Risk Of Events Research Articles

The impact of knowledge brokering on nurses’ empathy with patients receiving cardiac care: an experimental study

Background: Patients with cardiovascular diseases often experience fear of death, depression and anxiety, all of which are linked to a heightened risk of future cardiac events. Research indicates that improved empathy is associated with a reduced risk of such events, making the enhancement of empathy among cardiac nurses crucial. Knowledge brokering, a strategy that utilises various interventions to strengthen practice, is key to achieving this. Purpose: This study aims to examine the impact of knowledge brokering on nurses’ empathy towards patients receiving cardiac care. Methods: This experimental study involved 100 cardiac nurses who were randomly assigned to control and intervention groups. The intervention group received knowledge brokering using Dobbin’s seven-stage method. Empathy levels were measured using the Empathy Construct Rating Scale (ECRS), with scores ranging from +252 to -252, and analysed using SPSS version 21. Results: Findings showed a significant mean empathy change score (MECS) of 22.90 ± 50.93 in the intervention group (p=0.003) compared to 7.10 ± 60.20 in the control group (p=0.408). Notably, nurses with a baseline empathy score of ≥100 in the intervention group exhibited a significantly higher adjusted MECS than the control group (11.44 units versus -15.42 units). Conclusion: Knowledge brokering can enhance empathy in moderately empathic cardiac nurses, with its effectiveness influenced by the nurses’ initial empathy levels. This study contributes to a deeper understanding of the knowledge brokering strategy in healthcare settings.

Perioperative administration of sub-anesthetic ketamine/esketamine for preventing postpartum depression symptoms: A trial sequential meta-analysis

Objective Postpartum depression (PPD) is a major mental health issue affecting 10%–15% of women globally. This meta-analysis synthesized updated evidence on sub-anesthetic ketamine/esketamine’s efficacy in preventing PPD. Methods Randomized controlled trials (RCTs) comparing ketamine/esketamine to a placebo for PPD prevention were searched without language restriction. Primary outcomes were PPD risk at 1- and 4–6-week postpartum. Secondary outcomes included the difference in depression scores and risk of adverse events. Trial sequential analysis (TSA) was conducted to validate the reliability. Results A meta-analysis of 22 RCTs (n = 3,463) showed that ketamine/esketamine significantly decreased PPD risk at 1- (risk ratio [RR], 0.41; 95% confidence interval [CI], 0.3–0.57) and 4–6-week (RR, 0.47; 95%CI, 0.35–0.63) follow-ups. Consistently, participants receiving ketamine/esketamine had lower depression-related scores at 1- (standardized mean difference [SMD], −0.94; 95%CI, −1.26 to −0.62) and 4–6-week (SMD, −0.89; 95%CI, −1.25 to −0.53) follow-ups. Despite potential publication bias, TSA confirmed the evidence’s reliability. Subgroup analysis showed that ketamine/esketamine’s preventive effect on 1-week PPD was consistent, regardless of administration timing, type of agents, or total dosage (<0.5 vs. ≥0.5 mg/kg). For the 4–6-week period, PPD risk was favorably reduced only with postoperative administration or the use of esketamine, with the total dosage having no observed influence. Participants on ketamine/esketamine experienced more frequency of hallucinations (RR, 4.77; 95%CI, 1.39–16.44) and dizziness (RR, 1.36; 95%CI, 1.02–1.81). Conclusion Our findings advocate for the postoperative administration of low-dose ketamine/esketamine to avert PPD, which needed additional research for confirmation.

The safety of indocyanine green in patients with advanced chronic kidney disease or kidney transplantation – a scoping review

Near-infrared fluorescence imaging with indocyanine green (ICG) is increasingly being used in the field of image-guided surgery. Although ICG is considered non-nephrotoxic in current literature, caution is advised for the use of ICG in patients with advanced chronic kidney disease (CKD), including kidney transplant recipients. Therefore, a scoping review was performed to assess the safety of ICG in patients with advanced CKD or a renal allograft. This scoping review was guided by the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-analyses extension for Scoping Reviews). Web of Science, PubMed, and Embase were searched for articles and abstracts in which ICG was administered in patients with CKD or a renal allograft. The extracted data included the incidence of adverse events, kidney function after injection of ICG, preservation of transplant function, and type of other possible complications. The initial search resulted in 635 records of which nineteen studies were found eligible for the review. ICG was used for multiple purposes but never specifically as an objective to investigate possible nephrotoxicity. No adverse events were reported in the transplant group (n=250) or the CKD group (n= 74). Despite ICG-injection, preservation of transplant function after transplantation surgery was 94% in 198 patients, and no increase in possible ICG-related other complications was reported. This scoping review found no evidence that ICG increases the risk of adverse events in patients with CKD, including kidney transplant recipients. Therefore, the administration of ICG should not be withheld from these patients.

Assessing coronary artery stenosis exacerbated impact on left ventricular function and deformation in metabolic syndrome patients by 3.0 T cardiac magnetic resonance imaging

Abstract Background Metabolic syndrome (MetS) and coronary artery stenosis (CAS) independently increase the risk of cardiovascular events, while the impact of CAS on left ventricular (LV) function and deformation in MetS patients remains unclear. This study investigates how varying degrees of CAS exacerbate LV function and myocardial deformation in MetS patients. Methods One hundred thirty-one MetS patients who underwent CMR examinations were divided into two groups: the MetS(CAS−) group (n = 47) and the MetS(CAS+) group (n = 84). The MetS(CAS+) group was divided into MetS with non-obstructive CAS(NOCAS+) (n = 30) and MetS with obstructive CAS(OCAS+) group (n = 54). Additionally, 48 age- and sex-matched subjects were included as a control group. LV functional and deformation parameters were measured and compared among subgroups. The determinants of decreased LV global peak strains in all MetS patients were identified using linear regression. The receiver operating characteristic (ROC) curve and logistic regression model (LRM) evaluated the diagnostic accuracy of the degree of CAS for identifying impaired LV strain. Results Compared to MetS(CAS−), MetS(NOCAS+) showed a significantly increased LV mass index (p < 0.05). Global longitudinal peak strain was decreased gradually from MetS(CAS−) through MetS(NOCAS+) to MetS(OCAS+) (− 13.02 ± 2.32% vs. − 10.34 ± 4.05% vs. − 7.55 ± 4.48%, p < 0.05). MetS(OCAS+) groups showed significantly decreased LV global peak strain (GPS), PSSR and PDSR in radial and circumferential directions compared with MetS(NOCAS+) (all p < 0.05). The degree of CAS was independently associated with impaired global radial peak strain (GRPS) (β = − 0.289, p < 0.001) and global longitudinal peak strain (GLPS) (β = 0.254, p = 0.004) in MetS patients. The ROC analysis showed that the degree of CAS can predict impaired GRPS (AUC = 0.730) and impaired GLPS (AUC = 0.685). Conclusion Besides traditional biochemical indicators, incorporating CAS assessment and CMR assessment of the LV into routine evaluations ensures a more holistic approach to managing MetS patients. Timely intervention of CAS is crucial for improving cardiovascular outcomes in this high-risk population.

Treatment Preferences of Physicians Treating Adult Patients with Attention-Deficit/Hyperactivity Disorderin the United States and Canada: A Discrete Choice Experiment.

Factors influencing attention-deficit/hyperactivity disorder (ADHD) treatment preferences have been studied among patients but not physicians in the United States (US) and Canada. This study assessed treatment preferences of physicians treating adult patients with ADHD in both countries. An online discrete choice experiment (DCE) was conducted (October 4-20, 2023) among physicians from Dynata's US and Canadian panel who treated adult patients with ADHD. Preference weights for efficacy (improvement in ADHD symptoms) and safety [risks of adverse events (AEs)] attributes were estimated using a conditional logistic regression model, and were used to calculate the willingness to trade-off and relative importance of the attributes. Among 510 US and 347 Canadian physicians (64.1% and 69.2% male, respectively), improvement in ADHD symptoms had a significant positive impact, and the risks of AEs (except the risk of feeling jittery in Canada) had a significant negative impact on physician preferences for ADHD treatments. US physicians were willing to tradeoff 0.44, 0.35, 0.20, 0.17, and 0.17 percentage points of improvement in ADHD symptoms to avoid a one-percentage-point risk of insomnia, nausea, feeling jittery, anxiety, and dry mouth, respectively; among Canadian physicians, these were 0.31, 0.21, 0.12, 0.20, and 0.07, respectively. The relative importance of the efficacy versus safety attributes (i.e., the risks of AEs included in the DCE taken together) was 45.5% versus 54.5% in the US and 56.3% versus 43.7% in Canada. Efficacy was the most important single attribute for physicians treating adult patients with ADHD in both the US and Canada; however, the risks of AEs taken together had greater relative importance than efficacy alone among US but not Canadian physicians. These findings highlight potential discrepancies in physician and patient preferences based on existing evidence and underscore the importance of shared decision-making, which may in turn increase patients' treatment satisfaction.

A higher JAK2V617F allele burden may be a risk factor for hemorrhagic events in younger patients with polycythemia vera

ABSTRACT Objectives: Hemorrhagic events are a rare but potentially fatal complication in patients with polycythemia vera (PV). Methods: We analyzed the characteristics of hemorrhagic events in 267 patients with PV. Results: A median follow-up of 4.8 years revealed that 23 (8.6%) hemorrhagic events occurred. Significantly more hemorrhagic events occurred in younger patients aged below 60 years (n = 72) than in older patients aged 60 years or above (n = 191) (n = 12 [16.7%] vs. n = 11 [5.8%], respectively, P = 0.012). In univariate analysis among the younger patients, white blood cell (WBC) count ≥ 15 × 109/L (hazard ratio [HR] = 7.746, 95% confidence interval [CI] 2.082-28.830, P = 0.002), palpable splenomegaly (HR = 5.629, 95% CI 1.193–26.550, P = 0.029), and JAK2V617F allele burden ≥ 80% (HR = 22.850, 95% CI 2.885–181.00, P = 0.003) were associated with an increased risk of hemorrhagic events. In multivariate analysis, JAK2V617F allele burden ≥ 80% (HR = 9.394, 95% CI 1.046–84.380, P = 0.046) was a significant risk factor. Conclusions: There is an increased risk of hemorrhagic events after diagnosis in younger PV patients with a high JAK2V617F allele burden, high WBC count or palpable splenomegaly. It is important to consider treatment options that aim to avoid hemorrhagic events by reducing the JAK2V617F allele burden in younger PV patients.

Effect of intravenous tranexamic acid on postoperative drainage and elbow joint function after traumatic elbow stiffness release

To explore the effect of intravenous tranexamic acid on postoperative drainage and elbow joint function after traumatic elbow stiffness release. The clinical data of 44 patients with elbow joint stiffness who were treated with release surgery between March 2022 and December 2023 and met the selection criteria were retrospectively analyzed. Among them, 20 patients were given intravenous infusion of 100 mL (1 g/100 mL, once a day) of tranexamic acid solution for 3 consecutive days after surgery (group A), and 24 patients were not treated with tranexamic acid after surgery (group B). There was no significant difference in baseline data such as gender, age, side, body mass index, initial injury, and preoperative hemoglobin, visual analogue scale (VAS) score, and Mayo elbow function score (MEPS), elbow flexion and extension activity between the two groups ( P>0.05). The drainage volume at 1 day and 3 days after operation, total drainage volume, drainage tube indwelling time, postoperative hospital stay, VAS score before operation and at 1, 2, and 3 days after operation, MEPS score before operation, at 3 months after operation, and at last follow-up, and elbow flexion and extension activity before operation and at last follow-up were recorded and compared between the two groups. Both groups of patients successfully completed the operation, and there was no significant difference in operation time ( P>0.05). The drainage volume at 1 day and 3 days after operation, total drainage volume, drainage tube indwelling time, and postoperative hospital stay in group A were significantly less than those in group B ( P<0.05). Both groups of patients were followed up 6-12 months, with an average of 8.6 months. No complications such as wound infection, elbow joint varus and varus instability or dislocation, and pulmonary embolism or other thromboembolic events occurred in either group. The VAS scores of both groups were significantly higher at 1 day and 2 days after operation than before operation ( P<0.05); the VAS score of group A was significantly lower than that of group B ( P<0.05). The VAS scores of both groups decreased to the preoperative level at 3 months after operation, and there was no significant difference between the two groups ( P>0.05). At 3 months after operation and at last follow-up, the MEPS scores of both groups significantly improved when compared with those before operation ( P<0.05); there was no significant difference between the two groups ( P>0.05). At last follow-up, the postoperative elbow flexion and extension activity of the two groups significantly increased when compared with that before operation ( P<0.05); there was no significant difference in change of elbow flexion and extension activity between the two groups ( P>0.05). Intravenous tranexamic acid for 3 consecutive days after release of traumatic elbow stiffness can significantly reduce postoperative drainage volume, shorten drainage tube indwelling time and hospital stay, and relieve early postoperative pain, but it has no effect on the risk of thrombotic and embolic events and postoperative elbow function.

Radiotherapy in patients with brain metastases with and without concomitant immunotherapy: comparison of patient outcome and neurotoxicity.

Recently, immune checkpoint inhibitors (ICI) have been added to the treatment of brain metastases. While combining radiotherapy and ICI can enhance therapeutic effects, it might also increase the risk of severe autoimmune adverse events. This retrospective study aims to compare treatment responses and neurotoxicity in patients treated with radiotherapy alone versus those receiving a combination of radiotherapy and ICI. All patients with brain metastases who received radiotherapy at Hannover Medical School from 2017 to 2019 were included. The medical reports of all study participants were evaluated. Patients who received radiotherapy alone and those who received a combination of radiation and ICI were compared. A total of 248 patients were analyzed, with the most common tumor types being non-small cell lung cancer (NSCLC) and malignant melanoma. Half of the patients received whole-brain radiotherapy (WBRT) and the other half stereotactic radiotherapy (SRT). Of these, 29 patients received concurrent immunotherapy and radiotherapy, 30 completed immunotherapy before radiotherapy, and 29 started ICI after completing radiotherapy. Two cases lacked information on the duration of immunotherapy. Overall survival post-initial tumor diagnosis within the total cohort was 52months, with significantly worse survival for patients with multiple brain metastases (p = 0.020). No significant differences in survival or incidence of neurological adverse events were observed between patients with or without ICI. Combining radiotherapy and ICI did not significantly increase neurotoxicity or improve survival in this cohort, though the heterogeneity of the subgroups limits the generalizability of these findings.

Phase angle is a useful predicting indicator for protein-energy wasting and cardiovascular risk among maintenance hemodialysis patients.

Protein-energy wasting (PEW) is a major contributor to the high mortality among maintenance hemodialysis (MHD) patients. Cardiovascular disease (CVD) is the leading cause of death in dialysis patients, and PEW can significantly increase cardiovascular mortality in MHD patients. Previous studies have confirmed that PA may be a good objective indicator for determining the nutritional status and prognosis of MHD patients. Our study aimed to determine the predictive value of phase angle (PA) as detected by bioelectrical impedance analysis (BIA) on PEW and cardiovascular (CV) risk among MHD patients. Our retrospective observational study involved 161 adult patients with HD. The Cardiovascular risk score is a risk model based on the Japan Dialysis Outcome and Practice Patterns Study (J-DOPPS). We established LASSO logistic regression analysis model to identify key parameters related to body composition that can predict PEW in MHD patients. The area under the curve (AUC) values for PA, appendicular skeletal muscle mass index (ASMI), body cell mass (BCM), and mid-arm circumference (MAC) in predicting PEW in male MHD patients were relatively large, with 0.708, 0.674, 0.663, and 0.735, respectively. The predicted PEW values of these parameters were slightly lower in female patients than in men. We incorporated PA, ASMI, BCM, and MAC into a model that predicted the incidence of PEW in maintenance hemodialysis patients using LASSO technology. We discovered that the model predicted a greater AUC of PEW occurrence than any single factor, 0.877 for men and 0.76 for women. The results of the univariate logistic regression analysis showed that the low PA tertile array group had a greater incidence of PEW than the high PA group (P < 0.001). Additionally, we also found that lower PA was associated with higher CV risk scores. The PA detected by bioelectrical impedance analysis could predict the risk of PEW and cardiovascular events among patients with MHD. When used in conjunction, PA, ASMI, BCM, and MAC have a high diagnostic efficacy for PEW in patients on maintenance hemodialysis.

Efficacy and safety of rituximab in patients with lupus nephritis: A systematic review and meta-analysis.

Our aim was to systematically evaluate the efficacy and safety of rituximab (RTX) in patients with lupus nephritis (LN). PubMed, Embase, China National Knowledge Infrastructure (CNKI), Cochrane Library, and Wanfang Databases were searched to collect literature on the efficacy and safety of RTX in patients with LN. Odds ratios (ORs), weighted mean differences (WMDs), and standardized mean differences (SMDs) were used to represent treatment efficacy and overall outcome. The outcomes included complete renal remission rate, proteinuria, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, serum creatinine, any adverse events and serious adverse events. We explored the heterogeneity with I2 and assessed publication bias with funnel plot and Egger's test. Nine studies involving 723 patients (254 in the RTX group and 469 in the control group) were included in our systematic review and meta-analysis. RTX resulted in a higher complete renal remission rate (OR: 2.62; 95% CI 1.43 - 4.79, p = 0.024, I2 = 54.7%) than the control group. It significantly decreased SLEDAI scores (WMD = -3.79, 95% CI: -5.78 to -1.8, p < 0.001, I2 = 94.7%) as well as proteinuria (WMD = -0.9, 95% CI: -1.6 to -0.2, p < 0.001, I2 = 97.6%). There were no significant differences in any adverse events and serious adverse events between the RTX group and control group. RTX was an effective therapeutic agent in patients with LN, and it did not increase the risk of adverse events compared to the control group.

Updated evidence on cardiovascular and renal effects of GLP-1 receptor agonists and combination therapy with SGLT2 inhibitors and finerenone: a narrative review and perspectives.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have a reliable hypoglycaemic and weight-loss effect that can intervene in obesity, which is the basis of type 2 diabetes pathology. GLP-1RA therapy has shown potential benefits in reducing the risk of major adverse cardiovascular events and improving kidney outcomes in patients with diabetes at high risk for cardiovascular disease. More recent evidence is expanding their benefits to heart failure with preserved ejection fraction and clinically important renal outcomes in patients with and without diabetes. Some sub-analyses of large clinical trials suggest that GLP-1RA and sodium-glucose cotransporter 2 inhibitor combination therapy may provide more significant reductions in heart failure hospitalization and renal composite events than each alone. Moreover, the addition of finerenone to this combination therapy could potentially provide stronger cardiorenal protective benefits. Further studies are needed to assess the potential cardiovascular and renal benefits of combination therapy and to determine suitable patient population for the therapy.

Artificial intelligence, medications, pharmacogenomics, and ethics.

Artificial Intelligence (AI) and Machine Learning (ML) are revolutionizing various scientific and clinical disciplines including pharmacogenomics (PGx) by enabling the analysis of complex datasets and the development of predictive models. The integration of AI and ML with PGx has the potential to provide more precise, data-driven insights into new drug targets, drug efficacy, drug selection, and risk of adverse events. While significant effort to develop and validate these tools remain, ongoing advancements in AI technologies, coupled with improvements in data quality and depth is anticipated to drive the transition of these tools into clinical practice and delivery of individualized treatments and improved patient outcomes. The successful development and integration of AI-assisted PGx tools will require careful consideration of ethical, legal, and social issues (ELSI) in research and clinical practice. This paper explores the intersection of PGx with AI, highlighting current research and potential clinical applications, and ELSI including privacy, oversight, patient and provider knowledge and acceptance, and the impact on patient-provider relationship and new roles.

Effect of choline alfoscerate in older adult patients with dementia: an observational study from the claims data of national health insurance.

Choline alfoscerate, a cholinergic precursor with limited evidence of efficacy in dementia management, has been used for various cognitive impairments in Korea. Partly due to its insurance coverage, this agent appears to incur significant expense for the insurance system. Thus, we aimed to describe choline alfoscerate prescription patterns and analyze their long-term effects in an older adult cohort with dementia. This observational study used the National Health Insurance Service Senior Cohort Dataset. Choline alfoscerate -naïve patients who were diagnosed with dementia between 2003 and 2014 with at least 12 months of follow-up were selected. Time-dependent Cox regression was employed to estimate the association between drug exposure and the risk of treatment failure events. There were 11,463 eligible participants, of whom approximately 73% were female, and 19% had been exposed to choline alfoscerate. According to the main regression survival analysis, the association between longitudinal choline alfoscerate use and the risk of progression events related to treatment failure was unclear. However, a significant decrease of nearly 20% in the risk of all-cause mortality was associated with choline alfoscerate exposure, and a slight reduction in progression regarding treatment failure was observed with CA use only during the early stages of diagnosis. Age, sex, insurance premiums, several comorbidities and concurrent medications were significantly associated with the probability of the events according to the multivariate models. Further analyses are needed to confirm the early-stage and long-term effectiveness of choline alfoscerate in specific populations, which will help in considering its reimbursement.

Overcoming challenges into miraculous motherhood: successful pregnancy outcomes in patients with SLE: A case series

Systemic lupus erythematosus is a multisystem autoimmune disorder associated with multiple positive antibodies. Reproductive age group women have been found to develop SLE more commonly so than males, and pregnancy is associated with an increased rate of flare ups. The rate of pregnancy loss has decreased from 43% to 17% in recent years due to optimization of treatment and management during pre-pregnancy period. Recent studies have reported that both maternal and foetal outcome are favourable if SLE has been quiescent for at least 6 months prior to pregnancy. The effects of SLE over pregnancy and impact of pregnancy over SLE patients can be managed by optimization of pre-pregnancy treatment and management in antenatal period and follow-up. A multi-disciplinary team approach by an obstetrician, medical specialist and paediatrician for a successful management. Management of SLE to be continued in post-partum period and risk of flares and thrombotic events can be avoided by optimization of treatment in post-partum period till 6 weeks after delivery. Comprehensive maternal and new-born care has improved survival and quality of life outcomes in pregnant patients with SLE. Here, we present a series of three cases of SLE in pregnancy that had successful obstetric outcomes with an interdisciplinary management plan.

Adverse events after nivolumab and ipilimumab combined immunotherapy in advanced renal cell carcinoma: a multicentre experience in Poland.

Immune checkpoint inhibitors (ICIs) have been employed in the adjuvant and metastatic setting of renal cell carcinoma (RCC) treatment. Among ICIs, combined immunotherapy has the highest risk for immune-related adverse events (irAEs). We aimed to document the incidence of irAEs in RCC patients treated with nivolumab and ipilimumab as data from the European population remain limited. We analysed data from 88 RCC patients treated with nivolumab + ipilimumab between May 2022 and June 2024 across six high-volume oncology units in Poland. We reviewed irAEs and estimated their impact on survival parameters via univariate and multivariate Cox proportional hazards regression models, along with log-rank tests. With a median follow-up of 11.3 months, the median overall survival (OS) was not reached, whereas the median progression-free survival (PFS) was 12.8 months (6.3-19.3). A total of 74 irAEs were recorded in 50 patients. The most frequent events were endocrine (n = 20, 27%), hepatic (n = 15, 17%), general (n = 12, 13.6%), and cutaneous (n = 11, 12.5%). The occurrence of irAEs was associated with a 60% lower risk of disease progression (hazard ratio 0.44, 95% confidence interval 0.2-0.87, p = 0.018) without impacting OS and higher disease control rate (n = 45, 90% vs. n = 24, 63.2%, p = 0.004). In contrast, patients with hepatotoxicity had poorer outcomes, with a 2.6-fold greater risk of death (p = 0.05). IrAEs may serve as a predictive factor for the efficacy of the nivolumab + ipilimumab regimen in RCC patients. Special attention is needed for hepatotoxicity, as it can significantly impact survival outcomes.

Hormone replacement therapy in surgical menopause after gynecological malignancies

This review examines hormone replacement therapy (HRT) in cases of surgical menopause following gynecological malignancies. It aims to capture current knowledge, summarize recent findings, and provide recommendations for clinical settings. Unlike natural menopause, surgical menopause occurs abruptly, without an adjustment period, and is associated with a notably higher risk of fractures, arthritis, cognitive decline, dementia, Parkinson’s disease, and various metabolic disorders affecting glucose and lipid levels—all of which contribute to an increased risk of major cardiovascular events. In 2017, The North American Menopause Society recommended that, barring contraindications, HRT should be initiated in women who enter surgical menopause before age 45. If these women do not experience vasomotor symptoms or other issues, HRT should be maintained consistently at least until age 52. This guideline reflects contemporary knowledge and is the result of a multidisciplinary consensus, based on a review of existing literature and several randomized clinical trials focusing on women who have survived gynecological cancers and whose quality of life is significantly impacted by surgical or early menopause. Estrogen supplementation is particularly beneficial, as it is linked to marked improvements in quality of life, including delayed onset of chronic cardiovascular issues, reduced fracture risk, enhanced cognitive function, reduced inflammation, and improved self-esteem, as well as better social and work performance. Clinical implementation of HRT, however, requires a highly individualized approach. This approach must consider the type and stage of malignancy, histopathological characteristics, risk factors for recurrence (such as diet, concurrent medications, medical history, and genetic predispositions), and a thorough assessment of the potential benefits and risks of HRT, as well as the patient’s personal wishes and expectations.

A Proteomics-Based Approach for Prediction of Different Cardiovascular Diseases and Dementia.

Many studies have explored whether individual plasma protein biomarkers improve cardiovascular disease risk prediction. We sought to investigate the use of a plasma proteomics-based approach in predicting different cardiovascular outcomes. Among 51 859 UK Biobank participants (mean age, 56.7 years; 45.5% male) without cardiovascular disease and with proteomics measurements, we examined the primary composite outcome of fatal and nonfatal coronary heart disease, stroke, or heart failure (major adverse cardiovascular events), as well as additional secondary cardiovascular outcomes. An exposome-wide association study was conducted using relative protein concentrations, adjusted for a range of classic, demographic, and lifestyle risk factors. A prediction model using only age, sex, and protein markers (protein model) was developed using a least absolute shrinkage and selection operator-regularized approach (derivation: 80% of cohort) and validated using split-sample testing (20% of cohort). Their performance was assessed by comparing calibration, net reclassification index, and c statistic with the PREVENT (Predicting Risk of CVD Events) risk score. Over a median 13.6 years of follow-up, 4857 participants experienced first major adverse cardiovascular events. After adjustment, the proteins most strongly associated with major adverse cardiovascular events included NT-proBNP (N-terminal pro B-type natriuretic peptide; hazard ratio [HR], 1.68 per SD increase), proADM (pro-adrenomedullin; HR, 1.60), GDF-15 (growth differentiation factor-15; HR, 1.47), WFDC2 (WAP four-disulfide core domain protein 2; HR, 1.46), and IGFBP4 (insulin-like growth factor-binding protein 4; HR, 1.41). In total, 222 separate proteins were predictors of all outcomes of interest in the protein model, and 86 were selected for the primary outcome specifically. In the validation cohort, compared with the PREVENT risk factor model, the protein model improved calibration, net reclassification (net reclassification index +0.09), and c statistic for major adverse cardiovascular events (+0.051). The protein model also improved the prediction of other outcomes, including ASCVD (c statistic +0.035), myocardial infarction (+0.023), stroke (+0.024), aortic stenosis (+0.015), heart failure (+0.060), abdominal aortic aneurysm (+0.024), and dementia (+0.068). Measurement of targeted protein biomarkers produced superior prediction of aggregated and disaggregated cardiovascular events. This study represents an important proof of concept for the application of targeted proteomics in predicting a range of cardiovascular outcomes.

Treatment discontinuation in adults with atypical hemolytic uremic syndrome (aHUS): a qualitative study of international experts' perspectives with associated cost-consequence analysis.

Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy (TMA) related to congenital mutations impeding control of the alternative pathway of complement. Following approval of the complement C5 inhibitor eculizumab by the European Medicines Agency and the US Food and Drug Administration, initial guidelines suggested lifelong therapy. Yet, growing evidence indicates that discontinuation of eculizumab, or its long-acting form ravulizumab, is possible for many patients. This mixed-methods study sought to explore international experts' perspectives and experiences related to treatment duration in adult patients with aHUS, while also estimating the financial and potential health consequences of early discontinuation. Between January and December 2023, we conducted 10 qualitative interviews with experts in the treatment of aHUS, based upon which we constructed a quantitative decision tree, designed to estimate time on treatment and treatment- and disease-related adverse events. Thematic analysis of the interview data identified four main themes: (1) Concerns and prior experience; (2) High-risk vs. low-risk groups; (3) Patient preference and adherence; and (4) Funding for monitoring and re-treatment. Although most interviewees were in favour of considering treatment discontinuation for many patients (citing the high cost, burden, and potential side effects of lifelong treatment as key reasons), a prior negative experience of discontinuation seemed to make others more reluctant to stop. Deciding which patients required lifelong treatment and which not involved consideration of a wide range of factors, including patient- and system-related factors. Cost-consequence analysis demonstrated the financial savings associated with early treatment discontinuation at the expense of increased risk of recurrent TMA events. Close monitoring for these events had the potential to minimise any long-term injury, primarily renal, with an estimated one event per 100 patient years. For patients at high risk of TMA and with poor adherence to monitoring, rates of renal injury rose to three events per 100 patient years. aHUS treatment protocols are changing globally in response to new clinical evidence. Against this backdrop, our mixed-methods study provides compelling evidence on the complexity of factors influencing treatment discontinuation decisions in aHUS, as well as the financial and health consequences of early discontinuation.

TREATMENT OPTIONS FOR RECURRENT MALIGNANT DIFFUSE ASTROCYTOMA (WHO GRADE IV)

Objectives We present the case of a 37-year-old female who underwent partial resection in 2018 for a diffuse fibrillary astrocytoma (WHO II) that invaded almost the entire right cerebral hemisphere. The patient followed conventional radiotherapy and chemotherapy. She presents after 6 years of regularly follow-ups with left hemiparesis, intracranial hypertension syndrome and tumor recurrence on MRI. The patient underwent another surgical intervention and the new histopathological diagnosis was diffuse astrocytoma grade IV. Therapeutic options for these patients are limited considering the fact that a gross total resection or a conventional re-irradiation could impact the quality of life. Therefore, exploring new therapeutic methods, such as targeted molecular therapy like EGFR antagonists or proteasome inhibitors, or proton therapy, should be considered. Material and Methods We conducted extensive research in two public medical databases for information related to the molecular pathways and management of primary and recurrent malignant astrocytoma and relevant articles were selected. Subsequently, we correlated this information with our direct experience in our case and discussed the observed results. Results Treatment modalities for these patients include reintervention, re-irradiation and second line chemotherapeutics. In relapsing cases the goal of reintervention is both to alleviate symptoms and obtain tumoral tissue for immunohistochemical analysis for identification of the new mutations. Conventional re-irradiation for large lesions carries high risks of producing both short-term and long-term side effects, impacting the quality of life. Alternatively, proton therapy minimizes the risk of adverse events due to Bragg peak reducing the irradiation of the surrounding tissue. Conclusions Genetic characterization of these lesions can facilitate targeted molecular therapy and help in establishing the prognosis. Re-irradiation of malignant astrocytomas with proton therapy is an effective treatment measure allowing for comparable tumor control to conventional radiotherapy.

The Emerging Potential of Apolipoprotein C-III Inhibition for ASCVD Prevention: A State-of-the-Art Review.

Multiple agents are being developed that inhibit apolipoprotein (apo) C-III. This state-of-the-art review examines their potential for atherosclerotic cardiovascular disease (ASCVD) risk reduction. Apo C-III, an apolipoprotein on the surface of triglyceride-rich lipoproteins (TRLs), impairs clearance of TRLs through both lipoprotein lipase dependent and independent pathways, thereby resulting in increased concentrations of triglycerides. Apo C-III has also been shown to have pro-atherogenic effects when bound to high-density lipoprotein (HDL) particles. Classical and genetic epidemiology studies provide support for the concept that apo C-III is associated with an increased risk of ASCVD events. Drug efficacy of agents that silence APOC3 mRNA has been studied in populations with varying hypertriglyceridemia severity, including those with familial chylomicronemia syndrome, multifactorial chylomicronemia syndrome/severe hypertriglyceridemia, and mixed hyperlipidemia. Randomized controlled trials have reported significant reductions in TG and non-HDL cholesterol levels among these patients treated with APOC3 inhibitors. Upcoming clinical outcomes trials seek to establish a role for APOC3 inhibitors to reduce risk of ASCVD.