Long-term Risk Research Articles

Genital Burns Are Associated with Worse Psychosocial and Physical Outcomes.

Genital burns are unique and complex injuries that impact patients physically and emotionally. This study investigates the specific impact of genital burns on psychosocial and physical outcomes. A retrospective cohort study was conducted using the TriNetX database, encompassing over 117 million patients from U.S. healthcare institutions. Patients with genital burns were identified and categorized into sub-cohorts based on TBSA and burn degree. Propensity score matching and cohort balancing were performed based on age, gender, race, and ethnicity. Outcomes were analyzed both short-term (1 month) and long-term (5 years), focusing on psychiatric and physical aspects. This study identified 3,496 genital burn patients over a 15-year period. Analyses revealed that genital burns significantly increased short-term risk of death (RR: 2.8), anxiety (RR: 2.656), hospitalization (RR: 2.167), and any anxiety, PTSD, or depression (RR: 2.363), and long-term risk of death (RR: 1.658) and pruritus (RR: 1.58) (all p<0.05). Interestingly, genital burn patients showed a lower risk of chronic joint pain compared to other burn injuries (RR: 0.815) (p<0.05). These results occurred independently of the extent of TBSA. Genital burns have a distinctive impact on patients, leading to higher rates of certain psychiatric morbidities and physical complications. This study highlights the need for tailored care and consideration of the unique challenges faced by patients with genital burns, both in the immediate aftermath and in the long term. Understanding the specific impacts of genital burns is vital for healthcare practitioners to develop care strategies and better support for patients recovering from such injuries.

Maternal insecure attachment representation as a long-term risk factor for disrupted mother–child-interaction and child mental health

Maternal childhood maltreatment (CM) represents an important factor in the transmission of trauma that may lead to impaired child mental health. Apart from childhood maltreatment insecure attachment has been identified as a risk factor for insensitive caregiving behavior, which may affect child's mental health. The aim of this study is to identify the working mechanisms in the relationship between maternal CM and child mental health, considering maternal attachment representation, mother–child-interaction und maternal helplessness and fear. N = 103 mother–child-dyads from a longitudinal cohort study were examined at four different measuring points. Data was assessed using self and external report questionnaires as well as the AMBIANCE scales during the Strange Situation Procedure and the Adult Attachment Projective Picture System (AAP). Maternal CM experience did not predict an insecure attachment representation (OR = 2.46 [0.98, 6.53], p = .060). Maternal insecure attachment was associated with higher AMBIANCE scores (F(8, 94) = 11.46, p < .001), which indicates more disrupted communication between mother and child. AMBIANCE scores in turn predicted higher self-perceived helplessness (F(9, 93) = 8.62, p < .001) and fear (F(9, 93) = 7.40, p < .001) in mothers. Helplessness and fear both were associated with higher SDQ-scores, indicating more mental health problems in children (F(10, 92) = 3.98, p < .001; F(10, 92) = 3.87, p < .001). The results of this study highlight how even insecure attachment in a low-risk sample has a long-term impact on parenting behavior and child mental health, therefore underlining the need of early intervention programs in affected and at-risk families.

From Life-Skills Research and Training to Sustainability: A Case Study from a Spanish University

We are currently facing a potential ‘polycrisis’, a critical inflection point that requires a holistic response aimed at building collective foresight and preparedness for short-, medium-, and long-term risks. The role of higher education institutions and social stakeholders is decisive for sustainability goals. This paper presents a case study where academia, governance, and industry have aligned to challenge, inspire, and encourage universities to enhance student growth and bind macro-scale measures leading to a sustainable future. A teaching innovation project has served as a transforming lever, in combination with the private sector, to create a platform that reaches more than 50,000 undergraduate students and teaching staff. This structure, rooted in the 2031 Strategic Plan of the University of Granada, has also served to channel local and regional initiatives, establish effective partnerships with broad social members, raise awareness, and promote actions to advance in the pursuit of Sustainable Development Goals. A comprehensive overview is provided, which details its chronology, materials, results, challenges, impact, and descriptions of the various courses, programs, and actions. The paper concludes with recommendations for future research, policy and cooperation among stakeholders.

Long-term outcome and risk stratification in compensated advanced chronic liver disease after HCV-cure

Background &amp; Rationale: Around 750.000 patients/year will be cured from hepatitis C-virus (HCV)-infection until 2030. Those with compensated advanced chronic liver disease (cACLD) remain at risk for hepatic decompensation and de-novo hepatocellular carcinoma (HCC). Algorithms have been developed to stratify risk early after cure, however, data on long-term outcome and the prognostic utility of these risk stratification algorithms at later timepoints are lacking. Main Results: We retrospectively analysed a cohort of 2335 cACLD-patients (LSM≥10kPa) who achieved HCV-cure by interferon-free therapies from 15 European centres (median age 60.2±11.9 y, 21.1% obesity, 21.2% diabetes). During a median follow-up of 6 years, first hepatic decompensation occurred in 84 patients (3.6%, incidence rate [IR]: 0.74%/year, cumulative incidence at 6 y: 3.2%); 183 (7.8%) patients developed de-novo HCC (IR: 1.60%/year, cumulative incidence at 6 y: 8.3%), with both risks being strictly linear over time. Baveno VII criteria to exclude (FU-LSM &lt;12kPa &amp; FU-PLT &gt;150 G/L) or rule-in (FU-LSM ≥25kPa) clinically significant portal hypertension (CSPH) stratified the risk of hepatic decompensation with proportional hazards. Estimated probability of CSPH discriminated patients developing versus not developing hepatic decompensation in the grey-zone (i.e., patients meeting none of the above criteria). Published HCC risk stratification algorithms identified high- and low-incidence groups, however, the size of the latter group varied substantially (9.9%-69.1%). A granular ‘HCC-SVR’ model was developed to inform on an individual patient’s HCC-risk after HCV-cure. Conclusion: In patients with cACLD, the risks of hepatic decompensation and HCC remain constant after HCV-cure, even in the long-term (&gt;3 y). One-time post-treatment risk stratification based on non-invasive criteria provides important prognostic information that is maintained during long-term follow-up, as the hazards remain proportional over time.

Reliability of EuroSCORE II on Prediction of Thirty-Day Mortality and Long-Term Results in Patients Treated with Sutureless Valves

Background: EuroSCORE II (ES2) is a reliable tool for preoperative cardiac surgery mortality risk prediction; however, a patient’s age, a surgical procedure’s weight and the new devices available may cause its accuracy to drift. We sought to investigate ES2 performance related to the surgical risk and late mortality estimation in patients who underwent aortic valve replacement (AVR) with sutureless valves. Methods: Between 2012 and 2021, a total of 1126 patients with isolated aortic stenosis who underwent surgical AVR by means of sutureless valves were retrospectively collected from six European centers. Patients were stratified into three groups according to the EuroSCORE II risk classes (ES2 &lt; 4%, ES2 4–8% and ES2 &gt; 8%). The accuracy of ES2 in estimating mortality risk was assessed using the standardized mortality ratio (O/E ratio), ROC curves (AUC) and Hosmer–Lemeshow (HL) test for goodness-of-fit. Results: The overall observed mortality was 3.0% (predicted mortality ES2: 5.39%) with an observed/expected (O/E) ratio of 0.64 (confidential interval (CI): 0.49–0.89). In our population, ES2 showed a moderate discriminating power (AUC 0.65, 95%CI 0.56–0.72, p &lt; 0.001; HL p = 0.798). Good accuracy was found in patients with ES2 &lt; 4% (O/E ratio 0.54, 95%CI 0.23–1.20, AUC 0.75, p &lt; 0.001, HL p = 0.999) and for patients with an age &lt; 75 years (O/E ratio 0.98, 95%CI 0.45–1.96, AUC 0.76, p = 0.004, HL p = 0.762). Moderate discrimination was observed for ES2 in the estimation of long-term risk of mortality (AUC 0.64, 95%CI: 0.60–0.68, p &lt; 0.001). Conclusions: EuroSCORE II showed good accuracy in patients with an age &lt; 75 years and patients with ES2 &lt; 4%, while overestimating risk in the other subgroups. A recalibration of the model should be taken into account based on the complexity of actual patients and impact of new technologies.

Long-term association of remnant cholesterol with all-cause and cardiovascular disease mortality: a nationally representative cohort study

Background and objectivesDespite reducing low-density lipoprotein cholesterol (LDL-C) to the normal range, residual cardiovascular risk remain. Remnant cholesterol (RC) exerts a potential residual risk for cardiovascular disease (CVD) prevention, and the long-term longitudinal association between RC and mortality has yet to be well elucidated.MethodsThis study examined a nationally representative sample of 13,383 adults aged 20 years or older (mean age 45.7 and 52% women) who participated in the NHANES III (from1988 to1994). Causes of death were ascertained by linkage to death records through December 31, 2019. The relations of RC with all-cause and CVD mortality were tested using weighted Cox proportional hazard models.ResultsThrough a median follow-up of 26.6 years, 5,044 deaths were reported, comprising 1,741 deaths of CVD [1,409 deaths of ischemic heart disease (IHD) and 332 deaths of stroke] and 1,126 of cancer. Compared to those with RC &amp;lt;14.26 mg/dl (lowest quartile), participants with RC ≥29.80 mg/dl (highest quartile) had multivariable-adjusted HRs of 1.23 (95% CI: 1.07–1.42) for all-cause mortality, 1.22 (95% CI: 0.97–1.53) for CVD mortality, and 1.32 (95% CI: 1.03–1.69) for IHD mortality, and 0.89 (95% CI: 0.55–1.43) for stroke mortality, and 1.17 (95% CI 0.90–1.52) for cancer mortality. We observed that elevated RC levels increased CVD risk and IHD mortality despite LDL-C being in the normal range.ConclusionsElevated blood RC was associated with an increased long-term risk of all-cause, CVD, and IHD mortality. These associations were independent of socioeconomic factors, lifestyles, and history of diseases, and remained robust across the LDL-C stratum. Measuring RC levels might favor clinical assessment of early CVD risk. Further investigation is needed to elucidate the optimal range of RC levels for cardiovascular disease health in the general population.

Serum phosphate levels at diagnosis predict long-term risk for hypopituitarism in patients with acromegaly.

Excess growth hormone (GH) secretion in acromegaly has a major impact on mineral balance and serum phosphate levels. However, the clinical utilization of serum phosphate levels as a marker for long-term disease outcomes in acromegaly has not been evaluated. This is a retrospective study of patients with acromegaly who were followed in a tertiary center. Data were retrieved on patient characteristics, endocrine and biochemical evaluation, and tumor parameters. Comparisons were performed by measuring baseline phosphate levels and conductingcorrelation analysis and multivariable logistic regression. Sixty-one patients were followed for 4.5years (range 1-21). Patients with hyperphosphatemia (> 4.5mg/dl) at baseline had larger adenomas (15.0mm [8.0, 47.0] vs. 10.0mm [3.0, 24.0], p = 0.001), a rate chance of invasive adenoma (16 [80.0%] vs. 14 [46.7%], p = 0.02), and lower serum cortisol levels (226.0nmol/l [27.6, 516.0] vs. 294.0nmol/l [32.0, 610.0], p = 0.02). Baseline serum phosphate levels positively correlated with IGF-1 levels (r = 0.43, p = 0.003) and negatively correlated with morning plasma cortisol levels (r = -0.46, p = 0.002). Regarding long-term impact, baseline phosphate levels correlated with the number of pituitary axes involved 6months after diagnosis (r-0.34, p = 0.01). In multivariable analysis, baseline plasma phosphate levels were independently associated with risk for disease progression/recurrence (odds ratio [OR] 9.66, 95% confidence interval [CI] 1.5, 105.9, p = 0.03) and for invasive adenoma (OR 6.21, 95% CI 1.6, 28.7, p = 0.01). Elevated pretreatment serum phosphate levels are associated with a greater risk of disease persistence and recurrence and with altered pituitary function in patients with acromegaly.

Peroxiredoxin 4 deficiency induces accelerated ovarian aging through destroyed proteostasis in granulosa cells

Ovarian aging, a complex and challenging concern within the realm of reproductive medicine, is associated with reduced fertility, menopausal symptoms and long-term health risks. Our previous investigation revealed a correlation between Peroxiredoxin 4 (PRDX4) and human ovarian aging. The purpose of this research was to substantiate the protective role of PRDX4 against ovarian aging and elucidate the underlying molecular mechanism in mice. In this study, a Prdx4−/− mouse model was established and it was observed that the deficiency of PRDX4 led to only an accelerated decline of ovarian function in comparison to wild-type (WT) mice. The impaired ovarian function observed in this study can be attributed to an imbalance in protein homeostasis, an exacerbation of endoplasmic reticulum stress (ER stress), and ultimately an increase in apoptosis of granulosa cells. Furthermore, our research reveals a noteworthy decline in the expression of Follicle-stimulating hormone receptor (FSHR) in aging Prdx4−/− mice, especially the functional trimer, due to impaired disulfide bond formation. Contrarily, the overexpression of PRDX4 facilitated the maintenance of protein homeostasis, mitigated ER stress, and consequently elevated E2 levels in a simulated KGN cell aging model. Additionally, the overexpression of PRDX4 restored the expression of the correct spatial conformation of FSHR, the functional trimer. In summary, our research reveals the significant contribution of PRDX4 in delaying ovarian aging, presenting a novel and promising therapeutic target for ovarian aging from the perspective of endoplasmic reticulum protein homeostasis.

Evaluating recommendation-based dietary and physical activity strategies for prostate cancer prevention: a target trial emulation in the Health Professionals Follow-up Study.

The 2018 World Cancer Research Fund/American Institute for Cancer Research recommends sustained strategies of physical activity and diet for cancer prevention, but evidence for long-term prostate cancer risk is limited. Using observational data from 27,859 men in the Health Professionals Follow-up Study, we emulated a target trial of recommendation-based physical activity and dietary strategies and 26-year risks of prostate cancer, adjusting for risk factors via the parametric g-formula. Compared with no intervention, limiting sugar-sweetened beverages showed a 0.4% (0.0-0.9%) lower risk of lethal (metastatic or fatal) disease and 0.5% (0.1-0.9%) lower risk of fatal disease. Restricting consumption of processed foods showed a 0.4-0.9% higher risk of all prostate cancer outcomes. Estimated risk differences for clinically significant disease were close to null for strategies involving fruits and non-starchy vegetables, whole grains and legumes, red meat, and processed meat, as well as under a joint strategy of physical activity and diet. Compared with a "low adherence" strategy, maintaining recommended physical activity levels showed a 0.4% (0.1-0.8%) lower risk of lethal and 0.5% (0.2-0.8%) lower risk of fatal disease. Adhering to specific components of current physical activity and dietary recommendations may help to prevent lethal and fatal prostate cancer over 26 years.

Traumatic brain injury and long-term associations with work, divorce and academic achievement

ObjectiveTraumatic brain injuries (TBI), irrespective of severity, may have long-term social implications. This study explores the relationships between TBI severity and outcomes related to work stability, divorce, and academic achievement. MethodsUsing a Danish nationwide sample of persons with and without TBI, we employed case-control and longitudinal cohort designs. The case-control design utilized individuals aged 18 to 60 years and examined work stability. Each case, employed at time of TBI, was compared with 10 matched controls. The cohort design utilized individuals alive from 1980 to 2016 with and without TBI and assessed the likelihood of 1) divorce and 2) higher-level education. TBI exposures included concussion, skull fractures, or confirmed TBI. ResultsTBI cases exhibited higher odds ratios (OR) for work instability at all follow-ups compared to controls. Increased TBI severity was associated with a higher risk of work instability at 2-year follow-up (concussion: OR = 1.83; skull fracture: OR = 2.22; confirmed TBI: OR = 4.55), and with a higher risk of not working at 10-year follow-up (confirmed TBI: OR = 2.82; concussion: OR = 1.63). The divorce incidence rate ratio (IRR) was elevated in individuals with TBI (males: IRR = 1.52; females: IRR = 1.48) compared to those without TBI. Individuals with childhood TBI had reduced chances of attaining high school degree or higher (males: IRR = 0.79; females: IRR = 0.85) compared to those without TBI. ConclusionTBI is associated with an increased long-term risk of social consequences, including work instability, divorce, and diminished chances of higher education, even in cases with concussion.

Coffee consumption and cardiometabolic health: a comprehensive review of the evidence.

This review provides a comprehensive synthesis of longitudinal observational and interventional studies on the cardiometabolic effects of coffee consumption. It explores biological mechanisms, and clinical and policy implications, and highlights gaps in the evidence while suggesting future research directions. It also reviews evidence on the causal relationships between coffee consumption and cardiometabolic outcomes from Mendelian randomization (MR) studies. Findings indicate that while coffee may cause short-term increases in blood pressure, it does not contribute to long-term hypertension risk. There is limited evidence indicating that coffee intake might reduce the risk of metabolic syndrome and non-alcoholic fatty liver disease. Furthermore, coffee consumption is consistently linked with reduced risks of type 2 diabetes (T2D) and chronic kidney disease (CKD), showing dose-response relationships. The relationship between coffee and cardiovascular disease is complex, showing potential stroke prevention benefits but ambiguous effects on coronary heart disease. Moderate coffee consumption, typically ranging from 1 to 5 cups per day, is linked to a reduced risk of heart failure, while its impact on atrial fibrillation remains inconclusive. Furthermore, coffee consumption is associated with a lower risk of all-cause mortality, following a U-shaped pattern, with the largest risk reduction observed at moderate consumption levels. Except for T2D and CKD, MR studies do not robustly support a causal link between coffee consumption and adverse cardiometabolic outcomes. The potential beneficial effects of coffee on cardiometabolic health are consistent across age, sex, geographical regions, and coffee subtypes and are multi-dimensional, involving antioxidative, anti-inflammatory, lipid-modulating, insulin-sensitizing, and thermogenic effects. Based on its beneficial effects on cardiometabolic health and fundamental biological processes involved in aging, moderate coffee consumption has the potential to contribute to extending the healthspan and increasing longevity. The findings underscore the need for future research to understand the underlying mechanisms and refine health recommendations regarding coffee consumption.

Long-term health in individuals born preterm or with low birth weight: A cohort study.

To measure the association of prematurity and non-preterm low birth weight (LBW) with several long-term health outcomes. We selected adult participants from the Constances cohort. Associations between preterm birth (<37 weeks versus ≥37 weeks) and outcomes were measured using modified Poisson regression with adjustment for participant age and parental history. We used the same modeling methods to measure the association between LBW (i.e., <sex-specific 10th percentile) and outcomes in participants born ≥ 37 weeks. We tested for an interaction between exposures and sex. Among 30,295 participants, preterm birth (5.2%) was associated with (RR[CI95]): obesity (1.25[1.08-1.46]), hypertriglyceridemia (1.23[1.07-1.42]), high LDL-cholesterol (1.16[1.05-1.28]), high blood pressure (HBP) (1.22[1.08-1.36]), metabolic syndrome (1.35[1.06-1.71]), non-alcoholic fatty liver disease (1.26[1.08-1.47]), allergic and atopic symptoms (1.06[1.01-1.12]), and lack of tertiary education (1.11[1.02-1.20]). Women had a significantly higher risk of hypertriglyceridemia and metabolic syndrome. In non-preterm participants, LBW was associated with prediabetes/diabetes (1.30[1.12-1.52]), HBP (1.22[(1.12-1.33]) and lack of tertiary education (1.13[1.07-1.20]), whereas the risk of obesity (0.83[0.73-0.95]) and abdominal obesity (0.84[0.76-0.93]) was reduced. Preterm birth and non-preterm LBW are both risk factors for several adult outcomes. However, regarding excess fat storage, their long-term effect seems to be in the opposite direction. Preterm birth is associated with a higher long-term risk of obesity, whereas low birth weight is not. This study improves the understanding of the common idea that low birth weight is associated with a long-term risk of obesity, whereas it might depend on the cause of low birth weight. These findings provide new insights into the difficult distinction between the long-term adverse health effects of preterm birth and low birth weight.

Long-term risk factors of recurrent stroke, myocardial infarction and death in patients leaving hospital with a diagnosis of ischemic stroke or TIA

Objectives. The prevalence of patients with prior stroke is increasing globally. Accordingly, there is a need for up-to-date evidence of patient-related prognostic factors for stroke recurrence, post stroke myocardial infarction (MI) and death based on long-term follow-up of stroke survivors. For this purpose, the RIALTO study was established in 2004. Design. A prospective cohort study in which patients diagnosed with ischemic stroke (IS) or transient ischemic attack (TIA) in three Copenhagen hospitals were included. Data were collected from medical records and by structured interview. Data on first stroke recurrence, first MI and all-cause death were extracted from the Danish National Patient Registry and the Danish Civil Registration System. Results. We included 1215 patients discharged after IS or TIA who were followed up by register data from April 2004 to end of 2018 giving a median follow-up of 3.5–6.9 years depending on the outcome. At the end of follow-up 406 (33%) patients had been admitted with a recurrent stroke, 100 (8%) had a MI and 822 (68%) had died. Long-term prognostic predictors included body mass index, diabetes, antihypertensive and lipid lowering treatment, smoking, a sedentary lifestyle as well as poor self-rated health and psychosocial problems. Conclusions. Long-term risk of recurrent stroke and MI remain high in patients discharged with IS or TIA despite substantial improvements in tertiary preventive care in recent decades. Continued attention to the patient risk profile among patients surviving the early phase of stroke, including comorbidities, lifestyle, and psychosocial challenges, is warranted.

Emotional Eating Prevalence and Correlates in Adolescents in the United States.

Background: Adolescent obesity rates continue to rise. A better understanding of who engages in emotional eating, a maladaptive eating style, is needed. Despite emotional eating being a frequent research target, the prevalence of emotional eating in US adolescents is currently unknown. Methods: Nationally representative adolescents (n = 1622, m = 14.48 years, 63.8% non-Hispanic White, 50.6% female) reported eating behaviors in the National Cancer Institute's Family Life, Activity, Sun, Health, and Eating (FLASHE) study. Frequencies and one-way ANOVAs were conducted to examine the rates of emotional eating across demographic and weight status groups. Correlations between emotional eating and dietary intake were examined. Results: In total, 30% of adolescents engaged in emotional eating. Older adolescents (35% of 17-year-olds), females (39%), non-Hispanic White individuals (32%), and adolescents with obesity (44%) had significantly higher rates of emotional eating. Controlling for weight status, greater adolescent emotional eating was correlated with more frequent intake of energy-dense/nutrient-poor foods (β = 0.10, p < 0.001), junk food (β = 0.12, p < 0.001), and convenience foods (β = 0.13, p < 0.001). Conclusions: This study fills a critical gap by providing insight into how common adolescent emotional eating is and highlighting demographic factors that are associated with higher rates. Nearly a third of adolescents in the United States reported eating due to anxiety or sadness, with rates higher in older adolescents, girls, non-Hispanic White adolescents, and adolescents with obesity. Emotional eating was associated with consuming less healthy foods, which conveys immediate and long-term health risks. Practitioners can intervene with emotional eating to reduce obesity and comorbid health risks.

P-030 Semen parameters as predictors of long-term health: a systematic review

Abstract Study question Do semen parameters predict long-term health outcomes in men? Summary answer Semen parameters do not have a good predictive value for mortality, diabetes, cardiovascular disease (CVD) or cancer. What is known already One in 3 men attending infertility clinics have suboptimal semen analysis. Assisted conception treatments are offered to them as treatment for infertility and their care usually ends there. There is now a growing body of evidence male infertility predicts future development of medical comorbidities. Multiple studies have looked into the association between clinical male infertility, involuntary childlessness or suboptimal sperm analysis and the risk of cancer, cardiovascular risks, diabetes, autoimmune diseases and mortality. However, there is still conflicting evidence regarding long-term health risk in men with suboptimal semen quality. Study design, size, duration A systematic review methodology was used using PRISMA guideline. The papers were selected from PubMed/MEDLINE, EMBASE and EBM from databases’ inception to May 2023. Reviews and case series were excluded. The selected studies were assessed for quality and risk of bias using QUADAS-2. Meta-analysis was done where appropriate. The scope of the analysis was to identify whether semen parameters could predict long-term health outcomes in men. Participants/materials, setting, methods Only papers reporting on health outcomes in men having at least one semen analysis result before diagnosis were included. A 2x2 contingency table was done for each study where data was available and true positives and negatives, false positives and negatives were calculated. The analysis was performed using MetaDTA, which generated estimates for sensitivity (Sn) and specificity (Sp), hierarchical summary receiver operating characteristic (HSROC) spaces and diagnostic odds ratio (DOR) with 95% confidence intervals (CI). Main results and the role of chance Twenty studies from three continents (USA, Europe and Asia) were included reporting on mortality (5), lifespan (1), cardiovascular disease (CVD) (2), diabetes (3), cancer (5), testicular carcinoma in situ (4), prostate-specific antigen (2), hospitalizations (2) and Charlson Comorbidity Index (1). Based on extracted data we could only analyse the predictive value of azoospermia and oligospermia for all-cause mortality, diabetes, CVD and cancer as there was insufficient data for other parameters. The results showed high specificity and low sensitivity of azoospermia and oligospermia for all outcomes (all-cause mortality: Sp 0.968, Sn 0.055 and Sp 0.839, Sn 0.162; diabetes: Sp 0.967, Sn 0.037 and Sp 0.902, Sn 0.046; cancer: Sp 0.964, Sn 0.135 and Sp 0.949, Sn 0.105; CVD: Sp 0.904, Sn 0.101 and Sp 0.932, Sn 0.074). HSROC model with 95% predictive region showed limited accuracy of sperm concentration as a test for any of the outcomes. DOR (95%CI) for azoospermia and oligospermia also showed that sperm concentration cannot be used as predictive test for any of the outcomes: all-cause mortality (1.72, 0.75-3.94 and 1.005, 0.59-1.693), diabetes (1.10, 0.77-1.56 and 0.44, 0.29-0.68), cancer (4.16, 1.45-11.97 and 2.18, 0.38-12.38) and CVD (1.05, 0.75-1.46 and 1.09, 0.83-1.44) when compared to normospermia. Limitations, reasons for caution Risk of Bias assessment showed high or unclear risk of bias in 14 studies mainly due to population selection. Not all laboratories adhered to WHO methodology, increasing the heterogeneity in reporting semen results and cut-offs. Concentration was the predominant parameter reported. Wider implications of the findings To answer the question whether poor semen quality is a predictor for adverse long-term health outcomes in men requires larger and well-designed studies. Until then, we should not be advising men that there are implications on long term health based on semen analysis results, with any confidence. Trial registration number not applicable

Changes in Rehmanniae Radix processing and their impact on ovarian hypofunction: potential mechanisms of action

ObjectiveThis study evaluates the research developments concerning Rehmanniae Radix in ovarian hypofunction diseases. It explores the processing methods of Rehmanniae Radix, the variations in its compounds before and after processing, the mechanism of Rehmanniae Radix and its active compounds in improving ovarian function, and the advancements in clinical applications of traditional Chinese medicine (TCM) compound that include Rehmanniae Radix.MethodsComprehensive literature search was conducted using databases such as China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database, National Science and Technology Library, the Pharmacopoeia of the People’s Republic of China, Pubmed, and the Web of Science Database. The search utilized the following Medical Subject Headings (MeSH) and keywords: “Rehmanniae Radix,” “Drying Rehmannia Root,” “Rehmannia glutinosa,” “Rehmanniae Radix Praeparata,” “Traditional Chinese Medicine Processing,” “Pharmacological Effects,” “Ovarian Aging,” “Diminished ovarian reserve,” “Premature ovarian insufficiency,” “Premature Ovarian Failure,” “Ovarian hypofunction diseases”.ResultsThe ancient Chinese medical books document various processing techniques for Rehmanniae Radix. Contemporary research has identified changes in its compounds processing and the resultant diverse therapeutic effects. When processed into Rehmanniae Radix Praeparata, it is noted for its ability to invigorate the kidney. TCM compound containing Rehmanniae Radix is frequently used to treat ovarian hypofunction diseases, demonstrating significant clinical effectiveness. The key changes in its compounds processing include cyclic dilute ether terpene glycosides, phenylethanol glycosides, sugars, and 5-hydroxymethylfurfural. Its pharmacological action is primarily linked to the improvement of granulosa cell proliferation, antioxidative and anti-aging properties, and modulation of the immune and inflammatory microenvironment. Furthermore, Rehmanniae Radix also offers therapeutic benefits for cardiovascular and cerebrovascular diseases, osteoporosis and cognitive dysfunction caused by low estrogen levels. Thereby Rehmanniae Radix mitigates both the short-term and long-term health risks associated with ovarian hypofunction diseases.ConclusionProcessed Rehmanniae Radix has shown potential to improve ovarian function, and its compound prescriptions have a definite effect on ovarian dysfunction diseases. Therefore Rehmanniae Radix was garnering interest for both basic and clinical research, with promising application prospects as a future therapeutic agent for ovarian hypofunction diseases. However, further studies on its toxicology and the design of standardized clinical trials are necessary to fully establish its efficacy and safety.

O-088 Effect of low, medium and high risk chemotherapy on the ovarian reserve in children: results of the interim analysis of a prospective multicentric trial (CHANCE)

Abstract Study question How does the ovarian reserve of children diagnosed with cancer recover after chemotherapy that is considered as low or medium risk of future infertility? Summary answer The study showed no evidence that low and medium risk treatments impact the future ovarian function in children. What is known already Acute premature ovarian insufficiency (POI) post childhood cancer treatment is estimated around 6%, varying with treatment type and age at diagnosis. Long-term risk of treatment-related infertility is challenging to assess in this population as most of the data comes from retrospective trials involving adult cohorts of childhood cancer survivors. Benefit of fertility preservation at diagnosis is evident for high risk patients. However, for low or medium risk patients, the lack of knowledge on treatment effect on the ovarian reserve and on marker reliability in children complicates counselling. Study design, size, duration CHANCE is a prospective multicentric observational trial enrolling patients aged between 3 and 14 years at cancer diagnosis. We evaluated factors associated with the risk of future infertility such as hormonal levels, puberty and menstruation, and investigated the fertility preservation strategy. Parameters were assessed at screening, one year post-screening, end of the treatment, and during follow-up (FU) until 18 years of age. An interim analysis was planned considering the duration to reach the final endpoint. Participants/materials, setting, methods Between 2014 and 2023, 144 patients were enrolled. Patients were categorized in 3 groups by cumulative equivalent dose of cyclophosphamide (CED) received: &amp;lt;4000mg/m2 (low), 4000 to 8000mg/m2 (medium) and &amp;gt;8000 mg/m2 (high). Ninety-four patients with at least one year post-treatment follow-up were included in this analysis. Mean age at diagnosis was 8.4±4 years and 38% were prepubertal, with no difference between groups (p = 0.06 and 0.26, respectively). The median time of follow-up was 32.7 months. Main results and the role of chance Patients were categorized as low (n = 58), medium (n = 18) and high (n = 18) risk based on CED. Sarcoma were most frequent in high risk, while leukemia in low/medium risk groups (p &amp;lt; 0.0001). Fertility preservation was performed in 55.6%, 27.8% and 8.6% in high, medium and low risk group, respectively (p &amp;lt; 0.0001). The majority of them underwent ovarian tissue cryopreservation. POI was defined as induced puberty and/or FSH&amp;gt;25IU/l during FU. POI occurred in 10 out of 18 (55.6%) patients in high risk group, while in no patient in the low/medium risk groups except 1 with disease recurrence. POI was associated with high doses of chemotherapy (p &amp;lt; 0.0001) and increased age (p &amp;lt; 0.007). AMH levels significantly decreased in high and medium risk group during treatment. Recovery occurs in medium but not high risk groups (p = 0.84 and 0.02 between screening and values at 1-2 years and &amp;gt;3 years of FU using repeated measures analysis). Low AMH values (&amp;lt;0.5ng/ml) was observed at 2 years of FU in 14.3%, 28.6% and 69.2% of the patients in low, medium and high risk groups respectively. The impact of treatment, particularly in medium risk group, needs confirmation as around 35% of the patients were still prepubertal at the time of the analysis. Limitations, reasons for caution This is an interim analysis of a prospective trial designed to include 275 patients. Data should be cautiously interpreted due to not reaching the calculated optimal power population. Wider implications of the findings Our data confirmed that fertility preservation should be offered to all children and adolescent treated with high risk regimen. We did not provide evidence supporting its benefit for low/medium risk pre-pubertal children. For post-pubertal medium risk patients, fertility preservation may be considered during the FU based on patient decision. Trial registration number NCT02595255

Cardiovascular Risk Factor Management After Hypertensive Disorders of Pregnancy

Hypertensive disorders of pregnancy (HDP) are associated with significantly increased risk of developing future cardiovascular disease (CVD). Obstetricians play a crucial role in CVD prevention for postpartum women and birthing people with HDP because they are primarily responsible for immediate postpartum management and can assist with care transitions to other health care practitioners for long-term management of CVD risk factors. Standardized calculators can be used to evaluate long-term CVD risk, which can help guide intensity of treatment. Emerging technologies such as remote blood pressure monitoring demonstrate promise for improving outcomes among patients with HDP. After HDP, all patients should be advised of their increased CVD risk. A plan should be made to initiate lifestyle modifications and antihypertensive therapy to achieve optimal blood pressure control with a target of lower than 130/80 mm Hg, assess lipids within 2–3 years of delivery, and evaluate for development of type 2 diabetes. Other CVD risk factors such as nicotine use should similarly be identified and addressed. In this review, we summarize the essential components of managing CVD risk after a pregnancy complicated by HDP, including blood pressure monitoring, risk stratification tools, and evidence-based lifestyle recommendations.

Blood group is a long-term cardiovascular risk factor after carotid endarterectomy

Background ABO blood group system has been clinically related to an increased incidence of cardiovascular diseases. Preliminary data relating Rhesus (Rh) factor and these outcomes also have been published. Our aim was to analyse the impact of blood group on the short and long-term outcomes after carotid endarterectomy (CEA). Materials and methods From 2012 to 2019, patients from a referral centre who underwent CEA for atherosclerotic carotid stenosis were prospectively followed. Our primary outcomes were long-term major adverse cardiovascular events (MACEs) and all-cause mortality. Secondary outcomes were perioperative complications and myocardial injury after non-cardiac surgery (MINS). Median follow-up was 50 months (interquartile range 21–69). Time-to-event analysis was used to determine the effect of ABO and Rh groups in long-term outcomes. Results One hundred and eighty-four patients were included, with a mean age of 70.1 ± 9.1 years. Eighteen (25.7%) patients with O type and 48 (42.1%) patients with non-O type presented coronary artery disease (odds ratio [OR]: 2.313, 5–95% confidence interval (CI) 1.245–4.297, p = .008). Patients Rh+ presented significantly more congestive heart failure, 23 (14.7%), p = .03. The incidence of MACE in the long-term was higher in non-O patients (adjusted hazard ratio: 2.034; CI: 1.032–4.010, p = .040). Rh− patients, presented a higher incidence of perioperative MINS. However, there was no statistically significant association with long-term risk of MACE. Conclusion The incidence of MACE in long-term analysis was higher in non-O blood type and 30-day MINS was significantly more common amongst Rh− patients. The benefit from a more complete preoperative cardiac study in these patients should be performed.

Diffusive Leakage of scCO2 in Shaly Caprocks: Effect of Geochemical Reactivity and Anisotropy

Summary Supercritical carbon dioxide (scCO2) trapping mechanisms within carbon geostorage (CGS) primarily hinge on the upper caprock system, with shales being favored for their fine-grained nature and geological abundance. Experimental assessments of CO2 reactivity in brine-saturated shales reveal microstructural changes, raising concerns about long-term CO2 leakage risks. Existing models of scCO2 transport through caprocks lack consideration for shale anisotropy. This study addresses these gaps by investigating the diffusive properties and propagation of geochemical reactivity in shaly caprocks, accounting for anisotropy. Horizontal and vertical core samples from three shale formations with varying petrophysical characteristics underwent mineralogical, total organic carbon (TOC), porosity, and velocity measurements. scCO2 treatment for up to 3 weeks at 150°F and 3,000 psi was conducted. The propagation of geochemical reactivity was monitored by multiple surface X-ray fluorescence (XRF) measurements and fine polishing. A nuclear magnetic resonance (NMR)-based H2O-D2O fluid exchange protocol was used to quantify effective diffusivities and tortuosities parallel and perpendicular to bedding. Results indicate preferential surface reactivity toward carbonate minerals; however, the apparent reaction diffusivity of the shaly caprock is notably slow (~10−15 m2/s). This aligns with previous experimental and reactive transport modeling studies, emphasizing long timescales for carbonate dissolution reactions to influence shale caprock properties. Shale-effective diffusivities display anisotropy increasing with clay content, where diffusivities parallel to bedding exceed those perpendicular by at least three times. Faster horizontal diffusion in shaly confining zones should be considered when estimating diffusive leakage along faults penetrating these zones, a significant risk in CGS. Post-scCO2 treatment, diffusivity changes vary among samples, increasing within the same order of magnitude in the clay-rich sample. Nonsteady-state modeling of scCO2 diffusion suggests limited caprock penetration over 100 years, with a minimal increase from 5 m to 7 m post-scCO2 treatment for the clay-rich sample. This study extends existing literature observations on the slow molecular diffusion of scCO2 within shaly caprocks, integrating the roles of geochemical reactions and shale anisotropy under the examined conditions.