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Value of (18)F-FDG PET-CT imaging to predict epidermal growth factor receptor mutations in patients with lung squamous cell carcinoma

Zhonghua Zhong Liu Za Zhi. 2021 Jul 23;43(7):795-800. doi: 10.3760/cma.j.cn112152-20190111-00006.

ABSTRACT

Objective: To investigate the value of (18)F-fluorodeoxy glucose ((18)F-FDG) positron emission tomography/computed tomography (PET-CT) in predicting the epidermal growth factor receptor (EGFR) mutations in patients with lung squamous cell carcinoma. Methods: We retrospectively analyzed the clinical data and (18)F-FDG PET-CT imaging data of 206 patients with lung squamous cell carcinoma confirmed by pathology and underwent EGFR mutation test in the First Affiliated Hospital of Nanjing Medical University from June 2013 to October 2018. Receiver operating characteristic (ROC) curve analysis was performed to quantify the predictive value of maximum standard uptake value (SUV(max)), metabolic tumor volume (MTV), total lesion glycolysis (TLG). The Chisquared test was used to assess the difference in PET parameters. A multivariate Logistic regression analysis was performed to yield the parameters with statistic difference. Results: All of 206 patients with lung squamous cell carcinoma showed a high (18)F-FDG uptake. The median of SUV(max), MTV and TLG were 19.14, 37.69 cm(3) and 291.73, respectively. Among the 206 patients, EGFR mutations were identified in 14 cases, including 7 with exon 21 (L858R) mutation, 6 with exon 19 mutation and 1 with exon 20 mutation. ROC curve showed that the AUC of SUV(max), MTV and TLG were 0.624 (95% CI=0.454-0.794, P=0.122), 0.892 (95% CI=0.811-0.973, P<0.001) and 0.860 (95% CI=0.768-0.952, P<0.001), respectively. The median SUV(max) (19.14) was used as the cutoff points due to the small value of AUC. The cutoff point of MTV was 20.09 cm(3), the cutoff point of TLG was 211.07. Univariate analysis showed that the sex, smoking history, M stage, MTV and TLG were associated with EGFR mutations (all P<0.05). Logistic multivariate analysis showed that the sex, smoking history and TLG were the independent predictors of EGFR mutation (all P<0.05). Conclusion: TLG detected by (18)F-FDG PET/CT is an independent factor for predicting EGFR mutation in patients with lung squamous cell carcinoma, and has certain reference value for predicting EGFR mutation.

PMID:34289575 | DOI:10.3760/cma.j.cn112152-20190111-00006

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Changes of Temporal Processing and Hearing in Noise after Use of a Monoaural Hearing Aid in Patients with Sensorineural Hearing Loss: A Preliminary Study

J Audiol Otol. 2021 Jul;25(3):146-151. doi: 10.7874/jao.2021.00038. Epub 2021 Jul 10.

ABSTRACT

BACKGROUND AND OBJECTIVES: The relationship between hearing aid (HA) use and improvement in cognitive function is not fully known. This study aimed to determine whether HAs could recover temporal resolution or hearing in noise functions. Materials and.

METHODS: We designed a prospective study with two groups: HA users and controls. Patients older than 45 years, with a pure tone average threshold of worse than 40 dB and a speech discrimination score better than 60% in both ears were eligible. Central auditory processing tests and hearing in noise tests (HINTs) were evaluated at the beginning of the study and 1, 3, 6, and 12 months after the use of a monaural HA in the HA group compared to the control group. The changes in the evaluation parameters were statistically analyzed using the linear mixed model.

RESULTS: A total of 26 participants (13 in the HA and 13 in the control group) were included in this study. The frequency (p<0.01) and duration test (p=0.02) scores showed significant improvements in the HA group after 1 year, while the HINT scores showed no significant change.

CONCLUSIONS: After using an HA for one year, patients performed better on temporal resolution tests. No improvement was documented with regard to hearing in noise.

PMID:34289535 | DOI:10.7874/jao.2021.00038

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CRL4B complex promotes the development of pancreatic cancer by inhibiting secreted frizzled related protein 1

Zhonghua Zhong Liu Za Zhi. 2021 Jun 23;43(6):646-656. doi: 10.3760/cma.j.cn112152-20210108-00030.

ABSTRACT

Objective: To investigate the role of CUL4B-RING E3 ubiquitin ligase (CRL4B) complex in pancreatic tumorigenesis and the molecular mechanism. Methods: Pancreatic cells were divided into control group (transfected with negative control lentivirus), shCUL4B group (transfected with CUL4B lentivirus), shDDB1 group [transfected with DNA damage binding protein 1 (DDB1) lentivirus], and shCUL4B+ siSFRP1 group (transfected with CUL4B lentivirus and SFRP1-siRNA). RNA-seq was performed in pancreatic cancer cell lines with CUL4B and DDB1 knocked down respectively, to identify the target genes regulated by CRL4B complex. Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of target genes. Chromatin immunoprecipitation (ChIP) assay was used to identify the target genes directly regulated by CUL4B and DDB1. Western blot was used to detect the protein expression levels of the epithelial-mesenchymal transition (EMT) markers. The EdU cell proliferation test was used to detect cell proliferation ability. The scratch repair test and Transwell cell invasion test were used to detect cell migration and invasion ability. Finally, the sequencing data of pancreatic cancer-related tumor samples and normal samples in GEO, TCGA and GTEx databases were used to analyze the expression correlations of CUL4B, DDB1 and their downstream target genes. Results: RNA-seq results showed that target genes regulated by CRL4B complex involved in a number of malignant tumor-related signaling pathways. qRT-PCR results verified that the mRNA expression levels of the target genes of CUL4B or DDB1 knockdown groups were higher than those of the control group, and the difference was statistically significant (P<0.05). ChIP-PCR results showed that CRL4B complex directly bound to the promoter regions of the target genes, NME1 and SFRP1, and the enrichment of monoubiquitination of lysine at 119 of histone H2A (H2AK119ub1) in the promoter region of target gene was reduced after CUL4B knockdown. The proliferation rate in PANC-1 cell line of the control group was (32.10±3.58)%, higher than (13.95±1.66)% in the shCUL4B group and (22.38±0.77)% in the shCUL4B+ siSFRP1 group (P<0.05). The proliferation rate in AsPC-1 cell line of the control group was (35.47±7.80)%, higher than (19.60±3.58)% in the shCUL4B group and (30.09±0.81)% in the shCUL4B+ siSFRP1 group (P<0.05). The scratch repair experiment showed that the migration rate of PANC-1 cell line control group was (53.18±3.70)%, higher than that (17.46±2.62)% in the shCUL4B group and (44.99±9.18)% in the shCUL4B + siSFRP1 group (P<0.05). Western blot showed the expression levels of epithelial markers including α-catenin and γ-catenin in the control group were 1.00±0.03 and 1.01±0.11, respectively, lower than 1.44±0.01 and 1.21±0.06 in the shCUL4B group (P<0.05). The expression levels of mesenchymal markers including fibronectin and vimentin in the control group were 1.01±0.14 and 1.02±0.18, respectively, higher than 1.53±0.13 and 1.22±0.07 in the shCUL4B+ siSFRP1 group (P<0.05). The cell metastasis rate of the control group was (100.00±3.96)%, higher than the (35.49±0.34)% in the shCUL4B group and (107.06±2.77)% in the shCUL4B+ siSFRP1 group, the difference was statistically significant (P<0.05). The expressions of CUL4B and DDB1 were significantly upregulated in the pancreatic cancer tissues, and were negatively correlated with the expression of SFRP1 (r=-0.342 and r=-0.264, respectively). Conclusions: CRL4B complex inhibits the transcription of target gene SFRP1 and promotes the development of pancreatic cancer. Moreover, CRL4B complex is upregulated in pancreatic cancer, which provide a potential of therapeutic target for pancreatic cancer.

PMID:34289556 | DOI:10.3760/cma.j.cn112152-20210108-00030

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Dual versus single long-acting bronchodilator use could raise acute coronary syndrome risk by over 50%: A population-based nested case-control study

J Intern Med. 2021 Jul 21. doi: 10.1111/joim.13348. Online ahead of print.

ABSTRACT

BACKGROUND: Coronary heart disease occurs more frequently among patients with chronic obstructive pulmonary disease (COPD) compared to those without COPD. While some research suggests that long-acting bronchodilators might confer an additional risk of acute coronary syndrome (ACS), information from real-world clinical practice about the cardiovascular impact of using two versus one long-acting bronchodilator for COPD is limited. We undertook a population-based nested case-control study to estimate the risk of ACS in users of both a long-acting muscarinic antagonist (LAMA) and a long-acting beta2-agonist (LABA) relative to users of a LAMA.

METHODS: The study was based on the primary care PREDICT Cardiovascular Disease Cohort and linked data from regional laboratories and the New Zealand Ministry of Health’s national data collections. The underlying cohort (n = 29,993) comprised patients aged 45-84 years, who initiated treatment with a LAMA and/or LABA for COPD between 1 February 2006 and 11 October 2016. 1490 ACS cases were matched to 13,550 controls by date of birth, sex, date of cohort entry (first long-acting bronchodilator dispensing), and COPD severity.

RESULTS: Relative to current use of LAMA therapy, current use of LAMA and LABA dual therapy was associated with a significantly higher risk of ACS (adjusted OR = 1.72; [95% CI: 1.28-2.31]).

CONCLUSION: Dual long-acting bronchodilator therapy, rather than LAMA mono-therapy, could increase the risk of ACS by more than 50%. This has important implications for decisions about the potential benefit/harm ratio of COPD treatment intensification, given the modest benefits of dual therapy.

PMID:34289189 | DOI:10.1111/joim.13348

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Testing and e-learning activity designed to enhance student nurses understanding of continence and mobility

Int J Nurs Educ Scholarsh. 2021 Jul 20;18(1). doi: 10.1515/ijnes-2021-0033.

ABSTRACT

OBJECTIVES: The aim of this study was to test if the e-learning activity that we developed could improve student nurses’ knowledge of continence and mobility and whether or not students would find the style of learning beneficial.

METHODS: A quasi-experimental pre-post-test design was used to test if the continence and mobility e-learning activity could improve student nurses’ knowledge about assessing and managing the needs of continence and mobility. An 18-item true/false knowledge of continence quiz was completed by 116 student nurses and a Likert style feedback learning survey was completed by 135 nursing students.

RESULTS: There was a statistically significant increase in students’ knowledge about continence and its relationship to mobility following the e-learning activity. The e-learning activity also enhanced students’ knowledge, confidence and perceptions about older people.

CONCLUSIONS: The e-learning activity we developed has the potential to improve nursing students’ knowledge about continence and mobility in an enjoyable manner.

PMID:34289268 | DOI:10.1515/ijnes-2021-0033

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High anatomical accuracy of a novel high-resolution wide-band dielectric imaging system in cryoballoon-based ablation

Pacing Clin Electrophysiol. 2021 Jul 21. doi: 10.1111/pace.14324. Online ahead of print.

ABSTRACT

PURPOSE: Recently, a novel cardiac imaging system based on a wide-band dielectric technology (KODEX-EPD) was introduced to guide catheter ablation. The aim of the study was to evaluate this 3D wide-band dielectric imaging system (WDIS) during cryoballoon (CB)-based atrial fibrillation (AF) ablation focusing on accuracy of pulmonary vein (PV)-anatomy.

METHODS: In consecutive patients with symptomatic AF, CB-based ablation was performed in conjunction with the 3D WDIS. Selective PV-angiographies were performed, and 3D anatomy of the left atrium (LA) and PVs using the 3D WDIS was created. The ostial diameters of the ipsilateral right-sided and left-sided PVs and ostial diameters of the right-/left-sided upper/lower PVs demonstrated by selective angiographies were analyzed and compared to 3D WDIS-based PV visualization.

RESULTS: In 65 patients (42/65 (65%) male, age 65±9 years, 29/65 (45%) paroxysmal AF) a total of 260 PVs were identified. Median ostial PV-diameters for the ipsilateral left- and right-sided PVs were 38 [34; 43] and 37 [34; 40.3] mm when assessed fluoroscopically and 40 [35.7; 43] and 39 [35.0; 43] mm as demonstrated by 3D WDIS. There was no statistically significant difference between both methods regarding PV-diameter measurements. KODEX-EPD overestimated fluoroscopy measurements by 1.08 mm (95% limits of agreement of -1.93 mm and 4.1 mm).

CONCLUSION: The novel wide-band dielectric 3D-imaging system is feasible to create high-resolution images of cardiac structures during CB ablation procedures and accurately visualizes PV-anatomy. This article is protected by copyright. All rights reserved.

PMID:34289168 | DOI:10.1111/pace.14324

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Bacterial lysate add-on therapy to reduce exacerbations in severe asthma: a double-blind placebo-controlled trial

Clin Exp Allergy. 2021 Jul 21. doi: 10.1111/cea.13990. Online ahead of print.

ABSTRACT

BACKGROUND: Asthma exacerbations are frequently induced by respiratory tract infections (RTIs). Bacterial lysates have been described to possess immune-modulatory effects and reduce RTIs as well as asthma symptoms in children. However, whether bacterial lysates have similar effects in adult asthma patients is unknown.

AIMS: To reduce asthma exacerbations by add-on bacterial lysate therapy in adults with severe asthma and to characterize the clinical and immune-modulatory effects of this treatment.

METHODS: Asthma patients (GINA 4) with ≥2 annual exacerbations in the previous year, were included. The intervention regimen consisted of OM-85/placebo for ten consecutive days per month for six months during two winter seasons. Primary endpoint was the number of severe asthma exacerbations within 18 months. The study was approved by the national and local ethical review board and registered in the Dutch Trial Registry (NL5752). All participants provided written informed consent.

RESULTS: Seventy-five participants were included (38 OM-85; 37 placebo). Exacerbation frequencies were not different between the groups after 18 months (incidence rate ratio 1.07, 95%CI [0.68-1.69], p=0.77). With the use of OM-85, FEV1% increased with 3.81% (p=0.04) compared to placebo. Nasopharyngeal swabs taken during RTIs detected a virus less frequently in patients using OM-85 compared to placebo (30.5% vs. 48.0%, p=0.02). In subjects with type 2 inflammation adherent to the protocol (22 OM-85; 20 placebo), a non-statistically significant decrease in exacerbations in the OM-85 group was observed (IRR=0.71, 95%CI [0.39-1.26], p=0.25). Immune-modulatory effects included an increase in several plasma cytokines in the OM-85 group, especially IL-10 and interferons. Peripheral blood T- and B cell subtyping, including regulatory T-cells, did not show differences between the groups.

CONCLUSION: Although OM-85 may have immune modulatory effects, it did not reduce asthma exacerbations in this heterogeneous severe adult asthma group. Post-hoc analysis showed a potential clinical benefit in patients with type 2 inflammation.

PMID:34289183 | DOI:10.1111/cea.13990

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Patterns of thyroid dysfunctions in adolescent patients suffering from severe acne during isotretinoin treatment

Clin Exp Pharmacol Physiol. 2021 Jul 21. doi: 10.1111/1440-1681.13552. Online ahead of print.

ABSTRACT

Although oral isotretinoin has been widely used as a basic treatment of acne in adolescents, several studies have noted some alterations in thyroid functions during oral isotretinoin therapy. Therefore, the present study aims at evaluating the possible changes in thyroid-stimulating hormone (TSH), free thyroxin (fT4) and free triiodothyronine (fT3) levels during isotretinoin treatment and analyzing the possible factors which may contribute to such changes. In the present study, forty-seven patients received (0.5 mg/kg oral isotretinoin) for treatment of severe acne. TSH, fT4 and fT3 were measured at baseline, after 3 and 6 months. ANOVA tests were used for statistical analyses. The levels of fT4 and fT3 decreased significantly during isotretinoin treatment (from 0.85 ± 0.04 and 3.1 ± 0.26 at baseline to 0.81± 0.023 and 2.76 ±0.2 after 6 months respectively). The decrease was accompanied by significant elevation of TSH (0.66 ± 0.05 at baseline to 0.695 ± 0.05 after 6 months). The duration of therapy (but not the dose) has significantly affected all the hormonal changes. Previous incomplete or intermittent isotretinoin treatment had significantly influenced the changes in fT4 only, while gender affected the changes of TSH. Isotretinoin treatment can decrease fT4, fT3 and increase TSH. The pattern of these changes was affected by gender and previous isotretinoin therapy. Different doses of isotretinoin did not affect the hormonal changes, but the duration has been the major influencing factor.

PMID:34289152 | DOI:10.1111/1440-1681.13552

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Spin Infrequently Occurs in Abstracts of Systematic Reviews For The Pharmacological Treatment of Type 2 Diabetes Mellitus

Diabet Med. 2021 Jul 21:e14653. doi: 10.1111/dme.14653. Online ahead of print.

ABSTRACT

AIMS: Currently, there is a growing body of research demonstrating that spin – the misinterpretation and distortion of a study’s findings – is common in different fields of medicine. To our knowledge, no study has investigated its presence in systematic reviews focused on diabetic therapies.

METHODS: We performed a cross-sectional study by searching MEDLINE and Embase for systematic reviews focused on pharmacologic treatments for type 2 diabetes mellitus. Our search retrieved 26,490 records, from which 199 studies were extracted in a masked, duplicate fashion. Each study was evaluated for the nine most severe types of spin and other study design parameters. Spin was presented as frequencies and odds ratios to identify associations between study characteristics.

RESULTS: Spin was identified in the abstracts of 15 systematic reviews (15/199, 7.5%). Spin type 5 was the most common type identified (7/199, 3.5%). Spin types 1, 2, 4, and 8 were not identified. In the last 5 years (2016-2021), 7 systematic reviews contained spin within their abstract. There was no association between spins presence and any extracted study characteristic .

CONCLUSIONS: Our findings show that spin infrequently occurs in abstracts of systematic reviews focused on pharmacologic therapies for type 2 diabetes mellitus. However, any amount of spin can lead to the distortion of a reader’s interpretation of the study’s findings. Thus, we provide recommendations with rationale to prevent spin in future systematic reviews.

PMID:34289158 | DOI:10.1111/dme.14653

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Genetic variants of APEX1 p.Asp148Glu and XRCC1 p.Gln399Arg with the susceptibility of hepatocellular carcinoma

J Med Virol. 2021 Jul 21. doi: 10.1002/jmv.27217. Online ahead of print.

ABSTRACT

BACKGROUND: The DNA repair genes have a crucial function in the base excision repair (BER) mechanism among different cancerous disorders, particularly hepatocellular carcinoma. The foremost objective of this study is to explore the association of genetic variants of the APEX1 p.Asp148Glu and the XRCC1 p.Gln399Arg with the susceptibility of hepatocellular carcinoma and to identify the computational bioinformatics frameworks of these missense variants.

MATERIALS AND METHODS: A total of 250 participants were enrolled in this work, including 150 HCC patients and 100 cancer-free controls. The genomic DNA was characterized and genotyped by applying the PCR-CTPP method.

RESULTS: The frequency of the APEX (rs1130409*Glu) allele was statistically significant with increased risk of HCC (OR = 1.66, 95% CI = 1.12-2.45), while the XRCC1 (rs25487*Gln) allele conferred a protection against the progression of HCC (OR = 0.64, 95% CI = 0.42-0.96). Furthermore, HCC patients carrying the APEX1 p.Asp148Glu and the XRCC1 p.Gln399Arg variants indicated no significant difference with the clinical, and laboratory parameters (P-value > 0.05).

CONCLUSION: Our findings confirmed that the APEX1 p.Asp148Glu variant was associated with increased risk of HCC, while the XRCC1 p.Gln399Arg variant revealed protection against the development of HCC. This article is protected by copyright. All rights reserved.

PMID:34289138 | DOI:10.1002/jmv.27217