Nevin Manimala

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

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

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

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

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

Avian Dis. 2020 Dec 1;64(4):571-581. doi: 10.1637/0005-2086-64.4.571.

ABSTRACT

Histologic and bacteriologic features for groups of average 31-day-old broilers displaying three gross categories of femoral head alterations were documented. Categories included simple femoral head separation (FHS), femoral head transitional changes (FHT), and femoral head necrosis (FHN). Groups with grossly normal (NORM) femoral heads and cull birds with FHN and having gross signs of sepsis (Cull-FHN) were also included in the study. There was a 10% occurrence of positive bacterial cultures for all birds tested. Most positive cultures (33%) were found in the Cull-FHN group, while only a 12% occurrence was seen in the FHS group, and no positives were present in the FHT or FHN groups. A 14% total occurrence of femoral bacterial chondronecrosis with osteomyelitis or simple osteomyelitis (BCO-O) was observed. A progressive increase in the prevalence of BCO-O was apparent between groups going from NORM (0%), FHS (4%), FHT (14%), FHN (13%), and reaching a maximum of 67% in the Cull-FHN group. Minimal to mild femoral head cartilage necrosis was present in 40% of NORM broilers and 100% of the FHS, FHT, and FHN groups, but at moderate severity in 20% of the Cull-FHN group. Thus, the majority of FHN cases were associated with aseptic cartilage necrosis rather than BCO-O. These findings suggest that aseptic cartilage necrosis may be as important as septic necrosis as a cause of gross femoral head disease. A 26% overall occurrence was seen for hip synovitis-arthritis, but group differences were not statistically significant. Synovitis was not seen in the NORM group and was present in some (12%) of the FHS group but was observed at a high rate in both the FHN (43%) and the Cull-FHN (50%) groups. Morphometric measurements demonstrated that the area size of femoral fibrous cortical defects or “cutback zones” were generally larger for all gross categories relative to NORM, with a significant difference between NORM and FHS groups. This study underscores the multifactorial etiology of FHN and the importance of conducting both histologic and bacteriologic evaluations in which gross evidence of FHN or BCO-O occurs.

PMID:33647154 | DOI:10.1637/0005-2086-64.4.571

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

PLoS One. 2021 Mar 1;16(3):e0247826. doi: 10.1371/journal.pone.0247826. eCollection 2021.

ABSTRACT

Myocardial velocities carry important diagnostic information in a range of cardiac diseases, and play an important role in diagnosing and grading left ventricular diastolic dysfunction. Tissue Phase Mapping (TPM) Magnetic Resonance Imaging (MRI) enables discrete sampling of the myocardium’s underlying smooth and continuous velocity field. This paper presents a post-processing framework for constructing a spatially and temporally smooth and continuous representation of the myocardium’s velocity field from TPM data. In the proposed scheme, the velocity field is represented through either linear or cubic B-spline basis functions. The framework facilitates both interpolation and noise reducing approximation. As a proof-of-concept, the framework was evaluated using artificially noisy (i.e., synthetic) velocity fields created by adding different levels of noise to an original TPM data. The framework’s ability to restore the original velocity field was investigated using Bland-Altman statistics. Moreover, we calculated myocardial material point trajectories through temporal integration of the original and synthetic fields. The effect of noise reduction on the calculated trajectories was investigated by assessing the distance between the start and end position of material points after one complete cardiac cycle (end point error). We found that the Bland-Altman limits of agreement between the original and the synthetic velocity fields were reduced after application of the framework. Furthermore, the integrated trajectories exhibited consistently lower end point error. These results suggest that the proposed method generates a realistic continuous representation of myocardial velocity fields from noisy and discrete TPM data. Linear B-splines resulted in narrower limits of agreement between the original and synthetic fields, compared to Cubic B-splines. The end point errors were also consistently lower for Linear B-splines than for cubic. Linear B-splines therefore appear to be more suitable for TPM data.

PMID:33647070 | DOI:10.1371/journal.pone.0247826

PLoS One. 2021 Mar 1;16(3):e0247480. doi: 10.1371/journal.pone.0247480. eCollection 2021.

ABSTRACT

Coronary heart disease, an inflammatory disease, is the leading cause of death globally. White blood cell counts (including monocytes) are easily available biomarkers of systemic inflammation. Monocyte subtypes can be measured by flow cytometry and classified into classical (CD14high, CD16neg), intermediate (CD14high, CD16+) and non-classical (CD14+, CD16high) with distinct functional properties. The goal of this study was to investigate the association of monocyte total count and its subtypes with cardiovascular risk groups defined by the Framingham Risk Score, which is used to estimate the 10-year risk of developing myocardial infarction or predict mortality following coronary heart disease. We also aimed to investigate whether monocyte counts are associated with relevant cardiovascular risk factors not included in the Framingham Risk Score, such as carotid atherosclerotic plaque and intima-media thickness. Our data came from the LIFE-Adult study, a population-based cohort study of 10,000 randomly selected participants in Leipzig, Germany. Data was gathered using self-administered questionnaires and physical examinations. Carotid plaques and intima-media thickness were measured using carotid artery sonography. Monocyte subtypes in blood were determined by 10-color flow cytometry for a total of 690 individuals. In a multivariate regression analysis adjusting for the risk factors BMI, intima-media thickness, presence of carotid plaques and diabetes mellitus, monocyte subtypes and total count were found to be significantly associated with the dichotomized Framingham Risk Score (≥10% versus <10%): Odds ratios [95% confidence interval] for monocyte subtypes: classical: 11.19 [3.79-34.26]; intermediate: 2.27 [1.11-4.71]; non-classical: 4.18 [1.75-10.20]; total: 14.59 [4.61-47.95]. In absence of prospective data, the FRS was used as a surrogate for CHD. Our results indicate that monocyte counts could provide useful predictive value for cardiovascular disease risk.

PMID:33647042 | DOI:10.1371/journal.pone.0247480

PLoS One. 2021 Mar 1;16(3):e0247274. doi: 10.1371/journal.pone.0247274. eCollection 2021.

ABSTRACT

INTRODUCTION: The coronavirus 2019 (COVID-19) has overwhelmed the health systems of several countries, particularly those within the African region. Notwithstanding, the relationship between health systems and the magnitude of COVID-19 in African countries have not received research attention. In this study, we investigated the relationship between the pervasiveness of the pandemic across African countries and their Global Health Security Index (GHSI) scores.

MATERIALS AND METHODS: The study included 54 countries in five regions viz Western (16); Eastern (18); Middle (8); Northern (7); and Southern (5) Africa. The outcome variables in this study were the total confirmed COVID-19 cases (per million); total recoveries (per million); and the total deaths (per million). The data were subjected to Spearman’s rank-order (Spearman’s rho) correlation to determine the monotonic relationship between each of the predictor variables and the outcome variables. The predictor variables that showed a monotonic relationship with the outcome were used to predict respective outcome variables using multiple regressions. The statistical analysis was conducted at a significance level of 0.05.

RESULTS: Our results indicate that total number of COVID-19 cases (per million) has strong correlations (rs >0.5) with the median age; aged 65 older; aged 70 older; GDP per capita; number of hospital beds per thousand; Human Development Index (HDI); recoveries (per million); and the overall risk environment of a country. All these factors including the country’s commitments to improving national capacity were related to the total number of deaths (per million). Also, strong correlations existed between the total recoveries (per million) and the total number of positive cases; total deaths (per million); median age; aged 70 older; GDP per capita; the number of hospital beds (per thousand); and HDI. The fitted regression models showed strong predictive powers (R-squared>99%) of the variances in the total number of COVID-19 cases (per million); total number of deaths (per million); and the total recoveries (per million).

CONCLUSIONS: The findings from this study suggest that patient-level characteristics such as ageing population (i.e., 65+), poverty, underlying co-morbidities-cardiovascular disease (e.g., hypertension), and diabetes through unhealthy behaviours like smoking as well as hospital care (i.e., beds per thousand) can help explain COVID-19 confirmed cases and mortality rates in Africa. Aside from these, other determinants (e.g., population density, the ability of detection, prevention and control) also affect COVID-19 prevalence, deaths and recoveries within African countries and sub-regions.

PMID:33647032 | DOI:10.1371/journal.pone.0247274