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Nevin Manimala Statistics

Elevated Oxidative Stress and DNA Damage in Cortical Neurons of Chemotherapy Patients

J Neuropathol Exp Neurol. 2021 Aug 7:nlab074. doi: 10.1093/jnen/nlab074. Online ahead of print.

ABSTRACT

The unintended neurologic sequelae of chemotherapy contribute to significant patient morbidity. Chemotherapy-related cognitive impairment (CRCI) is observed in up to 80% of cancer patients treated with chemotherapy and involves multiple cognitive domains including executive functioning. The pathophysiology underlying CRCI and the neurotoxicity of chemotherapy is incompletely understood, but oxidative stress and DNA damage are highly plausible mechanisms based on preclinical data. Unfortunately, validating pathways relevant to CRCI in humans is limited by an absence of relevant neuropathologic studies of patient brain tissue. In the present study, we stained sections of frontal lobe autopsy tissue from cancer patients treated with chemotherapy (n = 15), cancer patients not treated with chemotherapy (n = 10), and patients without history of cancer (n = 10) for markers of oxidative stress (nitrotyrosine, 4-hydroxynonenal) and DNA damage (pH2AX, pATM). Cancer patients treated with chemotherapy had increased staining for markers of oxidative stress and DNA damage in frontal lobe cortical neurons compared to controls. We detected no statistically significant difference in oxidative stress and DNA damage by the duration between last administration of chemotherapy and death. The study highlights the potential relevance of oxidative stress and DNA damage in the pathophysiology of CRCI and the neurotoxicity of chemotherapy.

PMID:34363676 | DOI:10.1093/jnen/nlab074

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National Cardiovascular Data Registry-Acute Kidney Injury (NCDR) vs. Mehran risk models for prediction of contrast-induced nephropathy and need for dialysis after coronary angiography in a German patient cohort

J Nephrol. 2021 Aug 7. doi: 10.1007/s40620-021-01124-9. Online ahead of print.

ABSTRACT

BACKGROUND: Contrast-induced nephropathy (CIN) is a major adverse event in patients undergoing coronary angiography. The Mehran risk model is the gold-standard for CIN risk prediction. However, its performance in comparison to more contemporary National Cardiovascular Data Registry-Acute Kidney Injury (NCDR-AKI) risk models remains unknown. We aimed to compare both in this study.

METHODS AND RESULTS: Predictions of Mehran and NCDR-AKI risk models and clinical events of CIN and need for dialysis were assessed in a total of 2067 patients undergoing coronary angiography with or without percutaneous coronary intervention. Risk models were compared regarding discrimination (receiver operating characteristic analysis), net reclassification improvement (NRI) and calibration (graphical and statistical analysis). The NCDR risk model showed superior risk discrimination for predicting CIN (NCDR c-index 0.75, 95% CI 0.72-0.78; vs. Mehran c-index 0.69, 95% CI 0.66-0.72, p < 0.01), and continuous NRI (0.22; 95% CI 0.12-0.32; p < 0.01) compared to the Mehran model. The NCDR risk model tended to underestimate the risk of CIN, while the Mehran model was more evenly calibrated. For the prediction of need for dialysis, NCDR-AKI-D also discriminated risk better (c-index 0.85, 95% CI 0.79-0.91; vs. Mehran c-index 0.75, 95% CI 0.66-0.84; pNCDRvsMehran < 0.01), but continuous NRI showed no benefit and calibration analysis revealed an underestimation of dialysis risk.

CONCLUSION: In German patients undergoing coronary angiography, the modern NCDR risk model for predicting contrast-induced nephropathy showed superior discrimination compared to the GRACE model while showing less accurate calibration. Results for the outcome ‘need for dialysis’ were equivocal.

PMID:34363595 | DOI:10.1007/s40620-021-01124-9

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Psychological distress among Chinese patients with breast cancer undergoing chemotherapy: Concordance between patient and family caregiver reports

J Adv Nurs. 2021 Aug 7. doi: 10.1111/jan.15004. Online ahead of print.

ABSTRACT

AIMS: To examine patient-caregiver concordances about psychological distress among Chinese patients with breast cancer undergoing chemotherapy and identify factors related to concordance among patients and family caregivers.

DESIGN: Cross-sectional study.

METHODS: From October 2019 to June 2020, 137 patient-caregiver dyads were enrolled. Sociodemographic information, the distress thermometer (including the problem list), the Distress Disclosure Index and the Family Adaptability and Cohesion Evaluation Scale were used to collect data. Data were analysed using intraclass correlation coefficients (ICC), kappa statistics, two related samples test, chi-square tests and/or Fisher’s exact tests and binary logistic regression.

RESULTS: Overall, fair agreement was identified between patients’ and caregivers’ reports (intraclass correlation coefficients [ICC] = .528). Patients reported significantly higher psychological distress scores than paired caregiver reports. Lower psychological distress concordance was found among patients with comorbidities (odds ratio [OR], 0.352; 95% confidence interval [CI], 0.155-0.798) and lower levels of self-disclosure (OR, 0.402; 95% CI, 0.186-0.868).

CONCLUSION: There was relatively low concordance between patients’ reports and caregivers’ perceptions of psychological distress. Family caregivers tended to underestimate patients’ psychological distress. A comorbid condition and lower levels of self-disclosure contributed to this bias.

IMPACT: Having an awareness of the incongruence between patient and caregiver may help healthcare providers better interpret caregiver assessments. Healthcare providers should reinforce patient-caregiver dyadic psychosocial education to improve concordance. More psychological care and substantial emotional support should be provided for Chinese breast cancer patients undergoing chemotherapy by family caregivers and healthcare providers.

PMID:34363625 | DOI:10.1111/jan.15004

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Global effects of RAB3GAP1 dysexpression on the proteome of mouse cortical neurons

Amino Acids. 2021 Aug 7. doi: 10.1007/s00726-021-03058-9. Online ahead of print.

ABSTRACT

Mounting studies have demonstrated that RAB3GAP1 expression is modified in brain diseases with multiple neurobiological functions and processes and acts as a potentially significant target. However, the cellular and molecular events arising from RAB3GAP1 dysexpression are still incompletely understood. In this work, underexpression and overexpression of RAB3GAP1 were first induced into cultured mouse cortical neurons by transfection with lentivirus plasmids. Then we globally explored the effects of RAB3GAP1 dysexpression on the proteome of the neurons through the use of isobaric tag for relative and absolute quantitation (iTRAQ)-based quantitative proteomics with bioinformatics. A total of 364 proteins in the RAB3GAP1-underexpression group and 314 proteins in the RAB3GAP1-overexpression group were identified to be differentially expressed. Subsequent bioinformatics analysis indicated that the proteome functional expression profiles induced by RAB3GAP1 underexpression and overexpression were different, suggesting the potential differences in biological processes and cellular effects. Subsequent intergroup cross-comparison revealed some candidate target proteins regulated directly by RAB3GAP1. Further parallel reaction monitoring (PRM) analysis illustrated that Sub1, Ssrp1, and Top1 proteins might serve as new potentially important linkers in the RAB3GAP1-mediated autophagy pathway in the cortical neurons. Collectively, the current proteomics data furnished new valuable insights to better understand the regulatory molecular mechanism of neuronal RAB3GAP1.

PMID:34363538 | DOI:10.1007/s00726-021-03058-9

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Risk of mortality due to COVID-19 and air pollution in Pakistan

Environ Sci Pollut Res Int. 2021 Aug 7. doi: 10.1007/s11356-021-15654-z. Online ahead of print.

ABSTRACT

The present research aims to investigate the impact of air pollution on the number of mortalities caused by COVID-19 per Pakistani province. To do so, for each independent area of Pakistan, the observed mortality due to COVID-19 has been standardized over the entire population using standard age groups ranging from 0 to 4, 5 to 9, 10 to 14,…, 65, and above years, supported by the 2017 state people census. The impact of air pollution and COVID-19 transience among Pakistani areas, Islamabad Capital Territory (ICT), and the Federally Administered Tribal Region (FATA) was analyzed by a multiple-linear regression model, while the broad collection of attributes was observed by the resources of local spatial autocorrelation indicators, including the spatial portion of COVID-19 association. The result indicates that the observed mortality rate is much higher than predicted in certain provinces, namely, the Khyber Pakhtunkhwa and Punjab provinces, and the prevalence of PM10 was independently linked to mortality due to the corona virus. Additionally, the results of the local spatial autocorrelation indicators on the standardized mortality rate and PM10 define a collection of very higher ideologies in the broad range of KPK and the southern part of Punjab province, respectively, with a definite degree of connection between the two distributions in the Khyber Pakhtunkhwa region. In brief, this research seems to find a justification for confirming the existence of a correlation between the possibility of COVID-19 mortality and air pollution, more precisely considering air pollutants (i.e., particulate (PM10) and land take-over. To this end, the need to mediate in favor of measures aimed at eliminating emissions in the environment will be reiterated by speeding up current proposals and policies aimed at all causes of atmospheric pollution: urbanization, water and manufacturing, home heating, and transportation.

PMID:34363580 | DOI:10.1007/s11356-021-15654-z

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Induction therapy for acute lymphoblastic leukemia: incidence and risk factors for bloodstream infections

Support Care Cancer. 2021 Aug 7. doi: 10.1007/s00520-021-06471-8. Online ahead of print.

ABSTRACT

Among the treatment-related acute toxic effects, risks for bloodstream infections (BSIs) are associated with several variables. The authors carried out a retrospective cohort study with 259 children and adolescents with ALL, treated with the GBTLI-LLA 2009 protocol, in order to assess the incidence of BSIs in the induction phase; to determine the risk factors for these BSIs; and to identify the related microorganisms and sensitivity profile of the microorganisms related to these infections. BSIs were documented in 19.3% of patients. The isolated microorganisms were 39 Gram-negative bacteria, 21 Gram-positive bacteria, and four fungi. There was a statistically significant risk of BSI between the variables: protocol for T-line-derived leukemia (Derived T Protocol) (p = 0.020), oral manifestations (p = 0.015), central venous catheter (p = 0.008), and bladder catheter (p = 0.004). BSI is a frequent event in ALL patients during the induction phase. The identification of these factors can allow the elaboration and improvement of strategies for the intensification of supportive care, prevention, and rapid treatment of infections.

PMID:34363492 | DOI:10.1007/s00520-021-06471-8

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Sea water quality monitoring using remote sensing techniques: a case study in Tangier-Ksar Sghir coastline

Environ Monit Assess. 2021 Aug 7;193(9):557. doi: 10.1007/s10661-021-09242-4.

ABSTRACT

Water quality is an extremely important factor as it affects the ecological balance of ecosystems and the development of the social and economic wellbeing of the countries bordering it. Remote sensing multiconcept helps to understand the natural environment, managing water resources and assessing water pollution on local and regional levels. Landsat 8 data were used to monitor coastal water quality in the region of Tangier-Ksar Sghir. The main purpose of the current study is to establish a mathematical relationship between the amount of light emitted from the water bodies and the measured water parameters. The results permit to create a spatial distribution maps for the water quality parameters. The present work study three water parameters: total suspended solids (TSS), dissolved oxygen (DO), and total dissolved sediments (TDS). Thirty-four sampling points were used to represent water parameters measurements along the coastline. The 75% of the in situ measurements were used to build the statistical models by using the spectral characteristics obtained from the sensors, while the remaining 25% were used for testing the accuracy of the developed equations. For the correlation analysis and the regression development, the Statistical Package of the Social Sciences (SPSS) software was used. The final results of the statistical analysis showed a high correlation between the calculated data and the observed ones with R2 ˃ 0.713 and p value ˂ 0.001. The obtained values showed a high accuracy as well (RMSE ranging between 0.23 and 0.69 and SEE ranging between 0.01 and 0.47). SNAP software and Qgis were used to do the image processing and to create the spatial distribution maps for the water parameters in the coastline of Tangier-Ksar Sghir region.

PMID:34363536 | DOI:10.1007/s10661-021-09242-4

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In low-risk patients aged >70-75 with severe aortic stenosis, is transcatheter superior to surgical aortic valve replacement in terms of reported cardiovascular composite outcomes and survival?

Interact Cardiovasc Thorac Surg. 2021 Aug 7:ivab218. doi: 10.1093/icvts/ivab218. Online ahead of print.

ABSTRACT

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: In low-risk patients aged >70-75 with severe aortic stenosis, is transcatheter superior to surgical aortic valve replacement in terms of reported composite outcomes and survival? More than 73 papers were found using the reported search, of which 8 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. The only low-risk randomized control trial to date [Nordic Aortic Valve Intervention (NOTION)] regarding an elderly population did not show a statistically significant difference between the 2 approaches regarding the composite endpoint of death, stroke or myocardial infarction. A subgroup analysis of elderly patients in the 2 main low-risk randomized control trials did not yield statistically different results from those of the overall population; the results indicated the superiority of transcatheter aortic valve implantation regarding the composite of death, stroke or rehospitalization at 1 year [The Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients With Aortic Stenosis (PARTNER 3)] and non-inferiority regarding a composite of death or stroke at 2 years [Medtronic Evolut Transcatheter Aortic Valve Replacement in Low-Risk Patients (Evolut LR)]. The results from lower evidence studies are largely consistent with these findings. Overall, there is no compelling evidence indicating that older age should be an isolated criterion for the choice between transcatheter aortic valve replacement and surgical aortic valve replacement in otherwise low-risk patients. The superiority of either technique regarding the aforementioned composite short-term outcomes in this particular subgroup of patients is unclear.

PMID:34363475 | DOI:10.1093/icvts/ivab218

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The medial condylar wall is a reliable landmark to kinematically align the femoral component in medial UKA: an in-silico study

Knee Surg Sports Traumatol Arthrosc. 2021 Aug 7. doi: 10.1007/s00167-021-06683-9. Online ahead of print.

ABSTRACT

PURPOSE: Kinematic alignment (KA) aligns the femoral implant perpendicular to the cylindrical axis in the frontal and axial plane. Identification of the kinematic axes when using the mini-invasive sub-quadricipital approach is challenging in unicompartmental knee arthroplasty (UKA). This study aims to assess if the orientation of condylar walls may be suitable for use as an anatomical landmark to kinematically align the femoral component in medial UKA. It was hypothesised that the medial wall of the medial condyle would prove to be a reliable anatomical landmark to set both the frontal and axial alignment of the femoral component in medial UKA.

METHODS: 73 patients undergoing medial UKA had pre-operative CT imaging to generate 3D models. Those with osteophytes that impaired visualisation of the condylar walls were excluded. 28 patients were included in the study. The ideal KA was determined using the cylindrical axis in the frontal and axial plane. Simulations using the medial wall of the medial condyle (MWMC) and the lateral wall of the medial condyle (LWMC) were performed to set the frontal alignment. To set the axial alignment, the MWMC, LWMC, medial wall of the lateral condyle (MWLC), and medial diagonal line (MDL) anatomical landmarks were investigated. Differences between the ideal measured KA values and values obtained using landmarks were investigated.

RESULTS: Use of the MWMC let to similar frontal alignment compared to the ideal KA (2.9° valgus vs 3.4° valgus, p = 0.371) with 46.4% (13/28) of measurements being [Formula: see text] 1.0° different from the ideal KA and only 1 simulation with greater than 4.0° difference. Use of the MWMC led to very similar axial alignments compared to the ideal KA (0.5° internal vs 0.0°, p = 0.960) with 75.0% (21/28) of measurements being [Formula: see text] 1.0o different from the ideal KA, and a maximum difference of 3.0°. Use of the MWLC and MDL was associated with significant statistical differences when compared to the ideal KA (p < 0.001 for both).

CONCLUSIONS: The native orientation of the medial condylar wall seems to be a reliable anatomical landmark for aligning the femoral component in medial KA UKA in both the axial plane and frontal planes. Other assessed landmarks were shown to not be reliable. Clinical and radiographic assessments of the reliability of using the MWMC to set the frontal and axial orientation of the femoral component when performing a medial KA UKA are needed.

PMID:34363490 | DOI:10.1007/s00167-021-06683-9

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HLA Antibodies and Their Association with Blood Product Exposures in Pediatric Patients Undergoing Cardiac Transplantation

Paediatr Anaesth. 2021 Aug 7. doi: 10.1111/pan.14269. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Previous blood product exposures may result in the development of antibodies to human leukocyte antigens (HLA). Pediatric heart transplant recipients who have these antibodies experience increased morbidity and mortality after transplantation. In this study, our aims were to confirm the association of previous allogeneic blood product exposures with the formation of anti-HLA antibodies, determine which blood components pose the greatest risk of developing antibodies, and assess differences in outcomes after transplantation between patients who had anti-HLA antibodies and those who did not.

METHODS: This retrospective investigation included all children who underwent cardiac transplantation at Children’s Healthcare of Atlanta from January 1, 2015, through December 31, 2018. Chart reviews were performed to collect pertinent data. Anti-HLA antibodies were detected by single antigen bead testing. Antibody burden was tabulated using the calculated panel reactive antibody (cPRA) score immediately prior to transplantation. Statistical analyses were conducted to examine differences based on HLA antibody status and identify associations with outcomes of interest.

RESULTS: Our results show a significant association between pre-transplant blood product exposures and HLA antibody status. Children with a pre-transplant blood product exposure had 7.98 times the odds of developing an anti-HLA antibody compared to those without a pre-transplant blood product exposure (p=0.01). We also found a significant association between a previous red blood cell (RBC) exposure and HLA antibody status (p=0.01) which was not found for other blood component exposures. Patients who were HLA antibody positive were more likely to develop a donor specific antibody (DSA) after transplantation (p=0.04).

CONCLUSIONS: Exposure to previous allogeneic blood products affects the development of anti-HLA antibodies in children presenting for heart transplantation. Previous RBC exposures resulted in HLA antibody positivity more than other blood component exposures. Importantly, the presence of HLA antibodies was associated with the development of DSAs post-transplantation. Developing transfusion strategies to reduce allogeneic blood product exposures in children who may need future cardiac transplantation should be a high priority.

PMID:34363427 | DOI:10.1111/pan.14269