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Nevin Manimala Statistics

Glycemic deviation index: a novel method of integrating glycemic numerical value and variability

BMC Endocr Disord. 2021 Mar 19;21(1):52. doi: 10.1186/s12902-021-00691-z.

ABSTRACT

BACKGROUND: There are many continuous blood glucose monitoring (CGM) data-based indicators, and most of these focus on a single characteristic of abnormal blood glucose. An ideal index that integrates and evaluates multiple characteristics of blood glucose has not yet been established.

METHODS: In this study, we proposed the glycemic deviation index (GDI) as a novel integrating characteristic, which mainly incorporates the assessment of the glycemic numerical value and variability. To verify its effectiveness, GDI was applied to the simulated 24 h glycemic profiles and the CGM data of type 2 diabetes (T2D) patients (n = 30).

RESULTS: Evaluation of the GDI of the 24 h simulated glycemic profiles showed that the occurrence of hypoglycemia was numerically the same as hyperglycemia in increasing GDI. Meanwhile, glycemic variability was added as an independent factor. One-way ANOVA results showed that the application of GDI showed statistically significant differences in clinical glycemic parameters, average glycemic parameters, and glycemic variability parameters among the T2D groups with different glycemic levels.

CONCLUSIONS: In conclusion, GDI integrates the characteristics of the numerical value and the variability in blood glucose levels and may be beneficial for the glycemic management of diabetic patients undergoing CGM treatment.

PMID:33736619 | DOI:10.1186/s12902-021-00691-z

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Nevin Manimala Statistics

Genome-wide association study identifies new loci associated with risk of HBV infection and disease progression

BMC Med Genomics. 2021 Mar 18;14(1):84. doi: 10.1186/s12920-021-00907-0.

ABSTRACT

BACKGROUND: Recent studies have identified susceptibility genes of HBV clearance, chronic hepatitis B, liver cirrhosis, hepatocellular carcinoma, and showed the host genetic factors play an important role in these HBV-related outcomes.

METHODS: Collected samples from different outcomes of HBV infection and performed genotyping by Affymetrix 500 k SNP Array. GCTA tool, PLINK, and Bonferroni method were applied for analysis of genotyping and disease progression. ANOVA was used to evaluate the significance of the association between biomarkers and genotypes in healthy controls. PoMo, FST, Vcftools and Rehh package were used for building the racial tree and population analysis. FST statistics accesses 0.15 was used as a threshold to detect the signature of selection.

RESULTS: There are 1031 participants passed quality control from 1104 participants, including 275 HBV clearance, 92 asymptomatic persistence infection (ASPI), 93 chronic hepatitis B (CHB), 188 HBV-related decompensated cirrhosis (DC), 214 HBV-related hepatocellular carcinoma (HCC) and 169 healthy controls (HC). In the case-control study, one novel locus significantly associated with CHB (SNP: rs1264473, Gene: GRHL2, P = 1.57 × 10-6) and HCC (SNP: rs2833856, Gene: EVA1C, P = 1.62 × 10-6; SNP: rs4661093, Gene: ETV3, P = 2.26 × 10-6). In the trend study across progressive stages post HBV infection, one novel locus (SNP: rs1537862, Gene: LACE1, P = 1.85 × 10-6), and three MHC loci (HLA-DRB1, HLA-DPB1, HLA-DPA2) showed significant increased progressive risk from ASPI to CHB. Underlying the evolutionary study of HBV-related genes in public database, the derived allele of two HBV clearance related loci, rs3077 and rs9277542, are under strong selection in European population.

CONCLUSIONS: In this study, we identified several novel candidate genes associated with individual HBV infectious outcomes, progressive stages, and liver enzymes. Two SNPs that show selective significance (HLA-DPA1, HLA-DPB1) in non-East Asian (European, American, South Asian) versus East Asian, indicating that host genetic factors contribute to the ethnic disparities of susceptibility of HBV infection. Taken together, these findings provided a new insight into the role of host genetic factors in HBV related outcomes and progression.

PMID:33736632 | DOI:10.1186/s12920-021-00907-0

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Nevin Manimala Statistics

Combined Genotype Effects of TP53 and PAI-1 Polymorphisms in Breast Cancer Susceptibility: Multifactor Dimensionality Reduction and in silico Analysis

Hum Hered. 2021 Mar 18:1-10. doi: 10.1159/000514398. Online ahead of print.

ABSTRACT

INTRODUCTION: Breast cancer is a heterogeneous and multifactorial disease. TP53 and PAI-1 as important tumor suppressor genes are involved in the development, invasion, and metastasis of many cancers. This study’s objective was to demonstrate the combined genotype effects of these 2 genes by investigating their single nucleotide polymorphisms.

METHODS: In this case-control study, 200 individuals with breast cancer and 179 healthy individuals were studied. The genotypes were determined using the tetra-ARMS method. For data analysis, MDR, online javstat statistics package, and SPSS v.24 software were used. Also, in silico studies on the estimated effects of each of these polymorphisms were performed.

RESULTS: We showed a novel gene-gene interaction of these 2 genes and demonstrated a strong synergistic interaction for TP53/PAI-1, moderate synergistic interaction for PAI-1/age, and correlation for TP53/age. On the other hand, there was no association between the allelic and genotype frequency alone and in combination, with case-control status, using the parametric method, between TP53 and PAI-1.

DISCUSSION/CONCLUSION: Our findings suggest that the polymorphism of codon 72 of the TP53 gene was significantly associated with tumor stage (p < 0.023). In conclusion, we showed a gene-gene interaction between TP53 and PAI-1, in combination, using the MDR method.

PMID:33735891 | DOI:10.1159/000514398

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Nevin Manimala Statistics

Gene Therapy For Hemophilia B Using CB 2679d-GT: A Novel Factor IX Variant With Higher Potency Than Factor IX Padua

Blood. 2021 Mar 18:blood.2020006005. doi: 10.1182/blood.2020006005. Online ahead of print.

ABSTRACT

Sustained expression of therapeutic factor IX (FIX) levels has been achieved after adeno-associated viral (AAV) vector-based gene therapy in patients with hemophilia B. Nevertheless, patients are still at risk of vector dose-limiting toxicity, particularly liver inflammation justifying the need for more efficient vectors and a lower dosing regimen. A novel increased potency FIX (designated as CB 2679d-GT), containing three amino acid substitutions (R318Y, R338E, T343R), significantly outperformed the R338L-Padua variant after gene therapy. CB 2679d-GT demonstrated a statistically significant ~3-fold improvement in clotting activity when compared to R338L-Padua after AAV-based gene therapy in hemophilic mice. Moreover, CB 2679d-GT gene therapy showed a significantly reduced bleeding time (~5 to 8-fold) and total blood loss volume (~4-fold) compared with mice treated with the R338L-Padua, thus achieving a more rapid and robust hemostatic correction. FIX expression was sustained for at least 20 weeks with both CB 2679d-GT and R338L-Padua while immunogenicity was not significantly increased. This is a novel gene therapy study demonstrating the superiority of CB 2679d-GT highlighting its potential to obtain higher FIX activity levels and superior hemostatic efficacy following AAV directed gene therapy in hemophilia B patients than what is currently achievable with the R338L-Padua variant.

PMID:33735915 | DOI:10.1182/blood.2020006005

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Nevin Manimala Statistics

Causal analysis of fetal death in high-risk pregnancies

J Perinat Med. 2021 Mar 18. doi: 10.1515/jpm-2020-0352. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine the causes of fetal death among the stillbirths using two classification systems from 22 weeks of gestation in a period of three years in high-risk pregnancies. This is a retrospective observational study.

METHODS: The National Institute of Perinatal Health in Mexico City is a Level 3 care referral center attending high-risk pregnancies from throughout the country. The population consisted of patients with fetal death during a three-year period. Between January 2016 and December 2018, all stillbirths were examined in the Pathology Department by a pathologist and a medical geneticist. Stillbirth was defined as a fetal death occurring after 22 weeks of gestation.

RESULTS: Main outcome measures: Causal analysis of fetal death using the International Statistical Classification of Disease and Related Health Problems-Perinatal Mortality (ICD-PM) and initial causes of fetal death (INCODE) classification systems. A total of 297 stillborn neonates were studied. The distribution of gestational age in antepartum stillbirths (55.2%) showed a bimodal curve, 36% occurred between 24 and 27 weeks and 32% between 32 and 36 weeks. In comparison, the majority (86%) of intrapartum deaths (44.8%) were less than 28 weeks of gestation. Of the 273 women enrolled, 93 (34%) consented to a complete fetal autopsy. The INCODE system showed a present cause in 42%, a possible cause in 54% and a probable cause in 93% of patients.

CONCLUSIONS: The principal causes of antepartum death were fetal abnormalities and pathologic placental conditions and the principal causes of intrapartum death were complications of pregnancy which caused a premature labor and infections.

PMID:33735952 | DOI:10.1515/jpm-2020-0352

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Nevin Manimala Statistics

SARS-CoV-2 Lineages and Sub-Lineages Circulating Worldwide: A Dynamic Overview

Chemotherapy. 2021 Mar 18:1-5. doi: 10.1159/000515340. Online ahead of print.

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan, China, in early December 2019 has rapidly widespread worldwide, becoming one of the major global public health issues of the last centuries. Key Messages: Over the course of the pandemic, due to the advanced whole-genome sequencing technologies, an unprecedented amount of genomes have been generated, providing invaluable insights into the ongoing evolution and epidemiology of the virus during the pandemic. Therefore, this large amount of data played an important role in the SARS-CoV-2 mitigation and control strategies. Key Messages: The active monitoring and characterization of the SARS-CoV-2 lineages circulating worldwide is useful for a more specific diagnosis, better care, and timely treatment. In this review, a concise characterization of all the lineages and sub-lineages circulating and co-circulating across the world has been presented in order to determine the magnitude of the SARS-CoV-2 threat and to better understand the virus genetic diversity and its dispersion dynamics.

PMID:33735881 | DOI:10.1159/000515340

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Nevin Manimala Statistics

Analysis of Ascites-Challenged Blood in Patients with Liver Cirrhosis Using Rotational Thromboelastometry: How Robust Is the Evidence on Ascites-Attributed Fibrinolysis?

Digestion. 2021 Mar 18:1-6. doi: 10.1159/000513715. Online ahead of print.

ABSTRACT

INTRODUCTION: For over 30 years, ascites has been postulated to facilitate fibrinolysis in patients with liver cirrhosis. In contrast to previous research employing conventional coagulation tests, this study aimed to characterize hemostatic interactions between blood and ascites using the rotational thromboelastometry (ROTEM).

METHODS: Blood samples – pure or mixed with ascites in a ratio of 1:1 – from cirrhotic patients (n = 10) were subjected to ROTEM analysis. In addition, a negative control group was built with cirrhotic patients (n = 10) whose blood was mixed with physiologic sodium chloride (0.9% NaCl) solution in a ratio of 1:1. Subsequently, ROTEM measurements were subjected to statistical analysis.

RESULTS: During ascites challenge, clotting time (CT, measured in seconds) was significantly prolonged in EXTEM (blood: 70.40 ± 20.40 vs. ascites/blood: 109.8 ± 47.7) and APTEM (blood: 66.50 ± 14.55 vs. ascites/blood: 138.7 ± 105.8), likely reflecting a dilution effect. However, CT in INTEM remained unchanged, suggesting a sustained intrinsic pathway function. Maximal clot firmness (measured in millimeters) in FIBTEM decreased significantly (blood: 14.70 ± 9.55 vs. ascites/blood: 6.00 ± 5.66), thus indicating depletion of fibrinogen in ascites. Strikingly, maximum lysis (measured in %) significantly decreased in EXTEM (blood: 9.30 ± 2.79 vs. ascites/blood: 5.50 ± 2.84), APTEM (blood: 8.50 ± 3.10 vs. ascites/blood: 5.60 ± 2.88), and INTEM (blood: 7.50 ± 2.27 vs. ascites/blood: 5.10 ± 3.48).

CONCLUSIONS: ROTEM provided new evidence that ascites may not primarily induce fibrinolysis in cirrhotic patients. This finding seems to be of significant importance for the clinical management of cirrhotic patients experiencing complications, for example, abdominal hemorrhage after liver biopsy or paracentesis; here, replacement of prothrombin complex concentrates and/or fibrinogen concentrates may prove more beneficial than the use of fresh frozen plasma or antifibrinolytic drugs.

PMID:33735883 | DOI:10.1159/000513715

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Nevin Manimala Statistics

Applying the Exoscope to Lacrimal Surgery: Preliminary Experience

ORL J Otorhinolaryngol Relat Spec. 2021 Mar 18:1-6. doi: 10.1159/000513529. Online ahead of print.

ABSTRACT

PURPOSE: The aim of the study was to investigate the role of the exoscope as an assisting tool in endoscopic dacryocystorhinostomy (e-DCR).

MATERIALS AND METHODS: In this observational retrospective study, the application of the VITOM® exoscope was studied in a group of 21 patients undergoing mono- or bilateral DCR. The primary endpoint was to evaluate resolution of symptoms (epiphora/dacryocystitis) at the 6-month follow-up and time for surgery. Qualitative features of the exoscope (intraoperative view of the surgical field) and comparison with the typical setting for DCR were analyzed as secondary endpoints. A questionnaire was administered to surgical team members (ENT surgeon, ophthalmologist, and scrub nurse) to evaluate the perceived quality of this new technology (12 items valued as “good” = 2, “acceptable” = 1, and “not acceptable” = 0). A questionnaire score of 24 out of 24 was valued as “completely approved,” score 20-23 as “moderately approved,” and score ≤19 as “weakly approved.” Patients were divided into 3 consecutive groups, and questionnaire scores by each team member were analyzed for tendencies. Statistical analysis was performed to test significance at p < 0.05. Local Ethical Committee approval was obtained.

RESULTS: No significant differences were found between exoscope-set DCR and classic setting for concerned patient outcomes (failure rate: 3.2 vs. 3.8%, respectively, p = 0.896) and mean time for surgery (20′ vs. 23′, respectively, p = 0.091). The exoscope was valued by surgical team members as “completely approved” in 55.5% of cases, “moderately approved” in 39.7%, and “weakly approved” in 4.8%. Questionnaire scores by the ENT, ophthalmologist, and scrub nurse showed an average increase in the 3 consecutive groups (p = 0.119, p = 0.024, and p < 0.001, respectively).

CONCLUSIONS: The exoscope is a new tool that may support e-DCR. It has no effects on symptom outcomes (epiphora/dacryocystitis) and time for surgery compared to classic DCR. Based on self-perception, this new technology was accepted by all team members.

PMID:33735886 | DOI:10.1159/000513529

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Nevin Manimala Statistics

Analysis of Three Mutations in Italian Strains of SARS-CoV-2: Implications for Pathogenesis

Chemotherapy. 2021 Mar 18:1-5. doi: 10.1159/000515342. Online ahead of print.

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus initially detected in Wuhan in December 2019, responsible for coronavirus disease 2019 (COVID-19), a respiratory syndrome currently affecting >220 countries around the world, with >80 million cases registered and >1.8 million deaths.

OBJECTIVE: As several vaccines are still being developed and 2 have been approved, it is particularly important to perform evolutionary surveillance to identify mutations potentially affecting vaccine efficacy.

METHODS: DynaMut server has been used to evaluate the impact of the mutation found on SARS-CoV-2 isolates available on GISAID.

RESULTS: In this article, we analyze whole genomes sequenced from Italian patients, and we report the characterization of 3 mutations, one of which presents in the spike protein.

CONCLUSION: The mutations analyzed in this article can be useful to evaluate the evolution of SARS-CoV-2.

PMID:33735872 | DOI:10.1159/000515342

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Nevin Manimala Statistics

The Effect of Saffron Consumption on Liver Function: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials

Complement Med Res. 2021 Mar 18:1-10. doi: 10.1159/000515003. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The present systematic review and meta-analysis of randomized controlled trials aimed to determine the effects of saffron supplementation on liver function tests among adults.

METHODS: Electronic databases including PubMed, ISI Web of Science, and Scopus were searched up to January 2021. The risk of bias in individual studies was assessed using the Cochrane Collaboration tool. The overall estimates and their 95% CIs were calculated using random-effects models. Egger’s test and Begg’s rank-correlation were run to assess the presence of publication bias. p < 0.05 was considered statistically significant.

RESULTS: A total of 12 trials involving 608 participants were included in this systematic review and meta-analysis. Saffron supplementation had no significant effect on liver function tests including aspartate transaminase (AST) (weighted mean difference [WMD] = 0.23 U/L; 95% CI -2.22 to 2.69; p = 0.851; I2 = 74.0%), alanine aminotransferase (ALT) (WMD = -1.49 U/L; 95% CI -3.84 to 0.86; p = 0.213; I2 = 60.2%), and alkaline phosphatase (ALP) (WMD = -0.70 U/L; 95% CI -11.35 to 9.95; p = 0.898; I2 = 40.8%) compared to placebo.

CONCLUSION: Based on what was discussed, it seems that saffron supplementation could not improve liver function tests including AST, ALT, and ALP among the adult population. Further clinical trials with larger sample size, longer duration, and higher doses of saffron should be conducted exclusively among patients with liver dysfunction to elucidate the beneficial role of saffron consumption on liver function.

PMID:33735877 | DOI:10.1159/000515003