Nevin Manimala

Eur Rev Med Pharmacol Sci. 2021 Feb;25(4):2079-2092. doi: 10.26355/eurrev_202102_25113.

ABSTRACT

OBJECTIVE: Omega-3 fatty acids are commonly used as a lipid-lowering agent or dietary supplement for the purpose of prevention of cardiovascular diseases. However, even large-scale clinical trials have not shown significant results demonstrating clear clinical benefits in cardiovascular diseases. Thus, this umbrella review aims to summarize and evaluate the evidence of clinical effects of omega-3 fatty acids supplementation on cardiovascular outcomes through comprehensive analyses of previous randomized controlled trials (RCTs) or observational cohort studies.

MATERIALS AND METHODS: We conducted relevant publication search in PubMed, Embase, and Cochrane Database of Systematic Reviews. We retrieved and analyzed 3,298 articles published until August 28th, 2019.

RESULTS: We identified 29 relevant articles and analyzed 83 meta-analyses of RCTs or cohort studies therefrom. As a result, we identified 12 cardiovascular outcomes that are related to omega-3 fatty acids supplementation. Among them, total mortality from major cardiovascular causes (RR 0.92, 95% CI 0.86 to 0.98) had significant inverse associations, and moreover, statistical significances were maintained even in subgroup analysis of large-scale RCTs including more than 1,000 patients (RR 0.94, 95% CI 0.88 to 0.99).

CONCLUSIONS: Our umbrella review study shows that omega-3 fatty acids supplementation have a clinical benefit in reducing mortality from cardiovascular causes. However, many studies still have shown conflicting results, and therefore, further studies will be needed to verify the clinical benefit of omega-3 supplementation.

PMID:33660821 | DOI:10.26355/eurrev_202102_25113

Eur Rev Med Pharmacol Sci. 2021 Feb;25(4):2021-2030. doi: 10.26355/eurrev_202102_25105.

ABSTRACT

OBJECTIVE: Neurocognitive impairment is one of the most common manifestations of multiple sclerosis (MS). However, the pathophysiology of this issue is still poorly understood. The objective of this study is to investigate the relationship between vitamin D levels and cognitive function in patients with MS as assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB).

PATIENTS AND METHODS: This was a cross-sectional, case-control study; the subjects were 39 Saudi patients diagnosed with MS. For all participants, demographic information, including age, sex, and educational level, was collected. Participants were also evaluated using the disease steps scale and the PHQ-9 scale. Their vitamin D levels were assessed, and the participants completed a computerized cognitive assessment using the CANTAB.

RESULTS: From the total sample of 39 patients with MS, 31 (79.5%) were female. Physical disability due to MS was insignificant in 25 (64.1%) of the subjects and significant in 14 (35.9%). Seventeen (43.6%) of the participants had normal vitamin D levels; 22 (56.4%) had low vitamin D levels. The MS patients had lower MOT mean errors than the control group, and this difference was statistically significant (t = -4.313, p < 0.01). Moreover, the scores of the two groups for all subcategories of the memory domain were different at statistically significant levels. Furthermore, the control group had higher PAL total errors (adjusted), PAL total errors (6 shapes, adjusted), and PRM percent correct than the MS patients (p < 0.01). The control group also achieved lower scores on SWM between errors and SWM strategy than the MS patients (p < 0.01). The MOT mean error was found to correlate with the disease steps score (r = 0.394, p < 0.05) and with significant physical disability (r = 0.457, p< 0.01). In the memory domain, PAL total errors (adjusted) correlated with age (r = 0.381, p < 0.05), SWM between errors correlated with age at onset of disease (r = 0.345, p < 0.05), and vitamin D level (r = 0.335, p < 0.05) and SWM strategy correlated with the number of relapses in the past 12 months (r = -0.355, p < 0.05).

CONCLUSIONS: Cognitive performance was impaired in patients with MS. Vitamin D deficiency, a potentially modifiable risk factor, independently predicted cognitive impairment in MS patients.

PMID:33660814 | DOI:10.26355/eurrev_202102_25105

Eur Rev Med Pharmacol Sci. 2021 Feb;25(4):1997-2002. doi: 10.26355/eurrev_202102_25101.

ABSTRACT

OBJECTIVE: Kallikrein-8 (KLK8) is a secreted serine protease related to learning and memory. Evidence has confirmed the important role of KLK8 in neuroplasticity. However, the role of KLK8 in vascular dementia (VaD) is unclear.

PATIENTS AND METHODS: The study recruited 88 VaD patients and 72 normal controls. All subjects were tested for cognitive function by Mini-Mental State Examination (MMSE) upon admission, and their demographic and biochemical data were collected. A sandwich Enzyme-Linked Immunosorbent Assay (ELISA) test was used to detect serum KLK8 levels. The demographic and biochemical data of the two groups of subjects were compared. Spearman’s correlation and multivariate regression analysis were used to determine whether serum KLK8 in VaD patients is a risk factor for cognitive function.

RESULTS: A total of 88 VaD patients and 72 controls with normal cognitive function were recruited and divided into VaD group and control group. Except for TT3 (p=0.002), there was no statistically significant difference in other demographic and biochemical data between the two groups (p>0.05). The results of ELISA indicated that the serum KLK8 in VaD patients was significantly higher than that of the control population (p<0.001). Spearman correlation analysis indicated that the serum KLK8 in VaD was significantly inversely correlated with the MMSE score. The results of Spearman’s correlation analysis showed that the serum KLK8 level of VaD was significantly inversely correlated with the MMSE (r=-0.305, p=0.017). After correcting for interference factors, the correlation between the two is still significant (β=0.398, p=0.024).

CONCLUSIONS: Serum KLK8 may be an independent risk factor affecting the cognitive function of VaD, which is worthy of further research.

PMID:33660811 | DOI:10.26355/eurrev_202102_25101

Eur Rev Med Pharmacol Sci. 2021 Feb;25(4):1936-1943. doi: 10.26355/eurrev_202102_25093.

ABSTRACT

OBJECTIVE: To investigate the value of differential diagnosis between acinic cell carcinoma (ACC) and pleomorphic adenoma (PA) using the quantitative parameters of contrast-enhanced ultrasound (CEUS).

PATIENTS AND METHODS: Twenty-two ACC and 98 PA were retrospectively analyzed. These patients had been examined via routine pre-surgical two-dimensional ultrasound and CEUS. The examination results were confirmed by biopsy pathology. Qontrast 4.0 imaging analysis software was applied to obtain the maximum intensity (PEAK), time to peak (TTP), regional blood volume (RBV), regional blood flow (RBF), maximum signal intensity (SImax) and mean signal intensity (SImean) through quantitative analysis. The differences between ACC and PA were compared regarding the conventional ultrasound images and the quantitative parameters of CEUS. ROC curves were drawn to evaluate the diagnostic value of these parameters.

RESULTS: There were no statistically significant differences between salivary gland ACC and PA in the manifestations of conventional two-dimensional ultrasound examination regarding morphology, internal echo and the boundary (p > 0.05). However, there were significant differences in PEAK, RBV, RBF, SImax and SImean between ACC and PA (p < 0.05). Additionally, the five quantitative parameters of CEUS were all highly accurate diagnostic indicators. The maximum area under the curve of each parameter was 0.888, sensitivity 72.6%, specificity 90.9% and accuracy 81.8%.

CONCLUSIONS: The quantitative parameters of CEUS are helpful for differentially diagnosing salivary ACC and PA.

PMID:33660803 | DOI:10.26355/eurrev_202102_25093

Eur Rev Med Pharmacol Sci. 2021 Feb;25(4):1881-1889. doi: 10.26355/eurrev_202102_25083.

ABSTRACT

OBJECTIVE: The purpose of this study was to review the effectiveness of immune checkpoint inhibitors (ICIs) in the first-line treatment of advanced non-small cell lung carcinoma with wild-type epidermal grow factor receptor (EGFR) or anaplastic lymphoma kinase.

MATERIALS AND METHODS: After a standard literature search, we identified all randomized studies published on this issue. Our first inclusion criterion was the use of pembrolizumab, nivolumab, atezolizumab or durvalumab in the treatment arm versus chemotherapy in the control arm. The second criterion was the availability of information on overall survival at 2 years. The restricted mean survival time (RMST) was used to analyze the survival curves and rank the treatments.

RESULTS: From the eligible studies, we selected 5 randomized trials that met our inclusion criteria. These trials studied a total of 11 cohorts of patients in whom the treatment arm received ICI as monotherapy (n=3) or in combination with either chemotherapy (n=2) or other monoclonal antibodies (n=1). All the control groups (n=5) received chemotherapy. Pembrolizumab (alone or in combination) showed improvement in overall survival compared with controls, but with borderline statistical significance. Nivolumab, atezolizumab and durvalumab failed to demonstrate any survival advantage. Overall, the RMSTs provided more conservative results than those previously reported using the hazard ratio. In comparing the values of RMST across treatments, pembrolizumab combined with chemotherapy ranked first.

CONCLUSIONS: Our results summarized the efficacy of these treatments and showed that only pembrolizumab can have a role as the first-line treatment of NSCLC. These findings are at variance with those previously reported using the hazard ratio as the outcome measure.

PMID:33660798 | DOI:10.26355/eurrev_202102_25083

Nucleic Acids Res. 2021 Feb 28:gkab122. doi: 10.1093/nar/gkab122. Online ahead of print.

ABSTRACT

Sequence-based analysis and prediction are fundamental bioinformatic tasks that facilitate understanding of the sequence(-structure)-function paradigm for DNAs, RNAs and proteins. Rapid accumulation of sequences requires equally pervasive development of new predictive models, which depends on the availability of effective tools that support these efforts. We introduce iLearnPlus, the first machine-learning platform with graphical- and web-based interfaces for the construction of machine-learning pipelines for analysis and predictions using nucleic acid and protein sequences. iLearnPlus provides a comprehensive set of algorithms and automates sequence-based feature extraction and analysis, construction and deployment of models, assessment of predictive performance, statistical analysis, and data visualization; all without programming. iLearnPlus includes a wide range of feature sets which encode information from the input sequences and over twenty machine-learning algorithms that cover several deep-learning approaches, outnumbering the current solutions by a wide margin. Our solution caters to experienced bioinformaticians, given the broad range of options, and biologists with no programming background, given the point-and-click interface and easy-to-follow design process. We showcase iLearnPlus with two case studies concerning prediction of long noncoding RNAs (lncRNAs) from RNA transcripts and prediction of crotonylation sites in protein chains. iLearnPlus is an open-source platform available at https://github.com/Superzchen/iLearnPlus/ with the webserver at http://ilearnplus.erc.monash.edu/.

PMID:33660783 | DOI:10.1093/nar/gkab122

Faraday Discuss. 2021 Mar 4. doi: 10.1039/c9fd00122k. Online ahead of print.

ABSTRACT

Density functional theory (DFT) has been considered as a powerful tool for the identification of reaction mechanisms. However, it is still unclear whether the error of DFT calculations would lead to mis-identification of mechanisms. Here, taking the hydrogenation of acetylene and 1,3-butadiene as model reactions and employing a well-trained Bayesian error estimation functional with van der Waals correlation (BEEF-vdW), we try to estimate the error of DFT calculation results statistically, and therefore predict the reliability of the hydrogenation mechanisms identified. With an ensemble of 2000 functionals obtained around the BEEF-vdW functional as well as a descriptor developed to represent the possibility of different mechanisms, we found that the non-Horiuti-Polanyi mechanism is preferred on Ag(211) and Au(211), while the Horiuti-Polanyi mechanism is dominant on Cu(211). We further discovered that the descriptor is linearly correlated with the adsorption energies of reaction intermediates during acetylene and butadiene hydrogenation, and the hydrogenation of strongly adsorbed species are more likely to follow the Horiuti-Polanyi mechanism. We found the probability of following the non-HP mechanism obeys the order Cu(211) < Au(211) < Ag(211). Our work gives a more comprehensive explanation for the mechanisms of coinage metal catalyzed hydrogenation reactions, and also provides more theoretical insights into the development of new high-performance catalysts for selective hydrogenation reactions.

PMID:33660703 | DOI:10.1039/c9fd00122k

Pediatr Crit Care Med. 2021 Mar 5. doi: 10.1097/PCC.0000000000002698. Online ahead of print.

ABSTRACT

OBJECTIVES: Anticoagulation plays a key role in the management of children supported with extracorporeal membrane oxygenation. However, the ideal strategy for monitoring anticoagulation remains unclear. Our objective was to evaluate the utility of laboratory measures of anticoagulation in pediatric extracorporeal membrane oxygenation.

DESIGN: Retrospective cohort study.

SETTING: Quaternary care academic children’s hospital.

PATIENTS: Children in a noncardiac PICU cannulated to extracorporeal membrane oxygenation in 2010-2016.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Demographic data, laboratory values, and heparin doses were extracted from the enterprise data warehouse. Primary diagnoses, indications for cannulation, hemorrhagic and thrombotic complications, and survival outcomes were abstracted from the local registry used for Extracorporeal Life Support Organization reporting. Statistical models accounting for repeated measures using generalized estimating equations were constructed to evaluate correlations between heparin doses and laboratory values; among laboratory values; and between heparin dose or laboratory values and clinical outcomes. One hundred thirty-three unique patients-78 neonates and 55 older patients-were included in the study. There was no significant association between antifactor Xa level, activated partial thromboplastin time, activated clotting time, or heparin dose with hemorrhage or thrombosis (odds ratio ≅ 1 for all associations). There was weak-to-moderate correlation between antifactor Xa, activated partial thromboplastin time, and activated clotting time in both neonates and older pediatric patients (R2 < 0.001 to 0.456). Heparin dose correlated poorly with laboratory measurements in both age groups (R2 = 0.010-0.063).

CONCLUSIONS: In children supported with extracorporeal membrane oxygenation, heparin dose correlates poorly with common laboratory measures of anticoagulation, and these laboratory measures correlate poorly with each other. Neither heparin dose nor laboratory measures correlate with hemorrhage or thrombosis. Further work is needed to identify better measures of anticoagulation in order to minimize morbidity and mortality associated with extracorporeal membrane oxygenation.

PMID:33660700 | DOI:10.1097/PCC.0000000000002698

Nucl Med Commun. 2021 Mar 1. doi: 10.1097/MNM.0000000000001374. Online ahead of print.

ABSTRACT

PURPOSE: This retrospective study aimed to analyzed the F-18 fluorodeoxyglucose PET/computed tomography (F-18 FDG PET/CT) features of pulmonary sclerosing pneumocytoma (PSP) to improve the understanding and preoperative diagnostic efficacy of this rare disorder.

METHODS: FDG PET/CT images from 11 patients with 22 lesions (including one patient with 12 lesions) proven PSP in our hospital were reviewed. We summarized the PET/CT features of PSP and analyzed the correlation between FDG uptake and tumor size.

RESULTS: PET/CT imaging revealed all tumors located in each lobe of the two lungs randomly. All 22 tumors were round or oval nodules; 15 had smooth margins, six were lobulated, six were calcified, and one had a ground-glass halo sign. The mean diameter of these tumors was 19.2 ± 7.8 mm (range: 8-34 mm); the mean maximum standardized uptake value (SUVmax) was 2.8 ± 1.3 (range: 1.1-7.4). Sixteen of the lesions exhibited mild to moderate FDG uptake (mean SUVmax 2.3 ± 0.6), and six of the lesions exhibited intense FDG uptake (mean SUVmax 4.3 ± 1.6). A positive correlation was observed between FDG uptake and tumor size (P <0.05).

CONCLUSION: Single round or ovoid soft-tissue lesions with smooth margins, and mild to moderate FDG uptake on PET/CT images in middle-aged females, suggest a possible diagnosis of PSP. For some atypical cases with intense FDG uptake, a diagnosis of PSP also can be considered. A statistically significant positive correlation was found between SUVmax and PSP lesion size in our study.

PMID:33660695 | DOI:10.1097/MNM.0000000000001374

Nucl Med Commun. 2021 Mar 1. doi: 10.1097/MNM.0000000000001383. Online ahead of print.

ABSTRACT

BACKGROUND: Transarterial radioembolization (TARE) is widely used for the treatment of hepatocellular carcinoma (HCC), but early treatment response can be very difficult to assess. The aim was to evaluate 18F-fluorocholine PET/computed tomography (CT) to assess the treatment response in patients with intermediate or locally advanced HCC.

METHODS: Between March 2019 and July 2020, nine HCC patients treated with TARE, who underwent PET/CT at baseline and 1 month after treatment, were enrolled. The maximum, mean (SUVmean), and peak (SUVpeak) standardized uptake value (SUV), SUV normalized by lean body mass (SUL), and total lesion glycolysis (TLG) were measured. Statistical analysis used the Mann-Whitney test to evaluate the differences in parameters between responders (partial and complete response) and nonresponders (stable or progressive disease) at the 6-month follow-up, according to the modified Response Evaluation Criteria in Solid Tumors.

RESULTS: Three patients were nonresponders (progressive disease and stable disease) and six were responders. Delta SUVmean, delta SUL, and delta TLG could predict an early response (P = 0.02, P = 0.04, and P = 0.02, respectively). None of the pre-therapeutic parameters were correlated with the response. Post-therapeutic SUL, SUVmean, TLG, and SUVpeak were also predictive of the response.

CONCLUSIONS: Our preliminary results showed that changes in certain metabolic parameters (from baseline PET to 1-month PET) are predictive of the response to TARE in HCC (Delta SUVmean, delta TLG, and delta SUL). The absence of post-treatment inflammation could lead to a better prediction than MRI evaluation. This study suggests that 1-month 18F-choline PET/CT could modify the clinical management predicting responders.

PMID:33660694 | DOI:10.1097/MNM.0000000000001383