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PloS One 2024Danish women-who were HPV-vaccinated as girls-are now reaching an age where they are invited to cervical cancer screening. Because of their expected lower cervical... (Observational Study)
Observational Study
BACKGROUND
Danish women-who were HPV-vaccinated as girls-are now reaching an age where they are invited to cervical cancer screening. Because of their expected lower cervical cancer risk, we must reassess our screening strategies. We analyzed Danish HPV-vaccinated women's outcomes after the first screening test at age 23.
METHODS AND FINDINGS
Our study was embedded in Danish routine cytology-based screening. We conducted an observational study and included women born in 1994, offered the 4-valent HPV vaccine at age 14, and subsequently invited to screening at age 23. Cervical cytology was used for diagnostics and clinical management. Residual material was HPV tested with Cobas® 4800/6800. The most severe histology diagnosis within 795 days of screening was found through linkage with the Danish National Pathology Register. We calculated the number of women undergoing follow-up (repeated testing and/or colposcopy) per detected cervical intraepithelial neoplasia (CIN2+). A total of 6021 women were screened; 92% were HPV-vaccinated; 12% had abnormal cytology; 35% were high-risk HPV-positive, including 0.9% HPV16/18 positive, and 20% had follow-up. In women that were cytology-abnormal and HPV-positive (Cyt+/HPV+), 610 (98.5%) had been followed up, and 138 CIN2+ cases were diagnosed, resulting in 4.4 (95% CI 3.9-5.2) women undergoing follow-up per detected CIN2+. In contrast to recommendations, 182 (12.2%) cytology-normal and HPV-positive (Cyt-/HPV+) women were followed up within 795 days, and 8 CIN2+ cases were found, resulting in 22.8 (95% CI 13.3-59.3) women undergoing follow-up per detected CIN2+.
CONCLUSION
Overall, HPV prevalence was high in HPV-vaccinated women, but HPV16/18 had largely disappeared. In the large group of cytology-normal and HPV-positive women, 23 had been followed up per detected CIN2+ case. Our data indicated that primary HPV screening of young HPV-vaccinated women would require very effective triage methods to avoid an excessive follow-up burden.
TRIAL REGISTRATION
Trial registration number: NCT0304955.
Topics: Humans; Female; Denmark; Papillomavirus Vaccines; Uterine Cervical Neoplasms; Papillomavirus Infections; Early Detection of Cancer; Young Adult; Cohort Studies; Uterine Cervical Dysplasia; Adult; Adolescent; Vaccination; Human papillomavirus 18; Mass Screening
PubMed: 38917143
DOI: 10.1371/journal.pone.0306044 -
Trials Jun 2024The Movethehip trial investigates the effectiveness of an exercise and patient education intervention for adults with acetabular dysplasia. The intervention involves...
An exercise and patient education intervention to reduce pain and physical limitations in adults with acetabular dysplasia: study protocol for a process evaluation integrated within a randomised controlled trial (the MovetheHip trial).
BACKGROUND
The Movethehip trial investigates the effectiveness of an exercise and patient education intervention for adults with acetabular dysplasia. The intervention involves eight tailored one-to-one sessions with trained providers who employ supportive feedback tools. The present protocol reports a planned process evaluation, which aims to determine how the intervention functions by examining the implementation of the intervention (process, dose and reach), its acceptability, mechanisms of change and the influence of contextual factors.
METHODS
Two hundred trial participants aged 18-50 years will be recruited from a University Hospital in Denmark and randomised to the intervention or control group. Approximately ten providers will deliver the intervention. The process evaluation adopts a concurrent mixed-methods design. The implementation will be assessed using self-report questionnaires (at baseline and 6-month follow-up), training records and semi-structured focus group interviews with intervention providers (n = 10) and healthcare managers (n = 4-6). The mechanisms of change will be explored through semi-structured one-to-one interviews (at baseline and 6-month follow-up) with 15-20 purposefully sampled participants and by measuring changes in health outcomes (self-reported pain, physical functioning and quality of life completed at baseline and at 3- and 6-month follow-up). Additionally, change will be measured through an explorative examination of associations between dose and change in health outcomes, applying simple linear regression models. The acceptability of the intervention and the influence of contextual factors will be explored through one-to-one participant interviews and focus group interviews with 4-6 healthcare managers. The interviews will focus on expectations, experiences, events, personal understandings and interaction with interpersonal and organisational aspects. Interview data will be analysed using theoretical thematic analyses, and findings will be merged with quantitative data and reported jointly on a theme-by-theme basis.
DISCUSSION
The process evaluation conducted as part of the MovetheHip trial will illuminate how the intervention functions, and if the intervention is proven effective, the findings of the evaluation will contribute to pinpoint how the intervention may be optimised to facilitate future up-scaling and implementation.
TRIAL REGISTRATION
The MovetheHip protocol was approved by the Committee on Health Research Ethics in the Central Denmark Region. ClinicalTrials, NCT04795843. Registered on 20 March 2021.
Topics: Humans; Adolescent; Patient Education as Topic; Denmark; Exercise Therapy; Adult; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome; Young Adult; Acetabulum; Female; Time Factors; Male; Pain Measurement; Functional Status; Health Knowledge, Attitudes, Practice; Quality of Life; Hospitals, University; Disability Evaluation; Recovery of Function
PubMed: 38915128
DOI: 10.1186/s13063-024-08262-y -
BMC Women's Health Jun 2024The purpose of this study was to predict the risk factors for residual lesions in patients with high-grade cervical intraepithelial neoplasia who underwent total...
BACKGROUND
The purpose of this study was to predict the risk factors for residual lesions in patients with high-grade cervical intraepithelial neoplasia who underwent total hysterectomy.
METHODS
This retrospective study included 212 patients with histologically confirmed high-grade cervical intraepithelial neoplasia (CIN2-3) who underwent hysterectomy within 6 months after loop electrosurgical excision procedure (LEEP). Clinical data (e.g., age, menopausal status, HPV type, and Liquid-based cytology test(LCT) type), as well as pathological data affiliated with endocervical curettage (ECC), colposcopy, LEEP and hysterectomy, were retrieved from medical records. A logistic regression model was applied to estimate the relationship between the variables and risk of residual lesions after hysterectomy.
RESULTS
Overall, 75 (35.4%) patients had residual lesions after hysterectomy. Univariate analyses revealed that positive margin (p = 0.003), glandular involvement (p = 0.017), positive ECC (p < 0.01), HPV16/18 infection (p = 0.032) and vaginal intraepithelial neoplasia (VaIN) I-III (p = 0.014) were factors related to the presence of residual lesions after hysterectomy. Conversely, postmenopausal status, age ≥ 50 years, ≤ 30 days from LEEP to hysterectomy, and LCT type were not risk factors for residual lesions. A positive margin (p = 0.025) and positive ECC (HSIL) (p < 0.001) were identified as independent risk factors for residual lesions in multivariate analysis.
CONCLUSIONS
Our study revealed that positive incisal margins and ECC (≥ CIN2) were risk factors for residual lesions, while glandular involvement and VaIN were protective factors. In later clinical work, colposcopic pathology revealed that glandular involvement was associated with a reduced risk of residual uterine lesions. 60% of the patients with residual uterine lesions were menopausal patients, and all patients with carcinoma in situ in this study were menopausal patients. Therefore, total hysterectomy may be a better choice for treating CIN in menopausal patients with positive margins and positive ECC.
Topics: Humans; Female; Uterine Cervical Dysplasia; Hysterectomy; Retrospective Studies; Middle Aged; Risk Factors; Adult; Uterine Cervical Neoplasms; Neoplasm, Residual; Papillomavirus Infections; Margins of Excision; Electrosurgery; Aged
PubMed: 38915002
DOI: 10.1186/s12905-024-03212-x -
Biomedical Reports Aug 2024Retinopathy of prematurity (ROP) is a retinopathy caused by abnormal proliferation of blood vessels in premature infants. It can lead to retinal detachment and, in... (Review)
Review
Retinopathy of prematurity (ROP) is a retinopathy caused by abnormal proliferation of blood vessels in premature infants. It can lead to retinal detachment and, in severe cases, blindness, rendering ROP a critical condition. Advances in neonatal medicine have improved survival rates of low birth weight and low gestational age infants. However, this progress has also led to a rise in incidence of ROP. Currently, premature birth, low birth weight and high postpartum oxygen levels are independent risk factors for ROP. Other factors include mode of delivery, multiple births, anemia, blood transfusion, maternal pregnancy factors, neonatal bronchopulmonary dysplasia, use of surfactants, arterial ductus arteriosus and necrotizing enterocolitis. Laboratory indicators in premature infants such as platelet count, levels of blood glucose, inflammatory cells, lipid and hemoglobin and blood transfusion may also be associated with ROP. However, the etiology and pathogenesis of ROP are not fully understood. A number of factors may influence the onset and progression of ROP, including decreased platelet counts, decreased hemoglobin levels, increased white blood cell counts, increased blood glucose levels, and disorders of lipid metabolism. The present study reviewed the effects of platelet count, hemoglobin, blood glucose, inflammatory cells and factors, blood lipids, and plasma metabolic pathways on ROP.
PubMed: 38912168
DOI: 10.3892/br.2024.1799 -
The Korean Journal of Internal Medicine Jun 2024Recent research has increasingly focused on the role of the gastric microbiome in the development of gastric cancer. We aimed to investigate the changes in the...
BACKGROUND/AIMS
Recent research has increasingly focused on the role of the gastric microbiome in the development of gastric cancer. We aimed to investigate the changes in the microbiome during gastric carcinogenesis in structural and functional aspects, with a specific focus on the association between oral and gastric microbiomes.
METHODS
We collected saliva, gastric juice, and gastric tissue samples from 141 patients at different stages of gastric carcinogenesis and processed them for microbiome analysis using 16S rRNA gene profiling. The alpha and beta diversities were analyzed, and the differences in microbiome composition and function profiles were analyzed among the groups, as well as the correlation between changes in the oral and gastric microbiomes during carcinogenesis.
RESULTS
We observed significant differences in microbial diversity and composition between the disease and control groups, primarily in the gastric juice. Specific bacterial strains, including Schaalia odontolytica, Streptococcus cristatus, and Peptostreptococcus stomatis, showed a significant increase in abundance in the gastric juice in the low-grade dysplasia and gastric cancer groups. Notably, the correlation between the oral and gastric microbiota compositions, increased as the disease progressed. Predictive analysis of the metagenomic functional profiles revealed changes in functional pathways that may be associated with carcinogenesis (ABC transport and two-component systems).
CONCLUSIONS
During gastric carcinogenesis, the abundance of oral commensals associated with cancer increased in the stomach. The similarity in microbial composition between the stomach and oral cavity also increased, implying a potential role of oral-gastric bacterial interactions in gastric cancer development.
PubMed: 38910513
DOI: 10.3904/kjim.2023.490 -
BMJ Open Jun 2024Colposcopy is the most important diagnostic tool to detect cervical precancerous lesions and thereby prevention of cervical cancer. Due to age-dependent changes of the...
Improving diagnostic of cervical dysplasia among postmenopausal women aged ≥50 years using local vaginal oestrogen treatment prior to colposcopy: study protocol for a multicentre randomised controlled trial (the IDEAL study).
INTRODUCTION
Colposcopy is the most important diagnostic tool to detect cervical precancerous lesions and thereby prevention of cervical cancer. Due to age-dependent changes of the cervix, colposcopy is challenging in postmenopausal women, as the majority will have a non-visible transformation zone, resulting in increased risk of missing disease, a diagnostic cone biopsy and prolonged follow-up with repeated colposcopies. This study will be among the first to investigate, if treatment with vaginal oestrogen prior to colposcopy will improve the colposcopy performance, to ensure accurate and timely diagnosis of precancerous cervical lesions among postmenopausal women.
METHODS AND ANALYSIS
A randomised blinded controlled multicentre study. Enrolment will be performed at gynaecology departments in Central Denmark Region and Region of Southern Denmark. A total of 150 postmenopausal women aged ≥50 years referred for colposcopy due to abnormal cervical screening results will be randomised 1:1 to either pretreatment with vaginal application of Vagifem 30 µg or placebo once a day for 14 days prior to colposcopy. The primary outcome will be to compare the percentage of women in the two groups with a visible transformation zone at colposcopy, and biopsies representative of the transformation zone. Secondary outcomes will be the proportion of detected cervical intraepithelial neoplasia grade 2 or higher in the cervical biopsies; the proportion of diagnostics cone biopsies; the patients' report on possible side effects and compliance to the pretreatment.
ETHICS AND DISSEMINATION
The study has been approved by the Central Denmark Region Committee on Biomedical Research Ethics (1-10-72-34-22), the Central Denmark Regions' Research Unit (1-16-02-72-22) and The Danish Health Authority (Danish Medicine Agency; 2022015030). The study's EudraCT number is (1-23-456; 2022-000269-42) and it is registered on www.
CLINICALTRIALS
gov. The local Good Clinical Practice (GCP) unit will supervise and monitor the study closely before, during and after the study period. Findings will be disseminated in peer-reviewed scientific journals and presented in relevant conferences.
TRIAL REGISTRATION NUMBER
NCT05283421.
Topics: Humans; Female; Colposcopy; Uterine Cervical Dysplasia; Postmenopause; Middle Aged; Administration, Intravaginal; Uterine Cervical Neoplasms; Estrogens; Denmark; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Early Detection of Cancer
PubMed: 38910002
DOI: 10.1136/bmjopen-2023-082833 -
Neuroscience Letters Jun 2024Brain somatic variants in SLC35A2, an intracellular UDP-galactose transporter, are commonly identified mutations associated with drug-resistant neocortical epilepsy and...
Brain somatic variants in SLC35A2, an intracellular UDP-galactose transporter, are commonly identified mutations associated with drug-resistant neocortical epilepsy and developmental brain malformations, including focal cortical dysplasia type I and mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE). However, the causal effects of altered SLC35A2 function on cortical development remain untested. We hypothesized that focal Slc35a2 knockout (KO) or knockdown (KD) in the developing mouse cortex would disrupt cortical development and change network excitability. Through two independent studies, we used in utero electroporation (IUE) to introduce CRISPR/Cas9/targeted guide RNAs or short-hairpin RNAs into the embryonic mouse brain at day 14.5-15.5 to achieve Slc35a2 KO or KD, respectively, from neural precursor cells. Slc35a2 KO or KD caused disrupted radial migration of electroporated neurons evidenced by heterotopic cells located in lower cortical layers and in the sub-cortical white matter. Slc35a2 KO in neurons did not induce changes in oligodendrocyte number, importantly suggesting that the oligodendroglial hyperplasia observed in MOGHE originates from distinct cell autonomous effects of Slc35a2 mutations. Adult KO mice were implanted with EEG electrodes for 72-hour continuous recording. Spontaneous seizures were not observed in focal Slc35a2 KO mice, but there was reduced seizure threshold following pentylenetetrazol injection. Here we demonstrate that focal Slc35a2 KO or KD in vivo disrupts corticogenesis through altered neuronal migration and that KO leads to reduced seizure threshold. Together these results demonstrate a direct causal role for SLC35A2 in cortical development.
PubMed: 38909838
DOI: 10.1016/j.neulet.2024.137881 -
The Lancet. Microbe Jun 2024Microbiota alterations are common in patients hospitalised for severe infections, and preclinical models have shown that anaerobic butyrate-producing gut bacteria...
Association between butyrate-producing gut bacteria and the risk of infectious disease hospitalisation: results from two observational, population-based microbiome studies.
BACKGROUND
Microbiota alterations are common in patients hospitalised for severe infections, and preclinical models have shown that anaerobic butyrate-producing gut bacteria protect against systemic infections. However, the relationship between microbiota disruptions and increased susceptibility to severe infections in humans remains unclear. We investigated the relationship between gut microbiota and the risk of future infection-related hospitalisation in two large population-based cohorts.
METHODS
In this observational microbiome study, gut microbiota were characterised using 16S rRNA gene sequencing in independent population-based cohorts from the Netherlands (HELIUS study; derivation cohort) and Finland (FINRISK 2002 study; validation cohort). HELIUS was conducted in Amsterdam, Netherlands, and included adults (aged 18-70 years at inclusion) who were randomly sampled from the municipality register of Amsterdam. FINRISK 2002 was conducted in six regions in Finland and is a population survey that included a random sample of adults (aged 25-74 years). In both cohorts, participants completed questionnaires, underwent a physical examination, and provided a faecal sample at inclusion (Jan 3, 2013, to Nov 27, 2015, for HELIUS participants and Jan 21 to April 19, 2002, for FINRISK participants. For inclusion in our study, a faecal sample needed to be provided and successfully sequenced, and national registry data needed to be available. Primary predictor variables were microbiota composition, diversity, and relative abundance of butyrate-producing bacteria. Our primary outcome was hospitalisation or mortality due to any infectious disease during 5-7-year follow-up after faecal sample collection, based on national registry data. We examined associations between microbiota and infection risk using microbial ecology and Cox proportional hazards.
FINDINGS
We profiled gut microbiota from 10 699 participants (4248 [39·7%] from the derivation cohort and 6451 [60·3%] from the validation cohort). 602 (5·6%) participants (152 [3·6%] from the derivation cohort; 450 [7·0%] from the validation cohort) were hospitalised or died due to infections during follow-up. Gut microbiota composition of these participants differed from those without hospitalisation for infections (derivation p=0·041; validation p=0·0002). Specifically, higher relative abundance of butyrate-producing bacteria was associated with a reduced risk of hospitalisation for infections (derivation cohort cause-specific hazard ratio 0·75 [95% CI 0·60-0·94] per 10% increase in butyrate producers, p=0·013; validation cohort 0·86 [0·77-0·96] per 10% increase, p=0·0077). These associations remained unchanged following adjustment for demographics, lifestyle, antibiotic exposure, and comorbidities.
INTERPRETATION
Gut microbiota composition, specifically colonisation with butyrate-producing bacteria, was associated with protection against hospitalisation for infectious diseases in the general population across two independent European cohorts. Further studies should investigate whether modulation of the microbiome can reduce the risk of severe infections.
FUNDING
Amsterdam UMC, Porticus, National Institutes of Health, Netherlands Organisation for Health Research and Development (ZonMw), and Leducq Foundation.
PubMed: 38909617
DOI: 10.1016/S2666-5247(24)00079-X -
Medicina 2024To compare the diagnostic sensitivity of artificial intelligence (AI) assisted videocolposcopy with standard videocolposcopy performed by specialist colposcopists. (Comparative Study)
Comparative Study
INTRODUCTION
To compare the diagnostic sensitivity of artificial intelligence (AI) assisted videocolposcopy with standard videocolposcopy performed by specialist colposcopists.
METHODS
A descriptive retrospective cross-sectional study, 782 anonymized medical records from the Computerized System for Screening (SITAM) of women who underwent videocolposcopy with AI and colposcopy with common videocolposcopy performed by specialists, with their corresponding biopsies (gold standard) were analyzed. The relationship between the results of IA videocolposcopy and regular videocolposcopy and the results of biopsies was evaluated. The overall accuracy of each diagnostic procedure was calculated. The sensitivity and concordance of the results of AI videocolposcopy with the gold standard (biopsy) were determined.
RESULTS
A total of 395 patient records of patients with IA videocolposcopy and 387 with regular videocolposcopy were analyzed. The accuracy of results was 80% (IC 95%: 75-83%) in IA videocolposcopy and 65% (IC 95%: 60-69%) in regular videocolposcopy (p<0.001). Videocolposcopy results with IA and common colposcopy were significantly correlated with biopsy results, rs=0.75 vs. rs=0.57 respectively (p<0.001). The sensitivity of videocolposcopy with AI was 96% (95% CI: 94-98%), and 93% (95% CI: 89-95%) for regular colposcopy. The overall agreement of colposcopic impressions classified by videocolposcopy with AI and disease was higher than that of colposcopic interpretation by colposcopists (90% vs. 83%, Kappa 0.59 vs. 0.47, p<0.001).
CONCLUSION
The high diagnostic accuracy of AI videocolposcopy allows obtaining highly sensitive studies that help in the early detection of precursor lesions of cervical neoplasia.
Topics: Humans; Female; Artificial Intelligence; Cross-Sectional Studies; Retrospective Studies; Colposcopy; Uterine Cervical Neoplasms; Sensitivity and Specificity; Adult; Precancerous Conditions; Middle Aged; Biopsy; Uterine Cervical Dysplasia; Video Recording; Cervix Uteri; Reproducibility of Results
PubMed: 38907959
DOI: No ID Found -
Scientific Reports Jun 2024The causal relationship between Packed red blood cell (RBC) transfusion and necrotizing enterocolitis (NEC) remains uncertain. This study aims to provide an exploration... (Observational Study)
Observational Study
The causal relationship between Packed red blood cell (RBC) transfusion and necrotizing enterocolitis (NEC) remains uncertain. This study aims to provide an exploration of transfusion and NEC in very preterm infants. Using data from the Chinese Neonatal Network cohort study between 2019 and 2021, the analysis focused on very preterm infants (with a birth weight of < 1500 g or a gestational age of < 32 weeks) who developed NEC after receiving transfusions. The time interval between the prior transfusion and NEC was analyzed. An uneven distribution of the time interval implies an association of transfusion and NEC. Additionally, multivariable logistic analysis was conducted to detect the prognosis of defined transfusion-associated NEC(TANEC). Of the 16,494 infants received RBC transfusions, NEC was noted in 1281 (7.7%) cases, including 409 occurred after transfusion. Notably, 36.4% (149/409) of post-transfusion NEC occurred within 2 days after transfusion. The time interval distribution showed a non-normal pattern (Shapiro-Wilk test, W = 0.513, P < 0.001), indicating a possible link between transfusion and NEC. TANEC was defined as NEC occurred within 2 days after transfusion. Infants with TANEC had a higher incidence of death (adjusted OR 1.69; 95% CI 1.08 to 2.64), severe bronchopulmonary dysplasia (adjusted OR 2.03; 95% CI 1.41 to 2.91) and late-onset sepsis (adjusted OR 2.06; 95% CI 1.37 to 3.09) compared with infants without NEC after transfusion. Unevenly high number of NEC cases after RBC transfusions implies transfusion is associated with NEC. TANEC is associated with a poor prognosis. Further research is warranted to enhance our understanding of TANEC.
Topics: Humans; Enterocolitis, Necrotizing; Erythrocyte Transfusion; Infant, Newborn; Male; Female; Infant, Premature; Gestational Age; Infant, Very Low Birth Weight; Prognosis; Infant, Premature, Diseases; Incidence; Infant; Risk Factors; China
PubMed: 38906930
DOI: 10.1038/s41598-024-64923-7