Nevin Manimala

Mod Pathol. 2021 Feb 26. doi: 10.1038/s41379-021-00735-8. Online ahead of print.

ABSTRACT

Pleuropulmonary blastoma (PPB) is a primary embryonal malignancy of childhood that is characterized by distinct morphologic types: type Ir (regressed), type I (cystic), type II (cystic and solid), and type III (solid). Prognosis varies by PPB type. Most cases are associated with a germline pathogenic mutation in DICER1; however, there is limited data on the factor(s) at a cellular level that drive progression from type I to type III. In this study, we evaluated the expression of p53 and its prognostic implications. A total of 143 PPB cases were included in the study with the following distribution in PPB types: Ir (14%), I (23%), II (32%), and III (31%). P53 expression by immunohistochemistry (IHC) was recorded as four groups: 0%, 1-25%, 26-75%, and 76-100%. All type I PPBs showed 0-25% p53 expression compared to the higher p53 expression (>25%) in type III PPB (p < 0.0001), to support the argument that p53 has a role in tumor progression. In addition, type Ir with the architectural hallmarks of type I PPB, but lacking the primitive cell population, has negligible p53 expression. High p53 expression (staining observed in >25% of the tumor cells) was significantly associated with age over 1 year (p = 0.0033), neoadjuvant therapy (p = 0.0009), positive resection margin (p = 0.0008) and anaplasia (p < 0.0001). P53 expression was significantly associated with recurrence-free survival (p < 0.0001) and overall survival (p = 0.0350), with higher p53 expression associated with worse prognosis. Comparisons of concordance statistics showed no significant difference in prognostication when using morphologic types compared to p53 expression groups (p = 0.647). TP53 sequence was performed in 16 cases; the most common variant identified was a missense variant (12 cases), and in one case a frameshift truncating variant was noted. Based on these findings, we recommend performing p53 IHC in all newly diagnosed cases of types II and III PPB to further aid in risk stratification.

PMID:33637876 | DOI:10.1038/s41379-021-00735-8

Physiol Meas. 2021 Feb 26. doi: 10.1088/1361-6579/abea25. Online ahead of print.

ABSTRACT

OBJECTIVE: Heart rate (HR) monitoring provides a convenient and inexpensive way to predict energy expenditure (EE) during physical activity. However, there is a lot of variation among individuals in the EE-HR relationship, which should be taken into account in predictions. The objective is to develop a model that allows the prediction of EE based on HR as accurately as possible and allows an improvement of the prediction using calibration measurements from the target individual.

APPROACH: We propose a nonlinear (logistic) mixed model for EE and HR measurements and an approach to calibrate the model for a new person who does not belong to the data set used to estimate the model. The calibration utilizes the estimated model parameters and calibration measurements of HR and EE from the person in question. We compare the results of the logistic mixed model with a simpler linear mixed model for which the calibration is easier to perform.

MAIN RESULTS: We show that the calibration is beneficial already with only one pair of measurements on HR and EE. That is an important benefit over an individual-level model fitting which requires a larger number of measurements. Moreover, we present an algorithm for calculating the confidence and prediction intervals of the calibrated predictions. The analysis was based on up to eleven pairs of EE and HR measurements from each of 54 individuals of a heterogeneous group of people, who performed a maximal treadmill test.

SIGNIFICANCE: The proposed method allows accurate energy expenditure predictions based on only a few calibration measurements from a new individual without access to the original dataset, thus making the approach viable for example on wearable computers.

PMID:33636716 | DOI:10.1088/1361-6579/abea25

J Neurosurg. 2021 Feb 26:1-6. doi: 10.3171/2020.9.JNS202781. Online ahead of print.

ABSTRACT

OBJECTIVE: Middle meningeal artery (MMA) embolization is a promising treatment strategy for chronic subdural hematomas (cSDHs). However, studies comparing MMA embolization and conventional therapy (surgical intervention and conservative management) are limited. The authors aimed to compare MMA embolization versus conventional therapy for cSDHs using a propensity-adjusted analysis.

METHODS: A retrospective study of all patients with cSDH who presented to a large tertiary center over a 2-year period was performed. MMA embolization was compared with surgical intervention and conservative management. Neurological outcome was assessed using the modified Rankin Scale (mRS). A propensity-adjusted analysis compared MMA embolization versus surgery and conservative management for all individual cSDHs. Primary outcomes included change in hematoma diameter, treatment failure, and complete resolution at last follow-up.

RESULTS: A total of 231 patients with cSDH met the inclusion criteria. Of these, 35 (15%) were treated using MMA embolization, and 196 (85%) were treated with conventional treatment. On the latest follow-up, there were no statistically significant differences between groups in the percentage of patients with worsening mRS scores. Of the 323 total cSDHs found in 231 patients, 41 (13%) were treated with MMA embolization, 159 (49%) were treated conservatively, and 123 (38%) were treated with surgical evacuation. After propensity adjustment, both surgery (OR 12, 95% CI 1.5-90; p = 0.02) and conservative therapy (OR 13, 95% CI 1.7-99; p = 0.01) were predictors of treatment failure and incomplete resolution on follow-up imaging (OR 6.1, 95% CI 2.8-13; p < 0.001 and OR 5.4, 95% CI 2.5-12; p < 0.001, respectively) when compared with MMA embolization. Additionally, MMA embolization was associated with a significant decrease in cSDH diameter on follow-up relative to conservative management (mean -8.3 mm, 95% CI -10.4 to -6.3 mm, p < 0.001).

CONCLUSIONS: This propensity-adjusted analysis suggests that MMA embolization for cSDH is associated with a greater extent of hematoma volume reduction with fewer treatment failures than conventional therapy.

PMID:33636706 | DOI:10.3171/2020.9.JNS202781

J Neurosurg. 2021 Feb 26:1-5. doi: 10.3171/2020.8.JNS20386. Online ahead of print.

ABSTRACT

OBJECTIVE: Endovascular thrombectomy (EVT) and tissue plasminogen activator (tPA) are effective ischemic stroke treatments in the initial treatment window. In the extended treatment window, these treatments may offer benefit, but CT and MR perfusion may be necessary to determine patient eligibility. Many hospitals do not have access to advanced imaging tools or EVT capability, and further patient care would require transfer to a facility with these capabilities. To assist transfer decisions, the authors developed risk indices that could identify patients eligible for extended-window EVT or tPA.

METHODS: The authors retrospectively identified stroke patients who had concurrent CTA and perfusion and evaluated three potential outcomes that would suggest a benefit from patient transfer. The first outcome was large-vessel occlusion (LVO) and target mismatch (TM) in patients 5-23 hours from last known normal (LKN). The second outcome was TM in patients 5-15 hours from LKN with known LVO. The third outcome was TM in patients 4.5-12 hours from LKN. The authors created multivariable models using backward stepping with an α-error criterion of 0.05 and assessed them using C statistics.

RESULTS: The final predictors included the National Institutes of Health Stroke Scale (NIHSS), the Alberta Stroke Program Early CT Score (ASPECTS), and age. The prediction of the first outcome had a C statistic of 0.71 (n = 145), the second outcome had a C statistic of 0.85 (n = 56), and the third outcome had a C statistic of 0.86 (n = 54). With 1 point given for each predictor at different cutoffs, a score of 3 points had probabilities of true positive of 80%, 90%, and 94% for the first, second, and third outcomes, respectively.

CONCLUSIONS: Despite the limited sample size, compared with perfusion-based examinations, the clinical variables identified in this study accurately predicted which stroke patients would have salvageable penumbra (C statistic 71%-86%) in a range of clinical scenarios and treatment cutoffs. This prediction improved (C statistic 85%-86%) when utilized in patients with confirmed LVO or a less stringent tissue mismatch (TM < 1.2) cutoff. Larger patient registries should be used to validate and improve the predictive ability of these models.

PMID:33636705 | DOI:10.3171/2020.8.JNS20386

J Neurosurg. 2021 Feb 26:1-10. doi: 10.3171/2020.9.JNS201980. Online ahead of print.

ABSTRACT

OBJECTIVE: Primary central nervous system lymphoma (PCNSL) is a rare CNS tumor with a poor prognosis. It is usually diagnosed by needle biopsy and treated mainly with high-dose chemotherapy. Resection is currently not considered a standard treatment option. A possible prolonged survival after resection of PCNSL lesions in selected patients has been suggested, but selection criteria for surgery, especially for solitary lesions, have never been established.

METHODS: The authors retrospectively searched their patient database for records of adult patients (≥ 18 years) who were diagnosed and treated for a solitary PCNSL between 2005 and 2019. Patients were divided into groups according to whether they underwent resection or needle biopsy. Statistical analyses were performed in an attempt to identify variables affecting outcome and possible survival advantage and to characterize subgroups of patients who would benefit from resection of their tumor compared with undergoing biopsy only.

RESULTS: A total of 113 patients with a solitary lesion of PCNSL were identified; 36 patients underwent resection, and 77 had a diagnostic stereotactic biopsy only. The statically significant preoperative risk factors included age ≥ 70 years (adjusted HR 9.61, 95% CI 2.42-38.11; p = 0.001), deep-seated lesions (adjusted HR 3.33, 95% CI 1.13-9.84; p = 0.030), and occipital location (adjusted HR 4.26, 95% CI 1.08-16.78; p = 0.039). Having a postoperative Karnofsky Performance Scale (KPS) score < 80 (adjusted HR 3.21, 95% CI 1.05-9.77; p = 0.040) and surgical site infection (adjusted HR 4.27, 95% CI 1.18-15.47; p = 0.027) were significant postoperative risk factors after the adjustment and selection by means of other possible risk factors. In a subgroup analysis, patients younger than 70 years who underwent resection had a nonsignificant trend toward longer survival than those who underwent needle biopsy (median survival 35.0 months vs 15.2 months, p = 0.149). However, patients with a superficial tumor who underwent resection had significantly longer survival times than those who underwent needle biopsy (median survival 34.3 months vs 8.9 months, p = 0.014). Patients younger than 70 years who had a superficial tumor and underwent resection had significantly prolonged survival, with a median survival of 35.0 months compared with 8.9 months in patients from the same group who underwent needle biopsy (p = 0.007).

CONCLUSIONS: Specific subgroups of patients with a solitary PCNSL lesion might gain a survival benefit from resection compared with undergoing only a diagnostic biopsy.

PMID:33636699 | DOI:10.3171/2020.9.JNS201980

J Mech Behav Biomed Mater. 2021 Feb 13;117:104377. doi: 10.1016/j.jmbbm.2021.104377. Online ahead of print.

ABSTRACT

Osteogenesis imperfecta (OI), a brittle bone disease, is known to result in severe bone fragility. However, its ultrastructural origins are still poorly understood. In this study, we hypothesized that deficient intrafibrillar mineralization is a key contributor to the OI induced bone brittleness. To test this hypothesis, we explored the mechanical and ultrastructural changes in OI bone using the osteogenesis imperfecta murine (oim) model. Synchrotron X-ray scattering experiments indicated that oim bone had much less intrafibrillar mineralization than wild type bone, thus verifying that the loss of mineral crystals indeed primarily occurred in the intrafibrillar space of oim bone. It was also found that the mineral crystals were organized from preferentially in longitudinal axis in wild type bone to more randomly in oim bone. Moreover, it revealed that the deformation of mineral crystals was more coordinated with collagen fibrils in wild type than in oim bone, suggesting that the load transfer deteriorated between the two phases in oim bone. The micropillar test revealed that the compression work to fracture of oim bone (8.2 ± 0.9 MJ/m³) was significantly smaller (p < 0.05) than that of wild type bone (13.9 ± 2.7 MJ/m³), while the bone strength was not statistically different (p > 0.05) between the two genotype groups. In contrast, the uniaxial tensile test showed that the ultimate strength of wild type bone (50 ± 4.5 MPa) was significantly greater (p < 0.05) than that of oim bone (38 ± 5.3 MPa). Furthermore, the nanoscratch test showed that the toughness of oim bone was much less than that of wild type bone (6.6 ± 2.2 GJ/m³ vs. 12.6 ± 1.4 GJ/m³). Finally, in silico simulations using a finite element model of sub-lamellar bone confirmed the links between the reduced intrafibrillar mineralization and the observed changes in the mechanical behavior of OI bone. Taken together, these results provide important mechanistic insights into the underlying cause of poor mechanical quality of OI bone, thus pave the way toward future treatments of this brittle bone disease.

PMID:33636677 | DOI:10.1016/j.jmbbm.2021.104377

Water Res. 2021 Feb 15;194:116934. doi: 10.1016/j.watres.2021.116934. Online ahead of print.

ABSTRACT

Efficient management of sewer blockages requires increased preventive maintenance planning. Conventional approaches to the management of blockages in sewer pipe networks constitute largely unplanned maintenance stemming from a lack of adequate information and diagnosis of blockage causative mechanisms. This study mainly investigated a spatial statistical approach to determine the influence of explanatory factors on increased blockage propensity in sewers based on spatial heterogeneity. The approach consisted of the network K-function analysis, which provided an understanding of the significance of the spatial variation of blockages. A geographically-weighted Poisson regression then showed the degree of influence that explanatory factors had on increased blockage propensity in differentiated segments of the sewer pipe network. Lastly, blockage recurrence predictions were carried out with Random Forest ensembles. This approach was applied to three municipalities. Explanatory factors such as material type, number of service connections, self-cleaning velocity, sagging pipes, root intrusion risk, closed-circuit television inspection grade and distance to restaurants showed significant spatial heterogeneity and varying impacts on blockage propensity. The Random Forest ensemble predicted blockage recurrence with 60-80% accuracy for data from two municipalities and below 50% for the last. This approach provides knowledge that supports proactive maintenance planning in the management of blockages in sewer pipe networks.

PMID:33636665 | DOI:10.1016/j.watres.2021.116934

Nurse Educ Today. 2021 Feb 10;99:104811. doi: 10.1016/j.nedt.2021.104811. Online ahead of print.

ABSTRACT

BACKGROUND: Practice standards in nursing provide minimum expectations to enable the provision of high quality and safe care. There are currently no practice standards for post-registration graduate emergency nursing programs in Australia, leading to variation in graduate attributes and clinical expectations on completion of their program.

OBJECTIVES: The aim of this study was to establish consensus-based practice standards for graduate emergency nursing programs in Australia.

DESIGN: Delphi approach.

PARTICIPANTS: Australian nurses who identified as an emergency nurse and currently worked, or previously worked, in an emergency care environment.

METHODS: A modified two-round Delphi method was used. The survey was divided into four sections of data collection, including demographics, graduate emergency nursing course entry requirements, graduate expectations, and clinical care capabilities. Data were analysed using descriptive statistics including calculation of content validity index (CVI).

RESULTS: There were 204 respondents in Round One and 153 respondents in Round Two. Respondents agreed that nurses wanting to undertake graduate studies in emergency nursing require prior experience in the emergency care environment and should be working a minimum of 0.5 full time equivalent (FTE) whilst completing their studies. Thirty-nine statements presented under graduate attributes achieved a CVI of >0.8. All 70 clinical care capability statements presented in Round Two achieved a CVI of >0.8.

CONCLUSION: This study generated the evidence to establish minimum practice standards for Australian graduate emergency nursing programs. The standards centre around three key areas: graduate entry requirements, graduate attributes and clinical care capabilities. The standards provide a clear guide for employers, educators and clinicians, and inform capabilities for early career emergency nurses.

PMID:33636653 | DOI:10.1016/j.nedt.2021.104811

Nurse Educ Today. 2021 Feb 20;99:104818. doi: 10.1016/j.nedt.2021.104818. Online ahead of print.

ABSTRACT

BACKGROUND: With the constant urgent need to meet the demands of the future workforce, nursing education institutes are under increasing pressure to graduate more quality students. One way to achieve higher numbers of graduates would be to identify factors that predict nursing students’ academic success. No reports of such predictors were found for students in accelerated programs for non-nursing Bachelor’s degree graduates.

OBJECTIVES: This study was designed to examine the relationships between demographic characteristics, course grades in basic science and medical-surgical courses, and the final scores achieved by students in the Israel mandatory RN certification test.

DESIGN, SETTINGS, AND PARTICIPANTS: 164 students, enrolled in four courses of a second career in nursing program (accelerated program) in an academic nursing school in central Israel, participated in this retrospective study.

METHODS: Socio-demographic data and the final grades for basic science courses (chemistry and biochemistry, microbiology, anatomy and physiology, pathology, and pharmacology), the major Medical-Surgical course, and the RN certification test, were collected from the institutional database and analyzed.

RESULTS: Positive correlations were found between the mandatory RN certification test score, and the final grades of all the studies except the pathology course and Medical-Surgical course. The final RN certification test score was predicted by the final grades, with anatomy and physiology (p < 0.001), and pharmacology (p < 0.003), explaining 40% of the variance of the dependent variable. There were no statistical effects of demographic variables.

CONCLUSIONS: Early evaluation and prediction of academic success for nursing students in the second career program may guide effective interventions designed to promote students’ skills and improve their ability to complete the mandatory RN certification test successfully.

PMID:33636651 | DOI:10.1016/j.nedt.2021.104818

J Pharm Biomed Anal. 2021 Feb 15;197:113969. doi: 10.1016/j.jpba.2021.113969. Online ahead of print.

ABSTRACT

Previous studies have reported that nucleic acid methylation is a critical element in cardiovascular disease, and most studies mainly focused on sequencing and biochemical research. Here we developed an Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/ MS) method for the quantification analysis of the dissociative epigenetic modified nucleosides (5mdC, 5mrC, m⁶A) in Myocardial Infarction (MI) SD rats from different periods (1 week, 4 weeks, 8 weeks) after the surgery. The samples for analysis were obtained from heart tissue and blood of the rats. All the quantification results are compared with the sham-operated group. Total RNA and DNA were isolated by enzymatic hydrolytic methods before the UPLC-MS/MS analysis. The statistical analysis demonstrates the dynamic changes of modified nucleosides in MI rats, and it showed good specificity, accuracy, stability and less samples were needed in the method. In this paper, we discovered that the concentration of 5mdC, 5mrC, m⁶A from heart tissue significantly increased at 8 weeks after the surgery. Furthermore, UPLC-MS/MS helps us observe the similar change of the concentration of those 3 methylated biomarkers in peripheral blood after 8 weeks. The result shows that the dynamic process of those 3 methylated biomarkers in peripheral blood is related to the content of methylated biomarkers from the heart tissue. Based on the scientific evidence available, we proved that the methylation of genetic materials in peripheral blood is similar to myocardial infarction tissue. The relation between them indicates that peripheral blood could be a promising alternative to the heart tissue which monitor the level of methylation and MI diagnosis-aided.

PMID:33636646 | DOI:10.1016/j.jpba.2021.113969