Related Deaths Research Articles

Abstract LB121: Endothelial cells mediated paracrine signaling alters immune cell modulators on colorectal cancer cells

Abstract Background: Metastatic colorectal cancer (mCRC) is the second leading cause of cancer related deaths in the US. Various factors in the tumor microenvironment (TME) play significant roles in progression of CRC tumors and their response to various therapies. Previous studies from our laboratory and other groups have demonstrated that blood vessels and their constituent endothelial cells (ECs) exert strong effects on CRC cells by altering stemness, enhancing drug resistance, and increasing cell survival. Although ECs have also been shown to affect immune cell function or alter the tumor immune environment by direct or indirect mechanisms, their role in altering immune-modulating effectors on tumor cells, especially CRC cells, are poorly understood. Thus, elucidating the role of ECs in regulating immune-modulators in CRC cells and understanding the underlying mechanisms by which this occurs will provide important insights into the role of ECs on altering the immune-microenvironment of CRC tumors that likely affects tumor progression and, possibly, response to immunotherapies. Methods: A panel of CRC cells lines were exposed to conditioned media (CM) from CRC or multiple primary or immortalized liver parenchymal endothelial cells (LPECs), and alterations in some of the known immune-inhibitory ligands were measured by western blotting or flow cytometry. Molecular size-based fractionation of CRC-CM or LPEC-CM were performed and various sized fractions were utilized to detect fractions harboring inducers of immune-inhibitory ligands. Mass spectrometry was performed to identify possible factors in LPEC-CM. Western blotting of CRC cell lysates was performed to identify possible signaling changes following LPEC-CM treatment. Results: Our studies demonstrated that ECs were more efficient in inducing PD-L1 expression in CRC cells compared to other cell types present in the CRC tumor microenvironment. LPEC-CM induced PD-L1 expression in multiple CRC cells regardless of their genetic mutations or MSI-H/MSS status. Initial studies indicate that LPEC-CM can also enhance MHC-1 expression in CRC cells. Size-fractionation studies indicate that inducer/s of PD-L1 expression are present in a fraction >100kDa. Mass-spectrometry of this fraction has identified prospective candidates that can possibly induce PD-L1 on CRC cells. CRC cells treated with LPEC-CM led to enhanced levels of pSTAT3, a known PD-L1 transcription factor. Conclusions: Our studies, for the first time, demonstrate that ECs, through paracrine signaling, can educate CRC cells to overexpress immune-modulatory ligands. Further studies are being conducted to elucidate the molecular factors involved in these processes. These studies not only shed light on the complex role played by ECs in modulating the TME, but also warrants further investigations into the effects of these changes in CRC tumor progression and responses to therapies. Citation Format: FanFan, Lee M. Ellis, Rajat Bhattacharya. Endothelial cells mediated paracrine signaling alters immune cell modulators on colorectal cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB121.

Preoperative opioid use is associated with worse two-year patient-reported outcomes after hand surgery: A retrospective cohort study

IntroductionOpioid overprescribing has caused a substantial increase in opioid related deaths and billions of dollars in additional healthcare costs. Orthopaedic surgeons commonly prescribe opioids in the perioperative period; however, research has shown preoperative opioid use may be associated with worse postoperative outcomes. Despite this body of evidence, there are few studies investigating the association between preoperative opioid use and two-year outcomes after hand surgery. Materials and methodsThis study evaluated two-year postoperative patient-reported outcomes in patients who used opioids prior to hand surgery, and those who did not. Patients completed pre and postoperative questionnaires including Patient-Reported Outcomes Measurement Information System (PROMIS) domains, the Brief Michigan Hand Questionnaire (BMHQ), and other questionnaires related to pain, function, and satisfaction. 342 patients undergoing upper-extremity surgery were enrolled into a prospective orthopaedic surgery outcome registry, and 69.9% completed the follow-up surveys. Preoperative opioid use and its association to patient outcome scores was analyzed through bivariate analysis. Significant associations were further tested by multivariable analysis to determine independent predictors. ResultsPreoperative opioid use was associated with worse two-year PROMIS Fatigue (p ​< ​.01), PROMIS Anxiety (p ​< ​.01), PROMIS Depression (p ​< ​.01), SSQ-8 (p ​= ​.01), BMHQ (p ​= ​.01), NPS Hand (p ​< ​.01) and MODEMS met expectations (p ​= ​.03). No significant differences were observed in patient-reported outcome change scores. Multivariable analysis demonstrated that preoperative opioid use was predictive of worse two-year PROMIS Fatigue (p ​< ​.01), PROMIS Anxiety (p ​< ​.01), PROMIS Depression (p ​= ​.02), BMHQ (p ​= ​.01), SSQ-8 (p ​< ​.01), NPS Hand (p ​= ​.02) and MODEMS met expectations (p ​< ​.01). ConclusionPreoperative opioid use was associated with worse patient-reported outcomes two years after elective hand surgery. There was no significant difference in the improvement from baseline between the two groups. Clinically significant differences were observed in follow-up PROMIS Anxiety, BMHQ and NPS – Hand scores. Clinically significant change scores were noted in both groups for PROMIS PF, PROMIS PI, PROMIS SS, BMHQ, and NPS – Hand.

A meta-path, attention-based deep learning method to support hepatitis carcinoma predictions for improved cirrhosis patient management

Hepatitis carcinoma (HCC) accounts for the majority of liver cancer–related deaths globally. Cirrhosis often precedes HCC clinically in a strong, temporal relationship. Therefore, identifying cirrhosis patients at higher risk of HCC is crucial to physicians' clinical decision-making and patient management. Effective estimates of at-risk patients can facilitate timely therapeutic interventions and thereby enhance patient outcomes and well-being. We develop a novel, meta-path, attention-based deep learning method to identify at-risk cirrhosis patients. The proposed method integrates complex patient–medication interactions, essential patient–patient and medication–medication links, and the combined effects of medication and comorbidity to support downstream predictions. An empirical test of the proposed method's predictive utilities, relative to nine existing methods, uses a large sample of real-world cirrhosis patient data. The comparative results indicate that the proposed method can identify at-risk patients more effectively than all the benchmarks. The current research has important implications for clinical decision support and patient management, and it can facilitate patient self-management and treatment compliance too.

Socio-Demographic Factors Influencing Malaria Vaccine Acceptance for Under-Five Children in a Malaria-Endemic Region: A Community-Based Study in the Democratic Republic of Congo.

Two novel vaccines against malaria are proposed as a complementary control tool to prevent and reduce Plasmodium falciparum related disease and death in under-five children from moderate to high malaria transmission regions. The Democratic Republic of Congo (DRC) has committed to eradicate malaria by 2030, and significant efforts have been deployed to strengthen control and elimination measures. We aimed to understand factors influencing the malaria vaccine acceptability among the general population in eastern DRC. We conducted a survey among adult Congolese in Bukavu in March 2022. The questionnaire was adapted from the Behavioral and Social Drivers of vaccine uptake (BeSD) framework and was administered online and physically. Multivariate logistic regressions were built, and estimates were represented as adjusted odds ratios (aOR) and corresponding 95% confidence intervals (95%CI). Out of 1612 adults (median age: 39 years, 46.15% female) surveyed, only 7.26% were aware of the malaria vaccine. However, 46.53% expressed willingness to vaccinate themselves, and 52.60% were open to vaccinating their under-five children. Adjusting for confounding factors, non-student/non-healthcare worker professions (aOR = 0.58, 95%CI [0.42-0.78]) and middle-income status (aOR = 1.87, 95%CI [1.25-2.80]) were significantly associated with self-vaccination acceptance. Age played a role in under-five child vaccination acceptability, with 25 to over 64 years showing increased acceptability compared to the 18-24 age group. Additionally, non-student/non-healthcare worker professions (aOR = 1.88, 95%CI [1.37-2.59]), medium education levels (aOR = 2.64, 95%CI [1.29-5.79]), and residing in semi-rural areas (aOR = 1.63, 95%CI [1.27-2.10]) were predictors of under-five child vaccination acceptance. The acceptability of the malaria vaccine for self and for under-five children was suboptimal for effective malaria control in this community in the DRC. Our study constitutes a call for the Expanded Program on Immunization to closely work with various stakeholders to strengthen risk communication for community engagement prior to and during the introduction of this novel and lifesaving tool, malaria vaccination.

Health related quality of life and its predictive factors on cervical cancer patients in two teaching hospitals, Addis Ababa, Ethiopia

BackgroundCervical cancer is the second most prevalent and the leading cause of cancer related deaths among Ethiopian women; and about three fourth are diagnosed at advanced stages. Cervical cancer can affect the health-related quality of life (HRQOL) in multiple ways. The main aim of this study was to describe the HRQOL of cervical cancer patients and the predictive factors using validated tools.MethodsInstitution based cross-sectional study was conducted among 264 cervical cancer patients using the validated Amharic version of European Organization for Research and Treatment of Cancer (EORTC) modules; QLQ-C30 and QLQ CX24. Descriptive statistics were used to summarize the raw data. One way ANOVA was used to determine the significance of mean differences between the dependent and independent variables. Binary and multivariable regression analysis were used to measure the association between Global Health Status and independent factors. The level of significance was set at p-value < 0.05.ResultsOn EORTC QLQ-C30 scales, the mean Global Health Status (GHS) was 42.57 ± 23.31. The least and highest affected functions were physical and social, mean (SD) = 76.39 ± 23.24 and 50.40 ± 32.19, respectively. The financial difficulty was the most affected among the symptom scales, 57.83 ± 35.34. Only physical function and financial difficulty have shown an independent association with GHS, (AOR = 0.21, 95% CI = 0.05–0.84), (AOR = 0.21 95% CI = 0.07–0.59), respectively. Illiterate, can read and write, were among the predictor factors that showed an independent association with the Global Health Status. Among the EORTC QLQ-CX24 symptom scales, the highest affected score was for sexual worry, mean (SD) = 51.81 + 32.197.ConclusionsIn an effort to improve the Global Health Status of cervical cancer patients in Ethiopia; physical function and financial difficulty should be the priority areas. The Illiterate and those who lack formal education need due attention in order to improve the health-related quality-of-life.

Mathematical model for IL-2-based cancer immunotherapy

A basic mathematical model for IL-2-based cancer immunotherapy is proposed and studied. Our analysis shows that the outcome of therapy is mainly determined by three parameters, the relative death rate of CD4+ T cells, the relative death rate of CD8+ T cells, and the dose of IL-2 treatment. Minimal equilibrium tumor size can be reached with a large dose of IL-2 in the case that CD4+ T cells die out. However, in cases where CD4+ and CD8+ T cells persist, the final tumor size is independent of the IL-2 dose and is given by the relative death rate of CD4+ T cells. Two groups of in silico clinical trials show some short-term behaviors of IL-2 treatment. IL-2 administration can slow the proliferation of CD4+ T cells, while high doses for a short period of time over several days transiently increase the population of CD8+ T cells during treatment before it recedes to its equilibrium. IL-2 administration for a short period of time over many days suppresses the tumor population for a longer time before approaching its steady-state levels. This implies that intermittent administration of IL-2 may be a good strategy for controlling tumor size.

Uplifting and Uncanny Conversations Around Death and Dying: Qualitative Study Among Indian Adolescents and Emerging Adults

This study explores perspectives of adolescents and emerging adults on having conversations around death and dying, if there is a value in discussing death early in life, and to explore the views on likelihood of introducing death education in Indian curriculum. Using constructivist grounded theory of qualitative research, the study inquired the perspectives of adolescents and emerging adults employing semi-structured interviews. All participants showed interest in discussing the topic; they actively participated in sharing their views, something that they heard, and inquiring about cultural practices. In analyzing the interview data, mainly three themes emerged: 1. Understanding death in relation to shadow and spirit stories; 2. Existential view on death and managing grief and anxiety; 3. Social and cultural narratives into death education. This study sets out to address a gap in research among adolescents and emerging adult attitudes and opinions toward death. However, there is a need to understand barriers in normalizing conversations around death and dying in wider communities in India and further research is essential.

378 Hydroxypropyl beta cyclodextrin barrier prevents respiratory and eye viral infections

OBJECTIVES/GOALS: Susceptible mucocutaneous membranes of the eye and nasal cavity are easily infected by viruses leading to pink eye or respiratory infections whose direct cost has been estimated as $16 billion annually in the United States. We have developed a novel and effective barrier that will be agnostic to variants enveloped viruses like coronaviruses. METHODS/STUDY POPULATION: We evaluated the efficacy of hydroxypropyl cyclodextrin barrier in preventing respiratory coronavirus infections using 25 humanized angiotensin converting enzyme-2 receptor (hACE-2) mice under a BSL3 laboratory setting. We have shown the barrier is safe and efficacious in preventing coronavirus infections in in vitro respiratory cell lines. We instilled 10 uL aliquot of the barrier into the nostril of the mouse 30 minutes before exposing them to a 10uL titer containing 10,000 plaque forming units of the SARS-CoV-2 delta variant. The control mice received the SARS-CoV-2 infection but not the barrier. The mice were observed for 5 days after which they were sacrificed. We analyzed the lungs and nasal palates for viral load using reverse transcription-polymerase chain reaction. RESULTS/ANTICIPATED RESULTS: We observed our barrier to be effective in preventing SARS-CoV-2 delta variant infection in hACE2 mice models. The lungs and nasal secretions of treated mice were less infectious with lower viral load than the control mice. The lungs of treated mice showed decrease in IFN gene expression and many cytokines and chemokines that regulate virally induced inflammatory responses such as IL-1b, IL-8, CXCL9, CXCL10, and the CCLs. We observed the plasma Angiotensin I and Angiotensin II decreased with barrier treatment, correlating with the viral load observed in the lungs. These peptides may be useful biomarkers for monitoring viral load within the lungs of virally infected individuals. DISCUSSION/SIGNIFICANCE: This supports the barrier’s efficacy to reduce transmission and prevent infections of SARS-CoV-2. This easy to use barrier can augment the mucocutaneous layers of the eye and nasal cavity. Our agnostic barrier will reduce the economic and public health burden of seasonal respiratory and eye viral infections and their related deaths amongst the public.

Survey of Preeclampsia/Eclampsia in relation to maternal mortality at a tertiary hospital in Gambia

Obstetrics haemorrhage was the leading cause of maternal death for over 3 decades but since 2020s we have observed that preeclampsia/eclampsia cases are increasing. This survey aims to reveal the magnitude of preeclampsia in relation to maternal mortality in our setting. Methodology: A retrospective study was conducted at the Edward Francis Small Teaching Hospital from January to December 2022. Maternal annual audit report was used to extract specific data which was entered into a computer database and analysed with descriptive statistics. Results: Total maternities from Jan to Dec 2022 was 2893 deliveries. Total number of recorded Preeclampsia/Eclampsia was 427. The prevalence was 427/2893 (14.8%). There were 54 pregnancy related deaths, Preeclampsia/Eclampsia was 24 (44%); Haemorrhage 12 (22.2%); Sepsis 7 (12.9%). All Preeclampsia/Eclampsia related deaths were referred. Conclusion: The menace of preeclampsia/Eclampsia is overwhelming and has maintained the leading cause of maternal mortality in Gambia. Hence measures to predict this condition is highly needed.

Evaluation of cytotoxicity and apoptotic effects of Catharanthus roseus on the human lung cancer cell lines CaLu-6

Abstract Background Lung cancer is ranked as the fourth global important cause of cancer related deaths. Despite remarkable advances in drug design, the pharmaceutical industry grapples with significant scientific and financial challenges. While recent strides have been made in the development of chemically synthesized pharmaceutical drugs, nature continues to serve as a primary source of bioactive compounds. The synthesis and assessment of natural herbal remedies have been a focal point of cancer therapy research for many years. The synthesis and evaluation of natural herbal remedies have been a primary research for many years in cancer therapy and the obtained results support the continuous development of novel plant-derived products, mainly because natural herbal remedies have several benefits compared to traditional chemical pharmaceuticals. Methods This study aims to evaluate the potential cytotoxicity of Catharanthus roseus methanolic extract on Human Lung Cancer Cell Lines (CaLu-6). The evaluation was performed using apoptotic and membrane depolarization assays. In addition, the real time gene expression was used for assessing the levels of mRNA. Results The results demonstrated the possible and positive anticancerous activity of Catharanthus roseus methanolic extract compared to the positive control (p&lt;0.05). Conclusions Our results support the ongoing exploration of novel plant-derived products for cancer therapy, emphasizing the benefits offered by natural herbal remedies over traditional chemical pharmaceuticals. Further research in this direction could lead to the development of more effective and less toxic treatments for lung cancer.

Global, regional, and national burdens of early onset pancreatic cancer in adolescents and adults aged 15-49 years from 1990 to 2019 based on the Global Burden of Disease Study 2019: a cross-sectional study.

Early-onset pancreatic cancer (EOPC) in younger populations (age ≤50 years) is likely to be a more aggressive phenotype characterized by poor differentiation. The emerging analysis of the global burden of EOPC is limited and outdated. To systematically investigate the burden and trend of EOPC based on global populations. In this systematic analysis based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, the authors present the number of cases, age-standardized rates (ASRs) per 100000 population, and risk factors for 204 countries and territories. The average annual percentage changes (AAPCs) for the incidence, mortality, and disability-adjusted life-years (DALYs) of EOPC were calculated using joinpoint regression analysis. According to the GBD 2019 estimates, there were 36852 new cases of EOPC and 32004 related deaths. East Asia had the highest number of cases, with 11401 incidences and 10149 deaths. The ASRs were 0.94 per 100000 individuals for incidence and 0.81 per 100000 for mortality. From 1990 to 2019, the age-standardized incidence increased by 46.9%, mortality increased by 44.6%, and DALYs increased by 41.9% globally. In trend analysis, the global incidence (AAPC, 1.26), mortality (AAPC, 1.24), and DALYs (AAPC, 1.25) of EOPC showed an increasing pattern. The ASRs of incidence, mortality, and DALYs of EOPC in Africa, America, and Asia exhibited a continuous upward trend, while the trend in Europe was fluctuating. Asian males exhibited the fastest growth in incidence (AAPC, 2.15) and mortality (AAPC, 2.13), whereas males in the Americas experienced the slowest increase in new cases (AAPC, 0.72) and deaths (AAPC, 0.67). A certain proportion of EOPC DALYs were attributable to known risk factors: tobacco smoking (13.3%), high BMI, 5.6%, and high fasting plasma glucose 3.2%. Integrating the socio-demographic index (SDI), ASRs of incidence and mortality initially increased with rising SDI, reaching a peak in central Europe (1.5 per 100000 <ASRs <2.0 per 100000), and decreased with further increase in SDI in 2019. The findings offer valuable insights into the global distribution and magnitude of the EOPC burden. The burden is increasing at a rapid pace worldwide, particularly in Asia, and is notably high in central and eastern Europe. This highlights the need for additional preventive control efforts targeting high-risk populations.

The Efficacy and Safety of Venetoclax Combined with Azacitidine in the Treatment of Adult Patients with Acute Myeloid Leukemia Who Are Unfit for Intensive Chemotherapy

To observe the clinical efficacy and safety of venetoclax (VEN) combined with azacitidine (AZA) in the treatment of adult acute myeloid leukemia (AML) patients who are unfit for intensive chemotherapy. The clinical data of 21 adult patients with unfit AML who were treated with VEN combined with AZA in the Second Hospital of Shanxi Medical University from January 2021 to May 2022 were collected, and the efficacy and safety were analyzed retrospectively. After one course of treatment with VEN and AZA, 16 out of 21 unfit AML patients reached complete remission (CR)/CR with incomplete hematologic recovery (CRi), 2 patients reached partial remission (PR), the overall response rate (ORR) was 85.7%. Among the 16 patients with CR/CRi, 13 achieved minimal residual disease (MRD) negativity. Among the 11 patients with adverse prognosis, 8 achieved CR/CRi. By the deadline of follow-up, the median overall suivival (OS) of the entire cohort was not reached, with 1-year OS rate of 61.7%. The main adverse events of VEN combined with AZA were myelosuppression, gastrointestinal reactions and infections. There were 13 cases of leukopenia, 7 cases of neutropenia, 7 cases of anemia, 4 cases of thrombocytopenia, and these hematologic adverse events were all grade 3-4. There were 11 cases with gastrointestinal reactions and 7 cases with infections. The above adverse events were controllable and tolerable. No tumor lysis syndrome or infection related death occurred. VEN combined with AZA can quickly achieve deep remission in adult patients with unfit AML, and it shows a good safety profile.

The Human Papillomavirus Enigma: A Narrative Review of Global Variations in Oropharyngeal Cancer Epidemiology and Prognosis.

Oropharyngeal cancers (OPCs) in Asia account for 42% of the global burden and over 50% of related deaths. Human papillomavirus (HPV) is involved in over 70% of OPC cases in the Western hemisphere, but its role in the Eastern hemisphere is unclear. This study reviews OPC epidemiology, including prevalence, etiological factors (such as smokeless tobacco and HPV), and their interaction. Among the SEAR countries, India had the highest incidence of HPV-related OPCs at 38.4%, while data were unavailable for most African countries, with only a 14% incidence reported. Conversely, the American region exhibited one of the highest HPV positivity rates, reaching up to 65% in different states of the USA, while Brazil reported an incidence of up to 38%. In the European Union, the UK had the highest incidence of HPV-associated OPC, reaching up to 52%. In the Western Pacific region, New Zealand demonstrated the highest incidence at up to 78%. Smokeless tobacco consumption was higher in SEAR countries, which had a relatively lower incidence of HPV infection, suggesting a negative correlation between the two. Based on our literature search, the most common detection methods used globally are immunohistochemistry for p16 and polymerized chain reaction. OPCs are a global health concern, and proper identification and classification are vital. HPV-driven cancers have better survival rates, emphasizing the need for focused research on specific problem areas based on the burden of HPV-positive or HPV-negative cancers.

Integrating transcriptomics, glycomics and glycoproteomics to characterize hepatitis B virus-associated hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) ranks as the third most common cause of cancer related death globally, representing a substantial challenge to global healthcare systems. In China, the primary risk factor for HCC is the hepatitis B virus (HBV). Aberrant serum glycoconjugate levels have long been linked to the progression of HBV-associated HCC (HBV-HCC). Nevertheless, few study systematically explored the dysregulation of glycoconjugates in the progression of HBV-associated HCC and their potency as the diagnostic and prognostic biomarker.MethodsAn integrated strategy that combined transcriptomics, glycomics, and glycoproteomics was employed to comprehensively investigate the dynamic alterations in glyco-genes, N-glycans, and glycoproteins in the progression of HBV- HCC.ResultsBioinformatic analysis of Gene Expression Omnibus (GEO) datasets uncovered dysregulation of fucosyltransferases (FUTs) in liver tissues from HCC patients compared to adjacent tissues. Glycomic analysis indicated an elevated level of fucosylated N-glycans, especially a progressive increase in fucosylation levels on IgA1 and IgG2 determined by glycoproteomic analysis.ConclusionsThe findings indicate that the abnormal fucosylation plays a pivotal role in the progression of HBV-HCC. Systematic and integrative multi-omic analysis is anticipated to facilitate the discovery of aberrant glycoconjugates in tumor progression.

A single dose for me, A wealth of protection for us: The public health cost of individualism in the rollout of COVID-19 vaccine

ObjectiveThis study examines whether individualism weakens the effectiveness of the COVID-19 vaccine eligibility expansions in the United States in 2021, and assesses the associated social benefits or costs associated with individualism. MethodsWe construct a county-level composite individualism index as a proxy of culture and the fraction of vaccine eligible population as a proxy of vaccination campaign (mean: 41.34%). We estimate whether the COVID-19 vaccine eligibility policy is less effective in promoting vaccine coverage, reducing in COVID-19 related hospitalization and death using a linear two-way fixed effect model in a sample of 2866 counties for the period between early December 2020 and July 1, 2021. We also test whether individualism shapes people's attitudes towards vaccine using a linear probability model in a sample of 625,308 individuals aged 18–65 (mean age: 43.3; 49% male; 59.1% non-Hispanic white, 19.1% Hispanic, 12% African American; 5.9% Asian) from the Household Pulse Survey. ResultsThe effects of expanded vaccine eligibility are diminished in counties with greater individualism, as evidenced by lower effectiveness in increasing vaccination rates and reducing outpatient doctor visits primarily for COVID-related symptoms and COVID deaths. Moreover, our results show that this cultural influence on attitudes towards vaccine is more pronounced among the less educated, but unrelated to race. ConclusionAssuming an average level of vaccine eligibility policies and an average intensity of individualism across the nation, we calculate that the average social cost associated with an individualistic culture amid the pandemic is approximately $50.044 billion, equivalent to 1.32% of the total U.S. health care spending in 2019. Our paper suggests that strategies to promote public policy compliance should be tailored to accommodate cultural and social contexts.

고령자 웰다잉을 위한 법제 개선 방안 (4)

This paper deals with the topic of so-called education about death or preparation for death. This paper, as part of the studies from a legal perspective on the well-dying of the elderly, aims to analyze the current status of legislation and operation related to death (preparation) education and seek improvement points. The Elderly experience so-called ‘death anxiety’, where they feel fear and stress about their own death through the death of family members and relatives. The purpose of death education is to alleviate and resolve this ‘death anxiety’ through understanding the process and nature of death, to rediscover the value and meaning of life, and to have a positive attitude toward the remaining life and the future. Through death education, it becomes possible to exercise the correct ‘right to self-determination’ to independently decide how to end one’s life. This paper reviews the legal and institutional status of death education. The death education for the elderly is carried out as part of elderly education or leisure activities at leisure welfare facilities for the elderly (for example, welfare center for senior citizens, center for senior citizens, educational courses for senior citizens, etc.) under the Welfare of Senior Citizens Act. In addition, Jeju Island is the first and currently only local government in Korea to enact and implement an ordinance on death education. This paper proposes the following as a legal and institutional improvement plan for death education. First, it is necessary to systematically legislate various matters related to death education for the elderly. Next is to improve the death education contents delivery system for the elderly. Lastly, it is required to classify the subjects of death education by age and provide education contents appropriate for each age group, thereby promoting death education for the elderly and institutionalizing death education for youth.

General surgeon performed emergency craniotomies in regional Queensland hospitals: a 20-year state-wide study on patient outcomes.

Traumatic brain injuries account for up to 50% of trauma related deaths and if surgical intervention is indicated, consensus suggests a maximum of 4 hours to surgical decompression. The occurrence and outcomes of craniotomies performed by non-neurosurgeons in regional Queensland hospitals have never been reported previously in the literature. A retrospective review was performed at all regional Queensland hospitals without an on-site neurosurgical service from January 2001 to December 2022 to identify patients undergoing emergency craniotomy. Data recorded included basic demographics, history of anti-coagulant use, mechanism of injury, type of haemorrhage, Glasgow Coma Score and Glasgow Outcome Scale (GOS) on discharge. Radiological parameters measured included midline shift and maximal coronal depth of haematoma. The primary aim of this study was to assess the clinical and radiological outcomes of patients who underwent a craniotomy performed by general surgeons. Over the past 20 years there have been 23 emergency decompressive procedures (one excluded) performed in regional Queensland. Preoperative imaging demonstrated 9 extradural haematomas and 13 subdural haematomas. Six of 17 transferred cases required reoperation after transfer to a neurosurgical centre. Survival was observed in 9 of 22 cases, with 'good' functional outcome (GOS ≥3) observed in 7 cases. In no cases were rurally performed burr holes effective. Qualitatively, a larger craniotomy may be associated with better clinical and radiological outcomes. Although rare occurrences, our results demonstrate that general surgeon performed craniotomies are frequently efficacious in producing radiological and/or clinical improvement and should be considered as a potentially lifesaving procedure.

Using machine learning to predict outcomes of patients with blunt traumatic aortic injuries.

The optimal management of blunt thoracic aortic injury (BTAI) remains controversial, with experienced centers offering therapy ranging from medical management to TEVAR. We investigated the utility of a machine learning (ML) algorithm to develop a prognostic model of risk factors on mortality in patients with BTAI. The Aortic Trauma Foundation registry was utilized to examine demographics, injury characteristics, management and outcomes of patients with BTAI. A STREAMLINE (A Simple, Transparent, End-To-End Automated Machine Learning Pipeline Facilitating Data Analysis and Algorithm Comparison) model as well as logistic regression (LR) analysis with imputation using chained equations was developed and compared. From a total of 1018 patients in the registry, 702 patients were included in the final analysis. Of the 258 (37%) patients who were medically managed, 44 (17%) died during admission, 14 (5.4%) of which were aortic related deaths. Four hundred forty-four (63%) patients underwent TEVAR and 343 of which underwent TEVAR within 24 hours of admission. Among TEVAR patients, 39 (8.8%) patients died and 7 (1.6%) had aortic related deaths ( Table 1 ). Comparison of the STREAMLINE and LR model showed no significant difference in ROC curves and high AUCs of 0.869 (95% confidence interval, 0.813-0.925) and 0.840 (95% confidence interval, 0.779-0.900) respectively in predicting in-hospital mortality. Unexpectedly, however, the variables prioritized in each model differed between models. The top 3 variables identified from the LR model were similar to that from existing literature. The STREAMLINE model, however, prioritized location of the injury along the lesser curve, age and aortic injury grade. Machine learning provides insight on prioritization of variables not typically identified in standard multivariable logistic regression. Further investigation and validation in other aortic injury cohorts are needed to delineate the utility of ML models. Prognostic and Epidemiological; Level III.

Maturity measurement in road traffic injury prevention

Road traffic related death and injury continues to be a major challenge globally. Unsafe road use is particularly evident in low- and middle-income countries while also being a growing concern for private sector organisations. The Safe System approach is recognized internationally as the leading approach to improving road safety and previous work has codified the essential management functions and interventions evident in its successful implementation. Tracking the development of Safe System adoption within the public and private sectors is of interest for several reasons. This paper presents recent development and use of road safety maturity frameworks and discusses the utility of these approaches for road safety practitioners and researchers.

A Review on the Prevalence and Management of Colorectal Cancer

Cancer had become a common disease worldwide and cancer related death is also increasing in various parts of the world in spite of increased screening and diagnostic facilities available for early detection of cancer and availability of advanced care system. Changes in the diet and life style had led to alteration in the microenvironment of the cells leading to genetic changes and mutation. In this review, Colorectal cancer prevalence, risk factors for the development of colorectal cancer, pathogenesis, diagnosis and various treatment modalities available are discussed here.