Death In Patients Research Articles

Fear of death: everyday experience-based nurses ’observations in working with elderly and old patients ill with chronic cardiovascular diseases

Fear of death occurs when elderly and old patients (EOPs) are faced with life-threatening events or extreme psychological stress. For most, anticipation of death triggers negative emotions such as the fear of losing of oneself, helplessness, and a loss of control. Fear of death is one of the most prevalent psychiatric consequences of chronic health conditions. Nurses face challenges in caring for EOPs ill with chronic cardiovascular diseases (CCVDs) snd this is related to high emotional stress and fatigue associated with constant monitoring of patients and managing their anxiety and fears. Fear of death is a common concern among EOP with CCVDs. There is relatively little research that examines the relationship between EOPs ’CCVDs and experienced fear of death phenomena from the perspective of nurses. Research question, to which the answer was sought was ‘How do nurses de scribe the symptoms, signs of fear of death among EOPs ’ill with CCVDs and how they recognise the features of patients ’fear of death?’ A total of 15 nurses had participated in the study. Data were collected by using semi-structured interviews. The manifest qualitative content analysis for data anal ysis were applied. Findings revealed that the related emotional/psychological, physiological and be havioural changes were observed by nurses and the characteristics for recognising the feeling of death in patients were identified. Characteristics of EOPs ill with CCVDs and experiencing fear of death are related to changes in emotions, behaviour and physical/physiological symptoms/signs that are interrelated with their emotional state. The social, spiritual and creative needs of patients are intensi fied while they experience fear of death.

Artificial Intelligence for Clinical Decision-Making: Gross Negligence Manslaughter and Corporate Manslaughter.

This paper discusses the risk of gross negligence manslaughter (GNM) and corporate manslaughter charges (CM) when clinicians use an artificially intelligent system's (AIS's) outputs in their practice. I identify the elements of these offenses within the context of the law of England and Wales and explore how they could be applied in a potential scenario where a patient's death has followed AIS use by a clinician. The risk of a conviction due to making an AIS-augmented workplace mistake highlights the non-trivial nature of AIS adoption in healthcare, and that the consequences of its use must be considered by all interested parties prior to AIS adoption.

Liver Transplantation for the Cure of Neuroendocrine Liver Metastasis: A Systematic Review with Particular Attention to the Risk Factors of Death and Recurrence

Background/Objectives: Neuroendocrine neoplasms (NEN) are heterogeneous entities. Despite considerable advancement in the field, almost 50% of patients have metastatic disease, when liver transplantation (LT) is one of the possible treatments offering a cure in well-selected patients. Methods: The present study aims to systematically review all the literature from 2000 onwards on using LT for patients with NEN-LM, with particular attention to the risk factors of death and recurrence. Results: LT offers 5-year OS ranging from 52 to 74% and 5-year TFS rates ranging from 39 to 62%, with even better results published from 2009 onwards. The main risk factors for patient deaths are related to unfavorable primary tumor pathology, higher liver involvement, and simultaneous LT and primary resection. Similarly, recurrence is higher related to poor tumor grade and differentiation, and in the case of an older recipient age. Conclusions: Applying uniform criteria and a more in-depth understanding of the relevant prognostic factors contribute to a better selection of candidates for curative LT due to NEN metastases. LT for unresectable or liver-restricted NENs has a relevant place in the treatment algorithm and has achieved excellent results in recent decades, but more international efforts are needed to further improve outcomes.

Factors associated with unfavourable treatment outcomes among tuberculosis patients at health facilities of Maseru, Lesotho.

Tuberculosis (TB) treatment success rates (TSR) remain low in Lesotho. The country achieved TSR of 76% in 2020, which is far below the World Health Organization's 95% target set for 2030. This study determined the level of treatment success and factors associated with unfavourable treatment outcomes. This descriptive cross-sectional study used patient records to perform descriptive and logistic regression analyses. Sixty-one per cent of the 336 TB patients were male. Two hundred and eighty-nine had favourable outcomes, of which 10% died in the course of treatment. Patients ≤ 44 years old, and those with supported treatment, had lower odds of unfavourable treatment outcomes, respectively, adjusted odds ration [aOR] = 0.39 (95% CI: 0.19-0.78) and aOR = 0.22 (95% CI: 0.08-0.62),p 0.05.Contribution:The death of patients while on TB treatment needs to be addressed, including heightened advocacy for supported treatment.

MicroRNAs are enriched at COVID-19 genomic risk regions, and their blood levels correlate with the COVID-19 prognosis of cancer patients infected by SARS-CoV-2

BackgroundCancer patients are more susceptible to an aggressive course of COVID-19. Developing biomarkers identifying cancer patients at high risk of COVID-19-related death could help determine who needs early clinical intervention. The miRNAs hosted in the genomic regions associated with the risk of aggressive COVID-19 could represent potential biomarkers for clinical outcomes.Patients and methodsPlasma samples were collected at The University of Texas MD Anderson Cancer Center from cancer patients (N = 128) affected by COVID-19. Serum samples were collected from vaccinated healthy individuals (n = 23) at the Municipal Clinical Emergency Teaching Hospital in Timisoara, Romania. An in silico positional cloning approach was used to identify the presence of miRNAs at COVID-19 risk-associated genomic regions: CORSAIRs (COvid-19 RiSk AssocIated genomic Regions). The miRNA levels were measured by RT-qPCR.ResultsWe found that miRNAs were enriched in CORSAIR. Low plasma levels of hsa-miR-150-5p and hsa-miR-93-5p were associated with higher COVID-19-related death. The levels of hsa-miR-92b-3p were associated with SARS-CoV-2 test positivity. Peripheral blood mononuclear cells (PBMC) increased secretion of hsa-miR-150-5p, hsa-miR-93-5p, and hsa-miR-92b-3p after in vitro TLR7/8- and T cell receptor (TCR)-mediated activation. Increased levels of these three miRNAs were measured in the serum samples of healthy individuals between one and nine months after the second dose of the Pfizer-BioNTech COVID-19 vaccine. SARS-CoV-2 infection of human airway epithelial cells influenced the miRNA levels inside their secreted extracellular vesicles.ConclusionsMiRNAs are enriched at CORSAIR. Plasma miRNA levels can represent a potential blood biomarker for predicting COVID-19-related death in cancer patients.

Sleep restriction exacerbates cardiac dysfunction in diabetic mice by causing cardiomyocyte death and fibrosis through mitochondrial damage.

Diabetic cardiomyopathy (DCM) is a cardiovascular complication of diabetes mellitus with a poor prognosis and is the leading cause of death in diabetic patients. Sleep deficiency is not only recognized as an important risk factor for the development of type 2 DM, but is also associated with increased morbidity and mortality of cardiovascular disease. The underlying role and mechanisms of sleep restriction (SR) in DCM are far from clear. The KK/Upj-Ay mouse model of T2 DM was used as a study subject, and the small animal ultrasound imaging system was used to detect the function of the heart; immunopathological staining was used to clarify the histo-structural pathological alterations of the heart; and TUNEL staining, qPCR, transmission electron microscopy (TEM), and ELISA kits were used to detect apoptosis, oxidative stress, inflammation, and mitochondrial damage, and related molecular alterations. SR led to a significant increase in mortality, cardiac hypertrophy, necrosis, glycogen deposition and fibrosis further deteriorated in DM KK mice. SR increased cardiomyocyte death in KK mice through the Bax/Bcl2 pathway. In addition to this, SR not only exacerbated the inflammatory response, but also aggravated mitochondrial damage and promoted oxidative stress in KK mice through the PRDM16-PGC-1α pathway. Overall, SR exacerbates structural alterations and dysfunction through inflammation, oxidative stress, and apoptosis in DM KK mice, increasing the risk of death. Clinicians and diabetic patients are prompted to pay attention to sleep habits to avoid accelerating the transition of DCM to heart failure and inducing death due to poor sleep habits.

The Influence of Arrhythmia on the Outcomes of Pediatric Patients with Idiopathic Dilated Cardiomyopathy.

Children diagnosed with dilated cardiomyopathy (DCM) are at an increased risk of developing arrhythmias, which can significantly affect their overall prognosis. However, the implantation and effectiveness of implantable cardioverter-defibrillators (ICDs) pose challenges in the pediatric population. Therefore, it is crucial to determine the prevalence of arrhythmia-related death in pediatric patients with DCM. This study investigated the correlation between arrhythmias and mortality in pediatric patients with DCM. This retrospective cohort study examined children with idiopathic DCM referred to Rajaie Cardiovascular, Medical, and Research Institute in Tehran, Iran, from 2017 to 2023. All patients underwent a standard 12-lead electrocardiogram, 24-h Holter monitoring, cardiac magnetic resonance imaging, and echocardiography. Patient outcomes, including death, heart transplantation, and survival, were evaluated within one year of Holter monitoring. A total of 178 children (79 males) with a mean age of 83.06 ± 56.41months were included in the study. Overall, 72 deaths (40.4%) and 46 heart transplants (25.8%) were recorded and 60 patients (33.7%) survived. There was no significant association between patients' outcomes with ventricular arrhythmias, late gadolinium enhancement, corrected QT interval, and QRS interval prolongation; however, a significantly higher proportion of dead patients had abnormal heart rate variability (P = 0.034). Heart failure was the leading cause of death, with ventricular arrhythmia accounting for two out of 72 deaths. Both cases of ventricular arrhythmia were associated with severe cardiac dysfunction. Arrhythmia-related mortality is rare in children with idiopathic DCM, with severe heart failure being the primary cause of death in this population. Life-threatening arrhythmias primarily occur in DCM children with more compromised cardiac function.

Respiratory Support for Patients with Chronic Respiratory Failure: the Necessity of a Long-Term Homecare Ventilation Program

Severe respiratory failure, resulting from a wide range of acute and chronic diseases such as chronic obstructive pulmonary diseases, obstructive sleep apnoea, obesity hypoventilation syndrome (Pickwickian syndrome), COVID-19, bilateral pneumonitis, kyphoscoliosis, acute respiratory distress syndrome, amyotrophic lateral sclerosis, Guillain-Barré syndrome, and others, poses a significant challenge for healthcare systems worldwide. Treating severe respiratory failure often requires long-term or lifelong respiratory support, which places a heavy burden on both patients and healthcare systems. Despite the availability of free comprehensive care for patients with chronic kidney failure and heart failure, those requiring long-term respiratory support are often deprived of adequate medical and social assistance. This gap in care leads to frequent hospitalizations, disability, and premature death of patients with severe respiratory failure, further straining healthcare resources and increasing social tension. The solution of the problem is an organisation of ambulatory centre for homecare respiratory support for patients with severe chronic respiratory failure. Homecare respiratory support demonstrated worldwide cost-effectiveness by significantly enhancing patients clinical and social outcomes, restoring their work capacity, and reducing the need for hospitalizations. This article emphasizes the necessity of a comprehensive homecare respiratory support system and highlights how inadequate assistance can result in frequent hospitalizations, increased disability, and premature death, thereby imposing an additional strain on the healthcare system.

Machine Learning Algorithm-Aided Determination of Predictors of Mortality from Diabetic Foot Sepsis at a Regional Hospital in South Africa During the COVID-19 Pandemic.

Background and Objectives: Diabetic foot sepsis (DFS) accounts for approximately 60% of hospital admissions in patients with diabetes mellitus (DM). Individuals with DM are at risk of severe COVID-19. This study investigated factors associated with major amputation and mortality in patients admitted with DFS during the COVID-19 pandemic. Materials and Methods: Demographic information, COVID-19 and HIV status, clinical findings, laboratory results, treatment and outcome from records of patients with diabetic foot sepsis, were collected and analysed. Supervised machine learning algorithms were used to compare their ability to predict mortality due to diabetic foot sepsis. Results: Overall, 114 records were found and 57.9% (66/114) were of male patients. The mean age of the patients was 55.7 (14) years and 47.4% (54/114) and 36% (41/114) tested positive for COVID-19 and HIV, respectively. The median c-reactive protein was 168 mg/dl, urea 7.8 mmol/L and creatinine 92 µmol/L. The mean potassium level was 4.8 ± 0.9 mmol, and glycosylated haemoglobin 11.2 ± 3%. The main outcomes included major amputation in 69.3% (79/114) and mortality of 37.7% (43/114) died. AI. The levels of potassium, urea, creatinine and HbA1c were significantly higher in the deceased. Conclusions: The COVID-19 pandemic led to an increase in the rate of major amputation and mortality in patients with DFS. The in-hospital mortality was higher in patients above 60 years of age who tested positive for COVID-19. The Random Forest algorithm of ML can be highly effective in predicting major amputation and death in patients with DFS.

Radio-Biological Confrontation in the Diagnosis of Invasive Aspergillosis: About Two Cases and Review of Literature

Invasive pulmonary aspergillosis due to Aspergillus fumigatus is an often serious mycosis, usually occurring in severely immunocompromised patients. It is accompanied by a high mortality rate due to its often difficult and late diagnosis. Diagnosis is based on early chest computed tomography and mycological examination of respiratory samples. Both patients had presented with acute respiratory distress, developing in a context of fever and deterioration of the general condition despite the initiation of broad-spectrum empirical treatment. In each of them, a chest CT scan was performed, objectifying atypical cavitary images not suggesting pulmonary aspergillosis. Cytobacteriological examination of sputum and search for Mycobacterium tuberculosis were negative. Serology for aspergillus antigens and a sample of bronchoalveolar lavage fluid for a mycological study were requested. Direct examination of bronchoalveolar lavage fluid was negative, but culture allowed the identification of Aspergillus fumigatus. Galactomannan testing was positive. Given these results, treatment with injectable voriconazole was initiated in our two cases. The evolution was marked by a clinical improvement of one patient and the death of the other patient. Invasive pulmonary aspergillosis is a major concern due to the frequency of its complications. Its diagnosis must be early to ensure adequate management for a better prognosis.

Relationship between the AGT M235T genetic variant and the characteristics and prognosis of coronary atherosclerosis in patients with acute myocardial infarction.

Along with environmental components, genetic factors play an essential role in the pathophysiology and progression of acute myocardial infarction (AMI). There is limited and conflicting data on the influence of the AGT M235T genetic variant on coronary atherosclerosis and death in AMI patients. We carried out a prospective cohort study among 504 Vietnamese AMI patients selected between January 2020 and May 2021. All patients underwent invasive coronary angiography, had AGT M235T genetic variant genotyped using the polymerase chain reaction method, and were followed up for 12-month all-cause mortality. The proportions of the MM, MT, and TT genotypes were 0.4%, 20.8%, and 78.8%, respectively. There was no significant difference between the TT genotype and the MM + MT genotype groups regarding the position and number of stenosed coronary artery branches and the Gensini score. The AGT M235T genetic variant did not affect 12-month mortality (hazard ratio of TT vs. MM + MT: 1.185; 95% confidence interval: 0.596-2.354; P = 0.629). Subgroup analyses by age, sex, hypertension, diabetes mellitus, dyslipidemia, obesity, smoking, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker therapy also did not reveal an association between the AGT M235T variant and all-cause mortality. In summary, the AGT M235T genetic variant was not found to be associated with coronary atherosclerosis characteristics and 12-month mortality in Vietnamese patients with AMI. Further multicenter studies with larger sample sizes and extended follow-up periods are needed to investigate this issue.

Professional Bereavement in Nursing: An Evolutionary Concept Analysis.

Clarify and define the concept of professional bereavement in nursing. Rodgers' evolutionary method was used to identify the attributes, antecedents, and consequences of professional bereavement in nursing. Literature from inception to May 20, 2024, was searched from PubMed, Embase, Web of Science, CINAHL, PsycINFO, Scopus, Medline, EBSCO host, Proquest, Ovid, and Cochrane. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were adopted. The 32 articles included in the study provided data on the concept of professional bereavement in nursing. We propose the concept of professional bereavement in nursing as follows: Professional bereavement in nursing is the experience of a patient or colleague's death in the workplace, influenced by contextual, internal, and external factors. Nurses perceive personal and professional losses, exhibit a multidimensional liminal state, and experience personal impacts (life and worldview) and professional impacts (health-related productivity and professional ability). We developed a preliminary conceptual model of professional bereavement in nursing based on its attributes, antecedents, and consequences. This conceptual model promotes the development of theories related to professional bereavement. This is the first article to clarify and define professional bereavement in nursing. We have clarified the antecedents, attributes, and consequences of professional bereavement, which provides a conceptual framework for understanding professional bereavement. The conceptual framework guides the content of interventions and suggests future professional bereavement interventions from a dialectical perspective. Not applicable.

Predictors of polytrauma outcome in children on the first day of treatment in ICU

The objective was to identify predictors of polytrauma outcome in children on the first day of treatment in ICU.Materials and methods. Design – multicenter, cohort, retrospective, observational study. 225 children with polytrauma were examined. The average age of children was 10 (4–14) years. There were 148 (65.8%) boys. In 65.2% of cases, the injury was received as a result of a traffic accident, catatrauma occurred in 32.6% of polytrauma. The AIS score was 34 (25–48) and the PTS score was 5 (2.0–8.0). The duration of artificial lung ventilation was 12 (0–97) hours, and treatment in ICU – 5 (2–8) days. Death was in 14.2% of cases. Results. An increase in Glasgow Coma Scale (GCS) and SpO2 by one unit (1 point, 1%) was found to reduce the risk of adverse outcome by 44% and 9%, respectively, and an increase in creatinine concentration and international normalized ratio by one unit increased the probability of patient death by 4.3 and 15.8 times, respectively. A mathematical formula was developed to assess the risk of an unfavorable outcome of polytrauma in children at the time of admission to the ICU: OR = exp (3.74–0.58 · [GCS score] – 0.09 · [SpO2] + 0.06 · [Creatinine] + 2.62 · [INR]. Its accuracy is 96.4%; sensitivity 83.4%; specificity 98.7%.Conclusion. Predictors of unfavorable outcome of polytrauma in children at admission to ICU are low scores on the Glasgow Coma Scale, severe hypoxemia, coagulopathy and kidney damage.

Recent radiotherapy could reduce heart-related death in patients with esophageal cancer: SEER database analysis

BackgroundThere have been several reports showing that heart-related deaths are common in long-term survivors of esophageal cancer after radiation therapy; however, radiotherapy technology is evolving year by year. This study was carried out using the SEER database to determine whether the frequency of mortality from heart disease after radiotherapy has improved over time in patients with esophageal cancer.MethodsSEER*Stat statistical software version 8.3.9.2 (National Cancer Institute) was used to perform case listing and data extraction. We reviewed causes of death in 8,297 patients who were treated by radiotherapy without surgery between 2004 and 2015 (radiotherapy group). For comparison with this group, we also reviewed causes of death in 5,149 patients who were treated by surgery without radiotherapy (surgery group).ResultsIn the radiotherapy group, the cumulative heart-related death rate in patients with carcinoma in the middle to abdominal esophagus, for which it was considered that the heart was irradiated with a higher dose, was significantly higher than that in patients with carcinoma in the cervical to upper thoracic esophagus (p = 0.017). However, in the surgery group, the cumulative heart-related death rate in patients with carcinoma in the middle to abdominal esophagus tended to be lower than that in patients with carcinoma in the cervical to upper thoracic esophagus (p = 0.063). The cumulative heart-related death rate in patients treated in 2010–2015 was significantly lower than that in patients treated in 2004–2009 in the radiotherapy group (p = 0.011), although the cumulative heart-related death rate was not significantly different between patients treated in 2010–2015 and patients treated in 2004–2009 in the surgery group (p = 0.90).ConclusionsThe results suggest that recent advances in radiotherapy have enabled a reduction in radiation-induced heart disease in patients with esophageal cancer.

Identification of factors predicting low-risk febrile neutropenia admissions in adults with acute myeloid leukemia

AbstractFebrile neutropenia (FN) is the most common reason for hospital readmission after chemotherapy for acute myeloid leukemia (AML) and is a major driver of health care resource utilization. Although FN risk models exist, they have largely been developed and validated for solid tumors. We therefore examined whether baseline characteristics could predict which patients with AML and FN have a lower risk of progression to severe illness. We identified adults with high-grade myeloid neoplasms (≥10% blasts in the blood/marrow) who received intensive chemotherapy and who were admitted for FN between 2016 and 2023. We collected baseline clinical and disease variables. Outcomes were: infections identified, hospital length of stay (LOS), intensive care unit (ICU) admission, and survival. A lower-risk (LR) outcome was defined as LOS <72 hours without ICU admission or inpatient death. Univariate and multivariable (MV) logistic regression models were used to assess covariate associations with outcomes. We identified 397 FN admissions in 248 patients (median age, 61; [range, 29-77] years). The median hospital LOS was 6 days (range, 1-56) days; 10% required ICU admission, and 3.5% died inpatients. Only 15% of admissions were LR. Infection was identified in 59% of admissions. Physiologic parameters, including heart rate, blood pressure, and fever height, were the best predictors of LR admission and infection. We developed MV models to predict LR admission and infection with area under the curve (AUC) of 0.82 and 0.72, respectively. Established FN and critical illness models were not predictive of outcomes in AML, and we could not identify a LR group; thus, an AML-specific FN risk model requires further development and validation.

The role of NOP58 in prostate cancer progression through SUMOylation regulation and drug response.

Prostate cancer is one of the leading causes of cancer-related deaths in men. Its molecular pathogenesis is closely linked to various genetic and epigenetic alterations, including posttranslational modifications like SUMOylation. Identifying biomarkers that predict outcomes and specific therapeutic targets depends on a comprehensive understanding of these processes. With growing interest in SUMOylation as a mechanism affecting prostate cancer-related genes, this study aimed to investigate the central role of SUMOylation in prostate cancer prognostics, focusing on the significance of NOP58. We conducted a comprehensive bioinformatics analysis, integrating differential expression analysis, survival analysis, gene set enrichment analysis (GSEA), and single-cell transcriptomic analyses using data from The Cancer Genome Atlas (TCGA). Key genes were identified through intersections of Venn diagrams, Boralta algorithm signatures, and machine learning models. These signaling mechanisms were validated through experimental studies, including immunohistochemical staining and gene ontology analyses. The dual-gene molecular subtype analysis with SUMO1, SUMO2, and XPO1 genes revealed significant differences in survival outcomes across molecular subtypes, further emphasizing the potential impact of NOP58 on SUMOylation, a key post-translational modification, in prostate cancer. NOP58 overexpression was strongly associated with shorter overall survival (OS), progression-free interval (PFI), and disease-specific death in prostate cancer patients. Immunohistochemical analysis confirmed that NOP58 was significantly overexpressed in prostate cancer tissues compared to normal tissues. ROC curve analysis demonstrated that NOP58 could distinguish prostate cancer from control samples with high diagnostic accuracy. Gene Ontology analysis, along with GSVA and GSEA, suggested that NOP58 may be involved in cell cycle regulation and DNA repair pathways. Moreover, NOP58 knockdown led to increased BCL2 expression and decreased Ki67 levels, promoting apoptosis and inhibiting cell proliferation. Colony formation assays further showed that NOP58 knockdown inhibited, while its overexpression promoted, colony formation, highlighting the critical role of NOP58 in prostate cancer cell growth and survival. Additionally, NOP58 was linked to drug responses, including Methotrexate, Rapamycin, Sorafenib, and Vorinostat. NOP58 is a key regulator of prostate cancer progression through its mediation of the SUMOylation pathway. Its expression level serves as a reliable prognostic biomarker and an actionable therapeutic target, advancing precision medicine for prostate cancer. Targeting NOP58 may enhance therapeutic efficacy and improve outcomes in oncology.

MAiD in America: A Rapid Review of Medical Assistance in Dying in the United States and Its Implications for Practice for Health Care Professionals.

The evolving legal landscape associated with medical assistance in dying (MAiD) may pose significant challenges for hospice and palliative care professionals. In the United States, 10 states and 1 jurisdiction have passed legislation allowing MAiD. National organizations, such as the Hospice and Palliative Nurses Association, have created position statements to serve as guides to care. Given the clinical and ethical challenges associated with MAiD, a rapid review was conducted to provide current evidence for policymakers, health care professionals, and researchers to use when considering care management and policy initiatives. Using a systematic approach, publications related to MAiD between 2019 and 2024 were extracted and synthesized. The review provides definitions of terms that differentiate between MAiD, euthanasia, physician-assisted suicide, medically assisted death of the nonterminal patient, and death with dignity. A total of 23 articles were included in the review and categorized into 4 themes: (1) legal, regulatory, and policy concerns; (2) health care professional experience of MAiD; (3) patient and caregiver experience of and communication about MAiD; and (4) disparate access to MAiD.

Clinical features of suspected and unsuspected fatal pulmonary emboli in hospitalized patients.

Pulmonary embolism (PE) is often unsuspected by treating clinicians. Since the adoption of clinical prediction scores for PE and the widespread availability of computed tomography (CT)-pulmonary angiogram, there are few reports of clinical presentations of hospitalized patients who died of PE. To compare the clinical signs, symptoms, and comorbidities of hospitalized patients who died of PE for whom PE was suspected versus not suspected antemortem. Case-control study from January 1999 to December 2018 in one Veterans Affairs (VA) hospital. We compared groups to examine differences in clinical presentations of fatal PE over the two decades. Among 1345 autopsies performed during the study period, 52 patients (4%) with fatal PE were included in the final analyses. PE was unsuspected before death in 29/52 patients (56%). Comparing groups, there were significant differences for: dyspnea (suspected 91%; unsuspected: 59%, p = 0.01); active malignancy (suspected 74%; unsuspected: 28%, p = 0.002); and atrioventricular (AV) nodal blocking treatment (suspected: 62%; unsuspected 30%,p= 0.03). A greater proportion of patients with unsuspected PE lacked symptoms of PE (suspected 0%; unsuspected: 31%, p = 0.003). Fatal PE remains a common, unsuspected cause of inpatient death in the modern era. Symptoms of PE, active malignancy, and potentially confounding AV nodal blocking treatment were less frequent in patients with unsuspected PE. These data highlight the variation in presentation and the challenge of making the diagnosis in many hospitalized patients, particularly those without typical symptoms.

Abstract A017: Identifying proliferative and immune-modulatory drivers of small cell lung cancer (SCLC)

Abstract Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer that causes an estimated 200,000 patient deaths globally every year. Most (&amp;gt;70%) patients present with extensive stage (ES)-SCLC, and the disease primarily presents with a neuroendocrine (NE), immune-desert phenotype, with low expression of antigen-presenting machinery genes. Despite limited immune infiltration in the tumor, SCLC has reproducibly responded to immune checkpoint blockade. IMpower133 was a pivotal Phase III trial that added atezolizumab (anti-PD-L1) to platinum/etoposide chemotherapy for treatment of first-line ES-SCLC, which led to the first approval of an immune checkpoint blockade strategy in SCLC. While the inclusion of atezolizumab to the treatment regimen has extended the survival of some patients, SCLC remains an unmet medical need with a mOS of 12.3 months. Furthermore, we lack a deep molecular understanding of factors mediating response and resistance to standard of care therapies in SCLC. To understand the genetic drivers of SCLC that could be linked to immunotherapy resistance, we analyzed the matched whole-exome sequencing and RNA-seq data from baseline tumor samples collected from the IMpower133 trial. Previously, we applied the non-negative matrix factorization (NMF) approach to the RNA-seq data, which clustered patients into four subsets of SCLC, with varying degrees of immune infiltration, neuroendocrine program activation, and clinical benefit from immunotherapy. Notably, we identified an inflamed-neuroendocrine (I-NE) subset of patients that exhibit longer overall survival with chemoimmunotherapy compared to chemotherapy alone, and an inflamed-non-neuroendocrine (I-nonNE) subset of patients that did not show a similar benefit from the addition of immunotherapy to chemotherapy. Here, we interrogated the matched WES data for recurrent alterations that may identify subsets of tumors with distinct immunological features. We identified several genes whose alterations significantly affected the enrichment of immune-related gene signatures. In particular, we identified MANF and CSK, genes previously shown to be potential tumor suppressors, as genes whose alteration associates with an “immune desert” transcriptional program. Specifically, genetic deletions or low RNA expression was associated with significantly decreased gene expression of gene signatures associated with lymphocytes, macrophages, and antigen presentation machinery. These data suggest a potential mechanism by which commonly inactivated tumor suppressors may shape the “immune desert” phenotype of SCLC. Further work is needed to determine if and how these genes may directly or indirectly modulate the tumor-immune interaction. Citation Format: Myung Chang Lee, Velimir Gayevskiy, Stefanie Morris, Minu K Srivastava, Namrata S Patil, Stephen V Liu, Martin Reck, Sanjeev Mariathasan, David S Shames, David P MacPherson, Robert J Johnston, Barzin Y Nabet. Identifying proliferative and immune-modulatory drivers of small cell lung cancer (SCLC) [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr A017.

Deep-learning CT imaging algorithm to detect usual interstitial pneumonia pattern in patients with systemic sclerosis-associated interstitial lung disease: association with disease progression and survival.

Interstitial lung disease (ILD) is the most common cause of death in patients with systemic sclerosis (SSc), although disease behavior is highly heterogeneous. While a usual interstitial pneumonia (UIP) pattern is associated with worse survival in other ILDs, its significance in SSc-ILD is unclear. We sought to assess the prognostic utility of a deep-learning HRCT algorithm of UIP probability in SSc-ILD. Patients with SSc-ILD were included if HRCT images, concomitant lung function tests, and follow-up data were available. We used the Systematic Objective Fibrotic Imaging analysis Algorithm (SOFIA), a convolution neural network algorithm which provides probabilities of a UIP pattern on HRCT images. These were converted into the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED)-based UIP probability categories. Decline in lung function was assessed by mixed-effect model analysis and relationship with survival by Cox proportional hazards analysis. 522 patients were included in the study. 19.5% were classified as UIP not in the differential, 53.5% as low probability of UIP, 25.7% as intermediate probability of UIP, and 1.3% as high probability of UIP. A higher likelihood of UIP probability expressed as PIOPED categories was associated with worse baseline FVC, as well as with decline in FVC (p= 0.008), and worse 15-year survival (p= 0.001), both independently of age, gender, ethnicity, smoking history, and baseline FVC or Goh et al. staging system. A higher probability of a SOFIA-determined UIP pattern is associated with more advanced ILD, disease progression, and worse survival, suggesting that it may be a useful prognostic marker in SSc-ILD.