Known Cause Of Death Research Articles

A Pilot Study of Age Estimation and Cause of Death: Insights into Skeletal Aging

Background/Objectives: Forensic anthropological age estimations are often limited by a lack of diversity in reference samples, imprecision, and, for certain populations, inaccuracy. This study aims to explore the relationship between health, as indicated by cause of death, and skeletal age estimation, with the goal of determining whether including health information can improve accuracy and precision in age estimation. Methods: Skeletal age data were collected from the Maxwell Museum Documented Skeletal Collection using the Lovejoy et al. method for the auricular surface and the Suchey-Brooks method for the pubic symphysis. All individuals had a known cause of death, which was categorized into two broad groups: disease-related and trauma-related. Cause of death category served as a proxy for health status. Results: Individuals who died from disease-related causes often fell within the upper end of the age ranges for both the auricular surface and pubic symphysis methods. In contrast, those who died from trauma-related causes tended to fall within the lower end of these age ranges. Conclusions: These results indicate that incorporating factors such as health into existing forensic age estimation methods could enhance the precision of age estimates, particularly by addressing the influence of environmental and lifestyle factors on skeletal aging.

Epidemiology and classification for canine and feline mammary gland tumors: a histopathological survey of 437 mammary gland tumor biopsies performed in a secondary care hospital in Chiang Mai, Thailand from 2012 to 2019.

Metastatic disease resulting from mammary gland tumors (MGTs) is a known cause of death among dogs and cats. Keys to successful prevention and management strategies involve the accurate recording of diagnostic data. This retrospective study reviewed the epidemiology and classification of canine mammary gland tumors (CMTs) and feline mammary gland tumors (FMTs), as well as the factors including sex, age, and breed related to the occurrence of these tumors. Accordingly, 1,736 tumor biopsy cases were reported from 2012 to 2019 at Chiang Mai University Small Animal Hospital, Thailand, with 1,639 canine tumor biopsy cases and 97 feline tumor biopsy cases. The proportion of CMTs was reported at 24.5% (401/1,639) for all canine tumor biopsy cases. Benign and malignant tumors were reported at 14.5% (58/401) and 85.5% (343/401) for all CMT cases, respectively. The mean age of dogs affected by benign CMTs was 9.0±3.0 years, which was significantly lower than for malignant CMTs at 9.9±2.8 years (P=0.0239). According to histopathological classification, benign mixed tumors and simple carcinoma types were highest among benign and malignant CMT cases, respectively. Moreover, female dogs were at significantly higher risk of developing mammary gland tumors (OR = 45.8, 95% CI [3.9-86.0], P<0.0001) than male dogs, as well as older dogs (>8 years) (OR = 1.7, 95% CI [1.2-2.2], P=0.0001) compared to young ones (≤8 years). The proportion of FMTs was 37.1% (36/97) for all feline tumor biopsy cases. Benign and malignant tumors for all FMTs were reported at 16.7% (6/36) and 83.3% (30/36), respectively. According to histopathological classifications, adenoma and simple carcinoma were present in the highest proportion among benign and malignant FMTs, respectively. Female cats were at a significantly higher risk of developing mammary gland tumors than male cats (OR=25.7, 95% CI [3.9-272.8], P<0.0001). There was a high proportion of MGT cases compared with other tumor cases reported in a secondary care hospital in Chiang Mai, Thailand from 2012 to 2019, and malignant tumor biopsies have been more frequently observed than benign tumor biopsies in both CMT and FMT cases. The resulting data originating from this study can be an aid for veterinary oncologists in better educating clients and planning treatment and prevention strategies and it can be used as a basis for further experimental studies in the oncology section.

Diode laser ablation of progressive pigmented iris lesions in 317 cats (356 eyes) appears overall safe and effective in decreasing progression of iris pigmentation.

To describe a novel scoring system of feline pigmented iris lesions prior to utilization of diode laser ablation of progressive pigmented iris lesions and to retrospectively evaluate short- and long-term patient outcomes following transcorneal diode laser ablation. 317 client-owned cats (356 eyes) were included. Records of cats undergoing diode laser ablation from January 2000 to December 2018 were retrospectively reviewed. A novel clinical grading system to describe severity of feline iris hyperpigmentation was developed. Recorded parameters included signalment, operated-upon eye, presurgical iris pigmentation score, intraocular pressure, visual status, postoperative complications, repeat laser surgery, patient status at last follow-up, time to death, and presumptive or known cause of death. Complications included corneal ulceration (25/356 [7%]), glaucoma (18/356 [5%]), uveitis (4/356 [1.1%]), and corneal edema (3/356 [0.8%]). Enucleation was performed in 12 eyes due to blindness and secondary glaucoma. Repeat laser due to continued progression of pigment was performed in 18.5% of eyes. Two study patients were euthanized due to presumptive metastatic disease. Of the 250 cats for whom confirmation was available via phone call or medical records, 240 (96%) were alive at 1 year. Diode laser ablation appears safe overall and may be effective in decreasing progression of feline iris pigmentation. Complication risks appear minimal.

Illegal shooting is now a leading cause of death of birds along power lines in the western USA

Human actions, both legal and illegal, affect wildlife in many ways. Inaccurate diagnosis of cause of death undermines law enforcement, management, threat assessment, and mitigation. We found 410 dead birds collected along 196km of power lines in four western USA states during 2019-2022. We necropsied these carcasses to test conventional wisdom suggesting that electrocution is the leading cause of death of birds at electrical infrastructure. Of 175 birds with a known cause of death, 66% died from gunshot. Both raptors and corvids were more likely to die from gunshot than from other causes, along both transmission and distribution lines. Past mitigation to reduce avian deaths along power lines has focused almost exclusively on reducing electrocutions or collisions. Our work suggests that, although electrocution and collision remain important, addressing illegal shooting now may have greater relevance for avian conservation.

Serum lipoprotein(a), and plasminogen activator inhibitor-1 in uncomplicated type 2 diabetes mellitus: a case-control study.

A case-control study designed for the estimation of Lp(a) and PAI-1 in serum after collecting blood samples from type 2 diabetic patients at the Layla Qasim Diabetic Center in Erbil, Iraq. The study included 90 participants, of whom 30 were healthy controls (15 males and 15 females). The remaining 60 cases were patients with type 2 diabetes with a duration of up to 6 years (30 males and 30 females). Serum Lp(a) and PAI-1 levels were significantly lower in type 2 diabetic patients than in controls (P<0.01), this is an opposite result that usually happen in uncontrolled and complicated diabetic patients. The results were clearly stated a beneficial effect of Metformin on the levels of Lp(a) and PAI-1 in type 2 diabetes, so lowering their concentrations would help prevention of CAD, a known cause of death in diabetic patients.

Understanding the Impact of COVID-19 on Angioplasty Service and Outcome of Patients Treated for Chronic Limb-Threatening Ischaemia: A Single-Centre Retrospective Cohort Study.

We evaluated the impact of COVID-19 restriction on the angioplasty service and outcome of chronic limb-threatening ischaemia (CLTI) patients undergoing lower-limb angioplasty in a UK secondary care setting. Consecutive patients were analysed retrospectively. Pre-COVID-19 (08/2018-02/2020), 106 CLTI patients (91% Fontaine 4; 60% diabetes mellitus) and during COVID-19 (03/2020-07/2021) 94 patients were treated (86% Fontaine 4; 66% diabetes mellitus). While the average monthly number of patients treated did not change, the proportion of day cases significantly increased (53% to 80%), and hospitalised patients decreased. Patients treated in ≤14/5 days after referral significantly increased to 64/63%. Kaplan-Meier survival analysis (30-day/1-year) showed that neither wound healing nor mortality were significantly changed during COVID-19. In day cases, 1-year but not 30-day major amputations significantly increased, and clinically driven target-lesion revascularisation decreased during COVID-19. One-year mortality was significantly worse in hospitalised compared to day cases (14% vs. 43%) at similar wound healing rates (83% vs. 84%). The most frequent known cause of death was infectious disease (64%), while cardiovascular (21%) was less frequent. Despite COVID-19 restrictions, a safe and effective angioplasty service was maintained while shortening waiting times. Very high mortality rates in hospitalised patients may indicate that CLTI patients need to be referred and treated more aggressively earlier.

Mortality during or shortly after Curative-Intent Radio-(Chemo-)Therapy over the last decade at a large comprehensive cancer center.

Definitive surgical, oncological and radio-oncological treatment may result in significant morbidity and acute mortality. Mortality during or shortly after treatment in patients undergoing curative radio-(chemo)-therapy has not been studied systematically. We reviewed all curative radio-(chemo-)therapies at a large comprehensive cancer center over the last decade. The institutional record was screened for patients who received curative-intent radio-(chemo-)therapy and deceased during or within 30days after radiotherapy. Curative therapy was defined as prescribed dosage of EQD2≥50Gy for radiotherapy alone and EQD2≥40Gy for radiochemotherapies. Data on demographics, disease and treatment were assembled and assessed. Of 15,255 radiotherapy courses delivered at our center, 8,515 (56%) were performed with curative-intent. During or within 30days after radio-(chemo-)therapy, 78 patients died (0.9% of all curative-intent courses). Median age of the deceased patients was 70 (IQR, 62-78) years, and 36% (28/78) were female. Median pre-therapeutic ECOG-PS was 1 (IQR, 0-2) and Charlson-Comorbidity-Index was 3+ (IQR, 2-3+). The most common primary malignancies were head and neck cancer (33/78; 42%) and central nervous system tumors (13/78; 17%). Peritherapeutic mortality varied by primary tumor, with the highest prevalence observed in head and neck and gastrointestinal cancer patients with 2.9% (33/1,144) and 2.4% (8/332), respectively. Among patients with known cause of death (34/78; 44%), tumor progression (12/34; 35%) and pulmonary complications/causes (11/34; 35%) were most common. On multivariable regression analysis, a worse ECOG-PS was associated with a relatively earlier peri-radiotherapeutic death (p=0.014). Mortality during or within 30days of curative-intent radio-(chemo-)therapy was low, yet highest for head and neck (2.9%) and gastrointestinal tumor (2.4%) patients. Reasons for these findings include rapid tumor progression in some cancers, good patient selection, with ECOG-PS being most useful and predictive for avoiding early mortality. Future research should help refine predictors for peri-RT mortality.

#5078 “FISTULA FIRST, CATHETER LAST” IN THE VERY ELDERLY: ONE SIZE FITS ALL?

Abstract Background and Aims The demographic characteristics of incident and prevalent hemodialysis (HD) patients have been undergoing significant changes over the last decades, in what has been called an “epidemic of aging in renal replacement therapy” [1]. The higher proportion of very elderly patients has brought significant challenges to the nephrologists, namely regarding the choice and timing of vascular access (VA) creation. Despite the arteriovenous fistula (AVF) undeniable status has the preferred VA, the applicability of the “Fistula First” initiative in very elderly patients has been questioned. Method This single-center observational retrospective cohort study took place at the Coimbra Hospital and University Centre, a Portuguese tertiary referral hospital. Patients were selected from the Nephrology department's database of HD referrals. Inclusion criteria were HD referral between January 2017 and December 2021 and age equal or over 80-years old at time of referral. We collected data regarding demographic characteristics, comorbid conditions, first VA, pre-HD nephrology care and functional status at referral, as well as the time and cause of death during the follow-up period. Functional status was assessed through the Katz index of independence in activities of daily living and the comorbid conditions were assessed through the Charlson comorbidity index. Primary outcome was mortality, and follow-up ended on the 31st of May 2022. Variables associated independently with mortality were included in Cox proportional-hazards regression models. Results Our study sample included 288 patients, predominantly male (63.9%), with a median age of 83 and a diabetes prevalence of 42.8%. The VA at first dialysis was a central venous catheter (CVC) in 77.8% and 68.1% had an unplanned HD start. Eighty-four percent had at least 3 months of pre-HD nephrology care. The mean Charlson Index at HD referral was 9.1 and 50.6% presented a Katz index under 5. The mortality incidence rate during follow-up was 32.8/100 patient-year, with 90-days, one-year, and two-year survival rates of 88.2%, 69.1% and 51.4%, respectively. The main known causes of death were infections not related with the VA (29%) and cardiovascular disease (14%). Starting HD through a CVC was associated with worse survival in univariate analysis (Log-rank 15.4, p&amp;lt;0.001). Other mortality-related variables in survival analysis were age at HD referral [hazard ratio (HR) 1.082, p&amp;lt;0.001], absence of pre-HD nephrology care (Log-rank 14.6, p&amp;lt;0.001), urgent-start HD (Log-rank 24.3, p&amp;lt;0.001), Katz index (HR 0.67, p&amp;lt;0.001) and Charlson index (HR 1.28, p&amp;lt;0.001). In a Cox Proportional Hazards model, when adjusting for the other mortality predictors, CVC use at first HD and unplanned HD start did not present a statistically significant association with mortality (HR 1.587, p = 0.074; HR 1.508, p = 0.098, respectively). Conclusion In our study sample, most patients started HD through a CVC, despite the majority having at least 3 months of pre-HD nephrology care. When adjusting for other covariates in a multivariate model, the first VA did not present a strong association with survival outcomes. The appropriate VA in the very elderly patient is an ongoing debate, and doubts remain regarding the applicability of the “Fistula First, Catheter Last” policy in octogenarian and nonagenarian patients. Our results are in line with recent reports which suggest that initial CVC use with later placement of an AVF, shortly after HD initiation, does not confer worse prognosis than initial AVF use in very elderly patients [2]. One of the limitations of our study was not having collected data regarding timings of AVF construction and use, which might have been informative regarding the impact of catheter-dependence time in survival.

Real world evidence on long-term survival of patients with endometrial cancer in Germany: Analysis of population-based cancer registry data on 49808 women.

e17623 Background: Endometrial cancer (EC) is the most common gynecological cancer worldwide. The understanding of clinicopathological characteristics has changed within the last years. Limited data are available regarding the long-term survival of EC patients. Methods: Clinical data and survival data for patients with EC diagnosed in Germany between 2010 and 2020 were gathered from the German national center for population-based cancer registry. Differentiated by histological subtype, 5- and 7-year survival rates were calculated. Results: 49,808 patients with newly diagnosed EC between 2010 and 2020 were included in the analysis. Median age at diagnosis was 68.1 years (IQR 59.0;76.4). 5-year and 7-year overall survival was 67.5% and 56.7%, respectively, and decreased with increasing FIGO-stage: 83.7% and 72.6% for FIGO IA, 71.0% and 56.3% for FIGO IB, 59.8% and 47.3% for FIGO II, 48.2% and 38.7% for FIGO IIIA , 32.5% and 20.7% for FIGO IIIB, 40.0% and 30.6% for FIGO IIIC, 13.3% and 8.2% for FIGO IVA, 16.4% and 13.9% for FIGO IVB, respectively. Regarding histological subtype, endometrioid carcinoma showed the best 5-year and 7-year overall survival rates with 72.5% and 61.3%, respectively, followed by clear cell carcinoma with 41.2% and 34.0%, serous carcinoma with 35.5% and 24.8%, and lastly carcinosarcoma with 28.5% and 23.0%. Of 3,765 patients with known cause of death, 53.8% were due to endometrial cancer. 19.0% died of cardiovascular disease and 18.8% of other malignancies. Conclusions: Our data represents deeper insight in the characterization of long-term survival patients of this tumor entity.

De Novo Malignancy After Adult-to-Adult Living Donor Liver Transplantation: A Single-Center Long-Term Experience

The incidence of de novo malignancy (DNM) after liver transplantation (LT) is reported to be 3.1% to 14.4%. It is a known cause of death in long-term recipients. This study aimed to clarify the clinical features and risk factors of DNM. Recipients who underwent adult-to-adult living-donor LT (LDLT) and survived for >6 months were investigated. The medical records were retrospectively reviewed. This study was approved by the institutional review board. In total, 180 patients were included. The indications for LDLT were hepatocellular disease (n=62), metabolic liver disease (n=50), cholestatic disease (n=46), acute liver failure (n=12), and others (n=10). The median age at LDLT was 48 (18-71) years, and the follow-up period was 15 (0-29) years. De novo malignancy was diagnosed in 24 recipients (28 sites), including the digestive tract (n=9), genitourinary (n=5), gynecologic (n=5), lung (n=4), hematological (n=3), and others (n=2). The median duration from LDLT to DNM was 7 (0-19) years. Four patients were lost to follow-up due to advanced-stage cancer. R0 (curative treatment) for non-hematological DNM was achieved in 19 lesions (95%). The 10- and 20-year DNM incidence rates were 11% and 20%, respectively. The 20-year survival rates of DNM (59.6%) and non-DNM (59.9%) patients were not significantly different. De novo malignancy was significantly higher in patients with primary sclerosing cholangitis than in others (P < .05). Even in DNM recipients, early detection of malignancy and R0 treatment promises long-term outcomes comparable to those of non-DNM recipients.

Causes of death of patients with non-valvular atrial fibrillation in Asians.

The aim of this study was to determine the causes of death among Asian non-valvular atrial fibrillation (AF) patients who were registered in a nationwide AF registry, and to investigate the differences in the causes of death in AF patients compared between those who were taking and not taking oral anticoagulant (OAC). The COhort of antithrombotic use and Optimal INR Level in patients with non-valvular Atrial Fibrillation in Thailand (COOL-AF) study enrolled non-valvular AF patients from 27 centers in Thailand during 2014-2017 to create the COOL-AF Thailand registry. Cause of death was classified as cardiovascular (CV) death, non-CV death, or undetermined cause of death. All events were evaluated and verified by an independent adjudication committee. There was a total of 3,405 patients (mean age: 67.8 years, 41.8% female), and the mean follow-up duration was 31.8±8.7 months. Three hundred and eighty patients (11.2%) died during follow-up. CV death, non-CV death, and undetermined cause accounted for 121 (31.8%), 189 (49.7%), and 70 (18.4%) patients, respectively. Of those with a known cause of death, heart failure (10%), intracranial hemorrhage (ICH; 10%), sudden cardiac death (6.8%), and ischemic stroke (5.8%) were the most often observed causes of death. Concerning non-CV death, infection/sepsis (27.7%), cancer (5.5%), respiratory (5.2%), and major bleeding (4.5%) were the most prevalent causes of death. The use and type of OAC were found to be major determinants of ICH and major bleeding incidence. Death due to ischemic stroke was responsible for only 4.7% of all deaths in Asian AF patients. Non-CV death, such as infection/sepsis or malignancy, was more far more prevalent than CV death in Asian AF patients. An improved integrated care approach is needed to reduce the prevalence of non-CV death in Asian AF patients.

Comparing Survival Outcomes of Autologous and Allogeneic Hematopoietic Cell Transplantation in Patients with Relapsed/Refractory Nodal Peripheral T-Cell Lymphoma

Background Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of non-Hodgkin lymphoma and carries a poor prognosis. The four most common types are PTCL-NOS, angioimmunoblastic T cell lymphoma (AITL), and anaplastic large T cell lymphoma (ALCL) with or without ALK and together are grouped as nodal PTCL. In relapsed/refractory disease (r/r), the survival outcomes are poor and estimated to be approximately 13.7 months (Mak, Hamm et al. 2013). Hematopoietic cell transplantation (HCT) has been used to consolidate response and improve outcomes. However, the role of autologous HCT (auto HCT) and allogeneic HCT (allo HCT) remains controversial. Here we aim to compare the survival outcomes of auto HCT and allo HSCT in r/r PTCL. Methods We retrospectively reviewed clinical data on 53 patients at Moffitt Cancer Center who developed r/r nodal PTCL and received HCT from 12/2007 to 12/2021. Patients who had auto HCT during the first remission were excluded. Physician discretion, donor availability, among others, were the factors that influenced transplant type allocation. Clinical data were abstracted in accordance with institutional review board-approved protocol. Patients were divided into two subgroups: cohort A) auto HCT and cohort B) allo HCT. The baseline clinical data of two cohorts were summarized using descriptive statistics and compared using Kruskal-Wallis tests for continuous variables and Chi-squared tests for categorical variables. Overall survival (OS) was calculated from the date of HCT to death or censored to the last follow-up. Median OS was calculated using the Kaplan Meier method and compared two cohorts with a log-rank test. Univariate and multivariate Cox proportional hazard (PH) using the backward elimination method were used to evaluate the association between OS and types of transplants. Results Out of 53 patients, 30 (57%) patients received auto HCT (cohort A), while 23 (43%) patients received allo HCT (cohort B). All patients achieved either partial response (PR) or complete response (CR) prior to transplant. The patients in allo cohort B were younger at the time of transplant (median age: 60 years vs. 50 years for cohort A and B, respectively, p=0.06), had a higher proportion of refractory disease (27% vs. 65% for cohort A and B, respectively, p=0.005), and had a higher proportion of PTCL-NOS (33% vs. 65% for cohort A and B, respectively, p=0.006) (table 1). ECOG status at transplant and IPI at the time of diagnosis were not significantly different between the two groups. Median OS was 40 months in cohort A compared to 57 months in cohort B, however, no statistical difference was present (p=0.49) (Figure 1). In the univariate analysis, HR for allo HCT was 0.77 (p=0.5). When adjusted for ECOG status at transplant, histology subtypes, IPI score at diagnosis in the multivariate analysis, allo HCT was associated with prolonged OS with an HR of 0.41 (p=0.045). At the study cutoff with a median follow-up of 57 months in cohort A, 18 patients died. Out of 12 patients with a known cause of death in cohort A, 7 patients (38%) died from relapse disease. With a median follow-up of 73 months in cohort B, 10 patients died. Out of 10 patients with a known cause of death, 2 patients (20%) died from the relapsed disease. Conclusion Our data showed that allo HCT in r/r PTCL is associated with improved survival compared to auto HCT in multivariate analysis. Our result supports the use of allo HCT, especially in the younger/fit population and in refractory disease. Larger studies are needed to validate our results. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Nanomedicine for Treating Muscle Dystrophies: Opportunities, Challenges, and Future Perspectives.

Muscular dystrophies are a group of genetic muscular diseases characterized by impaired muscle regeneration, which leads to pathological inflammation that drives muscle wasting and eventually results in weakness, functional dependency, and premature death. The most known causes of death include respiratory muscle failure due to diaphragm muscle decay. There is no definitive treatment for muscular dystrophies, and conventional therapies aim to ameliorate muscle wasting by promoting physiological muscle regeneration and growth. However, their effects on muscle function remain limited, illustrating the requirement for major advancements in novel approaches to treatments, such as nanomedicine. Nanomedicine is a rapidly evolving field that seeks to optimize drug delivery to target tissues by merging pharmaceutical and biomedical sciences. However, the therapeutic potential of nanomedicine in muscular dystrophies is poorly understood. This review highlights recent work in the application of nanomedicine in treating muscular dystrophies. First, we discuss the history and applications of nanomedicine from a broader perspective. Second, we address the use of nanoparticles for drug delivery, gene regulation, and editing to target Duchenne muscular dystrophy and myotonic dystrophy. Next, we highlight the potential hindrances and limitations of using nanomedicine in the context of cell culture and animal models. Finally, the future perspectives for using nanomedicine in clinics are summarized with relevance to muscular dystrophies.

Sudden cardiac death in heart failure. A 20 years perspective from a Mediterranean cohort

Abstract Background Although sudden cardiac death (SCD) has progressively decreased in the last decade, it remains an important cause of death in patients with heart failure (HF). Differences based on clinical management and regional characteristics might be important. Purpose To assess the prevalence of SCD along 20 years of study in HF outpatients of different aetiologies managed in a multidisciplinary HF Clinic, and compare this prevalence with the expected proportional occurrence according to the acknowledged Seattle Proportional Risk Model (SPRM) score. Methods In a prospective observational registry of real-life HF outpatients, modes of death were classified as SCD (any unexpected death, witnessed or not, of a previously stable patient with no evidence of worsening HF or any other known cause of death) and non-SCD (progression of HF, acute myocardial infarction, stroke, procedural, other cardiovascular causes and non-cardiovascular). Results From August 2001 to May 2021, 2772 outpatients with known cause of death and with SPRM score available were included. Out of them, 1351 (48.7%) died during a median follow-up of 3.8 years [IQR 1.6–7.8], up to 20 years. Observed prevalence of SCD in the 1351 dead patients was 13.6% while predicted SPRM prevalence was 39.6%. Annual SPRM predicted SCD mortality rate was 3.0% while observed SCD annual mortality rate was 1.3%. Figure 1 depicts cumulative incidence of causes of death through the study period. A lower prevalence of SCD was observed in every quintile of SPRM risk (Figure 2). This lower prevalence of SCD was observed independently of left ventricular ejection fraction group, ischemic or non-ischaemic aetiology and implantable cardiac defibrillator (ICD). Although the baseline SPRM predicted risk of SCD showed a significant decreasing trend (p=0.005) along the periods of admission at the Unit, the lower observed prevalence of SCD was seen in all periods of admission. Conclusions The prevalence of SCD through a perspective of 20 years in a Mediterranean HF outpatient cohort managed in a multidisciplinary HF Clinic was significantly lower than that expected according to the SPRM independently of degree of predicted risk, ischaemic aetiology, period of admission and implanted ICD. Regional lifestyle and dietary habits may have an impact on the lower rate of SCD in this Mediterranean cohort, and deserve further in-depth analyses. Funding Acknowledgement Type of funding sources: None.

A survey of Eutylone Prevalence in New Zealand during 2020 and 2021

This study provides an insight into the prevalence of eutylone in New Zealand by analysis of the post-mortem forensic toxicology cases over the period 2020 and 2021, as well as analysis of suspected drug items collected from three music festivals between December 2020 and February 2021. Eutylone, also known as bk-EBDB or n-ethylbutylone, is a synthetic cathinone that has no known therapeutic use. In New Zealand it is sold recreationally as an alternative to methylendioxymethamphetamine (MDMA) and has increasingly been found as an adulterant or substitution substance in MDMA samples. Eutylone is known to cause harm and has been associated with fatalities [World Health Organization. “WHO Expert Committee on Drug Dependence: forty-fourth report.” (2022)]. In many cases, users are unaware that the eutylone is present believing they are taking MDMA. ESR undertakes post-mortem forensic toxicology casework for the whole of New Zealand. We investigated the post-mortem cases received during 2020 and 2021 for eutylone and investigated trends. In addition to the post-mortem forensic toxicology cases, ESR analysed 656 drug samples from three music festivals held between December 2020 and February 2021 for the presence of drugs including eutylone. The post-mortem blood samples were analysed using liquid chromatography with time of flight mass spectrometry (LC-TOFMS) for eutylone. Eutylone was detected in three cases during 2020 and in twelve (12) cases during 2021. Of the 12 cases from 2021, ten decedents were male, nine cases had a known cause of death (e.g. hanging), two cases were at or just after a music festival and two cases appeared to be drug overdoses where multiple drugs were involved. Eutylone was the only drug detected in three of the cases (all with a known cause of death). When other drugs were involved the most common were methamphetamine ( n = 4), MDMA ( n = 3), alcohol ( n = 3) and cannabis ( n = 3). For the 656 samples analysed from the three music festivals MDMA and eutylone were detected in 33% and 32% of the samples, respectively. This can be contrasted with a previous survey from December 2018 to March 2019 that found MDMA in 64% of samples and eutylone detected in less than 1% of the samples. If a mixture was present in a sample, it was common for it to contain both eutylone and MDMA. There was a significant increase in eutylone detections both in blood samples from post-mortem forensic toxicology casework and in seized drug samples over the time period studied, with associated increases in the harm, including deaths, associated with the drug use. It has been postulated that this trend was influenced by factors such as the limited supply of MDMA in New Zealand due to law enforcement activity including a large MDMA seizure prior to the survey period for the music festivals, COVID-19 restrictions and the use of eutylone as an adulterant or replacement drug.

Frequency and co‐occurrence of porous skeletal lesions in identified non‐adults from Portugal (19th to 20th centuries) and its association with respiratory infections as cause of death

AbstractPorous skeletal lesions (PSL) have been reported in scientific literature since the 19th century, yet their etiology(ies) remains a complex issue under debate. The aim of this study is twofold: evaluate the frequency, co‐occurrence, and association of PSL with biological sex and age at death and examine possible relationships between the presence/absence of PSL with the known cause of death (COD). Fifty‐six non‐adult skeletons from the Coimbra Identified Skeletal Collection (19th to 20th centuries) were evaluated. Lesion presence/absence was recorded macroscopically without previous knowledge of the biographic data. Forty‐nine individuals (87.5%) presented at least one type of PSL, and cribra femoralis was the most frequent (n = 39), followed by orbitalia (n = 26), humeralis (n = 15), and cranii (n = 6). Porous skeletal lesions affected males and females equally, and younger individuals presented a significantly higher frequency of cribra femoralis. Even without statistical significance, the co‐occurrence of cribra orbitalia, humeralis, and femoralis was common, as described in the “cribrous syndrome” where it is advocated a shared etiology for these lesions, based on macroscopic, microscopic, and radiological features. Individuals with a COD as respiratory infection, particularly pulmonary tuberculosis, exhibited a higher risk of expressing cribra orbitalia. The results of this investigation suggest an influence of age and infectious diseases in the expression of PSL, impacting the bioarchaeological interpretations. There is a need for further research in clinical, autopsy, and identified skeletal collection samples to further understand co‐occurrence, comorbidity, and possible frailty related to PSL.

Impact of Seizure Recurrence on 1-Year Functional Outcome and Mortality in Patients With Poststroke Epilepsy.

The functional outcome and mortality of patients with poststroke epilepsy (PSE) have not been assessed in a prospective study. Previous reports have suggested that patients with PSE may suffer from prolonged functional deterioration after a seizure. In this study, we prospectively investigated the functional outcome and mortality of patients with PSE and analyzed the effect of seizure recurrence on the outcomes. This is part of the Prognosis of Post-Stroke Epilepsy study, a multicenter, prospective observational cohort study, where 392 patients with PSE (at least 1 unprovoked seizure more than 7 days after the onset of the last symptomatic stroke) were followed for at least 1 year at 8 hospitals in Japan. This study included only PSE patients with a first-ever seizure and assessed their functional decline and mortality at 1 year. Functional decline was defined as an increase in modified Rankin Scale (mRS) score at 1 year compared with baseline, excluding death. The associations between the seizure recurrence and the outcomes were analyzed statistically. A total of 211 patients (median age of 75 years; median mRS score of 3) were identified. At 1 year, 50 patients (23.7%) experienced seizure recurrence. Regarding outcomes, 25 patients (11.8%) demonstrated functional decline and 20 (9.5%) had died. Most patients died of pneumonia or cardiac disease (7 patients each), and no known causes of death were directly related to recurrent seizures. Seizure recurrence was significantly associated with functional decline (odds ratio [OR] 2.96, 95% CI 1.25-7.03, p = 0.01), even after adjusting for potential confounders (adjusted OR 3.26, 95% CI 1.27-8.36, p = 0.01), but not with mortality (OR 0.79, 95% CI 0.25-2.48, p = 0.68). Moreover, there was a significant trend where patients with more recurrent seizures were more likely to have functional decline (8.7%, 20.6%, and 28.6% in none, 1, and 2 or more recurrent seizures, respectively; p = 0.006). One-year functional outcome and mortality of patients with PSE were poor. Seizure recurrence was significantly associated with functional outcome, but not with mortality. Further studies are needed to ascertain whether early and adequate antiseizure treatment can prevent the functional deterioration of patients with PSE.

Developmental changes in cardiac expression of KCNQ1 and SCN5A spliceoforms: Implications for sudden unexpected infant death.

Sudden unexpected infant death (SUID) occurs unpredictably and remains unexplained after scene investigation and autopsy. Approximately 1 in 7 cases of SUID can be related to a cardiac cause, and developmental regulation of cardiac ion channel genes may contribute to SUID. The goal of this study was to investigate the developmental changes in the spliceoforms of SCN5A and KCNQ1, 2 genes implicated in SUID. Using reverse transcription quantitative real-time polymerase chain reaction, we quantified expression of SCN5A (adult and fetal) and KCNQ1 (KCNQ1a and b) spliceoforms in 153 human cardiac tissue samples from decedents that succumbed to SUID ("unexplained") and other known causes of death ("explained noncardiac"). There is a stepwise increase in the adult/fetal SCN5A spliceoform ratio from <2 months (4.55 ± 0.36; n = 51) through infancy and into adulthood (17.41 ± 3.33; n = 5). For KCNQ1, there is a decrease in the ratio of KCNQ1b to KCNQ1a between the <2-month (0.37 ± 0.02; n = 46) and the 2- to 4-month (0.28 ± 0.02; n = 52) age groups. When broken down by sex, race, or cause of death, there were no differences in SCN5A or KCNQ1 spliceoform expression, except for a higher ratio of KCNQ1b to KCNQ1a at 5-12 months of age for SUID females (0.40 ± 0.04; n = 9) than for males (0.25 ± 0.03; n = 6) and at <2 months of age for SUID white (0.42 ± 0.03; n = 19) than for black (0.33 ± 0.05; n = 9) infants. This study documents the developmental changes in SCN5A and KCNQ1 spliceoforms in humans. Our data suggest that spliceoform expression ratios change significantly throughout the first year of life.

Extranodal Presentation in Limited Stage DLBCL As a Prognostic Marker in Three Sequential SWOG Trials S0014, S0313 and S1001 (NCT00005089, NCT00070018, NCT01359592)

Extranodal Presentation in Limited Stage DLBCL As a Prognostic Marker in Three Sequential SWOG Trials S0014, S0313 and S1001 (NCT00005089, NCT00070018, NCT01359592)

The Impact of Oral Hypoglycemics and Statins on Outcomes in Myelodysplastic Syndromes

The Impact of Oral Hypoglycemics and Statins on Outcomes in Myelodysplastic Syndromes