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Nevin Manimala Statistics

Prediction of adverse perinatal outcome and the mean time until delivery in twin pregnancies with suspected pre-eclampsia using sFlt-1/PIGF ratio

Pregnancy Hypertens. 2021 Feb 13;24:37-43. doi: 10.1016/j.preghy.2021.02.003. Online ahead of print.

ABSTRACT

PURPOSE: An elevated soluble fms-like tyrosine kinase-1 (sFlt-1) / placental growth factor (PlGF) ratio is associated with adverse perinatal outcome (APO) and the mean time until delivery (MTUD) in singleton pregnancies complicated by pre-eclampsia (PE). Data on APO and MTUD prediction in twin pregnancies using sFlt-1/PlGF ratio are scarce. We evaluated the predictive value of the sFlt-1/PIGF ratio regarding APO and MTUD in twin pregnancies with suspected PE and/or HELLP syndrome.

METHODS: This is a single center retrospective cohort study. All twin pregnancies with suspected PE/HELLP and determined sFlt-1/PIGF were included. Composite APO (CAPO) was defined as the presence of at least one of the following outcomes: respiratory distress syndrome (RDS), intubation, admission to neonatal intensive care unit (NICU) and arterial umbilical cord pH value < 7.10. Selective fetal growth restriction (s-FGR) was analyzed separately.

RESULTS: For final analysis, 49 twin pregnancies were included. Median sFlt-1/PIGF ratio was not significantly different in patients with CAPO compared to those without (89.45 vs. 62.00, p = 0.669). MTUD was significantly negative correlated with sFlt-1/PIGF ratio (r = -0.409, p < 0.001). For the whole study cohort, ROC analysis revealed no predictive value for sFlt-1/PIGF and CAPO (AUC = 0.618, 95% CI: 0.387-0.849, p = 0.254). However, sFlt-1/PIGF ratio showed a predictive value for s-FGR (AUC = 0.755, 95% CI: 0.545-0.965, p = 0.032).

CONCLUSION: In twin pregnancies with PE and/or HELLP, sFlt-1/PIGF ratio may be helpful for s-FGR prediction and decision-making regarding close monitoring of high-risk patients. However, further prospective studies are warranted to define the role of sFlt-1/PlGF ratio as outcome predictor in twin pregnancies.

PMID:33647841 | DOI:10.1016/j.preghy.2021.02.003

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Nevin Manimala Statistics

Rarity of congenital malformation and deformity in the fossil record of vertebrates – A non-human perspective

Int J Paleopathol. 2021 Feb 26;33:30-42. doi: 10.1016/j.ijpp.2020.12.002. Online ahead of print.

ABSTRACT

OBJECTIVE: A malformed pectoral joint of the middle Devonian antiarch fish Asterolepis ornata is described, and a survey of congenital malformations in the fossil record is provided.

MATERIALS: The specimen of A. ornata (MB.f.73) from Ehrman in Latvia, stored at the Museum für Naturkunde Berlin, Germany.

METHODS: A. ornata was macroscopically and radiologically investigated, and the overview on congenital malformation was based on an extensive literature survey.

RESULTS: In the deformed joint of A. ornata, the articular surfaces and muscle attachment sites are greatly reduced, indicating restricted mobility. Congenital malformations can be found since the middle Silurian and affect all groups of vertebrates, but they are rare. Teeth and the vertebral column are the most commonly affected anatomical regions, and the mechanisms causing these malformations probably remained the same through geological time.

CONCLUSIONS: Micro-CT of the deformed joint shows no disturbance of the normal trabecular pattern and no evidence of trauma or disease, suggesting a congenital hypoplasia, although an acquired deformity cannot be ruled out completely.

SIGNIFICANCE: Congenital malformations, even those that are rare, were part of the common history of vertebrates for more than 400 million years.

LIMITATIONS: Epidemiologic measures like incidence and prevalence usually cannot be applied to define rare diseases in the fossil record.

SUGGESTIONS FOR FURTHER RESEARCH: A broadly based analysis of species of fossil vertebrates with numerus recovered specimens (e.g. many bony fishes, amphibians, certain dinosaurs) might statistically affirm the occurrence of malformations and possible correlations with the paleoenvironment.

PMID:33647859 | DOI:10.1016/j.ijpp.2020.12.002

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Nevin Manimala Statistics

The potential role of follicular helper T cells and helper T cells type 1 in Warthin tumour

Pathol Res Pract. 2021 Feb 17;220:153386. doi: 10.1016/j.prp.2021.153386. Online ahead of print.

ABSTRACT

Warthin tumour (WT) is a benign tumour of the salivary gland that proliferates in both glandular epithelial and lymphoid tissue components, and rarely exhibits cystic changes. T follicular helper cells (Tfh) are involved in the formation and maintenance of germinal centres, the differentiation of B cells into plasma cells, and the maintenance of helper T cell type 2 (Th2)-dominant humoral immune responses. T-bet induces differentiation into helper T cell type 1 (Th1) by suppressing differentiation into Tfh and enhances cellular immune responses. The objective of this study was to enhance our understanding of the immune responses and relationship between Tfh and Th1 cells in patients with WTs. In this study, we classified WTs (n = 64) into solid-type (n = 25) and cyst-type (n = 39). We also performed immunostaining of the Tfh markers CXCR5 and CD40 L, and the Th1 marker T-bet for statistical analysis. The cyst-type exhibited significant atrophy of the germinal centre area (P = 0.0019), significantly fewer Tfh-positive lymphocytes in germinal centres (P < 0.0001), and significantly more T-bet-positive lymphocytes in the epithelium (P = 0.0017). We observed that Tfh were involved in the formation and maintenance of lymphoid follicles in WTs. In the cyst-type, Th2-dominant humoral immune responses were suppressed, and Th1-dominant cellular immune responses may have caused damage to tumour tissue.

PMID:33647861 | DOI:10.1016/j.prp.2021.153386

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Nevin Manimala Statistics

Innovative scanning electron microscopic investigation in blood samples of patients affected by leukaemia: A physical-chemical-biological approach

Micron. 2021 Feb 19;144:103037. doi: 10.1016/j.micron.2021.103037. Online ahead of print.

ABSTRACT

The study proposes an innovative, interdisciplinary observation on blood samples of patients coming from the region Marche (Italy) suffering from acute myeloid leukaemia (AML) by means of a scanning electron microscope coupled with an X-ray microprobe of an Energy Dispersive Spectroscope. A novel protocol of blood preparation was studied and prepared to identify exogenous, potentially toxic foreign bodies coming from an environmental contamination. The results on the four different blood fractions of 38 blood samples (erythrocytes, leukocytes, platelets, and plasma) indicate that the circulating blood of leukaemic patients shows the systematic presence of physical contaminants, with a frequency and concentration which are statistically meaningful as compared to the healthy controls. The chemical compositions of the particles were identified as well as the frequency of the elements they were composed of. The analysis of these chemical compositions demonstrated that these patients had undergone a remarkable environmental, occupational, industrial exposure at some time. A possible pathological mechanism based on a nano-bio-interaction between the internalized environmental particulate matter and the blood components is hypothesized and discussed.

PMID:33647774 | DOI:10.1016/j.micron.2021.103037

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Nevin Manimala Statistics

Colorectal liver metastases: ADC as an imaging biomarker of tumor behavior and therapeutic response

Eur J Radiol. 2021 Feb 22;137:109609. doi: 10.1016/j.ejrad.2021.109609. Online ahead of print.

ABSTRACT

PURPOSE: To correlate the ADC values of colorectal liver metastases, evaluated before (preADC) and after (postADC) neoadjuvant chemotherapy (ChT), as well as their difference (ΔADC), with the histological tumor regression grade (TRG) and to determine whether the preADC value can be predictive of the lesion ChT response.

METHOD: Twenty-four patients with colorectal liver metastases, who had undergone 3 T-MRI before and after ChT and were subsequently treated by parenchymal-spearing surgery, were retrospectively included. Diffusion-weighted MRI (DW-MRI) was performed using a spin-echo echo-planar sequence with multiple b values, obtaining an ADC map. Fitted ADC values were calculated for each lesion before and after ChT. The maximum diameter of each lesion in both examinations was recorded. Diameter variations and RECIST1.1 criteria were assessed. All MRI findings were histopathologically correlated to TRG of resected liver metastases. Statistical analysis was performed on a per-lesion basis.

RESULTS: A total of 58 colorectal liver metastases were analysed; after ChT, 8 out of 58 lesions disappeared. TRG1, TRG2, TRG3, TRG4 and TRG5 were observed in 6, 12, 12, 13 and 7 lesions, respectively. The preADC values showed a different distribution according to the TRG scores (p = 0.0027), even though the distribution was not linear. The postADC and ΔADC values were significant different based on the TRG system (both p < 0.0001). A significant correlation between the lesion TRG and the evaluation according to RECIST1.1 criteria was observed by a per-lesion analysis (p = 0.0009).

CONCLUSIONS: PostADC and ΔADC could be proposed as reliable biomarkers to assess tumor treatment response after preoperative ChT in patients with colorectal liver metastases.

PMID:33647779 | DOI:10.1016/j.ejrad.2021.109609

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Nevin Manimala Statistics

Concordance of genotypic resistance interpretation algorithms in HIV-1 infected patients: An exploratory analysis in Greece

J Clin Virol. 2021 Feb 20;137:104779. doi: 10.1016/j.jcv.2021.104779. Online ahead of print.

ABSTRACT

PURPOSE: Genotypic resistance-related mutations in HIV-1 disease are often difficult to interpret. Different algorithms have been developed to provide meaningful application into clinical context. We aimed to compare, for the first time in Greece, the results of genotypic resistance derived from three interpretation algorithms.

METHODS: The sequences of 120 HIV 1-infected patients were tested for genotypic resistance to 19 antiretroviral (ARV) drugs (n = 2280 sequences). The interpretation results of Rega, ANRS and ViroSeq algorithms were compared.

RESULTS: Complete concordance was found for 2/19 ARV drugs, namely lamivudine and emptricitabine. Concordance was high for nucleoside reverse transcriptase inhibitors (NRTIs) and low for protease inhibitors (PIs). In inter-algorithm pairs, agreement was high between Rega and ViroSeq (kappa = 0.701), especially by ARV class, namely NRTIs (k = 0.869) and NNRTIs (k = 0.562). The only exception was noted for rilpivirine, where agreement was higher between ANRS and Rega (k = 0.410) compared to other inter-algorithm pairs (k = 0.018-0.055). By contrast, for PIs all comparisons yielded concordance equivalent to chance (k = 0.000).

CONCLUSIONS: Our exploratory analysis provided evidence of significant inter-algorithm discordances, especially for PIs and NNRTIs highlighting the importance of matching the results of different algorithms to achieve optimized risk stratification. Ongoing research could assist clinical physicians in interpreting complex genotypic resistance patterns.

PMID:33647801 | DOI:10.1016/j.jcv.2021.104779

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Nevin Manimala Statistics

UMAP-assisted K-means clustering of large-scale SARS-CoV-2 mutation datasets

Comput Biol Med. 2021 Feb 22;131:104264. doi: 10.1016/j.compbiomed.2021.104264. Online ahead of print.

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a worldwide devastating effect. Understanding the evolution and transmission of SARS-CoV-2 is of paramount importance for controlling, combating and preventing COVID-19. Due to the rapid growth in both the number of SARS-CoV-2 genome sequences and the number of unique mutations, the phylogenetic analysis of SARS-CoV-2 genome isolates faces an emergent large-data challenge. We introduce a dimension-reduced K-means clustering strategy to tackle this challenge. We examine the performance and effectiveness of three dimension-reduction algorithms: principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE), and uniform manifold approximation and projection (UMAP). By using four benchmark datasets, we found that UMAP is the best-suited technique due to its stable, reliable, and efficient performance, its ability to improve clustering accuracy, especially for large Jaccard distanced-based datasets, and its superior clustering visualization. The UMAP-assisted K-means clustering enables us to shed light on increasingly large datasets from SARS-CoV-2 genome isolates.

PMID:33647832 | DOI:10.1016/j.compbiomed.2021.104264

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Nevin Manimala Statistics

Structure-based mimicking of hydroxylated biphenyl congeners (OHPCBs) for human transthyretin, an important enzyme of thyroid hormone system

J Mol Graph Model. 2021 Feb 19;105:107870. doi: 10.1016/j.jmgm.2021.107870. Online ahead of print.

ABSTRACT

In humans, transthyretin (hTTR) is a plasma protein act as a transporter of thyroxine (T4) in the blood. Polychlorinated biphenyls (PCBs) are used in coolants, transformers, plasticizers, and pesticide extenders, etc. due to their physical properties, chemical stability, and dielectric properties. Cytochrome P450 can oxidize the PCBs into hydroxylated PCBs (OHPCBs) which can further interact with hTTR results in hepatoxicity, loss of metabolic rate, memory problems, and neurotoxicity. Molecular docking results show that OHPCBs bind at the active site of hTTR with a more binding affinity as compared to T4. Further, molecular dynamics simulation has been done to confirm the stability of hTTR-OHPCBs complexes. Several analysis parameters like RMSD, RMSF, Rg, SASA, hydrogen bonds numbers, PCA, and FEL revealed that binding of OHPCBs with hTTR results in the formation of stable hTTR-OHPCBs complexes. Individual residues decomposition analysis confirms that Lys15, Leu17, Ala108, Ala109, Leu110, Ser117, and Thr119 of hTTR plays a major role in the binding of OHPCBs to form the lower energy hTTR-OHPCBs complexes. Molecular docking and simulations results emphasize that OHPCBs can efficiently bind at the active site of hTTR, which further leads to inhibition of transportation of T4 in human blood.

PMID:33647754 | DOI:10.1016/j.jmgm.2021.107870

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Nevin Manimala Statistics

Rapid eye movement sleep disturbance in patients with refractory epilepsy: A polysomnographic study

Sleep Med. 2021 Feb 9;81:101-108. doi: 10.1016/j.sleep.2021.02.007. Online ahead of print.

ABSTRACT

OBJECTIVE/BACKGROUND: Patients with epilepsy have disrupted sleep architecture and a higher prevalence of sleep disturbance. Moreover, obstructive sleep apnea (OSA) is more common among patients with refractory epilepsy. Few studies have compared subjective sleep quality, sleep architecture, and prevalence of OSA between patients with refractory epilepsy and those with medically controlled epilepsy. Therefore, this study aimed to evaluate the differences in sleep quality, sleep architecture, and prevalence of OSA between patients with refractory epilepsy and patients with medically controlled epilepsy.

PATIENTS: This retrospective case-control study included 38 patients with refractory epilepsy and 96 patients with medically controlled epilepsy. Sleep parameters and indices of sleep-related breathing disorders were recorded by standard in-laboratory polysomnography. The scores from sleep questionnaires on sleep quality and daytime sleepiness were compared between the two groups.

RESULTS: Patients with refractory epilepsy versus medically controlled epilepsy had statistically significantly decreased rapid eye movement (REM) sleep (13.5 ± 6.1% vs. 16.2 ± 6.1%) and longer REM latency (152.2 ± 84.1 min vs. 117.2 ± 61.9 min). Further, no differences were found in the prevalence of sleep-related breathing disorders, subjective sleep quality, prevalence of daytime sleepiness, and quality of life. Although not statistically significant, patients with refractory epilepsy have a lower rate of OSA compared with those with medically controlled epilepsy (21.1% vs. 30.2%).

CONCLUSIONS: Patients with refractory epilepsy had more disrupted REM sleep regulation than those with medically controlled epilepsy. Although patients with epilepsy have a higher risk of OSA, in this study patients with refractory epilepsy were not susceptible to OSA.

PMID:33647761 | DOI:10.1016/j.sleep.2021.02.007

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Nevin Manimala Statistics

The Effect of Computerized Clinical Decision Support on Adherence to VTE Prophylaxis Clinical Practice Guidelines among Hospitalized Patients

Int J Qual Health Care. 2021 Feb 27:mzab034. doi: 10.1093/intqhc/mzab034. Online ahead of print.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is an important patient safety concern resulting in significant mortality, morbidity, and a burden on healthcare resources. Despite the widespread availability of evidence-based clinical practice guidelines (CPGs) on VTE prophylaxis, we found that only 50.9% of our patients were receiving appropriate prophylaxis. This study aimed to evaluate the impact of automation of an adapted VTE prophylaxis CPG through a clinical decision support system (the VTE-CDSS) to prevent VTE among hospitalized adult patients through comprehensive multi-faceted implementation strategies.

METHODS: Quasi-experimental study design (pre- and post-implementation). The study was conducted at a large 900-bed tertiary teaching multi-specialty hospital in Riyadh, Saudi Arabia. A total of 1809 adult patients were included in the study: 871 during the pre-implementation stage and 938 in the post-implementation stage. Multi-faceted implementation interventions were utilized including leadership engagement and support, quality and clinical champions, staff training and education, and regular audit and feedback. Two rate-based process measures were calculated for each admission cohort (i.e. pre/post-implementation); the percentage of inpatients who have been assessed for VTE risk on admission and the percentage of inpatients who have received appropriate VTE prophylaxis. Additionally, two outcome measures were calculated including the prevalence of Hospital-acquired VTE events and the in-hospital all-cause mortality.

RESULTS: The percentage of inpatients who have been risk assessed for VTE on admission increased from 77.4% to 93.3% (P<0.01). the percentage of the those who have received appropriate VTE prophylaxis increased from 50.9 % to 81.4% (P<0.01). In total, the hospital-acquired VTE (HA-VTE) events decreased by 50 % from 0.33% to 0.15% (P<0.01) All-causes in hospital mortality did not show statistically significant difference before and after implementation of the VTE-CDSS (P>0.05).

CONCLUSION: The VTE-CDSS was able to improve patient safety by enhancing the adherence to the VTE prophylaxis best practice and adapted CPG. The adopted multifaceted implementation strategies’ approach had shown successful improvement of the compliance rate of risk assessment, adherence to prophylaxis recommendations, and substantial reduction of the HA-VTE prevalence. Furthermore, a successful CDSS needs to have a set of critical components to ensure better user compliance and positive patient outcomes for such a system.

PMID:33647102 | DOI:10.1093/intqhc/mzab034