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Early identification of sacroiliitis in patients with suspected spondyloarthritis: A challenging task

Curr Rheumatol Rev. 2023 May 29. doi: 10.2174/1573397119666230529105122. Online ahead of print.

ABSTRACT

OBJECTIVE: The purpose of this study was to assess the performance of computed tomography (CT) scan and magnetic resonance imaging (MRI) for detecting sacroiliitis in non-radiographic SpA (nr-SpA).

METHODS: This cross-sectional monocentric double-blind study included 63 patients consulting for symptoms suggestive of SpA between February 2014 and February 2017. Patients with conventional radiographs showing a confirmed sacroiliitis (grade 3 or 4) were not included. Eligible patients underwent CT and MRI of sacroiliac joints (SIJ). CT and MR images were interpreted by 2 experienced musculoskeletal radiologists blinded to clinical and laboratory data. Two professors in rheumatology blinded to radiologists’ conclusions analyzed clinical data, laboratory tests, HLA typing, X-rays, CT and MRI images, and divided the patients into 2 groups: confirmed nr-SpA or no SpA. This classification was considered the gold standard when analyzing the results.

RESULTS: 46 women and 17 men were included in this study. 47 patients were classified as confirmed nr-SpA (74.6%) and 16 patients as no SpA (25.4%). Sensitivity, specificity, and positive and negative predictive values of CT and MRI for detecting sacroiliitis were, respectively, estimated at 71.7%, 71.4%, 89.2%, 43.5%, and 51.2%, 100%, 100%, and 40%. CT and MRI findings were found to be statistically associated (p<0.001).

CONCLUSION: SIJ MRI is a highly specific method in the detection of sacroiliitis, but with a moderate sensitivity. SIJ CT scan, usually known as the third option after radiography and MRI, has much greater diagnostic utility than it has been documented previously.

PMID:37254543 | DOI:10.2174/1573397119666230529105122

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Polymorphic Variants of ASS1 Gene Related to Arginine Metabolism and the Risk of HCC

Protein Pept Lett. 2023 May 29. doi: 10.2174/0929866530666230529143121. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma is a primary liver cancer and 6th most common cancer globally. Inefficient diagnostic strategies and the limited availability of treatments are the foremost reasons. Variable factors directly impact the disease burden, among them, molecular alterations have been found to play a significant role. In liver, arginosuccinate synthase-1 is a center of arginine metabolism and rate limiting enzyme of urea cycle. It also triggers multiple mechanisms that lead to HCC pathogenesis.

OBJECTIVES: The aim of this study is to analyze the ASS1 gene expression, its polymorphic genotype and microsatellite instability among HCC patients from our Pakistani population.

METHOD: Blood samples were collected from disease and healthy control individuals. Allele-Specific PCR was performed for SNP analysis. MSI of tri and tetra nucleotide repeats were analyzed by PCR. The differential expression of ASS1 gene was also investigated. Furthermore, the reactome database and STRING software were utilized for finding correlations between ASS1 gene with other associated gene/proteins.

RESULTS: The GG wild-type genotype was more prevailed in the disease group as compared to the control. Significant downregulation in ASS1 and NOS2 genes was observed. Bioinformatics analysis reveals the correlation between ASS1 polymorphism and HCC development appears to be linked with the EMT pathway and polyamine production. Furthermore, MSI significantly resided in the disease group. Results were analyzed statistically to calculate the significance of obtained results.

CONCLUSION: Study concludes that the insight of HCC mechanism through population-specific genetic mutations and altered gene expression of ASS1 might be helpful in early diagnostic and therapeutic purposes.

PMID:37254538 | DOI:10.2174/0929866530666230529143121

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ERK/MAPK Signalling Pathway Regulates MMP2 Through ETS1 in Renal Clear Cell Carcinoma

Curr Mol Med. 2023 May 29. doi: 10.2174/1566524023666230529143837. Online ahead of print.

ABSTRACT

BACKGROUND: The c-ETS-1 (ETS1) expression is high in clear cell renal cell carcinoma (ccRCC) tissues; however, how it impacts ccRCC is currently unknown.

METHOD: The online STRING web source was used to construct a protein network interacting with ETS1. The Cell Counting Kit-8 was used to detect the cell viability. A clonogenic assay, a wound-healing assay, and a Transwell assay were used to detect cell proliferation, invasion and migration abilities. Western blot was used to detect the expression of proteins.

RESULT: The data showed the expression of ETS1 in ccRCC tissues to be significantly increased compared to adjacent tissues (p<0.05). The positive expression of ETS1 in ccRCC patients aged 20-100 was statistically significant compared to adjacent normal tissues (p<0.05). The grade of ETS1 positive expression (1-4) and lymph node metastasis (N1) in ccRCC were significantly higher than those in adjacent normal tissues (p<0.05). The tumour stage (stages 1-4) in ccRCC patients with positive ETS1 expression was significantly higher than that in adjacent normal tissues (p<0.05). Knockdown of ETS1 and PERK inhibitors significantly inhibited the proliferation, migration and invasion of ccRCC cells. Knockdown of ETS1 inhibited MMP-2 expression, and an extracellular signal-related kinase (ERK) inhibitor inhibited both ETS1 and MMP-2 expression.

CONCLUSION: A high expression of ETS1 is associated with the progression of ccRCC. This study suggests that ETS1 promotes proliferation by increasing MMP2 expression in ccRCC, and combined knockdown of ETS1 and inhibition of ERK can significantly inhibit the proliferation, migration and invasion of ccRCC. ETS1 may be a therapeutic and prognostic target for renal cell carcinoma.

PMID:37254537 | DOI:10.2174/1566524023666230529143837

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Effects of mobile apps intervention on medication adherence and type 2 diabetes mellitus control: A systematic review and meta-analysis

J Telemed Telecare. 2023 May 30:1357633X231174933. doi: 10.1177/1357633X231174933. Online ahead of print.

ABSTRACT

INTRODUCTION: The prevalence of non-adherence to antidiabetic treatment remains high despite various efforts. Thus, the positive effects of the antidiabetic treatment cannot be optimised and the disease progresses to complications. This present systematic review and meta-analysis aimed to evaluate the effects of mobile applications (apps) intervention on medication adherence and type 2 diabetes mellitus (T2DM) control.

METHODS: This research was conducted following the PRISMA guidelines. The databases that had been searched included Web of Science, PubMed, Scopus, Cochrane Library and Ovid from 2017 to 2022. Study characteristics were retrieved and study outcomes such as adherence status and diabetes control were extracted and quantitatively analysed through meta-analysis.

RESULTS: Eight studies met the final inclusion criteria and were included in the analysis, contributing to a total of 884 subjects. The methodological quality of the included studies was variable. Three studies reported statistically significant improvement in medication adherence through mobile apps intervention. Additionally, the mobile apps intervention proved effective in reducing glycaemic outcomes. As compared to non-mobile apps users, glycated haemoglobin (HbA1c) significantly decreased by 0.36% (95% CI -0.47% to -0.25%), whereas fasting plasma glucose (FPG) significantly decreased by 16.75 mg/dL (95% CI -17.60 mg/dL to -15.80 mg/dL).

CONCLUSION: Mobile apps intervention had beneficial impacts on medication adherence and glycaemic parameters. Future research should explore the best practical approach for real-world settings.

PMID:37254516 | DOI:10.1177/1357633X231174933

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The impact of COVID-19 on the interpretation of psycho-oncological support trial results: a quasi-experimental approach using the data from the new form of care “Integrated cross-sectoral psycho-oncology (nFC-isPO)”

BMC Health Serv Res. 2023 May 30;23(1):556. doi: 10.1186/s12913-023-09544-y.

ABSTRACT

OBJECTIVE: In addition to the common difficulties of ongoing trials, the COVID-19 pandemic posed several challenges to scientists worldwide and created an additional burden for vulnerable patient groups. In the nFC-isPO of individualised treatment for anxiety and depression in newly diagnosed patients with cancer caregivers (e.g. psycho-oncologists) reported elevated HADS scores in newly enrolled patients after the outbreak of the COVID-19 pandemic. Accordingly, the question arises whether the pandemic affected HADS scores. Therefore, stratified analyses by the time of enrolment (T1) were performed for patients with 12 months of care (T3).

METHODS: Patients with 12 months of care (N = 1,140) were analysed. A comparison within the regression discontinuity design according to the time points at which patients completed the baseline (T1) HADS questionnaire was conducted to examine differences between patients recruited before Q2/2020 (pre-pandemic) and after the coronavirus outbreak. Furthermore, mean HADS scores at T1 and T3 for all quarters during the study were compared.

RESULTS: Mean T1 and T3 HADS scores of patients with cancer during the pandemic are only slightly higher than those of the pre-pandemic group. No significant treatment effect was observed in either the pre-pandemic (p = 0.5495, Late = 1.7711) or the post-pandemic group (p = 0.9098, LATE=-0.2933). In contrast, the average local treatment effect in the post-pandemic group suggests a minimal decrease in HADS score in the predefined range and thus a positive treatment effect for isPO. Comparison of mean HADS scores at T1 and T3 did not show a large increase by pandemic-related timepoints, however, a decrease of approximately 2-3 points over each quarter at 12 months compared to baseline is observed.

CONCLUSION: The existing nFC-isPO care is resilient to crisis and may counteract external influences such as the Corona pandemic. Accordingly, the pandemic had little influence on the fears of patients with cancer in the nFC-isPO. This emphasises that psycho-oncology is vital for the reduction of stress, anxiety and depression in patients with cancer.

TRIAL REGISTRATION: The study was registered in the German Clinical Trials Registry on 30 October 2018 under the ID “DRKS00015326”.

PMID:37254172 | DOI:10.1186/s12913-023-09544-y

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Aseptic loosening of tumor prostheses in distal femur after revision surgery: a retrospective study

World J Surg Oncol. 2023 May 31;21(1):164. doi: 10.1186/s12957-023-03047-0.

ABSTRACT

BACKGROUND: Tumor prostheses of the distal femur after revision surgery is associated with high rates of aseptic loosening, which has introduced great challenges to the survival of patients, but only a few studies have evaluated their X-ray imaging. The purpose of this study was to analyze the risk factors for recurrence of aseptic loosening and make recommendations to reduce the incidence of aseptic loosening after revision surgery of tumor prostheses in the distal femur.

METHOD: A retrospective analysis was performed on 23 patients who had revision surgery for distal femur prostheses due to aseptic loosening between June 2002 and June 2021. They were divided into two groups based on the condition of the prostheses after revision surgery: loosening group (9 patients) and control group (14 patients). Following the initial replacement, the length and diameter of the prosthetic intramedullary stem were measured through the standard full-length anteroposterior X-ray imaging of both lower limbs. The osteotomy length, femoral length and diameter, femoral intramedullary stem diameter, hip-knee-ankle angle (HKAA), mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), and so on were measured as well. Following that, statistical analysis was performed.

RESULTS: Patients in the loosening group had statistically significant differences in the ratio of prostheses length to femur length (71.89 ± 6.62) and the ratio of intramedullary stem diameter to femoral diameter (25.50 ± 6.90) (P < 0.05), when compared to the control group. The HKAA (175.58 ± 2.78), mLDFA (94.42 ± 2.57), and the deviation angle between the lower limb alignment and the tibial prostheses force line (2.23 ± 1.09) in the loosening group were significantly different from those in the control group (P < 0.05) on postoperative radiographs of the entire length of the lower limbs. The lowest score in intramedullary manubrium I indicated less osteolysis, while the highest score in intramedullary manubrium III indicated the most serious osteolysis, and the difference was statistically significant (P < 0.05).

CONCLUSIONS: Our study suggests that the use of longer and thicker intramedullary stems can effectively decrease the occurrence of aseptic loosening. Additionally, it is important to avoid using the original prostheses and reconstruct the standard line of lower limb force to further reduce the incidence of aseptic loosening. It is crucial to closely monitor the distal segment of the intramedullary stem for osteolysis after surgery.

PMID:37254167 | DOI:10.1186/s12957-023-03047-0

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Strong interactions between highly dynamic lamina-associated domains and the nuclear envelope stabilize the 3D architecture of Drosophila interphase chromatin

Epigenetics Chromatin. 2023 May 30;16(1):21. doi: 10.1186/s13072-023-00492-9.

ABSTRACT

BACKGROUND: Interactions among topologically associating domains (TADs), and between the nuclear envelope (NE) and lamina-associated domains (LADs) are expected to shape various aspects of three-dimensional (3D) chromatin structure and dynamics; however, relevant genome-wide experiments that may provide statistically significant conclusions remain difficult.

RESULTS: We have developed a coarse-grained dynamical model of D. melanogaster nuclei at TAD resolution that explicitly accounts for four distinct epigenetic classes of TADs and LAD-NE interactions. The model is parameterized to reproduce the experimental Hi-C map of the wild type (WT) nuclei; it describes time evolution of the chromatin over the G1 phase of the interphase. The simulations include an ensemble of nuclei, corresponding to the experimentally observed set of several possible mutual arrangements of chromosomal arms. The model is validated against multiple structural features of chromatin from several different experiments not used in model development. Predicted positioning of all LADs at the NE is highly dynamic-the same LAD can attach, detach and move far away from the NE multiple times during interphase. The probabilities of LADs to be in contact with the NE vary by an order of magnitude, despite all having the same affinity to the NE in the model. These probabilities are mostly determined by a highly variable local linear density of LADs along the genome, which also has the same strong effect on the predicted positioning of individual TADs — higher probability of a TAD to be near NE is largely determined by a higher linear density of LADs surrounding this TAD. The distribution of LADs along the chromosome chains plays a notable role in maintaining a non-random average global structure of chromatin. Relatively high affinity of LADs to the NE in the WT nuclei substantially reduces sensitivity of the global radial chromatin distribution to variations in the strength of TAD-TAD interactions compared to the lamin depleted nuclei, where a small (0.5 kT) increase of cross-type TAD-TAD interactions doubles the chromatin density in the central nucleus region.

CONCLUSIONS: A dynamical model of the entire fruit fly genome makes multiple genome-wide predictions of biological interest. The distribution of LADs along the chromatin chains affects their probabilities to be in contact with the NE and radial positioning of highly mobile TADs, playing a notable role in creating a non-random average global structure of the chromatin. We conjecture that an important role of attractive LAD-NE interactions is to stabilize global chromatin structure against inevitable cell-to-cell variations in TAD-TAD interactions.

PMID:37254161 | DOI:10.1186/s13072-023-00492-9

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Biomarker-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection: statistical analysis plan for the BATCH trial and PRECISE sub-study

Trials. 2023 May 30;24(1):364. doi: 10.1186/s13063-022-06956-9.

ABSTRACT

INTRODUCTION: The BATCH trial is a multi-centre randomised controlled trial to compare procalcitonin-guided management of severe bacterial infection in children with current management. PRECISE is a mechanistic sub-study embedded into the BATCH trial. This paper describes the statistical analysis plan for the BATCH trial and PRECISE sub-study.

METHODS: The BATCH trial will assess the effectiveness of an additional procalcitonin test in children (aged 72 h to 18 years) hospitalised with suspected or confirmed bacterial infection to guide antimicrobial prescribing decisions. Participants will be enrolled in the trial from randomisation until day 28 follow-up. The co-primary outcomes are duration of intravenous antibiotic use and a composite safety outcome. Target sample size is 1942 patients, based on detecting a 1-day reduction in intravenous antibiotic use (90% power, two-sided) and on a non-inferiority margin of 5% risk difference in the composite safety outcome (90% power, one-sided), while allowing for up to 10% loss to follow-up.

RESULTS: Baseline characteristics will be summarised overall, by trial arm, and by whether patients were recruited before or after the pause in recruitment due to the COVID-19 pandemic. In the primary analysis, duration of intravenous antibiotic use will be tested for superiority using Cox regression, and the composite safety outcome will be tested for non-inferiority using logistic regression. The intervention will be judged successful if it reduces the duration of intravenous antibiotic use without compromising safety. Secondary analyses will include sensitivity analyses, pre-specified subgroup analyses, and analysis of secondary outcomes. Two sub-studies, including PRECISE, involve additional pre-specified subgroup analyses. All analyses will be adjusted for the balancing factors used in the randomisation, namely centre and patient age.

CONCLUSION: We describe the statistical analysis plan for the BATCH trial and PRECISE sub-study, including definitions of clinical outcomes, reporting guidelines, statistical principles, and analysis methods. The trial uses a design with co-primary superiority and non-inferiority endpoints. The analysis plan has been written prior to the completion of follow-up.

TRIAL REGISTRATION: BATCH: ISRCTN11369832, registered 20 September 2017, doi.org/10.1186/ISRCTN11369832.

PRECISE: ISRCTN14945050, registered 17 December 2020, doi.org/10.1186/ISRCTN14945050.

PMID:37254156 | DOI:10.1186/s13063-022-06956-9

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Effect of nutritional promotion intervention on dietary adherence among type II diabetes patients in North Shoa Zone Amhara Region: quasi-experimental study

J Health Popul Nutr. 2023 May 30;42(1):49. doi: 10.1186/s41043-023-00393-3.

ABSTRACT

BACKGROUND: Diabetes is a major global public health problem that requires self-management behavior. However, this is difficult to implement in practice and requires new approaches. The purpose of this study was to evaluate nutritional promotion interventions for dietary adherence and lessons learned to improve self-management.

METHODS: A quasi-experimental study was conducted from January 2020 to February 2021 in North Shoa Zone public hospital. The study enrolled 216 type II diabetic patients from four public hospitals. Study participants were randomly assigned to intervention and control groups at an individual level. Data were measured twice (baseline and end line survey after six months using interviewer-administered questionnaires). Data were entered into Epi Data V.3.1 and analyzed using SPSS version 22. Data were presented as means of standard deviations for continuous variables and percentages for categorical variables. Intervention and control groups were compared before and after intervention using independent t tests. A p-value less than 0.05 was considered significant for all statistical tests.

RESULTS: A total of 216 type II diabetics participated in this study. Nutritional promotion intervention programs increased adherence to the mean number of days adhering to a healthy diet (p < 0.0001). Specifically, the nutrition promotion program improved daily intake of fruits and vegetables, low glycemic index foods, high fiber foods, healthy fish oils, low sugar foods, and healthy eating plans (p ≤ 0.050). Mean fasting blood glucose levels were significantly decreased after the educational intervention (p ≤ 0.05).

CONCLUSION: This study demonstrates that a nutrition-promoting intervention can significantly change patients’ adherence to healthy eating behaviors and effectively improve their glycemic control. Health care providers should integrate programs that promote nutrition education into existing health systems service. Primary care platforms such as health posts and health centers can play a key role in integrating health promotion programs to improve self-management behaviors.

PMID:37254151 | DOI:10.1186/s41043-023-00393-3

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Head-to-head comparison of perfluorobutane contrast-enhanced US and multiparametric MRI for breast cancer: a prospective, multicenter study

Breast Cancer Res. 2023 May 30;25(1):61. doi: 10.1186/s13058-023-01650-3.

ABSTRACT

BACKGROUND: Multiparametric magnetic resonance imaging (MP-MRI) has high sensitivity for diagnosing breast cancers but cannot always be used as a routine diagnostic tool. The present study aimed to evaluate whether the diagnostic performance of perfluorobutane (PFB) contrast-enhanced ultrasound (CEUS) is similar to that of MP-MRI in breast cancer and whether combining the two methods would enhance diagnostic efficiency.

PATIENTS AND METHODS: This was a head-to-head, prospective, multicenter study. Patients with breast lesions diagnosed by US as Breast Imaging Reporting and Data System (BI-RADS) categories 3, 4, and 5 underwent both PFB-CEUS and MP-MRI scans. On-site operators and three reviewers categorized the BI-RADS of all lesions on two images. Logistic-bootstrap 1000-sample analysis and cross-validation were used to construct PFB-CEUS, MP-MRI, and hybrid (PFB-CEUS + MP-MRI) models to distinguish breast lesions.

RESULTS: In total, 179 women with 186 breast lesions were evaluated from 17 centers in China. The area under the receiver operating characteristic curve (AUC) for the PFB-CEUS model to diagnose breast cancer (0.89; 95% confidence interval [CI] 0.74, 0.97) was similar to that of the MP-MRI model (0.89; 95% CI 0.73, 0.97) (P = 0.85). The AUC of the hybrid model (0.92, 95% CI 0.77, 0.98) did not show a statistical advantage over the PFB-CEUS and MP-MRI models (P = 0.29 and 0.40, respectively). However, 90.3% false-positive and 66.7% false-negative results of PFB-CEUS radiologists and 90.5% false-positive and 42.8% false-negative results of MP-MRI radiologists could be corrected by the hybrid model. Three dynamic nomograms of PFB-CEUS, MP-MRI and hybrid models to diagnose breast cancer are freely available online.

CONCLUSIONS: PFB-CEUS can be used in the differential diagnosis of breast cancer with comparable performance to MP-MRI and with less time consumption. Using PFB-CEUS and MP-MRI as joint diagnostics could further strengthen the diagnostic ability. Trial registration Clinicaltrials.gov; NCT04657328. Registered 26 September 2020. IRB number 2020-300 was approved in Chinese PLA General Hospital. Every patient signed a written informed consent form in each center.

PMID:37254149 | DOI:10.1186/s13058-023-01650-3