-
The Lancet. Oncology Jun 2024There are limited data on the risks of obstetric complications among survivors of adolescent and young adult cancer with most previous studies only reporting risks for...
BACKGROUND
There are limited data on the risks of obstetric complications among survivors of adolescent and young adult cancer with most previous studies only reporting risks for all types of cancers combined. The aim of this study was to quantify deficits in birth rates and risks of obstetric complications for female survivors of 17 specific types of adolescent and young adult cancer.
METHODS
The Teenage and Young Adult Cancer Survivor Study (TYACSS)-a retrospective, population-based cohort of 200 945 5-year survivors of cancer diagnosed at age 15-39 years from England and Wales-was linked to the English Hospital Episode Statistics (HES) database from April 1, 1997, to March 31, 2022. The cohort included 17 different types of adolescent and young adult cancers. We ascertained 27 specific obstetric complications through HES among 96 947 women in the TYACSS cohort. Observed and expected numbers for births and obstetric complications were compared between the study cohort and the general population of England to identify survivors of adolescent and young adult cancer at a heighted risk of birth deficits and obstetric complications relative to the general population.
FINDINGS
Between April 1, 1997, and March 31, 2022, 21 437 births were observed among 13 886 female survivors of adolescent and young adult cancer from England, which was lower than expected (observed-to-expected ratio: 0·68, 95% CI 0·67-0·69). Other survivors of genitourinary, cervical, and breast cancer had under 50% of expected births. Focusing on more common (observed ≥100) obstetric complications that were at least moderately in excess (observed-to-expected ratio ≥1·25), survivors of cervical cancer were at risk of malpresentation of fetus, obstructed labour, amniotic fluid and membranes disorders, premature rupture of membranes, preterm birth, placental disorders including placenta praevia, and antepartum haemorrhage. Survivors of leukaemia were at risk of preterm delivery, obstructed labour, postpartum haemorrhage, and retained placenta. Survivors of all other specific cancers had no more than two obstetric complications that exceeded an observed-to-expected ratio of 1·25 or greater.
INTERPRETATION
Survivors of cervical cancer and leukaemia are at risk of several serious obstetric complications; therefore, any pregnancy should be considered high-risk and would benefit from obstetrician-led antenatal care. Despite observing deficits in birth rates across all 17 different types of adolescent and young adult cancer, we provide reassurance for almost all survivors of adolescent and young adult cancer concerning their risk of almost all obstetric complications. Our results provide evidence for the development of clinical guidelines relating to counselling and surveillance of obstetrical risk for female survivors of adolescent and young adult cancer.
FUNDING
Children with Cancer UK, The Brain Tumour Charity, and Academy of Medical Sciences.
PubMed: 38944050
DOI: 10.1016/S1470-2045(24)00269-9 -
Cell Genomics Jun 2024The phenotypic impact of compound heterozygous (CH) variation has not been investigated at the population scale. We phased rare variants (MAF ∼0.001%) in the UK...
The phenotypic impact of compound heterozygous (CH) variation has not been investigated at the population scale. We phased rare variants (MAF ∼0.001%) in the UK Biobank (UKBB) exome-sequencing data to characterize recessive effects in 175,587 individuals across 311 common diseases. A total of 6.5% of individuals carry putatively damaging CH variants, 90% of which are only identifiable upon phasing rare variants (MAF < 0.38%). We identify six recessive gene-trait associations (p < 1.68 × 10) after accounting for relatedness, polygenicity, nearby common variants, and rare variant burden. Of these, just one is discovered when considering homozygosity alone. Using longitudinal health records, we additionally identify and replicate a novel association between bi-allelic variation in ATP2C2 and an earlier age at onset of chronic obstructive pulmonary disease (COPD) (p < 3.58 × 10). Genetic phase contributes to disease risk for gene-trait pairs: ATP2C2-COPD (p = 0.000238), FLG-asthma (p = 0.00205), and USH2A-visual impairment (p = 0.0084). We demonstrate the power of phasing large-scale genetic cohorts to discover phenome-wide consequences of compound heterozygosity.
PubMed: 38944039
DOI: 10.1016/j.xgen.2024.100602 -
Interdisciplinary Cardiovascular and... Jun 2024The healthcare registries in Denmark present a unique opportunity to gain novel insights into the outcomes associated with both transcatheter and surgical approaches to...
Severe aortic stenosis treated with transcatheter aortic valve implantation or surgical aortic valve replacement with perimount in Western Denmark 2016-2022: a nationwide retrospective study.
OBJECTIVES
The healthcare registries in Denmark present a unique opportunity to gain novel insights into the outcomes associated with both transcatheter and surgical approaches to aortic valve replacement. Our objective is to enhance shared decision-making by comparing long-term mortality and clinical outcomes between treatments.
METHODS
This observational study included all patients with severe aortic stenosis undergoing elective isolated transfemoral transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR) in Western Denmark between January 2016 and April 2022. Patient population and clinical data were identified from the Western Danish Heart Registry and the National Danish Patient Registry, respectively. A propensity score-matched population was generated. Outcomes were investigated according to Valve Academic Research Consortium-3.
RESULTS
A total of 2269 TAVI patients and 1094 SAVR patients where identified. The propensity score-matched population consisted of 468 TAVI patients (mean[SD]age, 75.0[5.3] years) and 468 SAVR patients (mean[SD] age, 75.1[4.6]years). The Kaplan-Meier estimate for the 5-year all-cause mortality was 29.8% in the TAVI group and 16.9% for in the SAVR group (p = 0.019). The risk of all stroke or transient ischaemic attack after five year was 15.1% in the TAVI group and 11.0% in the SAVR group (p = 0.047).
CONCLUSIONS
This study underscores the importance of evaluating all patient factors when choosing an aortic valve replacement method. Surgical aortic valve replacement was a viable choice, especially for patients with New-York Heart Association class I/II, ≥75 age, left ventricular ejection fraction ≥50%, or longer life expectancy.
PubMed: 38944031
DOI: 10.1093/icvts/ivae122 -
Journal of Psychiatric Research Jun 2024Numerous studies on post-COVID syndrome (PCS) describe persisting symptoms of cognitive impairment. Previous studies, however, often investigated small samples or did...
Numerous studies on post-COVID syndrome (PCS) describe persisting symptoms of cognitive impairment. Previous studies, however, often investigated small samples or did not assess covariates possibly linked to cognitive performance. We aimed to describe 1) global and domain-specific cognitive performance in adults with PCS, controls with previous SARS-CoV-2 infection and healthy controls, 2) associations of sociodemographics, depressive symptoms, anxiety, fatigue, somatic symptoms and stress with cognitive performance and subjective cognitive decline (SCD), using data of the LIFE-Long-COVID-Study from Leipzig, Germany. Group differences in cognitive performance and associations with sociodemographic and neuropsychiatric covariates were assessed using multivariable regression analyses. Our study included n = 561 adults (M: 48.8, SD: 12.7; % female: 70.6). Adults with PCS (n = 410) performed worse in tests on episodic memory (b = -1.07, 95 % CI: -1.66, -0.48) and visuospatial abilities (b = -3.92, 95 % CI: -6.01, -1.83) compared to healthy controls (n = 64). No impairments were detected for executive function, verbal fluency, and global cognitive performance. Odds of SCD were not higher in PCS. A previous SARS-CoV-2 infection without PCS (n = 87) was not linked to cognitive impairment. Higher age and higher levels of stress and fatigue were linked to worse performance in several cognitive domains. Routine administration of tests for episodic memory and visuospatial abilities might aid in the identification of individuals at risk for cognitive impairment when reporting symptoms of PCS. Low numbers of participants with severe COVID-19 infections possibly limit generalizability of our findings.
PubMed: 38944016
DOI: 10.1016/j.jpsychires.2024.06.036 -
Ecotoxicology and Environmental Safety Jun 2024Millions of adults and children are exposed to high levels of lead, a neurotoxicant, each year. Recent evidence suggests that lead exposure may precipitate...
Millions of adults and children are exposed to high levels of lead, a neurotoxicant, each year. Recent evidence suggests that lead exposure may precipitate neurodegeneration, particularly if the exposure occurs early or late in life, with unique alterations to the structure or function of specific subfields of the hippocampus, a region involved in memory and Alzheimer's disease. It has been proposed that specific hippocampal subfields may thus be useful biomarkers for lead-associated neurological disease. We turned to a population-representative New Zealand birth cohort where the extent of lead exposure was not confounded by social class (the Dunedin Study; born 1972-1973 and followed to age 45) to test the hypothesis that early life lead exposure (blood-lead level at age 11 years) is associated with smaller MRI-assessed gray matter volumes of specific subfields of the hippocampus at age 45 years. Among the 508 Dunedin Study members with childhood lead data and adult MRI data passing quality control (93.9 % of those with lead data who attended the age-45 assessment wave, 240[47.2 %] female), childhood blood-lead levels ranged from 4 to 31 µg/dL (M[SD]=10.9[4.6]). Total hippocampal volumes were lower among adults with higher childhood blood-lead levels (b=-102.6 mm per 5 ug/dL-unit greater blood-lead level, 95 %CI: -175.4 to -29.7, p=.006, β=-.11), as were all volumes of the 24 hemisphere-specific subfields of the hippocampus. Of these 24 subfields, 20 demonstrated negative lead-associations greater than β=-.05 in size, 14 were statistically significant after adjustment for multiple comparisons (p<.05), and 9 remained significant after adjustment for potential confounders and multiple comparisons. Children exposed to lead demonstrate smaller volumes across all subfields of the hippocampus in midlife. The hypothesis that lead selectively impairs specific subfields of the hippocampus, or that specific subfields may be markers for lead-associated neurological disease, requires further evaluation.
PubMed: 38944006
DOI: 10.1016/j.ecoenv.2024.116658 -
International Immunopharmacology Jun 2024Lung adenocarcinoma (LUAD) is the most common and aggressive cancer with a high incidence. N1-specific pseudouridine methyltransferase (EMG1), a highly conserved...
BACKGROUND AND AIMS
Lung adenocarcinoma (LUAD) is the most common and aggressive cancer with a high incidence. N1-specific pseudouridine methyltransferase (EMG1), a highly conserved nucleolus protein, plays an important role in the biological development of ribosomes. However, the role of EMG1 in the progression of LUAD is still unclear.
METHODS
The expression of EMG1 in LUAD cells, and LUAD tissues, and adjacent noncancerous tissues was quantified using real-time polymerase chain reaction (PCR) and western blotting. The roles of EMG1 in LUAD cell proliferation, migration, invasion and tumorigenicity were explored in vitro and in vivo. Western blot analysis to underlying molecular mechanism of EMG1 regulating the biological function of LUAD. EMG1 expression and its impact on tumor prognosis were analyzed using a range of databases including GEPIA, UALCAN, cBioPortal, LinkedOmics, and Kaplan-Meier Plotter.
RESULTS
EMG1 expression was elevated in LUAD patients compared to normal tissues, and EMG1 expression was strongly correlated with prognosis in LUAD patients. EMG1 expression correlated with age, gender, N stage, T stage, and pathologic stage. EMG1 expression was strongly positively correlated with MRPL51, PHB2, SNRPG, ATP5MD, and TPI1, and strongly negatively correlated with MACF1, DOCK9, RAPGEF2, SYNJ1, and KIDINS220, the major enrichment pathways for EMG1 and related genes include Cell cycle, DNA Replication and Pathways in cancer signaling pathways. EMG1 expression level was significantly increased in LUAD cell lines and tissues. Knockdown of EMG1 could inhibit LUAD cell proliferation, migration, invasion, and tumorigenicity. Besides, EMG1 overexpression could promote LUAD cell proliferation, migration, and invasion. High expression of EMG1 predicts poor prognosis in LUAD patients, and EMG1 may play an oncogenic role in the tumor microenvironment by participating in the infiltration of LUAD immune cells.
CONCLUSIONS
EMG1 regulated various functions in LUAD by directly mediating Akt/mTOR/p70s6k signaling pathways activation. The results suggest that EMG1 may be a novel biomarker for assessing prognosis and immune cell infiltration in LUAD.
PubMed: 38943975
DOI: 10.1016/j.intimp.2024.112553 -
International Journal of Surgery Case... Jun 2024Subglottic stenosis (SGS) appears to be a commonly encountered condition in the paediatric age group. Single stage cricoid split laryngoplasty with costochondral rib...
INTRODUCTION AND IMPORTANCE
Subglottic stenosis (SGS) appears to be a commonly encountered condition in the paediatric age group. Single stage cricoid split laryngoplasty with costochondral rib grafting in paediatric patients is a unique, innovative, and advanced operation in nature. Morbidity and mortality rates can be minimized with early diagnosis and prompt treatment.
PRESENTATION OF CASE
Presenting the case of a 13-month-old child diagnosed with Grade II SGS who was managed for cricoid split laryngoplasty with a costochondral rib graft. It was a unique strategy for providing infants and neonates with symptomatic SGS with a safe and efficient substitute for long-term tracheostomy. When healing was completed, the patient regained the function of their airway. The approach was successful, and preventable to long-term tracheostomy.
DISCUSSION
Performing this procedure early in children has shown higher rates of success and it is safe and effective. Further extensive research and studies need to be conducted in this domain, and every patient's status should be reviewed time and again to tend to their specific needs, and the choice of procedure should be made optimally based on clinical evaluations.
CONCLUSION
Successful management of a 13-month-old child with Grade II subglottic stenosis through cricoid split laryngoplasty with costochondral rib grafting is a challenging and novel approach to treating single-stage SGS.
PubMed: 38943940
DOI: 10.1016/j.ijscr.2024.109952 -
International Journal of Surgery Case... Jun 2024Esophageal varices are dilated distal submucosal esophageal veins that connect the portal and systemic circulations. They are formed due to portal hypertension, which...
INTRODUCTION
Esophageal varices are dilated distal submucosal esophageal veins that connect the portal and systemic circulations. They are formed due to portal hypertension, which commonly resulted from cirrhosis. We presented an 8-year-old girl with esophageal varices without signs of cirrhosis. This case report aims to describe non-cirrhotic portal hypertension causing esophageal varices in a school-age girl.
PRESENTATION OF CASE
An 8-year-old girl presented with one month of progressive hematemesis. The patient had been diagnosed with esophageal varices since she was 6 years old. Liver function test was within normal limits, complete blood count revealed bicytopenia.
DISCUSSION
Due to well-preserved liver function, the patient underwent distal splenorenal shunt (DSRS). After the surgical procedure, the patient's clinical condition generally improved.
CONCLUSION
NCPH (non-cirrhotic portal hypertension) is treated similarly with cirrhotic portal hypertension. DSRS could be the treatment of choice for refractory esophageal varices.
PubMed: 38943932
DOI: 10.1016/j.ijscr.2024.109941 -
The International Journal on Drug Policy Jun 2024Alcohol pricing policies may reduce alcohol-related harms, yet little work has been done to model their effectiveness beyond health outcomes especially in Australia. We...
AIMS
Alcohol pricing policies may reduce alcohol-related harms, yet little work has been done to model their effectiveness beyond health outcomes especially in Australia. We aim to estimate the impacts of four taxation and minimum unit pricing (MUP) interventions on selected social harms across sex and age subgroups in Australia.
METHODS
We used econometrics and epidemiologic simulations using demand elasticity and risk measures. We modelled four policies including (A) uniform excise rates (UER) (based on alcohol units) (B) MUP $1.30 on all alcoholic beverages (C) UER + 10 % (D) MUP$ 1.50. People who consumed alcohol were classified as (a) moderate (≤ 14 Australian standard drinks (SDs) per week) (b) Hazardous (15-42 SDs per week for men and 14-35 ASDs for women) and (c) Harmful (> 42 SDs per week for men and > 35 ASDs for women). Outcomes were sickness absence, sickness presenteeism, unemployment, antisocial behaviours, and police-reported crimes. We used relative risk functions from meta-analysis, cohort study, cross-sectional survey, or attributable fractions from routine criminal records. We applied the potential impact fraction to estimate the reduction in social harms by age group and sex after implementation of pricing policies.
RESULTS
All four modelled pricing policies resulted in a decrease in the overall mean baseline of current alcohol consumption, primarily due to fewer people drinking harmful amounts. These policies also reduced the total number of crimes and workplace harms compared to the current taxation system. These reductions were consistent across all age and sex subgroups. Specifically, sickness absence decreased by 0.2-0.4 %, alcohol-related sickness presenteeism by 7-9 %, unemployment by 0.5-0.7 %, alcohol-related antisocial behaviours by 7.3-11.1 %, and crimes by 4-6 %. Of all the policies, the implementation of a $1.50 MUP resulted in the largest reductions across most outcome measures.
CONCLUSION
Our results highlight that alcohol pricing policies can address the burden of social harms in Australia. However, pricing policies should just form part of a comprehensive alcohol policy approach along with other proven policy measures such as bans on aggressive marketing of alcoholic products and enforcing the restrictions on the availability of alcohol through outlet density regulation or reduced hours of sale to have a more impact on social harms.
PubMed: 38943908
DOI: 10.1016/j.drugpo.2024.104502 -
Developmental Cognitive Neuroscience Jun 2024Heavy alcohol drinking is a major, preventable problem that adversely impacts the physical and mental health of US young adults. Studies seeking drinking risk factors...
Heavy alcohol drinking is a major, preventable problem that adversely impacts the physical and mental health of US young adults. Studies seeking drinking risk factors typically focus on young adults who enrolled in 4-year residential college programs (4YCP) even though most high school graduates join the workforce, military, or community colleges. We examined 106 of these understudied young adults (USYA) and 453 4YCPs from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) by longitudinally following their drinking patterns for 8 years from adolescence to young adulthood. All participants were no-to-low drinkers during high school. Whereas 4YCP individuals were more likely to initiate heavy drinking during college years, USYA participants did so later. Using mental health metrics recorded during high school, machine learning forecasted individual-level risk for initiating heavy drinking after leaving high school. The risk factors differed between demographically matched USYA and 4YCP individuals and between sexes. Predictors for USYA drinkers were sexual abuse, physical abuse for girls, and extraversion for boys, whereas 4YCP drinkers were predicted by the ability to recognize facial emotion and, for boys, greater openness. Thus, alcohol prevention programs need to give special consideration to those joining the workforce, military, or community colleges, who make up the majority of this age group.
PubMed: 38943839
DOI: 10.1016/j.dcn.2024.101413