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Nevin Manimala Statistics

The clinical characteristics and prognosis of cytogenetically normal AML with single mutations of CEBPA

Int J Lab Hematol. 2021 Jul 3. doi: 10.1111/ijlh.13612. Online ahead of print.

ABSTRACT

INTRODUCTION: CEBPA mutation is a common mutation in normal karyotype AML. CEBPAdm AML has been recognized as a separate entity, but there is still controversy to the prognosis of CEBPAsm patients.

METHODS: A total of 151 newly diagnosed cytogenetically normal AML patients treated at the Second Hospital Center of Shanxi Medical University from February 2017 to December 2019 were the subjects of the study. According to the number of mutations in the CEBPA gene, the patients were divided into three groups, CEBPAsm, CEBPAdm, and CEBPAwt patients. The clinical characteristics, gene mutations, response, and prognosis were retrospectively compared among the three groups.

RESULTS: CEBPAsm patients had lower hemoglobin values compared to CEBPAdm (P = .049). There was no statistical difference between the CEBPAsm cases and the CEBPAdm cases in the mutation types and the distribution of mutation regions (P > .050). Compared with CEBPAdm, cases with CEBPAsm were more likely associated with multiple other gene mutations (P = .023). Patients with CEBPAdm had a higher CR, ORR, and OS than those CEBPAwt (P < .050). CEBPAsm patients had a similar OS with CEBPAdm and CEBPAwt patients (P = .281). These CEBPAsm patients with VAF<30% had lower OS than the patients with VAF≥30%. FLT3-ITD mutations could reduce CEBPAsm patients’ OS (P = .019).

CONCLUSION: Our data first highlighted the impact of CEBPAsm VAF on OS, and the results showed the lower the VAF was, the shorter the OS tended to. The VAF of CEBPAsm could provide specific significance in some extent for the prognosis of patients.

PMID:34216417 | DOI:10.1111/ijlh.13612

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Nevin Manimala Statistics

Endometrial gene expression profiling of recurrent implantation failure after in vitro fertilization

Mol Biol Rep. 2021 Jul 3. doi: 10.1007/s11033-021-06502-x. Online ahead of print.

ABSTRACT

Recurrent implantation failure (RIF) is diagnosed when good-quality embryos repeatedly fail to implant after transfer in several in vitro fertilization (IVF) treatment cycles. Different expression profiles in maternal mRNAs could be referring to many diseases including RIF. This study aimed to reveal significantly dysregulated selected genes expression between healthy fertile women and RIF patients in the implantation window days of the natural menstrual cycle. MME, WWC1, TNC, and FOXP3 genes were chosen as target genes regarding their possible relations with the implantation process. Pathways with these genes were identified and the relationship between these pathways and RIF was investigated. In this study, the endometrial biopsy samples were collected in the secretory phase (cycle day 20-24) of the menstrual cycle from RIF patients (n = 34) and healthy fertile controls (n = 34). After “Pathway and network-oriented GWAS analysis” (PANOGA) and “Kyoto Encyclopedia of Genes and Genomes” (KEGG) pathway analysis; “Membrane Metalloendopeptidase” (MME), “WW and C2 Domain Containing 1” (WWC1), “Tenascin C” (TNC) and “Forkhead Box P3” (FOXP3) genes were chosen as target genes by regarding their possible relation with implantation process. Detection of differences in mRNA expressions between the control group and RIF patients has been performed with the droplet digital PCR (ddPCR) method. Results of the study showed that MME and WWC1 genes expression levels are significantly (p < 0,05) up-regulated 4.9 and 5.2 times respectively and TNC gene expression level is significantly (p < 0,05) down-regulated 9 times in the RIF samples compared to the control group. However, no statistically significant difference was observed between the patient group and the control group in the expression of the FOXP3 gene (p < 0.05). Changes are observed in the expression of the renin-angiotensin system pathway in which the MME gene is involved in the implantation process. The increase in MME gene expression can be speculated to cause implantation failure by restricting the invasion of trophoblast cells. Increasing WWC1 gene expression in the Hippo signaling pathway inhibits “Yes-associated protein 1” (YAP) expression, which is a transcriptional cofactor. Inhibition of YAP protein expression may impair the implantation process by causing the failure of endometrial decidualization. The TNC gene is located in the focal adhesion pathway and this pathway reduces cell adhesion on the endometrial surface to facilitate the attachment of the embryo to the endometrium. The reason for implantation failure might be that the intercellular connections are not suitable for implantation as a result of decreased expression of the focal adhesion pathway in which the TNC gene is effective. Considering the relations between the pathways of the target genes and the implantation process, changes in the expression of target genes might be a cause of RIF.

PMID:34216338 | DOI:10.1007/s11033-021-06502-x

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Nevin Manimala Statistics

Seasonal variations of macro-, micro-, and toxic elements in tissues of vimba bream (Vimba vimba) from the Danube River near Belgrade, Serbia

Environ Sci Pollut Res Int. 2021 Jul 3. doi: 10.1007/s11356-021-15073-0. Online ahead of print.

ABSTRACT

Vimba bream (Vimba vimba) individuals were collected from the Danube River near Belgrade, from May 2016 to May 2017. Samples of muscle and liver tissue were analyzed for concentrations of 25 elements (macro-, micro-, and toxic elements) using inductively coupled plasma optical emission spectrometry (ICP-OES). For both tissues, the highest concentrations of most elements were observed in late spring/early summer (months of May and June). Majority of statistically significant correlations between elements were positive in both tissues. Contributions of Ca, K, and Mg to human diet were in a similar range. The lowest contribution of all macroelements was observed for Na, while the contribution of Se was well above the recommended dietary allowance for this element. Levels of detected elements were well below MAC values prescribed by national and international regulations. The highest value of Hg liver/muscle index (>1) was observed in August, which could indicate a higher contamination of the sampling location in that month. Se:Hg molar ratio never drops below 1, which could indicate that Hg toxicity is prevented. THQ values showed little variation thought the year and were well below the threshold of 1, with the exception of THQ for Al in May (0.92). This element also strongly affects the hazard index.

PMID:34216343 | DOI:10.1007/s11356-021-15073-0

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Nevin Manimala Statistics

New methods for the additive hazards model with the informatively interval-censored failure time data

Biom J. 2021 Jul 3. doi: 10.1002/bimj.202000288. Online ahead of print.

ABSTRACT

The additive hazards model is one of the most commonly used models for regression analysis of failure time data and many inference procedures have been developed for it under various situations. In particular, Wang et al. (2018a, Computational Statistics and Data Analysis, 125, 1-9) discussed the situation where one observes informatively interval-censored data and proposed a likelihood estimation approach. However , it involves estimation of the unknown baseline cumulative hazard function and thus may be time-consuming . Corresponding to this, we propose two new procedures, an estimating equation-based one and an empirical likelihood-based one, and both do not need estimation of the cumulative hazard function and can be easily implemented. The asymptotic properties of the proposed methods are established and an extensive simulation study suggests that they work well in practical situations. An application is also provided.

PMID:34216403 | DOI:10.1002/bimj.202000288

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Nevin Manimala Statistics

Strain and strain rate echocardiographic imaging predict occurrence of atrial fibrillation in post-coronary artery bypass grafting patients

Egypt Heart J. 2021 Jul 3;73(1):62. doi: 10.1186/s43044-021-00188-z.

ABSTRACT

BACKGROUND: Atrial fibrillation (AF) occurs very frequently after coronary artery bypass grafting (CABG); it occurs in about 20-edictors can be used for the dedicatio40% of patients. It is associated with several adverse events. This study aimed to extrapolate a predictor for postoperative atrial fibrillation (POAF) occurrence which is reproducible and simple to be a part of routine echocardiography screening before CABG. This study included 89 patients scheduled for isolated coronary artery bypass surgery. History, clinical examination, and complete 2D echocardiography with LA speckle tracking analysis were done preoperatively. Patients were then followed up post-surgery for incidence of AF till discharge from the hospital. The patients were divided into 2 groups according to POAF occurrence.

RESULTS: Patients who developed postoperative AF had older age (P = 0.0032) and longer hospital stay (P = 0.021) and higher stroke incidence but statistically non-significant (14.3% vs 3.3%). The POAF patients showed less peak atrial longitudinal strain (PALS) value than non-POAF patients. The left atrial strain rate values showed a significant difference with the lower left atrial systolic strain rate and less negative (higher) early diastolic strain rate and late diastolic strain rate. After multivariate logistic regression analysis, the independent predictors for POAF were PALS (OR 0.770, 95% CI 0.627-0.946), late LA diastolic strain rate (LASRa) (OR 3.476, 95% CI 1.207-12.186), and age (OR 1.181, 95% CI 1.011-1.379).

CONCLUSION: Preoperative LA global strain assessed by 2D speckle tracking analysis could be helpful as a predictor for AF post-CABG surgery, and identification of these patients may reduce its morbidity and mortality. The study suggested PALS value less than 29.8 to be a predictor for the occurrence of POAF.

PMID:34216305 | DOI:10.1186/s43044-021-00188-z

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Sliding shape extraocular muscle transposition with plication: Long-term results

Int Ophthalmol. 2021 Jul 3. doi: 10.1007/s10792-021-01932-9. Online ahead of print.

ABSTRACT

AIM: This study aims to evaluate the long-term results of sliding shape extraocular muscle transposition, which is a novel operation method of delivering both vascular protection and strengthening of the muscles and transposition of the muscles.

METHODS: The patients’ files were scanned retrospectively. All patients underwent a complete eye examination in addition to motility examination, both preoperatively and postoperatively. Patients were followed up for at least 1 year. Pre- and postoperative deviation measurement values and transposition effects were compared statistically. The two parameters were evaluated separately.

RESULTS: In patients where 7-mm (or greater) resection was planned, the complete muscle widening transposition procedure was successful. Only two-thirds of transpositions could be achieved in patients who underwent less than 7 mm of strengthening. There was no anterior segment ischemia in the patients who underwent three rectus’ muscle surgery in the same eye. Transposition effects were perfect in those whose vertical deviation was not due to monocular elevation deficiency. While resection effect was excellent in those MED (monocular elevation deficiency) and CEOMF (congenital extraocular muscle fibrosis) cases, transposition effects were limited but found at similar rates as with the standard resection and transposition procedures in CCDD (congenital cranial dis-innervation diseases) (R2-1).

CONCLUSION: Even transposition effects were limited in CCDD. ‘Sliding shape’ design extraocular muscle plication was found to be a simple, safe, and effective procedure for patients who needed resection and transposition operation.

PMID:34216321 | DOI:10.1007/s10792-021-01932-9

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Clinical and Microbiologic Efficacy and Safety of Imipenem/Cilastatin/Relebactam in Complicated Infections: A Meta-analysis

Infect Chemother. 2021 Jun;53(2):271-283. doi: 10.3947/ic.2021.0051.

ABSTRACT

BACKGROUND: Antimicrobial resistance is on the rise. The use of redundant and inappropriate antibiotics is contributing to recurrent infections and resistance. Newer antibiotics with more robust coverage for Gram-negative bacteria are in great demand for complicated urinary tract infections (cUTIs), complicated intra-abdominal infections (cIAIs), hospital-acquired bacterial pneumonia (HABP), and ventilator-associated bacterial pneumonia (VABP).

MATERIALS AND METHODS: We performed this meta-analysis to evaluate the efficacy and safety profile of a new antibiotic, Imipenem/cilastatin/relebactam, compared to other broad-spectrum antibiotics for complicated infections. We conducted a systemic review search on PubMed, Embase, and Central Cochrane Registry. We included randomized clinical trials-with the standard of care as comparator arm with Imipenem/cilastatin/relebactam as intervention arm. For continuous variables, the mean difference was used. For discrete variables, we used the odds ratio. For effect sizes, we used a confidence interval of 95%. A P-value of less than 0.05 was used for statistical significance. Analysis was done using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I² statistic.

RESULTS: The authors observed similar efficacy at clinical and microbiologic response levels on early follow-up and late follow-up compared to the established standard of care. The incidence of drug-related adverse events, serious adverse events, and drug discontinuation due to adverse events were comparable across both groups.

CONCLUSION: Imipenem/cilastatin/relebactam has a non-inferior safety and efficacy profile compared to peer antibiotics to treat severe bacterial infections (cUTIs, cIAIs, HABP, VABP).

PMID:34216121 | DOI:10.3947/ic.2021.0051

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Dengue Virus is Hyperendemic in Nigeria from 2009 to 2020: A Contemporary Systematic Review

Infect Chemother. 2021 Jun;53(2):284-299. doi: 10.3947/ic.2020.0142.

ABSTRACT

BACKROUND: Data on Dengue virus (DENV) infection prevalence, geographic distribution and risk factors are necessary to direct appropriate utilization of existing and emerging control strategies. This study aimed to determine the pooled prevalence, risk factors of DENV infection and the circulating serotypes within Nigeria from January 1, 2009 to December 31, 2020.

MATERIALS AND METHODS: Twenty-one studies out of 2,215 available articles were eligible and included for this systematic review. Relevant articles were searched, screened and included in this study according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) criteria. The risk of bias in primary studies was assessed by Cochrane’s method. Heterogeneity of pooled prevalence was calculated using the chi-square test on Cochrane’s Q statistic, which was quantified by I-square values. The random-effects analyses of proportions were used to determine the pooled prevalence of DENV antibodies, antigen and RNA from eligible studies.

RESULTS: Of these, 3 studies reported co-circulation of all the 4 serotypes, while 2 separately reported co-circulation of DENV-1 &2 and DENV-1 to -3. All the antibody-based studies had significantly high heterogeneity (I² >90%, P <0.05), while the NS1 and PCR-based studies had low heterogeneity (I² <25%, P >0.05). The pooled prevalence of DENV IgM, IgG, RNA, NS1 and neutralizing antibodies were 16.8%, 34.7%, 7.7%, 7.7% and 0.7%, respectively. South-east Nigeria had the highest pooled DENV-IgG seropositivity, 77.1%. Marital status, gender, educational level and occupation status, the proximity of residence to refuse dumpsite, frequent use of trousers and long sleeve shirts were significantly associated with DENV IgG seropositivity (P <0.05).

CONCLUSION: Based on these findings, it can be inferred that Nigeria is hyperendemic for Dengue fever and needs concerted efforts to control its spread within and outside the country.

PMID:34216122 | DOI:10.3947/ic.2020.0142

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Performance of commercial PCR assays to detect toxigenic Clostridioides difficile in the feces of puppies

Vet Med Sci. 2021 Jul 3. doi: 10.1002/vms3.567. Online ahead of print.

ABSTRACT

Clostridioides difficile is an important enteric pathogen that causes significant morbidity and mortality in humans. With community-acquired infections on the rise, it is important to identify reservoirs of the pathogen. Companion animals can be asymptomatic carriers of C. difficile and may therefore represent a reservoir, but epidemiological studies of C. difficile within the pet-owner unit are needed, along with validated methods to detect C. difficile in both people and animals. The goal of this study was to assess the performance of commercial qPCR assays and a multiplex PCR for C. difficile compared to toxigenic culture. These assays were tested on up to 103 fecal samples from puppies, a population in which the prevalence of C. difficile is the highest. The sensitivities, specificities, positive predictive values and negative predictive values were respectively 84.2%, 87.7%, 61.5%, and 95.9% for the Cepheid GeneXpert; 66.7%, 66.7%, 29.6%, and 90.9% for the DiaSorin Simplexa; and 94.4%, 85.0%, 65.4%, and 98.1%, for the multiplex qPCR. The agreement was highest between the GeneXpert and the multiplex PCR (90.1% agreement, with a kappa statistic of 0.77). For diagnostic purposes, the positive predictive values of the assays were low. However, the high sensitivities of the assays could render them useful for epidemiologic purposes.

PMID:34216115 | DOI:10.1002/vms3.567

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The Safety and Efficacy of Anakinra, an Interleukin-1 Antagonist in Severe Cases of COVID-19: A Systematic Review and Meta-Analysis

Infect Chemother. 2021 Jun;53(2):221-237. doi: 10.3947/ic.2021.0016.

ABSTRACT

This study aims to assess anakinra’s safety and efficacy for treating severe coronavirus disease 2019 (COVID-19). Numerous electronic databases were searched and finally 15 studies with a total of 3,530 patients, 757 in the anakinra arm, 1,685 in the control arm were included. The pooled adjusted odds ratio (OR) for mortality in the treatment arm was 0.34 (95% confidence interval [CI], 0.21 – 0.54, I² = 48%), indicating a significant association between anakinra and mortality. A significant association was found regarding mechanical ventilation requirements in anakinra group compared to the control group OR, 0.68 (95% CI, 0.49 – 0.95, I² = 50%). For the safety of anakinra, we evaluated thromboembolism risk and liver transaminases elevation. Thromboembolism risk was OR, 1.59 (95% CI, 0.65 – 3.91, I² = 0%) and elevation in liver transaminases with OR was 1.35 (95% CI, 0.61 – 3.03, I² = 76%). Both were not statistically significant over the control group. Anakinra is beneficial in lowering mortality in COVID-19 patients. However, these non-significant differences in the safety profile between the anakinra and control groups may have been the result of baseline characteristics of the intervention group, and further studies are essential in evaluating anakinra’s safety profile.

PMID:34216117 | DOI:10.3947/ic.2021.0016