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Iranian Journal of Immunology : IJI May 2024The mechanisms of the function of interferon beta (IFN-β) and natalizumab (NTZ) in multiple sclerosis (MS) patients have not yet been fully understood. Over the past...
The Effect of Interferon Beta and Natalizumab on miR-20b Expression in Patients with Relapsing-Remitting Multiple Sclerosis is Potentially Mediated by Modulation of the Jak-STAT Signaling Pathway: A Case-control Study.
BACKGROUND
The mechanisms of the function of interferon beta (IFN-β) and natalizumab (NTZ) in multiple sclerosis (MS) patients have not yet been fully understood. Over the past decades, many studies have been conducted to evaluate gene expression changes especially regulatory non-coding RNAs such as microRNAs (miRNAs) following therapy in MS patients.
OBJECTIVE
To assess the changes in the expression of miR-20b in MS patients treated with IFN-β or NTZ.
METHODS
Sixty patients with relapsing-remitting MS (RRMS) and 30 healthy controls (HCs) were enrolled. The patients were categorized as untreated (N=20), IFN-β-treated (N=20), and NTZtreated (N=20). For the expression analysis, real-time PCR was performed on the whole blood. The bioinformatic tools were applied for signaling pathways enrichment analysis of miR-20b targetome.
RESULTS
The relative expression of miR-20b was significantly downregulated in the untreated patients compared with the HCs (-1.726-fold, p<0.001), while IFN-β-treated and NTZ-treated patients showed no statistical difference compared with the HCs (0.733-fold, p=0.99 for IFN-β and 1.025-fold, p=0.18 for NTZ). This indicates the restoration of miR-20b expression to normal level in the treated patients. Additionally, in silico analysis demonstrated that the Jak-STAT signaling pathway is enriched with miR-20b targets (p<0.0001).
CONCLUSION
Our findings suggest that the positive effects of IFN-β and NTZ in the RRMS patients could be potentially mediated by returning miR-20b expression to baseline.
PubMed: 38761094
DOI: 10.22034/iji.2024.100500.2694 -
BMC Nephrology May 2024Polypharmacy would increase the risk of adverse drug events and the burden of renal drug excretion among older people. Nevertheless, the association between the number...
BACKGROUND
Polypharmacy would increase the risk of adverse drug events and the burden of renal drug excretion among older people. Nevertheless, the association between the number of medication and the risk of chronic kidney disease (CKD) remains controversial. Therefore, this study aims to investigate the association between the number of medication and the incidence of CKD in older people.
METHODS
This study investigates the association between the number of medications and CKD in 2672 elderly people (≥ 65 years older) of the community health service center in southern China between 2019 and 2022. Logistic regression analysis was used to evaluate the relationship between polypharmacy and CKD.
RESULTS
At baseline, the average age of the study subjects was 71.86 ± 4.60, 61.2% were females, and 53 (2.0%) suffer from polypharmacy. During an average follow-up of 3 years, new-onset CKD developed in 413 (15.5%) participants. Logistic regression analysis revealed that taking a higher number of medications was associated with increase of CKD. Compared with people who didn't take medication, a higher risk of CKD was observed in the older people who taken more than five medications (OR 3.731, 95% CI 1.988, 7.003), followed by those who take four (OR 1.621, 95% CI 1.041, 2.525), three (OR 1.696, 95% CI 1.178, 2.441), two drugs (OR 1.585, 95% CI 1.167, 2.153), or one drug (OR 1.503, 95% CI 1.097, 2.053). Furthermore, age, systolic blood pressure (SBP), white blood cell (WBC), blood urea nitrogen (BUN) and triglyceride (TG) were also independent risk factors CKD (P < 0.05).
CONCLUSION
The number of medications was associated with CKD in older people. As the number of medications taken increased, the risk of CKD was increased.
Topics: Humans; Female; Male; Aged; Polypharmacy; Renal Insufficiency, Chronic; China; Longitudinal Studies; Independent Living; Incidence; Aged, 80 and over; Risk Factors
PubMed: 38760750
DOI: 10.1186/s12882-024-03606-x -
BMC Nephrology May 2024Recent studies have suggested that the N-terminal fragment of B-type natriuretic peptide (NT-proBNP) level serve as a significant risk factor for mortality in patients...
BACKGROUND
Recent studies have suggested that the N-terminal fragment of B-type natriuretic peptide (NT-proBNP) level serve as a significant risk factor for mortality in patients with end-stage renal disease. However, the relationship between NT-proBNP levels and technique failure in peritoneal dialysis-associated peritonitis (PDAP) remains unclear. This study investigated the relationship between NT-proBNP levels at the onset of PDAP and the risk of technique failure in patients with PDAP.
METHODS
A retrospective analysis was conducted on patients with PDAP from December 1, 2009, to December 31, 2021, at our peritoneal dialysis center. We recorded all demographic and baseline clinical data at the time of admission for each PDAP episode. Logistic and Cox regression analyses were performed to assess the association between NT-proBNP levels and technique failure.
RESULTS
Of 485 PDAP episodes included in this study, 130 episodes of technique failure were observed. Multivariate logistic analysis revealed that hospital stay, Na and NT-proBNP levels, and peritoneal dialysate white blood cell counts on days 3 and 5 were independently associated with technique failure. The receiver operating characteristic curve demonstrated that the NT-proBNP level was a better indicator than the other four variables in indicating technique failure. In the multivariate Cox regression analysis, after adjusting for confounding factors, higher NT-proBNP levels (HR of 3.020, 95% CI 1.771, 5.150, P < 0.001) were associated with PDAP technique failure.
CONCLUSIONS
This retrospective study identified the serum NT-proBNP level at the onset of PDAP as an independent risk factor for technique failure in these patients.
Topics: Humans; Natriuretic Peptide, Brain; Male; Female; Peritoneal Dialysis; Peptide Fragments; Middle Aged; Peritonitis; Retrospective Studies; Risk Factors; Kidney Failure, Chronic; Treatment Failure; Aged; Adult; Biomarkers
PubMed: 38760707
DOI: 10.1186/s12882-024-03603-0 -
BMJ Open May 2024The administration of immune checkpoint inhibitors (ICIs) may lead to renal adverse events, notably including renal dysfunction. To early predict the probability of...
Development and validation of a nomogram for predicting the occurrence of renal dysfunction after treatment of immune checkpoint inhibitor: a retrospective case-control study.
PURPOSE
The administration of immune checkpoint inhibitors (ICIs) may lead to renal adverse events, notably including renal dysfunction. To early predict the probability of renal dysfunction after ICIs therapy, a retrospective case-control study was conducted.
METHODS
Clinical information on ICIs-treated patients was collected. Multivariable logistic regression was applied to identify risk factors for renal dysfunction after ICIs treatment. Moreover, a nomogram model was developed and validated internally.
RESULTS
A total of 442 patients were included, among which 35 (7.9%) experienced renal dysfunction after ICIs treatment. Lower baseline estimated glomerular filtration rate (eGFR) (OR 0.941; 95% CI 0.917 to 0.966; p<0.001), concurrent exposure of platinum(OR 4.014; 95% CI 1.557 to 10.346; p=0.004), comorbidities of hypertension (OR 3.478; 95% CI 1.600 to 7.562; p=0.002) and infection (OR 5.402; 95% CI 1.544 to 18.904; p=0.008) were found to be independent associated with renal dysfunction after ICIs treatment. To develop a predictive nomogram for the occurrence of renal dysfunction after ICIs treatment, the included cases were divided into training and validation groups in a ratio of 7:3 randomly. The above four independent risk factors were included in the model. The area under the receiver operating characteristic curves of the predictiive model were 0.822 (0.723-0.922) and 0.815 (0.699-0.930) in the training and validation groups, respectively.
CONCLUSIONS
Lower baseline eGFR, platinum exposure, comorbidities of hypertension and infection were predictors of renal dysfunction in ICIs-treated patients with cancer. A nomogram was developed to predict the probability of renal dysfunction after ICIs treatment, which might be operable and valuable in clinical practice.
Topics: Humans; Nomograms; Male; Female; Retrospective Studies; Immune Checkpoint Inhibitors; Middle Aged; Case-Control Studies; Aged; Glomerular Filtration Rate; Risk Factors; Logistic Models; Neoplasms; Renal Insufficiency; Kidney Diseases
PubMed: 38760047
DOI: 10.1136/bmjopen-2023-082484 -
BMJ Open May 2024To develop a risk assessment model (DAnish REgister Ischaemic Stroke Classifier, DARE-ISC) for predicting 1-year primary ischaemic stroke/systemic embolism (SE) in the...
OBJECTIVES
To develop a risk assessment model (DAnish REgister Ischaemic Stroke Classifier, DARE-ISC) for predicting 1-year primary ischaemic stroke/systemic embolism (SE) in the general population. Secondly, to validate the accuracy DARE-ISC in atrial fibrillation (AF) patients where well-established models and risk scores exist.
DESIGN
Retrospective cohort study. DARE-ISC was developed using gradient boosting decision trees with information from 375 covariates including baseline information on relevant diagnoses, demographic characteristics, registered health-services, lifestyle-related covariates, hereditary stroke components, drug prescriptions and stress proxies.
SETTING
Danish nationwide registries.
PARTICIPANTS
All Danish individuals aged ≥18 from 2010 to 2017 (n=35 519 348 person-years). The model was trained on the 2010-2016 cohorts with validation in the 2017 cohort.
PRIMARY AND SECONDARY OUTCOME MEASURES
Model optimisation and validation were performed through comparison of the area under the receiver operating characteristic curve (AUC) and average precision scores. Additionally, the relative importance of the model covariates was derived using SHAP values.
RESULTS
DARE-ISC had an AUC (95% CI) of 0.874 (0.871 to 0.876) in the general population. In AF patients, DARE-ISC was superior to the GARFIELD-AF risk model and CHADS-VASc score with AUC of 0.779 (95% CI 0.75 to 0.806), 0.704 (95% CI 0.674 to 0.732) and 0.681 (95% CI 0.652 to 0.709), respectively. Furthermore, in AF patients, DARE-ISC had an average threefold and fourfold higher ratio of correctly identified strokes compared with the GARFIELD-AF risk model and CHADS-VASc score, as indicated by average precision scores of 0.119, 0.041 and 0.034, respectively.
CONCLUSIONS
DARE-ISC had a very high stroke prediction accuracy in the general population and was superior to the GARFIELD-AF risk model and CHADS-VASc score for predicting ischaemic stroke/SE in AF patients.
Topics: Humans; Atrial Fibrillation; Denmark; Male; Female; Risk Assessment; Ischemic Stroke; Middle Aged; Aged; Retrospective Studies; Registries; Adult; Risk Factors; ROC Curve; Aged, 80 and over
PubMed: 38760046
DOI: 10.1136/bmjopen-2023-076640 -
BMJ Open May 2024Around 2000 children are born in the UK per year with a neurodevelopmental genetic syndrome with significantly increased morbidity and mortality. Often little is known... (Observational Study)
Observational Study
INTRODUCTION
Around 2000 children are born in the UK per year with a neurodevelopmental genetic syndrome with significantly increased morbidity and mortality. Often little is known about expected growth and phenotypes in these children. Parents have responded by setting up social media groups to generate data themselves. Given the significant clinical evidence gaps, this research will attempt to identify growth patterns, developmental profiles and phenotypes, providing data on long-term medical and educational outcomes. This will guide clinicians when to investigate, monitor or treat symptoms and when to search for additional or alternative diagnoses.
METHODS AND ANALYSIS
This is an observational, multicentre cohort study recruiting between March 2023 and February 2026. Children aged 6 months up to 16 years with a pathogenic or likely pathogenic variant in a specified gene will be eligible. Children will be identified through the National Health Service and via self-recruitment. Parents or carers will complete a questionnaire at baseline and again 1 year after recruitment. The named clinician (in most cases a clinical geneticist) will complete a clinical proforma which will provide data from their most recent clinical assessment. Qualitative interviews will be undertaken with a subset of parents partway through the study. Growth and developmental milestone curves will be generated through the DECIPHER website (https://deciphergenomics.org) where 5 or more children have the same genetic syndrome (at least 10 groups expected).
ETHICS AND DISSEMINATION
The results will be presented at national and international conferences concerning the care of children with genetic syndromes. Results will also be submitted for peer review and publication.
Topics: Humans; Rare Diseases; Child; Child, Preschool; United Kingdom; Infant; Adolescent; Research Design; Female; Male; Observational Studies as Topic; Neurodevelopmental Disorders; Cohort Studies; Multicenter Studies as Topic; Genetic Diseases, Inborn; Quality Improvement; Parents
PubMed: 38760043
DOI: 10.1136/bmjopen-2024-085237 -
BMJ Open May 2024Multidomain interventions in older adults offer the best opportunity to prevent, delay or reverse existing symptoms in the earlier stages of frailty and improve...
DIALOR (DIgitAL cOaching for fRailty): protocol for a single-arm mixed-methods feasibility study of a digital health coaching intervention for older people with frailty in primary care.
BACKGROUND
Multidomain interventions in older adults offer the best opportunity to prevent, delay or reverse existing symptoms in the earlier stages of frailty and improve independence but can be costly, and difficult to deliver at scale. However, digital health interventions enable personalised care and empowerment through self-management of long-term conditions, used at any time and when combined with health coaching offer the potential to enhance well-being and facilitate the achievement of health-related goals. We aim to evaluate the feasibility and acceptability of a digital health platform for long-term disease management combined with health coaching for people living with mild-moderate frailty, targeting self-identified goals-activity, nutrition, mood, enhancing social engagement and well-being.
METHODS AND ANALYSIS
This is a non-randomised feasibility, single-group, pretest/post-test study, using qualitative and quantitative methods. The digital health coaching intervention (DIALOR-DIgitAL cOaching for fRailty) has been developed for implementation to older adults, aged 65 years or older with mild to moderate frailty and diagnosis of one or more long-term health conditions in the community. Participants will receive 12 weeks of health coaching and have access to a mobile health platform for 6 months. The primary outcome measure is the acceptability and feasibility of DIALOR along with a range of secondary outcome measures (including frailty, functioning measures, quality of life, social engagement, diet quality and self-reported indicators) collected at baseline and at 6 months. The findings will inform whether a wider effectiveness trial is feasible and if so, how it should be designed.
ETHICS AND DISSEMINATION
Ethical approval has been granted by the Southeast Scotland Research Ethics Committee 02 (reference: 22/SS/0064). Research findings will be disseminated in a range of different ways to engage different audiences, including publishing in open-access peer-reviewed journals, conference presentations, social media, dissemination workshop with patients, carers, and healthcare professionals and on institution websites.
Topics: Humans; Feasibility Studies; Aged; Primary Health Care; Mentoring; Frailty; Frail Elderly; Telemedicine; Quality of Life; Male; Female; Aged, 80 and over; Self-Management; Digital Health
PubMed: 38760042
DOI: 10.1136/bmjopen-2023-080480 -
The Lancet. Healthy Longevity May 2024A standard treatment for fit, older patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) is yet to be established. In the previous EXTREME...
Adapted EXTREME regimen in the first-line treatment of fit, older patients with recurrent or metastatic head and neck squamous cell carcinoma (ELAN-FIT): a multicentre, single-arm, phase 2 trial.
BACKGROUND
A standard treatment for fit, older patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) is yet to be established. In the previous EXTREME trial, few older patients were included. We aimed to evaluate the efficacy and tolerance of an adapted EXTREME regimen in fit, older patients with recurrent or metastatic HNSCC.
METHODS
This single-arm, phase 2 study was done at 22 centres in France. Eligible patients were aged 70 years or older and assessed as not frail (fit) using the ELAN Geriatric Evaluation (EGE) and had recurrent or metastatic HNSCC in the first-line setting that was not eligible for local therapy (surgery or radiotherapy), and an Eastern Cooperative Oncology Group performance status of 0-1. The adapted EXTREME regimen consisted of six cycles of fluorouracil 4000 mg/m on days 1-4, carboplatin with an area under the curve of 5 on day 1, and cetuximab on days 1, 8, and 15 (400 mg/m on cycle 1-day 1, and 250 mg/m subsequently), all intravenously, with cycles starting every 21 days. In patients with disease control after two to six cycles, cetuximab 500 mg/m was continued once every 2 weeks as maintenance therapy until disease progression or unacceptable toxicity. Granulocyte colony-stimulating factor was systematically administered and erythropoietin was recommended during chemotherapy. The study was based on the two-stage Bryant and Day design, combining efficacy and toxicity endpoints. The primary efficacy endpoint was objective response rate at week 12 after the start of treatment, assessed by central review (with an unacceptable rate of ≤15%). The primary toxicity endpoint was morbidity, defined as grade 4-5 adverse events, or cutaneous rash (grade ≥3) that required cetuximab to be discontinued, during the chemotherapy phase, or a decrease in functional autonomy (Activities of Daily Living score decrease ≥2 points from baseline) at 1 month after the end of chemotherapy (with an unacceptable morbidity rate of >40%). Analysis of the coprimary endpoints, and of safety in the chemotherapy phase, was based on the per-protocol population, defined as eligible patients who received at least one cycle of the adapted EXTREME regimen. Safety in the maintenance phase was assessed in all patients who received at least one dose of cetuximab as maintenance therapy. The study is registered with ClinicalTrials.gov, NCT01864772, and is completed.
FINDINGS
Between Sept 27, 2013, and June 20, 2018, 85 patients were enrolled, of whom 78 were in the per-protocol population. 66 (85%) patients were male and 12 (15%) were female, and the median age was 75 years (IQR 72-79). The median number of chemotherapy cycles received was five (IQR 3-6). Objective response at week 12 was observed in 31 patients (40% [95% CI 30-51]) and morbidity events were observed in 24 patients (31% [22-42]). No fatal adverse events occurred. Four patients presented with a decrease in functional autonomy 1 month after the end of chemotherapy versus baseline. During chemotherapy, the most common grade 3-4 adverse events were haematological events (leukopenia [22 patients; 28%], neutropenia [20; 26%], thrombocytopenia [15; 19%], and anaemia [12; 15%]), oral mucositis (14; 18%), fatigue (11; 14%), rash acneiform (ten; 13%), and hypomagnesaemia (nine; 12%). Among 44 patients who received cetuximab during the maintenance phase, the most common grade 3-4 adverse events were hypomagnesaemia (six patients; 14%) and acneiform rash (six; 14%).
INTERPRETATION
The study met its primary objectives on objective response and morbidity, and showed overall survival to be as good as in younger patients treated with standard regimens, indicating that the adapted EXTREME regimen could be used in older patients with recurrent or metastatic HNSCC who are deemed fit with use of a geriatric evaluation tool adapted to patients with head and neck cancer, such as the EGE.
FUNDING
French programme PAIR-VADS 2011 (sponsored by the National Cancer Institute, the Fondation ARC, and the Ligue Contre le Cancer), Sandoz, GEFLUC, and GEMLUC.
TRANSLATION
For the French translation of the abstract see Supplementary Materials section.
PubMed: 38759667
DOI: 10.1016/S2666-7568(24)00048-5 -
EBioMedicine May 2024Each high-risk HPV genotype has different oncogenic potential, and the risk of CIN3+ varies according to genotype. We evaluated the performance of different strategies...
BACKGROUND
Each high-risk HPV genotype has different oncogenic potential, and the risk of CIN3+ varies according to genotype. We evaluated the performance of different strategies of HPV-positivity triage combining cytology, p16/ki67 dual staining (DS), and extended genotyping.
METHODS
Samples from 3180 consecutive women from the NTCC2 study (NCT01837693) positive for HPV DNA at primary screening, were retrospectively analyzed by the BD Onclarity HPV Assay, which allows extended genotyping. Genotypes were divided into three groups based on the risk of CIN3+. HPV DNA-positive women were followed up for 24 months or to clearance.
FINDINGS
Combining the three groups of genotypes with cytology or DS results we identify a group of women who need immediate colposcopy (PPV for CIN3+ from 7.8 to 20.1%), a group that can be referred to 1-year HPV retesting (PPV in those HPV-positive at retesting from 2.2 to 3.8), and a group with a very low 24-month CIN3+ risk, i.e. 0.4%, composed by women cytology or DS negative and positive for HPV 56/59/66 or 35/39/68 or negative with the Onclarity test, who can be referred to 3-year retesting.
INTERPRETATION
Among the baseline HPV DNA positive/cytology or DS negative women, the extended genotyping allows to stratify for risk of CIN3+, and to identify a group of women with a risk of CIN3+ so low in the next 24 months that they could be referred to a new screening round after 3 years.
FUNDING
Italian Ministry of Health (grant number RF-2009-1536040). Hologic-Genprobe, Roche Diagnostics, and Becton & Dickinson provided financial and non-financial support.
PubMed: 38759278
DOI: 10.1016/j.ebiom.2024.105149 -
The Journal of International Medical... May 2024To explore the prevalence of type I and type II infection and investigate risk factors in a population from Hainan Province in China.
OBJECTIVE
To explore the prevalence of type I and type II infection and investigate risk factors in a population from Hainan Province in China.
METHODS
Data came from a large, cross-sectional study conducted from August 2022 to April 2023 involving five cities of Hainan. Subjects with confirmed 14C-urea breath test (UBT) and positive serological assay were included. All subjects had a gastroscopy. According to presence or absence of CagA/VacA proteins, subjects were classified as either type I (present) or type II strains (absent). Gastroscopic findings and several socio-demographic factors were examined for correlation with antibody serotyping.
RESULTS
In total, 410 subjects were investigated for strain types. The overall prevalence of the highly virulent, type I strain was 79% (324/410) and type II strain was 21% (86/410). There was a strong association between type I strain and peptic ulcer disease. Of several sociodemographic factors investigated, only smoking and data over baseline (DOB) values showed significant differences between type 1 and type II strains. Logistic regression analysis showed a lower risk of type I infection in smokers compared with non-smokers, and a higher risk of type I infection in subjects with medium and high data over baseline (DOB) values compared with subjects who had low DOB values.
CONCLUSION
Highly virulent, type I infections predominate in Hainan and the co-positivity of CagA and VacA antibodies are related to type I infection. We found that Type I was closely associated with peptic ulcer disease and the DOB values were generally high.
Topics: Humans; Helicobacter pylori; Male; Female; China; Helicobacter Infections; Middle Aged; Risk Factors; Cross-Sectional Studies; Adult; Bacterial Proteins; Prevalence; Antigens, Bacterial; Peptic Ulcer; Aged; Breath Tests; Antibodies, Bacterial
PubMed: 38759213
DOI: 10.1177/03000605241253454