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Nevin Manimala Statistics

Polyploid giant cancer cell characterization: New frontiers in predicting response to chemotherapy in breast cancer

Semin Cancer Biol. 2021 Mar 22:S1044-579X(21)00067-5. doi: 10.1016/j.semcancer.2021.03.017. Online ahead of print.

ABSTRACT

Although polyploid cells were first described nearly two centuries ago, their ability to proliferate has only recently been demonstrated. It also becomes increasingly evident that a subset of tumor cells, polyploid giant cancer cells (PGCCs), play a critical role in the pathophysiology of breast cancer (BC), among other cancer types. In BC, PGCCs can arise in response to therapy-induced stress. Their progeny possess cancer stem cell (CSC) properties and can repopulate the tumor. By modulating the tumor microenvironment (TME), PGCCs promote BC progression, chemoresistance, metastasis, and relapse and ultimately impact the survival of BC patients. Given their pro- tumorigenic roles, PGCCs have been proposed to possess the ability to predict treatment response and patient prognosis in BC. Traditionally, DNA cytometry has been used to detect PGCCs.. The field will further derive benefit from the development of approaches to accurately detect PGCCs and their progeny using robust PGCC biomarkers. In this review, we present the current state of knowledge about the clinical relevance of PGCCs in BC. We also propose to use an artificial intelligence-assisted image analysis pipeline to identify PGCC and map their interactions with other TME components, thereby facilitating the clinical implementation of PGCCs as biomarkers to predict treatment response and survival outcomes in BC patients. Finally, we summarize efforts to therapeutically target PGCCs to prevent chemoresistance and improve clinical outcomes in patients with BC.

PMID:33766651 | DOI:10.1016/j.semcancer.2021.03.017

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Nevin Manimala Statistics

Impact of electronic consultation (e-consult) on timeliness and guideline concordance of workups leading to thyroid nodule fine-needle aspiration biopsy

Endocr Pract. 2021 Mar 22:S1530-891X(21)00103-8. doi: 10.1016/j.eprac.2021.03.008. Online ahead of print.

ABSTRACT

OBJECTIVE: Electronic consultations (e-consults) are commonly used to obtain endocrinology input on clinical questions without a face-to-face visit, but there are sparse data on quality of care resulting from e-consults for specific conditions. We examined workups resulting in thyroid nodule fine-needle aspiration (FNA) biopsy to examine whether endocrinology e-consults were more timely and similarly guideline concordant as compared to endocrinology face-to-face visits, and whether endocrinology e-consults were more guideline concordant as compared to workups without endocrinology input.

METHODS: We conducted a retrospective chart review of 302 thyroid FNA biopsies conducted in the Veterans Affairs (VA) health system between 5/1/2017 and 2/4/2020 (e-consult, N=99; face-to-face visit, N=100; no endocrinology input, N=103). We used t-tests to compare timeliness and chi-square tests to compare the proportion of guideline-concordant workups. We used multivariable linear and logistic models to control for demographic factors.

RESULTS: FNAs preceded by endocrinology e-consult had more timely workups compared to those preceded by endocrinology face-to-face visits in terms of days elapsed between referral and FNA biopsy [geometric mean [95% confidence interval]: 44.7 [37.2, 53.7] days vs. 61.7 [52.5, 72.4] days, t(195)=2.55, P=0.01]. The difference in the summary measure of guideline concordance across groups was not statistically significant (P=0.38).

CONCLUSION: E-consults were faster than face-to-face consults and similar guideline concordant as compared to both face-to-face consults and no endocrinology input for workups resulting in FNA. Decisions about appropriate use of e-consults for thyroid nodules should account for these data while also considering potential benefits of direct patient-endocrinologist interaction for complex situations.

PMID:33766654 | DOI:10.1016/j.eprac.2021.03.008

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Nevin Manimala Statistics

Climate change and the dynamics of age-related malaria incidence in Southern Africa: A focus on Zambia

Environ Res. 2021 Mar 22:111017. doi: 10.1016/j.envres.2021.111017. Online ahead of print.

ABSTRACT

In the last decade, many malaria-endemic countries, like Zambia, have achieved significant reductions in malaria incidence among children <5 years old but face ongoing challenges in achieving similar progress against malaria in older age groups. In parts of Zambia, changing climatic and environmental factors are among those suspected factors behind high malaria incidence. Changes and variations in these factors potentially interfere with intervention program effectiveness and alter the distribution and incidence patterns of malaria differentially between young children and the rest of the population. We used parametric and non-parametric statistics to model the effects of climatic and socio-demographic variables on age-specific malaria incidence vis-à-vis control interventions. Linear regressions, mixed models, and Mann-Kendall tests were implemented to explore trends, changes in trends, and regress malaria against environmental and intervention variables. Our study shows that while climate parameters affect the whole population, their impacts are felt most by people aged ≥5 years. Climate variables influenced malaria substantially more than mosquito nets and indoor residual spraying interventions. We establish that climate parameters is negatively impacting malaria control efforts by exacerbating the transmission conditions via more conducive temperature and rainfall environments, which in turn are exacerbated by cultural and socioeconomic exposure mechanisms. We argue that an intensified communications and education intervention strategy for behavioural change specifically targeted at ≥5 aged population where incidence rates are increasing, is urgently required and call for further malaria stratification among the ≥5 age groups in the routine collection, analysis and reporting of malaria mortality and incidence data.

PMID:33766570 | DOI:10.1016/j.envres.2021.111017

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Nevin Manimala Statistics

Prenatal Exposure to Pesticides and Risk of Preeclampsia among Pregnant Women: Results from the ELFE Cohort

Environ Res. 2021 Mar 22:111048. doi: 10.1016/j.envres.2021.111048. Online ahead of print.

ABSTRACT

BACKGROUND: Preeclampsia is a pregnancy-specific syndrome caused by abnormal placentation. Although environmental chemicals, including some pesticides, are suspected of impairing placentation and promoting preeclampsia, its relationship with preeclampsia has been insufficiently explored.

OBJECTIVES: We aimed to investigate the relation between non-occupational exposure to pesticides during pregnancy and the risk of preeclampsia.

METHODS: The study cohort comprised 195 women with and 17,181 without preeclampsia from the ELFE birth cohort. We used toxicogenomic approaches to select 41 pesticides of interest for their possible influence on preeclampsia. We assessed household pesticide use (self-reported data), environmental exposure to agricultural pesticides (geographic information systems), and dietary exposure (food-frequency questionnaire with data from monitoring pesticide residues in food and water). Dietary exposures to pesticides were grouped into clusters of similar exposures to resolve collinearity issues. For each exposure source, pesticides were mutually adjusted, and odds ratios estimated with logistic regression models.

RESULTS: The quantity of prochloraz applied within a kilometer of the women’s homes was higher in women with than without preeclampsia (fourth quartile vs. others; adjusted odds ratio [aOR]=1.54; 95%CI: 1.02, 2.35), especially when preeclampsia was diagnosed before 34 weeks of gestation (aOR=2.25; 95%CI: 1.01, 5.06). The reverse was observed with nearby cypermethrin application (aOR=0.59, 95%CI: 0.36, 0.96). In sensitivity analyses, women with preeclampsia receiving antihypertensive treatment had a significantly higher probability of using herbicides at home during pregnancy than women without preeclampsia (aOR=2.20; 95%CI: 1.23, 3.93). No statistically significant association was found between dietary exposure to pesticide residues and preeclampsia.

DISCUSSION: While the most of the associations examined remained statistically non-significant, our results suggest the possible influence on preeclampsia of residential exposures to prochloraz and some herbicides. These estimations are supported by toxicological and mechanistic data.

PMID:33766571 | DOI:10.1016/j.envres.2021.111048

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Nevin Manimala Statistics

Predicting myocardial injury and other cardiac complications after elective noncardiac surgery with the Revised Cardiac Risk Index: the VISION study

Can J Cardiol. 2021 Mar 22:S0828-282X(21)00164-1. doi: 10.1016/j.cjca.2021.03.015. Online ahead of print.

ABSTRACT

BACKGROUND: The Revised Cardiac Risk Index (RCRI) is widely used to estimate risk of cardiac complications after noncardiac surgery; its estimates do not capture myocardial injury after noncardiac surgery (MINS). We evaluated the incidence of cardiac complications including MINS across RCRI risk classes and the RCRI’s ability to discriminate, before surgery, between patients who will experience these complications and those who will not.

METHODS: Secondary analysis of a prospective cohort study of 35,815 patients ≥45 years old who had elective inpatient noncardiac surgery between 2007 and 2013 at 28 centers in 14 countries. The primary outcome was a composite of MINS, myocardial infarction, non-fatal cardiac arrest, or cardiac death within 30 days after surgery. The secondary outcome was this composite without MINS.

RESULTS: The primary outcome occurred in 4,725 patients (13.2%); its incidences across RCRI classes I (no risk factors), II (1 risk factor), III (2 risk factors), and IV (≥3 risk factors) were 8.2%, 15.4%, 26.7%, and 40.1%, respectively, (C-statistic for discrimination 0.65 [95% CI, 0.62-0.68]). The secondary outcome occurred in 1,174 patients (3.3%) with incidences of 1.6%, 4.0%, 7.9%, and 12.9% (C-statistic 0.69 [0.65-0.72]). Thirty-five percent of primary outcome events and 26.9% of secondary outcome events occurred in patients with no RCRI risk factors.

CONCLUSION: The RCRI alone is not sufficient to guide postoperative cardiac monitoring because one in 12 patients ≥45 years old without any RCRI risk factors have a cardiac complication after major noncardiac surgery and most would be missed without systematic troponin testing.

PMID:33766613 | DOI:10.1016/j.cjca.2021.03.015

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Nevin Manimala Statistics

Childhood maltreatment and disordered eating attitudes and behaviors in adult men and women: Findings from Project EAT

Appetite. 2021 Mar 22:105224. doi: 10.1016/j.appet.2021.105224. Online ahead of print.

ABSTRACT

This study examined gender differences in the association between childhood maltreatment and disordered eating attitudes and behaviors in adulthood. Data were derived from 1,647 adults (ages 27-33) participating in a population-based, longitudinal study (Project EAT-IV: Eating Among Teens and Young Adults, 1998-2016). Childhood maltreatment (sexual abuse, physical abuse, emotional abuse, emotional neglect) and disordered eating attitudes and behaviors (overeating, binge eating, extreme weight control behaviors, unhealthy weight control behaviors, chronic dieting, weight and shape concerns) were assessed. Relative risk regression models were used to examine whether childhood maltreatment was related to individual disordered eating attitudes and behaviors. Gender differences in these associations were explored. A history of any childhood maltreatment was associated with more than 60% greater risk for chronic dieting and overeating, with additional associations found for binge eating, weight and shape concerns, and unhealthy weight control behaviors. All types of abuse and neglect were associated with at least one type of disordered eating outcome. Examination of the point estimates indicated that emotional neglect was most consistently related to higher risk for disordered eating attitudes and behaviors. Although there were no statistically significant gender differences in the association between childhood maltreatment and disordered eating attitudes and behaviors, the patterning of these effects highlighted unique qualitative similarities and differences in these relationships between men and women. Taken together, these findings implicate childhood maltreatment, particularly emotional neglect, as a meaningful risk factor for problematic eating outcomes in both men and women during adulthood.

PMID:33766616 | DOI:10.1016/j.appet.2021.105224

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Nevin Manimala Statistics

Effects of different surface treatments and adhesive self-etch functional monomers on the repair of bulk fill composites: a randomised controlled study

J Dent. 2021 Mar 22:103637. doi: 10.1016/j.jdent.2021.103637. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the effect of different adhesive protocols on the microtensile bond strength (μTBS) and integrity of the repaired bulk fill composite interface.

METHODS: Two hundred and seventy composite blocks made of bulk fill composites of different viscosity were randomly assigned to 18 surface conditioning groups (n = 15/group). The universal adhesive systems used were HeliobondTM, Tokuyama bond force IITM and Scotchbond UniversalTM. A nanohybrid resin composite was applied as the repair material. Negative and positive control groups were included. Stick shape specimens of each group were subjected to μTBS testing. Representative samples from all test groups were subjected to microscopic, profilometric and SEM examination to determine their mode of failure. The data were analysed statistically using two-way ANOVA test, Tukey’s test and the independent t-test (α = 0.05).

RESULTS: The mean μTBS of all test groups ranged between 28.5 and 46.8 MPa and varied with the type of adhesive system employed. Significantly highest μTBS values were obtained when Tokuyama bond force IITM and Scotchbond UniversalTM adhesives were used (p < 0.01) which were comparable to the coherent strength of the bulk fill resin composite in the positive control groups (p > 0.05). The viscosity of the bulk fill composite did not significantly influence repair bond strength. The microscopy and SEM examination of the failed interfaces revealed a mixture of adhesive and cohesive failures.

CONCLUSIONS: Under the tested conditions, significantly greater μTBS of repaired bulk fill composite was achieved when the substrate surface was treated with adhesive systems containing a functional monomer.

CLINICAL SIGNIFICANCE: Effecting a repair of a bulk fill resin composite restoration with the application of a functional monomer containing adhesive system, such as Tokuyama Bond Force IITM or Scotchbond UniversalTM, would seem to enhance the interfacial bond strength and integrity of the repaired resin composite interface.

PMID:33766513 | DOI:10.1016/j.jdent.2021.103637

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Nevin Manimala Statistics

sTREM-1 assessment as a diagnostic biomarker for suspected acute appendicitis in children

Asian J Surg. 2021 Mar 22:S1015-9584(21)00132-9. doi: 10.1016/j.asjsur.2021.02.025. Online ahead of print.

ABSTRACT

BACKGROUND: The typical history of acute appendicitis is observed in less than 60% of cases. Therefore, searching for a surrogate marker is mandatory. Our goal was to determine whether the soluble triggering receptor expressed on myeloid cells (sTREM-1) is an efficient biomarker for acute appendicitis.

METHODS: sTREM-1 serum levels were measured in addition to carrying out routine diagnostic tests (urine dipstick, complete blood count and CRP) in children admitted to the Emergency Department with suspected appendicitis. Statistical analysis was performed in order to examine whether sTREM-1 was a significant predictor of appendicitis.

RESULTS: Fifty three of 134 children enrolled in the study were diagnosed with appendicitis. There was no significant difference in serum sTREM-1 levels (p = 0.111) between children with or without appendicitis (n = 81). Leukocytes, neutrophils and CRP were significantly elevated in the appendicitis group (p < 0.001). The appendix diameter was significantly larger and the Alvarado score significantly higher in the appendicitis group (p < 0.001).

CONCLUSION: serum sTREM-1 is not a good marker for acute appendicitis. Customary tests in addition to a proper patient history and physical examination are still the most effective methods to diagnose acute appendicitis.

PMID:33766532 | DOI:10.1016/j.asjsur.2021.02.025

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Nevin Manimala Statistics

Serological surveillance of SARS-CoV-2: Six-month trends and antibody response in a cohort of public health workers

J Infect. 2021 Mar 22:S0163-4453(21)00132-8. doi: 10.1016/j.jinf.2021.03.015. Online ahead of print.

ABSTRACT

BACKGROUND: Antibody waning after SARS-CoV-2 infection may result in reduction in long-term immunity following natural infection and vaccination, and is therefore a major public health issue. We undertook prospective serosurveillance in a large cohort of healthy adults from the start of the epidemic in England.

METHODS: Clinical and non-clinical healthcare workers were recruited across three English regions and tested monthly from March to November 2020 for SARS-CoV-2 spike (S) protein and nucleoprotein (N) antibodies using five different immunoassays. In positive individuals, antibody responses and long-term trends were modelled using mixed effects regression.

FINDINGS: In total, 2246 individuals attended 12,247 visits and 264 were seropositive in ≥2 assays. Most seroconversions occurred between March and April 2020. The assays showed >85% agreement for ever-positivity, although this changed markedly over time. Antibodies were detected earlier with Abbott (N) but declined rapidly thereafter. With the EuroImmun (S) and receptor-binding domain (RBD) assays, responses increased for 4 weeks then fell until week 12-16 before stabilising. For Roche (N), responses increased until 8 weeks, stabilised, then declined, but most remained above the positive threshold. For Roche (S), responses continued to climb over the full 24 weeks, with no sero-reversions. Predicted proportions sero-reverting after 52 weeks were 100% for Abbott, 59% (95% credible interval 50-68%) Euroimmun, 41% (30-52%) RBD, 10% (8-14%) Roche (N) <2% Roche (S).

INTERPRETATION: Trends in SARS-CoV-2 antibodies following infection are highly dependent on the assay used. Ongoing serosurveillance using multiple assays is critical for monitoring the course and long-term progression of SARS-CoV-2 antibodies.

PMID:33766553 | DOI:10.1016/j.jinf.2021.03.015

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Nevin Manimala Statistics

Advancing Radiotherapy for Bladder Cancer: Randomised Phase II Trial of Adaptive Image-guided Standard or Dose-escalated Tumour Boost Radiotherapy (RAIDER)

Clin Oncol (R Coll Radiol). 2021 Mar 22:S0936-6555(21)00055-8. doi: 10.1016/j.clon.2021.02.012. Online ahead of print.

NO ABSTRACT

PMID:33766502 | DOI:10.1016/j.clon.2021.02.012