Vital Status Research Articles

Mortality and Morbidity in Adults With Rheumatic Heart Disease

Rheumatic heart disease (RHD) remains a public health issue in low- and middle-income countries (LMICs). However, there are few large studies enrolling individuals from multiple endemic countries. To assess the risk and predictors of major patient-important clinical outcomes in patients with clinical RHD. Multicenter, hospital-based, prospective observational study including 138 sites in 24 RHD-endemic LMICs. The primary outcome was all-cause mortality. Secondary outcomes were cause-specific mortality, heart failure (HF) hospitalization, stroke, recurrent rheumatic fever, and infective endocarditis. This study analyzed event rates by World Bank country income groups and determined the predictors of mortality using multivariable Cox models. Between August 2016 and May 2022, a total of 13 696 patients were enrolled. The mean age was 43.2 years and 72% were women. Data on vital status were available for 12 967 participants (94.7%) at the end of follow-up. Over a median duration of 3.2 years (41 478 patient-years), 1943 patients died (15% overall; 4.7% per patient-year). Most deaths were due to vascular causes (1312 [67.5%]), mainly HF or sudden cardiac death. The number of patients undergoing valve surgery (604 [4.4%]) and HF hospitalization (2% per year) was low. Strokes were infrequent (0.6% per year) and recurrent rheumatic fever was rare. Markers of severe valve disease, such as congestive HF (HR, 1.58 [95% CI, 1.50-1.87]; P < .001), pulmonary hypertension (HR, 1.52 [95% CI, 1.37-1.69]; P < .001), and atrial fibrillation (HR, 1.30 [95% CI, 1.15-1.46]; P < .001) were associated with increased mortality. Treatment with surgery (HR, 0.23 [95% CI, 0.12-0.44]; P < .001) or valvuloplasty (HR, 0.24 [95% CI, 0.06-0.95]; P = .042) were associated with lower mortality. Higher country income level was associated with lower mortality after adjustment for patient-level factors. Mortality in RHD is high and is correlated with the severity of valve disease. Valve surgery and valvuloplasty were associated with substantially lower mortality. Study findings suggest a greater need to improve access to surgical and interventional care, in addition to the current approaches focused on antibiotic prophylaxis and anticoagulation.

Hip Fracture Risk Assessment Tools for Adults Aged 80 Years and Older

While adults aged 80 years and older account for 70% of hip fractures in the US, performance of fracture risk assessment tools in this population is uncertain. To compare performance of the Fracture Risk Assessment Tool (FRAX), Garvan Fracture Risk Calculator, and femoral neck bone mineral density (FNBMD) alone in 5-year hip fracture prediction. Prognostic analysis of 3 prospective cohort studies including participants attending an index examination (1997 to 2016) at age 80 years or older. Data were analyzed from March 2023 to April 2024. Participants contacted every 4 or 6 months after index examination to ascertain incident hip fractures and vital status. Predicted 5-year hip fracture probabilities calculated using FRAX and Garvan models incorporating FNBMD and FNBMD alone. Model discrimination assessed by area under receiver operating characteristic curve (AUC). Model calibration assessed by comparing observed vs predicted hip fracture probabilities within predicted risk quintiles. A total of 8890 participants were included, with a mean (SD) age at index examination of 82.6 (2.7) years; 4906 participants (55.2%) were women, 866 (9.7%) were Black, 7836 (88.1%) were White, and 188 (2.1%) were other races and ethnicities. During 5-year follow-up, 321 women (6.5%) and 123 men (3.1%) experienced a hip fracture; 818 women (16.7%) and 921 men (23.1%) died before hip fracture. Among women, AUC was 0.69 (95% CI, 0.67-0.72) for FRAX, 0.69 (95% CI, 0.66-0.72) for Garvan, and 0.72 (95% CI, 0.69-0.75) for FNBMD alone (FNBMD superior to FRAX, P = .01; and Garvan, P = .01). Among men, AUC was 0.71 (95% CI, 0.66-0.75) for FRAX, 0.76 (95% CI, 0.72-0.81) for Garvan, and 0.77 (95% CI, 0.72-0.81) for FNBMD alone (P < .001 Garvan and FNBMD alone superior to FRAX). Among both sexes, Garvan greatly overestimated hip fracture risk among individuals in upper quintiles of predicted risk, while FRAX modestly underestimated risk among those in intermediate quintiles of predicted risk. In this prognostic study of adults aged 80 years and older, FRAX and Garvan tools incorporating FNBMD compared with FNBMD alone did not improve 5-year hip fracture discrimination. FRAX modestly underpredicted observed hip fracture probability in intermediate-risk individuals. Garvan markedly overpredicted observed hip fracture probability in high-risk individuals. Until better prediction tools are available, clinicians should prioritize consideration of hip BMD, life expectancy, and patient preferences in decision-making regarding drug treatment initiation for hip fracture prevention in late-life adults.

The role of dementia in the association between APOE4 and all-cause mortality: pooled analyses of two population-based cohort studies

The ε4 allele of the apolipoprotein E gene (APOE4) plays a role in neurodegeneration and in cardiovascular disease, but findings on its association with mortality are inconsistent. We aimed to examine the association between APOE4 and mortality, and the role of dementia in this association. In this pooled analysis, data on White participants aged 45-90 years who underwent APOE genotyping were drawn from two population-based cohorts: the Whitehall II study (UK), which began in 1985 and is ongoing, and the Three-City study (France), initiated in 1999 and ended in 2012. In the Three-City study, vital status was ascertained through linkage to the national registry of death Institut National de la Statistique des Études économiques, and dementia was ascertained via a neuropsychological evaluation and validation of diagnoses by an independent committee of neurologists and geriatricians. In the Whitehall II study, vital status was ascertained through linkage to the UK national mortality register, and dementia cases were ascertained by linkage to three national registers. Participants with prevalent dementia at baseline and participants missing an APOE genotype were excluded from analyses. Cox regression proportional hazard models were used to examine the association of APOE4 with all-cause, cardiovascular, and cancer mortality. The role of dementia in the association between APOE4 status and mortality was examined by excluding participants who developed dementia during follow-up from the analyses. An illness-death model was then used to examine the role of incident dementia in these associations. 14 091 participants (8492 from the Three-City study and 5599 from the Whitehall II study; 6668 [47%] of participants were women and 7423 [53%] were men), with a median follow-up of 15·4 years (IQR 10·6-21·2), were included in the analyses. Of these participants, APOE4 carriers (3264 [23%] of the cohort carried at least one ε4 allele) had a higher risk of all-cause mortality compared with non-carriers, with hazard ratios (HR) of 1·16 (95% CI 1·07-1·26) for heterozygotes and 1·59 (1·24-2·06) for homozygotes. Compared with APOE3 homozygotes, higher cardiovascular mortality was observed in APOE4 carriers, with a HR of 1·23 (1·01-1·50) for heterozygotes, and no association was found between APOE4 and cancer mortality. Excluding cases of incident dementia over the follow-up resulted in attenuated associations with mortality in homozygotes but not in heterozygotes. The illness-death model indicated that the higher mortality risk in APOE4 carriers was not solely attributable to dementia. We found a robust association between APOE4 and all-cause and cardiovascular mortality but not cancer mortality. Dementia explained a significant proportion of the association with all-cause mortality for APOE4 homozygotes, while non-dementia factors, such as cardiovascular disease mortality, are likely to play a role in shaping mortality outcomes in APOE4 heterozygotes. National Institutes of Health. For the French translation of the abstract see Supplementary Materials section.

Cancer survival in sub-Saharan Africa (SURVCAN-3): a population-based study

The Cancer Survival in Africa, Asia, and South America project (SURVCAN-3) of the International Agency for Research on Cancer aims to fill gaps in the availability of population-level cancer survival estimates from countries in these regions. Here, we analysed survival for 18 cancers using data from member registries of the African Cancer Registry Network across 11 countries in sub-Saharan Africa. We included data on patients diagnosed with 18 cancer types between Jan 1, 2005, and Dec 31, 2014, from 13 population-based cancer registries in Cotonou (Benin), Abidjan (CÔte d'Ivoire), Addis Ababa (Ethiopia), Eldoret and Nairobi (Kenya), Bamako (Mali), Mauritius, Namibia, Seychelles, Eastern Cape (South Africa), Kampala (Uganda), and Bulawayo and Harare (Zimbabwe). Patients were followed up until Dec 31, 2018. Patient-level data including cancer topography and morphology, age and date at diagnosis, vital status, and date of death (if applicable) were collected. The follow-up (survival) time was measured from the date of incidence until the date of last contact, the date of death, or until the end of the study, whichever occurred first. We estimated the 1-year, 3-year, and 5-year survival (observed, net, and age-standardised net survival) by sex, cancer type, registry, country, and human development index (HDI). 1-year and 3-year survival data were available for all registries and all cancer sites, whereas availability of 5-year survival data was slightly more variable; thus to provide medium-term survival prospects, we have focused on 3-year survival in the Results section. 10 500 individuals from 13 population-based cancer registries in 11 countries were included in the survival analyses. 9177 (87·4%) of 10 500 cases were morphologically verified. Survival from cancers with a high burden and amenable to prevention was poor: the 3-year age-standardised net survival was 52·3% (95% CI 49·4-55·0) for cervical cancer, 18·1% (11·5-25·9) for liver cancer, and 32·4% (27·5-37·3) for lung cancer. Less than half of the included patients were alive 3 years after a cancer diagnosis for eight cancer types (oral cavity, oesophagus, stomach, larynx, lung, liver, non-Hodgkin lymphoma, and leukaemia). There were differences in survival for some cancers by sex: survival was longer for females with stomach or lung cancer than males with stomach or lung cancer, and longer for males with non-Hodgkin lymphomas than females with non-Hodgkin lymphomas. Survival did not differ by country-level HDI for cancers of the oral cavity, oesophagus, liver, thyroid, and for Hodgkin lymphoma. For cancers for which population-level prevention strategies exist, and with relatively poor prognosis, these estimates highlight the urgent need to upscale population-level prevention activities in sub-Saharan Africa. These data are vital for providing the knowledge base for advocacy to improve access to prevention, diagnosis, and care for patients with cancers in sub-Saharan Africa. Vital Strategies, the Martin-Luther-University Halle-Wittenberg, and the International Agency for Research on Cancer. For the French and Portuguese translations of the abstract see Supplementary Materials section.

Colorectal Cancer Survival and Its Prognostic Factors in Karachi, Pakistan.

To determine the survival rates of colorectal cancer (CRC) in the Pakistani population and determine the prognostic factors for survival among the CRC patients. Retrospective cohort study. Place and Duration of the Study: The cancer registry of the Aga Khan University Hospital, Karachi, Pakistan, from 2010 to 2016. The abstracted data from the cancer registry was cleaned and updated regarding the vital status at the last follow-up. Survival analyses were performed using the Kaplan-Meier method. Adjusted hazard ratios (aHR) and their 95% confidence intervals (CIs) were estimated using a cox regression model to assess the prognostic factors for survival. The overall proportion of late-onset CRC (>50 years of age) was 55.3% and early-onset CRC (<=50 years of age) was higher than expected (45.7%). A high level of carcinoembryonic antigen (CEA) (>5 ng/ml) was associated with poor survival compared to patients with CEA levels of ≤5 ng/ml (aHR = 1.68, 95% CI = 1.04, 2.72). Patients, who experienced recurrence, showed poorer survival (aHR = 4.27, 95% CI = 2.55, 7.14). Patients, who did not undergo surgery, showed significantly poorer survival compared to those who underwent surgery (aHR = 5.53, 95% CI = 2.35, 13.03). The findings suggest that monitoring CEA levels, ensuring prompt surgical treatment and follow-up care for recurrent cases can improve survival outcomes in patients with colorectal cancer. Colorectal cancer (CRC), Surgery, Recurrence, Grade, Cancer registry.

Health disparities in acute myeloid leukemia: A decade-long analysis of Afro-Caribbean patients in a safety net New York City hospital.

e18515 Background: Acute Myeloid Leukemia (AML) in the Afro-Caribbean population is associated with poor outcomes due to disparities in health insurance and access to healthcare resources, among other factors, when compared to survival data in the national SEER database. This study reviews clinical characteristics and treatment outcomes of a cohort of 51 Afro-Caribbean patients who were diagnosed with AML and treated in the past 10 years in a urban safety net hospital in Brooklyn, New York. Methods: This is a retrospective review of patients diagnosed and treated for AML at New York City Health and Hospitals/Kings County from 2012 to 2022. Electronic Health Data was reviewed for clinicopathologic data and treatment outcomes. Analysis was performed through descriptive statistics with specific focus on insurance status and survival outcomes. Results: Our AML patient cohort had a mean age of 66, with 84% of patients identifying as Afro-Caribbean, and 51% being female. In this cohort, the AML risk stratification distribution based on 2022 European LeukemiaNet Risk classification includes 21 (41%) patients in the adverse-risk group, 23 (45%) patients in the intermediate-risk group, and 7 (14%) patients in the favorable-risk group. Of the 36 patients with molecular analysis data, 9 (25%) harbored a mutation in FLT3-ITD. Healthcare disparities are evident in insurance coverage, as 58% of patients lacked medical insurance, 19% had Medicare/Medicaid, and 23% had private insurance. At the time of this retrospective chart review, 35% of patients lacked any follow-up information, including appointments or status updates regarding their condition, vital status, or engagement with healthcare, possibly due to missed appointments, transfers, mortality, or other reasons. Of the 27 patients who were deemed transplant eligible, three (11%) successfully completed allogeneic bone marrow transplant. Reasons for non-transplantation include lack of a compatible donor, inadequate social support, insurance-related challenges, or patient refusal. Patients who completed induction and consolidation treatment with documented follow-up had a 23% survival rate at the five-year mark, compared to 31.7% overall survival rate reported in SEER data from 2013 to 2019. Conclusions: Our study highlights persistent healthcare disparities in Afro-Caribbean AML patients leading to poor survival outcomes. Despite treatment advancements, challenges related to insurance coverage, social support, follow-up care, and access to restricted, advanced care remain. Addressing these disparities calls for targeted interventions to enhance access and support systems for this vulnerable population.

Survival in de novo metastatic merkel cell carcinoma according to sites of metastases.

e21511 Background: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with a propensity to form regional and distant metastases. Due to the low incidence of MCC, there is a dearth of studies evaluating the impact of the sites of metastases on clinical outcomes. Recently, we found that liver and bone metastases were associated with shorter overall survival (OS) in patients with recurrent metastatic MCC. Herein, we report on the prognostic impact associated with specific metastatic sites in patients who presented with de novo Stage IV MCC at Dana-Farber Cancer Institute. Methods: Patients were included if they consented to participate in a biobanking study (DF/HCC #09-156) and presented with one or more distant sites of metastases on imaging at the time of diagnosis due to MCC. The following data were collected: age at diagnosis, gender, race, metastatic site(s) at the time of diagnosis, date of diagnosis, first-line treatment, treatment type, best response on imaging, progression, and vital status. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Fisher’s exact test was used for response rate analysis. Results were considered statically significant if p &lt; 0.05. Results: 34 participants presented with one or more distant metastatic sites of MCC between the years 2010 and 2022. There was no association between the number of metastatic sites at presentation and OS (p= 0.58), PFS (p= 0.79), or response rates (p= 0.53). Among the organ sites we examined, bone metastases were associated with shorter OS (8.2 versus 25.2 months, HR = 2.4; 95% CI 1.01 – 5.7, p= 0.04). There were non-significant associations between OS and metastases in lymph nodes (p= 0.07) and in liver (p= 0.16). The location of metastases was not associated with the response rate to first-line treatment. There was no statistically significant association between any site of metastases and PFS. Conclusions: In this cohort of patients with de novo metastatic MCC, the presence of bone metastases, but not the number of overall organs involved, was associated with significantly worse overall survival. If bone involvement is confirmed to be a negative prognostic factor in an independent dataset, it would warrant mechanistic studies to further our understanding of this interplay and a re-examination of the AJCC staging for metastatic disease.

SEGA frailty scale in emergency: back to basics

Can the SEGA scale, implemented in the emergency department, effectively predict morbidity and mortality? A prospective study was conducted from January 30, 2018, to July 16, 2018, at the Emergency Department of Chaumont Hospital. Patients aged over 65 were included, while those under 65, in palliative care, or in a life-threatening emergency were excluded. The SEGAm score was calculated for each included patient, and their outcomes were assessed at the end of the emergency department visit and one year later. A total of 278 subjects were included. Vital status at one year was known for all subjects, with no loss to follow-up or censoring. At one year, 56 patients out of 278 (20.1%, 95% CI 15.6% to 25.3%) had died, with less than half of these deaths (n = 25) occurring after readmission to the emergency department or during the emergency visit. The average age was 82 ± 8.2 years, with 158 women and 120 men. Regarding living arrangements, 130 (46.8%) lived at home without caregivers, 100 (36%) lived at home with caregivers, and 48 (17.3%) lived in nursing homes. The average Charlson Comorbidity Index was 5.49 ± 1.99, with an average number of medications of 7.52. The primary methods of referral were as follows: C15 for 144 patients (51.8%), general practitioner for 59 patients (21.2%), spontaneous consultation for 58 patients (20.9%), and family referral for 8 patients (2.9%). The main reasons for admission were falls for 55 patients (19.8%), dyspnea for 33 patients (11.9%), and other reasons for 60 patients (21.6%). Post-emergency department disposition included hospitalization for 167 patients (60.1%) and discharge for 111 patients (39.9%), with no deaths occurring during this period. The SEGAm frailty score (grid A) had an average completion time of 8.18 min ± 3.64. A score of ≤ 8 was found for 85 patients (30.6%), a score between 9 and 11 for 51 patients (18.3%), and a score ≥ 12 for 142 patients (51.1%). In this geriatric population, the risk of death at 12 months was estimated at 31% (95% CI 23.5% to 39.3%) for subjects with a SEGA score exceeding 12, compared to approximately 10% for those with lower SEGA scores. The risk of death or readmission was 52.8% (95% CI 44.3% to 61.2%) for subjects with a SEGA score exceeding 12, compared to 20% to 30% for those with lower SEGA scores. The SEGA score provides valuable prognostic information that is not fully captured by the Charlson score or reason for hospitalization.

Institutional review of pediatric oncology patients participating in early phase clinical trials.

10042 Background: Phase 1 or phase 1/2 trials are a first step in pediatric cancer drug development with a primary objective of evaluating safety and dosing of new therapies or new combinations. They most commonly enroll patients with relapsed/refractory or very rare cancers and currently there is a paucity of information regarding outcomes for pediatric patients enrolled on phase 1/2 trials. Thus, we sought to describe clinical outcomes of pediatric patients enrolled in phase 1 clinical trials over a 9-year period at a single institution. Methods: We queried our clinical trials management system to generate a list of all pediatric patients who were enrolled and treated on phase 1 or phase 1/2 trials from 2011-2019. We reviewed the electronic medical record to collect baseline demographic and clinical data. We also collected key efficacy and safety endpoints post-enrollment including: time to death (if applicable); objective response to trial therapy; duration on therapy; need for dose modification; and occurrence of DLT. Overall survival was calculated using Kaplan-Meier methods. Results: A total of 224 unique patients accounted for 258 enrollments and 253 episodes of treatment on trial. The median age at trial enrollment was 11 years (range 0-27 years) and 56.2% were male. The majority of patients were white (85.7%) and non-Hispanic (88.2%). English was the primary language for 86.3% of patients and 65.8% of patients had private insurance. Solid tumors were the most common malignancy at 41.0%, followed by brain tumors (34.1%), and hematologic malignancies (24.9%). The majority of patients (60%) had metastatic disease at time of first enrollment. Among episodes of treatment, 51.4% received targeted monotherapy. Median overall survival from first enrollment for 210 patients treated with available vital status was 12.8 months. Among episodes of treatment, 25.2% of patients had an objective response to trial therapy. Stratified by disease type, objective response was documented for 52.9% of patients with hematologic malignancies, 20.5% of patients with CNS tumors, and 15.8% of patients with solid tumors. Patients on trials with cytotoxic-only treatment had the highest objective response (47.5%), while patients treated with cytotoxic plus targeted therapies combinations had the lowest rate (18.9%). The median duration of therapy was 1.5 months. Twenty-seven patients (11.0%) required dose modification and 22 patients (9.0%) had DLT. Conclusions: We present clinical outcomes for a recent cohort of pediatric patients treated on early phase clinical trials. We identified differential response rates to phase 1 therapy by disease and trial-type in a single-center cohort treated over the past decade. These data are immediately informative to discussions between providers and patients/parents regarding expected phase 1 trial outcomes.

Survival outcomes in primary cutaneous diffuse large B-cell lymphoma, leg type.

e19074 Background: Primary cutaneous diffuse large B-cell lymphoma (PCDLBCL-LT) is an uncommon type of lymphoma predominantly affects elderly patients and is associated with poor outcome. Large-scale studies describing and evaluating the effect of different type of treatments on survival outcome are lacking. Methods: The National Cancer Database (NCDB) was queried for patients diagnosed with PCDLBCL-LT between 2004 and 2020. All patients aged ≥18 years diagnosed with PCDLBL-LT were included. We excluded patients with unknown chemotherapy and radiation therapy status or lost to follow-up (unknown vital status of last contact). Kaplan-Meier and multivariate Cox regression were used in the analyses. Results: The total cohort consisted of 967 patients with PCDLBCL-LT. Out of whom 516 (53%) were females, 841 (87%) were White non-Hispanic, 41 (4%) were White Hispanic and 37 (4%) were African Americans. 276 (29%) received chemotherapy, 203 (21%) received radiation only, 293 (30%) received chemoradiation, 147 (15%) did not receive any treatment and 48 (5%) had unknown treatment status. The median age at diagnosis was 78 years (range 23-90). The median follow-up time was 87 months (95% CI 74-99), the median overall survival (mOS) for the whole cohort was 42 months (95%CI 37-47). Among patients with known treatment status and vital status of last contact (N=841), patient who received chemoradiation had significantly better mOS compared to patients who received chemotherapy only, radiation only and no treatment (64 vs 41, 39 and 9 months, respectively P&lt;0.001). Patient who received chemotherapy only and radiation only as first line therapy had significantly better mOS compared to patients who received no treatment (41 and 39 vs 9 months, respectively P&lt;0.001), but there was no statistically significant difference in the mOS between chemotherapy only and radiation only (41 vs 39 months, P=0.359). On multivariate analysis, older age, male gender, and Charlson-Deyo score 2 and ≥3 were associated with worse OS (HR 1.061 95%CI 1.050-1.072; P&lt;0.001, HR 1.241 95%CI 1.093-1.482; P=0.017, HR 1.396 95%CI 1.004-1.941; P=0.047 and HR 2.454 95%CI 1.619-3.719; P&lt;0.001 respectively), all type of treatments including chemotherapy only, chemoradiation, and radiation only were associated with better OS (HR 0.576 95% CI 0.443-0.749; P&lt;0.001, HR 0.379 95%CI 0.290-0.495; P&lt;0.001 and HR 0.443 95%CI 0.339-0.578; P&lt;0.001, respectively). Conclusions: This large real-world analysis shows a survival benefit with combined treatment of chemoradiation in this uncommon type of lymphoma compared to single treatment modality.

Survival outcomes in primary orbital diffuse large B-cell lymphoma.

e19075 Background: Orbital diffuse large B-cell lymphoma is a rare entity accounts for less than 1% of all non-Hodgkin lymphoma cases. Large-scale studies describing and evaluating the effect of different type of treatments on survival outcome are lacking. Methods: The National Cancer Database (NCDB) was queried for patients diagnosed with primary orbital DLBCL between 2004 and 2020. All patients aged ≥ 18 years diagnosed with primary orbital DLBLC were included. We excluded patients with unknown chemotherapy and radiation therapy status or lost to follow-up (unknown vital status of last contact). Kaplan-Meier and multivariate Cox regression were used in the analyses. Results: The total cohort consisted of 404 patients with primary orbital DLBCL. Out of whom 233 (58%) were females, 326 (81%) were White non-Hispanic, 29 (7%) were White Hispanic and 16 (4%) were African Americans. 113 (28%) received chemotherapy only, 76 (19%) received radiation only, 113 (28%) received chemoradiation, 79 (20%) did not receive any treatment and 23 (6%) had unknown treatment status. The median age at diagnosis was 71 years (range 28-90). The median follow-up time was 132 months (95%CI 117-147), the median overall survival (mOS) for the whole cohort was 110 months (95%CI 82-138). Among patients with known treatment status and vital status of last contact (N=381), patient who received chemoradiation had significantly better mOS compared to patients who received radiation only (169 vs 67 months, P=0.002), but there was no statistically significant difference in mOS between chemoradiation and chemotherapy only (169 vs 124 months, P=0.068) or between chemotherapy only and radiation only (124 vs 67 months, P=0.213). On multivariate analysis, older age and Charlson-Deyo score of 2 were associated with worse OS (HR 1.072 95%CI 1.055-1.089; P&lt;0.001, HR 2.292 95%CI 1.099-4.778; P=0.027, respectively). Compared to no treatment, only chemoradiation was associated with better OS (HR 0.509 95%CI 0.332-0.778; P=0.002), whereas chemotherapy only and radiation only did not add a survival benefit (HR 0.909 95%CI 0.598-1.381; P=656 and HR 0.766 95%CI 0.496-1.185; P=0.231). Conclusions: This large real-world analysis shows a survival benefit with combined treatment of chemoradiation in primary orbital DLBCL compared to single treatment modality.

Clinical Advances and Current Status in the Treatment of Ureteral Calculi.

Ureteral calculi are a common urological disease with a consistently high incidence and an increasing trend each year. Ureteral calculi treatment is an essential and hot topic in the urology field and holds a vital status in the urological work system. Recently, with rapid advances in urology, there have been continuous updates and developments in treatment modalities, and many new methods and techniques have emerged and are being applied in clinical settings; This has effectively improved the clinical treatment outcomes of individuals with ureteral calculi. However, each treatment modality has its specific indications, and owing to the uneven distribution of medical resources and the effect of the patients' conditions and nature of the stones, standardization and randomness in selecting the treatment regimens for ureteral calculi are lacking. Therefore, selecting the diagnostic and therapeutic plan is vital for improving treatment efficacy. In this review, we summarize the findings of recent domestic and international studies to provide an outline of the progress and current status of ureteral calculi treatment from aspects such as pharmacotherapy, surgery, and minimally invasive treatment to provide a basis for treating this disease in clinical settings.

Prediabetes: prevalence, associations with cardiovascular risk factors and contribution to survival in the Russian population

Aim. To assess the prevalence of type 2 diabetes (T2D) and prediabetes in the Russian population aged 25-64 years, as well as the association of prediabetes with risk factors (RFs) of noncommunicable disease. To study the contribution of carbohydrate metabolism disorders to mortality and the occurrence of cardiovascular events.Material and methods. We included data from cross-sectional studies ESSE-RF and ESSE-RF2. The final sample included 26418 people (10268 men and 16150 women) who signed informed consent. A modular questionnaire was used. Biochemical parameters were determined in the National Medical Research Center for Therapy and Preventive Medicine with an Abbott Architect c8000 autoanalyzer using diagnostic kits from Abbott Diagnostics (USA). Impaired fasting glycemia (IFG) was defined as a fasting plasma glucose concentration of 6,1-6,99 mmol/L. The presence of T2D was determined by interview and/or fasting plasma glucose ≥7,0 mmol/L. Obesity was defined as a body mass index of ≥30,0 kg/m2. Abdominal obesity was defined as a waist circumference of ≥102 cm in men and ≥88 cm in women. A prospective observation cohort was formed from 14 regions of ESSE-RF and ESSE-RF2 (n=22812). The vital status of each examined person was clarified once every 2 years. Information on fatal and non-fatal events was collected. Statistical processing was performed using the open-source statistical programming language and R environment (version 4.1). Associations were assessed using logistic regression. Kaplan-Meier curves were used to estimate survival. Associations with endpoints were assessed using Cox proportional hazards models.Results. In the Russian population aged 25-64 years, the prevalence of T2D and prediabetes, assessed by IFG, was 6,9% (men — 7,1%, women — 6,7%) and 6,2% (men — 7,7, women — 5,0% (p&lt;0,001)), respectively. Age, low level of education, obesity, including abdominal obesity, hypertension, tachycardia, hyperuricemia and lipid metabolism disorders were significantly associated with prediabetes, and for men, additionally, stress. Prediabetes and T2D demonstrated a significant decrease of survival, including cardiovascular survival, and the occurrence of a composite endpoint. However, multivariate analysis adjusted for sex, age, and region of residence indicates a significant contribution of T2D, but not IFG.Conclusion. To reduce the T2D burden in the Russian Federation, patients with T2D should be identified early and RFs should be controled. Early detection of prediabetes plays a significant role in the prevention of T2D. In addition, T2D and prediabetes have common risk factors, and therefore common ways of prevention.

#1205 Protein intake and mortality in older adults with chronic kidney disease: a multicohort study

Abstract Background and Aims Limiting protein intake in older adults with chronic kidney disease (CKD) may reduce the risk of its progression, but whether it can adversely impact nutritional status and overall health is not well known. We aimed to study the associations of total, animal, and plant protein intake with all-cause mortality in older adults with CKD and replicated the analyses in those without CKD for comparison. Method We used data from three cohorts (Seniors-ENRICA 1 and Seniors-ENRICA 2 in Spain and SNAC-K in Sweden) of community-dwelling adults ≥60 years (2 555 with CKD and 6014 without). According to estimated glomerular filtration rates, urine albumin excretion, and diagnoses from electronic health records, 98% of participants with CKD were in stages 2 and 3. Cumulative protein intake was estimated via validated dietary histories and food frequency questionnaires. Vital status was ascertained with national death registers. Associations were estimated with Cox proportional hazards regression models, adjusted for sociodemographic, lifestyle, morbidity, and dietary variables. Results After a median follow-up of 10 years, 1 901 deaths were recorded. Higher total protein intake was associated with lower mortality among participants with CKD [hazard ratio (95% confidence interval) for 1.15 and 1.35 g/kg/day versus 1.0 g/kg/day = 0.93 (0.88, 0.98) and 0.85 (0.76, 0.95), respectively]. Low total protein intake was more detrimental to the youngest old (&amp;lt;75 years) and high total protein was less beneficial. Plant protein showed a stronger protective association with mortality than animal protein [0.73 (0.59, 0.90) and 0.91 (0.85, 0.98) per 0.2 g/kg/day increment, respectively]. Among participants without CKD, most hazard ratios were lower, especially in the oldest old, but no significant interactions between protein intake, CKD, and mortality arose. Conclusion Higher protein intake might have a positive impact on mortality in older adults with mild or moderate CKD, particularly plant protein. Recommendations for these patients may not differ substantially from those without CKD.

#2296 Time to get calciphylaxis on clinicians’ RaDaR?—a multicentre case series

Abstract Background and Aims Calciphylaxis is a rare, severe complication of chronic kidney disease mineral bone disorder. It is hosphorzed by arteriolar calcification of the subcutaneous fat and dermis, and associated with a mortality rate of approximately 50% within a year of diagnosis. The reported prevalence of calciphylaxis in dialysis patients ranges from 1–4%. Between March 2012 and March 2020 the UK calciphylaxis study (UKCS) recruited 139 patients from 36 enrolled renal centres; an average of 1 case every 2.6 years per centre. The multicentre case series presented here includes patients from two NHS Hospital Trusts in the UK. The aim is to raise awareness of i) calciphylaxis and possible risk factors and ii) the role of registry data in rare kidney diseases. Method Patients were included if they had a diagnosis of calciphylaxis between 01.02.2020 and 01.02.2022. Data regarding demographics, dialysis modality, BMI, medications, and mineral bone parameters were collected from clinical databases. A representative sample of results was recorded from initiation of renal replacement therapy through to diagnosis of calciphylaxis. Data regarding calciphylaxis lesions, treatments and current vital status are hosphorz. Results 17 patients with end stage kidney failure (ESKF) and clinical features of calciphylaxis were included; 8 of 17 (47%) had a skin biopsy of which 6 reported evidence of calcification. Median age was 57 years (IQR: 50-74), BMI 26.8 kg/m2 (IQR: 22.9-31.1), 100% were white, 53% female and 59% had diabetes. Median time from onset of ESKF to calciphylaxis diagnosis was 5.5 years (IQR: 1-16). 53% (9 of 17) had history of recurrent hypercalcaemia (corrected calcium &amp;gt;2.55 mmol/L) and 82% (14 of 17) recurrent hyperphosphatemia (phosphate &amp;gt;1.5 mmol/L). 41% (7 of 17) had refractory secondary hyperparathyroidism. Warfarin therapy exposure was recorded in 47% (8 of 17) patients; a finding consistent with the literature. 76% (13 of 17) had received active vitamin D and 76% (13 of 17) a calcium-based phosphate binder. 76% (13 of 17) had lower leg lesions; 2 of whom also had upper leg lesions. 1 patient had a thigh lesion and 2 patients had an abdominal wound. Median follow up time was 8.5 months (range 1-24). 9 of the 17 patients remain alive, of whom lesions have completely healed in 6 patients. All patients received sodium thiosulphate and 1 (transplant patient) received hyperbaric oxygen therapy and sodium thiosulphate. Only 1 patient has been enrolled into the UK registry of rare kidney diseases (RaDaR). Conclusion Calciphylaxis is a devastating condition for which there are no proven treatments. In this case series a history of hyperphosphataemia, calcium-based binder, alfacalcidol, and warfarin use were common. It remains unknown why some patients develop calciphylaxis and others do not. National registry data, such as RaDaR, plays a crucial role in furthering knowledge and understanding of rare diseases; it helps to determine calciphylaxis incidence, and inform possible prevention and treatment strategies. Yet, in reality, few patients maybe being recruited into RaDaR. The opportunity exists for an international calciphylaxis registry; for this to offer maximum impact individual countries need to explore, and where possible address, barriers to recruitment.

Geospatial disparities in survival of patients with breast cancer in sub-Saharan Africa from the African Breast Cancer-Disparities in Outcomes cohort (ABC-DO): a prospective cohort study

There is an urgent need to improve breast cancer survival in sub-Saharan Africa. Geospatial barriers delay diagnosis and treatment, but their effect on survival in these settings is not well understood. We examined geospatial disparities in 4-year survival in the African Breast Cancer-Disparities in Outcomes cohort. In this prospective cohort study, women (aged ≥18 years) newly diagnosed with breast cancer were recruited from eight hospitals in Namibia, Nigeria, South Africa, Uganda, and Zambia. They reported sociodemographic information in interviewer-administered questionnaires, and their clinical and treatment data were collected from medical records. Vital status was ascertained by contacting participants or their next of kin every 3 months. The primary outcome was all-cause mortality in relation to rural versus urban residence, straight-line distance, and modelled travel time to hospital, analysed using restricted mean survival time, Cox proportional hazards, and flexible parametric survival models. 2228 women with breast cancer were recruited between Sept 8, 2014, and Dec 31, 2017. 127 were excluded from analysis (58 had potentially recurrent cancer, had previously received treatment, or had no follow-up; 14 from minority ethnic groups with small sample sizes; and 55 with missing geocoded home addresses). Among the 2101 women included in analysis, 928 (44%) lived in a rural area. 1042 patients had died within 4 years of diagnosis; 4-year survival was 39% (95% CI 36-42) in women in rural areas versus 49% (46-52) in urban areas (unadjusted hazard ratio [HR] 1·24 [95% CI 1·09-1·40]). Among the 734 women living more than 1 h from the hospital, the crude 4-year survival was 37% (95% CI 32-42) in women in rural areas versus 54% (46-62) in women in urban areas (HR 1·35 [95% CI 1·07-1·71] after adjustment for age, stage, and treatment status). Among women in rural areas, mortality rates increased with distance (adjusted HR per 50 km 1·04, 1·01-1·07) and travel time (adjusted HR per h 1·06, 1·02-1·10). Among women with early-stage breast cancer receiving treatment, women in rural areas had a strong survival disadvantage (overall HR 1·54, 1·14-2·07 adjusted for age and stage; >1 h distance adjusted HR 2·14, 1·21-3·78). Geospatial barriers reduce survival of patients with breast cancer in sub-Saharan Africa. Specific attention is needed to support patients with early-stage breast cancer living in rural areas far from cancer treatment facilities. US National Institutes of Health (National Cancer Institute), Susan G Komen for the Cure, and the International Agency for Research on Cancer.

Treatment Interruptions and Mortality Among Puerto Rican Women With Gynecologic Cancers in Puerto Rico After Hurricanes Irma and María: A Retrospective Cohort Study.

Cancer patients are among the most vulnerable populations during and after a disaster. We evaluated the impact of treatment interruption on the survival of women with gynecologic cancer in Puerto Rico following Hurricanes Irma and María. A retrospective cohort study among a clinic-based sample of women with gynecological cancer diagnosed between January 2016 and September 2017 (n = 112) was done. Women were followed from their diagnosis until December 2019, to assess vital status. Kaplan-Meier survival curves and Cox proportional hazards models were performed. Mean age was 56 (± 12.3) years; corpus uteri (58.9%) was the most common gynecologic cancer. Predominant treatments were surgery (91.1%) and chemotherapy (44.6%). Overall, 75.9% were receiving treatment before the hurricanes, 16.1% experienced treatment interruptions, and 8.9% died during the follow-up period. Factors associated with treatment interruption in bivariate analysis included younger age (≤55 years), having regional/distant disease, and receiving > 1 cancer treatment (P < 0.05). Crude analysis revealed an increased risk of death among women with treatment interruption (HR: 3.88, 95% CI: 1.09-13.77), persisting after adjusting for age and cancer stage (HR: 2.49, 95% CI: 0.69-9.01). Findings underscore the detrimental impact of treatment interruption on cancer survival in the aftermath of hurricanes, emphasizing the need for emergency response plans for this vulnerable population.

Adherence to diabetes quality indicators in primary care and all-cause mortality: A nationwide population-based historical cohort study

Background In the last three decades, much effort has been invested in measuring and improving the quality of diabetes care. We assessed the association between adherence to diabetes quality indicators and all-cause mortality in the primary care setting. Methods A nationwide, population-based, historical cohort study of all people aged 45–80 with pharmacologically-treated diabetes in 2005 (n = 222,235). Data on annual performance of quality indicators (including indicators for metabolic risk factor management and glycemic control) and vital status were retrieved from electronic medical records of the four Israeli health maintenance organizations. Cox proportional hazards and time-dependent models were used to estimate hazard ratios (HRs) for mortality by degree of adherence to quality indicators. Results During 2,000,052 person-years of follow-up, 35.8% of participants died. An inverse dose–response association between the degree of adherence and mortality was shown for most of the quality indicators. Participants who were not tested for proteinuria or did not visit an ophthalmologist during the first-5-years of follow-up had HRs of 2.60 (95%CI:2.49–2.69) and 2.09 (95%CI:2.01–2.16), respectively, compared with those who were fully adherent. In time-dependent analyses, not measuring LDL-cholesterol, blood pressure, HbA1c, or HbA1c&gt;9% were similarly associated with mortality (HRs ≈1.5). The association of uncontrolled blood pressure with mortality was modified by age, with increased mortality shown for those with controlled blood pressure at older ages (≥65 years). Conclusions Longitudinal adherence to diabetes quality indicators is associated with reduced all-cause mortality. Primary care professionals need to be supported by health care systems to perform quality indicators.

Association between age at diagnosis and all-cause mortality in type 2 diabetes: the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study

AimsIt is unclear whether type 2 diabetes diagnosed in young adulthood is associated with increased severity than that occurring later in life beyond longer lifetime exposure to hyperglycemia. This study aimed at assessing the independent association of age at type 2 diabetes diagnosis with all-cause mortality.MethodsThis prospective cohort study enrolled 15,773 Caucasian patients with type 2 diabetes in 19 Italian centers in 2006–2008. Cardiometabolic risk profile and presence of complications and comorbidities were assessed at baseline and participants were stratified by quartiles of age at diabetes diagnosis. All-cause mortality was verified on 31 October 2015.ResultsValid information on vital status was retrieved for 15,656 participants (99.3%). Patients in the lowest quartile had the longest diabetes duration, the worst glycemic control and the highest prevalence of insulin treatment, obesity, atherogenic dyslipidemia, and smoking habits. All complications were inversely associated with age at diabetes diagnosis after adjustment for age and sex, but not after further adjustment for diabetes duration. Percentages of death, Kaplan–Meier estimates, and unadjusted hazard ratios and mortality rates increased from the lowest to the highest quartile. In contrast, when adjusting for age and sex, participants falling in the lowest quartile, showed the highest mortality risk [hazard ratio 1.321 (95% confidence interval 1.196–1.460), P < 0.0001]. However, differences among quartiles disappeared after adjustment for diabetes duration, complications/comorbidities, or other cardiovascular risk factors.ConclusionsType 2 diabetes onset in young adulthood is associated with increased mortality that is mainly driven by longer diabetes duration favoring the development of complications.Trial registration: ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July, 2008.

Profile of Nagasaki Islands Study (NaIS): A Population-based Prospective Cohort Study on Multi-disease.

In an aging society, it is important to visualize the conditions of people living with diseases or disabilities, such as frailty and sarcopenia, and determine the environmental and genetic factors underlying such conditions. Atherosclerosis and arterial stiffness are key conditions between these factors and noncommunicable diseases. In 2014, we launched a population-based prospective open-cohort study, the Nagasaki Islands Study (NaIS), which was conducted in Goto City, located in the remote islands of Nagasaki Prefecture, Japan, mostly involving middle-aged and older residents. We conducted our own health checkups along with the annual standardized checkups organized by the municipality; recruited study participants; and started to follow them for vital status (death), migration, and occurrence of diseases, such as myocardial infarction, stroke, fracture, and human T-cell leukemia virus type 1 (HTLV-1)-associated uveitis. Our checkups were conducted as baseline surveys in different areas of Goto City during the fiscal years 2014-2016, secondary surveys during 2017-2019, and tertiary surveys since 2021, consisting of medical interviews, physical examinations, blood and urine tests, body composition measurements, osteoporosis screening, arterial stiffness measurements, carotid ultrasonography, and dental examination. A total of 4,957 residents participated in either the baseline or secondary surveys and were followed; 3,594 and 3,364 residents (aged 27-96 and 28-98 years) participated in the baseline and secondary surveys, respectively. In conclusion, the NaIS has been undertaken to reveal the influence of aging and risk factors of noncommunicable diseases and disabilities, with an aim to contribute towards better healthcare in the future.