage (NSD) based on home addresses. Traffic scene data from the California Statewide Integrated Traffic Records System were matched to clinical records. Traffic safety was assessed by the streetlight coverage, the proximity of the collision to home addresses, and sidewalk coverage. Descriptive statistics and univariate analysis for key variables and outcomes were calculated using Kruskal-Wallis, Wilcoxon, χ2, or Fisher's exact tests. Statistical significance was attributed to p values of View on Web

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