Large Population Studies Research Articles

Evaluating Pediatric NAFLD with Controlled Attenuation Parameter: A Comprehensive Narrative Review

Non-alcoholic fatty liver disease (NAFLD) in the pediatric population has emerged as a significant health concern due to its alarming rise in prevalence. In children, the characteristics of the disease differ from those seen in adults. NAFLD may progress to more severe liver disease in children compared to adults with similar profiles. Liver biopsy remains the gold standard for diagnosis; its invasive nature and high cost limit its use as a first-line tool. Alternatively, magnetic resonance imaging (MRI) techniques, such as magnetic resonance imaging-estimated liver proton density fat fraction (MRI-PDFF), have shown a good correlation with the degree of histological steatosis, although their use is limited by high costs and limited accessibility. Controlled attenuation parameter (CAP), integrated with vibration-controlled transient elastography (VCTE) (FibroScan®), is a novel non-invasive, accessible, and effective method for diagnosing hepatic steatosis. In this article, we reviewed the existing literature on the diagnostic accuracy of CAP in pediatric NAFLD. The PubMed and EMBASE databases were searched. Seven relevant studies were identified, conducted in pediatric hospital populations with specific demographic characteristics. Two of these studies compared CAP with liver biopsy, one compared CAP with liver biopsy and MRI-PDFF, and the remaining four compared CAP with MRI. Overall, CAP proved to be accurate in detecting the presence or absence of fatty infiltration, positioning it as a promising tool to simplify the diagnosis of NAFLD in children. However, further studies in larger populations are needed to confirm these findings and facilitate its implementation in routine clinical practice.

Ferritin Outperforms Other Biomarkers in Predicting Bone Marrow Iron Stores in Hematological Patients.

Although iron deficiency anemia is common, interpreting iron laboratory test results can be challenging in patients with comorbidities. We aimed to study the accuracy of common iron biomarkers compared with bone marrow iron staining in a large retrospective dataset of hematological patients. We collected from 6610 patients (median age 66 years) results of iron staining, with their concurrent ferritin, transferrin saturation, soluble transferrin receptor, transferrin, hemoglobin, and mean red blood cell volume results from Helsinki University Hospital electronic health records. In receiver operating characteristics (ROC) analysis, ferritin had the highest area under curve (AUC) with 88% (95% CI 86-90%) for females and 89% (87-91%) for males in predicting reduced bone marrow iron. Using a ferritin cut-off of 30 µg/L resulted in high specificity rates of 97% in females and 99% in males. However, sensitivity rates were only 54% and 35%, respectively. Other studied biomarkers had inferior AUCs. Multivariate logistic regression models did not significantly perform better in prediction compared to ferritin alone. With 50% pre-probability for reduced iron stores, a ferritin of 30 µg/L (females) and 51 µg/L (males) had 95% positive predictive value for reduced iron stores. A 95% negative predictive value was achieved at 1750 µg/L (females) and 4967 µg/L (males). In our large population study, ferritin was the best single biomarker for iron deficiency in secondary care. Adding other blood tests in a multivariate model did not improve performance. However, in these hematological patients, even a high ferritin did not rule out iron deficiency with 95% certainty.

KCNJ5 Somatic Mutations are Associated with Better Long-Term Outcomes in Patients with Unilateral Primary Aldosteronism.

The association between KCNJ5 somatic mutations and long-term outcomes in patients with operated unilateral primary aldosteronism (uPA) is unclear. To evaluate associations among KCNJ5 somatic mutations, clinical characteristics, incident long-term cardiovascular events, and all-cause mortality in uPA patients after adrenalectomy in a large longitudinal population study. We enrolled uPA patients from the Taiwan Primary Aldosteronism Investigation database who had undergone adrenalectomy between 2013 and 2017 and followed them until 2020. The outcomes were achieving complete clinical success at 1 year after adrenalectomy, long-term major adverse cardiac and cerebrovascular events (MACCEs), and mortality. Of the 358 enrolled patients (46.7% men; mean age, 51.3 years), 188 (52.5%) harbored KCNJ5 somatic mutations. The baseline characteristics of younger age [odds ratio (OR)=2.44; P=0.001], lower body mass index (OR=2.04; P=0.005), lower potassium (OR=6.55; P<0.001), and larger tumor size (OR=2.05; P=0.023) were potential predictors of KCNJ5 somatic mutations. The operated uPA patients harboring KCNJ5 somatic mutations were associated with a higher likelihood of complete clinical success at 1 year after adrenalectomy (OR=1.98; P=0.016). KCNJ5 somatic mutation carriers [hazard ratio (HR)=0.46; P=0.044), those with a shorter duration of hypertension (HR=1.05; P=0.008), and those who achieved complete clinical success (HR=0.49; P=0.036) had a lower risk of MACCEs and mortality. Operated uPA patients harboring KCNJ5 somatic mutations had a lower risk of long-term MACCEs and mortality after adrenalectomy. However, better long-term outcomes in the operated uPA patients harboring KCNJ5 somatic mutations were attenuated in those with baseline lower potassium levels, shorter duration of hypertension, obesity, higher estimated glomerular filtration rate, and residual hypertension after adrenalectomy.

Ventricular Depolarization Abnormalities and Their Role in Cardiac Risk Stratification - A Narrative Review.

Ventricular depolarization refers to the electrical activation and subsequent contraction of the ventricles, visible as the QRS complex on a 12-lead electrocardiogram (ECG). A well-organized and efficient depolarization is critical for cardiac function. Abnormalities in ventricular depolarization may indicate various pathologies and can be present in all leads if the condition is general, or in a subgroup of anatomically contiguous leads if the condition is limited to the corresponding anatomic location of the heart. Furthermore, the assessment of depolarization abnormalities on the ECG may either be identified visually or this may depend on further processing. In recent decades, assessment of depolarization abnormalities has received a lot of attention for cardiac risk stratification. This risk stratification aims to identify patients at high risk of adverse cardiac events, to tailor preventive or therapeutic interventions. In this review, we provide an oversight of different techniques for assessing abnormal ventricular depolarization and their value in diagnosing certain conditions, in risk stratification of adverse events, and in guiding therapeutic decisions. This includes QRS alterations directly corresponding to cardiac conditions, such as bundle branch blocks, or the presence of a delta wave, and also metrics aiming to qualitatively or quantitatively assess myocardial scarring, such as QRS (micro)fragmentation and QRS-scoring, and techniques assessing abnormal late depolarizations, such as signal-averaged ECG. While most established assessments of abnormal depolarization rely on human interpretation and are limited by visual detection, recently introduced analyses, such as QRS micro-fragmentation, aim to tackle these limitations. Besides eliminating bias, these automated analyses bypass the need for human interpretation, thereby paving the way for large population studies.

Predictive and prognostic nomogram models for liver metastasis in colorectal neuroendocrine neoplasms: a large population study.

In recent years, the incidence of patients with colorectal neuroendocrine neoplasms (CRNENs) has been continuously increasing. When diagnosed, most patients have distant metastases. Liver metastasis (LM) is the most common type of distant metastasis, and the prognosis is poor once it occurs. However, there is still a lack of large studies on the risk and prognosis of LM in CRNENs. This study aims to identify factors related to LM and prognosis and to develop a predictive model accordingly. In this study, the Surveillance, Epidemiology, and End Results (SEER) database was used to collect clinical data from patients with CRNENs. The logistic regression analyses were conducted to identify factors associated with LM in patients with CRNENs. The patients with LM formed the prognostic cohort, and Cox regression analyses were performed to evaluate prognostic factors in patients with liver metastasis of colorectal neuroendocrine neoplasms (LM-CRNENs). Predictive and prognostic nomogram models were constructed based on the multivariate logistic and Cox analysis results. Finally, the capabilities of the nomogram models were verified through model assessment metrics, including the receiver operating characteristic (ROC) curves, calibration curve, and decision curve analysis (DCA) curve. This study ultimately encompassed a total of 10,260 patients with CRNENs. Among these patients, 501 cases developed LM. The result of multivariate logistic regression analyses indicated that histologic type, tumor grade, T stage, N stage, lung metastasis, bone metastasis, and tumor size were independent predictive factors for LM in patients with CRNENs (p < 0.05). Multivariate Cox regression analyses indicated that age, primary tumor site, histologic type, tumor grade, N stage, tumor size, chemotherapy, and surgery were independent prognostic factors (p < 0.05) for patients with LM-CRNENs. The predictive and prognostic nomogram models were established based on the independent factors of logistic and Cox analyses. The nomogram models can provide higher accuracy and efficacy in predicting the probability of LM in patients with CRNENs and the prognosis of patients with LM. The factors associated with the occurrence of LM in CRNENs were identified. On the other hand, the relevant prognostic factors for patients with LM-CRNENs were also demonstrated. The nomogram models, based on independent factors, demonstrate greater efficiency and accuracy, promising to provide clinical interventions and decision-making support for patients.

Length of hospital stay not affected by empirical treatment with ceftriaxone versus cefuroxime for bacteraemia

AbstractAimThe preferred antibiotic treatment for bacteraemia in infants continues to be debated. We examined the duration of hospital stays as a surrogate for the effectiveness of initial treatment with ceftriaxone versus cefuroxime.MethodsThis was a retrospective review of the medical records of all infants aged 3–36 months, admitted with suspected occult bacteraemia to the paediatric department at Laniado Hospital, Israel, between 2016 and 2022. The effect of antibiotic treatment, namely ceftriaxone versus cefuroxime, on hospital stays was determined, in both the total study population and population subgroups.ResultsWe identified 217 patients (59.0% male) with a median age of 13 months and 12.4% had positive blood cultures. Approximately three‐quarters (75.6%) received cefuroxime as their initial treatment for bacteraemia and the other quarter (24.4%) received ceftriaxone. The median length of hospital stay was 3.0 (interquartile range 3.0–4.0), with no statistically significant difference between the two drugs. However, we did notice a statistically significant shorter median length of hospital stay among fully vaccinated infants treated with cefuroxime rather than ceftriaxone (p = 0.055).ConclusionThe length of hospital stay among infants diagnosed with bacteraemia was not affected by whether they initially received ceftriaxone or cefuroxime. Further studies in larger populations are needed.

Pre-pregnancy body mass index and lactational mastitis: The Japan Environment and Children's Study.

The association between maternal physique and prevalence of lactational mastitis (LM) in a large study population has not been reported. In this study, we aimed to evaluate the association between pre-pregnancy body mass index (BMI) and LM prevalence. We analyzed data collected from participants enrolled in the Japan Environment and Children's Study, a nationwide birth cohort study conducted between 2011 and 2014. Data from women with singleton births at and after 22weeks of gestation were analyzed. LM occurrence was identified from medical record transcripts obtained 1-month post-childbirth. Based on the pre-pregnancy BMI, participants were categorized into Group 1 (< 18.5kg/m2), Group 2 (18.5-24.9kg/m2), and Group 3 (≥ 25.0kg/m2). Excluding participants who were not breastfeeding, multivariable logistic regression models were used to evaluate the odds ratios (ORs) for LM in women who were breastfeeding in each BMI category. Group 2 was designated as the reference group. Maternal demographic and socio-economic characteristics were used as confounding factors. We analyzed 83,170 participants. The adjusted OR for LM in Group 3 was 0.752 (95% confidence interval, 0.606-0.932). The adjusted OR for LM in Group 1 was not significantly changed. High pre-pregnancy BMI was associated with decreased LM prevalence compared with that in the reference group. The maternal preconception physique may be associated with LM prevalence.

Guidelines for Diagnosis of Noise-Induced Hearing Loss and Their Specificity.

A recent paper by Moore, Lowe and Cox has proposed guidelines for diagnosing noise-induced hearing loss (NIHL). It is referred to here as the MLC guidelines. Our aim was to assess the specificity of those guidelines (i.e., freedom from false-positive outcomes) and compare with pre-existing guidelines. We applied the MLC guidelines and pre-existing guidelines to three data sets composed of adults who do not have a history of material noise exposure and therefore cannot have NIHL. National Health Service (NHS) ENT clinic. Five hundred thirty-six patients with hearing difficulty and/or tinnitus who denied material noise exposure. Two large archival population studies of hearing were also assessed, which included 3250 participants without material noise exposure. False-positive outcome from guidelines. The MLC guidelines demonstrated moderate or high false-positive rates overall, the magnitude depending on the noise exposure scenario and whether clinical or population samples were considered. For the procedure applicable to steady broadband noise exposure, the false-positive rate averaged 56% in the population samples, compared to 31% for previous guidelines. For exposure to intense impulse sounds, the MLC guidelines take a different approach and the false-positive rate was about 70% in the population samples and even higher in the clinic sample. For exposure to intense tones, the MLC guidelines take yet another approach and the false-positive rate reached 80%. The MLC guidelines demonstrate poorer specificity than previous guidelines. Medical experts should be aware of their poor specificity and consequential likelihood of false-positive diagnoses of NIHL.

Free-living monitoring of ALS progression in upper limbs using wearable accelerometers

BackgroundWearable technology offers objective and remote quantification of disease progression in neurological diseases such as amyotrophic lateral sclerosis (ALS). Large population studies are needed to determine generalization and reproducibility of findings from pilot studies.MethodsA large cohort of patients with ALS (N = 202) wore wearable accelerometers on their dominant and non-dominant wrists for a week every two to four weeks and self-entered the ALS Functional Rating Scale-Revised (ALSFRS-RSE) in similar time intervals. Wearable device data were processed to quantify digital biomarkers on four upper limb movements: flexion, extension, supination, and pronation using previously developed and validated open-source methodology. In this study, we determined the association between digital biomarkers and disease progression, studied the impact of study design in terms of required sensor wear-time and sensor position, and determined the impact of self-reported disease onset location on upper limb movements.ResultsThe main investigation considered data from a sensor placed on the non-dominant wrist. Participants with higher ALSFRS-RSE scores performed more frequent and faster upper limb movements compared to participants with more advanced disease status. Digital biomarkers exhibited statistically significant change over time while their rate of change was more profound compared to survey responses. Using data from the dominant wrist and changing data inclusion criteria did not alter our findings. ALS disease onset location significantly impacted use of upper limbs. Results presented here were comparable to an earlier study on twenty patients with ALS.DiscussionDigital health technologies provide sensitive and objective means to quantify ALS disease progression. Interpretable approaches, such as the one used in this paper, can improve patient evaluation and hasten therapeutic development.

Analysis of exonic deletions in a large population study provides novel insights into NRXN1 pathology

The NRXN1 locus is a hotspot for non-recurrent copy number variants and exon-disrupting NRXN1 deletions have been associated with increased risk of neurodevelopmental disorders in case-control studies. However, corresponding population-based estimates of prevalence and disease-associated risk are currently lacking. Also, most studies have not differentiated between deletions affecting exons of different NRXN1 splice variants nor considered intronic deletions. We used the iPSYCH2015 case-cohort sample to obtain unbiased estimates of the prevalence of NRXN1 deletions and their associated risk of autism, schizophrenia, depression, and ADHD. Most exon-disrupting deletions affected exons specific to the alpha isoform, and almost half of the non-exonic deletions represented a previously reported segregating founder deletion. Carriage of exon-disrupting NRXN1 deletions was associated with a threefold and twofold increased risk of autism and ADHD, respectively, whereas no significantly increased risk of depression or schizophrenia was observed. Our results highlight the importance of using population-based samples in genetic association studies.

Urinary Metabolite Profiles of Participants with Overweight and Obesity Prescribed a Weight Loss High Fruit and Vegetable Diet: A Single Arm Intervention Study.

Thus far, no studies have examined the relationship between fruit and vegetable (F and V) intake, urinary metabolite quantities, and weight change. Therefore, the aim of the current study was to explore changes in urinary metabolomic profiles during and after a 10-week weight loss intervention where participants were prescribed a high F and V diet (7 servings daily). Adults with overweight and obesity (n = 34) received medical nutrition therapy counselling to increase their F and V intakes to national targets (7 servings a day). Data collection included weight, dietary intake, and urine samples at baseline at week 2 and week 10. Urinary metabolite profiles were quantified using 1H NMR spectroscopy. Machine learning statistical approaches were employed to identify novel urine-based metabolite biomarkers associated with high F and V diet patterns at weeks 2 and 10. Metabolic changes appearing in urine in response to diet were quantified using Metabolite Set Enrichment Analysis (MSEA). Energy intake was significantly lower (p = 0.02) at week 10 compared with baseline. Total F and V intake was significantly higher at week 2 and week 10 (p < 0.05). In total, 123 urinary metabolites were quantified. At week 10, 21 metabolites showed significant changes relative to baseline. Of these, 11 metabolites also significantly changed at week 2. These overlapping metabolites were acetic acid, dimethylamine, choline, fumaric acid, glutamic acid, L-tyrosine, histidine, succinic acid, uracil, histamine, and 2-hydroxyglutarate. Ridge Classifier and Linear Discriminant Analysis provided best prediction accuracy values of 0.96 when metabolite level of baseline was compared to week 10. Urinary metabolites quantified represent potential candidate biomarkers of high F and V intake, associated with a reduction in energy intake. Further studies are needed to validate these findings in larger population studies.

Multifaceted Role of Apolipoprotein C3 in Cardiovascular Disease Risk and Metabolic Disorder in Diabetes.

Apolipoprotein C3 (APOC3) plays a critical role in regulating triglyceride levels and serves as a key predictor of cardiovascular disease (CVD) risk, particularly in patients with diabetes. While APOC3 is known to inhibit lipoprotein lipase, recent findings reveal its broader influence across lipoprotein metabolism, where it modulates the structure and function of various lipoproteins. Therefore, this review examines the complex metabolic cycle of APOC3, emphasizing the impact of APOC3-containing lipoproteins on human metabolism, particularly in patients with diabetes. Notably, APOC3 affects triglyceride-rich lipoproteins and causes structural changes in high-, very low-, intermediate-, and low-density lipoproteins, thereby increasing CVD risk. Evidence suggests that elevated APOC3 levels-above the proposed safe range of 10-15 mg/dL-correlate with clinically significant CVD outcomes. Recognizing APOC3 as a promising biomarker for CVD, this review underscores the urgent need for high-throughput, clinically feasible methods to further investigate its role in lipoprotein physiology in both animal models and human studies. Additionally, we analyze the relationship between APOC3-related genes and lipoproteins, reinforcing the value of large-population studies to understand the impact of APOC3 on metabolic diseases. Ultimately, this review supports the development of therapeutic strategies targeting APOC3 reduction as a preventive approach for diabetes-related CVD.

Life's Essential 8 and Poor Brain Health Outcomes in Middle-Aged Adults.

Mounting evidence points to a strong connection between cardiovascular risk during middle age and brain health later in life. The American Heart Association's Life's Essential 8 (LE8) constitutes a research and public health construct capturing key determinants of cardiovascular health. However, the overall effect of the LE8 on global, clinically relevant metrics of brain health is still unknown. We tested the hypothesis that worse LE8 profiles are associated with higher composite risk of the most important clinical endpoints related to poor brain health. We conducted a two-stage (discovery and replication) prospective study using data from the UK Biobank (UKB) and All of Us (AoU), 2 large population studies in the United Kingdom and the United States, respectively. The primary exposure was the LE8 score, a validated tool that captures 8 modifiable cardiovascular risk factors (blood pressure, glucose, cholesterol, body mass index, smoking, physical activity, diet, and sleep duration), organized in 3 categories (optimal, intermediate, and poor). The primary outcome was a composite of stroke, dementia, or late-life depression. We evaluated associations using multivariable Cox proportional hazard models. The discovery stage included 316,127 UKB participants (mean age 56, 52% female). Over a mean (SD) follow-up time of 4.9 (0.4) years, the unadjusted risk of the composite outcome was 0.7% (95% CI 0.61-0.74), 1.2% (95% CI 1.11-1.22), and 1.8% (95% CI 1.70-1.91) in participants with optimal, intermediate, and poor cardiovascular health, respectively (p < 0.001). This association remained significant in multivariable Cox models (intermediate vs optimal cardiovascular health hazard ratio [HR], 1.37; 95% CI 1.24-1.52, and poor vs optimal cardiovascular health HR, 2.11; 95% CI 1.88-2.36, p trend <0.001). The replication stage included 68,407 AoU participants (mean age 56, 60% female). Over a mean (SD) follow-up time of 2.9 (1.41) years, the unadjusted risk of the composite outcome was 2.8% (95% CI 2.49-3.05), 6% (95% CI 5.76-6.22), and 9.7% (95% CI 9.24-10.24) in participants with optimal, intermediate, and poor cardiovascular health, respectively (p < 0.001). This association remained significant in multivariable Cox models (intermediate vs optimal cardiovascular health, HR 1.35; 95% CI 1.21-1.51, and poor vs optimal cardiovascular health, HR 1.94; 95% CI 1.72-2.18; p trend <0.001). Among middle-aged adults enrolled in 2 large population studies, poor cardiovascular health profiles were associated with two-fold higher risk of developing a composite outcome that captures the most important diseases related to poor brain health. Because the evaluated risk factors are all modifiable, our findings highlight the potential brain health benefits of using the Life's Essential 8 to guide cardiovascular health optimization.

Physical Activity Reduces Metabolic Risk via Iron Metabolism: Cross-National Evidence Using the Triglyceride-Glucose Index.

Purpose: Studies suggest that the triglyceride-glucose index (TyG) is a novel and comprehensive marker of metabolic health. While most research indicates that increased physical activity (PA) is linked to improved metabolic health, some studies argue that the previous markers may not fully capture this relationship. This study uses TyG as a marker of metabolic health to examine the association between PA and TyG. Methods: Data are from cross-sectional surveys in three large population studies in China and the United States: CHARLS, CHNS, and NHANES. Regression models were applied to analyze the relationship between PA and TyG, with covariates adjusted in a stepwise manner. Stratified analysis was used to explore this relationship among different population groups, and, since it has been suggested that iron metabolism plays an important role in metabolic health, it was used as a mediating variable to construct a mediation model for analysis and discussion. Results: Higher PA was significantly associated with lower TyG levels across all three databases (p < 0.001), and this relationship remained robust after full adjustment for covariates. This negative association was more pronounced in older males (over 45 years). Iron metabolism also mediated this relationship, with mediation proportions ranging from 10% to 12.5%. Conclusions: There is a significant inverse association between PA and TyG, suggesting a link between increased PA and metabolic health, with iron metabolism moderating this relationship, especially among older males.

Diagnostic Accuracy and Safety of Endoscopic – Guided Office-Based Biopsies for Laryngeal and Pharyngeal Lesions at St. Luke’s Medical Center

Objective: To determine the sensitivity, specificity, positive predictive value, negative predictive value and safety of endoscopic guided office-based biopsies (OBB) in diagnosing laryngeal and pharyngeal neoplasms at the St. Luke’s Medical Center in Quezon City and Global City. Methods:Design: Diagnostic Accuracy StudySetting: Two Tertiary Private Training HospitalsParticipants: Records of patients with pharyngeal and laryngeal lesions who underwent endoscopic-guided OBB were included in the study describing safety. Only patients with subsequent operative biopsies were included in assessing diagnostic accuracy. Results: Thirty-six (36) patients were included: 28 (77.78%) males and 8 (22.22%) females, with median age of 61.5 (IQR 52-73 years). Nearly half (16/36; 44.44%) of the office-based biopsies yielded malignant histopathology results, 19.44% had high grade dysplasia while 36.11% had benign findings. Of 10 patients with operative biopsy for definitive diagnosis, 8 were correctly diagnosed with carcinoma while one had a change in diagnosis from benign to malignant. Office based biopsy was well tolerated and had no complications reported. Overall, the sensitivity of OBB in predicting malignancy was 88.89%, specificity was 100%, positive predictive value was 100%, and negative predictive value was 50%. Conclusion: Office-based biopsy is an accurate, reliable and safe modality for screening suspicious pharyngeal and laryngeal neoplasms, and may be part of routine screening during initial endoscopy among selected patients with suspicious pharyngeal and laryngeal neoplasms. Further investigation and larger population studies may provide more robust insights on effectiveness and safety of office-based biopsy in diagnosis of pharyngeal and laryngeal neoplasms.

Global Assessment of Training Needs in Addiction Medicine

Introduction: A minority of addiction patients receive appropriate treatment directly from trained professionals in addiction medicine. Most countries have not recognized addiction medicine (AM) as a specialty in its own right or within psychiatry/other specialties. Therefore, the effectiveness and organization of AM training around the world need to be improved. Unfortunately, standard instruments are rarely used in most studies to assess training needs. This study aimed to determine international competencies in AM among professionals in as many countries as possible using a standard instrument such as the AM Training Needs Assessment (AM-TNA). Method: We examined competencies in AM with the AM-TNA using an online survey. A General Competency Level in Addiction Medicine (GLOCIAM30) was calculated by dividing the total score by the number of 30 items. This GLOCIAM30 was used to measure the general level of competency in AM and to compare individual competencies. Results: One hundred ninety-nine respondents from 45 countries completed the survey. Ninety-five of the 199 respondents (49.0%) had a GLOCIAM30 higher or equal to 4 (fairly competent). The highest skill level was found for the competency “Assessing substance use problems by taking the patient’s history.” Nine of the 45 countries had 8 or more respondents (n = 129). After post hoc analysis, there was no difference between these countries. Respondents could reasonably estimate whether the competency level in their country was higher or lower than the world average. Conclusions: This study is the first international attempt to examine competencies in AM. Although a much larger study population is needed to establish an overall goal for competencies in AM, our study provided an initial direction for such a gold standard in benchmarking procedures.

Exposure to air pollutants and breast cancer risk: mediating effects of metabolic health biomarkers in a nested case–control study within the E3N-Generations cohort

BackgroundGrowing epidemiological evidence suggests an association between exposure to air pollutants and breast cancer. Yet, the underlying mechanisms remain poorly understood. This study explored the mediating role of thirteen metabolic health biomarkers in the relationship between exposure to three air pollutants, i.e. nitrogen dioxide (NO2), polychlorinated biphenyls 153 (PCB153), and benzo[a]pyrene (BaP), and breast cancer risk.MethodsWe used data from a nested case–control study within the French national prospective E3N-Generations cohort, involving 523 breast cancer cases and 523 matched controls. The four-way decomposition mediation of total effects for thirteen biomarkers was applied to estimate interaction and mediation effects (controlled direct, reference interaction, mediated interaction, and pure indirect effects).ResultsThe analyses indicated a significant increase in breast cancer risk associated with BaP exposure (odds ratio (OR)Q4 vs Q1 = 2.32, 95% confidence intervals (CI): 1.00–5.37). PCB153 exposure showed a positive association only in the third quartile (ORQ3 vs Q1 = 2.25, CI 1.13–4.57), but it appeared to be non-significant in the highest quartile (ORQ4 vs Q1 = 2.07, CI 0.93–4.61). No association was observed between NO2 exposure and breast cancer risk. Estradiol was associated with an increased risk of breast cancer (OR per one standard deviation (SD) increment = 1.22, CI 1.05–1.42), while thyroid-stimulating hormone was inversely related to breast cancer risk (OR per 1SD increase = 0.87, CI 0.75–1.00). We observed a suggestive mediated effect of the association between the three pollutants and breast cancer risk, through albumin, high-density lipoproteins cholesterol, low-density lipoprotein cholesterol, parathormone, and estradiol.ConclusionAlthough limited by a lack of statistical power, this study provides relevant insights into the potential mediating role of certain biomarkers in the association between air pollutant exposure and breast cancer risk, highlighting the need for further in-depth studies in large populations.

Single cell variant to enhancer to gene map for coronary artery disease.

Although genome wide association studies (GWAS) in large populations have identified hundreds of variants associated with common diseases such as coronary artery disease (CAD), most disease-associated variants lie within non-coding regions of the genome, rendering it difficult to determine the downstream causal gene and cell type. Here, we performed paired single nucleus gene expression and chromatin accessibility profiling from 44 human coronary arteries. To link disease variants to molecular traits, we developed a meta-map of 88 samples and discovered 11,182 single-cell chromatin accessibility quantitative trait loci (caQTLs). Heritability enrichment analysis and disease variant mapping demonstrated that smooth muscle cells (SMCs) harbor the greatest genetic risk for CAD. To capture the continuum of SMC cell states in disease, we used dynamic single cell caQTL modeling for the first time in tissue to uncover QTLs whose effects are modified by cell state and expand our insight into genetic regulation of heterogenous cell populations. Notably, we identified a variant in the COL4A1/COL4A2 CAD GWAS locus which becomes a caQTL as SMCs de-differentiate by changing a transcription factor binding site for EGR1/2. To unbiasedly prioritize functional candidate genes, we built a genome-wide single cell variant to enhancer to gene (scV2E2G) map for human CAD to link disease variants to causal genes in cell types. Using this approach, we found several hundred genes predicted to be linked to disease variants in different cell types. Next, we performed genome-wide Hi-C in 16 human coronary arteries to build tissue specific maps of chromatin conformation and link disease variants to integrated chromatin hubs and distal target genes. Using this approach, we show that rs4887091 within the ADAMTS7 CAD GWAS locus modulates function of a super chromatin interactome through a change in a CTCF binding site. Finally, we used CRISPR interference to validate a distal gene, AMOTL2, liked to a CAD GWAS locus. Collectively we provide a disease-agnostic framework to translate human genetic findings to identify pathologic cell states and genes driving disease, producing a comprehensive scV2E2G map with genetic and tissue level convergence for future mechanistic and therapeutic studies.

Airway management in pediatric patients undergoing microvascular free tissue transfer reconstruction after mandibulectomy

ObjectivesMicrovascular free tissue transfer (MVFTT) for head and neck reconstruction is infrequently performed in pediatric patients. There is a paucity of data on perioperative airway management in pediatric MVFTT, such as the need for tracheostomy, which can pose higher morbidity to young patients due to potential long-term effects on the softer, more pliable laryngotracheal cartilage. Our objective was to report airway outcomes on pediatric patients undergoing MVFTT after segmental mandibulectomy with or without tracheostomy. MethodsRetrospective chart review of pediatric patients who underwent MVFTT reconstruction after segmental mandibulectomy at a tertiary care center from 2014 to 2023. Demographic variables, surgical characteristics, and hospital clinical outcomes were recorded. Statistical analyses were performed with JMP Pro, Version 16.0.0 (2021) SAS Institute Inc., Cary, NC, 1989–2021. ResultsTen patients (median age 11.5 years old, IQR: 9.0–13.3) underwent fibular free flap reconstruction. Mandibular pathologies included 3 ameloblastoma, 2 mesenchymal chondrosarcoma, 2 desmoplastic fibroma, 1 Ewing sarcoma, 1 chondroblastic osteosarcoma, and 1 desmoid tumor. Two patients received upfront tracheostomy at time of initial surgery for a subtotal mandibulectomy and a sub-hemimandibulectomy, respectively. Both patients were decannulated within 1 week after surgery and prior to discharge. The median ICU and hospital length of stay for patients who underwent tracheostomy was 3.5 days [IQR: 3.0–4.0] and 8.5 days [IQR: 8.0–9.0] respectively. Of the remaining 8 patients without tracheostomy, surgical defects were hemimandibulectomy and anterior subtotal mandibulectomy. Median intubation duration was 1.0 day [IQR: 1.0–2.5]. The median ICU and hospital length of stay for these patients were 3.0 days [IQR: 2.0–6.3] and 8.5 days [IQR: 7.3–13.0], respectively. No patient had to be reintubated for respiratory failure following extubation or had long-term airway complications during the follow-up period. ConclusionsFibular free flap reconstruction without tracheostomy can be feasible in pediatric patients with mandibular defects, which can potentially reduce hospital resources required for fresh tracheostomy care needs and avoid additional surgical morbidity. Further studies in larger populations and prospective approaches are warranted.

Colour vision deficiency is associated with increased prevalence of amblyopia, strabismus and ametropia: a large population study

AimsTo examine the association between colour vision deficiency (CVD) and other ophthalmic disorders including amblyopia, strabismus and ametropia in a large population study.MethodsThe retrospective, cross-sectional study included 916 388 Israeli...