Cumulative Incidence Research Articles

Challenges in a Biological Definition of Alzheimer Disease.

It has been suggested that the diagnostic landscape of Alzheimer disease (AD) is undergoing a profound transformation, marked by a shift toward a biomarker-based approach, as proposed by the Revised Criteria for Diagnosis and Staging of Alzheimer's Disease. These criteria advocate for diagnosing AD solely on biomarkers, without requiring clinical symptoms. This article explores the drivers behind this transition, primarily influenced by the Food and Drug Administration's approval of amyloid-lowering treatments. We evaluate the proposed criteria, which allow for an AD diagnosis based on amyloid "A" or phosphorylated tau "T1" positivity through surrogate amyloid PET imaging, CSF, or plasma biomarkers, and consider the arguments for and against their use. The merits of the new criteria include a clearer definition of AD, which is currently used interchangeably to refer to both the presence of neuropathology and the clinical syndrome. We argue that a purely biological definition risks a category error and emphasize the need for longitudinal data to establish the lifetime risk of dementia in amyloid-positive and tau-positive individuals. We also caution against limiting the scope of biomarker-based AD diagnosis to amyloid and tau alone. In conclusion, we recommend that the criteria remain within the research domain for the present while advocating for the considered adoption of plasma biomarkers in clinical practice.

Relationship Between Race, Predelivery Cardiology Care and Cardiovascular Outcomes in Pre-Eclampsia/Eclampsia Among a Commercially Insured Population

Background: It is unknown whether predelivery cardiology care is associated with future risk of major adverse cardiovascular events (MACE) in Preeclampsia/Eclampsia (PrE/E). We sought to determine the cumulative incidence of MACE by race and whether predelivery cardiology care was associated with the hazard of MACE up to 1-year post-delivery for Black and White patients with PrE/E. Methods: Using Optum’s de-identified Clinformatics® Data Mart Database, we identified Black and White patients with PrE/E who had a delivery between 2008 and 2019. MACE was defined as the composite of heart failure, acute myocardial infarction, stroke, and death. Cumulative incidence functions were used to compare incidence of MACE by race. Regression models were used to assess hazard of MACE by cardiology care for each race. Separate hazards were calculated for the first 14 days and the remainder of the year. Results: Among 29,336 patients (83.4% White, 16.6% Black, 99.5% commercially insured, mean age 30.9 years) with PrE/E, 11.2% received cardiology care (10.9% White, 13.0% Black). Black patients had higher incidence of MACE than White patients at 1-yr post-delivery (2.7% vs 1.4%) with the majority within 14 days of delivery (Black: 58.7%; White: 67.8%). After adjusting for age and comorbidities, receipt of cardiology care was associated with lower hazard of MACE for White patients within 14 days following delivery (HR 0.31, 95%CI: 0.21-0.46, p<0.001) but not Black patients (HR 1.00, 95%CI: 0.60-1.67; p= 0.999). The effect of the interaction between race and cardiology care was significant in the first 14 days (p<0.001) but not the remainder of the year (p=0.56). Conclusions: Among a well-insured population of patients with PrE/E, Black patients had a higher cumulative incidence of MACE up to a year post-delivery. Cardiology care was associated with a lower hazard of MACE only for White patients during the first 14 days following delivery.

Global maternal health country typologies: A framework to guide policy

Maternal mortality remains a large challenge in global health. Learning from the experience of similar countries can help to accelerate progress. In this analysis we develop a typology of country groupings for maternal health and provide guidance on how policy implications vary by country typology. We used estimates from the Global Maternal Health (GMatH) microsimulation model, which was empirically calibrated to a range of fertility, process, and mortality indicators and provides estimates for 200 countries and territories. We used the 2022 estimates of the maternal mortality ratio (MMR) and lifetime risk of maternal death (LTR) and used a k-means clustering algorithm to define groups of countries based on these indicators. We estimated the means of other maternal indicators for each group, as well as the mean impact of different policy interventions. We identified 7 groups (A-G) of country typologies with different salient features. High burden countries (A-B) generally have MMRs above 500 and LTRs above 2%, and account for nearly 25% of global maternal deaths. Countries in these groups are estimated to benefit most from improving access to family planning and increasing facility births. Middle burden countries (C-E) generally have MMRs between 100–500 and LTRs between 0.5%-3%. Countries in these groups account for 55% of global maternal deaths and would benefit most from increasing facility births and improving quality of care. Low burden countries (F-G) generally have MMRs below 100 and LTRs below 0.5%, account for 20% of global maternal deaths, and would benefit most from improving access to family planning and community-based interventions and linkages to care. Indicators vary widely across groups, but also within groups, highlighting the importance of considering multiple indicators when assessing progress in maternal health. Policy impacts also differ by country typology, providing policymakers with information to help prioritize interventions.

Risk stratification in the clinical application of minimal residual disease assessment in acute myeloid leukemia

AbstractBackgroundIn acute myeloid leukemia (AML), further investigation is warranted to integrate measurable residual disease (MRD) with genetic characteristics for formulating a dynamic prognostic system for predicting response and selecting appropriate postremission therapeutic strategies.MethodsThe authors incorporated MRD with genetic risk classification and assessed its impact on transplantation decision making within different risk cohorts, comprising 769 patients with newly diagnosed AML across three clinical trials. Only patients who achieved complete remission (CR) within two courses of chemotherapy were selected.ResultsIn the favorable‐risk and intermediate‐risk groups, patients who underwent transplantation according to the protocol experienced significant 3‐year overall survival (OS) benefits compared with those who did not (favorable‐risk group: hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20–0.73l p = .004; intermediate‐risk group: HR, 0.53; 95% CI, 0.33–0.85; p = .008). In the intermediate‐risk group, early detection of MRD positivity, even after the initial course of chemotherapy, was associated with a significantly elevated cumulative incidence of relapse (47.2% vs. 36.0%; p = .009) and a notable extension of OS with allogeneic hematopoietic stem cell transplantation (HR, 0.47; 95% CI, 0.28–0.79; p = .004). Conversely, patients who achieved MRD negativity at either of the two time points had comparable OS in the favorable‐risk and intermediate‐risk groups, regardless of whether they underwent transplant or not. In the adverse‐risk group, allogeneic hematopoietic stem cell transplantation led to improvements in OS irrespective of MRD status (HR, 0.51; 95% CI, 0.38–0.69; p < .001).ConclusionsEarly clearance of MRD demonstrated significant prognostic value, particularly for patients in the favorable‐risk and intermediate‐risk groups. Positive MRD status after two courses of intensive chemotherapy were associated with a higher relapse rate and inferior OS, necessitating allogeneic hematopoietic stem cell transplantation.

Validation of a prognostic blood-based sphingolipid panel for men with localized prostate cancer followed on active surveillance

BackgroundWe previously reported that increases in circulating sphingolipids are associated with elevated risk of biopsy Gleason grade group (GG) upgrading in men on Active Surveillance (AS) for prostate cancer. Here, we aimed to validate these findings and establish a blood-based sphingolipid biomarker panel for identifying men on AS who are at high-risk of biopsy GG upgrading.MethodsMen diagnosed with low- or intermediate-risk prostate cancer in one of two AS cohorts (CANARY PASS and MDACC) were followed for GG upgrading after diagnostic and confirmatory biopsy. The PASS cohort consisted of 544 patients whereas the MDACC Cohort consisted of 697 patients. The number of patients with GG upgrading during course of study follow-up in the PASS and MDACC cohorts were 98 (17.7%) and 133 (19.1%), respectively. Plasmas collected prior to confirmatory biopsy were used for mass spectrometry-based quantitation of 87 unique sphingolipid species. A neural network layer based on 21 sphingolipids was developed in the CANARY PASS cohort for predicting biopsy GG upgrading. Tertile-based thresholds for low-, intermediate-, and high-risk strata were subsequently developed for the sphingolipid panel as well as a model that combined the sphingolipid panel with PSA density and rate of core positivity on diagnostic biopsy. The resultant models and risk thresholds for GG upgrading were validated in the MDACC cohort. Performance was assessed using Cox proportional hazard models, C-index, AUC, and cumulative incidence curves.ResultsThe sphingolipid panel had a HR (per unit standard deviation increase) of 1.36 (95% CI: 1.07–1.70) and 1.35 (95% CI: 1.11–1.64) for predicting GG biopsy upgrading in the PASS and MDACC cohort, respectively. The model that combined the sphingolipid panel with PSA density and rate of core positivity achieved a HR of 1.63 (95% CI: 1.33-2.00) and 1.44 (1.25–1.66), respectively. Tertile-based thresholds, established in the PASS cohort, were applied to the independent MDACC cohort. Compared to the low-risk group, MDACC patients in the high-risk strata had a GG biopsy upgrade HR of 3.65 (95% CI: 2.21–6.02), capturing 50% of the patients that had biopsy upgrading during study follow-up.ConclusionsThe sphingolipid panel is independently associated with GG biopsy upgrading among men in two independent AS cohorts who have previously undergone diagnostic and confirmatory biopsy. The sphingolipid panel, together with clinical factors, provides a potential means for risk stratification to better guide clinical management of men on AS.

Optimal threshold of portal pressure gradient for patients with ascites after covered TIPS: a multicentre cohort study

Abstract Background Transjugular intrahepatic portosystemic shunt (TIPS) is recommended for treating recurrent and refractory ascites. However, determining the target portal pressure gradient (PPG) has been inconclusive. This multicentre cohort study explored the post-TIPS PPG potential range associated with improving survival. Methods The study enrolled 276 patients, all of whom underwent covered TIPS for ascites treatment across four medical centers. The cumulative incidences of clinical outcomes were compared among groups categorized by potential PPG thresholds. Results During the whole follow-up period with a medium follow-up of 21.6 (7.5, 41.6) months, 122 (44.2%) experienced liver-related death, and 73 (26.4%) patients experienced a recurrence of ascites. Multivariable analysis revealed PPG < 7 mmHg (p = 0.007) and the recurrence of ascites (p = 0.033) are independent risk factors for survival, while the PPG ≥ 11 mmHg was an independent risk factor for the recurrence of ascites (p = 0.012). Patients with ≥ 7 mmHg had a lower rate of liver-related death than patients with post-TIPS PPG < 7 mmHg (51.0% vs 66.6%, p = 0.004), while those with post-TIPS PPG ≥ 11 mmHg exhibited a higher cumulative incidence of ascites compared to those with post-TIPS PPG < 11 mmHg (44.6% vs 33.7%, p = 0.023). The robustness of the results was confirmed. Conclusion Our study highlighted the existence of an optimal post-TIPS PPG range in patients with recurrent and refractory ascites. Patients may experience improved survival and ascites control with a post-TIPS PPG of 7–11 mmHg. Graphical Abstract

The introduction of a highly virulent PRRSV strain in pig farms is associated with a change in the pattern of influenza A virus infection in nurseries

The present study aimed to determine the dynamics of influenza A virus (IAV) infection in two endemically infected farms (F1 and F2), where a longitudinal follow-up of piglets was performed from birth to 8–12 weeks of age. During the study, a highly virulent isolate of porcine reproductive and respiratory syndrome virus (PRRSV) was introduced on both farms. This allowed us to examine the impact of such introduction on the patterns of infection, disease, and the antibody response of pigs to IAV infection. The introduction of the new PRRSV strain coincided with a change in the dynamics of IAV infection on both farms. In F1, the cumulative incidence of IAV increased from 20% before the outbreak to 67.5%, together with the existence of animals that tested positive for IAV (RT‒qPCR) in nasal swabs for two or more consecutive samples. In F2, the cumulative incidence of IAV increased from 50% before the PRRSV outbreak to 70%, and the proportion of prolonged IAV shedders increased sharply. Additionally, some animals were infected with the same IAV twice during the observation period. In contrast to previous reports, our study revealed that prolonged shedding was not related to the titres of maternally derived antibodies at the time of infection but was significantly (p < 0.05) related to PRRSV infection status. Notably, both before and after the PRRSV outbreak, a high proportion of IAV-infected piglets did not seroconvert, which was significantly (p < 0.05) related to the hemagglutination inhibition titres against IAV when infected.

Cancer incidence and mortality among patients with new-onset atrial fibrillation: A population-based matched cohort study

BackgroundUnderstanding the risk of cancer after the diagnosis of another condition can present opportunities for earlier diagnosis. We examined the risk of cancer diagnosis conditional on prior diagnosis of atrial fibrillation (AF). MethodsLinked electronic health records were used to identify patients aged ≥18 with new-onset AF and age-sex-matched controls. Cumulative incidence of and mortality from cancer (overall and cancer-site specific) within three months, three months to five years and beyond five years from diagnosis of AF were examined. Findings were further validated using Mendelian randomisation (MR). ResultsThe cohort included 117,173 patients with new-onset AF and 117,173 matched controls (median age 78). In the first three months, 2.2% of AF patients were diagnosed with cancer vs. 0.47% in controls (relative risk: 4.7 [95%CI 4.2-5.4] in men and 4.4 [95%CI 3.8-5.0] in women). Nearly 80% of cancers related to thoracic or abdominal organs. Differences in cumulative incidence were only evident in women between three months and five years (subdistribution hazard ratio=1.1 [95%CI 1.01-1.12]) and absent in all patients beyond five years. MR analysis did not support the presence of a causal association between AF and major cancer subtypes. ConclusionThere is a large short-term increase in cancer incidence and mortality following new-onset AF. The findings may reflect incidental identification of AF or paraneoplastic manifestation. New-onset AF confers high short-term risk of cancer diagnosis, at levels comparable with symptomatic risk threshold mandating urgent assessment for suspected cancer.

The association between stress hyperglycemia ratio and clinical outcomes in patients with sepsis-associated acute kidney injury: a secondary analysis of the MIMIC-IV database

BackgroundThe stress hyperglycemia ratio (SHR) is associated with poor outcomes in critically ill patients. However, the relationship between SHR and mortality in patients with sepsis-associated acute kidney injury (SA-AKI) remains unclear.MethodsThe data of patients with SA-AKI, identified based on the KDIGO criteria, were retrospectively collected from the Beth Israel Deaconess Medical Center between 2008 and 2019. SHR was calculated as follows: (glycemia [mmol/L]) / (1.59 × HbA1c [%] – 2.59). Primary outcomes were 30-day and 1-year mortality. The cumulative incidence of all-cause mortality was assessed using Kaplan–Meier survival analysis. Multivariable-adjusted logistic and Cox models and restricted cubic spline curves were used to analyze the correlation between SHR and all-cause mortality. Post-hoc subgroup analysis was performed to compare the effects of SHR across different subgroups.Results1161 patients with SA-AKI were identified and categorized into four SHR quartiles as follows: Q1 (0.26, 0.90), Q2 (0.91, 1.08), Q3 (1.09, 1.30), and Q4 (1.31, 5.42). The median age of patients was 69 years, with 42.7% of the patients being women and 20.2% of the patients having chronic kidney disease. The 30-day and 1-year mortality were 22.1% and 35.0% respectively. Kaplan–Meier survival analysis indicated a gradual decrease in survival probability with increasing SHR quartiles. An increased SHR exhibited a strong correlation with 30-day mortality (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.18–1.90; P < 0.001) and 1-year mortality (HR, 1.32; 95% CI, 1.06–1.65; P = 0.014). SHR has a nonlinear relationship with 1-year mortality but not with 30-day mortality (P-nonlinear = 0.048 and 0.114, respectively). The results of subgroup analysis were mostly consistent with these findings.ConclusionAn increased SHR is independently associated with 30-day and 1-year mortality in patients with SA-AKI. Therefore, SHR may serve as an effective tool for risk stratification in patients with SA-AKI.

Populationwide Screening for Chronic Kidney Disease

ImportanceSodium-glucose cotransporter-2 (SGLT2) inhibitors have changed clinical management of chronic kidney disease (CKD) and made populationwide screening for CKD a viable strategy. Optimal age of screening initiation has yet to be evaluated.ObjectiveTo compare the clinical benefits, costs, and cost-effectiveness of population-wide CKD screening at different initiation ages and screening frequencies.Design, Setting, and ParticipantsThis cost-effectiveness study used a previously published decision-analytic Markov cohort model that simulated progression of CKD among US adults from age 35 years and older and was calibrated to population-level data from the National Health and Nutrition Examination Survey (NHANES). Effectiveness of SGLT2 inhibitors was derived from the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial. Mortality, quality-of-life weights, and cost estimates were obtained from published cohort studies, randomized clinical trials, and US Centers for Medicare &amp;amp;amp; Medicaid Services data. Analyses were performed from June 2023 through September 2024.ExposuresOne-time or periodic (every 10 or 5 years) screening for albuminuria, initiated at ages between 35 and 75 years, with and without addition of SGLT2 inhibitors to conventional CKD therapy (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers).Main Outcomes and MeasuresCumulative incidence of kidney failure requiring kidney replacement therapy (KRT); life years, quality-adjusted life years (QALYs), lifetime health care costs (2024 US currency), and incremental cost-effectiveness ratios discounted at 3% annually.ResultsFor those aged 35 years, starting screening at age 55 years, and continuing every 5 years through age 75 years, combined with SGLT2 inhibitors, decreased the cumulative incidence of kidney failure requiring KRT from 2.4% to 1.9%, increased life expectancy by 0.13 years, and cost $128 400 per QALY gained. Although initiation of screening every 5 years at age 35 or 45 years yielded greater gains in population-wide health benefits, these strategies cost more than $200 000 per additional QALY gained. The comparative values of starting screening at different ages were sensitive to the cost and effectiveness of SGLT2 inhibitors; if SGLT2 inhibitor prices drop due to patent expirations, screening at age 55 years continued to be cost-effective even if SGLT2 inhibitor effectiveness were 30% lower than in the base case.Conclusions and RelevanceThis study found that, based on conventional benchmarks for cost-effectiveness in medicine, initiating population-wide CKD screening with SGLT2 inhibitors at age 55 years would be cost-effective.

Comparing five-year and ten-year predicted cardiovascular disease risk in Aotearoa New Zealand: national data linkage study of 1.7 million adults.

There is no consensus on the optimal time horizon for predicting cardiovascular disease (CVD) risk to inform treatment decisions. New Zealand and Australia recommend 5 years, whereas most countries recommend 10 years. We compared predicted risk and treatment-eligible groups using 5-year and 10-year equations. Individual-level linked administrative datasets identified 1,746,665 New Zealanders without CVD, aged 30-74 years in 2006, with follow-up to 2018. Participants were randomly allocated to derivation and validation cohorts. Sex-specific 5-year and 10-year risk prediction models were developed in the derivation cohort and applied in the validation cohort. 28,116 (3.2%) and 62,027 (7.1%) first CVD events occurred during 5-years and 10-years follow-up respectively (cumulative risk, derivation cohort). Median predicted 10-year CVD risk (3.8%) was approximately 2.5 times 5-year risk (1.6%) and 95% of individuals in the top quintile of 5-year risk were also in the top quintile of 10-year risk, across age/gender groups (validation cohort). Using common guideline-recommended treatment thresholds (5% 5-year, 10% 10-year risk), approximately 14% and 28% of women and men respectively were identified as treatment-eligible applying 5-year equations compared to 17% and 32% of women and men applying 10-year equations. Older age was the major contributor to treatment eligibility in both sexes. Predicted 10-year CVD risk was approximately 2.5 times 5-year risk. Both equations identified mostly the same individuals in the highest risk quintile. Conversely, commonly used treatment thresholds identified more treatment-eligible individuals using 10-year equations and both equations identified approximately twice as many treatment-eligible men as women. The treatment threshold, rather than the risk horizon, is the main determinant of treatment eligibility.

Changes in the estimated glucose disposal rate and incident cardiovascular disease: two large prospective cohorts in Europe and Asia

Background and aimsPrevious study found that estimated glucose disposal rate (eGDR) was significantly associated with cardiovascular disease (CVD). However, little is known about the change in eGDR over time and its association with the development of CVD. The aim of this study was to investigate the association of change in eGDR with CVD risk.MethodsThis study used data of two prospective cohorts: UK Biobank and China Health and Retirement Longitudinal Study (CHARLS) with two measurements of eGDR. Changes in the eGDR were classified using K‑means clustering analysis, and the cumulative eGDR was also calculated. Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) after adjusting for potential confounders.ResultsA total of 11,682 individuals from the UK Biobank, and 4,974 individuals from the CHARLS were included. The median follow-up periods were 9.7 years in the UK Biobank and 3.0 years in the CHARLS. Compared with persistently high level of eGDR (class 1), individuals with low level increasing (class 3) and persistently low level of eGDR (class 4) showed elevated risks of incident CVD in both UK Biobank (HR = 2.79, 95% 2.15–3.62 for class 3; HR = 3.19, 95% 2.50–4.08 for class 4) and CHARLS (HR = 1.66, 95% 1.29–2.13 for class 3; HR = 1.69, 95% 1.34–2.14 for class 4). In addition, lower level of cumulative eGDR were associated with elevated risks of incident CVD. The dose-response curve between cumulative eGDR and CVD risk showed a negative linear relationship.ConclusionDifferent changes in eGDR level are associated with different risks of incident CVD. Dynamic monitoring of eGDR level is of significant importance for the CVD prevention and treatment.

Age, sex and sexual orientation effects in the Safetxt trial: secondary data analysis of a randomised controlled trial

BackgroundIncreasing rates of sexually transmitted infections (STIs) and antimicrobial resistance among young people underscore the urgent need for preventative interventions. Interventions should be evidence-based and tailored to the unique risks...

Association Between Direct Oral Anticoagulant Score and Bleeding Events in Patients With Atrial Fibrillation Following Transcatheter Aortic Valve Replacement: A Retrospective Multicenter Cohort Study.

The Direct Oral Anticoagulant (DOAC) Score can predict bleeding risk in patients with atrial fibrillation taking DOACs; however, it lacks external validation. Therefore, this study aimed to assess the association between the DOAC Score and bleeding events in patients with atrial fibrillation who underwent transcatheter aortic valve replacement. This retrospective multicenter cohort study included patients with atrial fibrillation who underwent transcatheter aortic valve replacement, as registered in a Japanese multicenter registry. The primary end point was the incidence of bleeding. Patients were categorized based on their DOAC Score: low and moderate- (≤7 points), high- (8-9 points), and very high-risk (≥10 points) groups. Among 1230 patients (mean age 84.6±5.1 years; 457 men), 465 (37.8%) received a vitamin K antagonist, and the remaining patients received DOACs. The low and moderate-, high-, and very high-risk groups included 380 (30.1%), 497 (40.4%), and 353 patients (28.7%), respectively. The 3-year cumulative incidence of all bleeding events was significantly different among the 3 groups (low and moderate risk: 6.6%, high risk: 6.9%, and very high risk: 14.0%; P<0.01). Multivariable Cox regression analysis revealed that significant increments in the DOAC Score were associated with a risk of all bleeding events at 3 years in the overall cohort (hazard ratio [HR], 1.22 [95% CI, 1.08-1.38]; P<0.01), in the DOAC cohort (HR, 1.20 [95% CI, 1.01-1.42]; P=0.04), and in the vitamin K antagonist cohort (HR, 1.25 [95% CI, 1.04-1.50]; P=0.02). The DOAC Score was significantly associated with bleeding events in patients with atrial fibrillation after transcatheter aortic valve replacement, aiding in clinical decision-making for anticoagulant management. URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023585; Unique identifier: UMIN000020423.

Preoperative bleeding risk assessment in cardiac surgery patients

One of the most important aspects in achieving successful outcomes in cardiac surgery is the evaluation of the risk of bleeding during and after the procedure. Preoperative anemia, intraoperative bleeding, and transfusion therapy contribute to a cumulative risk of adverse events. Given the limitations of traditional coagulation tests, a more comprehensive and patient-centered approach is necessary. Factors affecting the risk of bleeding should be considered from the perspective of both individual patient characteristics and the specific type and extent of the planned surgical intervention. The risk assessment should be informed by individual and familial history, as well as previous episodes of bleeding or other relevant information. The use of bleeding risk scales can play a crucial role in this process, providing valuable insights into the likelihood of bleeding complications. In conclusion, a comprehensive approach that takes into account the unique characteristics of each patient and the specific details of the surgical procedure is essential for minimizing the risk of complications and ensuring successful outcomes.

Innovative Nanocomposites for Drug Delivery: A Novel Approach for Diabetic Foot Ulcer

Abstract: Diabetic Foot Ulcer (DFU) is a chronic wound, and a person with diabetes has an increased lifetime risk of foot ulcers (19%-34%) and high morbidity (65% recurrence in 3-5 years, 20% lifetime amputation). Recent data have shown rising amputation rates, especially in the younger and minority populations. This abstract discusses innovative approaches for addressing this issue. This highlights the use of nanotechnology-based drug nanocomposite systems for natural wound healing therapies, with a focus on nanoparticles, nano-emulsions, and nanogels. This review also emphasizes the potential of hydrogels for drug delivery, highlighting their versatility in various medical applications. Furthermore, it delves into the use of silver nanoparticles (AgNP’s) for treating diabetic wounds while acknowledging the need to address potential toxicity concerns. Finally, the abstract discusses the utilization of traditional herbal medicine and the integration of modern science to advance wound care, particularly focusing on wound microbiome, immune response, and controlled herbal medicine delivery. This study also highlights clinical trials conducted on DFU. Overall, these abstracts highlight the importance of exploring diverse and innovative solutions to chronic wound management.

Development and validation of the competing risk nomogram and risk classification system for predicting cancer-specific mortality in patients with cervical adenosquamous carcinoma treated via radical hysterectomy

In this study, we established and validated a competing risk nomogram for predicting the cumulative incidence of cervical adenosquamous carcinoma (ASC)-specific death in patients undergoing radical hysterectomy. Patients diagnosed with ASC between 2010 and 2019 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The cumulative incidence function (CIF) for various variables influencing ASC-specific mortality was computed. A Fine-Gray competing risk model was used to identify independent predictors, formulating a competing risk nomogram. A multivariate Cox proportional hazards model was also applied for comparative analysis. The performance of the nomogram was assessed using metrics such as the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). A corresponding risk classification system was constructed based on nomogram-derived scores. Factors such as advanced age, racial background (Black race), higher tumor grade, increased tumor size, advanced TNM stage, and receipt of radiotherapy without chemotherapy were found to be positively associated with elevated ASC-specific mortality. Additionally, age, T stage, M stage, and chemotherapy were identified as independent predictors correlated with ASC-specific mortality. The established nomogram exhibited accurate discriminatory capabilities and superior net benefits compared to the traditional TNM staging system. Additionally, the high-risk group consistently demonstrated higher probabilities of ASC-specific death in both the training and validation sets. The developed nomogram proficiently quantified the incidence of ASC-specific death in patients subjected to radical hysterectomy for ASC. This tool could help clinicians in formulating personalized treatment strategies and devising follow-up protocols.

Risk of Cardiovascular Disease in Patients With Classical Hodgkin Lymphoma: A Danish Nationwide Register-Based Cohort Study.

Risk of cardiovascular disease (CVD) in patients with classical Hodgkin lymphoma (cHL) undergoing contemporary treatment is unclear. cHL patients ≥ 18 years at diagnosis treated with doxorubicin-containing chemotherapy between 2000 and 2022 were matched 1:5 with comparators on birth year, sex, and Charlson Comorbidity Index at time of matching (score of 0 or ≥ 1). Cause-specific cumulative incidence of a composite of CVDs with corresponding 95% confidence intervals (CIs) were computed with death and lymphoma relapse as competing events (i.e., by censoring individuals at such occurrences) using the Aalen-Johansen estimator. A total of 1905 patients and 9525 comparators with a median follow-up of 10 years (interquartile range, [IQR]: 5.9-17.4). Median age was 39 years (IQR: 27-56), median cumulative doxorubicin dose was 250 mg/m2 (IQR: 200-300). The CVD cumulative incidences were 4.7% (95% CI: 3.6-5.7) for patients versus 2.6% (95% CI: 2.3-2.9) for comparators at 5 years, 8.9% (95% CI: 7.2-10.5) versus 5.5% (95% CI: 4.9-6.0) at 10 years, and 17.0% (95% CI: 14.1-19.9) versus 8.2% (95% CI: 7.4-9.0) at 15 years. CVD remains a substantial effect after contemporary treatment for cHL, suggesting that awareness of symptoms and a low threshold for referral to diagnostic examination are still important measures during survivorship.

Postmarketing Surveillance of Inferior Vena Cava Filters Among US Medicare Beneficiaries

Inferior vena cava filters (IVCFs) are commonly used to prevent pulmonary embolism in selected clinical scenarios, despite limited evidence to support their use. Current recommendations from professional societies and the US Food and Drug Administration endorse timely IVCF retrieval when clinically feasible. Current IVCF treatment patterns and outcomes remain poorly described. To evaluate temporal trends and practice patterns in IVCF insertion and retrieval among older US patients and report the incidence of periprocedural and long-term safety events of indwelling and retrieved IVCFs. Prespecified, retrospective, observational cohort of Medicare Fee-for-Service (FFS) beneficiaries, leveraging 100% of samples of inpatient and outpatient claims data from January 1, 2013, to December 31, 2021. First-time IVCF insertion while insured by Medicare FFS. The primary safety outcome was the composite of all-cause death, filter-related complications (eg, fracture, embolization), operating room visits following filter-related procedures, or new diagnosis of deep vein thrombosis (DVT). Events were considered periprocedural if they occurred within 30 days of IVCF insertion or retrieval and long-term if they occurred more than 30 days after. Among 270 866 patients with IVCFs placed during the study period (mean age, 75.1 years; 52.8% female), 64.9% were inserted for first-time venous thromboembolism (VTE), 26.3% for recurrent VTE, and 8.8% for VTE prophylaxis. Of these patients, 63.3% had major bleeds or trauma within 30 days of IVCF insertion. The volume of insertions decreased from 44 680 per year in 2013 to 19 501 per year in 2021. The cumulative incidence of retrieval was 15.3% at a median of 1.2 years and 16.8% at maximum follow-up of 9.0 years. Older age, more comorbidities, and Black race were associated with a decreased likelihood of retrieval, whereas placement at a large teaching hospital was associated with an increased likelihood of retrieval. The incidence of caval thrombosis and DVT among patients with nonretrieved IVCFs was 2.2% (95% CI, 2.1%-2.3%) and 9.2% (95% CI, 9.0%-9.3%), respectively. The majority (93.5%) of retrieval attempts were successful, with low incidence of 30-day complications (mortality, 0.7% [95% CI, 0.6%-0.8%]; filter-related complications, 1.4% [95% CI, 1.2%-1.5%]). In this large, US real-world analysis, IVCF insertion declined, yet retrievals remained low. Strategies to increase timely retrieval are needed, as nonretrieved IVCFs may have long-term complications.

Quadrivalent Conjugate Vaccine and Invasive Meningococcal Disease in US Adolescents and Young Adults

Beginning in 2005, the US implemented routine immunization of adolescents with a quadrivalent conjugate vaccine (MenACWY) for the prevention of invasive meningococcal disease (IMD). To assess whether MenACWY immunization was associated with a reduced IMD burden among the US adolescent population and how the downward trajectory of IMD that began in the mid-1990s might have evolved in the absence of vaccination efforts. In this decision analytical study, a bayesian hierarchical Poisson regression model was developed to investigate the potential trajectory of IMD among US adolescents and young adults without vaccination and evaluate the direct association of vaccination with IMD burden. The model included the entire age-stratified US population and was fitted to national incidence data for serogroups C, W, and Y from January 1, 2001, to December 31, 2021, with stratification by vaccination status for IMD cases. Simulated counterfactual scenario of absent vaccination from 2005 to 2021, while retaining the incidence rate of IMD for unvaccinated individuals estimated during model fitting. The main outcomes were the estimated numbers of IMD cases and deaths averted by MenACWY vaccination among US adolescents and young adults aged 11 to 23 years. Among the entire US population from 2005 to 2021, MenACWY vaccination prevented an estimated 172 (95% credible interval [CrI], 85-345) cases of IMD among US adolescents 11 to 15 years of age and 328 (95% CrI, 164-646) cases of IMD among those aged 16 to 23 years. Absent vaccination, the cumulative incidence of IMD in these age groups would have been at least 59% higher than reported over the same period with vaccination. Using case fatality rates of unvaccinated individuals derived from national data, vaccination averted an estimated 16 (95% CrI, 8-31) deaths among adolescents aged 11 to 15 years and 38 (95% CrI, 19-75) deaths among those aged 16 to 23 years. This decision analytical model suggests that the MenACWY vaccination program in the US was associated with a reduced burden of meningococcal disease. Without vaccination, the incidence rates per 100 000 adolescents and young adults would have been substantially higher than those observed during the vaccine era.