Multiple Registry Research Articles

Disparities in diabetes-related outcomes in prostate cancer patients - role of social determinants of health and race

Abstract Background Prostate cancer (PC) patients on androgen deprivation therapy (ADT) with diabetes mellitus (DM) are at increased risk of cardiovascular events (CVE) and all-cause mortality (ACM), with metformin use linked to lower ACM. Purpose To analyze the impact of low socioeconomic status (SES), low educational levels, and Non-Hispanic Black (NHB) race on the relationship between DM, and its treatments, and CVE, cardiovascular mortality (CVm), prostate cancer-specific mortality (PCsm), and ACM within 2 years of PC diagnosis in patients ± ADT. Methods We utilized SEER-Medicare (national database for individuals 65 or older covered under US federal health insurance program merged with multiple state cancer registries with ~50% US cancers covered) to study a cohort of PC patients diagnosed from 2009 to 2017, identifying PC cases with ICD-10 - C61 and DM via the Medicare chronic condition file. CVE included Afib, AMI, peripheral artery disease, ischemic stroke, and heart failure. Two patient cohorts were analyzed: those enrolled in Medicare Parts A and B with PC (cohort 1), and those exclusively on ADT (± diabetic medications) and enrolled in Medicare Part D (cohort 2). Outcomes were evaluated using Fine-Gray and Cox models, with further analysis by subgroups: NHB, SES, and education. Results We analyzed 74,052 PC patients, with 6,682 having comprehensive Part D data. Of these, 35% in cohort 1 and 16% in cohort 2 had DM, with median ages of 73 and 72, respectively. Diabetes was more prevalent among NHB men than Non-Hispanic White (NHW), 49% vs 33% in cohort 1 and 25% vs 15% in cohort 2. In cohort 1, 9% and 8.5% of overall and DM individuals were on ADT. Risk factor details are in Table 1, and CVE, CVm, PCsm, and ACM are included in Table 2, showing higher risks of various cardiovascular outcomes for DM patients, particularly for those with low-education levels. In cohort 1, we demonstrated a higher risk of all outcomes across all subgroups with DM (p<0.001). No significant interaction with race was present except in those with lower education levels, where NHW men with lower education showed an increased risk of CVE (sHR 1.15, 95%CI 1.10-1.21, P<0.001). In cohort 2, compared to metformin, the use of all other DM medications was associated with higher ACM. Additionally, those on other DM medications with lower education levels had higher CVE rates. Non-DM individuals with low SES had lower CVE rates, while NHB non-DM individuals had higher PCsm. Conclusion Our study highlights disparities in PC patients with DM in relation to cardiovascular and ACM, with NHB men and those with lower SES and educational status having worse outcomes. Metformin use in patients with low education levels was associated with reduced ACM and CVE risk, indicating its potential protective effect. These findings emphasize the need for further research on the disparities in PC and effects of diabetes medications across different subpopulations.

Exploring the Intersection of Blood Transfusion and Same-Day Computed Tomography Imaging: An Overview of Clinical Risks and Practices.

The use of transfusions, whether involving whole blood or specific blood components, is essential for managing various clinical conditions. Many cases are acute, often requiring post-transfusion imaging evaluation. While there is no absolute contraindication for chest imaging following blood transfusion, it should be approached cautiously. We conducted a comprehensive search across multiple databases and registries. Research studies were limited to full-text original articles, reviews, and case reports published in English, involved human subjects, and focused on the interplay between blood transfusions and contrast-enhanced imaging. Scientific analyses were excluded if they did not focus on transfusion practices in the context of imaging or failed to address issues such as hemoglobin thresholds, transfusion reactions, or the clinical implications of contrast agents. Our research fills this gap by emphasizing the need for a cautious, multidisciplinary approach to post-transfusion computed tomography (CT) scans, especially in the presence of contrast agents. This study calls for increased awareness of the heightened risk of complications, such as autoimmune hemolysis, when both procedures are performed together. New insights from our research recommend individualized assessments and close patient monitoring when combining these interventions. Nevertheless, patients need to be hemodynamically and clinically stable before undergoing CT. Discussions. Symptoms that develop within the first 24 h post-transfusion are classified as secondary post-transfusion reactions unless proven otherwise. The prevalence of side effects from same-day CT scans and blood transfusions is challenging to quantify, as few studies focus on this combination. Transfusions and contrast-enhanced CT scans share overlapping adverse reactions and carry significant risks. Acute hemolytic red blood cell transfusion reactions are among the most frequent side effects, with a prevalence of 1:12,000-38,000. Conclusion. Our study contributes new insights to the literature by filling the gap concerning the interplay between transfusions and contrast media, paving the way for more informed clinical protocols to enhance patient safety.

Conservative management of brain arteriovenous malformations: results of the prospective observation registry of a pragmatic trial.

Many patients recruited in the Treatment of Brain Arteriovenous Malformations Study (TOBAS) are managed conservatively. The aim of this study was to monitor what happened to those patients. TOBAS comprises two randomized controlled trials and multiple prospective registries. All patients with brain arteriovenous malformations (AVMs) can participate. This report concerns patients selected for conservative management. The primary trial outcome measure is related death or dependency (modified Rankin Scale [mRS] score > 2) at 10 years. Secondary outcomes include intracranial hemorrhages, nonhemorrhagic neurological events, and serious adverse events (SAEs). For this report, outcome results are presented using patient-years, Kaplan-Meier survival curves, and Cox log-rank tests. There was no blinding. From June 2014 to May 2021, 1010 patients were recruited, of whom 498 (49%) were proposed the prospective observation registry. After exclusions, 434 (87%) patients remained for analysis. The majority of patients had unruptured AVMs (378/434 [87%]), of which 195 (52%) were low grade (Spetzler-Martin grade I or II). During a mean follow-up period of 3.2 years (total 1368 patient-years), the primary outcome occurred in 23 of 434 (5%) patients, corresponding to an incidence of 1.7 (95% CI 1.1-2.5) per 100 patient-years. For unruptured AVMs the incidence was 1.1 (95% CI 0.7-1.9) per 100 patient-years, and for low-grade unruptured AVMs it was 0.6 (95% CI 0.2-1.7) per 100 patient-years. Poor outcomes were more frequent in patients with a history of rupture (HR 5.6 [95% CI 2.4-13.0], p < 0.001), infratentorial AVMs (HR 2.9 [95% CI 1.1-7.3], p = 0.027), and age ≥ 55 years (HR 3.2 [95% CI 1.4-7.6], p = 0.007). Major intracranial hemorrhage occurred in 35 of 434 (8%) patients (incidence of 2.6 [95% CI 1.9-3.6] per 100 patient-years; 2.0 [95% CI 1.3-2.9] per 100 patient-years for unruptured AVMs and 1.3 [95% CI 0.6-2.6] per 100 patient-years for low-grade unruptured AVMs). Major AVM hemorrhages were more frequent in ruptured (HR 4.4 [95% CI 2.1-8.9], p < 0.001), large (HR 2.6 [95% CI 1.1-6.6], p = 0.039), and high-grade (HR 2.5 [95% CI 1.2-5.3], p = 0.013) AVMs and those with deep venous drainage (HR 2.1 [95% CI 1.1-4.2], p = 0.032). SAEs occurred in 48 of 434 (11%) patients (incidence of 3.6 [95% CI 2.7-4.8] per 100 patient-years). For unruptured AVMs the incidence was 2.8 (95% CI 2.0-4.0) per 100 patient-years, and for low-grade unruptured AVMs it was 1.8 (95% CI 1.0-3.2) per 100 patient-years. Nearly half of TOBAS participants were observed. Rates of untoward neurological events were within expected boundaries.

ID: 342538 SCS for Painful Diabetic Peripheral Neuropathy: Consistent Outcomes from Multiple RCTs and Prospective Registry Data

ID: 342538 SCS for Painful Diabetic Peripheral Neuropathy: Consistent Outcomes from Multiple RCTs and Prospective Registry Data

Left Atrial Appendage Occlusion vs Standard of Care After Ischemic Stroke Despite Anticoagulation

Patients with atrial fibrillation (AF) who have ischemic stroke despite taking oral anticoagulation therapy (OAT) have a very high risk of recurrence. Left atrial appendage occlusion (LAAO) is a mechanical stroke prevention strategy that may provide additional protection in patients with thromboembolic events under OAT. To compare percutaneous LAAO with continuing OAT alone regarding stroke prevention in patients with AF who had a thromboembolic event despite taking OAT. This cohort study was a propensity score-matched comparison of the STR-OAC LAAO cohort, an international collaboration of 21 sites combining patients from multiple prospective registries of patients who underwent LAAO between 2010 and 2022. STR-OAC LAAO cohort patients who had follow-up longer than 3 months were propensity score-matched to a previously published control cohort comprising patients from an established international collaboration of investigator-initiated prospective studies. This control cohort included patients with nonvalvular AF, recent ischemic stroke or transient ischemic attack, and follow-up longer than 3 months who were taking OAT before the index event. Analyses were adjusted for imbalances in gender, age, hypertension, diabetes, and CHA2 DS2-VASc score. Left atrial appendage occlusion vs continuation of oral anticoagulation therapy alone (control group). The primary outcome was time to first ischemic stroke. Four hundred thirty-three patients from the STR-OAC LAAO cohort (mean [SD] age, 72 [9] years; 171 [39%] females and 262 [61%] males; mean [SD] CHA2 DS2-VASc score, 5.0 [1.6]) were matched to 433 of 1140 patients (38%) from the control group. During 2-year follow-up, 50 patients experienced ischemic stroke: an annualized event rate of 2.8% per patient-year in the STR-OAC LAAO group vs 8.9% per patient-year in the control group. Left atrial appendage occlusion was associated with a lower risk of ischemic stroke (hazard ratio, 0.33; 95% CI, 0.19-0.58; P < .001) compared with the control group. After LAAO, OAT was discontinued in 290 patients (67%), and the remaining 143 patients (33%) continued OAT after LAAO as an adjunctive therapy. In patients with nonvalvular AF and a prior thromboembolic event despite taking OAT, LAAO was associated with a lower risk of ischemic stroke compared with continued OAT alone. Randomized clinical trial data are needed to confirm that LAAO may be a promising treatment option for this population with a very high risk of stroke.

Cohort profile: the PRIMETIME 1 (PRecIsion MEdicine based on kidney TIssue Molecular interrogation in diabetic nEphropathy) cohort – a longitudinal Danish nationwide study of individuals with diabetes and a performed kidney biopsy

PurposeIndividuals with diabetes and chronic kidney disease are at high risk of kidney failure, cardiovascular events and premature mortality and more research is warranted to further improve the prevention and...

Long-Term Disability After Traumatic Spinal Injuries: A Military Retrospective Study.

Traumatic spinal injuries (TSI) pose a significant life-long burden, impacting both military and civilian populations. Assessing long-term outcomes is crucial for comprehending the enduring consequences of the initial insult and informing effective prevention and management strategies. Most existing studies have narrowly focused on subsets of traumatic cord injuries, leaving a gap in understanding the broader impact of severe spinal trauma. This study aims to examine severe TSIs in military personnel, who may face unique risk factors and injury patterns, and its association with long-term disability. A retrospective cohort study was conducted on all military personnel who suffered traumatic injuries (Injury Severity Score ≥ 9) from 1997 to 2020. Severe spinal injuries were defined using the spinal Abbreviated Injury Scale ≥ 3 (n = 95), and compared to all other injuries as a reference group (n = 1,394). Data were extracted and cross-referenced from three distinct nationwide registries-pre-hospital, admission, and rehabilitation. Logistic regression analysis was used to evaluate the impact of spinal injuries on long-term disabilities (defined as the highest possible disability tier). The study received approval from the institutional review board of the Israel Defense Forces Medical Corps. Motor vehicle accidents and falls were the primary causes of spinal injuries (50.5% and 15.8%, respectively). The median age at injury was 20 years (interquartile range 19-22). Personnel with spinal trauma had a significantly higher prevalence of Injury Severity Score ≥ 25 (46.3% vs. 19.9%, P < .001), longer median hospital stays (11 vs. 8 days, P = .036), and increased intensive care unit admissions (55% vs. 40%, P = .05). The median follow-up duration was 10.9 years (interquartile range 6.7-14.3). Spinal injuries were associated with a more than 10-fold increase in the adjusted odds ratio for severe permanent disability (11.92, 95% CI, 5.95-23.72). Upon long-term follow-up, military personnel with severe TSI exhibit a significantly higher prevalence of debilitating disability compared to those with significant non-spinal traumatic injuries. These findings highlight the critical need for targeted prevention strategies and improved management of spinal injuries to reduce long-term disability. Strengths of this study include its extensive follow-up period and the use of multiple nationwide registries. However, the study may be limited by potential discrepancies in identity matching across databases and the reliance on disability claims, which may underrepresent the true prevalence of long-term disability. Future research should explore the efficacy of early interventions and rehabilitation strategies in mitigating long-term disability following spinal injuries. This study underscores the importance of developing evidence-based policies to enhance care for individuals with TSIs.

Lipid-lowering therapy in patients with coronary heart disease: an Italian real-life survey. Results from the Survey on Risk FactOrs and CardiovascuLar secondary prEvention and drug strategieS (SOFOCLES) in Italy.

In patients at high cardiovascular risk, a low-density lipoprotein cholesterol (LDL-C) reduction of ≥50% from baseline and an LDL-C goal of <70 mg/dL (or <55 mg/dL in very high-risk patients) are recommended. Multiple registry and retrospective studies have shown that patients with high atherosclerotic cardiovascular risk often do not reach the targets defined by the European Society of Cardiology guidelines as a result of suboptimal management of LDL-C. Here, we report the data on lipid-lowering therapy and lipid targets from the Survey on Risk FactOrs and CardiovascuLar secondary prEvention and drug strategieS (SOFOCLES), an observational, prospective study designed to collect data on patients with ischemic heart disease treated at cardiac outpatient clinics across the Italian national territory. We included patients with known coronary heart disease (CHD) who underwent follow-up visits at various outpatient cardiology clinics. A total of 2532 patients were included (mean age: 67±17 years, 80% male). Among patients with available laboratory data (n=1712), 995 (58%) had LDL-C<70 mg/dL, 717 (42%) had LDL-C≥70 mg/dL, and 470 (27%) had LDL-C<55 mg/dL. Patients who more frequently achieved the recommended LDL-C levels were male, had diabetes, had a higher educational level, and performed intense physical activity. Statins were used in 2339 (92%) patients, high-intensity statins (e.g., rosuvastatin 20/40 mg or atorvastatin 40/80 mg) in 1547 patients (61% of the whole population and 66% of patients on statins), and ezetimibe in 891 patients (35%). Patients receiving high-intensity statins tended to be younger, not to have diabetes, and to have been included in a cardiac rehabilitation program. In a real-world sample of Italian patients with CHD, adherence to lipid-lowering therapy fell markedly short of optimal levels. Many patients did not achieve the LDL-C target of 70 mg/dL, and even fewer reached the LDL-C target of 55 mg/dL. Notably, patients with a lower educational level had a greater likelihood of being undertreated. Strategies aimed at improving preventive interventions for CHD and overcoming social disparities should be evaluated and optimized.

Validating Orthopaedic Data Evaluation Panel (ODEP) Ratings Across 9 Orthopaedic Registries: Total Hip Implants with an ODEP Rating Perform Better Than Those without an ODEP Rating.

Orthopaedic Data Evaluation Panel (ODEP) ratings of total hip (TH) and total knee (TK) implants are informative for assessing implant performance. However, the validity of ODEP ratings across multiple registries is unknown. Therefore, we aimed to assess, across multiple registries, whether TH and TK implants with a higher ODEP rating (i.e., an A* rating) have lower cumulative revision risks (CRRs) than those with a lower ODEP rating (i.e., an A rating) and the extent to which A* and A-rated implants would be A*-rated on the basis of the pooled registries' CRR. Implant-specific CRRs at 3, 5, and 10 years that were reported by registries were matched to ODEP ratings on the basis of the implant name. A meta-analysis with random-effects models was utilized for pooling the CRRs. ODEP benchmark criteria were utilized to classify these pooled CRRs. A total of 313 TH cups (54%), 356 TH stems (58%), 218 TH cup-stem combinations (34%), and 68 TK implants (13%) with unique brand names reported by registries were matched to an ODEP rating. Given the low percentage that matched, TK implants were not further analyzed. ODEP-matched TH implants had lower CRRs than TH implants without an ODEP rating at all follow-up time points, although the difference for TH stems was not significant at 5 years. No overall differences in CRRs were found between A* and A-rated TH implants, with the exception of TH cup-stem combinations, which demonstrated a significantly lower CRR for A*A*-rated cup-stem combinations at the 3-year time point. Thirty-nine percent of A*-rated cups and 42% of A*-rated stems would receive an A* rating on the basis of the pooled registries' CRR at 3 years; however, 24% of A-rated cups and 31% of A-rated stems would also receive an A* rating, with similar findings demonstrated at longer follow-up. At all follow-up time points, ODEP-matched TH implants had lower CRRs than TH implants without an ODEP rating. Given that the performance of TH implants varied across countries, registries should first validate ODEP ratings with use of country-specific revision data to better guide implant selection in their country. Data source transparency and the use of revision data from multiple registries would strengthen the ODEP benchmarks. Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Impact of Sodium-Glucose Cotransporter-2 Inhibitors on Heart Failure in Patients With Type 2 Diabetes Mellitus: A Systematic Review.

Type 2 diabetes mellitus (T2DM) is a major global health concern with a strong association with increased cardiovascular morbidity and mortality. The prevalence of heart failure is significantly higher in the T2DM population compared to non-diabetic individuals. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have emerged as a promising therapeutic class for managing T2DM, with potential cardioprotective effects.This systematic review aims to comprehensively evaluate the impact of SGLT-2 inhibitors on cardiovascular outcomes in adult patients with T2DM. A comprehensive electronic search was conducted across multiple databases and registries from May 8to June 6, 2024, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Studies published between January 2019 and June 6, 2024 that evaluated the effects of SGLT-2 inhibitors on cardiovascular outcomes in adults with T2DM were included. The risk of bias was assessed using appropriate tools based on thestudy design. A narrative synthesis was planned to summarize the findings. The search strategy identified 25 studies (22 randomized controlled trials, three cohort studies) for inclusion in the systematic review.Most of the included studies demonstrated a low overall risk of bias, although some observational studies had some limitations. The studies investigated the effects of various SGLT-2 inhibitors, including empagliflozin, canagliflozin, dapagliflozin, and others, on cardiovascular endpoints such as heart failure-related hospitalizations, mortality, cardiac structure and function, and biomarkers.The findings suggest that SGLT-2 inhibitors may have a beneficial impact on reducing the risk of heart failure-related hospitalizations and potentially improving other cardiovascular outcomes in patients with T2DM. This comprehensive systematic review provides valuable insights into the emerging role of SGLT-2 inhibitors in mitigating cardiovascular complications associated with T2DM. The findings have important clinical implications and may inform evidence-based guidelines and treatment strategies aimed at improving cardiovascular outcomes in this high-risk patient population.

CNS and Thorax Injury and Associated Risks Factors in Equestrian Sports.

Equestrian sports continue to gain popularity in the United States and are associated with a high injury rate, especially involving the central nervous system and thorax. Due to this high rate of injury and the potential for long-term consequences associated with participation, an understanding of the unique risks of this sport is needed. To describe severe injury in equestrian sports and review the role that protective gear plays in injury mitigation. The PubMed Database was searched using the search terms "equestrian" and "horse" combined with "spinal cord injury," "head injury," "traumatic brain injury," "experience levels," and "demographics." A total of 53 papers were selected based on their relevance of epidemiology, risk factors, and management of injuries sustained during equestrian activities. Case studies, randomized controlled trials, prospective studies, and retrospective studies were all included for further review. Systematic review. Level 4. None. Injuries to the thorax, including fractures, pneumothoraces, internal organ contusions, and crush injuries, have been cited in multiple national and international trauma registries as the most prevalent injury location in equestrians; however, head and neck injuries, high cervical spine fractures, and closed head injuries are reported to be associated with the highest rates of mortality. Helmets provide protection against skull fracture and traumatic brain injury. Vests were not associated with diminished rates of spinal cord injuries; however, they may provide protection to the thorax. Riding experience also plays a role in reducing the prevalence of injury. Equestrian-related activities are associated with a high risk of injury despite protective measures. Protective gear can mitigate some injury risk but does not protect against spinal injury. Continued investigation into improving protective equipment, rider education, and preventative strategies to mitigate this risk is needed.

Virtual Pooled Registry-Cancer Linkage System: an improved method for ascertaining cancer diagnoses.

The National Cancer Institute funds many large cohort studies that rely on self-reported cancer data requiring medical record validation. This is labor intensive, costly, and prone to underreporting or misreporting of cancer and disparity-related differential response. US population-based central cancer registries identify incident cancer within their catchment area, yielding all malignant neoplasms and benign brain and central nervous system tumors with standardized data fields. This manuscript describes the development, implementation, and features of a system to facilitate linkage between cohort studies and cancer registries and the release of cancer registry data for matched cohort participants. The Virtual Pooled Registry-Cancer Linkage System (VPR-CLS) provides an online system to link cohorts with multiple state cancer registries by 1) securely transmitting a study file to registries, 2) providing an optimized linkage algorithm to generate preliminary match counts, and 3) providing a streamlined process and templated forms for submitting and tracking data requests for cohort participants who matched with registries. In 2022, the VPR-CLS launched with 45 registries, covering 95% of the US state populations and Puerto Rico. Registries have linked with 15 studies having 14 273-10.9 million participants. Except in 1 study, linkage sensitivity ranged from 87.0% to 99.9%. Numerous registries have adopted the VPR-CLS templated institutional review board-registry application (n = 39), templated data use agreement (n = 25), and central institutional review board (n = 16). The VPR-CLS markedly improves ascertainment of cancer outcomes and is the preferred approach for determination of outcomes from cohort studies, postmarketing surveillance, and clinical trials.

Non-invasive brain stimulation for treatment-resistant schizophrenia: protocol of a systematic review and network meta-analysis

BackgroundNon-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a comprehensive synthesis of evidence is lacking. Thus, we will conduct a systematic review and network meta-analysis to investigate the comparative efficacy and safety of NIBS techniques as an add-on to antipsychotics for treatment-resistant schizophrenia.MethodsWe will include single- and double-blind randomized-controlled trials (RCT) comparing any NIBS technique with each other or with a control intervention as an add-on to antipsychotics in adult patients with treatment-resistant schizophrenia. We will exclude studies focusing on predominant negative symptoms, maintenance treatment, and single sessions. The primary outcome will be a change in overall symptoms, and secondary outcomes will be a change in symptom domains, cognitive performance, quality of life, functioning, response, dropouts, and side effects. We will search for eligible studies in previous reviews, multiple electronic databases and clinical trial registries from inception onwards. At least two independent reviewers will perform the study selection, data extraction, and risk of bias assessment. We will measure the treatment differences using standardized mean difference (SMD) and odds ratio (OR) for continuous and dichotomous outcomes, respectively. We will conduct pairwise and network meta-analysis within a frequentist framework using a random-effects model, except for rare event outcomes where we will use a fixed-effects Mantel–Haenszel method. We will investigate potential sources of heterogeneity in subgroup analyses. Reporting bias will be assessed with funnel plots and the Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) tool. The certainty in the evidence will be evaluated using the Confidence in Network Meta-analysis (CINeMA) approach.DiscussionOur network meta-analysis would provide an up-to-date synthesis of the evidence from all available RCTs on the comparative efficacy and safety of NIBS for treatment-resistant schizophrenia. This information could guide evidence-based clinical practice and improve the outcomes of patients.Systematic review registrationPROSPERO-ID CRD42023410645.

Two-phase biomarker studies for disease progression with multiple registries

Two-phase biomarker studies for disease progression with multiple registries

Developing a Coordinated Registry Network for devices used for acute ischemic stroke intervention: basilar artery occlusion quality assessment pilot

BackgroundReal-world data can be helpful in evaluating endovascular therapy (EVT) in ischemic stroke care. We conducted a pilot study to aggregate data on basilar artery occlusion (BAO) EVT from existing...

The establishment of a multiple myeloma clinical registry in the Asia–Pacific region: The Asia–Pacific Myeloma and Related Diseases Registry (APAC MRDR)

BackgroundMultiple myeloma (MM) is the second most common haematological cancer worldwide. Along with related diseases including monoclonal gammopathy of undetermined significance (MGUS), plasma cell leukaemia (PCL) and plasmacytoma, MM incidence is rising, yet it remains incurable and represents a significant disease burden. Clinical registries can provide important information on management and outcomes, and are vital platforms for clinical trials and other research. The Asia–Pacific Myeloma and Related Diseases Registry (APAC MRDR) was developed to monitor and explore variation in epidemiology, treatment regimens and their impact on clinical outcomes across this region. Here we describe the registry’s design and development, initial data, progress and future plans.MethodsThe APAC MRDR was established in 2018 as a multicentre collaboration across the Asia–Pacific, collecting prospective data on patients newly diagnosed with MM, MGUS, PCL and plasmacytoma in Korea, Singapore, Malaysia and Taiwan, with China recently joining. Development of the registry required a multidisciplinary team of clinicians, researchers, legal and information technology support, and financial resources, as well as local clinical context from key opinion leaders in the APAC region. Written informed consent is obtained and data are routinely collected throughout treatment by hospital staff. Data are stored securely, meeting all local privacy and ethics requirements. Data were collected from October 2018 to March 2024.ResultsOver 1700 patients from 24 hospitals have been enrolled onto the APAC MRDR to date, with the majority (86%) being newly diagnosed with MM. Bortezomib with an immunomodulatory drug was most frequently used in first-line MM therapy, and lenalidomide-based therapy was most common in second-line. Establishment and implementation challenges include regulatory and a range of operational issues.ConclusionThe APAC MRDR is providing ‘real-world’ data to participating sites, clinicians and policy-makers to explore factors influencing outcomes and survival, and to support high quality studies. It is already a valuable resource that will continue to grow and support research and clinical collaboration in MM and related diseases across the APAC region.

Prosthetic outcomes after amputation and the impact of mobility level on survival

ObjectiveLower extremity amputation continues to be necessary in a significant number of patients with peripheral vascular disease. The 5-year survival following lower limb loss is markedly reduced. Many of these patients are never fitted with a prosthesis, and there is a dearth of knowledge regarding the barriers to prosthetic attainment. The goal of this study was to identify the risk factors for not receiving a prosthesis and the effect of mobility level on survival following major amputation. MethodsThis was a retrospective analysis of all patients that underwent lower extremity amputation by surgeons in our practice from January 1, 2010, to December 31, 2019. Abstracted data included: age, sex, race, body mass index, comorbidities, American Society of Anesthesiologists score, statin use, level of amputation, stump revision, fitting for prosthesis, type of prosthesis, and the United States’ Medicare Functional Classification Level, also called K level. Survival was determined using a combination of sources, including the Social Security Death Master File, searches of multiple genealogic registries, and general internet searches. Multivariable logistic regression was used to determine risk factors associated with prosthesis attainment. Multivariable Cox proportional hazard regression with time-dependent covariates was performed to assess risk factors associated with 5-year mortality. ResultsA total of 464 patients were included in this study. The mean age was 65 years, and mean body mass index was 27 kg/m2. The majority of patients were male (68%), White (56%), diabetic (62%), and hypertensive (76%), and underwent below-the-knee amputation (69%). Prosthetic attainment occurred in 185 (40%). On multivariable analysis, age >81 years and current tobacco use were associated with no prosthetic fitting. Overall 5-year survival was 41.9% (95% confidence interval [CI], 37.6%-46.6%) (below-the-knee amputation, 47.7% [95% CI, 42.5%-53.5%]; above-the-knee amputation, 28.7% [95% CI, 22.1%-37.2%]). On multivariable analysis, age >60 years, congestive heart failure, above-the-knee amputation, and no prosthetic attainment were associated with decreased survival. Increasing K level was incrementally associated with improved survival. ConclusionsThis study has identified several patient factors associated with prosthetic attainment, as well as multiple factors predictive of reduced survival after amputation. Being referred for prosthetic fitting was associated with improved survival not explained by patient characteristics and comorbidities. The Medicare Functional Classification Level K level predicts survival. More research is needed to determine the barriers to prosthetic attainment and if improving a patients K level will improve survival.

Abstract 832: Gender differences in urinary tract cancer susceptibility associated with radon in water: A population based study from Finland

Abstract Background: Radon as a common source of environmental radiation, while its carcinogenic effect on urinary tract cancer has not been fully investigated. Methods: Men and women who have continuously lived in Finland from year 1987 onward and reached 40+ years old at the beginning of 2017 were followed up for urinary tract cancer, including bladder cancer (ICD-O 3 code C67) and kidney cancer (C64-C66 and C68) for 5 years until the end of 2021. The residential location and type of buildings of the cohort members were traced from year 1987 until 2016 annually and linked to the average cumulative exposure of radon concentration in well water on municipality level. Newly diagnosed UTC cases were identified based on the Finnish cancer register. Pre-existing health conditions, such as hypertension, diabetes, chronic kidney disease, calculus of kidney and lower urinary tract, family history of cancer, as well as socioeconomic factors were ascertained from multiple registry databases. Data were analyzed with Cox proportional hazards model conditional on birth cohorts and adjusted with available covariates. Findings: Among 1,019,331 men and 1,192,960 women with 30-years average radon exposure, 4206 and 2226 urinary tract cancer cases were diagnosed during follow-up period from 2017 until correspondingly. Men with higher radon exposure (&amp;gt;500 Bq/m3) had about 14% higher risks of UTC in total (HR 1.14, 95% CI 1.07-1.21), 19% higher risks of bladder cancer (HR 1.19, 95%CI 1.09-1.32), 10% higher risks of kidney cancer (HR 1.10, 95%CI 1.02-1.20) comparing with lower exposed samples. Women with higher radon exposure had about 1% higher risks of UTC in total (HR 1.01, 95%CI 0.93-1.10), 3% higher risks of bladder cancer (HR 1.03, 95%CI 0.88-1.22), 1% higher risks of kidney cancer (HR 1.01, 95%CI 0.92-1.11). In the sub-population who only lived in houses during the 30-years exposure period, men with higher radon exposure had about 24% higher risks of UTC (HR 1.24, 95% CI 1.12- 1.36), 30% higher risks of bladder cancer (HR 1.30, 95%CI 1.12-1.51), 20% higher risks of kidney cancer (HR 1.20, 95%CI 1.06-1.36). No significant association was observed in women who only lived in houses during exposure period. Conclusions: For men, higher radon exposure was significantly associated with elevated risks of UTC. No significant association was observed in women. Further investigates were needed to explore the mechanisms of gender differences in UTC susceptibility associated with radon exposure. Keywords: Radon, Radiation, Cancer, Urinary tract cancer, Kidney cancer, Bladder cancer Citation Format: Peng Yunzhi Li. Gender differences in urinary tract cancer susceptibility associated with radon in water: A population based study from Finland [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 832.

Sex impacts treatment decisions in multiple sclerosis.

Individual disease-modifying treatment (DMT) decisions might differ between female and male people with MS (pwMS). To identify sex-related differences in DMT strategies over the past decades in a real-world setting. In this cohort study, data from the Austrian Multiple Sclerosis Treatment Registry (AMSTR), a nationwide prospectively collected registry mandatory for reimbursement, were retrospectively analyzed. Of 4840 pwMS, those with relapsing-remitting MS, aged at least 18years, who started DMT and had at least two clinical visits, were identified. At baseline, demographics, Expanded Disability Status Scale (EDSS) score, annualized relapse rate (ARR) in the prior 12months and MRI lesion load were assessed. At follow-up, ARR, EDSS scores, and DMT were determined. A total of 4224 pwMS were included into the study and had a median of 10 (IQR 5-18) clinical visits over an observation period of 3.5 (IQR 1.5-6.1) years. Multivariable Cox regression analysis revealed that the probability of DMT escalation due to relapse activity was lower in female than male pwMS (HR 4.1 vs. 8.3 per ARR). Probability of discontinuing moderate-effective DMT was higher in female pwMS when they were younger (HR 1.03 per year), and lower in male pwMS at higher age (HR 0.92). Similarly, female pwMS were more likely to stop highly effective DMT than male pwMS (HR 1.7). Among others, the most frequent reason for DMT discontinuation was family planning in female pwMS. All sex-related effects were independent of disease activity, such as MRI lesion load, baseline ARR or EDSS. Real-world treatment decisions are influenced by sex-related aspects. Awareness of these associations should prevent unwarranted differences in MS care.

Management of pediatric hemolytic uremic syndrome.

Classical clinical triad of hemolytic uremic syndrome (HUS) is microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury associated with endothelial cell injury. Several situations, including infections, medications, malignancies, and transplantation can trigger endothelial damage. On the HUS spectrum, atypical hemolytic uremic syndrome (aHUS) deserves special attention in pediatric patients, as it can cause endstage kidney disease and mortality. A dysfunction in the alternative complement pathway, either acquired or genetic, has been shown to be the main underlying cause. In the last decades, breathtaking advances have been made in understanding the pathophysiology of this rare disease, which has led to more efficient treatment. Recent studies have implicated genes in pathways beyond the alternative complement system, such as DGKE, TSEN2, and INF2 highlighting the importance of personalized management. Eculizumab has brought about dramatic improvements in the treatment of aHUS. Beyond eculizumab, there are many alternative therapeutics in the pipeline that target the complement system. Because of the rarity of aHUS, data from multiple patient registries are very important. The present report aimed to summarize the most important aspects of diagnosing and treating aHUS based on the Turkish national registry and the literature so as to improve clinical practice.